Arylglyoxals in Synthesis of Heterocyclic Compounds - ACS Publications

Review pubs.acs.org/CR

Arylglyoxals in Synthesis of Heterocyclic Compounds Bagher Eftekhari-Sis,*,† Maryam Zirak,‡ and Ali Akbari† †

Department of Chemistry, Faculty of Science, University of Maragheh, Golshahr, P.O. Box. 55181-83111, Maragheh, Iran Department of Chemistry, Payame Noor University, P.O. Box 19395-3697, Tehran, Iran

‡

5.6.1. Dioxophospholanes 6. Synthesis of Six-Membered Heterocycles 6.1. N-Heterocyclic Compounds 6.1.1. Tetrahydropyridines 6.1.2. Pyridines 6.1.3. Tetrahydroquinolines and Quinolines 6.1.4. Isoquinolines 6.1.5. β-Carbolines 6.1.6. Pyridazines 6.1.7. Fused Pyridazines 6.1.8. Pyrimidines 6.1.9. Piperazinones and Pyrazinones 6.1.10. Pyrazines 6.1.11. Quinoxalines 6.1.12. Fused Pyrazines and Pteridines 6.1.13. Triazinones 6.1.14. Triazines 6.1.15. Fused Triazines 6.2. O-Heterocyclic Compounds 6.2.1. Pyrans and Pyranones 6.2.2. Dioxanes 6.3. S-Heterocyclic Compounds 6.3.1. Thiopyrans 6.4. N,O-Heterocyclic Compounds 6.4.1. 1,3-Oxazines 6.4.2. Morpholines 6.4.3. Oxadiazines 6.5. N,S-Heterocyclic Compounds 6.5.1. 1,4-Thiazines and 1,4-Benzothiazines 6.5.2. Benzothiadiazines 6.6. S,O-Heterocyclic Compounds: Benzoxathiin 7. Synthesis of Seven-Membered Heterocycles 7.1. N-Heterocyclic Compounds 7.1.1. Tetrahydroazepines 7.1.2. Diazepines and Benzodiazepines 7.2. N,O-Heterocyclic Compounds: Oxazepanes 8. Miscellaneous Heterocycles 8.1. Porphyrins 8.2. Cyclens 9. Conclusion Author Information Corresponding Author Notes Biographies Acknowledgments Dedication Abbreviations References

CONTENTS 1. Introduction 2. Arylglyoxals 2.1. Physical Properties and Reactivity of Arylglyoxals 2.2. Synthesis of Arylglyoxals 3. Synthesis of Three-Membered Heterocycles 3.1. Aziridines 3.2. Oxiranes 4. Synthesis of Four-Membered Heterocycles 4.1. Azetidines and β-Lactams 4.2. β-Lactones 5. Synthesis of Five-Membered Heterocycles 5.1. N-Heterocyclic Compounds 5.1.1. Pyrrolidines and Pyrrolines 5.1.2. Pyrroles 5.1.3. Pyrrolizidines, Pyrrolizines, and Indolizidines 5.1.4. Pyrazolines and Pyrazoles 5.1.5. Imidazolidin-2,4-diones and Imidazolin2-ones 5.1.6. Imidazoles 5.1.7. Fused Imidazopyridines, -Pyrimidines, and -Pyrazines 5.1.8. 1,2,3-Triazoles and Tetrazoles 5.2. O-Heterocyclic Compounds 5.2.1. Tetrahydro- and Dihydrofurans 5.2.2. Furans 5.2.3. Benzofurans and Furofurans 5.2.4. Dioxolanes 5.3. S-Heterocyclic Compounds 5.3.1. Thiophenes 5.4. N,O-Heterocyclic Compounds 5.4.1. Isoxazoles 5.4.2. Oxazolidines, Oxazolines, and Benzoxazolines 5.4.3. Oxazoles 5.5. N,S-Heterocyclic Compounds 5.5.1. Thiazolidines and Thiazolines 5.5.2. Thiazoles and Benzothiazoles 5.5.3. Thiadiazolidines and Thiadiazoles 5.6. O,P-Heterocyclic Compounds © XXXX American Chemical Society

B B B C C C D D D E F F F G J K M P S T U U W X Z Z Z AA AA AB AC AD AD AE AF AG

AG AH AH AH AI AK AL AM AO AQ AS AS AU AV AW AY AZ BA BB BB BC BD BD BD BD BE BG BG BG BH BH BI BI BI BI BJ BJ BJ BJ BK BL BL BL BL BL BM BM BM

Received: April 28, 2012

A

dx.doi.org/10.1021/cr300176g | Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

1. INTRODUCTION Heterocycles are an extraordinarily important class of compounds, making up more than half of all known organic compounds. Heterocycles are present in a wide variety of drugs, most vitamins, many natural products, biomolecules, and biologically active compounds, including antitumor, antibiotic, anti-inflammatory, antidepressant, antimalarial, anti-HIV, antimicrobial, antibacterial, antifungal, antiviral, antidiabetic, herbicidal, fungicidal, and insecticidal agents. Also, they have been frequently found as a key structural unit in synthetic pharmaceuticals and agrochemicals. Some of these compounds exhibit a significant solvatochromic, photochromic, and bioand chemiluminescence properties. Most of the heterocycles possess important applications in materials science such as dyestuff, fluorescent sensor, brightening agents, information storage, plastics, and analytical reagents. In addition, they have applications in supramolecular and polymer chemistry, especially in conjugated polymers. Moreover, they act as organic conductors, semiconductors, molecular wires, photovoltaic cells, organic light-emitting diodes (OLEDs), light harvesting systems, optical data carriers, chemically controllable switches, and liquid crystalline compounds. Heterocycles are also of considerable interest because of their synthetic utility as synthetic intermediates, protecting groups, chiral auxiliaries, organocatalysts, and metal ligands in asymmetric catalysts in organic synthesis. Therefore, substantial attention has been paid to develop efficient new methods to synthesize heterocycles. 1,2-Dicarbonyl compounds are among the most attractive precursors that are used to synthesize heterocyclic compounds. Arylglyoxals (ArCOCHO, AGs), aromatic α-keto aldehydes containing both aldehyde and ketone functional groups with different reactivity, play an important role in this area. To the best of our knowledge, there is no review on synthesis of heterocyclic compounds using AGs and their derivatives. However, there have been many published articles on different reactions of AGs and their derivatives, such as allylation,1 arylation,2 Cannizzaro,3 Henry,4 Mannich,5 reductive amination,6 reductive coupling with dienes,7 and Wittig8 reactions; in this review, AGs were considered as precursors in reactions that led to construction of the heterocycles. In addition to some common heterocyclic compounds, other uncommon heterocycles such as pyrrolizidine, indolizidine, furofuran, dioxophospholane, β-carboline, benzoxathiin, fused heterocycles, and some seven membered heterocycles such as azepine, diazepine, and oxazepane are also reported starting with AGs and their derivatives. Hence, the main purpose of this review is to show the application of AGs in heterocyclic syntheses, all types of reactions, such as cyclocondensation, cycloaddition, Pictet− Spengler, and any sequences of other reactions such as Ugi− Wittig, Ugi cyclocondensation, aldol-Paal−Knorr, and Wittig dehydrative cyclization are included. The reactions in which AGs or their derivatives were produced in situ and then converted into heterocyclic compounds are also included. While the preparation of phenylglyoxal (PG) and its use date back to 1887, the synthesis of heterocyclic compounds using AGs and their derivatives have increased in recent years. So, about half of reviewed articles have been published in the past decade (2000−2011). This review has the aim of covering the literature up to the end of 2011, showing the distribution of publications involving use of arylglyoxals for preparing of heterocycles, which was elaborated using the Web of Science, ACS Publications, Wiley Online Library, Science Direct, RSC

Publishing, Thieme Chemistry, and other sites with the keywords phenylglyoxal, arylglyoxal, glyoxal, α-ketoaldehyde, and 1,2- or α-dicarbonyl compounds and from a selection of papers related to the synthesis of heterocyclic compounds starting with AGs and their derivatives. Some references are more recent that were available to us during the elaboration of this manuscript. We have arranged the data in terms of the type of heterocycle formed, starting with three-, four-, five-, six-, and seven-membered and miscellaneous rings in the heteroatom order of N, O, S, N,O, N,S, O,S, and O,P in the order of an increasing number of heteroatoms, that is, first with one heteroatom, two heteroatoms, and three heteroatoms.

2. ARYLGLYOXALS 2.1. Physical Properties and Reactivity of Arylglyoxals

Phenylglyoxal (PG),9 the simplest AG, is a yellow liquid that polymerizes upon standing. Upon heating, the polymeric material cracks to give back the yellow aldehyde. PG is recrystallized in hot water to form a colorless crystalline hydrate. The AG-hydrate appears to contain either one or onehalf molecule of water and presumably has the structure 1 or 2 (Scheme 1), which upon heating loses a molecule of water and regenerates the anhydrous AG. Scheme 1. Hydrate Forms of AG

The data of conformational analysis of PG, studied with gasphase electron diffraction, revealed that two carbonyl groups of PG are nonplanar with the torsional angle OCCO of about 130°. Moreover, the phenyl ring is nearly coplanar with the carbonyl group.10 AGs possessing adjacent aldehyde and ketone functional groups with different reactivity show interesting chemical properties. Due to existence of an electron-withdrawing ketone group, the reactivity of the aldehyde of AG is greater than that of benzaldehyde, a simple aromatic aldehyde. AG forms hydrate 1, which is unstable in the case of most simple aldehydes. Frequently, the aldehyde group of AG reacts rapidly with different nucleophiles, which then undergo cyclization either by the aldehyde group residue, which provides one atom of heterocycle along with producing an aroyl substituent on the obtained rings, or by ketone of AG to provide two atoms of the heterocyclic rings. In addition, AGs and AG-imines can act as dienophiles in [4 + 2] and [2 + 2] cycloaddition reactions via CO and CN bonds, respectively. In some cases, AGhydrates act as nucleophile via oxygen atom of OH group. Additionally, PG selectively modifies the amino acid arginine residues in proteins.11a AGs such as 4-hydroxy-3-hydroxymethylphenylglyoxal and 3,5-dihydroxyphenylglyoxal are used for preparation of selective bronchodilators such as salbutamol and terbutaline. Also, some AG-hydrates, such as 4-hydroxy-3B


Chemical Reviews

Review

Table 1. Synthesis of Arylglyoxals method oxidation of aryl methyl ketones

condition

prepared AG (Ar)

SeO2, dioxane−water, reflux

11b, 13

48% HBr (aq), DMSO, 55 °C, 0.5−24 h DMSO, rt, 9 h Et2NOH, MeOH, reflux, 2 h α-picoline N-oxide, 0 °C, then Na2CO3, water NaOAc·3H2O, DMSO, 20−25 °C, 25−55 min

Ph, 4-BrC6H4, 3-MeOC6H4, 4-PhC6H4, 2-naphthyl Ph 4-BrC6H4, 4-ClC6H4, 4-NO2C6H4, 4-PhC6H4

22 23 20

DMDO, acetone, rt

Ph, 2-furyl, 2-pyridyl, 3-pyridyl, 2-thienyl

21

(HMPA)MoO(O2)2, Hg(OAc)2, DCE-MeOH, 0 °C, 15 min NBS, dry DMSO, rt, 20 h (PhSe)2, (NH4)2S2O8, water−CH3CN, 60 °C, then chromatographed on SiO2, DCM-ROH (99/1) (1) DMSO, KOt-Bu, t-BuOH, rt, 4 h, then HCl, water, rt, 30 h; (2) Cu(OAc)2·H2O, CHCl3, rt, 1 h

Ph Ph ArCOCH(OH)OR: Ar = Ph, 4-BrC6H4, 4-MeOC6H4; R = Me, menthyl, i-Pr Ph, 4-BrC6H4, 4-MeOC6H4, 4-MeC6H4

24 25 26 17

piperidine-1-yl-COCH(OEt)2, p-Me2NC6H4Li, ether, reflux, 2 h, then HCl, water, N2 (atm.), rt, 41 h

p-Me2NC6H4

11b

1,3-Cl2-5,5-Me2hydantoin, Cu(OTf)2, CHCl3, reflux, 5−8 h

ArCOCHCl2: Ph, 4-BrC6H4, 4-ClC6H4, 4-FC6H4, 4-MeOC6H4, 3,4(MeO)2C6H3, 3,4,5-(MeO)3C6H2, 4-MeC6H4, 4-NO2C6H4, 2naphthyl

27

H2SeO3, dioxane−water, reflux, 4 h SeO2, EtOH, 10% HNO3 (aq), 90 °C, 1 h (PhSe)2, (NH4)2S2O8, MeOH, reflux, 1−4 h

oxidation of phenacyl bromide

oxidation of phenacyl nitrate esters oxidation of α-diazo ketones oxidation of aryl acetylene

reaction of methyl benzoate with KDMSO then oxidation reaction of organolithium compound with diethoxyacetylpiperidine chlorination of aryl methyl ketones

ref

Ph, 4-BrC6H4, 4-ClC6H4, 4-OHC6H4, 4-OH-3-MeOC6H3,4MeOC6H4, 3-MeOC6H4, 4-NO2C6H4, 4-AcNHC6H4, 4MeO2CC6H4, 4-HO2CC6H4, 2-furyl, 2-thienyl, 2,4,6-Me3C6H2 5-Me-2-furyl, 5-Me-4-NO2-2-furyl Ph ArCOCH(OMe)2: Ph, 2-OHC6H4, 4-MeC6H4, 4-NO2C6H4, 4PhC6H4, 2-furyl, 2-naphthyl, 2-thienyl, 3-thienyl 2-PhC6H4, 4-BrC6H4, 4-MeOC6H4, 4-NO2C6H4, 4-PhC6H4 Ph, 4-BrC6H4, 4-ClC6H4, 4-NO2C6H4, 4-PhC6H4

14 15 19 16 18

oxidation of corresponding α-diazo ketones by dimethyl dioxirane in 85−100% yields.21 Also, AGs were synthesized by reaction of phenacyl bromides with N,N-diethylhydroxylamine in MeOH under reflux conditions in 55−90% yields.22 Similar conversion of phenacyl bromide to PG using α-picoline N-oxide was reported. These methods offer a useful and mild nonoxidative route to AGs.23 p-Dimethylaminophenylglyoxal was prepared by the hydrolysis of its diethylacetal, which was prepared by the action of p-(Me2N)C6H4Li on diethoxyacetylpiperidine.11b PG was also prepared by oxidation of phenyl acetylene with metal−peroxide complex, (HMPA)MoO(O2)2, in the presence of Hg(OAc)2 in DCE at 0 °C,24 or by NBS induced DMSO oxidation of phenyl acetylene at room temperature.25 AG-hemiacetals were prepared by oxidation of terminal alkynes using (NH4)2S2O8 and (PhSe)2 as catalyst in aqueous media under heating at 60 °C, followed by purification with chromatography on silica gel using a mixture of 1:99 ROH−DCM as eluent.26 α,α-Dichloroketones, possessing similar structure with AG-hydrates, were readily synthesized by Cu(OTf)2-catalyzed α-chlorination of methyl ketones with 1,3-dichloro-5,5-dimethylhydantoin in CHCl3 under reflux condition in high yields.27 The methods to synthesize of AGs, along with experimental procedures and synthesized AGs are summarized in Table 1.

methoxyphenylglyoxal hydrate, 4-acetamidophenylglyoxal hydrate, and 2-furylglyoxal hydrate, show antiviral activity in the embryonated egg against several viruses, including influenza (PR-8) and Newcastle disease (NJKD strain) viruses.11b,c 2.2. Synthesis of Arylglyoxals

Various methods are reported in the literature for the production of AGs. PG was first prepared by thermal decomposition of the sulfite derivative of the PG-oxime.12 Oxidation of aryl methyl ketones by SeO2 is one of the most important methods for the preparation of AGs. Riley and coworkers13 dealt with the general aspect of this reaction and reported good efficiency of utilization of SeO2 for the formation of PG. Also, oxidation of aryl methyl ketones to AGs by selenious acid (H 2 SeO 3 ) was reported.14 Sharma and Chandalia15 reported the oxidation of acetophenone by aqueous HNO3 in the presence of SeO2 as a selective catalyst in a redox cycle, with a view to changing the use of SeO2 as a stoichiometric oxidizing agent. Floyd et al.16 described the synthesis of AG by the reaction of acetophenones with aqueous HBr in DMSO in good to high yields. Also conveniently, AG can be prepared from methyl benzoates by reaction with KCH2S(O)CH3 to give ArC(O)CH(SCH3)(OH), followed by oxidation with Cu(OAc) 2.17 Alternatively, oxidation of phenacyl bromides with DMSO at room temperature afforded AGs in 48−95% yields.18 Treatment of aryl and heteroaryl methyl ketones with catalytic amounts of (PhSe)2 and an excess amount of (NH4)2S2O8 in MeOH under reflux conditions afforded AG-acetals in 60−95% yields.19 Kornblum et al.20 reported the synthesis of AGs via nitrate esters in 82−86% yields. Nitrate esters were obtained by reaction of phenacyl bromide derivatives with silver nitrate in CH3CN and were converted to AGs using NaOAc in DMSO at room temperature. PG and some heteroarylglyoxals such as 2-furyl, 2-thienyl, 2-pyridyl, and 3-pyridylglyoxals were conveniently prepared by

3. SYNTHESIS OF THREE-MEMBERED HETEROCYCLES 3.1. Aziridines

Aziridines, the smallest saturated azaheterocycles, are structurally unique and possess many interesting chemical properties.28 They are versatile building blocks for the synthesis of diverse nitrogen-containing compounds,29 such as chiral amino acids,30 tetrahydropyridines, indolizidine, and alkaloids,31 via ringopening and ring-expansion reactions.32 Moreover, the aziridine moiety is present in a wide variety of natural biologically active C


Chemical Reviews

Review

compounds,33 such as antitumor and antibiotic agents,33c,34 and has been frequently found as a key structural unit in synthetic pharmaceuticals.35 Two of the most important methods for the synthesis of aziridines are the aziridination by carbene transfer to imines and the nitrene or nitrene equivalents transfer to olefins.36 Ring closure of amino alcohols,37 aminolysis of epoxides,38 functionalization of aziridines,39 and aza-Darzens reactions40 are among the other reported routes to preparation of aziridines. In this context, Akiyama et al.41 described the threecomponent synthesis of aroylaziridine 4 via enantioselective and stereoselective aza-Darzens reaction catalyzed by a chiral phosphoric acid 5 (Scheme 2). AG-imines 3, in situ generated

much attention has been paid to the development of new methods for the synthesis of epoxides such as epoxidation of alkenes,53 dehydrochlorination of chlorohydrins,54 and preparation from carbonyl compounds using sulfur ylides.55 There is one report on synthesis of oxirane starting from an AG in the literature, in which, Fuson et al.56 reported the synthesis of sym-dibenzoyloxirane 7 in low yield by the reaction of PG with phenacyl bromide 6 in 10% NaOH solution at room temperature for 15 min (Scheme 3). Also, sym-dibenzoyloxirane was synthesized by epoxidation of sym-dibenzoylethylene using 10% NaOH and NaOCl solutions. Scheme 3. Synthesis of sym-Dibenzoyloxirane 7

Scheme 2. Synthesis of Aroylaziridines 4 via Aza-Darzens Reactiona

4. SYNTHESIS OF FOUR-MEMBERED HETEROCYCLES 4.1. Azetidines and β-Lactams

The azetidine moiety is found in the structure of many natural products such as nicotianamine,57 medicanine,58 antifungal and antibiotic polyoxins,59 or pharmacologically important molecules, such as thrombin inhibitor melagatran,60 which exhibit a broad range of biological activities.61 2-Azetidinones, the βlactam skeletons, are the key structural element of the most widely used class of drugs for the treatment of bacterial infections.62 They exhibit a wide range of biological activities such as antidepressant,63 anti-inflammatory,64 anticancer,65 antimicrobial,66 antitubercular,67 cholesterol absorption inhibition,68 and antibiotic69 activity. Also, 2-azetidinones were employed as synthons for synthesis of many biologically important classes of organic compounds.70 However, there are different methods for construction of azetidine and β-lactam structures;71 Staudinger [2 + 2] cycloaddition of ketenes with imines is one of the most important routes to β-lactams.72 Accordingly, Pedrosa et al.73 described the synthesis of azetidin-3-ols 10 in 56−58% yields via Yang photocyclization reaction of perhydrobenzoxazines 9 that were prepared by heating of amino menthol derivatives 8 with AG-hydrate in toluene or benzene at reflux conditions. Transformation of 10 into the final azetidine derivatives 12 was achieved in five steps. The protection of the hydroxyl group as benzyl ether, followed by reductive ring-opening of the N,O-ketal moiety using in situ generated AlH3 by reaction of AlCl3 with LiAlH4 in THF at reflux conditions afforded the menthol derivatives 11. The overall yields for two steps are 80−82%. Oxidation of 11 with PCC in the presence of 3 Å MS in DCM at room temperature for 5−12 h resulted in 8-aminomenthone derivatives, which, without isolation, were treated with KOH in THF−MeOH− H2O (2:1:1) at room temperature for 6−8 days to give azetidine derivatives that were isolated as N-tosyl derivatives 12 by treatment with TsCl and DIPEA in EtOAc at room temperature for 3 days followed by addition of 15% HCl solution. The overall yields for three steps are 25−31% (Scheme 4). Tanaka et al.74 described the stereoselective synthesis of 4benzoyl-3-vinylazetidin-2-ones 14 via Pd-catalyzed carbonylation of an allyl phosphate 13 in the presence of PG-imines 3 and c-Hex2NMe, a tertiary amine, under CO pressure in 50−

a

Ar = Ph, 4-BrC6H4, 4-ClC6H4, 4-FC6H4, 4-CF3C6H4, 4-MeOC6H4, 4MeC6H4, 4-biphenyl, 1-naphthyl, 2-thienyl; 91−100%; ee = 92−97%.

from AG-hydrates and p-anisidine in the presence of 5 and MgSO4 in toluene at room temperature, underwent aziridination by addition of α-diazoacetate at −30 °C to furnish 4 in 91−100% yields with 92−97% ee. The stereochemistry of 4 was determined as cis using 1H NMR technique, and the trans isomer was not observed. At the same condition, aziridination did not occur with aldimine derived from benzaldehyde and panisidine. Also, one example of the Yb(OTf)3 catalyzed three component reaction of PG with diphenylmethylamine and αdiazoacetate in the presence of 4 Å MS in hexane at room temperature was reported to afford the corresponding aziridine in 85% yield with high stereoselectivity (syn/anti = 94/6).42 3.2. Oxiranes

Oxiranes (epoxides), the smallest oxygen-containing saturated heterocycles, are broadly found in many natural products, such as azinomycins A and B,43 cryptophycin A and B,44 triptolide and triptonid,45 epoxomicin,46 and psorospermin,47 which exhibit biological activity such as antitumor,45,48 antileukemic,49 anti-inflammatory,50 and immunosuppressive51 activities. Also, epoxides are among the most versatile intermediates in organic synthesis because they can be converted into highly valuable products via ring-opening or rearrangement reactions.52 Thus, D


Chemical Reviews

Review

Scheme 4. Synthesis of Azetidin-3-ols 12

63% yields with high syn selectivity. Different reaction conditions were examined and 2 mol % Pd2dba3CHCl3, 8 mol % Ph3P, and 1 mmol of c-Hex2NMe under 30 kg cm−2 pressure of CO for 0.5 mmol of PG-imine, and 0.75 mmol of 13 in THF at room temperature was selected as optimum condition. In the case of 3 with R = 4-MeOC6H4 and R = n-Pr, only cis isomer was obtained. Treatment of benzoyl lactam 14a with PhSiH3 in the presence of 5 mol % Co(acac)2 under an O2 atmosphere in THF at room temperature for 3 h resulted in the formation of hemiacetal 15, a useful intermediate for the synthesis of carbapenams (Scheme 5).

Scheme 6. Synthesis of 4-Benzoylazetidin-2-one 18 and 19 via Staudinger Cycloaddition Reactiona

Scheme 5. Stereoselective Synthesis of 4-Benzoylazetidin-2ones 14 a For a, ∗ = (R); SiR3 = Si(i-Pr)3; conditions DIPEA, −20 °C, 83%, 18a/19a = 20/80. For b, ∗ = (S); SiR3 = SiMe2Ph; conditions Et3N, 40 °C, 75%, 18b/19b = 75/25.

19b in 75% yield via Staudinger [2 + 2] cycloaddition reaction of ketene 17b derived from (S)-3-(dimethylphenylsilyloxy)butanoyl chloride 16b with PG-imine 3. The reaction was carried out in the presence of Et3N in DCM at 40 °C for 20−24 h (Scheme 6). Also, the synthesis of α-phenylthio-β-lactams 22 as only cis isomer was reported through [2 + 2] cycloaddition reaction of PG-imines 3 with ketene, which was in situ prepared from a mixture of the potassium salt of (phenylthio)acetic acid, Et3N, and cyanuric chloride 20 in CCl4 at room temperature via intermediate 21. The benzoyl substituent in 3 obviously influences the syn-stereoselectivity on β-lactam formation (Scheme 7).77 There are other reports on the construction of 4-benzoyl-βlactam ring via [2 + 2] cycloaddition reaction of PG-imines with ketene generated in situ by reaction of propionyl chloride78 or arylacetyl chloride79 with Et3N in DCM.

As shown in Scheme 6, a diastereoselective route to synthesis of the carbapenem antibiotic intermediates 18a and 19a was developed by Lynch and co-workers75 via the reaction of PGimine 3 and acid chloride 16a. The reaction was carried out in the presence of DIPEA in DCM at −20 °C for 16 h to give cis 4-benzoylazetidin-2-ones 18a and 19a in a 1:4 ratio via ketene intermediate 17a. Palomo et al.76 reported the similar procedure for synthesis of 4-benzoylazetidin-2-ones 18b and

4.2. β-Lactones

β-Lactones are attractive intermediates in natural product and polymer synthesis.80 The important reactions of β-lactones involve ring opening, including polymerization, to yield poly(βhydroxyalkanoate)s (PHAs).81 The most important routes to synthesize β-lactones are nucleophile-catalyzed aldol-lactonizations and Lewis acid-catalyzed [2 + 2] cycloadditions.80c,82 E


Chemical Reviews

Review

Scheme 7. Synthesis of α-Phenylthio-β-lactams 22 via [2 + 2] Cycloaddition Reaction

5. SYNTHESIS OF FIVE-MEMBERED HETEROCYCLES 5.1. N-Heterocyclic Compounds

5.1.1. Pyrrolidines and Pyrrolines. Pyrrolidines are an important class of heterocycles found in numerous natural products,84 pharmaceuticals,85 and bioactive molecules86 with antibacterial, antifungal, and cytotoxic activities.87 They also serve as neuroexcitatory agents,88 antibiotics89 and glycosidase inhibitors.90 They have a wide range of applications as organocatalysts,91 building blocks in organic synthesis,92 chiral auxiliaries, and ligands for asymmetric synthesis.93 Many syntheses of pyrrolidines have been reported.94 Additionally, pyrrolines are common structural scaffolds in natural products and pharmaceutical agents95 that exhibit biological activity96 and serve as useful synthetic intermediates97 especially in the synthesis of biologically active pyrroles and pyrrolidines.98 There are different methods for construction of pyrroline derivatives.98,99 As shown in Scheme 9, Pedrosa and co-workers100 described the synthesis of 3-phenyl-1-tosyl-4-vinylpyrrolidin-3-ols 30 in six steps, starting from PG and (−)-8-aminomenthol 26. By condensation of PG with 26 in DCM at room temperature 2benzoyl-1,3-oxazine 27 was obtained in quantitative yield. A mixture of diastereomeric 3-hydroxypyrrolidines 28a,b or 28a′,b′ were formed by alkylation of 27 with prenyl or crotyl bromide in the presence of K2CO3 in refluxing acetonitrile, followed by carbonyl−ene reaction under thermal conditions. Different thermal conditions were examined, and in the case of N-crotyl derivative (R = H), the best results were obtained when reaction was carried out in xylene under reflux conditions for 218 h; the corresponding 3-hydroxypyrrolidines 28a,b were obtained in 80% yield with 88:12 ratio of 28a/28b. But in the case of N-prenyl derivative (R = Me), reaction at 170 °C for 21 h without using any solvent afforded the 3-hydroxypyrrolidines 28a′,b′ in 80% yield with 75:25 ratio of 28a′/28b′. The conversion of 28a,a′ into mentone derivatives 29a,a′ was achieved by reductive ring opening of 28a,a′ with AlH3, in situ generated by treatment of AlCl3 with LiAlH4, in THF at −10 °C for 10 min, followed by oxidation with PCC in the presence of 4 Å MS in DCM at room temperature for 6−8 h. Mentone derivatives 29a,a′, without isolation, were converted into the final pyrrolidines 30 by elimination with KOH in H2O− MeOH−THF (1:1:2) at room temperature and tosylation with TsCl in the presence of DIPEA in EtOAc at room temperature for 36 h. The overall yields for three last steps are 39−45%. A similar procedure using different AGs, such as p-Me-, pMeO-, o-NO2-, or p-NO2-PG, was reported by Andrés et al.101 in which the keto−ene cyclization sequence was investigated using different Lewis acids. The best results were obtained when 1.5 equiv of Me2AlCl or Et2AlCl in DCM was used. The 1,3-dipolar cycloaddition reaction of azomethine ylides 33, derived from N-(cyanomethyl)- and N-(α-cyanobenzyl)imines 32, with N-methylmaleimide 34 or dimethyl fumarate 35, was described in refluxing CHCl3 (Scheme 10). Reactions were conducted via in situ generation of imines 32 by the reaction of PG with 31 in CHCl3 under heating conditions followed by adding of dipolarophiles 34 or 35 to furnish corresponding pyrrolidines 36 or 37 in quantitative yields with endo/exo ratio of 100/0. Pyrroline 38 was obtained in quantitative yield when 36b was chromatographed over silica gel with CHCl3−Et2O (3:1) via elimination of HCN.102 The synthesis of N-substituted 4-cyano-2,5-dihydro-5oxopyrrole-2-carboxamides 40 was reported by Bossio et

In this context, the synthesis of β-lactones 25 was reported by He et al.83 via chiral N-heterocyclic carbene 23b catalyzed enantioselective [2 + 2] cycloaddition reactions of alkyl(aryl)ketenes 24 with AGs (Scheme 8). Treatment of AGs with Scheme 8. Chiral NHC Catalyzed Synthesis of β-Lactones 25a

a

Ar′ = Ph, 2-ClC6H4, 4-ClC6H4; Ar′-R = (CH2)6; R = Et, i-Pr, Ph; Ar = Ph, 4-BrC6H4, 4-MeOC6H4, 4-MeC6H4, 1-naphthyl, 2-naphthyl; 55−99%, dr (trans/cis) = 80−100%; ee = 4−99%.

different ketenes 24 in the presence of NHC 23b (10−12 mol %) in THF at room temperature and stirring overnight afforded 25 in 63−99% yields with 4−99% ee. AGs having electrondonating groups as well as electron-withdrawing substituents worked well and the corresponding β-lactones 25 were obtained in high yields with excellent diastereo- and enantioselectivities. The symmetric cyclic ketene, cycloheptylidenemethanone, gave the corresponding β-lactone in only 63% yield with very low enantioselectivity (4% ee). NHC 23b was generated in situ from the action of Cs2CO3 on triazolium salt 23a in THF at room temperature in 1 h. Under similar conditions, the cycloaddition reaction of ethyl(2chlorophenyl)ketene with 4-chlorobenzaldehyde did not afford the corresponding β-lactone. F


Chemical Reviews

Review

Scheme 9. Synthesis of Pyrrolidin-3-ols 30 via Carbonyl−Ene Reactiona

a

a, R = H; a′, R = Me.

5-methoxypyrrole-2-carboxamides 41 were obtained in 73− 89% yields (Scheme 11).

Scheme 10. Synthesis of Pyrrolidines 36 and 37 via 1,3Dipolar Cycloaddition Reaction

Scheme 11. Synthesis of 4-Cyano-5-oxodihydropyrroles 40 via Ugi Reactiona

a

R = c-Hex, n-Hex; Ar = Ph, 4-ClC6H4; Ar′ = Ph, 3-ClC6H4, 4ClC6H4, 4-MeC6H4; 40, 40−60%; 41, 73−89%.

Beck et al.104 described the synthesis of highly substituted 5oxo-2,5-dihydro-1H-pyrrole-2-carboxamides 44 via four-component reaction of AGs, isocyanides, primary amines, and phosphono acetic acids 42 in MeOH at room temperature to afford Ugi products 43, followed by Wittig ring-closing reaction [using the Horner/Wadsworth/Emmons variant (HWE)] using 10 equiv of Et3N as base in the presence of 4.5 equiv of LiCl in THF at room temperature for 12 h (Scheme 12). 5.1.2. Pyrroles. Pyrroles are an important class of heterocycles that are broadly found in natural products,105 pharmaceuticals,106 and bioactive molecules107 and also used in material science.108 Many methods have been developed for pyrrole synthesis,109 which include Knorr, Paal−Knorr, and Hantzsch syntheses and 1,3-dipolar cycloaddition reactions. Trost et al.110 reported the synthesis of two isomeric pyrroles, 1-benzyl-2-phenylpyrrole 50 and 1-benzyl-3-phenyl-

al.103 via Ugi reaction among AGs, anilines, isocyanides, and cyanoacetic acid. The reactions were carried out by in situ generation of AG-imines 3, via reaction of AGs with anilines in toluene at reflux conditions by removal of water using a Dean− Stark apparatus, followed by stirring with isocyanides and cyanoacetic acid in Et2O at room temperature for 6 days to give Ugi adducts 39. The obtained mixture was treated with Et3N in EtOH to afford 40 in 40−60% yields. By treatment of a saturated solution of 40 in CHCl3 with a large excess of CH2N2 in Et2O and stirring at room temperature for 10 h, the 4-cyanoG


Chemical Reviews

Review

Scheme 12. Synthesis of Dihydropyrroles 44 via Ugi−HWE Reactionsa

Scheme 13. Synthesis of Two Isomeric Pyrroles 46 and 47

a

R = allyl, t-Bu, c-Hex, MeO2CCH2, PhCH2CH(CO2Me), 2pyridylCH2; R′ = Bn, n-Pentyl, i-Pentyl, n-Pr, c-Pr, Me3CCH2CH2, BocNHCH2CH2CH2, 3,4-(MeO)2C6H3CH2CH2; R″ = H, Ph; Ar = Ph, 4-MeOC6H4, 3,4-(MeO)2C6H3, 4-morpholino-C6H4, 4-biphenyl, 2-naphthyl; 7−95%.

pyrrole 51, by cyclization of 1-phenyl-2-acetoxy-3-buten-1-one 47 and 2-acetoxy-2-phenyl-3-butenal 49 with benzylamine in the presence of a catalytic amount of Pd(PPh3)4 in dry THF under reflux conditions in 65% and 9% yields, respectively. The PG-ketal 46 was prepared from α,α-dichloroacetophenone 45 upon treatment with methanolic NaOMe. By Grignard addition of vinylmagnesium bromide to 46 and acetylation of the resultant alcohol using Ac2O in the presence of DMAP in dry pyridine at room temperature and finally by deketalization using a few drops of 60% aqueous solution of HClO4 in acetone, 47 was obtained. Alternatively, 49 was obtained by Grignard addition of vinylmagnesium bromide to PG-acetal 48 in THF at room temperature, followed by hydrolysis with pTsOH in acetone, and then acetylation using Ac2O in the presence of DMAP and pyridine in DCM (Scheme 13). PGacetal 48 is readily available by direct acetalization of PG. The synthesis of 3-hydroxypyrroles 54 via reaction of enamino esters and nitrile 52 with PG-hydrate was investigated by Feliciano et al.111 (Scheme 14). The reaction was conducted in refluxing MeOH to afford corresponding 3-hydroxypyrroles 54 in 52−62% yields. In the proposed reaction mechanism, C3−C4 bonds of the pyrroles were formed by nucleophilic addition of enamino esters 52, through the C atom, to the aldehyde group of PG; then by regeneration of the enamine, intermediates 53 were produced. By condensation of the amino group with the ketone along with removal of a molecule of water, intermediates 53 were converted into the corresponding pyrroles 54. 3-Hydroxypyrroles 54 were acetylated to acetate 55 using Ac2O in pyridine at room temperature. A similar reaction was carried out using N-hydroxyalkyl substituted enamino methyl esters 56a,b in MeOH under reflux conditions, which resulted in pyrrolinones 57a,b in 45−60% yields, while corresponding 3-hydroxypyrroles 58a,b were not isolated. This can be attributed to the formation of hydrogen bonds between the hydroxyl group of hydroxyalkyl substituent and the carbonyl group of the pyrrolinone, which induced relative stabilization to pyrrolinones 57a,b. Unlikely, steric hindrance between the hydroxyalkyl substituent and the phenyl group at the C2-position of pyrroles induced destabilization to the 3-hydroxypyrroles 58a,b. This statement was proven when reaction was carried out using unsubstituted enamino ester 57c, in which 5-phenyl-4-hydroxypyrrole 58c was isolated as the

Scheme 14. Synthesis of 3-Hydroxypyrroles 54 Using Enamino Esters and Nitrilea

a

Y = CO2Me, CO2Et, CN; 54, 52−62%.

only product. However, the 2-pyrrolin-5-one 57c was detected as initial product of the reaction, but converted into 58c at room temperature via equilibrium with starting materials and recombination to 58c. Interestingly, the reaction with methyl 3p-tolylaminocrotonate 56d resulted to methoxypyrrole 59 in 30% yield, via intermediate 57d, by addition of MeOH to the carbonyl group of pyrrolinone 57d, followed by lose of a molecule of water (Scheme 15).112 Khalili and co-workers113 described a new interesting onepot method for synthesis of 2-alkyl-5-aryl-(1H)-pyrrole-4-ols 60 via three-component reaction of 1,3-dicarbonyl compounds with AGs in the presence of an excess amount of NH4OAc in water at room temperature. The reaction mixture solidified rapidly (in 10−30 min) and afforded 60 in 20−98% yields (Scheme 16). β-Ketoesters and acetylacetone worked well in H


Chemical Reviews

Review

Scheme 15. Synthesis of Pyrrolines 57 Using N-Hydroxyalkyl Enamino Esters

Scheme 16. Synthesis of 3-Hydroxypyrroles 60a

Scheme 17. Synthesis of Pyrrole-3-ols 64 via Aldol-Paal− Knorr Reaction Sequencea

a

R = Me, n-Pr; R' = Ot-Bu, OEt, OMe, Me; Ar = Ph, 4-BrC6H4, 4ClC6H4, 4-FC6H4, 4-MeOC6H4, 4-biphenyl; 60, 20−98%.

a

this reaction, but in the case of 1,3-dicarbonyl compounds possessing phenyl substitution at the carbonyl group, those were recovered and 4- or 5-aryl-2-aryloyl-(1H)-imidazole 61 was obtained as a two-isomer mixture via condensation of two molecules of PG with NH4OAc. Also, the similar threecomponent reaction was carried out under ultrasound irradiation to afford the corresponding pyrroles 60 in high yields in very short reaction times.114 The Vilsmeier−Haack reaction of 60 (R = R′ = Me) with POCl3/DMF was investigated, and indole-5,7-dicarbaldehydes were obtained in 31−53% yields.115 Recently, we reported a method to synthesize N-alkyl(aryl)2,4-diaryl-2-methyl-1H-pyrrole-3-ol derivatives 64 in 61−82% yields via an aldol-Paal−Knorr reaction sequence (Scheme 17). 1,4-Dicarbonyl compound 63 was synthesized in 89% yield via aldol reaction of 1-(p-methoxyphenyl)propan-2-one 62 with PG-hydrate in the presence of a catalytic amount of DABCO in water at room temperature. Then conversion of 63 to various fully substituted pyrroles 64 was performed by refluxing a solution of primary amines and 63 in toluene in the presence of a catalytic amount of p-TsOH.116 A facile route for the synthesis of 3-methylthio-substituted pyrroles 67 was developed by Yin et al.117 starting from

acetophenones (Scheme 18). A plausible reaction mechanism involves the formation of AGs by DMSO-induced oxidation of α-iodoacetophenones, which were in situ generated by iodination of acetophenones by action of CuO and I2, and then conversion into 2-(methylthio)-1,4-diaryl-2-butene-1,4diones 66 in 65−94% yields via aldol-type reaction with sulfur ylides 65, followed by loss of MeI and then dehydration. The Zor E-isomer of 66 was reacted with KI and conc. HCl in acetone at room temperature to give saturated 1,4-diketones, which were transformed to the corresponding pyrroles 67 in 80−92% yields when heated in the presence of ammonium formate in AcOH under reflux conditions for 2−4 h. As shown in Scheme 19, a three-component reaction between dialkyl acetylenedicarboxylates (DAAD), anilines, and AGs to synthesize polysubstituted pyrrole derivatives 69 was described by Anary-Abbasinejad et al.118 The reaction was carried out by addition of AGs to a mixture of DAAD, Ph3P, and an aniline derivative in DCM at room temperature to afford 69 in 84−90% yields. It is illustrated that ylide 68 was produced in situ as a reaction intermediate and underwent Wittig reaction with the AG, which then cyclizes to 69 by losing a molecule of water. I

R = Bn, n-Pr, Ph, 4-ClC6H4, 4-MeOC6H4; 61−82%.


Chemical Reviews

Review

Quiroga et al.119 reported the three-component reaction between dimedone 70, 6-aminopyrimidines 71, and AGs to synthesize fused pyrido[2,3-d]pyrimidines 75. Reaction was conducted by heating of the equimolar amounts of AG, 70, and 71 in EtOH in the presence of a catalytic amount of AcOH for 9 h. Interestingly, the unexpected cyclization process led to pyrrolo[2,3-d]pyrimidine derivatives 72−74 in 38−60% yields (Scheme 20). Also, the three-component condensation of an enaminone with PG and morpholine leading to tetrahydroindoles was reported.120 By reaction of N-silyl-1-azaallyl anion 77 with PG in THF at −75 °C for 1 h, then warming to room temperature for 2 h under N2 atmosphere, followed by reduction with NaBH4 at room temperature and then treatment with conc. HCl, 2Hpyrrole 78 was obtained in 21% yield. When reduction was carried out using LiAlH4 under reflux conditions, 2H-pyrrole 78 and pyrrole 79 were obtained in 20% and 44% yields, respectively.121 N-Silyl-1-azaallyl anion 77 was prepared by reaction of benzonitrile and 2-(trimethylsilyl)methyl pyridine 76 in the presence of a base such as LDA or n-BuLi in THF at −75 °C (Scheme 21).122 5.1.3. Pyrrolizidines, Pyrrolizines, and Indolizidines. Bridgehead nitrogen heterocycles are of interest because they constitute an important class of natural and unnatural products,123 which display biological and pharmacological activities,124 and are important as precursors in the synthesis of many biologically active compounds. Consequently, there has been an ongoing interest in the synthesis of pyrrolizidine,125 pyrrolizines,126 and indolizidine127 heterocycles. Accordingly, Felluga et al.128 recently reported the reaction of PG with β-nitrostyrene 80 and an equimolar amount of Lproline 81 in i-PrOH at room temperature that gives substituted pyrrolizidine 82 in 80% yield as a single regioisomer. The reaction mechanism involves the in situ generation of 1,3-azomethine ylide 83 derived from PG and 81 by decarboxylation, then 1,3-dipolar cycloaddition reaction with 80 (Scheme 22).

Scheme 18. Synthesis of 3-Methylthiopyrroles 67a

a

Ar = Ph, 4-MeOC6H4, 4-MeC6H4, 2-benzofuryl, 2-thienyl; 80−92%.

Scheme 19. Synthesis of Pyrroles 69 via Wittig−Dehydrative Cyclization Reactionsa

a

R = t-Bu, Et, Me; Ar = 4-BrC6H4, 4-NO2C6H4; Ar′ = Ph, 4-ClC6H4, 4-MeC6H4; 84−90%.

Scheme 20. Synthesis of Pyrrolo[2,3-d]pyrimidines 72−74

J


Chemical Reviews

Review

Scheme 21. Synthesis of 2H-Pyrrole 78 and Pyrrole 79 via Azaallyl Anion 77

Scheme 23. Synthesis of Dihydropyrrolizines 86−88

Scheme 22. Synthesis of Pyrrolizidine 82 via 1,3-Dipolar Cycloaddition Reaction

due to their occurrence in a number of biologically active molecules131 with antibacterial, antiviral,132 antiamoebic, antidiabetic,133 antitumor,134 anti-inflammatory,135 antidepressant,136 and MAO-inhibitory activities. In addition pyrazolines possess important applications as dyestuffs, analytical reagents, and agrochemicals.137 Pyrazolines are synthesized by the condensation/addition of hydrazines onto α,β-unsaturated carbonyl compounds138 and cycloaddition of azomethine imines with alkynes.139 Additionally, pyrazoles are a motif found in a number of small molecules that possess a wide range of agricultural and pharmaceutical activities such as herbicidal, fungicidal, insecticidal, analgesic, antipyretic, and anti-inflammatory properties.140 Also they have applications in supramolecular and polymer chemistry and as ligands for transition metal-catalyzed reactions.141 Conventional approaches for the preparation of substituted pyrazoles involve either condensation of hydrazines with 1,3-dicarbonyl compounds or 1,3dipolar cycloaddition reactions.142 Del Buttero et al.143 described a route for synthesis of dihydropyrazoles 97 via 1,3-dipolar cycloaddition of 3(R)phenyl-4(S)-(4-benzoyl-E,E-1,3-butadienyl)-2-azetidinone with nitrilimines 99, in situ generated by reaction of hydrazonoyl chloride 98 with 1 equiv of AgOAc in dioxane at room temperature (Scheme 25). Reaction was carried out in the dark for 24 h to afford a complex mixture of the four isomeric dihydropyrazoles 97 via site-selective and regioselective but not stereoselective cycloaddition. The 2-azetidinone derivative was prepared in 48% yield by a three-step synthetic sequence as outlined in Scheme 25. By treatment of PG with (triphenylphosphoranylidene)-acetaldehyde 95 in Wittig reaction, followed by reaction with p-anisidine in EtOH at room temperature for 5 min, imine derivative 96 was obtained, which was converted into 2-azetidinone by reaction with phenylacetyl

Treatment of 2-nitromethylenpyrrolidine 84 with PG in EtOAc at room temperature for 2 h gave product 85 in 92% yield, which transformed to substituted dihydro-1H-pyrrolizines 86 by heating in various alcohols in the presence of conc. HCl in 75−87% yields. Interestingly, by heating of 85 in molten phenol in the presence of HCl, nucleophilic substitution occurred at C-4 of phenol, and 4-hydroxyphenyl substituted pyrrolizines 87 were obtained in 41% yield. Cyclization reaction in a 2,2,2-trifluoroethanol/HCl solution afforded the chloro derivative 88 in 88% yield (Scheme 23).129 Grigg et al.130 described the 1,3-dipolar cycloaddition reaction between N-methylmaleimide 34 and azomethine ylides, which were in situ prepared by condensation reaction of PG with α-amino esters 89−91 (Scheme 24). The reaction was conducted by heating of a solution of 89−91, PG, and 34 in CH3CN or dry DMF at 80 or 120 °C, respectively. Reaction of 89 and 90 in refluxing CH3CN afforded single cycloadducts pyrroloisoquinoline 92 and indolizinoindole 93 in 78% and 73% yields, respectively, while in the case of the reaction between 91, PG, and 34 in DMF at 120 °C for 16 h, pyrrolothiazole 94 was obtained in 73% yield with a 2.7/1/1 ratio of 94a/94b/94c cycloadducts. 5.1.4. Pyrazolines and Pyrazoles. Pyrazolines are one of the most important five membered heterocyclic compounds, K


Chemical Reviews

Review

Scheme 24. Synthesis of Pyrroloisoquinoline 92, Indolizinoindole 93, and Pyrrolothiazole 94 via 1,3-Dipolar Cycloaddition Reaction

Scheme 25. Synthesis of Dihydropyrazoles 97 via 1,3-Dipolar Cycloaddition Reactiona

a

Ar = 4-MeC6H4, 4-BrC6H4.

under heating at 110 °C for 1 h. 3-Benzoyl-4-hydroxy-5phenylpyrazoles 103 were obtained, when the reaction was performed in the presence of water, by cyclocondensation of PG with PG-hydrazones 102, which were generated in situ by transhydrazonation of PG with 100 (Scheme 26). To prove this statement, oxohydrazones 102 were prepared separately and

chloride in the presence of Et3N in DCM in the Staudinger [2 + 2] cycloaddition reaction. Begtrup et al.144 reported the synthesis of 4-hydroxypyrazoles 101 in 15−86% yields via reaction of aldehyde hydrazones 100 with PG under anhydrous conditions in n-BuOAc containing AcOH in the presence of MgSO4. Reactions were performed L


Chemical Reviews

Review

treated with PG under same reaction conditions and produced the corresponding benzoylpyrazoles 103.

Scheme 27. Synthesis of Pyrazole 107 and Pyridazinone 110

Scheme 26. Synthesis of 4-Hydroxy-5-phenylpyrazoles 101 and 103a

a

R = Me, Ph; R′ = H, Me, Ph; 101, 15−86%; 103, 52−100%.

Meanwell et al.145 reported the Wittig reaction of the Horner−Wadsworth−Emmons type reagents, phosphonates 104, with PG in the presence of NaOEt to produce C-5 unsaturated hydantoin derivatives 105a,b in 89−100% yields. The spiro substituted pyrazoline 106 was obtained in 85% yield by treatment of 105a with hydrazine in EtOH at room temperature. Pyrazoline 106 was transformed to pyrazole 107 in 77% yield when heated in AcOH under reflux conditions for 4.5 h. The compound 105b was converted to pyridazinone 110 by reduction using zinc in AcOH, followed by treatment of 108 with an excess amount of hydrazine in ethanol, then by loss of an urea molecule from 109 (Scheme 27). 3-Benzoyl-4-phenyl-1-methylpyrazole 114 was synthesized by condensation of PG with protected 1-methyl-1-phenacylhydrazine 111 in the presence of AcOH in EtOH, followed by treatment with 75% H2SO4 at room temperature for 2 weeks. By reaction of 111 with PG, hydrazone 112 was produced, which underwent deketalization to 113 in treatment with 75% H2SO4 and then intramolecular condensation to yield 114 in 56% yield. Aldol type condensation of the methylene with the carbonyl group of PG to produce 5-benzoyl-4-phenyl-1methylpyrazole 115 did not occur (Scheme 28).146 A similar reaction was reported using phenyl-, p-bromophenyl-, and pmethylphenylglyoxals to furnish the corresponding 3-aroylpyrazoles.147 5.1.5. Imidazolidin-2,4-diones and Imidazolin-2-ones. Imidazolin-2-one and imidazolidin-2,4-dione (hydantoin) derivatives have received great attention because of their interesting biological activities,148 such as antioxidant,149 cardiotonic,150 herbicidal,151 aldose reductase inhibitors,152 antitubercular,153 antitumor,154 antiarrhythmics,155 anticonvulsants,156 anti-inflammatory,157 and antiandrogens activity.158 There are many known methods in the literature for the synthesis of imidazolin-2-ones159 and hydantoins160 via reaction of carbodiimides with α-bromoaryl acetic acids,160c α-amino amides with triphosgene,160d and α-amination process of esters.160e Paul et al.161 developed a facile and efficient microwaveinduced solvent-free synthesis of 1,5-disubstituted hydantoins and thiohydantoins 117 in 80−95% yields via condensation of the AGs with phenylurea or phenylthiourea 116 using

Scheme 28. Synthesis of 3-Benzoylpyrazole 114

polyphosphoric ester (PPE) as a reaction mediator (Scheme 29). Also, the synthesis of 117 using PPE under neat conditions was investigated using an oil bath (3 min and 120 °C), in which the yields were low in comparison to microwave irradiation. The advantages of this protocol include a simple reaction setup, high product yields, short reaction times, and elimination of solvents and acid. A similar reaction was carried out using a fluorine containing AG, 2,4-dichloro-5-fluorophenylglyoxal, with different arylureas M


Chemical Reviews

Review

Scheme 29. Synthesis of Hydantoins and Thiohydantoins 117 via Condensation of Urea Derivatives with AGa

Scheme 30. Synthesis of 1,3,4-Thiadiazol-2-yl Substituted Hydantoin 120

a

R, R′ = c-Hex, H, Ph, 4-BrC6H4, 3-ClC6H4, 4-ClC6H4, 3,4-Cl2C6H3, 4-HOC6H4, 3-IC6H4, 4-IC6H4, 4-MeOC6H4, 4-MeC6H4, 4-MeCONHC 6 H 4 , 3-NO 2 C 6 H 4 , 4-NO 2 C 6 H 4 , 2,4-(NO 2 ) 2 C 6 H 3 , 4HO3SC6H4; Ar = Ph, 4-BrC6H4, 4-ClC6H4, 2,4-Cl2-5-FC6H2, 2-Cl-4FC6H3, 3-Cl-4-FC6H3, 4EtOC6H4, 4-FC6H4, 2-F-5-MeC6H3, 4-F-3MeC6H3, 3-F-4-MeOC6H3, 2,4-F2C6H3, 4-MeC6H4, 4-MeOC6H4, 4NO2C6H4; X = O, S; ref 161, cond. = PPE, MW, 2.5−3.5 min, 80− 95%; ref 162, cond. = acidic alumina, MW, 7−10 min, 9−95%; ref 163, cond. = HCl−AcOH, EtOH, reflux, 4 h, 59−85%; ref 164, cond. = HCl−AcOH (15/0.5), reflux, 4−10 h, 59−64%; ref 165, cond. = 50% KOH, reflux, 3 min, 26−85%.

or arylthioureas 116 under microwave irradiation on acidic alumina as a solid support, and the corresponding hydantoins or thiohydantoins 117 were obtained in 9−95% yields in short reaction times. Also, the synthesis of 117 was investigated using acidic alumina under conventional heating (80−100 °C), in which 117 was formed in poor yields in long reaction time. The antibacterial activity of the products against Escherichia coli and Streptococcus was investigated, and compounds having 4-Cl, 4Me, and 2,4-(NO2)2 substitutions exhibited the highest degree of inhibition.162 Also, the synthesis of fluoroaryl containing hydantoins 117 was reported by condensation of 116 with fluoroarylglyoxals, 4F-, 2-Cl-4-F-, 3-Cl-4-F-, 2-F-5-Me-, 4-F-3-Me-, 3-F-4-MeO-, and 2,4-F2-phenylglyoxal, using HCl−AcOH as catalyst in refluxing absolute EtOH. The corresponding hydantoins 117 were obtained in 59−85% yields.163 Also, Muccioli and co-workers164 described the synthesis of 1,5-diaryl- and 1,3,5-triarylhydantoin derivatives 117 in 59− 64% yields. The 1,5-diphenyl derivatives were synthesized by refluxing a mixture of PG and 116 for 4 h in glacial AcOH in the presence of HCl. Also, 1,3,5-triphenyl derivatives were obtained using 1,3-diarylurea or 1,3-diarylthiourea by the same procedure. 1,3-Dicyclohexyl-5-phenylhydantoin was synthesized from 1,3-dicyclohexylurea and PG. The 1,3,5-triphenylhydantoin derivatives and their thio isosteres exhibited interesting affinity and selectivity for the human CB 1 cannabinoid receptor. Also, the condensation reactions of PG with urea, phenyl urea, and methyl urea were carried out in basic solution under thermal conditions.165 As outlined in Scheme 30, one example of the condensation of PG-hydrate with urea having 5-t-butyl-1,3,4-thiadiazol-2-yl substituent 118 was reported using aqueous NaOH in EtOH at room temperature to afford dihydroxyimidazolidin-2-one 119, which was converted to the corresponding hydantoin 120 by refluxing in the presence of p-TsOH in CH3CN in 87% yield. Treatment of hydantoin 120 with NaBH4 in EtOH afforded the 4-hydroxyimidazolidin-2-one 121 in 76% yield as only trans isomer.166 Shtamburg et al.167 reported the condensation reaction of AG-hydrate with N-hydroxyurea 122 in water via 3,4,5trihydroxy-5-arylimidazolidin-2-ones 123b as reaction intermediate, which underwent intramolecular proton transfer resulting in zwitterion 123c, followed by removal of a molecule

of water by hydride rearrangement to yield 5-aryl-3hydroxyhydantoins 124 in 46−77% yields (Scheme 31). The reaction was carried out by addition of AG-hydrate to the solution of 122 in water at room temperature. Scheme 31. Synthesis of 3-Hydroxyhydantoins 124a

a

Ar = Ph, 4-ClC6H4, 4-MeC6H4, 2-thienyl; 46−77%.

Kostyanovsky et al.168 studied the reaction of PG with Nalkoxy-N′-arylurea 125 and 126. The reaction was carried out in DCM at room temperature. When N-benzyloxy-N′-(2bromophenyl)urea was used, because of retardation of the further cyclization into expected 5-phenylimidazolidin-2-one derivative by the bulky o-bromo substituent, only acyclic N[(benzoyl)(hydroxy)methyl]-N-benzyloxy-N′-(2bromophenyl)urea was obtained in 80% yield. But reaction with 125 and 126 led to cyclic products, hydantoins 127b and 128b in 46% and 6% yields, respectively. In addition to 128b, dihydroxyimidazolidinone 128a was produced in the reaction of 126 with PG in 56% yield as the major product (Scheme 32). Probably, this can be attributed to participation of N-1, containing aryl substituent, in 127a and 128a to removal of the hydroxy group to give 129, which regenerated to enol 130 that under tautomerization transformed to hydantoins 127b and 128b. In the case of 128a, p-nitro substituent on phenyl group N


Chemical Reviews

Review

Scheme 32. Synthesis of 3-Alkoxyhydantoins 127b and 128b

Kolos et al.170 studied the one-pot condensation reaction of 4-hydroxycoumarin 133 with AG and 116 to synthesize aroyl derivatives of chromeno[4,3-d]pyrimidines 135 via Biginelli reaction. The reaction was carried out by heating of a mixture of 133, AGs, and 116 in EtOH in the presence of a catalytic amount of AcOH under reflux conditions for 15−50 min, and interestingly, imidazol-2-ones 134 were obtained in 45−70% yields (Scheme 34). Gozalishvili et al.171 described a similar reaction using 1,3dimethylbarbituric acid 136. The reaction was conducted by heating the solution of equimolar amounts of 136, AGs, and

with electron-withdrawing characteristic retarded the generation of 129 with positive charge on N-1 atom, leading to low yield of 128b. Recently, an efficient synthesis of hydantoins 132 has been developed from the condensation reaction of 1,3-dicarbonyl compounds and acetophenones in the presence of CuO and I2 in DMSO at 70 °C, followed by addition of ureas 116 and heating at 100 °C (Scheme 33). This protocol involves an Scheme 33. Synthesis of Hydantoins 132 via Two Coupled Domino Processesa

Scheme 34. Synthesis of Coumarin-3-yl Substituted Imidazol-2-ones 134a

a

R = Ph, 4-ClC6H4, 4-FC6H4, 3,4,5-(MeO)3C6H2, 4-NO2C6H4, 2furyl; R′ = OEt, OMe, Ph; R″ = H, Et, Me, n-Pr; Ar = Ph, 4-BrC6H4, 4ClC6H4, 4-FC6H4, 4-HOC6H4, 4-MeOC6H4, 4-MeC6H4, 4-NO2C6H4, 2-benzofuryl, 2-furyl, 2-naphthyl, 2-thienyl; 42−76%.

integration of two coupled domino processes: iodine-promoted synthesis of unsymmetrical 1,4-enediones 131 via Knoevenagel condensation of the in situ generated AG with 1,3-dicarbonyl compounds (domino I) and the sequential transformation into 132 via aza-Michael addition of urea and cyclocondensation with carbonyl group, followed by oxidative dehydrogenation and 1,2-rearrangement of aryl groups (domino II).169 Oxidative dehydrogenation occurred by action of I2.

a

Ar = Ph, 4-BrC6H4, 4-ClC6H4, 4-IC6H4, 4-MeC6H4, 2-thienyl; R = H, Me, Ph; R′ = H, Me; 45−70%.

O


Chemical Reviews

Review

116 in MeOH in the presence of a catalytic amount of AcOH under reflux conditions for 25−40 min to produce imidazol-4yl-pyrimidine-2,4,6-triones 137 in 62−87% yields (Scheme 35).

Scheme 37. Synthesis of Imidazolin-4-one 141

Scheme 35. Synthesis of 4-[(Pyrimidine-2,4,6-trione)-5yl]imidazole-2-ones 137a

Scheme 38. Synthesis of 2-Iminoimidazolidin-4-one 143 via Condensation of PG with 142

a

Ar = 4-C6H4, 4-IC6H4, 4-MeC6H4; 62−87%.

Another similar reaction was carried out using 1,3-dicarbonyl compounds, in which by treatment of PG with N,N′-dimethyl urea 116 in the presence of ZnCl2 under reflux conditions or in the presence of ZnCl2/AlCl3 (1:3) on silica gel under microwave irradiation, the multisubstituted imidazolin-2-one derivatives 138 were produced in 50−66% or 35−46% yields, respectively (Scheme 36).172

compounds such as cimetidine, losartan, 178 fungicides, herbicides,179 plant growth regulators,180 and therapeutic agents.181 Due to their wide range of biological, industrial, and synthetic applications, there are several methods reported in the literature for the synthesis of imidazoles.182 By Ugi four component reaction of AGs, primary amines, carboxylic acids, and isocyanides 144 on Wang resin, ketoamides 145 were obtained, which underwent further cyclization to the corresponding imidazoles 146 in 16−56% overall yields, when treated with 60 equiv of NH4OAc in AcOH at 100 °C for 20 h, followed by reaction with 10% TFA-DCM at 23 °C for 20 min (Scheme 39). The Ugi reaction was carried out in a mixture of CHCl3−MeOH−pyridine (1:1:1) at 65 °C for 3 days.183

Scheme 36. Synthesis of Imidazol-2-ones 138a

Scheme 39. Synthesis of Imidazoles 146 via Ugi Reaction on Wang Resina

a

R = OEt, OMe, Me; reflux, 50−66%; MW, 35−46%.

Waugh et al.173 described the condensation reaction between PG-hydrate and benzamidine 139 in water in the presence of KOH at room temperature to produce hydroxyphenacylbenzamidine 140, which was cyclized to imidazole derivative 141 under heating in 64% yield (Scheme 37). Also, the reaction of PG with aliphatic amidines was reported.174 Treatment of guanidine hydrochloride 142 with PG-hydrate in the presence of TFA in refluxing benzene by azeotropic removal of water using Dean−Stark apparatus afforded the trifluoroacetate salt of 2-imino-5-phenylimidazolidin-4-one 143 (Scheme 38).175 5.1.6. Imidazoles. The imidazole moiety is present in a wide range of naturally occurring molecules176 and has broadly been found in biomolecules, including biotin, the essential amino acid histidine, histamine, and the pilocarpine alkaloids.177 Imidazole structures are present in important synthetic

a

n = 2, 10; Ar = Ph, 4-FC6H4, 4-MeOC6H4; R = Bn, i-Bu, Ph, 4MeOC6H4; R′ = Bn, n-Bu, Ph, 4-FC6H4; 16−56%. P


Chemical Reviews

Review

Sung et al.184 reported a similar procedure to synthesize alternating benzene/imidazole systems in solution media by multicomponent reaction of c-hexylisocyanide, benzoic acid, nbutylamine, and PG-hydrate in MeOH at room temperature, then by cyclization of obtained α-amido-β-ketoamide with in situ generated NH3 by heating of (NH4)2CO3 in AcOH under nitrogen atmosphere for 2 h in 55% yield. Also, the reaction was carried out using isophthalic acid 147a and terephthalic acid 147b and corresponding bis-imidazoles 149a,b with five consecutive aromatic rings were synthesized via Ugi products 148 as intermediate in 40% and 43% yields, respectively (Scheme 40). Because of the large steric hindrance, an attempt to use o-phthalic acid failed.

Scheme 41. Synthesis of Two Isomeric Aroylimidazoles 150a

a Ar = Ph, 4-BrC6H4, 4-ClC6H4, 4-FC6H4, 4-MeOC6H4, 3,4(MeO)2C6H3, 3,4-(OCH2O)C6H3, 4-biphenyl; 46−86%; a/b = 2.8− 7.5.

S4N4 in dioxane at reflux conditions for 6−15 h afforded the 2aroyl-5-arylimidazoles 150b in 10−33% yields. In some cases, depending on the substitution on the AG (Ar = Ph, 4-MeC6H4, 4-MeOC6H4, and 4-CNC6H4), 2-aroyl-5-aryloxazoles 151 were obtained in 17−32% yields, in addition to 150b. Imidazoles 150b and oxazoles 151 were synthesized via AG-imine, as an intermediate, which was formed by the reaction of AG with NH3 formed by decomposition of S4N4 at refluxed dioxane (Scheme 42).

Scheme 40. Synthesis of Bis-imidazoles 149 via Ugi Products 148a

Scheme 42. Synthesis of 2-Aroylimidazoles 150b via Reaction of AG with S4N4a

a Ar = Ph, 4-BrC6H4, 4-ClC6H4, 4-NCC6H4, 4-MeOC6H4, 4-MeC6H4, 2-thienyl; 150b, 10−33%; 151, 0−32%.

a

The electrochemical reduction of phenacyl azides in the presence of LiClO4 in DMF188 and pyrolysis of phenacyl azides at 180−240 °C189 resulted in aroylimidazoles 150 via AG-imine as intermediate of the reaction. Bratulescu190 reported one example of the conversion of PG to 4-phenylimidazoles 152 in reaction with urotropine as an in vitro source of formaldehyde in the presence of NH4OAc and a few drops of AcOH under solvent free microwave irradiation in 79% yield (Scheme 43).

a, meta; b, para.

Scheme 43. Synthesis of 4-Phenylimidazole 152 via Reaction of AG with Urotropine

Recently, Khalili and co-workers185 reported a green and simple method for the synthesis of two isomeric aroylimidazoles 150 by treatment of AG-hydrate with an excess amount of NH4OAc in water at room temperature in 48−86% yields (Scheme 41). The desired imidazoles 150 were obtained in 30−45 min. The isomeric ratio was determined by 1H NMR using NH signal intensities of two isomers. Also the thermotauto-isomerization process between two isomers was studied by NMR techniques. The short reaction time and obtaining pure products directly by filtration are some advantages of this method. A similar procedure was used for the synthesis of a naturally occurring and biologically active alkaloid, 2-(phydroxybenzoyl)-4-(p-hydroxyphenyl)imidazole, isolated from the red ascidian Botryllus leachi.186 Kong et al.187 reported the reaction of AG-hydrate with tetrasulfur tetranitride (S4N4). Heating a mixture of AG and

Zuliani et al.191 reported the reaction of AG with aldehydes in the presence of NH4OAc in MeOH at room temperature, which selectively resulted in 2,4(5)-diarylimidazoles 153 in 52− 83% yields, suffering from the formation of unwanted 2-aroyl4(5)-arylimidazoles 150 (Scheme 44). The reaction of PG with benzaldehyde in the presence of NH4OAc was investigated under different conditions, and it was observed that the Q


Chemical Reviews

Review

Scheme 44. Synthesis of 2,4(5)-Diarylimidazoles 153a

A similar procedure was used to synthesize the imidazole moiety of L-733,725, 156, a new immunosuppressant drug candidate. Different aldehydic components such as glycolaldehyde dimer 157, chloroacetaldehyde 160, glyoxalic acid 162, and hemiacetal of methyl glyoxalate 163 were treated with 3,5dimethoxyphenylglyoxal or PG in the presence of NH4OAc to obtain the precursor of the imidazole alcohol 166 (Scheme 45). By treatment of 157 with 3,5-dimethoxyphenylglyoxal hydrate in the presence of NH4OH, a 2/1 mixture of the desired imidazole 158 and the imidazole 159 was produced. When 160 was used, only the hydrated oxazole 161 was isolated. Reaction with 162 afforded the decarboxylated imidazole 152 in 61% yield. But, when 163 was used, the desired aryl imidazole ester 164 was obtained in 75% yield. The ester group of the THFprotected imidazole was reduced to the alcohol 166 in high yield using LiBH4 in the presence of MeOH in THF at 10−15 °C for 2 h, which was subjected to further reactions to yield L733,725.195 Also, the synthesis of 164 was investigated in large scale using 5.0 mol of 3,5-dimethoxyphenylglyoxal hydrate, and 850 g (63%) of 164 was obtained. The condensation reaction of acetate salt of 3-hydroxyamino2-butanone oxime 167 with AG-hydrate was studied by Amitina et al.196 The reaction was carried out in MeOH at room temperature leading to α-aroylnitrone 168, which upon heating in the presence of AcOH, underwent cyclization− dehydration sequences to afford 1-hydroxyimidazoles 170 in 46−84% yields via intermediate 169 (Scheme 46). In the case of 4-methoxy-, 4-ethoxy-, and 3,4-diethoxyphenylglyoxal, when

a 153: Reference 191: Ar and Ar' = Ph, 3-ClC6H4, 4-ClC6H4, 3CF3C6H4, 4-CF3C6H4, 3-MeOC6H4, 4-MeOC6H4, 3-NO2C6H4, 4NO2C6H4; 52−83%. Reference 193: Ar = Ph, Ar' = Ph, 2-benzofuryl, 2-furyl, 3-furyl, c-Hex, 3-pyridyl, 4-pyridyl, 3-thienyl.

selectivity of the reaction was affected by solvent. MeOH at room temperature afforded the best yield of 153 (83%). The evaluation of 153 for inhibition of the human neuronal Nav1.2 sodium channel isoform192 and hNav1.2 sodium channel193 was investigated, and m-CF3 substituted derivative 154 showed high activity for Nav1.2 sodium channel. A similar procedure for synthesis of 153 was applied by Husain et al. using NH4OAc in AcOH.194 Scheme 45. Synthesis of Imidazole Moiety of L-733,725

R


Chemical Reviews

Review

Scheme 46. Synthesis of 1-Hydroxyimidazoles 170a

Synthesis of 2,2-dimethyl-4-phenyl-2H-imidazole 176 was reported via condensation reaction of PG with acetone in the presence of NH3 in 72% yield. The reaction was carried out by bubbling of NH3(g) through a solution of acetone in Et2O, following by dropwise addition of the solution of PG in dry Et2O, in which the carbonyl carbon of acetone provided the C2 of imidazole 176 (Scheme 48).198 Scheme 48. Synthesis of 2,2-Dimethyl-4-phenyl-2Himidazole 176

Spongotine A and B, bisindole alkaloids isolated from marine sponges possessing an imidazole moiety, have been synthesized by different groups using 3-indolylglyoxal as starting material or intermediate.199 5.1.7. Fused Imidazopyridines, -Pyrimidines, and -Pyrazines. Substituted fused heterocycles can be found in many types of synthetic and naturally occurring medicinal substances200 such as coelenterazine, an imidazolopyrazinone derivative.201 It was found that imidazo[1,2-a]pyrazinones exhibit a significant solvatochromism 202 and bio- and chemiluminescence.201a,203 Imidazo[1,5-a]pyridines204 possess various applications such as dyes,205 optical data carriers,206 pesticides, fungicides,207 hypoglycemic agents,208 and compounds exhibiting antitumor,209 anti-inflammatory, antipyretic, and analgesic activity.210 Oxidative condensation−cyclization of aldehydes with 2-aminomethylpyridines211b−d or Pictet− Spengler strategy211e−g are among the most important routes to synthesize of these types of fused heterocycles.211 The reaction of 2-amino-N-heterocyclic compounds 177 with AG-hydrates was investigated by Alcaide et al.212 Reactions were carried out by addition of AG-hydrates to a solution of 177 in DCM in the presence of BF3·OEt2 or in benzene without using any catalyst at room temperature for 7− 264 h, and corresponding bicyclic imidazo[l,2-a]-derivatives 181−183 were obtained in 35−100% yields. Pyridone imine 179 was proposed as reaction intermediate, which was generated either by the rearrangement of intermediate carbinolamine 178 or by direct reaction of 177 with the aldehyde group of the AG through the N atom of heterocyclic ring, which then cyclized to 180 and dehydrated to 181−183 (Scheme 49). There are other reports on condensation reactions of 177 with PG.213 Devillers and co-workers214 reported the synthesis of imidazopyrazinones 183, substituted at C-2 or C-2 and C-6 by condensation reaction of 2-aminopyrazines 177 (X = CH, Y = N) with AGs or AG-acetals in the presence of HCl in refluxing EtOH under argon atmosphere for 4 h (Scheme 50). Antioxidant activity of the obtained products was investigated, and they behaved as quenchers of superoxide anion.215 Also the solvatochromism of 183 was investigated by Fujio et al.216 A similar condensation reaction with PG was reported by Barlin et al.217 using 177 in an ethanolic solution of conc. HCl to yield 183 and 184 in 46−62% yields (Scheme 51). The synthesis of 5-acylamido-6-phenylimidazo[2,1-b]thiazoles 187 and 2-phenyl-3-acylamidoimidazo[1,2-a]pyridines 188 was described by Drach et al.218 through the

a

Ar = Ph, 4-ClC6H4, 4-EtOC6H4, 3,4-(EtO)2C6H3, 4-MeOC6H4, 4NO2C6H4; 46−84%.

reaction was carried out by heating in MeOH in the presence of AcOH for 2 h, directly afforded corresponding 1-hydroxyimidazoles 170. In the case of 4-chloro- and 4-nitrophenylglyoxal in addition to 170, the pyrazine 1,4-dioxides 171 were obtained in 8−12% yields. Also, a similar reaction was carried out by heating of acetate salts of 2-hydroxyaminocyclohexanone and cyclopentanone oxime 172 with pentafluorophenylglyoxal hydrate in MeOH to afford 174 in 26−30% yields via cyclization of intermediate 173 with elimination of HF (Scheme 47). In addition to 174, pyrazine 1,4-dioxides 175 were obtained in low yields.197 Scheme 47. Synthesis of Benzo[e]imidazo[1,2b][1,2]oxazin-10-one 174

S


Chemical Reviews

Review

Scheme 49. Synthesis of Bicyclic Imidazo[1,2-a]pyridine, Pyrimidine, and Pyrazines 181−183a

Scheme 52. Synthesis of Imidazothiazoles 187 and Imidazopyridines 188a

a

R = Me, MeO; 187, 55−62%; 188, 60−68%.

(phenylamino)methylpyrrolidine 189, which was conducted in refluxing toluene by azeotropic removal of water in 83% yield (Scheme 53).219 Then, obtained 190 was subjected to reaction Conditions = benzene, rt, or BF3·OEt2, DCM, rt; 7−264 h. 181: X = Y= CH; Ar = Ph, 4-ClC6H4, 4-MeOC6H4, 4-MeC6H4, 4-NO2C6H4; R = H, 6-Cl, 8-MeO, 5-Me, 6-Me, 7-Me, 8-Me; 35−100%. 182: X = N, Y = CH; Ar = Ph, 4-ClC6H4, 4-MeC6H4; 40−72%. 183: X = CH, Y = N; Ar = Ph, 4-ClC6H4, 4-MeOC6H4; 53−100%. a

Scheme 53. Synthesis of Pyrroloimidazole 190

Scheme 50. Synthesis of C-2 and C-6 Disubstituted Imidazopyrazinones 183a

a

Ref 214, R = Ph, 4-HOC6H4, 4-MeOC6H4; ref 215, R = H.

Scheme 51. Synthesis of Imidazopyridazines 184a

a

with metalated methyldiphenylphosphine oxides to give hydroxyl aminal 191, which was converted into diol 192 by hydrolysis with 2% HC1 followed by reduction with LiAlH4 with >97% ee.220 Also, the reaction of 190 with Grignard reagents was reported, which followed by hydrolysis with 2% HCl afforded the corresponding α-hydroxyaldehydes in 67− 82% yields with 94−96% ee.219 5.1.8. 1,2,3-Triazoles and Tetrazoles. 1,2,3-Triazole has become one of the most important heterocycles in current chemistry research,221 due to its important industrial, agrochemical, and pharmaceutical applications,222 especially in biological science,223 material chemistry,224 and medicinal chemistry.225 One of the most attractive ways to prepare these compounds involves the thermal 1,3-dipolar cyclo-

X, Y = N, CH; R= H, Cl; 184, 46−62%; 183, 49%.

reaction of 2-aminothiazole 186 and 2-aminopyridine 177 (X = Y = CH) with ω-chloro-ω-acylaminoacetophenones 185, which were prepared by condensation of PG with amides, followed by reaction with thionyl chloride or phosphorus pentachloride. The reaction was carried out by standing of a solution of 185 and 186 or 177 in THF at room temperature for 24 h, followed by evaporation of THF and reflux of the residue in MeOH for 1 h (Scheme 52). There is a report on synthesis of hexahydro-1H-pyrrolo[1,2c]imidazole 190 via reaction of PG-hydrate with 2T


Chemical Reviews

Review

addition of azides with alkynes.221b,226 Additionally, the chemistry of the tetrazole ring is gaining increasing attention due to its importance in a variety of synthetic and industrial processes227 and excellent properties as a metabolically stable isosteric replacement for the carboxylic acid moiety228 and as a cis-peptide bond mimetic.229 Tetrazoles have also been used as precursors to other heterocycles230 and in high energy compounds.231 The synthesis of tetrazoles from a cycloaddition reaction between a nitrile and an azide is well documented.232 The reaction of α-hydroxyacetophenones 193 and phenylhydrazines was studied by Tang and Hu233 leading to 2,4diaryl-1,2,3-triazoles 196. The reaction occurred via CuCl2catalyzed oxidative cyclization reaction in refluxing glacial AcOH. Similar to the formation of sugar osazone, by treatment of 193 with phenylhydrazine, PG-bisphenylhydrazone 194 was obtained, which underwent oxidative cyclization using CuCl2 to give intermediates 195. Finally, intermediates 195 were transformed to 196 by losing an arylnitrene molecule under thermal conditions in 52−86% yields (Scheme 54).

Scheme 55. Synthesis of Benzoyltetrazole 201

Scheme 54. Synthesis of 1,2,3-Triazoles 196a

Scheme 56. Synthesis of Tetrahydrofurans 203 via [3 + 2] Cycloaddition Reaction of 202a

a

SiR3 = Sit-BuPh2, SiMe2Ph, Si(i-Pr)2Ph; Ar = Ph, 4-ClC6H4, 4MeOC6H4, 4-MeC6H4, 2-furyl, 2-naphthyl, 2-thienyl; temp = 0 °C, 56−90%, trans/cis = 59/41−99/1; temp = −78 °C, 57%-quant., trans/ cis = 26/74−48/52.

a

Ar = Ph, 4-BrC 6 H4 , 4-ClC 6 H 4 , 4-FC 6 H 4 , 4-HOC 6 H 4 , 3,4(HO)2C6H3, 4-MeOC6H4, 3,4-(MeO)2C6H3; Ar′ = Ph, 4-ClC6H4, 4MeOC6H4, 2-MeC6H4; 52−86%.

while at −78 °C, products cis-203 were obtained, stereoselectively. Beck et al.241 reported the synthesis of 5-acylamino butenolides 205 by a sequence of a Passerini reaction and an intramolecular Horner−Wadsworth−Emmons (HWE) modification of the Wittig reaction. The reaction was carried out via multicomponent reaction of AGs, isocyanides, and 42 in Et2O or THF to afford Passerini adducts 204, which underwent intramolecular HWE reaction using LiBr and Et3N in THF to furnish 205 in 13−87% yields (Scheme 57). The reaction was performed either in one pot or with the isolation of the Passerini products 204. By treatment of AGs, isocyanides, and cyanoacetic acid in Passerini reaction, N-substituted 3-aryl-2-cyanoacetoxy-3-oxopropionamides 206 were obtained, which were cyclized to 207 in the presence of Et3N. The reaction was conducted by treatment of a solution of AGs and isocyanides with cyanoacetic acid in Et2O at room temperature for 6 h, followed by addition of a solution of Et3N or piperidine in MeOH to a solution of obtained solid 206 in MeOH and stirring at room temperature for 10 min. Acidification of the reaction mixture with 6 N HCl until pH = 4 afforded the dihydrofuran-2-ones 207 in 78−85% yields. The reaction of 207 (Ar = 4-ClC6H4, R = c-Hex) with an excess amount of CH2N2 in Et2O−CHCl3 at room temperature in 6 h yielded corresponding 5-methoxy furan 208b via hydroxy furan 208a in 73% yield (Scheme 58).242

One example of the construction of tetrazole 201, using PGmonohydrazone 198, was reported by Yates et al.234 via basecatalyzed reaction with α-diazoacetophenone 197 in MeOH at room temperature for 1 h. The PG-monohydrazone 198 was formed in situ by reduction of 197 by methanolic NaOMe. The resulting intermediate 199 underwent cyclization to 200 which by elimination of acetophenone resulted in 201 (Scheme 55). 5.2. O-Heterocyclic Compounds

5.2.1. Tetrahydro- and Dihydrofurans. Tetrahydrofuran and dihydrofuran skeletons are frequently found in natural products,235 biologically active compounds,236 and valuable intermediates for organic synthesis.237 Thus, much attention has been paid to the development of new methods for the synthesis of tetrahydrofuran237f,238 and dihydrofurans,239 including [3 + 2] cycloaddition reactions, oxidative cyclization reactions and cyclization of alkenols and alkynols. Fuchibe et al.240 reported the [3 + 2] cycloaddition reactions of cyclopropylmethylsilanes 202 and AGs in the presence of SnCl4 to afford 2-silylmethyl substituted tetrahydrofurans 203. The reaction of 202 with PG was examined using different Lewis acids in different solvents, and SnCl4 in DCM was selected as optimum conditions based on high yields of 203 (Scheme 56). The stereoselectivity of the reactions was dependent on the reaction temperature. When reaction was carried out at 0 °C, products trans-203 were the major isomer, U


Chemical Reviews

Review

Scheme 59. Synthesis of 5-Hydroxy Dihydrofurans 211a

Scheme 57. Synthesis of Dihydrofuran-2-ones 205 via Passerini−HWE Reactionsa

a

R = allyl, n-Bu, t-Bu, c-Hex, t-BuO2CCH(Me), t-BuO2CCH2CH2, MeO2CCH(CH2CHMe2); R′ = H, Ph, 4-FC6H4, 3-MeOC6H4; Ar = Ph, 4-HOC6H4, 4-biphenyl, 2-naphthyl, 2-thienyl; 13−87%.

Scheme 58. Synthesis of Dihydrofuran-2-ones 207 via Passerini Reactiona a

R = t-Bu, Et, Me; Ar = Ph, 4-BrC6H4, 4-NO2C6H4; 71−85%; cis/trans = 10/90−62/38.

Scheme 60. Synthesis of Formoins 212 via Benzoin Condensation of AGa

a

Ar = Ph, 4-MeC6H4, 2-furyl, selenophen-2-yl, 2-thienyl; 27−71%.

Scheme 61. Synthesis of Formoin Diacetate 216

a

R = c-Hept, c-Hex, c-Pent; Ar = Ph, 4-ClC6H4, 4-MeC6H4, 2-thienyl; 206, 78−82%; 207, 78−85%.

Anary-Abbasinejad et al.243 described the reaction between AG-hydrates, DAAD, and Ph3P to give dihydrofuran derivatives 211. Treatment of DAAD with Ph3P and AG-hydrates in DCM at room temperature gave rise to DAAD−PPh3 zwitterions 209, which by protonation and conjugate addition with AGs to give 210 followed by intramolecular Wittig reaction afforded 211 in 71−85% yields (Scheme 59). The dihydrofurans 211 were isolated as two diastereomers. The cis/trans ratio was determined to be 10/90 to 62/38 using 1H NMR spectroscopy. Peter et al.244 worked on the benzoin condensation of AGs using potassium cyanide in aqueous EtOH. The reaction was carried out by adding of a solution of KCN in 50% aqueous EtOH to an ice-cold solution of AGs in EtOH and stirring. The reaction was solidified and corresponding formoins 212 were prepared in 27−71% yields (Scheme 60). Also, formoin diacetate 216 was prepared by refluxing of PG in Ac2O containing pyridine in good yield via benzoin condensation. The plausible reaction mechanism involves the removal of a proton from the diacetyl derivative 213 by pyridine to generate an anion 214 and its reaction with another molecule of PG to afford intermediate 215, which then cyclized to 216 (Scheme 61).245

The synthesis of [2-alkoxy-5-amino-4-cyanofuran-3(2H)ylidene]malononitriles 221 was reported by Bardasov et al.246 via reaction of 3-aroylcyclopropane-1,1,2,2-tetracyanides 217 with NaOMe or sodium 2-hydroxyethoxide in the corresponding alcohols in 42−85% yields. Also, the reaction was investigated with sodium salts of acetone and acetaldehyde oximes, in which corresponding 221 were obtained in 19−87% yields (Scheme 62). The reaction was performed by adding of a suspension of cyclopropane derivative 217 in appropriate solvent to a solution of either NaOMe in MeOH, NaOCH2CH2OH in ethylene glycol, or sodium salts of oximes in CH3CN with stirring at room temperature for 24 h, then neutralization with 5% H2SO4. The 217 was transformed to 220 via dianion intermediates 218 and 219. The precursor 217 V


Chemical Reviews

Review

Scheme 62. Synthesis of Furanylidene Malononitriles 221a

Reduction of 223 to 225 occurred by action of CH2O·BF3, in situ generated in the conversion of 223 to 224. To trap the furfuryl carbocation intermediate 223, the BF3·OEt2-catalyzed reaction of 222a in the presence of an electron-rich furan derivative such as 225 (Ar = 4-MeC6H4) was investigated in the presence of water in THF at 23 °C for 30 min, in which a dimeric furan 226 was obtained in 49% yield (Scheme 64). Compounds 222 were prepared by Knoevenagel condensation of AGs with acetylacetone in boiling CH3CN without any catalyst in 98% yield. By treatment of 222a with Ph3P in CHCl3 under reflux conditions for 30 min, deoxygenation occurred to give 225a (Ar = Ph) in 88% yield (Scheme 64). When pentenedione 222a was treated with conc. HCl in THF at 23 °C chloromethylfurane 229 was produced in 87% yield, which was transformed into 2-ethoxymethylfuran 230a in boiling ethanol for 30 min or converted into the corresponding furfuryl alcohol 230b by hydrolysis in refluxing water−THF for 3 h (Scheme 63). Diels−Alder (DA) reaction of 222a with cyclopentadiene was also carried out in EtOAc at 23 °C for 2 h, and 2-oxabicyclo[3.3.0]octene 227 was obtained together with the corresponding DA cycloadduct 228 (Scheme 64). On the other hand, the BF3·OEt2-catalyzed condensation of 222 with acetylacetone or ethyl acetoacetate afforded 231 (50%) together with isomeric 232 or corresponding furan carboxylate 233 (31%), respectively (Scheme 65).260,261 The 1,4-diones 66 were converted into 3-methylthiosubstituted furans 234 using SnCl2 in a mixture of conc. HCl and AcOH (4/6, mL/mL) under reflux conditions in 69−90% yields. Removal of the methylthio group using Raney-Ni in refluxing EtOH gave the 2,5-diaryl furans 235 in 85−91% yields. Also, by treatment of the 1,4-diones 66 with a solution of 30% HBr in AcOH in the presence of a drop of H2SO4 in CHCl3 at 0 °C, the corresponding bromofurans 236 were obtained in 58−92% yields (Scheme 66).262 Yang and co-workers263 provided an efficient synthesis of indole−furan conjugates from the reaction of indoles, aryl methyl ketones, and 1,3-dicarbonyl compounds (Scheme 67). Aryl methyl ketones were converted into 66 and 131 via AG intermediates using CuO, I2, and DMSO by self-condensation or condensation with 1,3-dicarbonyl compounds, respectively (Schemes 18 and 33). Treatment of indoles with obtained 66 and 131 afforded the 3-(furan-3-yl)indole derivatives 237 via linear domino Friedel−Crafts alkylation/Paal−Knorr cyclization. Different Lewis and Brønsted acids and solvents were investigated for construction of the furan skeleton, and MsOH

a

Ar = Ph, 4-BrC6H4, 4-MeOC6H4, 3,4-(MeO)2C6H3, 3-NO2C6H4, 2thienyl; R/solvent = Me/MeOH, HOCH2CH2/HOCH2CH2OH, MeCHN- or Me2CN-/CH3CN; 42−85%.

was prepared by three-component reaction of AG with 2bromomalononitrile and malononitrile in i-PrOH at room temperature in 68−82% yields. 5.2.2. Furans. Furans and their derivatives are very useful as starting materials to produce pharmaceutically and industrially important compounds.247 Furan moieties exist in numerous bioactive natural products, such as kallolides,248 cembranolides,249 calicogorgins, furan fatty acids,250 cytotoxic furanocembranes,251 gersolanes,252 pseudopteranes,253 rosefuran,254 agassizin, furodysin,255 and α-clausenan,256 and are frequently used as intermediates in organic synthesis.257 Although a variety of furan syntheses are known,258 especially Paal−Knorr reaction,259 the development of new and convenient strategies is of considerable interest. Onitsuka and co-worker260 studied the BF3·OEt2-catalyzed reaction of 3-acetyl-1-aryl-2-pentene-1,4-diones 222 in the presence of water in THF under reflux conditions, which afforded bis-furans 224, with a small amount of 225 via intramolecular cyclization reaction. It is known that relatively stable furfuryl carbocation 223 is the intermediate of the reaction of 222 under wet reaction conditions (Scheme 63).

Scheme 63. Synthesis of Furan Derivatives via BF3·OEt2-Catalyzed Reaction of 1,4-Diones 222a

a

Ar = Ph, 4-FC6H4, 4-ClC6H4, 4-MeC6H4, 4-MeOC6H4; 224, 21−79%; 225, 3−10%. W


Chemical Reviews

Review

Scheme 64. Synthesis of Furan Derivatives via Reactions of 1,4-Diones 222

Scheme 65. BF3·OEt2-Catalyzed Synthesis of Furans 231− 233a

Scheme 66. Synthesis of 2,5-Diarylfurans 234−236a

a

Ar = Ph, 4-BrC6H4, 4-ClC6H4, 4-EtOC6H4, 4-MeOC6H4, 4-MeC6H4, 2-benzofuryl, 1-naphthyl, 2-naphthyl, 2-thienyl, 3-thienyl; 234, 69− 90%; 235, 85−91%; 236, 58−92%.

tautomeric form 243b led to the formation of 2,5-diphenylfuran 244 in water. But, when PG was heated in cyclohexane, only the reduced forms 245 and 246 were prepared. In water at 200 °C after 6 h, only a small amount of 245 was obtained (Scheme 69). 5.2.3. Benzofurans and Furofurans. Benzofuran moieties are widely presented in many naturally occurring and biologically active compounds, which display various pharmacological activities266 and antifungal,267 antibacterial,268 antineoplastic,269 antiviral,270 antioxidative,271 anti-inflammatory272 and angiogenesis inhibitory273 properties. Substituted benzofurans have wide range of applications such as of fluorescent sensors,274 oxidants,275 brightening agents, and a variety of drugs and in other fields of chemistry and agriculture.276 Therefore, a number of routes leading to substituted benzofurans have been described in the literature,277 such as Pd-catalyzed coupling/cyclization reactions of alkynes with ohydroxyaryl halides,277k,l carbonylative annulation of o-hydroxyarylacetylenes,277m tandem Michael addition/cyclization of quinones with 1,3-dicarbonyl compounds,277n SmI2 or Bu3SnHmediated radical cyclization,277o,p and Claisen rearrangement

a

Ar = Ph, 4-ClC6H4, 4-FC6H4, 4-MeOC6H4, 4-MeC6H4; 231, 15− 77%; 232, 8−59%.

in refluxing CH3CN was selected for good efficiency, which gave the desired indole−furan conjugates 237a and 237b in 24−99% and 47−97% yields, respectively. 3-Alkylthiofurans 241 were synthesized via photoaddition of PG with 1-alkylthio-1-propynes 238 in benzene, followed by treatment of the obtained 1,4-enediones 240 with SnC12 and HCl in AcOH at 80 °C for 10 min. Irradiation of the PG with 238 gave 240, through oxete intermediates 239, in 20−25% yields. The intermediates 239 were produced via [2 + 2] cycloaddition of the alkyne’s triple bond with the aldehyde group of PG (Scheme 68).264 The high-temperature chemistry of PG in water and cyclohexane was studied at 200 °C by Katritzky et al.265 Disproportionation of PG produced benzoylmethanol 243, which converted to acetophenone and starting PG via further disproportionation. Condensation of acetophenone with X


Chemical Reviews

Review

Additionally, furofurans exhibit a wide variety of biological activities including antitumor,278 antimitotic,279 antiviral,280 antioxidant,281 and antihypertensive activities,282 inhibition of platelet activating factor (PAF)283 and Ca2+ channels,284 cAMP phosphodiesterase inhibition,285 sodium-selective diuretic properties,286 and microsomal monooxygenase inhibitory effects for insects.287 Several synthetic approaches to furofurans have been reported in the literature.288 Talinli et al.289 studied the reaction of AGs with phenolic compounds such as resorcinol and 2-naphthol under acidic conditions, in which the reaction products were changed depending on the type of the phenolic compounds. By treatment of AGs with 2 equiv of resorcinol in toluene in the presence of p-TsOH at 70−80 °C, 2-phenyl-3-(2,4-dihydroxy)6-hydroxy-benzo[b]furans 248 were obtained in 52−60% yields via a sequence of Friedel−Crafts semiacetalization reactions followed by removal of a molecule of water (Scheme 70).

Scheme 67. Synthesis of Indole−Furan Conjugates 237 via Domino Friedel−Crafts/Paal−Knorr Reactionsa

Scheme 70. Synthesis of Benzofurans 248a

a

237a: R = Ph, 4-ClC6H4, 4-FC6H4, 3,4,5-(MeO)3C6H2, 4-MeC6H4, 3NO2C6H4, 4-NO2C6H4, 2-furyl; R′ = OEt, OMe, Me, Ph; R″ = H, Me; Ar = Ph, 4-BrC6H4, 4-ClC6H4, 3,4-Cl2C6H3, 4-FC6H4, 4-OHC6H4, 4MeOC6H4, 4-MeC6H4, 4-NO2C6H4, 2-benzofuryl, 1-naphthyl, 2naphthyl, 3-thienyl; reflux, 8−10 h, 24−99%. 237b: Ar = Ph, 4BrC6H4, 4-ClC6H4, 4-FC6H4, 4-MeOC6H4, 4-MeC6H4, 4-NO2C6H4, 2naphthyl, 3-thienyl; reflux, 5 h, 47−97%.

Scheme 68. Synthesis of 3-Alkylthiofurans 241a

a

Ar = Ph, 4-ClC6H4; 52−60%.

Compounds 247 were proposed as reaction intermediates. But reaction of AGs with 2-naphthol resulted in formation of benzo[b]naphtho[2,1-f ]oxepin-13-ones 249 (Scheme 71), Scheme 71. Reaction of AG with 2-Naphthol and Synthesis of Benzooxepine 249a a

R = t-Bu, Et, Me, Ph; 240, 20−25%; 241, 80−95%.

Scheme 69. High-Temperature Chemistry of PG

a

X = H, Br; Y = H, Cl, OMe; 35−60%.

which was attributed to prevention of semiacetalization step by the steric bulk of the naphthol ring. The reaction was carried out by heating the mixture of AGs with 2 equiv of 2-naphthol in AcOH in the presence of H2SO4 as catalyst at 50 °C and compounds 249 were obtained in 35−60% yields. An InCl3-catalyzed three-component reaction of phenols, AG-hydrates, and p-TsNH2 was reported by Chen et al.290 that

followed by Pd-catalyzed intramolecular oxidative cyclization.277q Y


Chemical Reviews

Review

afforded 2-aryl-3-aminobenzofuran derivatives 250. The reaction of p-(t-Bu)phenol with PG-hydrate was examined using different Lewis acids, and the best results were obtained when InCl3 was used as catalyst. Reactions were carried out by mixing of AG-hydrate, p-TsNH2, and catalytic amounts of InCl3 in DCM at room temperature and stirring for 30 min, then by addition of phenols and heating at 40 °C for 6−16 h to give 250 in 45−94% yields (Scheme 72). Reaction of phenols

Scheme 74. Synthesis of Hexahydrofurofurandiones 255 via Reformatsky Reactiona

Scheme 72. InCl3-Catalyzed Synthesis of 3Aminobenzofurans 250a

a

R = H, Me; Ar = Ph, 4-BrC6H4, 4-t-BuC6H4, 4-ClC6H4, 4-EtC6H4, 4FC6H4, 4-MeC6H4; 28−85%.

a

Ar = Ph, 4-ClC6H4, 4-MeOC6H4; R = H, 4-Br, 4-t-Bu, 2,4-di-t-Bu, 4Cl, 4-F, 4-MeO, 4-Ph; 45−94%.

(258) and furo[2′,3′:2,3]furo[5,4-c]isoquinoline-10-carbonitrile 262 via route b (259) and intermediate 261 in a ratio of 2:3 (Scheme 75).293 The compound 257 was prepared by the condensation of 2-methyl-1,3-(2H,4H)-isoquinolinedione 256 with PG.294 5.2.4. Dioxolanes. 1,3-Dioxolanes are found in biologically active compounds such as dioxolane nucleosides with anticancer295 activity and act as inhibitors of herpes simplex viruses (HSV)296 and isozyme-selective heme oxygenase (HO).297 In the literature, some synthetic routes, starting from tartaric acid and carbohydrate derivatives,298 dicarbonyl compounds via radical addition to the carbonyl carbon,299 carbonyl ylides via 1,3-dipolar cycloaddition to aromatic aldehydes,300 and 2-hydroxyethyl vinyl ethers via Pd-catalyzed cyclization,301 are commonly used to obtain dioxolanes. In addition, 1,3-dioxolanes were synthesized widely for protection of carbonyl groups.302 Shao and Li303 have described the synthesis of hemialdals 263 by direct oxidation of acetophenones using DMSO in the presence of a catalytic amount of I2, in which the AG-hydrate was produced as reaction intermediate, which on further heating in toluene using Dean−Stark apparatus to remove produced water resulted in 263. Hemialdals 263 were converted into 2,4,5-triacyl-1,3-dioxolanes 264 in 43−70% yields with excellent stereoselectivity, when treated with αbromoacetophenone and Et3N in the presence of LiBr in THF at room temperature for 15−60 min (Scheme 76). Also the reaction of AG-hydrates with α-bromoketones under similar conditions to produce 264 in 35−61% yields with excellent anti selectivity were reported. As the authors mentioned, the reactions proceeded via 263 as intermediate. Hemiacetal 265 was also employed in the reaction with α-bromoacetophenone to give the corresponding dioxolane 264 in moderate yield and excellent stereoselectivity (anti/syn > 99:1) (Scheme 77).304 Manning et al.305 described the reaction of acetophenone with nitrosyl chloride in the presence of l,2-propanediol. The reaction was performed by slowly adding the nitrosyl chloride to the solution of acetophenone in benzene in the presence of 8 equiv of 1,2-propanediol. PG was in situ generated and underwent reaction with 1,2-propanediol to produce bisdioxolane 266 in 36% yield (Scheme 78).

containing electron-donating groups led to the corresponding 250 in high yields, while phenols with electron-withdrawing substituents afforded the 250 in moderate yields. A one-pot three-component reaction of 4-hydroxycoumarin 133 or dimedone 70 with AGs and isocyanides was reported, which afforded furocoumarins 251 or benzofurans 252, respectively. The reactions were carried out in refluxing CH3CN without any catalyst for 5 h to give corresponding products in 88−92% yields (Scheme 73).291 Scheme 73. Synthesis of Furocoumarins 251 and Benzofurans 252a

a

Ar = Ph, 4-BrC6H4, 4-ClC6H4, 4-NO2C6H4; R = t-Bu, c-Hex; 88− 92%.

Shchepin et al.292 described the Reformatsky reaction of AGs with methyl 2-bromopropionate and methyl 2-bromo-2methylpropionate in ether−HMPA mixture under heating conditions. The both carbonyl groups of the AGs were attacked by initially arising Reformatsky reagent 253 to provide zinc bromide alcoholate 254, which spontaneously cyclized to bicyclic products, hexahydrofurofurandiones 255, under the reaction conditions in 28−85% yields. (Scheme 74). The Michael reaction of 2-methyl-4-phenacylidene-1,3(2H,4H)-isoquinolinedione 257 with malononitrile was described in the presence of Et2NH as a catalyst in a benzene−EtOH solvent mixture at 60 °C to furnish a mixture of 1H-pyrano[2,3-c]isoquinoline-2-carbonitrile 260 via route a

5.3. S-Heterocyclic Compounds

5.3.1. Thiophenes. Thiophenes and their polycyclic derivatives comprise an important heterocyclic class that exhibit remarkable electrochemical,306 optical,307 physical,308 and Z


Chemical Reviews

Review

Scheme 75. Synthesis of Furofuran 262

Scheme 76. Synthesis of 2,4,5-Triaroyl-1,3-dioxolanes 264a

Scheme 78. Synthesis of Bis-dioxolane 266 via PG Intermediate

Mac Dowell et al.318 reported the synthesis of 8Hindeno[2,1-b]thiophene 270 by the method shown in Scheme 78. 3-Phenyl-2,5-thiophenedicarboxylic acid 268 was prepared in 57% yield by the Hinsberg−Stobbe type of condensation between PG and diethyl thiodiglycolate 267 using NaOEt followed by saponification. The 268 was converted into 270 via intermediate 269 by ring closure with AlCl3, followed by Wolff−Kishner reduction, which caused both decarboxylation and reduction in 64% yield (Scheme 79). A similar synthesis of 2,5-di-p-toluoyl-3-phenylthiophene 272 was reported by reaction of diketo sulfide 271 with PG in warm MeOH in the presence of NaOMe in 67.8% yield (Scheme 80).319 1,4-Diones 66 prepared through AGs (Scheme 18) were converted into saturated 1,4-diketones in the presence of KI and conc. HCl in acetone at room temperature, which afforded 3-methylthio-substituted thiophenes 273 by treatment with Lawesson’s reagent in refluxing toluene for 2 h in 75−88% yields (Scheme 81).320

a

Ar = Ph, 4-AcOC6H4, 4-CbzNHC6H4, 4-ClC6H4, 4-FC6H4, 4MeOC6H4, 4-MeC6H4; Ar′ = Ph, 4-AcOC6H4, 4-ClC6H4, 4-FC6H4, 4-MeC6H4, Et, 2-furyl, Me, 2-thienyl, styryl; 263, 32−53%; 264, 43− 70%; a/b = 68/32−75/25; anti/syn > 99/1.

Scheme 77. Synthesis of 2,4,5-Triaroyl-1,3-dioxolanes 264 via Hemiacetal 265

biological309 properties. Also, thiophenes have wide range of applications in advanced materials310 such as conjugated polymers,306b,311 organic conductors,312 semiconductors,313 and light emitting devices314 and in treatment of various diseases315 as pharmaceuticals.316 Thiophene derivatives have been prepared by various methods,317 such as Gewald317d,e and Paal−Knorr317i,j reactions.

5.4. N,O-Heterocyclic Compounds

5.4.1. Isoxazoles. The isoxazole nucleus is a prominent structural motif found in numerous natural products and synthetic compounds with vital medicinal value.321 Also, isoxazoles have applications in functional materials,322 such as liquid crystalline compounds,323 and exhibit GABAA antagoAA


Chemical Reviews

Review

Scheme 82. Synthesis of Isoxazoles 276a

Scheme 79. Synthesis of Indenothiophene 270

a

Ar= Ph, 4-ClC6H4, 4-MeOC6H4; Ar′ = Ph, 4-ClC6H4, 4-FC6H4, 4MeOC6H4; 39−63%.

Scheme 80. Synthesis of 2,5-Ditolylthiophene 272 5.4.2. Oxazolidines, Oxazolines, and Benzoxazolines. Oxazolidines and oxazolines are common useful metal ligands in asymmetric catalysts336 and also are utilized in organic synthesis as synthetic intermediates337 or protecting groups.338 Oxazolidines and oxazolines appear in numerous medicinally active compounds and natural products of biological significance,339 such as quinocarcin.340 A number of methods exist for preparation of oxazolidine and oxazoline derivatives,341 such as 1,3-dipolar cycloaddition of vinyl epoxides with imines,341i−k carboamination of O-vinyl-1,2-amino alcohol,341m aminohydroxylations of alkenes,341f cyclization of β-hydroxyamides,341c,n,o and acid-catalyzed reaction of aldehydes with 1,2hydroxyalkyl azides.341p (R)-Piperidin-3-ol 277 was reported as a chiral auxiliary for stereoselective synthesis of α-hydroxy aldehydes 280 by Choi and co-workers.342 (5R,7R)-7-Benzoyl-6-oxa-1-azabicyclo[3.2.1]-octane 278 was obtained by condensation of PGhydrate with 277 in the presence of 4 Å MS in dry DCM under reflux conditions in 85% yield. The reactions of 278 with Grignard reagent to give carbinols 279 showed excellent stereoselectivity, because of the chelation of the metal between the carbonyl oxygen and the ether oxygen. The stereoselectivity was low when RLi or RMgCl was used, while RMgBr led to excellent stereoselectivity. Hydrolysis of the 279 to α-hydroxy aldehydes 280 was carried out by stirring in the presence of silica gel in DCM at room temperature for 2 h (Scheme 83). Agami et al.343 have reported the synthesis of N-Boc-2benzoyloxazolidine 282 as a chiral auxiliary to enantiopure 1,2diols 284 via diastereoselective nucleophilic additions by Grignard reagents. The 282 was prepared either by stirring of a solution of (1R,2S)-norephedrine 281 and PG-hydrate in THF in the presence of anhydrous MgSO4 at room temperature for 0.5 h or by stirring of a solution of 281 and PG in the presence of 4 Å MS in DCM at room temperature for 0.5 h, followed by refluxing of a solution of obtained oxazolidine with Boc2O in EtOAc. The Grignard reaction was carried out in THF or Et2O at 0 °C. Hydrolysis of 283 using TFA in DCM followed by reduction with NaBH4 furnished enantiopure 284 (Scheme 84). Also the addition reaction of organometallic compounds to the chiral 2-benzoyl-3-oxa-1-azabicyclo[3.3.0]octane 286, which was prepared via condensation of PG-hydrate and (S)-prolinol 285 in DCM in the presence of 4 Å MS, was reported. The reactions were performed in Et2O, THF, or THF−HMPA to afford the corresponding carbinols 287 in over 80% yields. The

Scheme 81. Synthesis of 3-Methylthiothiophenes 273a

a

Ar = Ph, 4-MeC6H4, 2-benzofuryl, 2-furyl; 75−88%.

nist,324 analgesic,325 antibacterial,326 anti-inflammatory,325a,327 hypoglycemic,328 COX-2 inhibitory,329 antinociceptive,330 and anticancer331 activity. Isoxazole derivatives have served as versatile building blocks in organic synthesis.332 Many synthetic methods, including 1,3-dipolar cycloaddition of nitrile oxides333e−h and condensation of hydroxylamine with 1,3dicarbonyl compounds333q and α,β-unsaturated carbonyl compounds,333b have been employed in the synthesis of isoxazoles.333 Juhász-Tóth et al.334 reported the synthesis of 5-substituted3-acylisoxazoles 276 from 2-azido-3-hydroxy-1,4-diketones 275 in 39−63% yields. By treatment of α-azido acetophenones 274 with various AG-hydrates in the presence of DBU at 0 °C in dry THF, products 275 were obtained in good yields. Further reaction of 275 with a slight excess amount of MsCl in the presence of Et3N at −15 °C in dry DCM resulted in the formation of 276, presumably via the corresponding nitrene intermediate (Scheme 82). An attempt at silylation of 275 (Ar = 4-ClC6H4, Ar′ = Ph) using TBDMS-Cl in the presence of imidazole in DMF at room temperature did not produced the TBDMS-protected product, but only the corresponding 276 was obtained in 44% yield.335 AB


Chemical Reviews

Review

Scheme 83. Stereoselective Synthesis of α-Hydroxy Aldehydes 280 via Oxazolidine 278a

Scheme 85. Synthesis of Fused Oxazolidines 286a

a R = n-Bu, c-Hex, Me; M = MgBr, Et2O, −78 °C, 287a/b = 88/12− 96/4; M = Ti(i-OPr3), Et2O, −78 °C → rt, 287a/b = 96/4−99/1; M = Li, THF−HMPA, −78 °C, 287a/b = 10/90−21/79; M = Li−CeCl3, THF, −78 or −85 °C, 287a/b = 16/84−28/72.

Scheme 86. Synthesis of Oxazolones 289 via Ugi Reactiona a R = n-Bu, Et, Me, i-Pr, vinyl; M = MgBr, MgCl, Li; 279, 62−85%; M = Li, 279a/b = 39/61−40/60; M = MgBr, MgCl, 279a/b = 77/23− 98/2.

Scheme 84. Synthesis of Enantiopure Diols 284 via N-BocOxazolidine 282a

a

Ar = Ph, 4-ClC6H4, 4-FC6H4, 4-MeOC6H4, 4-MeC6H4, 6-MeOnaphth-2-yl; Ar′ = Ph, 3-ClC6H4, 4-ClC6H4, 4-MeOC6H4, 4-MeC6H4; 61−89%.

benzoxazine 291 and dibenzoxazolines 294 were produced. The product distribution was affected by the AG/o-aminophenol molar ratio. With a 1/2 molar ratio of AG/oaminophenol, the reaction led to 294 as major products, while with a molar ratio of 1/1, 291 was the major product. The products 291 were obtained via initial condensation of the amine with the keto group of the AGs, 290, but 294 were produced via condensation of two o-aminophenol molecules with both aldehyde and ketone groups, 293 (Scheme 87). It is known that 294 is in equilibrium with tautomeric ketimine form 295.347 5.4.3. Oxazoles. Oxazoles are a common structural motif found in numerous molecules that display antiviral (i.e., hennoxazole A),348 antifungal (i.e., leucascandrolide A),349 and antibacterial activities350 and also are contained in the structure of disorazole A,351 anti-inflammatory drug oxaprozin,352 virginiamycin M2,353 and antibiotic ostreogrycin A354 as well as in the immunosuppressant merimepodib (VX-497),355 which display attractive biological activities.356 General synthetic methods for them include the condensation of carboxylic acids with 2-aminoethanol followed by dehydrative cyclization to obtain 2-oxazolines357 and then oxidation to the oxazoles358 and cyclodehydration of α-acylaminoketone and Robinson−Gabriel synthesis.359p,q There are other alternative methods to construction of the oxazole ring.359

a

RMgX = allylMgBr, EtMgBr, MeMgI, vinylMgCl; 283, 54−70%, de = 2−95; 284, 51−61%.

reaction conditions and diastereoselectivity are illustrated in Scheme 85.344 A one-pot Ugi four-component synthesis of 2(3H)́ oxazolone 4-carboxamides 289 was reported by GarciaValverde et al.345 by treatment of AGs with anilines in the presence of activated 3 Å MS in DCM at room temperature, then addition of cyclohexyl isocyanide and anhydrous trichloroacetic acid. The products 289 were obtained in 61− 89% yields. The proposed reaction mechanism involves initially formation of the Ugi products 288 followed by nucleophilic addition of the ketone enolate onto the chloroacetate carbonyl group, and finally elimination of chloroform to give the corresponding 289 (Scheme 86). The condensation reaction of AG with o-aminophenol was investigated by Belgodere et al.,346 and a mixture of 1,4AC


Chemical Reviews

Review

Scheme 87. Synthesis of Dibenzoxazolines 294a

a Ar = Ph, 4-ClC6H4, 4-MeOC6H4, 4-MeC6H4, 4-NO2C6H4; AG/o-aminophenol molar ratio = 1:2; 291/294 = 10/90−20/80; AG/o-aminophenol molar ratio = 1:1; 291/294 = 23/77−65/35.

Scheme 88. Synthesis of Oxazole Phosphonic Acid Derivatives 297 and 299a

a 299a: Ar = Ph, 4-MeC6H4; X = Y = OH, cond. water, 20−25 °C, 5 h, 63−76%. 299b: Ar = 4-MeC6H4; X = Y = NHR (R = Et, n-Pr), cond. 2.5 equiv of RNH2, dry dioxane, 20−25 °C, 5 h, 63−76%. 299c: Ar = 4-MeC6H4; X = BnNH, Y = OMe, conds. 2 equiv of BnNH2, dry dioxance, 20−25 °C, 1 h, then MeONa, MeOH, 20−25 °C, 12 h, 64%. 299d: Ar = 4-MeC6H4; X = O(CH2CH2)2N, Y = OH, cond. 2 equiv of morpholine, dry dioxane, 20−25 °C, 4 h, then water, 20−25 °C, 12 h, 57%.

Belyuga et al.360 described the synthesis of methyl (2-aryl-5phenyl-1,3-oxazol-4-yl)phosphonates 297 in 69−73% yields by treatment of Arbuzov products 296 with excess amounts of SOCl2 under reflux conditions for 2 h. α-Chloro-α-acylamino ketones 185, which were generated by reaction of PG with amides followed by action of SOCl2, were transformed to 296 in 76−82% yields, when treated with trimethyl phosphite in refluxing benzene for 4 h. (1,3-Oxazol-4-yl)phosphonates 297 were converted into corresponding phosphonic acid 299a, phosphonic dialkylamides 299b, methyl N-benzyl phosphonamidate 299c, and phosphonic morpholide 299d via phosphonic dichlorides 298 in further reactions as illustrated in Scheme 88.

reactions as chiral auxiliaries.364 There are a number of approaches for construction of the thiazolidine and thiazoline rings,365 such as cycloaddition reactions of 2-vinylthiirane with various heterocumulenes,365k intramolecular cyclization of aminoethyl thiolesters 3 6 5 g and N-(β-hydroxyethyl)thioamides,365o−q and condensation of thioethanol amine with nitriles,365l esters,365m and imines.365n One example of the condensation of aminothiol 300 (X = SH) with PG was reported in refluxing CH3CN producing 2benzoylthiazolidine 301 as a mixture of two diastereoisomers. Interestingly, N-methylphenylglycinol 300 (X = OH) afforded morpholinone 303 under the same conditions via phenyl migration within intermediate 302 (Scheme 89).366 The reaction of p-MeO−PG and PG with L-cysteine methyl ester was reported by Pinho e Melo et al.367 to yield a mixture of diastereoisomeric thiazolidines 304a,b and 305a,b, respectively. Treatment of thiazolidine 304a with prop-2-ynyloxyacetyl chloride 306 in the presence of K2CO3 in dry DCM under N2 atmosphere at room temperature for 18 h, followed

5.5. N,S-Heterocyclic Compounds

5.5.1. Thiazolidines and Thiazolines. Thiazolidine and thiazoline moieties occur in a variety of natural and non-natural products,361 with anticonvulsant, sedative, antidepressant, antiinflammatory, antihypertensive, antihistaminic, and antiarthritic activities.362 In addition, these compounds are useful in synthetic organic chemistry,363 especially in diastereoselective AD


Chemical Reviews

Review

Scheme 89. Synthesis of 2-Benzoylthiazolidine 301a

a

under reflux conditions for 6 h, two products, the chiral 1H,3Hpyrrolo[1,2-c]thiazole 310 and pyrrolo[1,2-c][1,4]thiazine 311 were obtained in 17% and 29% yields, respectively (Scheme 90). Pearson et al.368 described the synthesis of 6-substituted-3benzoylpenems 316 in four steps, by condensation of PG with azetidinones 313 in toluene followed by conversion of obtained 314 to chloro derivatives. Subsequent treatment with triphenylphosphine in the presence of 2,6-lutidine in dioxane at room temperature afforded the phosphorane derivatives 315, which were converted into penems 316 by ozonolysis in the presence of TFA followed by heating to 105 °C in toluene. Also, transformation of phosphoranes 315 to penems 316 was performed using silver nitrate in the presence of DMAP in CH3CN, and then formylation by acetic formic anhydride in the presence of DMAP and NaI, followed by heating at 85 °C in toluene, in which, in addition to penem 316, cis-isomer was isolated in 15% yield (Scheme 91). 5.5.2. Thiazoles and Benzothiazoles. Thiazole is an important scaffold in heterocyclic chemistry and is present in many pharmacologically active substances369 with anti-inflammatory,370 herbicidal,371 antitumoral,372 cardiodepressant,373 antiviral,374 antifungal,375 antiprion,376 and antibacterial activities.377 Also they have wide range applications in organic functional materials such as fluorescent dyes378 and liquid

X= OH, SH.

by reaction with 4 equiv of LiI in refluxing EtOAc for 6 h, and then acidification with aqueous HCl, afforded the Nacylthiazolidine 307. By heating of 307 in refluxing Ac2O for 6 h, chiral 3-benzoyl-1H,3H-pyrrolo[1,2-c]thiazole derivative 308 was obtained in 42% yield via intramolecular 1,3-dipolar cycloaddition of intermediate 312. By a similar procedure on 304b, the enantiomer of 308 was obtained. In contrast, the acylation reaction of 305a,b led to same thiazolidine, which reacted with LiI in EtOAc followed by treatment with aqueous HCl to give thiazolidine 309. With heating of 309 in Ac2O Scheme 90. Synthesis of Pyrrolothiazolidines 308 and 310

AE


Chemical Reviews

Review

Scheme 91. Synthesis of Penems 316 Containing Fused Thiazoline Structurea

a

R= H, Et, MeCH(OSit-BuMe2); R′ = CHCHCO2Et (cond. a); R′ = CPh3 (cond. b).

crystals.379 Widely used routes to thiazoles synthesis, such as Hantzsch thiazole synthesis,380o dehydrative cyclization of αamidoketones using Lawesson’s reagent,380j,k reaction of thioamides or thioureas with α-haloketone derivatives,380a−g,l,m and propargyl alcohols or bromides380h,i,n are reported in the literature.380 Additionally, substituted benzothiazole is an important class of heterocyclic compound that exhibits a wide range of biological properties such as antitumor381 and antimicrobial,382 and also histamine H3-receptor antagonists.383 Many reports have appeared in the literature describing the formation of benzothiazoles,384 including condensation reaction of o-aminothiophenol with carboxylic acid derivatives or aldehyde followed by oxidation384h−j and intramolecular cyclization of thioanilides.384f,k−o Kolos et al.385 reported the reaction of thioureas and thioacetamide with 317, which were obtained by Knoevenagel condensation of 136 with AGs. The thioureas or thioacetamide were treated with 317 in refluxing EtOH or MeOH and the corresponding 2-aminothiazoles 319 or 2-methylthiazoles 318 were obtained in 45−76% or 37−56% yields, respectively (Scheme 92). Also, the one-pot three-component reactions of 136 and AGs with thioureas or thioacetamides were carried out in refluxing EtOH or MeOH for 1 h to give corresponding thiazoles in 39−40% or 73−75% yields, respectively. Also, the reaction of 185 with thioamides was investigated to give substituted thiazoles 320 containing acylamide residues in 64−94% yields (Scheme 93). Deprotection of the acyl group was carried out using saturated solution of HBr in glacial AcOH to afford 5-amino-4-phenylthiazole 321 in 87−90% yields.218 The condensation reaction of o-aminothiophenol with AG was carried out in the presence of 5 mol % cetyltrimethyl ammonium bromide (CTAB) in water under reflux conditions for 4 h, and the corresponding 2-aroylbenzothiazoles 323 were prepared in 80−85% yields. As the authors mentioned, oxygen from the air can act as oxidant for oxidation of thiazoline to the thiazole ring (Scheme 93).386 Also, products 323 were prepared by Cu(I)-catalyzed reaction of disulfide arylamines 322 with PG in AcOH at 80 °C in the open-air system in 66−85% yields (Scheme 94).387 5.5.3. Thiadiazolidines and Thiadiazoles. Thiadiazoles exhibit wide biological behavior,388 such as anti-HIV,389 antiinflammatory,390 anticancer,391 antituberculosis,392 anticonvulsant,393 and antihypertensive activities.394 As a result of these applications, 1,3,4-thiadiazole395 derivatives have been targets of a number synthetic studies. Additionally, thiadiazolidine 1,1-

Scheme 92. Synthesis of Thiazoles 318 and 319a

a

R = H, Me; R′ = H, 2-BrC6H4CO; Ar = Ph, 4-BrC6H4, 4-FC6H4, 4MeOC6H4, 2-thienyl; X = O, S; 318, 37−56%; 319, 45−76%.

Scheme 93. Synthesis of 5-Acylamidothiazoles 320 and 5Aminothiazoles 321a

a

R = BnO, MeO, Me, Ph; R′ = Me, Ph; 320, 64−94%; 321, 87−90%.

dioxides are important heterocycles due to pharmacological properties.396 The method for synthesis of 3-imino-1,2,5-thiadiazolidine 1,ldioxides 325 was described by the reaction of PG-hydrate with sulfamide 324 in the presence of NaCN. The reaction was AF


Chemical Reviews

Review

Scheme 94. Synthesis of 2-Aroylbenzothiazoles 323a

Scheme 96. Synthesis of 2-Amino-1,3,4-thiadiazole 329 and Imino-1,3,4-thiadiazoline 330a

a

Reference 386: cond. = CTAB (5 mol %), water, reflux, 4 h; X = H, Ar = Ph, 4-BrC6H4, 4-ClC6H4, 4-MeC6H4; 80−85%. Reference 387: cond. = Cu(I) 5 mol %, AcOH, air, 80 °C, 5 h; X = 6-Br, 5-CN, 6MeO; Ar = Ph; 66−85%.

carried out by refluxing the solution of PG-hydrate and NaCN with an excess amount of 324 in aqueous ethanol to produce 325 in 20% yield. Probably, the cyanide-mediated cleavage of PG furnished benzaldehyde, which condensed with 324 and cyanide anion to yield 325, which converted to 3-oxo-1,2,5thiadiazolidine 1,1-dioxides 327 when heated with ethanolic HC1 for 24 h to give ethyl 2-sulfamido-substituted ester 326, followed by reaction with NaOMe in MeOH under reflux conditions for 3 h, in 54% overall yield (Scheme 95).397

a

R = H, Me; R′ = H, Me; R″ = H, Me, Ph.

thione 334 were obtained through nucleophilic attack of terminal nitrogen atom to the carbonyl group. But in the case of thiosemicarbazone 328e, thiadiazole 329 was produced via oxidative cyclization along with nucleophilic attack of sulfur atom to the CN bond (Scheme 97).399

Scheme 95. Synthesis of 3-Oxo-1,2,5-thiadiazolidine 1,1Dioxide 327

Scheme 97. Behavior of 328 in aq. NaOH and Synthesis of Thiadiazole 329a

a

328a,b: R = R′ = H; R″ = H, Me; 2 N NaOH, rt, 24 h. 328c,d: R = H; R′ = Me; R″ = H, Me; 2 N NaOH, rt, 15 min, or 5% NaOH, reflux, 5 min, then 10% HCl. 328e: R = R′ = Me; R″ = H; 2 N NaOH, rt, 15 min.

Werber and co-workers398 reported the FeCl3-mediated oxidative cyclization of thiosemicarbazones 328, which were prepared by reaction of PG-hydrate with corresponding thiosemicarbazide in very dilute and cold aqueous solution. The reactions were carried out by heating of the mixture of 328 and FeCl3 in water, and depending on the R and R′ substituents on 328, thiadiazoles 329 (with R = H) and thiadiazolines 330 (with R = Me and R′ = H) were obtained. The benzoyl group on 329 and 330 was removed by nucleophilic attack of NaOH in refluxing EtOH to give 331 and 332, respectively (Scheme 96). Also, the behavior of 328 was investigated in aq. NaOH at room temperature and different cycloadducts were obtained according to the substituent on the terminal nitrogen atom. In the case of 328a−d (R = H), the corresponding dihydro-1,2,4triazine-3-thione 333 and 5-hydroxytetrahydro-1,2,4-triazine-3-

5.6. O,P-Heterocyclic Compounds

5.6.1. Dioxophospholanes. Ramirez et al.400 reported the synthesis of unsaturated dioxophospholane 335 via reaction of PG with a large excess amount of trimethyl phosphite (TMP) in DCM under N2 atmosphere at 0 °C. Pentaoxyphosphorane 335 was obtained in 48% yield, which was transformed to 2:1 adduct 336 in quantitative yield when reacted with a second molecule of PG. Dioxophospholane 336 was obtained as two diastereoisomers, meso-336b and racemic-336a, in 65/35 ratio. Also the reaction of biacetyl-TMP 1:1 adduct 337 with PG was investigated, and dioxophospholane 338 was obtained in quantitative yield as two diastereoisomers, 338a and 338b (Scheme 98). Also, the same products 338a,b were obtained by the reaction of biacetyl with 335. AG


Chemical Reviews

Review

Scheme 98. Synthesis of Dioxophospholanes 335, 336, and 338

6. SYNTHESIS OF SIX-MEMBERED HETEROCYCLES

elimination reaction of the hydroxylamine obtained from reaction of silyl enol ether 342 with nitrosobenzene (Scheme 100).

6.1. N-Heterocyclic Compounds

6.1.1. Tetrahydropyridines. Tetrahydropyridines are one of the fundamental heterocycles due to their biological activity401 and wide range of applications in pharmaceuticals and synthetic intermediates.402 Consequently, their synthesis has received much attention.403 The aza-DA reaction is potentially one of the most versatile and rapid routes to substituted piperidines.404 The aza-DA reaction of different dienes with PG-imine 3, which was in situ generated by reaction of p-anisidine and PGhydrate, was reported using lanthanide triflates, such as Yb(OTf)3 and Sc(OTf)3, in the presence of MgSO4 in CH3CN at room temperature. When 2,3-dimethyl-1,3butadiene was used, corresponding tetrahydropyridine 339 was isolated in 44% yield. In the case of Danishefsky’s diene (R′ = R‴ = H, R = OMe, R″ = OSiMe3), the corresponding 2,3dihydropyridin-4(1H)-one 340 was obtained in 76% yield. But in the case of cyclopentadiene, the PG-imine 3 acted as diene and tetrahydro-1H-cyclopenta[c]quinoline 341 was obtained in 94% yield (Scheme 99).405 Also the same authors reported a similar reaction with aniline, p-anisidine, and p-chloroaniline in very high to quantitative yield.406 Sasaki et al.407 reported the aza-DA reaction of AG-imines 3 with dienes in the presence of BF3·OEt2 at room temperature to afford tetrahydropyridine derivatives 343 in 7−52% yields. The AG-imines 3 were in situ generated by Et3N-catalyzed

Scheme 100. In Situ Generation of AG-imines 3 via Reaction of 342 with Nitrosobenzene and Their Aza-DA Reactiona

a R = Ph, R′ = H, Ar = Ph; 25%; R = H, R′ = Me, Ar = Ph, 4-BrC6H4, 4-MeOC6H4, 4-MeC6H4, 2-furyl, 2-pyridyl; 7−52%.

Zhang et al.408 described the Yb(OTf)3-catalyzed solid phase aza-DA reaction of PG-hydrate, dienes, and immobilized benzylamine 344 in DCM at room temperature. After cleavage of products from the solid support 345, the tetrahydropyridine derivatives 346 were obtained in excellent yields with high levels of purity. Cleavage of resin support was achieved using 5 equiv of 1-chloroethyl chloroformate (Scheme 101). The aza-DA reaction of diene 348 with imines, derived from amine hydrochloride and PG, was reported by Chou et al.;409 the reaction was accomplished by stirring of a mixture of 348, amine, and PG in DMF at room temperature to afford Nsubstituted 2-benzoyl-4-(phenylthio)-1,2,3,6-tetrahydropyridines 349 in 63−95% yields. The diene 348 was prepared by desulfonylation of 3-(phenylthio)-3-sulfolene 347 (R = H), using NaHCO3 in the presence of hydroquinone (HQ) in toluene under reflux condition (Scheme 102). In the case of 2methyl-4-(phenylthio)-3-sulfolene 347 (R = Me), the reactions were dependent on temperature, and in the case of benzylamine at room temperature only trans isomer was obtained in 60% yield. The reaction temperature and diastereoselectivity are illustrated in Scheme 102.410 Cycloaddition reactions of methanol addition adducts of PGimines 350, prepared by reaction of PG-hydrate with anilines in MeOH, with different dienes was reported by Lucchini et al.411

Scheme 99. Synthesis of Tetrahydropyridine 339 and Pyridone 340 via Aza-DA Reaction

AH


Chemical Reviews

Review

major products in 59−70% yields (exo/endo = 44/15−57/13), but with electron-releasing groups such as Me (350c) substituents, hexahydrophenanthridine derivative 341c′ was isolated as major product in 61% yield. Heating of 343 (R′ = Me and R″ = H or Me) in refluxing toluene with a stoichiometric amount of BF3·OEt2 for 4 h led to pyrido[1,2a]indole derivatives 354a,b or 355a,b, respectively (Scheme 103). There is also another report on HAD reaction of PGimine with 1,3-butadiene, cyclopentadiene, and cyclohexadiene using BF3·OEt2.412 6.1.2. Pyridines. Pyridines are found as skeletal moieties of many biologically active compounds and natural products,413 which exhibit anti-HBV,414 antibacterial,415 and anti-ischemic activity,416 and as potassium channel openers,417 agonists for adenosine A1 receptor,418 and agonists for human adenosine A2B receptor.419 Moreover, they have many applications in supramolecular chemistry, due to their π-stacking ability along with H-bonding capacity.420 Thus, the synthesis of pyridines has attracted much attention, and a number of procedures have been developed.421 Among these, very convenient approaches were the oxidative aromatization of 1,4-DHPs,422 multicomponent reaction of aldehydes with malononitrile423 or acetophenone derivatives424 in the presence of nitrogen source and catalyst, and Bohlmann−Rahtz pyridine synthesis.425 Also, a combination of the wide variety of methods for the synthesis of substituted 1,2,4-triazines, coupled with the aza-DA reaction with various dienophiles, allows the synthesis of functionalized pyridines. Diring et al.426 described a protocol for the efficient synthesis of substituted 6-phenyl-2,2′-bipyridine derivatives 358, which were suitable ligands for the synthesis of cyclometalated complexes. 2,6-Disubstituted 1,2,4-triazine derivatives 357a, which were synthesized by the condensation reaction of PG with 2-pyridyl amidrazone 356, were converted into 6-phenyl2,2′-bipyridine derivatives 358 via [4 + 2] cycloaddition reaction with monofunctionalized alkynes in o-dichlorobenzene at high temperature followed by reverse-DA reaction. When 4ethynyltoluene, 2-ethynyl-9,9-dimethylfluorene, and 3-ethynyl9-methylcarbazole were used, the major products were the 3aryl isomers 358b (9−42% yields), whereas the 4-aryl isomers 358a were isolated in low yield (8−13%). Electron-rich terminal alkynes, such as 3-ethynylperylene and 1-ethynylpyrene, provided almost exclusively the 3-aryl isomers 358b. Also, benzyne was treated with 357a to give the fused isoquinoline molecule 359 in low yield. Benzyne was prepared in situ from anthranilic acid and isoamyl nitrite (Scheme 104). The synthesis of terpyridines and higher oligopyridines 364 was reported by Pabst et al.427 via [4 + 2] cycloaddition reaction of aryl or heteroaryl substituted 1,2,4-triazines 361 and 362 with bicyclo[2.2.1]hepta-2,5-diene 363, followed by [4 + 2] cycloreversions of nitrogen and cyclopentadiene in odichlorobenzene at 140 °C in 50−79% yields. Intermediates 361 and 362 were prepared via condensation reaction of 2pyridylglyoxal with amidrazone 356 or bis-amidrazone 360 in aqueous EtOH at room temperature (Scheme 105). Also, a similar procedure was used for preparing of superbranched oligopyridines 366 starting from condensation of pyridine-2,4,6-tricarboxtrisamidrazone 365 with 2-pyridyland 2-thienylglyoxals (Scheme 106).428 A similar reaction was reported for synthesis of bipyridine derivatives in which triazines were synthesized by cyclocondensation reaction of 2-pyridylamidrazone with arylglyoxal-1-hydrazono-2-oximes, which were prepared by nitrosation

Scheme 101. Synthesis of Tetrahydropyridines 346 via Solid Phase Aza-DA Reaction

Scheme 102. Desulfonylation of 347 and Their Aza-DA Reactiona

a 349a: R = H; R′ = Me, Bn, Ph; rt, 63−95%. 349b: R = Me; R′ = Bn; rt, 60%, trans only; 0 °C, 60%, cis/trans = 2/7; −20 °C, 52%, cis/trans = 2/5. 349c: R = R′ = Me; 90 °C, 78%, cis/trans = 2/7; 60 °C, 88%, cis/trans = 1/2; rt, 76%, cis/trans = 1/3; −10 °C, 52%, cis/trans = 3/4; −20 °C, 75%, cis/trans = 1/1.

Reactions were carried out by adding of 1.5 equiv of diene to a stirred solution of 350 and 1 equiv of BF3·OEt2 in DCM at room temperature for a few minutes to produce the corresponding substituted tetrahydropyridines 343. When 1,3butadiene was subjected to the DA reaction with 350a,b, 6benzoyltetrahydropyridines 343a,b were isolated in 0−16% yields, while tetrahydroquinoline derivatives 351a,b were isolated as major products in 40−77% yields, in which PGimines act as diene component. With 2-methyl-1,3-butadiene and 2,3-dimethyl-1,3-butadiene, the corresponding tetrahydropyridines 343a′−b″ were obtained in 65−88% yields as major products. In addition to 343a′, tetrahydrofurane derivative 352 was isolated as two stereoisomers only in 7% yield, in the case of 2-methyl-1,3-butadiene. By treatment of cyclopentadiene with 350a,b, the corresponding 341a,b were isolated in 87− 88% yields. When AlCl2OMenth was used as catalyst at −20 °C, only 3-benzoylazabicyclo[2.2.1]hept-5-ene 353a was isolated in low yield (8%). In treatment of 1,3-cyclohexadiene with 350a−c, the product distribution was affected by the substituent on 350. With electron-withdrawing groups such as nitro and chloro substituents (350 a,b), the 3benzoylazabicyclo[2.2.2]oct-5-enes 353a′,b′ were obtained as AI


Chemical Reviews

Review

Scheme 103. Aza-DA Reaction of 350 with Different Dienes

nolines 374b (n = 2) via 1,2,4-triazines 368 in 41−84% yields. Substitution of methyl sulfinate with anions of active methylene compounds 373 afforded alkyne tethered to C-3 of the 1,2,4triazines, which underwent the intramolecular inverse electron demand DA reaction (Scheme 108). Also, the condensation reaction of PG with acylhydrazide 375 in the presence of NH4OAc in refluxing AcOH was investigated, in which in situ generated 1,2,4-triazine underwent the intramolecular inverse electron demand DA reaction to afford 374a (X = Y = H) in 35% yield as a 1:1 mixture of two regioisomers (Scheme 109). The intramolecular inverse electron demand DA reaction between imidazole and 1,2,4-triazines linked by a trimethylene tether from the imidazole N-1 position, 378, to produce cycloadducts 381 was studied by Lahue et al.434 Reactions were carried out in either refluxing tri-iso-propylbenzene or refluxing Ph2O and afforded unexpected product 1,2,3,4-tetrahydro-1,5naphthyridines 380 in 75−89% yields. The reactions proceeded by a cycloaddition with subsequent loss of nitrogen, followed by presumed stepwise loss of a nitrile (intermediate 379). 1,2,4Triazines 378 were prepared by either condensation of

of acetophenones, then by treatment with hydrazine hydrate in good yields.429 Similarly, the 2-thienyl pyridine was synthesized.430 An efficient method for synthesis of polysubstituted 2,3dihydrofuro[2,3-b]pyridines (n = 0) and 3,4-dihydro-2Hpyrano[2,3-b]pyridines (n = 1) 371−372 from 1,2,4-triazines 368 was reported by Hajbi et al.431 via inverse electron demand DA reaction under microwave irradiation. The 3-methylsulfonyl-1,2,4-triazine 368 was synthesized by condensation of PG with S-methylthiosemicarbazide 367, followed by MCPBA oxidation. The 368 was transformed to 1,2,4-triazine substituted alkynols 369 and 370 in three or four steps. The intramolecular inverse electron demand DA reaction of 369 and 370 was carried out by heating of the solution of 369 or 370 in chlorobenzene under microwave irradiation, and corresponding pyridines 371 or 372 were obtained in 91− 93% or 67−99% yields, respectively (Scheme 107). Also, a similar procedure was applied by Taylor and Macor.432 Taylor and co-workers433 reported the synthesis of 2,3cyclopentanopyridines 374a (n = 1) and 5,6,7,8-tetrahydroquiAJ


Chemical Reviews

Review

Scheme 104. Synthesis of Bipyridines 358 via Inverse Electron Demand DA Reaction of Triazines 357a

a

Ar = 4-MeC6H4, 9-Me-carbazole-3-yl, 9,9-Me2-fluorene-2-yl, perylene-3-yl, pyrene-1-yl; 358a, 8−13%; 358b, 9−42%.

Scheme 105. Synthesis of Oligopyridines 364 via DA−Inverse DA Reactions of Triazines

3,4-dihydrofuran 165, catalyzed by salen−AlCl complex 383. The reaction was carried out by addition of 165 and 383 to a mixture of PG-hydrate and aniline in dry CH3CN and stirring at room temperature for 7 h to afford the cycloaddition product 382 in the endo/exo ratio of 10:90 (Scheme 111). The three-component aza-DA reaction of PG-hydrate, anilines, and 165 or cyclopentadiene catalyzed with Ph3P·HClO4 was reported by Nagarajan et al.447 The reactions were carried out in CH3CN at room temperature to produce the isomeric mixture of furoquinolines 382 in the ratio of 35:65 in an overall yield of 77%. Reaction with cyclopentadiene resulted in the corresponding 341 in 82−93% yields. Also, reaction of PG-imine with cyclopentadiene using KHSO4 as catalyst in MeOH448 or Nafion-Sc as catalyst in a water− EtOH−toluene (1:7:4) solvent system449 at room temperature was reported. There is another report on aza-DA reaction of cyclopentadiene with imines derived from PG.450

acylhydrazide 376 with PG in the presence of NH4OAc in AcOH or condensation of amidrazone 377 with AGs (Scheme 110). 6.1.3. Tetrahydroquinolines and Quinolines. Quinolines and the related tetrahydroquinolines constitute a group of heterocycles largely occurring in natural products,435 which exhibit broad biological activity436 such as antibacterial,437 fungicidal,438 pesticidal,439 antimalarial,440 antioxidant,441 antidepressive,442 anti-inflammatory,443 and antidiabetic activities.444 A variety of approaches, such as aza-DA reaction,445d,o−r Friedländer annulation,445s−u alkynylation−cyclization reactions,445v,w Combes synthesis,445x and Döbner−Von Miller and Conrad−Limpach445y reactions have been developed for the synthesis of tetrahydroquinoline and quinoline skeletons.445 Magesh et al.446 described the DA reaction of PG-imine 3, in situ generated from reaction of PG-hydrate and aniline, with AK


Chemical Reviews

Review

Scheme 106. Synthesis of Superbranched Oligopyridines 366 via Triazinesa

Scheme 108. Synthesis of Cyclopentanopyridines and Tetrahydroquinolines 374 via Triazinesa

a a, n = 1; b, n = 2; Ar = Ph, 4-ClC6H4, X = COMe, CO2Me, CN; Y = CO2Me, CO2Et, CN; 41−84%.

Scheme 109. Synthesis of Cyclopentanopyridine 374 (X = Y = H) via Triazine a

Het = 2-pyridyl; cond. = p-xylene, reflux, 6 d, 46%. Het = 2-thienyl; cond. = o-Cl2C6H4, 145−150 °C, 1 d, 30%.

Tarantin et al.451 described the reaction of methyl 12aminodehydroabietate with AGs to afford 384 and its aza-DA reaction with ethyl vinyl ether, cyclopentadiene, and indene. The reactions were carried out in 2,2,2-trifluoroethanol in the presence of BF3·OEt2 at room temperature. With ethyl vinyl ether, as shown in Scheme 112, quinolines 386 were obtained by elimination of EtOH molecule from intermediate 385, followed by oxidation with atmospheric oxygen, in 20−37% yields. In the reaction with cyclopentadiene and indene, quinolines 387a,b were isolated in 38−96% yields. The (6R)/ (6S) ratio of 387a and 387b was determined using 1H NMR spectra as 1:1−2:1 and 1:1−3:2, respectively. Saggiomo and co-workers452 reported the Doebner reactions of AG-hydrates, p-chloroanilines, and pyruvic acid 388 to produce 2-benzoylcinchoninic acids 389 in 21−39% yields. The reaction was carried out by addition of pyruvic acid 388 to a suspension of an aniline and an AG-hydrate in AcOH and H2SO4 and heating to 115 °C for 50 min. Products 389 were converted to 2-benzoyl-4-quinolinemethanols 390 (which exhibit moderate antimalarial activity, especially in the case of Cl and CF3 substitution on benzoyl moiety) in four steps in 5− 59% yields, as illustrated in Scheme 113.

The condensation reaction of o-aminophenylglyoxal-dimethylacetal 391 with several cyclic and acyclic ketones was reported in the presence of sodium in absolute EtOH to give quinoline-4-carbaldehyde-dimethylacetal derivatives 392 in 85− 97% yields, which were hydrolyzed to corresponding aldehydes 393 using 2 N HCl. Also the reaction of 391 with ethyl acetoacetate and diethyl malonate was carried out at 150−160 °C to afford 394 in 70−94% yields (Scheme 114).453 6.1.4. Isoquinolines. The isoquinoline ring system is found in pharmaceuticals454 and in a variety of natural products such as alkaloids.455 Due to their substantial applicability, the synthesis of isoquinoline derivatives has received considerable attention.456 The most common routes to isoquinolines are

Scheme 107. Synthesis of Furo[2,3-b]- and Pyrano[2,3-b]pyridines 371 and 372 via Triazines 369 and 370a

a

n = 0, 1; 371, R = H, 220 °C, 0.75−2 h, 91−93%; 372, Ar = 4-MeOC6H4, 4-MeC6H4, 4-NO2C6H4, 2-thienyl, 180−240 °C, 2.5−8 h, 67−99%. AL


Chemical Reviews

Review

Scheme 110. Synthesis of Tetrahydro-1,5-naphthyridines 380 via Triazines

Pictet−Spengler reaction,456e−g Bischler−Napieralski reaction,456h,i and recently, catalyzed cyclization of o-halobenzylamines and o-alkynyl benzyl azides.456j−l Nimgirawath et al.457 described a method for synthesis of 1aroyl-1,2,3,4-tetrahydroisoquinolines 396 via Pictet−Spengler reaction between AG-hydrates and 2-arylethylamine 395. The reaction was studied under various conditions, and it was found that refluxing with 3 N aq. HCl for 5 h afforded 396 in 25−75% yields (Scheme 115), but formic acid was less effective than 3 N HCl, while AcOH, TFA, and p-TsOH were completely ineffective. Treatment of PG with cysteine methyl ester resulted in thiazolidine 305, which was converted to isoquinoline 398 and 399 with pyrrolidinocyclohexene in the presence of AgCO3 and DBU via aza-diene 397 in 35% and 14% yields, respectively (Scheme 116).458 6.1.5. β-Carbolines. β-Carbolines are present in numerous natural and synthetic organic compounds and possess various biological activities459 such as hypnotic, anxiolytic, antimicro-

Scheme 111. Synthesis of Hexahydro-Furoquinolines 382 via Aza-DA Reaction

Scheme 112. Aza-DA Reaction of AG-Imines 384 with Different Dienesa

a

Ar = Ph, 4-ClC6H4, 4-MeOC6H4, 4-MeC6H4. AM


Chemical Reviews

Review

Scheme 113. Synthesis of Quinolinemethanols 390a

Scheme 115. Synthesis of Tetrahydroisoquinolines 396a

a

R = H, OMe; R′ = H, OMe; R, R′ = OCH2O; Ar = Ph, 4-ClC6H4, 4MeOC6H4, 3,4-(MeO)2C6H3, 4-MeC6H4; 25−75%.

Scheme 116. Synthesis of Hydroisoquinolines through AzaDiene 397

a R = Cl, CF3; Ar = Ph, 4-ClC6H4, 3,4-Cl2C6H3, 3,5-Cl2C6H3, 3CF3C6H4, 4-CF3C6H4, 3,5-(CF3)2C6H3; 5−59%.

bial, anti-HIV, antiviral, antitumor,460 anticonvulsant,461 and antioxidant activity462 and inhibition of topoisomerase I.463 Carboline derivatives are also useful as intermediates for natural product synthesis.464 There are a number of reports for synthesis of β-carbolines in the literature,465 using Pictet− Spengler reaction methodology,465n−p and Pd-catalyzed iminoannulation of indolcarbaldehydes with alkynes.465q−s The synthesis of 1-substituted β-carbolines 401−403 was described by Yang et al.466 via modified Pictet−Spengler reaction between L-tryptophan 400 and AG-hydrates. Different solvents, such as MeOH, acetone, CH3CN, THF, 1,4-dioxane, DMSO, and DMF, and various acids, such as H2SO4, p-TsOH, and HCl, were examined as reaction conditions, and p-TsOH in MeOH was selected for the best results. The reaction was carried out by addition of 1.0 equiv of PG-hydrate to a stirred suspension of 1.3 equiv of 400 and 1.0 equiv of p-TsOH·H2O in MeOH with heating at 50 °C for 2 h (Scheme 117). This methodology was applied for the synthesis of luzongerine A 404, isolated from Illigera luzonensis. Also, Kulkarni et al.467 developed a three-step, one-pot, microwave-assisted synthesis

of 401 via a condensation/cyclization/dehydrogenation sequence, involving coupling of 400 with AGs using Pd/C/ K-10 catalyst system in 79−96% yields in 2−12 min. Treatment of iminophosphorane 405 with AGs in toluene at 160 °C afforded l-aroyl-β-carboline derivatives 406 in 60−65% yields via aza-Wittig−electrocyclic ring-closing reactions, followed by dehydrogenation under the reaction conditions. Compounds 406 (X = F, Cl), under treatment with either HCO2H or pyridinium hydrochloride at 170 °C, underwent cyclization through the indole nitrogen atom leading to 407 in 90% yield. Hydrolysis of 406 (X = NO2) with LiOH in THF/

Scheme 114. Synthesis of Quinoline-4-carbaldehydes 393 and 394

AN


Chemical Reviews

Review

Scheme 117. Synthesis of β-Carbolines 401−403 via Pictet−Spengler Reactiona

a R = H, CO2H; R' = H, 5-F, 5-MeO; Ar = Ph, 4-BrC6H4, 4-FC6H4, 4-CF3C6H4, 4-MeOC6H4, 4-MeC6H4, 5-MeO-naphth-2-yl; cond. = p-TsOH, MeOH, 50 °C, 2 h; 401, 15−20%; 402, trace−40%; 403, 3−6%; cond. = Pd/C/K-10, MW, 130 °C, 2−12 min; 401, 79−96%.

Scheme 118. Synthesis of β-Carbolines 406 and Their Conversion into 407 and 408

N2 atmosphere in EtOH in 87% yield, with 34:1 ratio of two regioisomers 410a/410b (Scheme 119). Benson and co-workers470 reported the intramolecular inverse electron demand DA reaction between indole and 1,2,4-triazine linked by a trimethylene tether from the indole N1 position, which was prepared either by condensation of PG with acylhydrazide intermediate 420 in the presence of NH4OAc or by condensation of PG with amidrazone 421. By heating of 422a or 422b at 232 °C in tri-iso-propylbenzene for 1.5 h, the corresponding canthine skeleton 423a or 423b was obtained in 87% or 93% yield, respectively (Scheme 120). 6.1.6. Pyridazines. The pyridazine ring is broadly present in biologically471 and pharmacologically active compounds472 such as antidepressants. Pyridazines are also of considerable interest because of their synthetic utility473 and applications in physical organic chemistry.474 A number of pyridazine syntheses, including cycloaddition reactions of 1,2,4,5-tetrazines with different dienophiles475a,b,l and cyclocondensation of 1,4dicarbonyl compounds with hydrazine,475m,n are reported in the literature.475

H2O at room temperature followed by selective reduction of the nitro group by catalytic hydrogenation in the presence of PtO2, provided the amino derivative in 80% yield, which was transformed to fascaplysin 408 in 60% yield by diazotization and further heating of the resulting diazonium salt (Scheme 118).468 The inverse electron demand DA reaction between indole and 1,2,4-triazine 410 was reported by Benson et al.469 using small amount of diglyme as solvent at 180 °C. β-Carboline 415 was obtained via cycloaddition−reversion adduct 414, as intermediate, in 50% yield. 2-Phenyl-β-carboline 416 was produced by hydrolysis of the ester group in 415, with subsequent decarboxylation in very low yield. The yield of 416 was increased when reaction was carried out in wet diglyme. In addition to 415, the rearranged adduct 413 was obtained via intermediates 411 and 412 in 5% yield. Quinoline 419 was also obtained in 21% isolated yield through the ring-opened diimine 417, followed by hydrolysis to 418 with subsequent ring closure. 1,2,4-Triazine 410 was prepared by condensation reaction of PG-hydrate with ethyl oxalamidrazonate 409 under AO


Chemical Reviews

Review

Scheme 119. Synthesis of β-Carboline 415 and Quinoline 419 via Triazines

Scheme 120. Synthesis of Canthine 423 via Triazines

Rimaz et al.476 recently described an efficient threecomponent one-pot method for synthesis of pyridazine-4carboxylates 424 in 70−97% yields via reaction of hydrazine hydrate (5 equiv), 1,3-dicarbonyl compounds (1 mmol), and AGs (1 mmol) in water at room temperature as shown in

Scheme 121. Also a similar reaction was performed using ultrasound irradiation to produce the corresponding pyridazines 424 in good yields in short reaction times in contrast to the conventional procedure.114 AP


Chemical Reviews

Review

Scheme 121. Synthesis of Pyridazine-4-carboxylate 424a

Scheme 123. Synthesis of 3,5-Disubstituted Pyridazines 430a

a

R = t-Bu, Et, Me; Ar = Ph, 4-BrC6H4, 4-ClC6H4, 4-FC6H4, 3,4(MeO)2C6H3, 3,4-(OCH2O)C6H3; 70−97%.

The synthesis of steroidal pyridazine derivatives 427 from 2acetylestradiol 425 was reported by Ismail and co-workers.477 Treatment of 425 with AGs in refluxing Ac2O afforded the corresponding 1,4-dicarbonyl compounds 426, which were transformed to the corresponding 427 when heated with hydrazine hydrate in EtOH in the presence of a few drops of glacial AcOH under reflux conditions (Scheme 122).

a

R = H, Me; Ar = Ph, 2-(N-Me-pyrrolyl), 2-naphthyl, 2-thienyl; 31− 62%.

aminopyridazine 435 in 75% yield (Scheme 124).479 A similar reaction was carried out by Bourotte et al.480 using benzylamine or 2,4-dimethoxybenzylamine (DMB). Two regioisomers, 433 and 434, were obtained by cyclocondensation of PG with the enamine intermediate 432. The 6-phenyl derivative 433 was obtained as the major product. The conversion of 433b,c into the corresponding 4-bromo derivatives was achieved by treatment with HBr/AcOH under reflux conditions. Under these conditions, the protecting group DMB was also removed, whereas the benzyl group was not removed. Obtained 4-bromo pyridazines underwent Suzuki and Sonogashira coupling reactions with various reagents to give 3-aminopyridazines 436 substituted at position 4 (Scheme 124). 6.1.7. Fused Pyridazines. Due to the wide range of biological and pharmacological activity,481 such as monoamine oxidase inhibitory,482 cytotoxic,483 anthelmintic,484 antiviral,485 and antibacterial486 activities, some synthetic routes for construction of fused pyridazines are found in the literature.484,485,487 Morrison and co-workers488 described the cyclizations of AG-hydrates with 6-hydrazinoisocytosines 437 to give pyrimido[4,5-c]pyridazines 438. Reactions were carried out by heating the mixture of 437 and AG-hydrate in different solvents such as water, MeOH, and AcOH. In the case of PGhydrate in MeOH, only 4-phenyl isomer 438a was isolated in 50% yield, while using m-HOC6H4COCHO, two isomers, 438a,b were obtained in a/b = 5/1 ratio. In water as solvent, only 438b was isolated in 49% yield. Also the PG-oxime was subjected to this reaction in AcOH and afforded the 3-phenyl isomer 438b in 58% yield (Scheme 125). The method for synthesis of 3- and 4-substituted pyrimido[4,5-c]pyridazines 441 from reaction of uracil 439 with AGhydrates was reported by Turbiak et al.489 The reaction was conducted by treatment of AG-hydrates with 439 under different conditions. By treatment of 439 with PG-hydrate in refluxing EtOH or water, hydrazone 440 was obtained. When reaction was carried out in DCE, solely 441b was obtained, while reactions in aqueous NaOAc resulted in a mixture of both regioisomers, 3- and 4-substituted pyrimidopyridazinedione 441a,b (Scheme 126). A one-pot procedure was reported to synthesize of 3arylpyrimido[4,5-c]pyridazines 442 by stirring a mixture of 136 with AGs in the presence of pyridine in water at room temperature for 20 min, followed by addition of an excess amount of hydrazine hydrate and stirring for additional minutes. The products 442 were obtained in 43−93% yields (Scheme 127).490

Scheme 122. Synthesis of Steroidal Pyridazines 427a

a

Ar = Ph, 4-BrC6H4, 4-MeC6H4; R = H, 18−25%; R = OAc, 30−38%.

Marriner and co-workers478 reported the reaction of AGhydrates with in situ generated aldehyde enolates via rhodiumcatalyzed enal hydrogenation of 428 to afford β-hydroxy-γ-keto aldehydes 429, which were converted into 3,5-disubstituted pyridazines 430 by treatment with excess hydrazine in MeOH. By treatment of 1 equiv of KOAc, AG-hydrate (1 mmol), and then 5 equiv of 428 with a solution of Rh(COD)2OTf (1 mol %) and Ph3P (2.4 mol %) in DCE under an Ar atmosphere followed by flushing with H2 and stirring under 1 atm of H2 at ambient temperature, intermediates 429 were obtained, which in reaction with excess hydrazine in MeOH at room temperature for 45 min provided pyridazines 430 in 30−62% yields (Scheme 123). Also, another example of the construction of pyridazine ring 433a (R = morpholino) was described by nucleophilic addition of 1-aminoethylmorpholine and then hydrazine hydrate onto the 1,1-bis(thiomethyl)-2-nitroethylene 431 in refluxing EtOH followed by condensation with PG in 51% yield. The catalytic hydrogenation of the nitro group of 433a with H2/Pd/C gave AQ


Chemical Reviews

Review

Scheme 124. Synthesis of 3-Aminopyridazines 435 and 436a

R′ = Ph, 2-BrC6H4, 4-ClC6H4, 2-MeOC6H4, 4-MeC6H4, 2-thienyl, CR″ (R″ = TMS, Ph, (CH2)3OBn, CH2NHBoc); cond. = R′B(OH)2, Pd(Ph3P)4, Na2CO3, EtOH−toluene, Ar (atm.), 110 °C, 20 h, or alkyne, PdCl2, CuI, Ph3P, Et3N, CH3CN, Ar (atm.), 70 °C, 12 h. 433 + 434, 70− 76%; 433/434 = 60/40−70/30; 436b, R = Bn, 40−79%; 436c, R = H, 45−92%. a

Scheme 125. Synthesis of Pyrimido[4,5-c]pyridazines 438a

Scheme 127. Synthesis of 3-Arylpyrimido[4,5-c]pyridazines 442a

a

X = O, S; Ar = Ph, 4-BrC6H4, 4-ClC6H4, 4-FC6H4, 4-MeOC6H4, 3,4(MeO)2C6H3, 3,4-(OCH2O)C6H3, 4-NO2C6H4; 43−93%.

(6H,8H)-diones 443 were obtained in 76−92% yields. The AG-hydrazones 198, in situ prepared by condensation of AGs with hydrazine, was proposed as the reaction intermediate (Scheme 128).491

a

X = O·H2O, R = Me, solvent = MeOH, reflux, 3−4 h: Ar = Ph, 438a, 50%; Ar = 3-HOC6H4, 86%, 438a/438b = 5/1. X = O·H2O, R = H, solvent = water, reflux, 1 h: Ar = Ph, 438b, 49%. X = NOH, R = Me, solvent = AcOH, 55 °C, 20 h: Ar = Ph, 438b, 58%.

Scheme 128. Synthesis of 4-Arylpyrimidopyridazie-diones 443a

Scheme 126. Synthesis of Pyrimido[4,5-c]pyridazinediones 441a

a

Ar = Ph, 3-BrC6H4, 4-BrC6H4, 4-ClC6H4, 4-FC6H4, 3-MeOC6H4, 4MeOC6H4, 3,4-(MeO)2C6H3, 3,4-(OCH2O)C6H3, 4-NO2C6H4; 76− 92%. a

Ar = Ph, cond. = EtOH, reflux, 24 h, 440, 50%; Ar = Ph, 4-ClC6H4, 4Cl-3-NO2C6H3, 3-FC6H4, 4-FC6H4, 4-CF3C6H4, 4-MeOC6H4, cond. = DCE, reflux, 1.5−24 h, 441b, 22−85%; cond. = NaOAc, water, reflux, 1 h, 441, 43−65%, b/a = 0.2−1.

One example of the conversion of PG to pyrazolo[3,4c]pyridazines 447 in four steps was reported. The pyridazinone 445 was obtained via condensation reaction of PG and cyanoacetohydrazide 444 in EtOH at room temperature followed by treatment with sodium in EtOH. Compound 445 was transformed into 447, in 88% yield, by treatment with excess POCl3 in dioxane under reflux conditions to produce

By treatment of 1,3-dimethylbarbituric acid 136 with AGs in the presence of NH2NH2·2HCl in EtOH under reflux conditions, 4-aryl-6,8-dimethylpyrimido[4,5-c]pyridazine-5,7AR


Chemical Reviews

Review

446, followed by reaction of 446 with hydrazine hydrate in refluxing absolute EtOH (Scheme 129).492

Scheme 131. Synthesis of Aroyl-HHP 450 and Tetrahydropyrimidine 451a

Scheme 129. Synthesis of Pyrazolo[3,4-c]pyridazines 447

Cond. = ether, reflux, 40 min; 450, 89%. Cond. = EtOH, 65 °C (5 min) → rt (1 d); 451, 17%.

a

antifungal,505 antidepressant,506 antimigraine,507 antithrombotic,508 antiaggregating,509 and nootropic activity.510 Furthermore, these heterocyclic compounds are present in several biologically active compounds, such as μ-opioid receptor agonists,511 NNRTI’s (non-nucleoside reverse transcriptase inhibitors),512 Leu-enkephalin analogs,513 cholecystokinin receptor antagonists,514 RGD mimetics,515 and the neurokinin-2 receptor ligand.516 Some progress has recently been made toward the development of synthetic methods for these heterocycles,517 such as condensation of ethylenediamine derivatives with α-haloacetic acids,517i−l and from dipeptidyl chloromethyl ketones.517m,n The condensation reaction of tetraamines 452, 456, and 460 with PG-hydrate was reported by Tripier and co-workers.518 The reactions were carried out by slowly adding a solution of PG-hydrate in absolute EtOH to a solution of the convenient linear tetraamines 452 and 456 or tetraazamacrocycle 460 in absolute EtOH at room temperature under vigorous stirring. In the case of linear polyamines 452 and 456, depending on the nature (lateral or central) of the diiminium intermediates 453 and 457, gem/cis 454 and vic/cis or trans 458 were produced by intramolecular nucleophilic addition of amine to intermediates 453 and 457, respectively. With cyclic tetraamines 460, tetracyclic bis-aminals 462 with cis configuration at the bisaminal bridge were obtained via six-membered diiminium rings 461. Piperazinone derivatives 455, 459, and 463 were prepared from 454, 458, and 462 in boiling water in good yields (Scheme 132). However, condensation of PG with 452, 456, and 460 in boiling water gave directly 455, 459, and 463, respectively. Mukaiyama et al.519 reported the synthesis of 5-arylimidazo[1,5-a]pyrazine derivatives 467 in six steps. By treatment of AGs with glycinamide hydrochloride 464 in MeOH−water at −20 °C,520 the pyrazin-2-one derivatives 465 were prepared in 61−73% yields. Imidazo[1,5-a]pyrazine core 466 was synthesized by protection of the nitrogen in the pyrazine ring with pmethoxybenzyl chloride (PMB-Cl) in the presence of NaH and n-Bu 4 NI in DMF−THF solvent mixture, followed by condensation with tosylmethyl isocyanide (TsMIC) in the presence of NaH in THF at room temperature. Cleavage of the PMB group using TfOH/TFA and then treatment with POCl3 under reflux conditions for 1.5 h yielded the 8-chloro derivatives, in which the chloride at the 8-position was substituted with various anilines in the presence of sodium bis(trimethylsilyl)amide (NaHMDS) in THF at 60 °C for 2 h to produce the 5-arylimidazo[1,5-a]pyrazine 467 in 20−83% yields (Scheme 133). Also, the condensation reaction of 2-(hydroxyamino)acetamide 468 with AG-hydrates was reported in MeOH in the presence of NaOH (12.5 N) to give 6-aryl-2(1H)pyrazinone 4-oxides 469 in 24−50% yields (Scheme 134).521 The Ugi four-component reaction between AGs, amines, benzoylformic acid 470, and isocyanides was reported to afford

6.1.8. Pyrimidines. Hexahydropyrimidines (HHPs) and dihydropyrimidinones (DHPMs) constitute an important class of natural and unnatural products, many of which exhibit biological493 and pharmacological activity,494 such as parasiticides,495 antifungals, antibacterials,496 antihypertensives,497 mitotic kinesin inhibitors,498 α1a-adrenergic receptor antagonists,499 and hepatitis B virus replication inhibitors.500 The HHP skeleton is present in a number of alkaloids.501 These findings make it highly necessary to develop efficient methods for the synthesis of HHPs502 and DHPMs.503 The Biginelli reaction is one of the most useful methods to access DHPMs. The synthesis of aroyl derivatives of DHPMs 448 was reported by Balalaie et al.172 via Biginelli reaction of PG-hydrate with 1,3-dicarbonyl compounds and urea in the presence of ZnCl2 in EtOH at reflux conditions in 59−73% yields or in the presence of ZnCl2/AlCl3 (1:3) on silica gel under microwave irradiation in 26−42% yields (Scheme 130). However, the condensation reaction with N,N′-dimethylurea led to the preparation of multisubstituted imidazolin-2-one derivatives 138 (Scheme 36). Scheme 130. Synthesis of Aroyl-DHPMs 448 via Biginelli Reactiona

a

R= Me, OMe, OEt; reflux, 59−73%; MW, 26−42%.

Mibu and co-workers504 described the reaction of 1,3propanediamine 449 with PG to give 3-pyrimidine derivatives 450 and 451. When reaction was carried out in ether, the HHP derivative 450 was obtained as a sole product (89%), while reaction in EtOH afforded a tetrahydropyrimidine derivative 451 in 17% yield (Scheme 131). 6.1.9. Piperazinones and Pyrazinones. The piperazine or piperazinone core is present in compounds possessing AS


Chemical Reviews

Review

Scheme 132. Synthesis of Pyrazinones 455, 459, and 463

Scheme 134. Synthesis of Pyrazinone 4-Oxide 469a

Scheme 133. Synthesis of Imidazo[1,5-a]pyrazinones 466 and Imidazo[1,5-a]pyrazines 467a

a

Ar = Ph, 4-BrC6H4, 4-ClC6H4, 3,4-Cl2C6H3, 4-MeOC6H4, 3NO2C6H4, 4-NO2C6H4, 4-PhOC6H4; 24−50%.

the products 471, which upon heating with an excess of NH4OAc in AcOH for 3 h cyclized to pyrazinones 472 in good yields (Scheme 135).522 The cyclocondensation reaction of 3-indolylglyoxals 473 with aminoamide 474 to produce the pyrazine core 475 of dragmacidin D 476 was investigated; however this method was not reported as a suitable route to synthesis of 476 (Scheme 136).523 3-Indolylglyoxals 473 were synthesized by modified Rosenmund reduction of corresponding acid chloride by the action of Bu3SnH. Similarly, treatment of PG-hydrate with 2-amino amides in the presence of NaOH in water−MeOH at −40 °C for synthesis of the 2-pyrazinone moiety was reported.524 There are other reports on construction of pyrazinone rings through condensation reactions of AGs.525

a

Ar = Ph, 4-MeOC6H4; Ar′ = Ph, 2,4-Cl2C6H3, 2,4-F2C6H3, 2-Me-4MeOC6H3, 2-MeC6H4, 2,4-Me2C6H3.

AT


Chemical Reviews

Review

DMSO at 44−46 °C with 110 min half-life. Product 481 was synthesized by reaction of 478 with α-amino propionitrile in the presence of TiCl4 in CHCl3 (Scheme 137).

Scheme 135. Synthesis of Pyrazinones 472 via Ugi Reactiona

Scheme 137. Synthesis of 2-Aminopyrazine 1-Oxide 481

a R = 3-ClC6H4, 4-ClC6H4, 4-MeOC6H4, 4-MeC6H4, 4-ClC6H4CH2, Me2CHCH2; R′ = c-Hex, n-Hex, 4-MeC6H4; Ar = Ph, 4-ClC6H4, 4MeOC6H4, 4-MeC6H4; 471, 42−77%; 472, 67−85%.

6.1.10. Pyrazines. Pyrazines are important pharmacophores present in a number of biologically active compounds such as antimycobacterial, antibacterial, antidiabetic, and hypnotic/sedative agents.526 Some pyrazines have been known as flavor components in foods527 and as pheromones in various species of insects528 and ants.529 Also, they have applications as versatile synthetic intermediates530 and in metal coordination chemistry as N,N′-bidentate ligands.531 Accordingly, the synthetic methods, such as condensation of αdiketones with 1,2-diamines or α-aminoketones followed by oxidation532m−q leading to the substituted pyrazines have been developed.532 The preparation of 2-amino-3-methyl-6-phenylpyrazine 1oxide 481, a model for structural elucidation of Cypridina etioluciferamine, was developed by Karpetsky et al.533 using PG-2-oxime 478. The conversion of the PG-acetal to 477 was accomplished by hydroxylamine in the presence of NaOAc in MeOH in 93% yield. The next step, the acidic hydrolysis of 477 to 478, was carried out in glyme using pH = 3.5 buffer (1 N AcOH, 0.1 N NaOAc) under reflux conditions in which 2,5dihydroxy-3,6-diphenyl-5,6-dihydropyrazine 1,4-dioxide 480, the dimer of 478, was obtained as product via 479. Intermediate 478 was reproduced by heating of 480 in

Condensation of p-methoxyphenylglyoxal with 2,3-diaminopropionic acid hydrobromide 482 to synthesize pyrazine carboxylic acid 483 in methanolic NaOH solution was the first step of the synthesis of botryllazine B 484, a naturally occurring alkaloid that was first isolated from the red ascidian Botryllus leachi (Scheme 138).186 Vogl and Taylor534 described the synthesis of 2-aminopyrazine-3-carboxamides 486 by the condensation of PG with aminomalonamidamidine dihydrochloride 485. Reaction was

Scheme 136. Synthesis of Pyrazinone Core of Dragmacidin D 476a

a

475: R = H, OMe; R' = H, CH2CH2OBn, CH(Me)OBn, CH(Me)CO2Me; R" = H, Br. AU


Chemical Reviews

Review

Scheme 138. Synthesis of Pyrazine Carboxylic Acid 483

Scheme 140. Synthesis of Thieno[2,3-b]pyrazine 489

VCl3, AlCl3) in the presence of (NH4)6Mo7O24·4H2O as catalyst in refluxing o-dichlorobenzene. Dicyanopyrazines 495 were prepared by condensation of diaminomaleonitrile 494 with AGs. The reaction was carried out by refluxing of a mixture of AGs with 494 in dioxane/water solvent system for 2 h (Scheme 142). Taylor et al.538 described the intramolecular nitrile/1,2,4triazine DA cycloaddition to synthesize benzopyrano[3,4b]pyrazine 500. 3-(o-Hydroxyphenyl)-1,2,4-triazines 498 were prepared by three-component condensation of salicylic acid hydrazide 497 with PG-hydrate in the presence of excess NH4OAc and then alkylated with bromoacetonitrile using NaH in the presence of 15-crown-5 in THF under reflux conditions to give cyanomethyl phenyl ethers 499 in 40−43% yields. By heating of 499 in refluxing Ph2O for 13 h, 500 was obtained in 39% yield via cycloaddition−cycloreversion of N2 (Scheme 143). 6.1.11. Quinoxalines. Quinoxalines display a broad spectrum of biological539 and pharmacological540 activities such as insecticides, fungicides, herbicides, anthelmintics, antibacterial,541 antimycobacterial, antiprotozoal, anticancer,542 and antibiotic properties. Quinoxaline derivatives have found applications in dyes,543 electron luminescent materials,544 and chemically controllable switches,545 as building blocks for the synthesis of anion receptors,546 cavitands,547 dehydroannulenes,548 and organic semiconductors,543,549 and as electrontransport materials in multilayer OLEDs.550 A number of synthetic strategies have been developed for the preparation of substituted quinoxalines,551 including condensation of aryl-1,2diamines with α-functionalized ketones, usually dicarbonyl compounds or their equivalents.551f−j Ayaz et al.552 reported a facile procedure to prepare 2,3diarylquinoxalines 503 via a two-step Petasis deprotection− cyclodehydration−oxidation sequence. The Petasis reaction between AGs, 501, and arylboronic acid was conducted under MW irradiation at 120 °C to afford 502, which under deprotection−cyclodehydration−oxidation using 20% TFA in DCE at room temperature afforded 503 in 35−98% yields (Scheme 144). The synthesis of thermostable polyquinoxalines 505 was reported by Banihashemi et al.553 via condensation of 2,2′diiodobiphenyl-4,4′-diglyoxal dihydrate 504 with several aromatic tetraamine compounds either in HMPA solution or as a melt condensation at 300−350 °C under nitrogen atmosphere (Scheme 145). Also different model compounds

carried out in dilute NH4OH (pH = 8−9) at 0−20 °C. The yield was 36.6%, and only the 5-phenyl-2-aminopyrazine regioisomer was isolated (Scheme 139). Scheme 139. Synthesis of 2-Aminopyrazine-3-carboxamide 486

Zhang et al.535 reported the regioselective condensation reaction of 2,3-diamino-3-phenylthioacrylonitrile 487 with PGacetal to produce 3-cyano-5-phenyl-3-phenylthiopyrazine 488a. When reaction was conducted in i-PrOH in the presence of excess TFA, 488a was obtained in high selectivity. Using mineral acids or weak acids in MeOH and EtOH resulted in low yield and low selectivity. When PG was employed, the regioisomers 488a,b were obtained in 30−60% yields without selectivity. Product 488a was converted into thieno[2,3b]pyrazine 489 via activation of the phenylthio group in 488a as the sulfone using a 3:1 mixture of AcOH and chloroacetic acid with 3.1 equiv of sodium perborate, followed by treatment of the obtained crude mixture with 1.1 equiv of methyl thioglycolate in EtOH with Hunig’s base in 93% yield (Scheme 140). The synthesis of thienopyrazine isocyanate 492, the synthetic intermediate of fiduxosin 493, was reported by Haight et al.536 involving the condensation of aminomalononitrile with PGoxime in i-PrOH to produce 2-amino-3-cyano-5-phenylpyrazine N-oxide 490, which was converted into 492 in four steps through 491 (Scheme 141). Jaung and co-workers537 reported the synthesis of the tetrapyrazinoporphyrazinato metal complexes 496 by reaction of dicyanopyrazines 495 with the appropriate metal salt (CuCl, AV


Chemical Reviews

Review

Scheme 141. Synthesis of Thienopyrazine Isocyanate 492

Scheme 142. Synthesis of Tetrapyrazinoporphyrazinato Metal Complexes 496a

Scheme 143. Synthesis of Benzopyrano[3,4-b]pyrazine 500 via Triazine 499b

a

M = Al(OH), V(O), Cu; Ar = 4-i-BuC6H4, 4-n-C8H17C6H4, 4-nC12H25C6H4, 4-n-C16H33C6H4; 64−84%.

Scheme 144. Synthesis of 2,3-Diarylquinoxalines 503 via Petasis Reactiona were prepared by the condensation of 504 with diamines such as 2-phenylenediamine, 3,4-diaminobenzoic acid, and 3,4diaminopyridine in refluxing EtOH or AcOH. Also, Wrasidlo et al.554 reported the synthesis of the high molecular weight polyquinoxalines via condensations of either 3,3′,4,4′-tetraaminodiphenyl sulfone or benzophenone with various bisglyoxals by heating in m-cresol, then quenching with MeOH. As illustrated in Scheme 146, 1,4-di-N-oxide-quinoxaline-2carboxamide derivatives 508 were prepared by Moreno et al.555 By treatment of the PG and benzyl isocyanide under Passerini reaction, the β-ketoamide 506 was obtained, which underwent the Beirut reaction with appropriate benzofuroxanes 507 in the presence of CaCl2 and ethanolamine as catalysts. Synthesized 508 were evaluated for in vitro antituberculosis activity against Mycobacterium tuberculosis strain H37Rv. Results indicate that compounds provide an efficient approach for further development of antituberculosis agents. There are several other reports on the condensation of AGs with different 1,2-diamines for construction of pyrazine or quinoxaline rings and application of them.556

a R = H, Me; Ar = Ph, 4-FC6H4, 4-CF3C6H4; Ar′ = 3-FC6H4, 2,4,6F3C6H2, 3-CF3C6H4, 2-MeOC6H4, 4-MeC6H4, 2-naphthyl, trans-βstyryl; 35−98%.

6.1.12. Fused Pyrazines and Pteridines. Heterocyclic compounds possessing a fused pyrazine moiety show important biological activities,557 including anti-HIV,558 antimalarial,559 antiviral,560 anticancer,561 psychotropic,562 and aldose reductase inhibitor activities.563 Additionally, the pteridine structures are present in natural products such as folic acid, biopterin, and neopterin and are also found in synthetic anticancer drug AW


Chemical Reviews

Review

Scheme 145. Synthesis of Thermostable Polyquinoxalines 505

Scheme 146. Synthesis of Quinoxaline-2-carboxamides 508a

Scheme 147. Synthesis of Pyrazinothiadiazine 2,2-Dioxide 510a

a

X = O, NOH.

Scheme 148. Synthesis of Pyrazino[2,3-c]pyridazine 512

a

R = H, Cl; R′ = H, Cl, F, OMe, CH3, CF3; 6−36%.

an unusual methylation under acidic conditions in 68% yield (Scheme 149).568 The cyclocondensation reaction of the amino-substituted heterocycles such as 5,6-diaminopyrimidines 515 or 2,3diamino- or 3,4-diaminopyridines 516 and 517 with AGhydrates forming the pyrazine ring 518−520 was reported in single step. The regioselectivity of the reaction was controlled

methotrexate.564 While condensation reaction of 5,6-diaminopyrimidines with 1,2-dicarbonyl compounds is commonly used to prepare of pteridine derivatives,565e there are a number of alternative methods to prepare this class of heterocycles in the literature.565 Campillo et al.566a described the synthesis of pyrazino[2,3c][1,2,6]thiadiazine 2,2-dioxide 510 via condensation between 3,4,5-triamino-2H-1,2,6-thiadiazine 1,1-dioxide 509 and PG. Two possible isomers having phenyl substituted at positions 6 and 7 can be obtained. By reaction of 509 with PG-oxime, exclusively, the 6-phenyl-7H-pyrazinothiadiazines was obtained. However, when PG was used, the 7-phenyl-6H-derivative was obtained (Scheme 147).566 Similarly, as shown in Scheme 148, the condensation reaction of PG with 3,4-diaminopyridazine 511 to give 6(7)phenylpyrazino[2,3-c]pyridazine 512 in ethanolic HCl was reported.567 7-Methoxy-8-methyl-6-phenyldihydropyrazine 514 was prepared by ring closure of 5,6-diaminotriazine 513 with PG in MeOH via addition of the MeOH at C(7) and N(8) through

Scheme 149. Synthesis of Dihydropyrazinotriazine 514

AX


Chemical Reviews

Review

Scheme 150. Regioselective Synthesis of Pyrimido- and Pyridinopyrazines 518−520a

a X, Y = H, OH, NH2; Ar = Ph, 3-HOC6H4, 4-HOC6H4, 3,4-(HO)2C6H3; cond. = NaOH, MeOH−water, pH = 9−10, rt (3 h) → reflux (3 h), 518a−520a; cond. = Me2CNOH, HCl, water, pH = 3−4, rt (3 h) → reflux (6 h), 518b−520b.

by pH and also by using AGs or AG-oximes. Reactions were conducted in two different conditions, (a) using AG-hydrates in MeOH−water at pH = 9−10 (using NaOH), which afforded 518a−520a, and (b) via in situ generation of AG-oximes from AG-hydrates using Me2CNOH and their reaction in water at pH = 3−4 (using HCl) to afford regioisomers 518b−520b (Scheme 150).569 Ma and co-workers570 described the synthesis of the substituted 2,4-diaminopteridine derivatives 518b by treatment of 515 (X = NH2, Y = NRR′) with different substituted PGoxime under N2 atmosphere in refluxing MeOH. The inhibitory activity of the compounds 518b against iNOS were evaluated, and the results indicated that 518b with Y = NHi-Pr and Ar = p-Me and p-MeOC6H4 exhibited potent inhibitory activity similar to that of methotrexate (MTX). A similar reaction was reported using 2-amino- and 2-methylthio-4,5,6-triaminopyrimidine dihydrohalides in refluxing MeOH.571 The condensation reaction of PG-oxime and its o-methoxy derivative with aminomalononitrile gave 490 (Scheme 141), which was converted into 2,4-diamino-6-substituted pteridine 8-oxides 521 upon cyclization with guanidine 142 in refluxing MeOH in quantitative yield (Scheme 151).572

Scheme 152. Synthesis of Regioisomers 6- or 7Arylpteridines 523a

a R = H, Me; Ar = Ph, 4-ClC6H4; acidic alumina, 523a, 63−70%; neutral alumina, 523b, 71−75%.

6.1.13. Triazinones. Due to the biological activity of triazinone derivatives,574 such as antagonists at the corticotropin releasing factor receptor,574a anticancer activity,574b,c anti-HIV,574d and inhibitory activity of 5-lipoxygenase,574e a number of methodologies have been reported for synthesis of 1,2,4-triazinones.575 Lalezari576 reported the cyclization and rearrangement reactions of substituted arylglyoxalaldoxime semicarbazones 524 to 6-substituted 1,2,4-triazine-3,5(2H,4H)-diones 525. The reaction was carried out by refluxing of 524 in water in the presence of K2CO3. Compounds 524 underwent cyclization with loss of ammonia to produce 6-aryl-1,2,4-triazine-3(2H)one 4-oxide, in which the oxygen atom of the N-oxide was shifted to the neighboring carbon atom to form 525 in 45−67% yields (Scheme 153). Also, Lalezari and co-workers577 reported the conversion of 524 to 6-aryl-1,2,4-triazine-3(2H)-ones using 5% HCl under reflux conditions, which on boiling with hydrogen peroxide in glacial AcOH was converted into 525 in 65% yield. By reaction of PG with 2,4-disubstituted thiosemicarbazide 526 in water at room temperature, the corresponding semicarbazone 527 was synthesized, which was cyclized to 5-

Scheme 151. Synthesis of Pteridine 8-Oxides 521a

a

Ar = Ph, 2-MeOC6H4.

Reaction of 5,6-diaminouracils 522 with AGs over acidic and neutral Al2O3 under MW irradiation was reported by Singh and Geetanjali. When the condensation reaction was carried out by using acidic alumina under MW irradiation 6-arylpteridines 523a were obtained in 63−70% yields, but using neutral alumina afforded the corresponding regioisomer, 7-arylpteridines 523b in 71−75% yields (Scheme 152).573 AY


Chemical Reviews

Review

Scheme 153. Synthesis of 1,2,4-Triazine-3,5-diones 525a

As shown in Scheme 156, the condensation reaction of AGs with arylamidrazones 536 was carried out in MeOH to produce Scheme 156. Synthesis of 3,6-Diaryl-1,2,4-triazines 357a

a

Ar = Ph, 4-BrC6H4, 4-ClC6H4, 4-FC6H4, 4-MeOC6H4, 4-MeC6H4, 4MeSC6H4, 4-NO2C6H4; 45−67%.

hydroxy-l,2,4-triazine-3-thione 528 when treated with TFA in benzene at room temperature for 15 h. Refluxing of 527 in alcohols such as MeOH and EtOH in the presence of TFA for 8 h gave corresponding 5-alkoxy-1,2,4-triazine-3-thione derivatives 529 in 73−76% yields. Compound 527 was converted into 1,3,4-thiadiazolium cation 530 in the presence of TFA (Scheme 154).578

a

Ar = Ph, 2-ClC6H4, 3-ClC6H4, 4-ClC6H4, 2-MeC6H4, 3-MeC6H4, 4MeC6H4, 3-CF3C6H4; Ar′ = Ph, 4-BrC6H4, 4-ClC6H4, 2-FC6H4, 3FC6H4, 4-FC6H4, 4-CF3C6H4, 2-pyridyl; 357a, 39−76%; 357b, 1− 16%.

Scheme 154. Synthesis of Triazine-3-thiones 528 and 529a

1,2,4-triazine derivatives 357 as two regioisomers, in which 3,5disubstituted 1,2,4-triazines 357a were obtained as major regioisomers in 39−76% yields588 and were investigated as potential anti-inflammatory588a and herbicidal agents.588b Limanto and co-workers589 reported the regioselective synthesis of 5-substituted 3-amino-1,2,4-triazines 535a by condensation of aminoguanidine 534 with ketoaminals 533, prepared by nucleophilic displacement of α,α-dibromoacetophenones with excess morpholine. The reactions were performed in MeOH in the presence of AcOH, and products 535 were obtained in 45−76% yields with >95% regioselectivity (Scheme 157). Directly using PG-hydrate in reaction with Scheme 157. Synthesis of Aryl-Substituted 3-Amino-1,2,4triazines 535a

a Cond. = TFA, benzene, rt, 15 h; 528, 78%; Cond. = TFA, ROH, reflux, 8 h; 529, 73−76%.

Also, as outlined in Scheme 155, the reaction of PG-hydrate with thiocarbohydrazide 531 in water gave the 4-amino-1,2,4triazine-3-thione 532 in 72% yield.579 Scheme 155. Synthesis of 4-Amino-1,2,4-triazine-3-thione 532

a

Ar = Ph, 4-BrC6H4, 4-MeOC6H4, 6-MeOnaphth-2-yl; X = Cl, Br; 45−76%, 98−99% regioselectivity.

6.1.14. Triazines. 1,2,4-Triazines are a well-known class of nitrogen heterocycles with a range of applications,580 particularly in pharmaceuticals,581 herbicides, pesticides, and dyes.582 They exhibit physical, biological, and chemical properties,580,582a such as antitumor,583 antiviral,584 and antifungal585 activities. The chemistry of 1,2,4-triazines has been extensively studied.586 3-Pyridyl-1,2,4-triazines are interesting compounds due to their application in transition metal analysis.587 Condensation of the amidrazones with 1,2dicarbonyl compounds provides one of the most straightforward syntheses of 1,2,4-triazines.580

aminoguanidine acetate in either THF or H2O afforded a 1:1 regioisomeric mixture of the corresponding aminotriazines 535a,b (Ar = Ph) in 50% yield, while reaction in MeOH, slightly improved the ratio of products a/b to 3:1. Matikainen et al.590 reported the intramolecular cyclization reaction of phenylglyoxal bis(amidinohydrazone) into the isomeric mixture of 535a,b. The reaction was conducted under Ar atmosphere at 210 °C without using solvent, and 535 was obtained in 60% yield. The ratio of the two isomers was not studied. AZ


Chemical Reviews

Review

Scheme 160. Synthesis of Bis-triazines 541 and 542a

Triazine 537 was isolated from reaction of PG-hydrate with aniline in AcOH−EtOH (10/50) under heating conditions in 13% yield via DA reaction between PG-imine 3 and PGbisimine 536 (Scheme 158).591 Scheme 158. Synthesis of 1,2,4-Triazines 537 via DA Reaction

Bruce and co-workers592 developed a synthetic approach to a series of 5,5′-linked bis-(1,2,4-triazine)s 540, which are potential monomers in DA polymerization processes. Arylene-bisglyoxals 539 were synthesized by oxidation of bis(αbromophenylacetyl)-substituted aromatic compounds with DMSO or by reaction of diacetyl-substituted aromatic compounds 538 with HBr in DMSO. Conversion of 539 into 540 was carried out by reaction with S-methylthiosemicarbazidium iodide in aqueous EtOH in the presence of NaHCO3 at room temperature (Scheme 159).

a

Ar = Ph, 4-HOC6H4, 4-NO2C6H4.

There are other reports on similar condensation reactions of AGs with substituted amidrazones for construction of 1,2,4triazines in the literature.594 6.1.15. Fused Triazines. Fused triazine moiety can be considered as a bioisostere, which also displayed pharmacological and biological activities,595 such as anticancer activity595j and antagonistic activity against A1 and A2A adenosine receptors.595k−m Fused triazines have been synthesized generally by a previously reported method.596 By treatment of 1-NH-Boc-protected 1,2-diaminopyrroles 543 with PG-hydrate in the presence of conc. HCl in THF at 0 °C, followed by standing at room temperature for 22−72 h, highly substituted pyrrolo[1,2-b]-1,2,4-triazines 544 were obtained as two regioisomers, 544a and 544b, in 11−44% and 8−75% yields, respectively. Reactions were carried out by one-pot cleavage of the protecting group and subsequent condensation with PG-hydrate (Scheme 161).597 The preparation of imidazo[1,2-b]-1,2,4-triazines 546 were reported by Lalezari et al.598 via treatment of PG-oxime with 4-

Scheme 159. Synthesis of 5,5′-Linked Bis-(1,2,4-triazine)s 540

Scheme 161. Synthesis of Pyrrolotriazines 544a

Also, the condensation reaction of AG-hydrates and 539a with amidrazone 356 (Ar′ = 2-pyridyl) and bis-amidrazone 360a was reported in refluxing absolute EtOH to give the corresponding mono- and bis-triazines 357, 541, and 542 in 78−89% yields (Scheme 160).593

a

R = 4-NO2C6H4, CN, piperidin-1-ylcarbonyl, (EtO)2OP; a, 11−44%; b, 8−75%. BA


Chemical Reviews

Review

substituted 1,2-diaminoimidazoles 545. The reactions were conducted by refluxing a solution of PG-oxime and 545 in EtOH for 1 h, followed by addition of HCl and refluxing for additional 4 h to give 546a in 31−59% yields. When HCl was added at the beginning of the reaction, a mixture of two regioisomers, 546a,b, was produced. When reactions were carried out using PG-hydrate in water under reflux conditions, 546b were obtained in 40−83% yields (Scheme 162).

Scheme 164. Synthesis of Pyrido[1,2-b]-1,2,4-triazinium Salts 551−554a

Scheme 162. Synthesis of Imidazotriazines 546a

a

Ar = Ph, 4-BrC6H4, 4-ClC6H4, 2-naphthyl; X = NOH, EtOH, reflux (1 h), then dil. HCl, reflux (4 h); 546a, 31−59%; X = O·H2O, HCl, water, reflux, 10 h; 546b, 40−83%; 546a, minor product.

A similar reaction between PG and 7,8-diamino-1,3dimethylxanthine 547 was carried out in the presence of boric acid in AcOH at 100 °C and 1,3-dimethyl-7-phenyl[1,2,4]triazino[2,3-f ]purine-2,4(1H,3H)-dione 548 was obtained in 96% yield (Scheme 163).599

a

Ar = Ph, 4-ClC6H4, 4-BrC6H4.

6.2. O-Heterocyclic Compounds

Scheme 163. Synthesis of Triazinopurinedione 548

6.2.1. Pyrans and Pyranones. Pyrans and pyranones are versatile building blocks that have been extensively used in natural products601 and for the synthesis of many biologically active compounds,602 such as pheromones, terpenoids,603 antibiotics,604 and immunosuppressive,605 antitumor,606 antiulcer,607 antiproliferative,608 and antiparasitic609 agents. There are a number of methods for construction of these heterocycles, such as hetero-DA (HDA) reactions of aldehydes with dienes or α,β-unsaturated carbonyl compounds with electron-rich carbon−carbon unsaturated bonds.610 Oi and co-workers611 studied the HDA reaction of different dienes with AGs using cationic chiral BINAP−palladium or −platinum complexes as catalyst to produce 2-benzoyl-3,6dihydro-2H-pyrans 555. A variety of chiral diphosphine ligands were tested for the HDA reaction of 2,3-dimethyl-1,3-butadiene with PG, and (S)-BINAP was selected as the ligand due to high yield of cycloadduct with high ee. The reaction was carried out by stirring a mixture of a diene with an AG in CDCl3 in the presence of 3 Å MS and a catalytic amount of [Pt(SBINAP)(PhCN)2](BF4)2 at 0 °C for 24 h, which afforded pyrans 555 in 21−80% yields (Scheme 165). Heteroene612 products were not observed under these reaction conditions. Also, one example of the HDA reaction of PG with cyclohexadiene was investigated using a different chiral palladium catalyst, [(S)-MeObiphepPd(NCAr)2(SbF6)2], in DCM at 0 °C in the presence of 4 Å MS, and corresponding cycloadduct was obtained in 55−80% conversion with 98−99% ee and a 98:2 diastereomeric ratio.613 Tonoi et al.614 described the HDA reaction of TIPSsubstituted Danishefsky’s diene 556 with AGs catalyzed with DPENTf. The reaction was carried out by addition of AGs and 556 to a solution of DPENTf in toluene at −78 °C, followed by

Reaction of AG-hydrates with 1,2-diaminopyridinium salt 549 under different conditions was reported by Hajós et al.600 Under basic conditions, using NaOH in CH3CN at room temperature, 2,5-dihydro-2-hydroxypyridotriazines 550 were produced, which were converted into the covalent hydrate salt 552 when treated with 70% HClO4 in 65−78% yields. Salts 552 underwent dehydration when dissolved in TFA, and 3arylpyrido[l,2-b]-1,2,4-triazinium salt 553 was detected using NMR spectra. When a suspension of 550 (Ar = 4-ClC6H4) in DCM was treated with Me3O·PF6 at room temperature, 551 was prepared in 77% yield. Reaction of 549 with AG-hydrates in acidic media [70% HClO4−MeOH, 1:2 (v/v)] at room temperature resulted in 2-arylpyrido[l,2-b]-1,2,4-triazinium salt 554 in 70−82% yields (Scheme 164). BB


Chemical Reviews

Review

Scheme 165. Synthesis of Pyrans 555 via HDA Reactiona

a

Et2O−EtOAc (3:1). The reaction between 559a and AGs occurred exclusively at the aldehyde group to afford zinc bromide alcoholates 560a, which were cyclized to 561a in 80− 93% yields under the reaction conditions (Scheme 167). Also, a similar reaction of AGs with zinc enolate 559b,c was investigated to form 3-aroyl-4,4-dimethyl-2-oxaspiro[5.5]undecane-1,5-diones 561b and 1-aroyl-4,4-dimethyl-2oxaspiro[5.5]undecane-3,5-diones 561c. The reactions were carried out by dropwise addition of bromo derivatives in ether to fine zinc turnings and a catalytic amount of HgCl2 in Et2O− EtOAc solvent mixture. After completion of the reaction, a solution of the AG in ethyl acetate was added and refluxed for 30 min. Then upon cooling and hydrolyzing with 5% HCl, the products were obtained in 50−65% yields (Scheme 167).616 6.2.2. Dioxanes. The dioxane moiety is a common structural motif in several bioactive molecules.617 Also 1,3dioxane is one of the most important protecting group of carbonyl compounds. There are a number of methodologies, such as reaction of carbonyl compounds with 1,3-diols, for preparing dioxane derivatives.618 Reactions of optically pure 1-aryl-2,2-dimethylpropane-1,3diols 562 with AGs were carried out in refluxing benzene catalyzed with p-TsOH with azeotropic removal of water. When BF3·OEt2 was used as Lewis acid, products 563 were obtained in low yields along with a polymeric material. The products were obtained as diastereomerically pure cyclic ketals 563 in 40−72% yields. Reactions took place at the keto group (Scheme 168).619

Ar = Ph, 4-ClC6H4, 4-MeOC6H4, 4-MeC6H4.

hydrolysis with TFA to give 2-aroyl-2H-pyran-4(3H)-ones 557 in 46−74% yields with 77−87% ee (Scheme 166). Scheme 166. Synthesis of Pyran-4-ones 557 via HDA Reactiona

Scheme 168. Synthesis of Cyclic Ketals 563a

a

Ar = Ph, 4-CF3C6H4, 4-MeOC6H4; 46−74%; ee = 77−87%. a

Shchepin et al.615 reported the Reformatsky reaction of methyl 4-bromo-3-oxo-2,2,4-trimethylpentanoate 558a with zinc and AGs to produce 2,3,5,6-tetrahydropyran-2,4-diones 561a containing an aroyl group in the 6 position. The reaction was performed in two steps: first zinc enolate 559a was prepared and then the AG was added to the solution of 559a in

X = H, Cl; Ar = Ph, 2-ClC6H4, 4-MeC6H4; 40−72%.

́ et al.620 reported a synthesis of 2-acyl-1,3Becerra-Martinez dioxanes 565 by the reaction of 3,10-pinanediol derivatives 564 with PG-acetal, which were subjected to nucleophilic addition using MeMgBr to afford carbinols 566 in 88−98% yields with

Scheme 167. Synthesis of 6-Aroylpyran-2,4-diones 561 via Reformatsky Reactiona

a

561a: R = R' = Me; Ar = Ph, 4-BrC6H4, 4-t-BuC6H4, 4-ClC6H4, 4-EtC6H4, 4-FC6H4, 4-MeC6H4, 2,4,6-Me3C6H2, 2,3,5,6-Me4C6H, 4-PhC6H4; 80− 93%; 561b: R = Me; R'−R' = (CH2)5; Ar = Ph, 4-BrC6H4; 63−65%; 561c: R−R = (CH2)5; R' = Me; Ar = Ph, 4-BrC6H4; 50−54%. BC


Chemical Reviews

Review

≥87:13 dr. Synthesis of 2-acyl-1,3-dioxanes 565 was conducted using p-TsOH in benzene with azeotropic removal of water (Scheme 169).

butadiene or 1,3-cyclohexadiene, corresponding thiopyrans, 2benzoyl-4,5-dimethyl-3,6-dihydro-2H-thiopyran 571a or 3benzoyl-2-thiabicyclo[2.2.2]oct-5-ene 571b, were obtained in 85% or 89% yields, respectively. The reactions were carried out in CH3CN at room temperature, in which thioaldehyde 570 was produced as reaction intermediate, which was trapped with dienes via HDA reaction. HDA reaction with cyclohexadiene occurred with very high selectivity in favor of the endo isomer (Scheme 171).626

Scheme 169. Synthesis of Dioxanes 565 and Their Reaction with MeMgBra

Scheme 171. Synthesis of Dihydrothiopyrans 571 via HDA Reaction

a

R = H, Me; 88−98%, a/b ≥ 13/87.

Griffiths and Gutsche 621 described the synthesis of mandelaldehyde dimers 569 via hydrolysis of dimethyl acetals 567, which were synthesized by reduction of the AG-acetals with LiAlH4 (using NaBH4 in the case of nitro substituent) in refluxing THF. AG-acetals were prepared by the action of trimethyl orthoformate and methanol on AGs in the presence of NH4Cl at room temperature for 24 h. The hydrolysis step was carried out using 0.5 N HCl at room temperature to afford 568, which were converted into dimers 569 in 20−75% yields (Scheme 170).

6.4. N,O-Heterocyclic Compounds

6.4.1. 1,3-Oxazines. 1,3-Oxazines are an intermediate for the synthesis of medicinally active molecules627 that exhibit biological and pharmacological activities such as analgesic,628 antitubercular,629 anticancer,630 anti-HIV,631 antihypertensive,632 antibiotic,633 antithromobotic,634 anticonvulsant,635 and antiulcer.636 Moreover, certain kinds of 1,3-oxazines are of interest as photochromic compounds.637 A number of methods for construction of the 1,3-oxazine structure including the reaction of a diol638 or olefin639 with a nitrile under acidic conditions, cyclodehydration of hydroxyl amides,640 elimination of water from β-acylamino-aldehydes641 or ketones642 are reported in the literature.643 The nucleophilic addition to 2-benzoyl-1,3-oxazines, which were prepared by condensation of 3-amino alcohols with PG, were investigated by different research groups. Ko et al.644 reported the stereoselective reduction of chiral N-tosyl-2benzoyl-1,3-oxazines 573a,b, prepared by condensation of Dglucose 572 with PG-hydrate in refluxing benzene in the presence of p-TsOH. Protection of carbinols 574a,b using BnBr or Ac2O followed by acidic hydrolysis (5% HCI/EtOH 1:5) gave the corresponding 2-benzyloxy aldehyde or 2-hydroxy aldehyde in 96% or 92% yields, respectively, which reduced to corresponding diols 575 or 576 using LiAlH4 or NaBH4 (Scheme 172). Also, as shown in Scheme 173, chiral N-tosyl-2-benzoyl-1,3oxazine 578, which was prepared by condensation of 1,3-amino alcohol 577, derived from (1R)-(+)-camphor, with PG-hydrate was subjected to reduction to 579 using various reducing agents, and high diastereoselectivity was observed in the case of chelating reducing agents such as LiAlH4 and L-Selectride.645 A similar reaction was investigated by addition of Grignard and organolithium reagents to and hydride reduction of benzoyl-

Scheme 170. Synthesis of Mandelaldehyde Dimers 569a

a Ar = Ph, 4-ClC6H4, 4-CF3C6H4, 4-MeOC6H4, 4-MeC6H4, 4NO2C6H4; 567, 27−80%; 569, 20−75%.

6.3. S-Heterocyclic Compounds

6.3.1. Thiopyrans. The sulfur-containing six-membered heterocyclic compounds display a wide range of biological activities622 and have applications for the synthesis of heterocyclic compounds623 and organic materials for electronic devices.624 The HDA reaction of dienes with thiocarbonyl compounds is one of the most important methods for the synthesis of thiopyran derivatives.625 By treatment of bis(trimethylsilyl)sulfide and CoCl2·6H2O with PG-hydrate in the presence of dienes, 2,3-dimethyl-1,3BD


Chemical Reviews

Review

Scheme 172. Synthesis of 1,3-Oxazines 573 and Their Conversion into Diols 575 and 576a

[Red] = NaBH4, LiAlH4, L-Selectride, LiAlH(Ot-Bu)3, n-Bu4NBH4, DIBAL; solvent = EtOH, ether, THF, DCM, toluene; temp = −78, 0 or 20 °C; 574a,c: R = Me; 83−98%; de = 0−98%; 574b,d: R = pivaloyl; 89−98%; de = 0−68%.

a

The reaction of PG with 3-amino-1-propanol in the presence of K2CO3 in refluxing benzene with removal of water using Dean−Stark apparatus was also reported.648 6.4.2. Morpholines. The morpholine skeleton is present in a number of pharmacologically active molecules649 that exhibit anti-inflammatory activity650 and have a wide range of applications in the treatment of depression,651 obesity652 and asthma. Also, they are chiral building blocks for the synthesis of variety of pharmacologically active compounds.653 The most important methods for preparation of morpholines include the reaction of aminoethanol with 1,2-electrophiles such as αketoaldehydes, epoxides, allyl halide, and α-halo esters and αchloroacetyl chloride, with further reactions,654 and reaction of amines with diethanol amine or its equivalents.655 A protocol for synthesis of 2-hydroxymorpholines 585 was reported by Berrée et al.656 via a one-pot three-component Petasis coupling reaction. The reaction was carried out by stirring of a mixture of 1,2-amino alcohol 584, PG, and arylboronic acid in EtOH at room temperature for 24 h to give corresponding 585 in 53−92% yields with 83/17−89/11 diastereoselectivity (Scheme 175). The reactions of PG-hydrate with (R)-phenylglycinol 586a and (1S,2R)-norephedrine 586b were investigated in the presence of excess MgSO4 in DCM to give the corresponding oxazolidines 587, in which initially formed 587 underwent a fast stereospecific rearrangement to the corresponding 2hydroxy-3-phenyl-1,4-oxazines 588 in 87−91% yields (Scheme 176).657 By treatment of PG-hydrate with L-ephedrine 589 under different conditions such as in the presence of 4 Å MS in ether at 20 °C or 4 Å MS in EtOH at 20 °C or Amberlyst-15 in refluxing toluene, regiospecifically, 2-benzoyloxazolidine 590 was obtained with a quantitative yield via condensation of 589 with the more reactive aldehyde group of PG. 2-Benzoyloxazolidine 590 was obtained as two diastereomers, which rearranged to 4,5-dimethyl-3,6-diphenylmorpholin-2-one 591 at ambient temperature after 12 days (Scheme 177).658

Scheme 173. Synthesis of 1,3-Oxazines 578 Derived from (1R)-(+)-Camphor and Their Reduction to 579a

a [Red] = NaBH4, KBH4, LiAlH4, LiAlH(Ot-Bu)3, LiEt3BH, NaEt3BH, DIBAL, n-Bu4NBH4, L-Selectride; solvent = EtOH, ether, toluene, THF, DCM; temp = 0 or −70 °C; de = 8−98%.

1,3-benzoxazine derived by reaction of PG with 8-benzylaminomenthol.646 Condensation reaction between cis-piperidine ethanol 580a and PG-hydrate in refluxing DCM in the presence of 4 Å MS afforded one isomer of perhydro-2-benzoyl-1,3-oxazine 581a in 85% yield. 1,3-Oxazine 581b was obtained by a similar condensation with trans-piperidine ethanol 580b in 86% yield. The reaction of 581a,b with Grignard, organolithium, or reducing reagents at −78 °C gave the corresponding carbinols 582 and 583 in high diastereomeric excess (Scheme 174).647 BE


Chemical Reviews

Review

Scheme 174. Synthesis of 1,3-Oxazines 581 Derived from Piperidine Ethanols 580a

a

Reagents = RMgX, RLi, DIBAL; R = n-Bu, t-Bu, Et, Me, c-pentyl, n-Pr, i-Pr, vinyl; X = Br, Cl; 582, >80%, a/b = 53/47−95/5; 583, >80%, a/b = 95/5.

Scheme 177. Synthesis of Diphenylmorpholine-2-one 591a

Scheme 175. Synthesis of 2-Hydroxymorpholines 585 via Petasis Coupling Reactiona

a

Ar = Ph, 92%, dr = 89/11; Ar = 2-MeOC6H4, 53%, dr = 83/17.

Conditions: 4 Å MS, Et2O, 20 °C or 4 Å MS, EtOH, 20 °C or Amberlyst-15, toluene, reflux.

a

Scheme 176. Synthesis of 2-Hydroxymorpholines 588 via Oxazolidines 587a

Scheme 178. Synthesis of Oxazine Core of Aprepitant 593

a

a, R = Ph, R′ = H; b, R = Me, R′ = Ph; 588a, X = OH, X′ = H, 87%; 588b, X = H, X′ = OH, 91%.

A protocol for synthesis of aprepitant, 594, a potent substance P (SP) receptor antagonist, was described by Zhao and co-workers. The enantiopure oxazinone 593 starting material was synthesized via condensation reaction of 4fluorophenylglyoxal hydrate with amino alcohol 592 in the presence of AcOH under reflux conditions and azeotropic removal of produced water in 90% yield with >98% dr. The conversion of oxazinone 593 to 594 was carried out in further steps (Scheme 178).659 As shown in Scheme 179, Gualandi et al.660 reported the diborane-induced reduction of fused oxazino-oxazine 595, which was prepared by condensation of PG-hydrate and (S)phenylglycinol 596a in DCM in the presence of MgSO4 at

room temperature, to produce β-amino alcohol 596. By treatment of 596 with Ph3P in the presence of DEAD in THF at room temperature for 24 h, 1,2-ethylenediaziridine 597 was obtained in 78% yield, which was used as ligand in the Pdcatalyzed allylic alkylation of dimethyl malonate. Preparation of morpholine derivatives 600 was reported by Pedrosa et al.661 through selenocyclofunctionalization of chiral 3-allyl-2-hydroxymethyl-substituted perhydro-1,3-benzoxazine derivatives 598. As illustrated in Scheme 180, the chiral BF


Chemical Reviews

Review

601. The reactions were carried out in the presence of TFA in MeOH at room temperature for 2 days, and 6-aroyl-5-hydroxy5,6-dihydro-4H-1,2,5-oxadiazines 603 were produced in 54− 97% yields via intermediate 602 (Scheme 181).

Scheme 179. Synthesis of Oxazino-oxazine 595

Scheme 181. Synthesis of Oxadiazines 603a

a

R = Ph, 4-ClC6H4; R′ = H, Me; Ar = Ph, 4-BrC6H4, 4-ClC6H4, 4MeOC6H4; 54−97%.

perhydro-1,3-benzoxazines 598 were prepared in three steps, starting from PG.662 Selenocyclofunctionalization of alcohols 598 was carried out using PhSeCl in DCM in the presence of SnCl4 or in THF with methanol as an additive. Then by reductive deselenenylation using Ph3SnH in the presence of catalytic amounts of AIBN in refluxing toluene, morpholines 599 were produced. N-Tosyl derivatives 600 were produced by treatment of 599 with AlH3, in situ generated by action of LiAlH4 on AlCl3 in THF, followed by elimination of the menthol moiety using PCC in DCM at room temperature, then KOH in THF−MeOH−H2O, which afforded the enantiopure morpholines that were converted into 600 by treatment with TsCl and DIPEA in EtOAc (Scheme 180). 6.4.3. Oxadiazines. Oxadiazines are important heterocycles due to their key biological activities.663 They are also synthetic intermediate for other heterocyclic compounds.664 On the other hand, 1,2,5-oxadiazines are not very general heterocyclic systems.665 Accordingly, Amitina and co-workers666 reported the reactions of AGs with Z-isomers of hydroxylamino oximes

6.5. N,S-Heterocyclic Compounds

6.5.1. 1,4-Thiazines and 1,4-Benzothiazines. 1,4Thiazine and 1,4-benzothiazine derivatives possess a wide spectrum of biological667 and pharmacological activities, such as calcium channel blockers,668 phosphodiesterase 7 inhibitors,669 5-HT3 antagonists,670 antipsychotics agents,671 sedatives,672 and Na+/H+ exchange inhibitors.673 There are a number of published reports on synthesis of 1,4-thiazine structures using aminothiophenols or reaction of amines with sulfur powder in the presence of I2.674 2H-1,4-Thiazines 607 were synthesized via HDA reaction of acrylic dienophiles with hydrazono thioketones 605, which were prepared in two steps starting from AG-hydrates. Monohydrazones 604 were synthesized by reaction of 1,1dimethylhydrazide or 1-aminopiperidine with AG-hydrates in EtOH at room temperature; then by treatment of 604 with Lawesson’s reagent in benzene at room temperature,

Scheme 180. Synthesis of Enantiopure Morpholines 600a

a

R, R′ = H, Me; R−R′ = (CH2)4; R″ = H, Me. BG


Chemical Reviews

Review

Scheme 183. Synthesis of 1,4-Benzothiazines 609 and 610a

corresponding thiocarbonyl compounds 605 were obtained in 25−55% yields. Compounds 605 were used as heterodienes in DA cycloaddition reactions with acrylic dienophiles using benzene as solvent in the presence of HQ as additives to afford 3,4-dihydro-2H-1,4-thiazines 606, which converted to 2H-1,4thiazines 607 under heating via elimination of an amine molecule in 26−58% yields (Scheme 182).675 Scheme 182. Synthesis of 1,4-Thiazines 607 via HDA Reactiona

a

Ar = Ph, 4-MeOC6H4.

Scheme 184. Synthesis of Acylamido-1,4-benzothiazines 611a

a Ar = Ph, 4-BrC6H4, 4-ClC6H4; NR2 = NMe2, piperidine; EWG = CHO, COMe, CO2Me, CN; 26−58%. a

R = Me, Ph, MeO; 60−86%.

676

MacKenzie et al. described the synthesis of benzothiazines 609 by condensation of PG-hydrazonyl bromides 608 with oaminothiophenol. The reaction was conducted by addition of 608 to a solution of o-aminothiophenol in EtOH containing NaOEt and stirring for 30 min to afford desired product in 72− 84% yields, which exists predominantly in its tautomeric hydrazone form 609a. For investigation of existence of tautomeric forms, the condensation reaction of o-N-methylaminothiophenol with 608 to produce 4-methyl-3-phenyl-2phenylazo-4H-1,4-benzothiazine 610 was also carried out in EtOH in the presence of NaOEt (Scheme 183). Treatment of 185, obtained from reaction of PG with amides followed by SOCl2 (Scheme 52) with o-aminothiophenol afforded 1,4-benzothiazines 611 in 60−86% yields (Scheme 184).218 6.5.2. Benzothiadiazines. Benzothiadiazine 1,1-dioxide derivatives exhibit wide biological and pharmacological activities.677 Accordingly, several methods have been developed for the synthesis of benzothiadiazines 1,1-dioxides derivatives.678 Topliss et al.679 reported the synthesis of 3-hydroxybenzyl3,4-dihydro-1,2,4-benzothiadiazine 1,1-dioxide 614 by condensation of a substituted orthanilamide 612 with PG-acetal in the presence of HCl in EtOH. The condensation reaction gave 614 rather than 3-benzoyl-3,4-dihydrobenzothiadiazine 613. It seems that 613a was first formed, which was transformed to 614 by enolization of the carbonyl group and migration of the double bond to the 3,4-position via intermediate 613b (Scheme 185).

Scheme 185. Synthesis of 1,2,4-Benzothiadiazine 1,1Dioxide 614

Grivas.680 Reaction was carried out by passing of dry HCl (g) through a solution of 615 and PG-hydrate in ethanol at 50 °C.

6.6. S,O-Heterocyclic Compounds: Benzoxathiin

Unexpectedly, the reaction yielded 2-benzoyl-4H-3,1-benzox-

In an attempt to synthesize 616, the reaction of PG-hydrate with 2-mercaptobenzamide 615 was investigated by John C.

athiin-4-one 617 in 28% yield (Scheme 186). BH


Chemical Reviews

Review

biological686 and pharmacological activities687 such as antibiotic,688 antimalarial,689 anti-HIV,690 and anticancer agents.691 The benzodiazepines are the most widely prescribed minor tranquilizers in current use, and they are known to act on the central nervous system. A variety of methods exist in the literature for the preparation of these heterocycles,692 such as the condensation reaction of 1,2-diamines with 1,3-dielectrophilic compounds,692f,h intramolecular cycloadditions of (oazidobenzamido)alkenes and alkynes,692i,j aza-Wittig ring closure of [o-(iminophosphoranyl)benzamido]carbonyls,692k intramolecular Michael additions of (o-aminobenzamido)enones.692l Sañudo and co-workers693 reported the synthesis of 5oxobenzo[e][1,4]diazepine-3-carboxamides 624 by Ugi reaction−Staudinger/aza-Wittig cyclization sequences. The Ugi reaction between AGs, para-substituted benzylamines, cyclohexyl isocyanide, and 2-azidobenzoic acid 622 was conducted in MeOH at room temperature to afford products 623 in 45−90% yields, which was converted into 624 by stirring with Ph3P (1.5 equiv) under nitrogen in toluene at room temperature in 59− 99% yields (Scheme 188).

Scheme 186. Synthesis of 3,1-Benzoxathiin-4-one 617

7. SYNTHESIS OF SEVEN-MEMBERED HETEROCYCLES 7.1. N-Heterocyclic Compounds

7.1.1. Tetrahydroazepines. Due to the occurrence of tetrahydroazepines in natural products681 and biologically and pharmaceutically active compounds,682 various approaches, mainly ring-closing metathesis (RCM) reaction,683o−q have been developed to prepare tetrahydroazepine derivatives.683 Pedrosa et al.684 described the synthesis of enantiopure 2,3,4,7-tetrahydro-1H-azepin-3-ols 621a and 1,2,3,4,5,8-hexahydroazocin-3-ols 621b through diastereoselective addition of allylic or homoallylic Grignard reagents 619 to N-allyl-2acylperhydro-1,3-benzoxazines 618 followed by RCM reaction. The starting 618 was prepared in two steps by condensation of (−)-8-aminomenthol 26 with PG followed by alkylation with allylic bromides in the presence of K2CO3 in refluxing CH3CN. By treatment of an excess of 619 with 618 in ether at −10 °C, the corresponding alcohols were produced, which were subjected to RCM using ruthenium(II) complex to give azepines 620a (n = 1) and azocines 620b (n = 2). Compounds 620a,b were transformed to the final 621 via reductive ringopening of the N,O-acetal moiety by treatment with in situ generated AlH3 in THF at reflux followed by oxidation with PCC in DCM at room temperature and then treatment with KOH in THF/MeOH (Scheme 187). 7.1.2. Diazepines and Benzodiazepines. The 1,4diazepine and 1,4-benzodiazepine structures have been found in the naturally occurring antibiotics and are important biomolecules in medicinal chemistry685 with a wide range of

Scheme 188. Synthesis of 5-Oxobenzo[e][1,4]diazepine-3carboxamides 624a

a

Ar = Ph, 4-FC6H4, 4-CF3C6H4, 4-MeOC6H4, 3,4-(MeO)2C6H3, 3,4(OCH2O)C6H3, 4-MeC6H4, 6-MeO-2-naphthyl; Ar′ = Ph, 4-ClC6H4, 4-FC6H4, 4-MeOC6H4, 4-MeC6H4.

Scheme 187. Synthesis of Tetrahydroazepine-3-ols 621a and Hexahydroazocin-3-ols 621ba

a

R, R′, R″ = H, Me; a, n = 1; b, n = 2. BI


Chemical Reviews

Review

presence of SnCl4 at −78 °C afforded a mixture of products 631 and 630 in ratio of 93/7. Compound 631 was converted into 1,4-oxazepane 632 by nucleophilic ring-opening of the N,O-acetal moiety using AlH3 (Scheme 191).662

Recently, a similar reaction was reported by Lecinska et al.694 using 3-azido-(S)-2-(N-Boc-amino)propanoic acid 625 to produce enantiomerically pure tetrahydro-1,4-diazepine-3carboxamides 627 via Ugi products 626 in 61−98% yields (Scheme 189).

Scheme 191. Synthesis of 1,4-Oxazepane 632 Scheme 189. Synthesis of 5-Oxotetrahydro-1,4-diazepines 627a

a

R = H, (S)-NHBoc, (R/S)-Me; Ar = Ph, 4-FC6H4, 4-CF3C6H4, 4MeOC6H4; R′ = n-Bu, Bn, 4-ClC6H4CH2, 4-MeOC6H4CH2, 4MeC6H4CH2.

One example of the condensation of PG with 3-aminoquinazolinone 628 was reported by Tolkunov and Bogza695 via Pictet−Spengler reaction. Reaction was carried out either in refluxing TFA or by heating in HCl to give quinazolino[3,2c][2,3]benzodiazepin-14(6H)-one 629 in 65% yield (Scheme 190).

8. MISCELLANEOUS HETEROCYCLES 8.1. Porphyrins

Porphyrins are important building blocks in many multicomponent systems developed for artificial photosynthesis,699 molecular electronics700 such as molecular wires,701 photovoltaic cells,702 and organic light-emitting diodes (OLEDs),703 as functional elements of light-harvesting systems,704 phototherapy,705 and coordination networks.706 Porphyrins are also one of the most studied DNA binding agents.707 There are many methodologies for synthesis of porphyrins in the literature, commonly condensation of dipyrromethanes or pyrroles with aldehydes along with oxidation.708 Trans-substituted porphyrin 634 was prepared by condensation reaction of dipyrromethane 633 with PG-hydrate in the presence of BF3·OEt2 in DCM at room temperature, followed by adding of DDQ, in 14% yield (Scheme 192).709 Thermal behavior of hetaryl analogs of the unsymmetrical benzoins 635 and 636, obtained from reaction of PG-hydrate with N-methylpyrrole and indoles,710 was investigated. When the pyrrole 635 was heated at 150 °C, tetramerization occurred, and the porphyrin 638 was isolated. In the case of the indole 636 (R = H), the dimer 639 is isolated in a small yield, whereas the N-methylindole 636 (R = Me) resulted in a high yield of the dimer 639 (Scheme 193).711

Scheme 190. Synthesis of Quinazolino[3,2c][2,3]benzodiazepin-14(6H)-one 629

There is one report on the synthesis of seven-membered Oheterocylic compounds starting from AGs in the literature (Scheme 71).289

8.2. Cyclens

7.2. N,O-Heterocyclic Compounds: Oxazepanes

Cyclic tetraamines have attracted increasing attention due to their versatile coordination properties. 1,4,7,10-Tetraazacyclododecane (cyclen or [12]aneN4) and its N-functionalized derivatives have been extensively used in medical purposes712 and pursued713 because the generated metal chelates have wide applications as contrast agents in MRI,714 radiodiagnostic and radiotherapeutic agents,715 luminescent probes,716 fluorescent sensors,717 molecular recognition, catalysis compounds,718 and anti-HIV and anticancer agents.719 The synthesis of such 12-

1,4-Oxazepanes are found as an important structural framework in natural products like neurotoxin batrachotoxin.696 Oxazepanes are important in diverse fields of biochemistry owing to their wide range of biological activities.697 While there is no common route for synthesis of oxazepane, a number of synthetic routes have been reported till date.698 Selenocyclofunctionalization of the secondary alcohol 598, prepared starting with PG (Scheme 180), using PhSeCl in the BJ


Chemical Reviews

Review

Scheme 194. Synthesis of Tetrasubstituted-[12]aneN4 641a

Scheme 192. Synthesis of Porphyrin 634 Using Dipyrromethane 633

a

Ar = Ph, 3-CNC6H4, 2-fluorenyl, 3-phenanthryl; X = CO2H, PMeO2H.

compounds. We have started with the methods for synthesis of AGs, followed by presenting of their applications in heterocycle syntheses in order of number of atoms in heterocyclic rings with consideration of the heteroatom. Reactions of AGs were performed in two different ways: (a) reactions took place in the more reactive aldehyde group and AGs provided one atom in the ring of the heterocycles to produce a benzoyl substituent or (b) both aldehyde and ketone groups of AG contributed to the reaction to provide two atoms of the heterocyclic rings. Moreover, AG derivatives such as AGacetals, -imines, -oximes, and -hydrazones, which show different reactivity and selectivity in contrast with AGs, also worked well in construction of heterocyclic compounds. From the perspective of the application of AGs in this field, AGs and their derivatives are unique structures that led to a broad spectrum of heterocycles. While different types of reactions such as cyclocondensation, cycloaddition, Pictet−Spengler and Ugi−Wittig, Ugi-cyclocondensation, aldol−Paal−Knorr and Wittig−dehydrative cyclization sequences were demonstrated for synthesis of five- and six-membered heterocycles, the future evolution of other methodologies promises new approaches to synthesize new heterocylic systems, especially seven-membered and fused heterocycles, previously thought to be inaccessible. Recently considerable interest has been shown to one-pot domino reactions via in situ generation of AGs or their derivatives (domino 1) followed by transformation to heterocycles (domino 2). Because of the broad spectrum of

membered tetraaza rings has been achieved using high-dilution syntheses.720 The cyclo-condensation of triethylenetetramine 452 with AGs in the presence of FeCl3 was reported to afford [12]aneN4 type diimine complex intermediates, which were reduced and demetalated in situ with NaBH4 to give the [12]aneN4 640 in up to 60% overall yields. The reactions were carried out in dry methanol, followed by addition of excess NaBH4. Compounds 640 were transformed into the corresponding tetraacetate or tetramethylphosphinate derivatives 641 via reaction with ClCH2CO2− or with (CH2O)n−MeP(OEt)2 followed by acidic hydrolysis (Scheme 194).721 Nucleophilic trifluoromethylation of AG-imines with Ruppert−Prakash reagent (CF3SiMe3) gave the corresponding Osilylated β-imino-α-(trifluoromethyl)alcohols, which underwent reduction and desilylation with NaBH4 to yield the β-amino-α(trifluoromethyl)alcohols 642. The β-amino alcohols 642 were used to synthesize diverse trifluoromethylated heterocycles, including aziridines 643, 1,3-oxazolidin-2-ones 644, 1,2,3oxathiazolidine 2-oxides 645, 1,3-oxazolidines 646, 1,3,2oxazaphospholidine 2-oxides 647, and morpholine-2,3-diones 648 as outlined in Scheme 195.722

9. CONCLUSION In this review, we have presented an overview of the use of AGs and their derivatives in the synthesis of heterocyclic

Scheme 193. Synthesis of Porphyrin 638 and Indolo[3,2-b]carbazole 639

BK


Chemical Reviews

Review

Scheme 195. Synthesis of Different Heterocycles Using AGImines through β-Amino Alcohols 642a

Bagher Eftekhari-Sis was born in 1980 in Sis, Shabestar, Iran. He obtained his B.Sc. in Applied Chemistry from University of Tabriz in 2004 and M.Sc. in Organic Chemistry from Sharif University of Technology with Prof. Mohammed M. Hashemi in 2006. Also, He received his Ph.D. under the supervision of Prof. Mohammed M. Hashemi in 2009 and then joined the Chemistry Department of the University of Maragheh. His research field involves the synthetic utility of arylglyoxals, especially in synthesis of heterocycles, and recently on polymer-supported catalysts, OLEDs, dual sensor polymers, and bioimaging.

Maryam Zirak was born in Til, Shabestar, Iran. She received her B.Sc. in Pure Chemistry and M.Sc. in Organic Chemistry from University of Tabriz. She obtained her Ph.D in 2010 from University of Tabriz on the topic of pyrone-based heterocycles and its applications in Medicinal Chemistry under the advisement of Prof. Aziz Shahrisa. Recently, she joined the Chemistry Department of the Payame Noor University of Mahabad-West Azerbaijan, Iran, and her research field involves the development of new methodologies for synthesis of heterocycles.

a

Ar = Ph, 4-CF3C6H4, 4-MeOC6H4, 4-NO2C6H4; R = t-Bu, i-Pr, (S)PhCH(Me).

synthesized heterocycles using AGs and their derivatives, the reported methods could be of interest in material science and medicinal and natural products synthesis.

AUTHOR INFORMATION Corresponding Author

*E-mail: [email protected]; [email protected]. Notes

The authors declare no competing financial interest. Biographies Ali Akbari was born in 1981 in Naghadeh, Iran. He received his B.Sc. in Applied Chemistry from the University of Tabriz in 2005 and completed his M.Sc. in the field of Organic Chemistry at the Chemistry and Chemical Engineering Research Center of Iran in 2009. Then he joined the group of Dr. Eftekhari-Sis as a research assistant at the University of Maragheh until summer 2011.

ACKNOWLEDGMENTS The corresponding author thanks Dr. M. Amini (University of Maragheh), M. Razzaghi (Southern Illinois University Edwardsville), M. Samet (University of Minnesota), M. G. Nazari, H. Abbasi (University of Tabriz), and Prof. A. Rahimi (University of Maragheh) for kind help. We would also thank the anonymous reviewers for their constructive comments. BL


Chemical Reviews

Review

DEDICATION

TFA TFAA Tf TfOH THF TIPS TMP TsCl TsMIC p-TsOH

Dedicated to Professors M. M. Hashemi, F. Matloubi Moghaddam, A. Pourjavadi, M. R. Saidi, and A. Shahrisa.

ABBREVIATIONS acac acetylacetone AcO acetate AGs arylglyoxals AIBN 2,2′-azoisobutyronitrile aq aqueous atm atmosphere BINAP 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl Bn benzyl Boc t-butoxycarbonyl CAN ceric ammonium nitrate c-Hex cyclohexyl conc concentration cond conditions COD 1,5-cycloocatdiene c-Pr cyclopropyl CTAB cetyl trimethyl ammonium bromide DA Diels−Alder DAAD dialkyl acetylene dicarboxylate DABCO 1,4-diazabicyclo[2.2.2]octane dba dibenzylideneacetone DBU 1,8-diazabicycloundec-7-ene DCE 1,2-dichloroethane DCM dichloromethane DDQ 2,3-dichloro-5,6-dicyano-1,4-benzoquinone DEAD diethyl azodicarboxylate DHPMs 3,4-dihydropyrimidine-2-ones DIBAL-H diisobutylaluminium hydride DIPEA diisopropylethylamine DMAP 4-dimethylaminopyridine DMB 3,5-dimethoxybenzyl DMF N,N-dimethylformamide DMSO dimethylsulfoxide DPENTf 1,2-N,N′-bis-(trifluoromethanesulfonylamino)1,2-diphenylethane glyme dimethoxyethane HAD hetero-Diels−Alder HHPs hexahydropyrimidines HMPA hexamethylphosphoramide HQ hydroquinone HWE Horner−Wadsworth−Emmons Menth menthyl MeObiphep 2,2′-bis[di(3,5-di-t-butyl-4-methoxyphenyl)phosphino]-6,6′-dimethoxy-1,1′-biphenyl MS molecular sieves MsCl methanesulfonyl chloride MW microwave NBS N-bromosuccinimide NaHMDS sodium hexamethyldisilazide OLEDs organic light-emitting diodes PCC pyridinium chlorochromate PG phenylglyoxal PMB p-methoxybenzyl PMP p-methoxyphenyl PPE polyphosphoric acid ester py pyridine sym symmetrical TBDMS t-butyldimethylsilyl

trifluoroacetic acid trifluoroacetic anhydride trifluoromethanesulfonyl trifluoromethanesulfonic acid or triflic acid tetrahydrofuran triisopropylsilyl trimethyl phosphite p-toluenesulfonyl chloride p-toluenesulfonylmethyl isocyanide p-toluenesulfonic acid

REFERENCES (1) (a) Chan, T. H.; Yang, Y. Tetrahedron Lett. 1999, 40, 3863. (b) Akiyama, T.; Iwai, J.; Sugano, M. Tetrahedron 1999, 55, 7499. (c) Kang, S.-K.; Baik, T.-G.; Jiao, X.-H. Synth. Commun. 2002, 32, 75. (d) Jin, Y. Z.; Yasuda, N.; Furuno, H.; Inanaga, J. Tetrahedron Lett. 2003, 44, 8765. (2) Zhang, Q.; Xu, C.-M.; Chen, J.-X.; Xu, X.-L.; Ding, J.-C.; Wu, H.Y. Appl. Organomet. Chem. 2009, 23, 524. (3) (a) Ishihara, K.; Yano, T.; Fushimi, M. J. Fluorine Chem. 2008, 129, 994. (b) Schmitt, E.; Schiffers, I.; Bolm, C. Tetrahedron Lett. 2009, 50, 3185. (4) Blay, G.; Hernández-Olmos, V.; Pedro, J. R. Chem.Eur. J. 2011, 17, 3768. (5) Kobayashi, S.; Araki, M.; Yasuda, M. Tetrahedron Lett. 1995, 36, 5773. (6) (a) Itoh, T.; Nagata, K.; Miyazaki, M.; Ishikawa, H.; Kurihara, A.; Ohsawa, A. Tetrahedron 2004, 60, 6649. (b) Itoh, T.; Nagata, K.; Kurihara, A.; Miyazaki, M.; Ohsawa, A. Tetrahedron Lett. 2002, 43, 3105. (7) Jang, H.-Y.; Huddleston, R. R.; Krische, M. J. Angew. Chem., Int. Ed. 2003, 42, 4074. (8) Wu, J.; Sun, L.; Dai, W.-M. Tetrahedron 2006, 62, 8360. (9) Akbari, A. Synlett 2012, 23, 951. (10) Shen, Q.; Hagen, K. J. Phys. Chem. 1993, 97, 985. (11) (a) Takahashi, K. J. Biol. Chem. 1968, 243, 6171. (b) Tiffany, B. D.; Wright, J. B.; Moffett, R. B.; Heinzelman, R. V.; Strube, R. E.; Aspergren, B. D.; Lincoln, E. H.; White, J. L. J. Am. Chem. Soc. 1957, 79, 1682. (c) Moffett, R. B.; Tiffany, B. D.; Aspergren, B. D.; Heinzelman, R. V. J. Am. Chem. Soc. 1957, 79, 1687. (12) von Pechmann, H. Chem. Ber. 1887, 20, 2904. (13) (a) Riley, H. L.; Morley, J. F.; Friend, N. A. C. J. Chem. Soc. 1932, 1875. (b) Riley, H. A.; Gray, A. R. Org. Synth. 1935, 15, 67; Org. Synth. Collect. Vol. 1943, 2, 509. (c) Bousset, R. Bull. Soc. Chim. France 1939, 6, 986. (14) Saldabol, N. O.; Popelis, J.; Slavinska, V. Chem. Heterocycl. Compd. 2002, 38, 783. (15) Sharma, V. K.; Chandalia, S. B. J. Chem. Technol. Biotechnol. 1986, 36, 456. (16) Floyd, M. B.; Du, M. T.; Fabio, P. F.; Jacob, L. A.; Johnson, B. D. J. Org. Chem. 1985, 50, 5022. (17) Mikol, G. J.; Russell, G. A. Org. Synth. 1968, 48, 109; Org. Synth. Collect. Vol. 1973, 5, 937. (18) Kornblum, N.; Powers, J. W.; Anderson, G. J.; Jones, W. J.; Larson, H. O.; Levand, O.; Weaver, W. M. J. Am. Chem. Soc. 1957, 79, 6562. (19) Tiecco, M.; Testaferri, L.; Tingoli, M.; Bartoli, D. J. Org. Chem. 1990, 55, 4523. (20) Kornblum, N.; Frazier, H. W. J. Am. Chem. Soc. 1966, 88, 865. (21) Ihmels, H.; Maggini, M.; Prato, M.; Scorrano, G. Tetrahedron Lett. 1991, 32, 6215. (22) Gunn, V. E.; Anselme, J.-P. J. Org. Chem. 1977, 42, 754. (23) Kato, T.; Goto, Y.; Yamamoto, Y. Yakugaku Zasshi 1964, 84, 287. (24) Ballistreri, F.; Failla, S.; Tomaselli, G. A.; Curci, R. Tetrahedron Lett. 1986, 27, 5139. (25) Wolfe, S.; Pilgrim, W. R.; Garrard, T. F.; Chamberlain, P. Can. J. Chem. 1971, 49, 1099. BM


Chemical Reviews

Review

Mangelinckx, S.; Toernroos, K. W.; De Kimpe, N. Org. Lett. 2006, 8, 3129. (v) Lu, Z.; Zhang, Y.; Wulff, W. D. J. Am. Chem. Soc. 2007, 129, 7185. (w) Hashimoto, T.; Nakatsu, H.; Yamamoto, K.; Maruoka, K. J. Am. Chem. Soc. 2011, 133, 9730. (37) (a) Olofsson, B.; Wijtmans, R.; Somfai, P. Tetrahedron 2002, 58, 5979. (b) Olofsson, B.; Khamrai, U.; Somfai, P. Org. Lett. 2000, 2, 4087. (c) Tomasini, C.; Vecchione, A. Org. Lett. 1999, 1, 2153. (d) Woydowski, K.; Liebscher, J. Synthesis 2000, 1444. (e) Legters, J.; Thijs, L.; Zwanenburg, B. Tetrahedron Lett. 1989, 30, 4881. (f) Deiana, L.; Dziedzic, P.; Zhao, G.-L.; Vesely, J.; Ibrahem, I.; Rios, R.; Sun, J.; Córdova, A. Chem.Eur. J. 2011, 17, 7904. (g) Kim, H. Y.; Talukdar, A.; Cushman, M. Org. Lett. 2006, 8, 1085. (38) (a) Gini, F.; Del Moro, F.; Macchia, F.; Pineschi, M. Tetrahedron Lett. 2003, 44, 8559. (b) Lindstrom, U. M.; Somfai, P. Chem.Eur. J. 2001, 7, 94. (39) Righi, G.; Potini, C.; Bovicelli, P. Tetrahedron Lett. 2002, 43, 5867. (40) (a) Aggarwal, V. K. Synlett 1998, 329. (b) Aggarwal, V. K.; Thompson, A.; Jones, R. V. H.; Standen, M. C. H. J. Org. Chem. 1996, 61, 8368. (c) Aggarwal, V. K. Angew. Chem. 2001, 113, 1482; Angew. Chem., Int. Ed. 2001, 40, 1433. (d) Kano, T.; Hato, Y.; Yamamoto, A.; Maruoka, K. Tetrahedron 2008, 64, 1197. (e) Troyer, T. L.; Muchalski, H.; Hong, K. B.; Johnston, J. N. Org. Lett. 2011, 13, 1790. (f) Deyrup, J. A. J. Org. Chem. 1969, 34, 2724. (g) McLaren, A. B.; Sweeney, J. B. Org. Lett. 1999, 1, 1339. (41) Akiyama, T.; Suzuki, T.; Mori, K. Org. Lett. 2009, 11, 2445. (42) Nagayama, S.; Kobayashi, S. Chem. Lett. 1998, 685. (43) (a) Nagaoka, K.; Matsumoto, M.; Oono, J.; Yokoi, K.; Ishizeki, S.; Nakashima, T. J. Antibiot. 1986, 39, 1527. (b) Hodgkinson, T. J.; Shipman, M. Tetrahedron 2001, 57, 4467. (c) Coleman, R. S.; Perez, R. J.; Burk, C. H.; Navarro, A. J. Am. Chem. Soc. 2002, 124, 13008. (d) Landreau, C. A. S.; LePla, R. C.; Shipman, M.; Slawin, A. M. Z.; Hartley, J. A. Org. Lett. 2004, 6, 3505. (44) Trimurtulu, G.; Ohtani, I.; Patterson, G. M. L.; Moore, R. E.; Corbett, T. H.; Valeriote, F. A.; Demchik, L. J. Am. Chem. Soc. 1994, 116, 4729. (45) Kupchan, S. M.; Court, W. A.; Dailey, R. G., Jr.; Gilmore, C. J.; Bryan, R. F. J. Am. Chem. Soc. 1972, 94, 7194. (46) Hanada, M.; Sugawara, K.; Kaneta, K.; Toda, S.; Nishiyama, Y.; Tomita, K.; Yamamoto, H.; Konishi, M.; Oki, T. J. Antibiot. 1992, 45, 1746. (47) (a) Kupchan, S. M.; Streelman, D. R.; Sneden, A. T. J. Nat. Prod. 1980, 43, 296. (b) Cassady, J. M. J. Nat. Prod. 1990, 53, 23. (48) (a) Liou, S.-S.; Shieh, W.-L.; Cheng, T.-H.; Won, S.-J.; Lin, C.N. J. Pharm. Pharmacol. 1993, 45, 791. (b) Lin, C.-N.; Liou, S.-S.; Lee, T.-H.; Chuang, Y.-C.; Won, S.-J. J. Pharm. Pharmacol. 1996, 48, 539. (c) Woo, S.; Jung, J.; Lee, C.; Kwon, Y.; Na, Y. Bioorg. Med. Chem. Lett. 2007, 17, 1163. (d) Lee, K. Y.; Chang, W.-T.; Qiu, D.-M.; Kao, P. N.; Rosen, G. D. J. Biol. Chem. 1999, 274, 13451. (e) Shamon, L. A.; Pezzuto, J. M.; Graves, J. M.; Mehta, R. R.; Wangcharoentrakul, S.; Sangsuwan, R.; Chaichana, S.; Tuchinda, P.; Cleason, P.; Reutrakul, V. Cancer Lett. 1997, 112, 113. (f) Yang, S.; Chen, J.; Guo, Z.; Xu, X. M.; Wang, L.; Pei, X. F.; Yang, J.; Underhill, C. B.; Zhang, L. Mol. Cancer Ther. 2003, 2, 65. (g) Tengchaisri, T.; Chawengkirttikul, R.; Rachaphaew, N.; Reutrakul, V.; Sangsuwan, R.; Sirisinha, S. Cancer Lett. 1998, 133, 169. (h) Chang, W. T.; Kang, J. J.; Lee, K. Y.; Wei, K.; Anderson, E.; Gotmare, S.; Ross, J. A.; Rosen, G. D. J. Biol. Chem. 2001, 276, 2221. (i) Armstrong, R. W.; Salvati, M. E.; Nguyen, M. J. Am. Chem. Soc. 1992, 114, 3144. (j) Fujiwara, T.; Saito, I.; Sugiyama, H. Tetrahedron Lett. 1999, 40, 315. (k) Hartley, J. A.; Hazrati, A.; Kelland, L. R.; Khanim, R.; Shipman, M.; Suzenet, F.; Walker, L. F. Angew. Chem., Int. Ed. 2000, 39, 3467. (49) (a) Kupchan, S. M.; Schubert, R. M. Science 1974, 185, 791. (b) Carter, B. Z.; Mak, D. H.; Schober, W. D.; McQueen, T.; Harris, D.; Estrov, Z.; Evans, R. L.; Andreeff, M. Blood 2006, 108, 630. (50) Zheng, Y. L.; Lin, J. F.; Lin, C. C.; Xu, Y. Acta Pharmacol. Sin. 1994, 15, 540. (51) (a) Gu, W. Z.; Chen, R.; Brandwein, S.; McAlpine, J.; Burres, N. Int. J. Immunopharmacol. 1995, 17, 351. (b) Yang, S. X.; Gao, H. L.;

(26) Santoro, S.; Battistelli, B.; Gjoka, B.; Si, C.-W. S.; Testaferri, L.; Tiecco, M.; Santi, C. Synlett 2010, 1402. (27) Jagdale, A. R.; Chouthaiwale, P. V.; Sudalai, A. Indian J. Chem. 2009, 48B, 1424. (28) (a) Aziridines and Epoxides in Organic Synthesis; Yudin, A. K., Ed.; Wiley-VCH: Weinheim, Germany, 2006. (b) Padwa, A. Comprehensive Heterocyclic Chemistry III; Katritzky, A. R., Ramsden, C. A., Scriven, E. F. V., Taylor, R. J. K., Eds.; Elsevier: Oxford, U.K., 2008; Vol. 1, pp 1−104. (c) Sweeney, J. B. Chem. Soc. Rev. 2002, 31, 247. (d) Tanner, D. Angew. Chem., Int. Ed. 1994, 33, 599. (29) (a) Yadav, J. S.; Reddy, B. V. S.; Jyothirmai, B.; Murty, M. S. R. Synlett 2002, 53. (b) Katagiri, T.; Takahashi, M.; Fujiwara, Y.; Ihara, H.; Uneyama, K. J. Org. Chem. 1999, 64, 7323. (c) Chuang, T.-H.; Sharpless, K. B. Org. Lett. 2000, 2, 3555. (d) Wu, J.; Hou, X.-L.; Dai, L.-X. J. Chem. Soc., Perkin Trans. 1 2001, 1314. (e) Hou, X.-L.; Fan, R.H.; Dai, L.-X. J. Org. Chem. 2002, 67, 5295. (f) Caiazzo, A.; Dalili, S.; Yudin, A. K. Org. Lett. 2002, 4, 2597. (g) Davoli, P.; Moretti, I.; Prati, F.; Apler, H. J. Org. Chem. 1999, 64, 518. (30) Cardillo, G.; Gentilucci, L.; Tolomelli, A. Aldrichimica Acta 2003, 36, 39. (31) (a) Watson, I. D. G.; Yu, L.; Yudin, A. K. Acc. Chem. Res. 2006, 39, 194. (b) Kumar, K. S. A.; Chaudhari, V. D.; Puranik, V. G.; Dhavale, D. D. Eur. J. Org. Chem. 2007, 4895. (c) Smith, A. B., III; Kim, D.-S. Org. Lett. 2004, 6, 1493. (d) Trost, B. M.; Dong, G. Org. Lett. 2007, 9, 2357. (e) Caldwell, J. J.; Craig, D. Angew. Chem., Int. Ed. 2007, 46, 2631. (32) (a) Sweeney, J. B. Chem. Soc. Rev. 2002, 31, 247. (b) Tanner, D. Angew. Chem., Int. Ed. 1994, 33, 599. (33) (a) Benbow, J. W.; McClure, K. F.; Danishefsky, S. J. J. Am. Chem. Soc. 1993, 115, 12305. (b) Gerhart, F.; Higgins, W.; Tardif, C.; Ducep, J. B. J. Med. Chem. 1990, 33, 2157. (c) Sweeney, J. B. Chem. Soc. Rev. 2002, 31, 247. (34) (a) Kasai, M.; Kono, M. Synlett 1992, 778. (b) Hodgkinson, T. J.; Shipman, M. Tetrahedron 2001, 57, 4467. (35) (a) Skibo, E. B.; Islam, I.; Heileman, M. J.; Schulz, W. G. J. Med. Chem. 1994, 37, 78. (b) Moonen, K.; Laureyn, I.; Stevens, C. V. Chem. Rev. 2004, 104, 6177. (c) Toda, A.; Aoyama, H.; Mimura, N.; Ohno, H.; Fujii, N.; Ibuka, T. J. Org. Chem. 1998, 63, 7053. (d) Hwang, G.-I.; Chung, J.-H.; Lee, W. K. J. Org. Chem. 1996, 61, 6183. (e) Park, C. S.; Choi, H. G.; Lee, H.; Lee, W. K.; Ha, H.-J. Tetrahedron: Asymmetry 2000, 11, 3283. (f) Ibuka, T.; Mimura, N.; Aoyama, H.; Akaji, M.; Ohno, H.; Miwa, Y.; Taga, T.; Nakai, K.; Tamamura, H.; Fujii, N.; Yamamoto, Y. J. Org. Chem. 1997, 62, 999. (36) (a) Patwardhan, A. P.; Pulgam, V. R.; Zhang, Y.; Wulff, W. D. Angew. Chem. 2005, 117, 6325; Angew. Chem., Int. Ed. 2005, 44, 6169 and references therein. (b) Mueller, P.; Fruit, C. Chem. Rev. 2003, 103, 2905. (c) Evans, D. A.; Bilodeau, M. T.; Faul, M. M. J. Am. Chem. Soc. 1994, 116, 2742. (d) Li, Z.; Quan, R. W.; Jacobsen, E. N. J. Am. Chem. Soc. 1995, 117, 5889. (e) Li, Z.; Conser, K. R.; Jacobsen, E. N. J. Am. Chem. Soc. 1993, 115, 5326. (f) Ma, L.; Du, D.-M.; Xu, J. Chirality 2006, 18, 575. (g) Wang, X.; Ding, K. Chem.Eur. J. 2006, 12, 4568. (h) Gillespie, K. M.; Sanders, C. J.; O’Shaughnessy, P.; Westmoreland, I.; Thickitt, C. P.; Scott, P. J. Org. Chem. 2002, 67, 3450. (i) Yoshimura, A.; Nemykin, V. N.; Zhdankin, V. V. Chem.Eur. J. 2011, 17, 10538. (j) Zdilla, M. J.; Abu-Omar, M. M. J. Am. Chem. Soc. 2006, 128, 16971. (k) Groves, J. T.; Takahashi, T. J. Am. Chem. Soc. 1983, 105, 2073. (l) Mansuy, D.; Mahy, J.-P.; Dureault, A.; Bedi, G.; Battioni, P. J. Chem. Soc., Chem. Commun. 1984, 1161. (m) Mahy, J.-P.; Bedi, G.; Battioni, P.; Mansuy, D. J. Chem. Soc., Perkin Trans. 2 1988, 1517. (n) Au, S.-M.; Zhang, S.-B.; Fung, W.-H.; Yu, W.-Y.; Che, C.-M.; Cheung, K.-K. Chem. Commun. 1998, 2677. (o) Au, S.-M.; Huang, J.S.; Yu, W.-Y.; Fung, W.-H.; Che, C.-M. J. Am. Chem. Soc. 1999, 121, 9120. (p) McGarrigle, E. M.; Myers, E. L.; Illa, O.; Shaw, M. A.; Riches, S. L.; Aggarwal, V. K. Chem. Rev. 2007, 107, 5841. (q) Antilla, J. C.; Wulff, W. D. Angew. Chem. 2000, 112, 4692; Angew. Chem., Int. Ed. 2000, 39, 4518. (r) Robiette, R. J. Org. Chem. 2006, 71, 2726. (s) Hou, X. L.; Wu, J.; Fan, R. H.; Ding, C. H.; Luo, Z. B.; Dai, L. X. Synlett 2006, 181. (t) Li, Y.; Chan, P. W. H.; Zhu, N.-Y.; Che, C.-M.; Kwong, H.-L. Organometallics 2004, 23, 54. (u) Denolf, B.; BN


Chemical Reviews

Review

(57) Kinoshita, E.; Yamakoshi, J.; Kikuchi, M. Biosci., Biotechnol., Biochem. 1993, 57, 1107. (58) Fushiya, S.; Tanura, T.; Tashiro, T.; Nozoe, S. Heterocycles 1984, 22, 1039. (59) Isono, K.; Asahi, K.; Suzuki, S. J. Am. Chem. Soc. 1969, 91, 7490. (60) Erickson, B. I.; Carlsson, S.; Halvarsson, M.; Risberg, B.; Mattson, C. Thromb. Haemostasis 1997, 78, 1404. (61) (a) Cromwell, N. H.; Phillips, B. Chem. Rev. 1979, 79, 331. (b) Moore, J. A.; Ayers, R. S. In Chemistry of Heterocyclic CompoundsSmall Ring Heterocycles; Hassner, A., Ed.; Wiley: New York, 1983; Part 2, pp 1−217. (c) Davies, D. E.; Storr, R. C. In Comprehensive Heterocyclic Chemistry; Lwowski, W., Ed.; Pergamon: Oxford, U.K., 1984; Vol. 7, Part 5, pp 237−284. (62) Samarendra, C. I.; Maiti, N.; Micetich, R.; Daneshtalab, M.; Atchison, K.; Phillips, O. A.; Kunugita, C. J. Antibiot. 1994, 47, 1030. (63) Gurupadayya, B. M.; Gopal, M.; Padmashali, B.; Manohara, Y. N. Indian J. Pharm. Sci. 2008, 70, 572. (64) Kumar, A.; Rajput, C. S.; Bhati, S. K. Bioorg. Med. Chem. 2007, 15, 3089. (65) (a) Veinverg, G.; Shestakova, I.; Vorona, M.; Kanepe, I.; Lukevics, E. Bioorg. Med. Chem. Lett. 2004, 14, 147. (b) Banik, B. K.; Becker, F. F.; Banik, I. Bioorg. Med. Chem. 2004, 12, 2523. (66) (a) Chavan, A. A.; Pai, N. R. Molecules 2007, 12, 2467. (b) Mistry, K.; Desai, K. R. Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem. 2006, 45, 1762. (67) Singh, G. S.; Mbukwa, E.; Pheko, T. Arkivoc 2007, ix, 80. (68) Udapi, R. H.; Mayur, Y. C.; Bhatt, A. R. Indian J. Heterocycl. Chem. 1997, 6, 281. (69) Deiccolo, C. L. M.; Mata, E. G. Tetrahedron Lett. 2004, 45, 4085. (70) (a) The Organic Chemistry of β-Lactams; Georg, G. I., Ed.; VCH: New York, 1993. (b) Sammes, P. G. Chem. Rev. 1976, 76, 113. (71) (a) Mandal, P. K.; Cabell, L. A.; McMurray, J. S. Tetrahedron Lett. 2005, 46, 3715. (b) Stanković, S.; Catak, S.; D’hooghe, M.; Goossens, H.; Tehrani, K. A.; Bogaert, P.; Waroquier, M.; Speybroeck, V. V.; De Kimpe, N. J. Org. Chem. 2011, 76, 2157. (c) Agami, C.; Coutya, F.; Rabasso, N. Tetrahedron Lett. 2002, 43, 4633. (d) Morimoto, H.; Wiedemann, S. H.; Yamaguchi, A.; Harada, S.; Chen, Z.; Matsunaga, S.; Shibasaki, M. Angew. Chem., Int. Ed. 2006, 45, 3146. (e) Ye, L.; He, W.; Zhang, L. Angew. Chem., Int. Ed. 2011, 50, 3236. (f) Guo, S.; Xie, Y.; Hu, X.; Xia, C.; Huang, H. Angew. Chem., Int. Ed. 2010, 49, 2728. (72) (a) Karlsson, S.; Sörensen, J. H. Org. Process Res. Dev. 2012, 16, 586. (b) Ibrahim, Y. A.; Al-Azemi, T. F.; Abd El-Halim, M. D.; John, E. J. Org. Chem. 2009, 74, 4305. (c) Liang, Y.; Jiao, L.; Zhang, S.; Yu, Z.X.; Xu, J. J. Am. Chem. Soc. 2009, 131, 1542. (d) Leon, F.; Rivera, D. G.; Wessjohann, L. A. J. Org. Chem. 2008, 73, 1762. (e) Dubey, A.; Srivastava, S. K.; Srivastava, S. D. Bioorg. Med. Chem. Lett. 2011, 21, 569. (f) Zhang, Y.-R.; He, L.; Wu, X.; Shao, P.-L.; Ye, S. Org. Lett. 2008, 10, 277. (g) Li, B.; Wang, Y.; Du, D.-M.; Xu, J. J. Org. Chem. 2007, 72, 990. (h) Wang, Y.; Liang, Y.; Jiao, L.; Du, D.-M.; Xu, J. J. Org. Chem. 2006, 71, 6983. (i) Jiao, L.; Liang, Y.; Xu, J. J. Am. Chem. Soc. 2006, 128, 6060. (j) Lee, E. C.; Hodous, B. L.; Bergin, E.; Shih, C.; Fu, G. C. J. Am. Chem. Soc. 2005, 127, 11586. (73) Pedrosa, R.; Andrés, C.; Nieto, J.; del Pozo, S. J. Org. Chem. 2005, 70, 1408. (74) Tanaka, H.; Hai, A. K. M. A.; Sadakane, M.; Okumoto, H.; Torii, S. J. Org. Chem. 1994, 59, 3040. (75) Lynch, J. E.; Riseman, S. M.; Laswell, W. L.; Tschaen, D. M.; Volante, R. P.; Smith, G. B.; Shinkai, I. J. Org. Chem. 1989, 54, 3792. (76) Palomo, C.; Aizpurua, J. M.; Iturburu, M.; Urchegui, R. J. Org. Chem. 1994, 59, 240. (77) van der Veen, J. M.; Bari, S. S.; Krishnan, L.; Manhas, M. S.; Bose, A. K. J. Org. Chem. 1989, 54, 5758. (78) Wang, Z. X.; Xu, J. X. Sci. China: Chem. 2011, 54, 1711. (79) (a) Del Buttero, P.; Molteni, G.; Papagni, A.; Pilati, T. Tetrahedron 2003, 59, 5259. (b) Alcaide., B.; Dominguez., G.; Plumet, J.; Sierra, M. A. Heterocycles 1988, 27, 1317. (80) (a) Wang, Y.; Tennyson, R. L.; Romo, D. Heterocycles 2004, 64, 605. (b) Müller, H.-M.; Seebach, D. Angew. Chem., Int. Ed. 1993, 32,

Xie, S. S.; Zhang, W. R.; Long, Z.-Z. Int. J. Immunopharmacol. 1992, 14, 963. (c) Qiu, D. M.; Zhao, G. H.; Aoki, Y.; Shi, L. F.; Uyei, A.; Nazarian, S.; Ng, J. C.-H.; Kao, P. N. J. Biol. Chem. 1999, 274, 13443. (52) (a) Ojima, I. Catalytic Asymmetric Synthesis, 2nd ed.; Wiley: New York, 2000. (b) Xia, Q.-H.; Ge, H.-Q.; Ye, C.-P.; Liu, Z.-M.; Su, K.-X. Chem. Rev. 2005, 105, 1603. (c) Bandini, M.; Cozzi, P. G.; Melchiorre, P.; Umani-Ronchi, A. J. Org. Chem. 2002, 67, 5386. (d) Bandini, M.; Cozzi, P. G.; Melchiorre, P.; Umani-Ronchi, A. Angew. Chem., Int. Ed. 2004, 43, 84. (e) Westermaier, M.; Mayr, H. Chem.Eur. J. 2008, 14, 1638. (f) Bertolini, F.; Crotti, P.; Macchia, F.; Pineschi, M. Tetrahedron Lett. 2006, 47, 61. (g) Bertolini, F.; Crotti, P.; Di Bussolo, V.; Macchia, F.; Pineschi, M. J. Org. Chem. 2007, 72, 7761. (h) Bellamy, E.; Bayh, O.; Hoarau, C.; Trécourt, F.; Quéguiner, G.; Marsais, F. Chem. Commun. 2010, 7043. (i) Schneider, C.; Brauner, J. Eur. J. Org. Chem. 2001, 4445. (j) Zhou, H.; Campbell, E. J.; Nguyen, S. T. Org. Lett. 2001, 3, 2229. (k) Zhao, H.; Pagenkopf, B. L. Chem. Commun. 2003, 2592. (l) Restorp, P.; Somfai, P. Eur. J. Org. Chem. 2005, 3946. (m) Schaus, S. E.; Jacobsen, E. N. Org. Lett. 2000, 2, 1001. (n) Saha, B.; Lin, M.-H.; Rajan Babu, T. V. J. Org. Chem. 2007, 72, 8648. (o) Mirmashhori, B.; Azizi, N.; Saidi, M. R. J. Mol. Catal. A: Chem. 2006, 247, 159. (p) Martínez, F.; del Campo, C.; Llama, E. F. J. Chem. Soc., Perkin Trans. 1 2000, 1749. (q) Suda, K.; Baba, K.; Nakajima, S.; Takanami, T. Chem. Commun. 2002, 2570. (r) Suda, K.; Kikkawa, T.; Nakajima, S.; Takanami, T. J. Am. Chem. Soc. 2004, 126, 9554. (s) Deng, X.-M.; Sun, X.-L.; Tang, Y. J. Org. Chem. 2005, 70, 6537. (t) Shen, Y.-M.; Wang, B.; Shi, Y. Angew. Chem., Int. Ed. 2006, 45, 1429. (u) Kita, Y.; Furukawa, A.; Futamura, J.; Ueda, K.; Sawama, Y.; Hamamoto, H.; Fujioka, H. J. Org. Chem. 2001, 66, 8779. (v) Kita, Y.; Futamura, J.; Ohba, Y.; Sawama, Y.; Ganesh, J. K.; Fujioka, H. J. Org. Chem. 2003, 68, 5917. (w) Islas-Gonzáles, G.; Benet-Buchholz, J.; Maestro, M. A.; Riera, A.; Pericàs, M. A. J. Org. Chem. 2006, 71, 1537. (x) Maslak, V.; Matović, R.; Saičić, R. N. Tetrahedron Lett. 2002, 43, 5411 and references cited therein. (y) Shen, Y.-M.; Wang, B.; Shi, Y. Tetrahedron Lett. 2006, 47, 5455. (z) Moghadam, M.; Tangestaninejad, S.; Mirkhani, V.; Shaibani, R. Tetrahedron 2004, 60, 6105 and references cited therein. (53) (a) Cativiela, C.; Figueras, F.; Fraile, J. M.; García, J. I.; Mayoral, J. A. Tetrahedron Lett. 1995, 36, 4125. (b) Choudary, B. M.; Kantam, M. L.; Bharathi, B.; Reddy, Ch. V. Synlett 1998, 1203. (c) Yamaguchi, K.; Mori, K.; Mizugaki, T.; Ebitani, K.; Kaneda, K. J. Org. Chem. 2000, 65, 6897. (d) Fraile, J. M.; García, J. I.; Mayoral, J. A.; Sebti, S.; Tahir, R. Green Chem. 2001, 3, 271. (e) Lee, S.; MacMillan, D. W. C. Tetrahedron 2006, 62, 11413 and references cited therein. (f) Sheldon, R. A. Green Chem. 2007, 9, 1273. (g) Sheldon, R. A.; Kochi, J. K. Metal-Catalyzed Oxidations of Organic Compounds; Academic: New York, 1981. (h) Adam, W. Peroxide Chemistry; Wiley-VCH: Weinheim, Germany, 2000. (i) Bäckvall, J.-E. Modern Oxidation Methods; WileyVCH: Weinheim, Germany, 2004. (j) Jacobsen, E. N. In Catalytic Asymmetric Synthesis; Ojima, I., Ed.; VCH: New York, 1993; pp 159− 202. (k) Shi, Y. Acc. Chem. Res. 2004, 37, 488. (l) Yang, D. Acc. Chem. Res. 2004, 37, 497. (m) Wang, Z. X.; Tu, Y.; Shi, Y. J. Am. Chem. Soc. 1996, 118, 9806. (n) Wang, Z. X.; Tu, Y.; Frohn, M.; Shi, Y. J. Org. Chem. 1997, 62, 2328. (o) Julia, S.; Masana, J.; Vega, J. C. Angew. Chem., Int. Ed. 1980, 92, 968. (p) Porter, M. J.; Skidmore, J. J. Chem. Soc., Chem. Commun. 2000, 1215. (54) Weissermel, K.; Arpe, H.-J. Industrial Organic Chemistry, 4th ed., completely revised; Wiley-VCH: Weinheim, Germany, 2003. (55) (a) Solladié-Cavallo, A.; Bouérat, L.; Roje, M. Tetrahedron Lett. 2000, 41, 7309. (b) Bellenie, B. R.; Goodman, J. M. J. Chem. Soc., Chem. Commun. 2004, 1076. (c) Aggarwal, V. K.; Coogan, M. P.; Stenson, R. A.; Jones, R. V. H.; Fieldhouse, R.; Blacker, J. Eur. J. Org. Chem. 2002, 319. (d) Aggarwal, V. K.; Ford, J. G.; Thompson, A.; Jones, R. V. H.; Standen, M. C. H. J. Am. Chem. Soc. 1996, 118, 7004. (e) Li, A.-H.; Dai, L.-X.; Hou, X.-L.; Huang, Y.-Z.; Li, F.-W. J. Org. Chem. 1996, 61, 489. (f) Zanardi, J.; Leriverend, C.; Aubert, D.; Julienne, K.; Metzner, P. J. Org. Chem. 2001, 66, 5620. (g) Aggarwal, V. K.; Richardson, J. Chem. Commun. 2003, 2644. (h) Aggarwal, V. K.; Winn, C. L. Acc. Chem. Res. 2004, 37, 611. (56) Fuson, R.; Johnson, R. J. Am. Chem. Soc. 1946, 68, 1668. BO


Chemical Reviews

Review

477. (c) Pommier, A.; Pons, J.-M. Synthesis 1995, 729. (d) Rieth, L. R.; Moore, D. R.; Lobkovsky, E. B.; Coates, G. W. J. Am. Chem. Soc. 2002, 124, 15239. (e) Lall, M. S.; Ramtohul, Y. K.; James, M. N. G.; Vederas, J. C. J. Org. Chem. 2002, 67, 1536. (81) (a) Tanahashi, N.; Doi, Y. Macromolecules 1991, 24, 5732. (b) Hori, Y.; Suzuki, M.; Yamaguchi, A.; Nishishita, T. Macromolecules 1993, 26, 5533. (82) (a) Calter, M. A.; Tretyak, O. A.; Flaschenriem, C. Org. Lett. 2005, 7, 1809. (b) Zhu, C.; Shen, X.; Nelson, S. G. J. Am. Chem. Soc. 2004, 126, 5352. (c) Schneider, C. Angew. Chem., Int. Ed. 2002, 41, 744. (83) He, L.; Lv, H.; Zhang, Y.-R.; Ye, S. J. Org. Chem. 2008, 73, 8101. (84) (a) Michael, J. P. Nat. Prod. Rep. 2005, 22, 603. (b) Cheng, Y.; Huang, Z. T.; Wang, M. X. Curr. Org. Chem. 2004, 8, 325. (85) (a) Aurrecoechea, J. M.; Fernández, A.; Gorgojo, J. M.; Saornil, C. Tetrahedron 1999, 55, 7345. (b) Braekman, J. C.; Daloze, D. In Studies in Natural Products Chemistry; Atta-ur-Rahman, Ed.; Elsevier: Amsterdam, 1990; Vol. 6, pp 421−466. (c) O’Hagan, D. Nat. Prod. Rep. 2000, 17, 435. (d) O’Hagan, D. Nat. Prod. Rep. 1997, 14, 637. (e) O’Hagan, D. Nat. Prod. Rep. 2000, 17, 435. (f) Uchide, N.; Kunio, O. J. Antimicrob. Chem. 2003, 52, 8. (86) (a) Bianco, A.; Maggini, M.; Scorrano, G.; Toniolo, C.; Marconi, G.; Villani, C.; Prato, M. J. Am. Chem. Soc. 1996, 118, 4072. (b) Royles, B. J. L. Chem. Rev. 1995, 95, 1981. (87) Domagala, J. M.; Hagen, S. E.; Joannides, T.; Kiely, J. S.; Laborde, E.; Schroeder, M. C.; Sesnie, J. A.; Shapiro, M. A.; Suto, M. J.; Vanderroest, S. J. Med. Chem. 1993, 36, 871. (88) Johnston, G. A. R.; Curtis, D. R.; Davies, J.; McCulloch, R. M. Nature 1974, 248, 804. (89) Hussaini, S. R.; Moloney, M. G. Org. Biomol. Chem. 2003, 1, 1838. (90) Blanco, M. J.; Sardina, F. J. Tetrahedron Lett. 1994, 35, 8493. (91) (a) Seayad, J.; List, B. Org. Biomol. Chem. 2005, 3, 719. (b) Dalko, P. I.; Moisan, L. Angew. Chem., Int. Ed. 2004, 43, 5138. (92) (a) Notz, W.; Tanaka, F.; Barbas, C. F., III Acc. Chem. Res. 2004, 37, 580. (b) Felpin, F. X.; Lebreton, J. Eur. J. Org. Chem. 2003, 3693. (93) (a) Huryn, D. M. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, U.K., 1991; Vol. 1, pp 64−71. (b) Enders, D.; Klatt, M. Synthesis 1996, 1403. (c) Corey, E. J.; Yuen, P. W.; Hannon, F. J.; Wierda, D. A. J. Org. Chem. 1990, 55, 784. (d) Kim, B. H.; Lee, H. B.; Hwang, J. K.; Kim, Y. G. Tetrahedron: Asymmetry 2005, 16, 1215. (e) Fache, F.; Schulz, E.; Tommasino, M. L.; Lemaire, M. Chem. Rev. 2000, 100, 2159. (f) Whitesell, J. K. Chem. Rev. 1989, 89, 1581. (94) (a) Ballini, R.; Bosica, G.; Fiorini, D.; Palmieri, A.; Petrini, M. Chem. Rev. 2005, 105, 933. (b) Galliford, C. V.; Beenen, M. A.; Nguyen, S. T.; Scheidt, K. A. Org. Lett. 2003, 5, 3487. (c) Besev, M.; Engman, L. Org. Lett. 2002, 4, 3023. (95) (a) Butler, M. S. J. Nat. Prod. 2004, 67, 2141. (b) Bellina, F.; Rossi, R. Tetrahedron 2006, 62, 7213. (96) (a) Smith, T. A.; Croker, S. J.; Loeffler, R. S. T. Phytochemistry 1986, 25, 683. (b) Anderson, W. K.; Milowsky, A. S. J. Med. Chem. 1987, 30, 2144. (97) (a) Brown, H. C.; Vara Prasad, J. V. N.; Gupta, A. K. J. Org. Chem. 1986, 51, 4296. (b) Palmer, B. D.; Denny, W. A. Synth. Commun. 1987, 17, 601. (c) Kawaguchi, M.; Hayashi, O.; Kanamoto, M.; Hamada, M.; Yamamoto, Y.; Oda, J. Agric. Biol. Chem. 1987, 51, 435. (98) (a) Batey, R. A.; Simoncic, P. D.; Lin, D.; Smyj, R. P.; Lough, A. J. Chem. Commun. 1999, 651. (b) Ulbrich, H.; Fiebich, B.; Dannhardt, G. Eur. J. Med. Chem. 2002, 37, 953. (99) (a) Rüegg, U. T.; Burgess, G. Trends Pharmacol. Sci. 1989, 10, 218. (b) Castellano, S.; Fiji, H. D. G.; Kinderman, S. S.; Watanabe, M.; de Leon, P.; Tamanoi, F.; Kwon, O. J. Am. Chem. Soc. 2007, 129, 5843. (100) Pedrosa, R.; Andrés, C.; Rosón, C. D.; Vicente, M. J. Org. Chem. 2003, 68, 1852. (101) Andrés, C.; González, I.; Nieto, J.; Rosón, C. D. Tetrahedron 2009, 65, 9728.

(102) Tsuge, O.; Uneo, K.; Kanemasa, S.; Yorozu, K. Bull. Chem. Soc. Jpn. 1986, 59, 1809. (103) Bossio, R.; Marcaccini, S.; Pepino, R. Synthesis 1994, 765. (104) Beck, B.; Picard, A.; Herdtweck, E.; Dömling, A. Org. Lett. 2004, 6, 39. (105) Jones, R. A., Ed. Pyrroles, Part II; Wiley: New York, 1992. (106) Gilchrist, T. L. J. Chem. Soc., Perkin Trans. 1 1999, 2849. (107) (a) Muchowski, J. M. Adv. Med. Chem. 1992, 1, 109. (b) Cozzi, P.; Mongelli, N. Curr. Pharm. Des. 1998, 4, 181. (c) Bleicher, K. H.; Wüthrich, Y.; Adam, G.; Hoffmann, T.; Sleight, A. J. Bioorg. Med. Chem. Lett. 2002, 12, 3073. (d) Haackling, A. E.; Stark, H. ChemBioChem 2002, 3, 946. (e) Yanagimoto, K.; Lee, K.-G.; Ochi, H.; Shibamoto, T. J. Agric. Food Chem. 2002, 50, 5480. (f) Bergauer, M.; Hübner, H.; Gmeiner, P. Bioorg. Med. Chem. Lett. 2002, 12, 1937. (g) Borthwick, A. D.; Crame, A. J.; Ertl, P. F.; Exall, A. M.; Haley, T. M.; Hart, G. J.; Mason, A. M.; Pennell, A. M. K.; Singh, O. M. P.; Weingarten, G. G.; Woolven, J. M. J. Med. Chem. 2002, 45, 1. (h) Andreani, A.; Cavalli, A.; Granaiola, M.; Guardigli, M.; Leoni, A.; Locatelli, A.; Morigi, R.; Rambaldi, M.; Recanatini, M.; Roda, A. J. Med. Chem. 2001, 44, 4011. (i) Fürstner, A.; Grabowski, E. J. ChemBioChem 2001, 2, 706. (j) Seki, M.; Mori, K. Eur. J. Org. Chem. 2001, 503. (k) Hidalgo, F. J.; Alaiz, M.; Zamora, R. Chem. Res. Toxicol. 2001, 14, 582. (108) (a) Higgins, S. A. Chem. Soc. Rev. 1997, 26, 247. (b) Lee, C.-F.; Yang, L.-M.; Hwu, T.-Y.; Feng, A.-S.; Tseng, J.-C.; Luh, T.-Y. J. Am. Chem. Soc. 2000, 122, 4992. (c) Ogawa, K.; Rasmussen, R. C. J. Org. Chem. 2003, 68, 2921. (d) Naji, A.; Cretin, M.; Persin, M.; Sarrazin, J. J. Membr. Sci. 2003, 212, 1. (e) Zotti, G.; Zecchin, S.; Schiavon, G.; Berlin, A. Chem. Mater. 2002, 14, 3607. (f) de Lacy Costello, B. P. J.; Evans, P.; Guernion, N.; Ratcliffe, N. M.; Sivanand, P. S.; Teare, G. C. Synth. Met. 2001, 118, 199. (g) Tietze, L. F.; Kettschau, G.; Heuschert, U.; Nordmann, G. Chem.Eur. J. 2001, 7, 368. (109) (a) Trofimov, B. A.; Sobenina, L. N.; Demenev, A. P.; Mikhaleva, A. I. Chem. Rev. 2004, 104, 2481. (b) Black, D. S. 1HPyrrole. In Science of Synthesis; Thieme: Stuttgart, Germany, 2001; Chapter 13, p 441. (c) Liu, J.-H.; Yang, Q.-C.; Mak, T. C. W.; Wong, H. N. C. J. Org. Chem. 2000, 65, 3587. (d) Boger, D. L.; Boyce, C. W.; Labroli, M. A.; Sehon, C. A.; Jin, Q. J. Am. Chem. Soc. 1999, 121, 54. (e) Gilchrist, T. L. J. Chem. Soc., Perkin Trans. 1 2001, 2491. (f) Azizian, J.; Karimi, A. R.; Arefrad, H.; Mohammadi, A. A.; Mohammadizadeh, M. R. Mol. Diversity 2003, 6, 223. (g) Jafari, A. A.; Mahmoudi, H.; Mirjalili, B. F. J. Iran. Chem. Soc. 2011, 8, 851. (h) Zhang, X.; Sui, Z. Tetrahedron Lett. 2003, 44, 3071. (i) QuicletSire, B.; Quintero, L.; Sanchez-Jimenez, G.; Zard, S. Z. Synlett 2003, 75. (j) Kim, J. T.; Kel’in, A. V.; Gevorgyan, V. Angew. Chem., Int. Ed. 2003, 42, 98. (k) Bullington, J. L.; Wolff, R. R.; Jackson, P. F. J. Org. Chem. 2002, 67, 9439. (l) Attanasi, O. A.; De Crescentini, L.; Favi, G.; Filippone, P.; Mantellini, F.; Santeusanio, S. J. Org. Chem. 2002, 67, 8178. (m) Smith, N. D.; Huang, D.; Cosford, N. D. P. Org. Lett. 2002, 4, 3537. (n) Balme, G. Angew. Chem., Int. Ed. 2004, 43, 6238. (110) Trost, B. M.; Keinan, E. J. Org. Chem. 1980, 45, 2741. (111) Feliciano, A. S.; Caballero, E.; Pereira, J. A. P.; Puebla, P. Tetrahedron 1989, 45, 6553. (112) Caballero, E.; Puebla, P.; Domercq, M.; Medarde, M.; López, J.-L.; Feliciano, A. S. Tetrahedron 1994, 50, 7849. (113) Khalili, B.; Jajarmi, P.; Eftekhari-Sis, B.; Hashemi, M. M. J. Org. Chem. 2008, 73, 2090. (114) Eftekhari-Sis, B.; Vahdati, S. Efficient Synthesis of Pyrroles and Pyridazines in Water Under Ultrasound Irradiation. Presented at the 2nd International Conference of Young Scientists−“Chemistry Today”, Tbilisi, Georgia, April 21−23, 2012. (115) Eftekhari-Sis, B.; Zirak, M.; Akbari, A.; Hashemi, M. M. J. Heterocycl. Chem. 2010, 47, 463. (116) Eftekhari-Sis, B.; Akbari A. Amirabedi, M. Chem. Heterocycl. Compd. 2010, 46, 1330. (117) Yin, G.; Wang, Z.; Chen, A.; Gao, M.; Wu, A.; Pan, Y. J. Org. Chem. 2008, 73, 3377. (118) Anary-Abbasinejad, M.; Charkhati, K.; Anaraki-Ardakani, H. Synlett 2009, 1115. BP


Chemical Reviews

Review

(133) Ahn, J. H.; Kim, H.-M.; Jung, S. H.; Kang, S. K.; Kim, K. R.; Rhee, S. D.; Yang, S.-D.; Cheon, H. G.; Kim, S. S. Bioorg. Med. Chem. Lett. 2004, 14, 4461. (134) Taylor, E. C.; Patel, H. H. Tetrahedron 1992, 48, 8089. (135) Bansal, E.; Srivastava, V. K.; Kumar, A. Eur. J. Med. Chem. 2001, 36, 81. (136) Prasad, Y. R.; Rao, A. L.; Prasoona, L.; Murali, K.; Kumar, P. R. Bioorg. Med. Chem. Lett. 2005, 15, 5030. (137) Elguero, J. Pyrazoles. In Comprehensive Heterocyclic Chemistry II; Katritzky, A. R., Rees, C. W., Scriven, E. F. V., Eds.; Pergamon: Oxford, U.K., 1996; Vol. 3, pp 1−76. (138) (a) Alex, K.; Tillack, A.; Schwarz, N.; Beller, M. Org. Lett. 2008, 10, 2377. (b) Cui, S. L.; Wang, J.; Wang, Y. G. Org. Lett. 2008, 10, 13. (139) (a) Suárez, A.; Downey, C. W.; Fu, G. C. J. Am. Chem. Soc. 2005, 127, 11244. (b) Shapiro, N. D.; Shi, Y.; Toste, F. D. J. Am. Chem. Soc. 2009, 131, 11654. (c) Oishi, T.; Yoshimura, K.; Yamaguchi, K.; Mizuno, N. Chem. Lett. 2010, 39, 1086. (140) (a) Lahm, G. P.; Cordova, D.; Barry, J. D. Bioorg. Med. Chem. 2009, 17, 4127. (b) Fustero, S.; Roman, R.; Sanz-Cervera, J. F.; SimonFuentes, A.; Bueno, J.; Villanova, S. J. Org. Chem. 2008, 73, 8545. (c) Lamberth, C. Heterocycles 2007, 71, 1467. (d) Li, Y.; Zhang, H.-Q.; Liu, J.; Yang, X.-P.; Liu, Z.-J. J. Agric. Food Chem. 2006, 54, 3636. (e) El-Emary, T. I.; Abdel-Mohsen, S. A. Phosphorus, Sulfur Silicon Relat. Elem. 2006, 181, 2459. (f) de Paulis, T.; Hemstapat, K.; Chen, Y.; Zhang, Y.; Saleh, S.; Alagille, D.; Baldwin, R. M.; Tamagnan, G. D.; Conn, P. J. J. Med. Chem. 2006, 49, 3332. (g) Bekhit, A. A.; AbdelAziem, T. Bioorg. Med. Chem. 2004, 12, 1935. (h) Meazza, G.; Zanardi, G.; Piccardi, P. J. Heterocycl. Chem. 1993, 30, 365. (141) (a) Singer, R. A.; Caron, S.; McDermott, R. E.; Arpin, P.; Do, N. M. Synthesis 2003, 1727. (b) Kowalcyk, R.; Skarzewski, J. Tetrahedron 2005, 61, 623. (c) Halcrow, M. A. Dalton Trans. 2009, 2059. (142) (a) Yet, L. In Comprehensive Heterocyclic Chemistry III; Katritzky, A. R., Ramsden, C. A., Scriven, E. F. V., Taylor, R. J. K., Eds.; Elsevier: Oxford, U.K., 2008; Vol. 4. (b) Fustero, S.; SánchezRoselló, M.; Barrio, P.; Simón-Fuentes, A. Chem. Rev. 2011, 111, 6984. (c) Mamaghani, M.; Tabatabaeian, K.; Mirzaeinejad, M.; Nikpassand, M. J. Iran. Chem. Soc. 2006, 3, 89. (143) Del Buttero, P.; Molteni, G.; Pilati, T. Tetrahedron 2005, 61, 2413. (144) Begtrup, M.; Nytoft, H. P. J. Chem. Soc., Perkin Trans. 1 1985, 81. (145) Meanwell, N. A.; Roth, H. R.; Smith, E. C. R.; Wedding, D. L.; Wright, J. J. K. J. Org. Chem. 1991, 56, 6897. (146) Kano, K.; Scarpetti, D.; Warner, J. C.; Anselme, J.-P.; Springer, J. P.; Arison, B. H. Can. J. Chem. 1986, 64, 2211. (147) Kano, K.; Scarpetti, D.; Anselme, J.-P. Tetrahedron Lett. 1985, 26, 6151. (148) (a) du Mont, W.-W.; Mugesh, G.; Wismach, C.; Jones, P. G. Angew. Chem., Int. Ed. 2001, 40, 2486. (b) Avalos, M.; Babiano, R.; Cintas, P.; Jiménez, J. L.; Palacios, J. C.; Silvero, G.; Valencia, C. Tetrahedron 1999, 55, 4377. (149) Watanabe, K.; Morinaka, Y.; Hayashi, Y.; Shinoda, M.; Nishi, H.; Fukushima, N.; Watanabe, T.; Ishibashi, A.; Yuki, S.; Tanaka, M. Bioorg. Med. Chem. Lett. 2008, 18, 1478. (150) Silver, P. J.; Hamel, L. T.; Bentley, R. G.; Dillon, K.; Connell, M. J.; O’Conner, B.; Ferrari, R. A.; Pagani, E. D. Drug Dev. Res. 1990, 21, 93. (151) Tan, S.; Evans, R. R.; Dahmer, M. L.; Singh, B. K.; Shaner, D. L. Pest Manage. Sci. 2005, 61, 246. (152) Kelbaugh, R. R.; Sarges, R. U.S. Patent 4,147,797, 1979; Chem. Abstr. 1979, 91, 20511z. (153) Gupta, R. J.; Gupta, A. S. Indian J. Chem., Sect. B 1979, 16, 71. (154) Rodgers, T. R.; LaMontagne, M. P.; Markovac, A.; Ash, A. B. J. Med. Chem. 1977, 20, 591. (155) Havera, H. J.; Stryeker, W. G. U.S. Patent 3,835,151, 1973; Chem. Abstr. 1974, 81, 152224m. (156) Dziedzic, B.; Szadowska, A.; Kamińska, A. Acta Pol. Pharm. 1978, 35, 423.

(119) (a) Quiroga, J.; Acosta, P. A.; Cruz, S.; Abonía, R.; Insuasty, B.; Nogueras, M.; Cobo, J. Tetrahedron Lett. 2010, 51, 5443. (b) Cruz, S.; Quiroga, J.; de la Torre, J. M.; Cobo, J.; Low, J. N.; Glidewell, C. Acta Crystallogr., Sect. C: Cryst. Struct. Commun. 2006, C62, 554. (120) Nagarajan, K.; Shah, R. K. J. Indian Chem. Soc. 1989, 66, 681. (121) Konakahara, T.; Watanabe, A.; Maehara, K.; Nagata, M.; Hojahmat, M. Heterocycles 1993, 35, 1171. (122) (a) Konakahara, T.; Takagi, Y. Heterocycles 1980, 14, 393. (b) Konakahara, T.; Sato, K. Bull. Chem. Soc. Jpn. 1983, 56, 1241. (c) Konakahara, T.; Kurosaki, Y. J. Chem. Res. (S) 1989, 130. (123) (a) Roeder, E. Pharmazie 2000, 55, 711. (b) Mattocks, A. R. Chemistry and Toxicology of Pyrrolizidine Alkaloids; Academic Press: London, U.K., 1986. (c) Roeder, E.; Wiedenfeld, H. Pharmazie 2009, 64, 699. (d) Bull, L. B.; Culvenor, C. C. J.; Dick, A. J. The Pyrrolizidine Alkaloids: Their Chemistry, Pathogenicity and Other Biological Properties; North-Holland Publishing: Amsterdam, 1968. (e) Smith, L. W.; Culvenor, C. C. J. J. Nat. Prod. 1981, 44, 129. (124) (a) Robins, D. J. Nat. Prod. Rep. 1994, 11, 613 and references therein. (b) Michael, J. P. Nat. Prod. Rep. 2007, 24, 191. (c) Daly, J. W.; Spande, T. F.; Garraffo, H. M. J. Nat. Prod. 2005, 68, 1556. (d) Daly, J. W. J. Med. Chem. 2003, 46, 445. (e) Swinbourne, F. J.; Hunt, J. H.; Klinkert, G. Adv. Heterocycl. Chem. 1987, 23, 103. (f) Rajaraman, S.; Jimenez, L. S. Tetrahedron 2002, 58, 10407. (g) Portevin, B.; Tordjman, C.; Pastoureau, P.; Bonnet, J.; De Nanteuil, G. J. Med. Chem. 2000, 43, 4582. (125) (a) Yoda, H.; Asai, F.; Takabe, K. Synlett 2000, 1001. (b) Calveras, J.; Casas, J.; Parella, T.; Joglar, J.; Clapés, P. Adv. Synth. Catal. 2007, 349, 1661. (c) Affolter, O.; Baro, A.; Frey, W.; Laschat, S. Tetrahedron 2009, 65, 6626. (d) Romero, A.; Wong, C.-H. J. Org. Chem. 2000, 65, 8264. (e) Pearson, W. H.; Hines, J. V. J. Org. Chem. 2000, 65, 5785. (f) Denmark, S. E.; Martinborough, E. A. J. Am. Chem. Soc. 1999, 121, 3046. (g) Denmark, S. E.; Herbert, B. J. Am. Chem. Soc. 1998, 120, 7357. (h) Denmark, S. E.; Herbert, B. J. Org. Chem. 2000, 65, 2887. (i) Denmark, S. E.; Cottell, J. J. J. Org. Chem. 2001, 66, 4276. (j) Ikota, N. Tetrahedron Lett. 1992, 33, 2553. (k) Tang, M.; Pyne, S. G. J. Org. Chem. 2003, 68, 7818. (l) Denmark, S. E.; Hurd, A. R. J. Org. Chem. 2000, 65, 2875. (m) Denmark, S. E.; Hurd, A. R. Org. Lett. 1999, 1, 1311. (126) (a) Barluenga, J.; Tomás, M.; Kouznetsov, V.; Suárez-Sorbino, A.; Rubio, E. J. Org. Chem. 1996, 61, 2185. (b) Katritzky, A. R.; Fali, C. N.; Li, J. J. Org. Chem. 1997, 62, 4148. (c) Atwell, G. J.; Fan, J.-Y.; Tan, K.; Denny, W. A. J. Med. Chem. 1998, 41, 4744. (127) (a) Varga, T. R.; Nemes, P.; Mucsi, Z.; Scheiber, P. Tetrahedron Lett. 2007, 48, 1159. (b) Yuguchi, M.; Tokuda, M.; Orito, K. Bull. Chem. Soc. Jpn. 2004, 77, 1031. (c) Jung, M. E.; Choi, Y. M. J. Org. Chem. 1991, 56, 6729. (d) Smith, A. B., III; Kim, D.-S. J. Org. Chem. 2006, 71, 2547. (e) Kim, G.; Jung, S.; Lee, E.; Kim, N. J. Org. Chem. 2003, 68, 5395. (f) Riesinger, S. W.; Lofstedt, J.; PettessonFasth, H.; Backvall, J. E. Eur. J. Org. Chem. 1999, 64, 3277. (g) Berry, M. B.; Rowlands, G. J.; Craig, D.; Jones, P. S. Chem. Commun. 1997, 2141. (128) Felluga, F.; Forzato, C.; Nitti, P.; Pitacco, G.; Valentin, E.; Zangrando, E. J. Heterocycl. Chem. 2010, 47, 664. (129) Pilipecz, M. V.; Mucsi, Z.; Nemes, P.; Scheiber, P. Heterocycles 2007, 71, 1919. (130) Grigg, R.; Rankovic, Z.; Thornton-Pett, M.; Somasunderam, A. Tetrahedron 1993, 49, 8679. (131) (a) Hayat, F.; Salahuddin, A.; Umar, S.; Azam, A. Eur. J. Med. Chem. 2010, 45, 4669. (b) Abid, M.; Azam, A. Bioorg. Med. Chem. Lett. 2006, 16, 2812. (c) Banday, A. H.; Mir, B. P.; Lone, I. H.; Suri, K. A.; Kumar, H. M. S. Steroids 2010, 75, 805. (d) Joshi, R. S.; Mandhane, P. G.; Diwakar, S. D.; Dabhade, S. K.; Gill, C. H. Bioorg. Med. Chem. Lett. 2010, 20, 3721. (e) Prasad, Y. R.; Rao, A. L.; Prasoona, L.; Murali, K.; Kumar, P. R. Bioorg. Med. Chem. Lett. 2005, 15, 5030. (132) (a) Havaldar, F. H.; Fernandes, P. S. J. Indian Chem. Soc. 1988, 65, 691. (b) Satti, N. K.; Suri, K. A.; Suri, O. P. Indian Drugs 1987, 24, 492. BQ


Chemical Reviews

Review

Chen, J.; Zhao, J.; Zhao, Y.; Li, L.; Zhang, H. Synthesis 2003, 2661. (d) Balalaie, S.; Hashemi, M. M.; Akhbari, M. Tetrahedron Lett. 2003, 44, 1709. (e) Balalaie, S.; Arabanian, A. Green Chem. 2000, 2, 274. (f) D’Souza, D. M.; Müller, T. J. J. Chem. Soc. Rev. 2007, 36, 1095. (g) Zaman, S.; Mitsuru, K.; Abell, A. D. Org. Lett. 2005, 7, 609. (h) Sparks, R. B.; Combs, A. P. Org. Lett. 2004, 6, 2473. (183) Zhang, C.; Moran, E, J,; Woiwode, T. F.; Short, K. M.; Mjalli, A. M. M. Tetrahedron Lett. 1996, 37, 751. (184) Sung, K.; Wu, S.-H.; Chen, P.-I. Tetrahedron 2002, 58, 5599. (185) Khalili, B.; Tondro, T.; Hashemi, M. M. Tetrahedron 2009, 65, 6882. (186) Mahboobi, S.; Sellmer, A.; Burgemeister, T.; Lyssenko, A.; Schollmeyer, D. Monatsh. Chem. 2004, 135, 333. (187) Kong, Y. C.; Kim, K. J. Heterocycl. Chem. 1999, 36, 911. (188) Batanero, B.; Escudero, J.; Barba, F. Org. Lett. 1999, 1, 1521. (189) Boyer, J. H.; Straw, D. J. Am. Chem. Soc. 1952, 74, 4506. (190) Bratulescu, G. Synthesis 2009, 2319. (191) Zuliani, V.; Cocconcelli, G.; Fantini, M.; Ghiron, C.; Rivara, M. J. Org. Chem. 2007, 72, 4551. (192) Fantini, M.; Rivara, M.; Zuliani, V.; Kalmar, C. L.; Vacondio, F.; Silva, C.; Baheti, A. R.; Singh, N.; Merrick, E. C.; Katari, R. S.; Cocconcelli, G.; Ghiron, C.; Patel, M. K. Bioorg. Med. Chem. 2009, 17, 3642. (193) Rivara, M.; Baheti, A. R.; Fantini, M.; Cocconcelli, G.; Ghiron, C.; Kalmar, C. L.; Singh, N.; Merrick, E. C.; Patel, M. K.; Zuliani, V. Bioorg. Med. Chem. Lett. 2008, 18, 5460. (194) (a) Husain, A.; Drabu, S.; Kumar, N. Acta Pol. Pharm., Drug Res. 2009, 66, 243. (b) Drabu, S.; Husain, A.; Kumar, N. Pharm. Res. 2009, 1, 133. (195) Song, Z.; DeMarco, A.; Zhao, M.; Corley, E. G.; Thompson, A. S.; McNamara, J.; Li, Y.; Rieger, D.; Sohar, P.; Mathre, D. J.; Tschaen, D. M.; Reamer, R. A.; Huntington, M. F.; Ho, G.-J.; Tsay, F.-R.; Emerson, K.; Shuman, R.; Grabowski, E. J. J.; Reider, P. J. J. Org. Chem. 1999, 64, 1859. (196) Amitina, S. A.; Tikhonov, A. Y.; Grigor’ev, I. A.; Gatilov, Y. V.; Selivanov, B. A. Chem. Heterocycl. Compd. 2009, 45, 691. ́ (197) Amitina, S. A.; Eltsov, I. V.; Rybalova, T. V.; Gatilov, Y. V.; Grigoŕev, I. A. Russ. Chem. Bull. 2004, 53, 1700. (198) Hortmann, A. G.; Koo, J.-Y.; Yu, C.-C. J. Org. Chem. 1978, 43, 2289. (199) (a) Murai, K.; Morishita, M.; Nakatani, R.; Kubo, O.; Fujioka, H.; Kita, Y. J. Org. Chem. 2007, 72, 8947. (b) Guinchard, X.; Vallée, Y.; Denis, J.-N. J. Org. Chem. 2007, 72, 3972. (200) (a) Fused Five-and Six-Membered Rings with Ring Junction Heteroatom; Jones, G., Ed.; Comprehensive Heterocyclic Chemistry II, Vol. 8; Pergamon: Oxford, U.K., 1996. (b) Fused Five-and SixMembered Rings without Ring Junction Heteroatom; Ramsden, C. A., Ed.; Comprehensive Heterocyclic Chemistry II, Vol. 7; Pergamon: Oxford, U.K., 1996. (201) (a) Ohmiya, Y.; Hirano, T. Chem. Biol. 1996, 3, 337. (b) Head, J. F.; Inouye, S.; Teranishi, K.; Shimomura, O. Nature 2000, 405, 372. (c) Nakamura, H.; Wu, C.; Inouye, S.; Murai, A. J. Am. Chem. Soc. 2001, 123, 1523. (202) Nakai, S.; Yasui, M.; Nakazato, M.; Iwasaki, F.; Maki, S.; Niwa, H.; Ohashi, M.; Hirano, T. Bull. Chem. Soc. Jpn. 2003, 76, 2361. (203) (a) Goto, T. Pure Appl. Chem. 1968, 17, 421. (b) Hirano, T.; Negishi, R.; Yamaguchi, M.; Chen, F. Q.; Ohmiya, Y.; Tsuji, F. I.; Ohashi, M. Tetrahedron 1997, 53, 12903. (204) Sulojeva, E.; Yure, M.; Gudriniece, E. Chem. Heterocycl. Compd. 2000, 36, 885. (205) (a) Deady, L. W.; Stanborough, M. S. Aust. J. Chem. 1981, 34, 1295. (b) Takahashi, T.; Satake, K. J. Pharm. Soc. Jpn. 1955, 75, 20. (c) Knott, E. B. J. Chem. Soc. 1951, 3033. (206) Nakayama, Y.; Hayashi, K.; Irie, M. Bull. Chem. Soc. Jpn. 1991, 64, 202. (207) Scholl, H. J.; Klauke, E. DE Patent 2062347, 1973; Chem. Abstr. 1973, 77, 152194. (208) Kuhla, D. E. U.S. Patent 4044015, 1977; Chem. Abstr. 1977, 88, 50828.

(157) (a) Menezes, E. H. C.; Góes, A. J. S.; Diu, M. B. S.; Galdino, S. L.; Pitta, I. R.; Luu-Duc, C. Pharmazie 1992, 46, 457. (b) Schulte, K. E.; Von, W. V. Eur. J. Med. Chem.−Chim. Ther. 1978, 13, 25. (158) (a) Claussuer, A.; Goubet, F.; Teutsch, J.-J. PCT Int. Appl. WO 9719064, 1997; Chem. Abstr. 1997, 127, 50640v. (b) Payen, O.; Top, S.; Vessières, A.; Brulé, E.; Plamont, M.-A.; McGlinchey, M. J.; Müller-Bunz, H.; Jaouen, G. J. Med. Chem. 2008, 51, 1791. (159) (a) Lee, J. T.; Mah, H.; Nam, K. D.; Shin, D.; Ha, D.-C.; Hahn, H.-G. J. Comb. Chem. 2008, 10, 803. (b) Handke, I.; Schaumann, E.; Ketcham, R. J. Org. Chem. 1988, 53, 5298. (160) (a) Lampson, G. P.; Singher, H. O. J. Org. Chem. 1956, 21, 684. (b) Attanasi, O. A.; De Crescentini, L.; Favi, G.; Nicolini, S.; Perrulli, F. R.; Santeusanio, S. Org. Lett. 2011, 13, 353. (c) Olimpieri, F.; Volonterio, A.; Zanda, M. Synlett 2008, 3016. (d) Zhang, D.; Xing, X.; Cuny, G. D. J. Org. Chem. 2006, 71, 1750. (e) Zhao, B.; Du, H.; Shi, Y. J. Am. Chem. Soc. 2008, 130, 7220. (f) Attanasi, O. A.; De Crescentini, L.; Favi, G.; Nicolini, S.; Perrulli, F. R.; Santeusanio, S. Org. Lett. 2011, 13, 353. (161) Paul, S.; Gupta, M.; Gupta, R.; Loupy, A. Synthesis 2002, 75. (162) Patel, V. M.; Desai, K. R. Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem. 2005, 44, 1084. (163) Joshi, K. C.; Pathak, V. N.; Goyal, M. K. J. Heterocycl. Chem. 1981, 18, 1651. (164) (a) Muccioli, G. G.; Wouters, J.; Charlier, C.; Scriba, G. K. E.; Pizza, T.; Di Pace, P.; De Martino, P.; Poppitz, W.; Poupaert, J. H.; Lambert, D. M. J. Med. Chem. 2006, 49, 872. (b) Muccioli, G. G.; Fazio, N.; Scriba, G. K. E.; Poppitz, W.; Cannata, F.; Poupaert, J. H.; Wouters, J.; Lambert, D. M. J. Med. Chem. 2006, 49, 417. (165) (a) Fisher, H. J.; Ekeley, J. B.; Ronzio, A. R. J. Am. Chem. Soc. 1942, 64, 1434. (b) Kjær, A. Acta Chim. Scand. 1950, 4, 892. (166) Hough, T. L.; Hough, I. R.; Pannell, R. W. J. Heterocycl. Chem. 1986, 23, 1125. (167) Shtamburg, V. G.; Anishchenko, A. A.; Shtamburg, V. V.; Shishkin, O. V.; Zubatyuk, R. I.; Mazepa, A. V.; Rakipov, I. M.; Kostyanovsky, R. G. Mendeleev Commun. 2008, 18, 102. (168) Kostyanovsky, R. G.; Shtamburg, V. G.; Shishkin, O. V.; Zubatyuk, R. I.; Shtamburg, V. V.; Anishchenko, A. A.; Mazepa, A. V. Mendeleev Commun. 2010, 20, 167. (169) Gao, M.; Yang, Y.; Wu, Y.-D.; Deng, C.; Shu, W.-M.; Zhang, D.-X.; Cao, L.-P.; She, N.-F.; Wu, A.-X. Org. Lett. 2010, 12, 4026. (170) Kolos, N. N.; Gozalishvili, L. L.; Sivokoń, E. N.; Knyazeva., I. V. Russ. J. Org. Chem. 2009, 45, 119. (171) Gozalishvili, L. L.; Beryozkina, T. V.; Omelchenko, I. V.; Zubatyuk, R. I.; Shishkin, O. V.; Kolos, N. N. Tetrahedron 2008, 64, 8759. (172) Balalaie, S.; Soleiman-Beigi, M.; Rominger, F. J. Iran. Chem. Soc. 2005, 2, 319. (173) Waugh, R. C.; Ekeley, J. B.; Ronzio, A. R. J. Am. Chem. Soc. 1942, 64, 2028. (174) Cole, J. O.; Ronzio, A. R. J. Am. Chem. Soc. 1944, 66, 1584. (175) Atwood, J. L.; Barbour, L. J.; Heaven, M. W.; Raston, C. L. J. Chem. Crystallogr. 2003, 33, 175. (176) (a) Faulkner, D. J. Nat. Prod. Rep. 2000, 17, 7. (b) Ho, J. Z.; Hohareb, R. M.; Ahn, J. H.; Sim, T. B.; Rapoport, H. J. Org. Chem. 2003, 68, 109. (177) Grimmett, M. R. In Comprehensive Heterocyclic Chemistry II; Katritsky, A. R., Scriven, E. F. V., Eds.; Pergamon: Oxford, U.K., 1996; Vol. 3, pp 77−220. (178) Lombardino, J. G.; Wiseman, E. H. J. Med. Chem. 1974, 17, 1182. (179) Maier, T.; Schmierer, R.; Bauer, K.; Bieringer, H.; Buerstell, H.; Sachser, B. German Patent 317094, 1983. (180) Schmierer, R.; Mildenberger, H.; Buerstell, H. German Patent 3614364, 1987; Chem. Abstr. 1988, 108, 37838. (181) Lo, Y. S.; Nolan, J. C.; Maren, T. H.; Welstead, W. J., Jr.; Gripshover, D. F.; Shamblee, D. A. J. Med. Chem. 1992, 35, 4790. (182) (a) Lantos, I.; Zhang, W. Y.; Shui, X.; Eggleston, D. S. J. Org. Chem. 1993, 58, 7092. (b) Bleicher, K. H.; Gerber, F.; Wüthrich, Y.; Alanine, A.; Capretta, A. Tetrahedron Lett. 2002, 43, 7687. (c) Liu, J.; BR


Chemical Reviews

Review

(230) Moderhack, D. J. Prakt. Chem. 1998, 340, 687. (231) Ostrovskii, V. A.; Pevzner, M. S.; Kofman, T. P.; Shcherbinin, M. B.; Tselinskii, I. V. Targets Heterocycl. Syst. 1999, 3, 467. (232) (a) Sisido, K.; Nabika, K.; Isida, T.; Kozima, S. J. Organomet. Chem. 1971, 33, 337. (b) Bethel, P. A.; Hill, M. S.; Mahon, M. F.; Molloy, K. C. J. Chem. Soc., Perkin Trans. 1 1999, 3507. (c) Demko, Z. P.; Sharpless, K. B. J. Org. Chem. 2001, 66, 7945. (233) Tang, W.-J.; Hu, Y.-Z. Synth. Commun. 2006, 36, 2461. (234) Yates, P.; Mayfield, R. J. Can. J. Chem. 1977, 55, 145. (235) (a) Garson, M. J. Chem. Rev. 1993, 93, 1699. (b) Yasumoto, T.; Murata, M. Chem. Rev. 1993, 93, 1897. (c) Alali, F. Q.; Liu, X.; McLaughlin, J. L. J. Nat. Prod. 1999, 62, 504. (d) Collum, D. B.; McDonald, J. H., III; Still, W. C. J. Am. Chem. Soc. 1980, 102, 2117, 2118, 2120. (e) Marshall, J. A.; Yu, B. J. Org. Chem. 1994, 59, 324. (f) Yamada, O.; Ogasawara, K. Synlett 1995, 427. (g) Paolucci, C.; Musiani, L.; Venturelli, F.; Fava, A. Synthesis 1997, 1415. (h) Doyle, M. P.; Forbes, D. C.; Protopopova, M. N.; Stanley, S. A.; Vasbinder, M. M.; Xavier, K. R. J. Org. Chem. 1997, 62, 7210. (i) Bauer, T. Tetrahedron 1997, 53, 4763. (236) (a) Bartlett, P. A. Tetrahedron 1980, 36, 2. (b) Ireland, R. E.; Anderson, R. C.; Badoud, R.; Fitzsimmons, B. J.; McGarvey, G. J.; Thaisrivongs, S.; Wilcox, C. S. J. Am. Chem. Soc. 1983, 105, 1988. (c) Lord, M. D.; Negri, J. T.; Paquette, L. A. J. Org. Chem. 1995, 60, 191. (d) Schmitz, F. J.; McDonald, F. J.; Vanderah, D. J. J. Org. Chem. 1978, 43, 4220. (e) Maurer, B.; Hauser, A.; Ohloff, G. Helv. Chim. Acta 1980, 63, 2503. (f) Ottinger, H.; Soldo, T.; Hofmann, T. J. Agric. Food Chem. 2001, 49, 5383. (g) Shin, S. S.; Byun, Y.; Lim, K. M.; Choi, J. K.; Lee, K.-W.; Moh, J. H.; Kim, J. K.; Jeong, Y. S.; Kim, J. Y.; Choi, Y. H.; Koh, H.-J.; Park, Y.-H.; Oh, Y. I.; Noh, M.-S.; Chung, S. J. Med. Chem. 2004, 47, 792. (237) (a) Kupchan, S. M.; Davies, V. H.; Fujita, T.; Cox, M. R.; Restivo, R. J.; Bryan, R. F. J. Org. Chem. 1973, 38, 1853. (b) Semple, J. E.; Wang, P. C.; Lysenko, Z.; Joullie, M. M. J. Am. Chem. Soc. 1980, 102, 7505. (c) Fraga, B. M. Nat. Prod. Rep. 1992, 9, 217. (d) Benassi, R. In Comprehensive Heterocyclic Chemistry II; Katritzky, A. R., Rees, C. W., Scrivan, E. F. V., Bird, C. W., Eds.; Elsevier: Oxford, U.K., 1996; Vol. 2, p 259. (e) Ward, R. S. Nat. Prod. Rep. 1999, 16, 75. (f) Koert, U. Synthesis 1995, 115. (238) (a) Alvarez, E.; Candenas, M.-L.; Perez, R.; Ravelo, J. L.; Martin, J. D. Chem. Rev. 1995, 95, 1953. (b) Ajamian, A.; Gleason, J. L. Org. Lett. 2001, 3, 4161. (c) Sekido, M.; Aoyagi, K.; Nakamura, H.; Kabuto, C.; Yamamoto, Y. J. Org. Chem. 2001, 66, 7142. (d) Keinan, E.; Sinha, A.; Yazbak, A.; Sinha, S. C.; Sinha, S. C. Pure Appl. Chem. 1997, 69, 423. (e) Sinha, S. C.; Sinha, A.; Sinha, S. C.; Keinan, E. J. Am. Chem. Soc. 1997, 119, 12014. (f) Sinha, S. C.; Keinan, E.; Sinha, S. C. J. Am. Chem. Soc. 1998, 120, 9076. (g) Liu, G.; Lu, X. Tetrahedron Lett. 2003, 44, 467. (h) Lipshutz, B. H.; Barton, J. C. J. Am. Chem. Soc. 1992, 114, 1084. (i) Mihelich, E. D.; Hite, G. A. J. Am. Chem. Soc. 1992, 114, 7318. (j) Yamazaki, S. Chem.Eur. J. 2008, 14, 6026. (239) (a) Darcel, C.; Bruneau, C.; Albert, M.; Dixneuf, P. H. Chem. Commun. 1996, 919. (b) Chen, J.; Song, Q.; Li, P.; Guan, H.; Jin, X.; Xi, Z. Org. Lett. 2002, 4, 2269. (c) Shieh, S.-J.; Tang, T.-C.; Lee, J.-S.; Lee, G.-H.; Peng, S.-M.; Liu, R.-S. J. Org. Chem. 1996, 61, 3245. (d) Nikam, S. S.; Chu, K. H.; Wang, K. K. J. Org. Chem. 1986, 51, 745. (e) Kang, S.-K.; Baik, T.-G.; Kulak, A. N. Synlett 1999, 324. (f) Walkup, R. D.; Guan, L.; Mosher, M. D.; Kim, S. W.; Kim, Y. S. Synlett 1993, 88. (g) Yoneda, E.; Kaneko, T.; Zhang, S.-W.; Onitsuka, K.; Takahashi, S. Org. Lett. 2000, 2, 441. (h) Eom, D.; Kang, D.; Lee, P. H. J. Org. Chem. 2010, 75, 7447. (i) Ichikawa, J.; Fujiwara, M.; Wada, Y.; Okauchi, T.; Minami, T. Chem. Commun. 2000, 1887. (j) Feldman, K. S.; Wrobleski, M. L. J. Org. Chem. 2000, 65, 8659. (k) Kilroy, T. G.; O’Sullivan, T. P.; Guiry, P. J. Eur. J. Org. Chem. 2005, 4929. (l) Buzas, A.; Istrate, F.; Gagosz, F. Org. Lett. 2006, 8, 1957. (m) Deng, Y.; Shi, Y.; Ma, S. Org. Lett. 2009, 11, 1205. (n) Nishino, H.; Hguyen, V.; Yoshinaga, S.; Kurosawa, K. J. Org. Chem. 1996, 61, 8264. (o) Zhu, S.; Chen, L.; Wang, C.; Liang, R.; Wang, X.; Ren, Y.; Jiang, H. Tetrahedron 2011, 67, 5507. (240) Fuchibe, K.; Aoki, Y.; Akiyama, T. Chem. Lett. 2005, 34, 538.

(209) Houlihan, W. J.; Munder, P. G.; Handley, D. A.; Cheon, S. H.; Parrino, V. A. J. Med. Chem. 1995, 38, 234. (210) (a) Kubo, K.; Ito, N.; Isomura, Y.; Sozu, I.; Homma, H.; Murakami, M. Yakugaku Zasshi 1979, 99, 880. (b) Kubo, K.; Ito, N.; Isomura, Y.; Sozu, I.; Homma, H.; Murakami, M. Chem. Pharm. Bull. 1979, 27, 1207. (211) (a) Suloeva, E.; Yure, M.; Gudriniece, E. Chem. Heterocycl. Compd. 1999, 35, 1121. (b) Bluhm, M. E.; Ciesielski, M.; Görls, H.; Döring, M. Angew. Chem., Int. Ed. 2002, 41, 2962. (c) Langry, K. C. J. Org. Chem. 1991, 56, 2400. (d) Shibahara, F.; Sugiura, R.; Yamaguchi, E.; Kitagawa, A.; Murai, T. J. Org. Chem. 2009, 74, 3566. (e) DiMauro, E. F.; Kennedy, J. M. J. Org. Chem. 2007, 72, 1013. (f) Chernyak, N.; Gevorgyan, V. Angew. Chem., Int. Ed. 2010, 49, 2743. (g) Sharma, S.; Kundu, B. J. Comb. Chem. 2009, 11, 720. (h) Teranishi, K.; Goto, T. Bull. Chem. Soc. Jpn. 1990, 63, 3132. (212) Alcaide, B.; Plumet, J.; Sierra, M. A.; Vicent, C. J. Org. Chem. 1989, 54, 5763. (213) (a) Alcaide, B.; Pérez-Ossorio, R.; Plumet, J.; Sierra, M. A. Tetrahedron Lett. 1986, 27, 1627. (b) Sugiura, S.; Kakoi, H.; Inoue, S.; Goto, T. Yakugaku Zasshi 1970, 90, 441. (c) Doise, M.; Blondeau, D.; Sliwa, H. Heterocycles 1992, 34, 2079. (214) Devillers, I.; Dive, G.; De Tollenaere, C.; Falmagne, B.; de Wergifosse, B.; Rees, J,-F.; Marchand-Brynaert, J. Bioorg. Med. Chem. Lett. 2001, 11, 2305. (215) Devillers, I.; de Wergifosse, B.; Bruneau, M.-P.; Tinant, B.; Declercq, J.-P.; Touillaux, R.; Rees, J.-F.; Marchand-Brynaert, J. J. Chem. Soc., Perkin Trans. 2 1999, 1481. (216) Fujio, S.; Hashizume, D.; Takamuki, Y.; Yasui, M.; Iwasaki, F.; Maki, S.; Niwa, H.; Ikeda, H.; Hirano, T. Tetrahedron Lett. 2004, 45, 8531. (217) Barlin, G. B.; Brown, D. J.; Kadunc, Z.; Petrič, A.; Stanovnik, B.; Tišler, M. Aust. J. Chem. 1983, 36, 1215. (218) Drach, B. S.; Dolgushina, I. Yu.; Sinitsa, A. D. Chem. Heterocycl. Compd. 1974, 10, 810. (219) Mukaiyama, T.; Sakito, Y.; Asami, M. Chem. Lett. 1978, 7, 1253. (220) O’Brien, P.; Warren, S. Tetrahedron Lett. 1995, 36, 2681. (221) (a) Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem., Int. Ed. 2001, 40, 2004. (b) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B. Angew. Chem., Int. Ed. 2002, 41, 2596. (c) Wu, P.; Fokin, V. V. Aldrichimica Acta 2007, 40, 7. (222) Fan, W.-Q.; Katritzky, A. R. In Comprehensive Heterocyclic Chemistry II; Katritzky, A. R., Rees, C. W., Scriven, E. F. V., Eds.; Pergamon Press: Oxford, U.K., 1996; Vol. 4, pp 1−126. (223) (a) Sivakumar, K.; Xie, F.; Cash, B. M.; Long, S.; Barnhill, H. N.; Wang, Q. Org. Lett. 2004, 6, 4603. (b) Costa, M. S.; Boechat, N.; Rangel, É. A.; da Silva, F. de C.; de Souza, A. M. T.; Rodrigues, C. R.; Castro, H. C.; Junior, I. N.; Lourenço, M. C. S.; Wardell, S. M. S. V.; Ferreira, V. F. Bioorg. Med. Chem. 2006, 14, 8644. (224) (a) Ye, C. F.; Gard, G. L.; Winter, R. W.; Syvret, R. G.; Twamley, B.; Shreeve, J. M. Org. Lett. 2007, 9, 3841. (b) Nandivada, H.; Jiang, X.; Lahann, J. Adv. Mater. 2007, 19, 2197. (225) (a) Moorhouse, A. D.; Moses, J. E. ChemMedChem 2008, 3, 715. (b) Whiting, M.; Muldoon, J.; Lin, Y.-C.; Silverman, S. M.; Lindstrom, W.; Olson, A. J.; Kolb, H. C.; Finn, M. G.; Sharpless, K. B.; Elder, J. H.; Fokin, V. V. Angew. Chem., Int. Ed. 2006, 45, 1435. (226) (a) L’abbe, G. Chem. Rev. 1969, 69, 345. (b) Huisgen, R. In 1,3-Dipolar Cycloaddition Chemistry; Padwa, A., Ed.; Wiley: New York, 1984. (c) Tornøe, C. W.; Christensen, C.; Meldal, M. J. Org. Chem. 2002, 67, 3057. (d) Himo, F.; Lovell, T.; Hilgraf, R.; Rostovtsev, V. V.; Noodleman, L.; Sharpless, K. B.; Fokin, V. V. J. Am. Chem. Soc. 2005, 127, 210. (227) Butler, R. N. In Comprehensive Heterocyclic Chemistry; Katritzky, A. R., Ress, C. W., Scriven, E. F. V., Eds.; Pergamon: Oxford, U.K., 1996; Vol. 4, p 621. (228) Herr, R. J. Bioorg. Med. Chem. 2002, 10, 3379. (229) (a) Zabrocki, J.; Smith, G. D.; Dunbar, J. B.; Iijima, H.; Marshall, G. R. J. Am. Chem. Soc. 1988, 110, 5875. (b) Zabrocki, J.; Marshall, G. R. Methods Mol. Med. 1999, 23, 417. BS


Chemical Reviews

Review

(241) Beck, B.; Magnin-Lachaux, M.; Herdtweck, E.; Dömling, A. Org. Lett. 2001, 3, 2875. (242) Bossio, R.; Marcaccini, S.; Pepino, R.; Torroba, T. Synthesis 1993, 783. (243) Anary-Abbasinejad, M.; Shams, N.; Hassanabadi, A. Phosphorus, Sulfur Silicon Relat. Elem. 2010, 185, 1823. (244) Peter, M.; Gleiter, R.; Rominger, F.; Oeser, T. Eur. J. Org. Chem. 2004, 3212. (245) Ritchie, E.; Taylor, W. C. Aust. J. Chem. 1971, 24, 2137. (246) Bardasov, I. N.; Kayukova, O. V.; Kayukov, Y. S.; Ershov, O. V.; Nasakin, O. E.; Tafeenko, V. A. Russ. J. Org. Chem. 2009, 45, 1325. (247) (a) Bosshard, P.; Eugster, C. H. The development of the chemistry of furans, 1952−1963. In Advances in Heterocyclic Chemistry; Katritzky, A. R., Boulton, A. J., Ed.; Academic: New York, 1966; Vol. 7, pp 377−488. (b) Dean, F. M. Recent advances in furan chemistry. Part I. In Advances in Heterocyclic Chemistry; Katritzky, A. R., Ed.; Academic Press: New York, 1982; Vol. 30, pp 167−238. (248) Look, S. A.; Burch, M. T.; Fenical, W.; Qitai, Z.; Clardy, J. J. Org. Chem. 1985, 50, 5741. (249) Fenical, W.; Okuda, R. K.; Bandurraga, M. M.; Culver, P.; Jacobs, R. S. Science 1981, 212, 1512. (250) (a) Glass, R. L.; Krick, T. P.; Sand, D. M.; Rahn, C. H.; Schlenk, H. Lipids 1975, 10, 695. (b) Batna, A.; Spiteller, G. Lipids 1994, 29, 397. (251) Williams, D.; Andersen, R. J.; Van Duyne, G. D.; Clardy, J. J. Org. Chem. 1987, 52, 332. (252) Rodríguez, A. D.; Shi, J.-G.; Huang, S. D. J. Org. Chem. 1998, 63, 4425. (253) Bandurraga, M. M.; Fenical, W.; Donovan, S. F.; Clardy, J. J. Am. Chem. Soc. 1982, 104, 6463. (254) (a) Büchi, G.; sz. Kovats, E.; Enggist, P.; Uhde, G. J. Org. Chem. 1968, 33, 1227. (b) Bach, T.; Krüger, L. Eur. J. Org. Chem. 1999, 2045. (255) Hochlowski, J. E.; Walker, R. P.; Ireland, C.; Faulkner, D. J. J. Org. Chem. 1982, 47, 88. (256) Rao, G. S. R. S.; Ravindranath, B.; Kumar, V. P. S. Phytochemistry 1984, 23, 339. (257) (a) Lipshutz, B. H. Chem. Rev. 1986, 86, 795. (b) Griffith, G. A.; Hillier, I. H.; Moralee, A. C.; Percy, J. M.; Roig, R.; Vincent, M. A. J. Am. Chem. Soc. 2006, 128, 13130. (258) (a) Marshall, J. A.; Wang, X.-J. J. Org. Chem. 1992, 57, 3387. (b) Marshall, J. A.; Bartley, G. S. J. Org. Chem. 1994, 59, 7169. (c) Marshall, J. A.; Sehon, C. A. J. Org. Chem. 1995, 60, 5966. (d) Hashmi, A. S. K.; Ruppert, T. L.; Knöfel, T.; Bats, J. W. J. Org. Chem. 1997, 62, 7295. (e) Sperry, J. B.; Whitehead, C. R.; Ghiviriga, I.; Walczak, R. M.; Wright, D. L. J. Org. Chem. 2004, 69, 3726. (259) (a) Gilchrist, T. L. J. Chem. Soc., Perkin Trans. 1 1999, 2849. (b) Hou, X. L.; Cheung, H. Y.; Hon, T. U.; Kwan, P. L.; Lo, T. H.; Tong, S. Y.; Wong, H. N. C. Tetrahedron 1998, 54, 1955. (c) Dean, F. M. Adv. Heterocycl. Chem. 1982, 30, 237. (260) Onitsuka, S.; Nishino, H. Tetrahedron 2003, 59, 755. (261) Onitsuka, S.; Nishino, H.; Kurosawa, K. Tetrahedron Lett. 2000, 41, 3149. (262) Yin, G.; Wang, Z.; Chen, A.; Gao, M.; Wu, A.; Pan, Y. J. Org. Chem. 2008, 73, 3377. (263) Yang, Y.; Gao, M.; Wu, L.-M.; Deng, C.; Zhang, D.-X.; Gao, Y.; Zhu, Y.-P.; Wu, A.-X. Tetrahedron 2011, 67, 5142. (264) Mosterd, A.; Matser, H. J.; Bos, H. J. T. Tetrahedron Lett. 1974, 15, 4179. (265) Katritzky, A. R.; Luxem, F. J.; Siskin, M. Energy Fuels 1990, 4, 525. (266) (a) Proksch, P.; Proksch, M.; Towers, G. H. N.; Rodriguez, E. J. Nat. Prod. 1983, 46, 331. (b) Parodi, F. J.; Fischer, N. H.; Flores, H. E. J. Nat. Prod. 1988, 51, 594. (c) Tomaszewski, Z.; Johnson, M. P.; Huang, X.; Nichols, D. E. J. Med. Chem. 1992, 35, 2061. (d) Jia, Z.; Zhao, Y. J. Nat. Prod. 1994, 57, 146. (e) Sauter, M.; Adam, W. Acc. Chem. Res. 1995, 28, 289. (f) Bakunova, S. M.; Bakunov, S. A.; Wenzler, T.; Barszcz, T.; Werbovetz, K. A.; Brun, R.; Hall, J. E.; Tidwell, R. R. J. Med. Chem. 2007, 50, 5807.

(267) (a) Masubuchi, M.; Kawasaki, K.; Ebiike, H.; Ikeda, Y.; Tsujii, S.; Sogabe, S.; Fujii, T.; Sakata, K.; Shiratori, Y.; Aoki, Y.; Ohtsuka, T.; Shimma, N. Bioorg. Med. Chem. Lett. 2001, 11, 1833. (b) Masubuchi, M.; Ebiike, H.; Kawasaki, K.; Sogabe, S.; Morikami, K.; Shiratori, Y.; Tsujii, S.; Fujii, T.; Sakata, K.; Hayase, M.; Shindoh, H.; Aoki, Y.; Ohtsuka, T.; Shimma, N. Bioorg. Med. Chem. 2003, 11, 4463. (268) Abdel-Aziz, H. A.; Mekawey, A. A. I.; Dawood, K. M. Eur. J. Med. Chem. 2009, 44, 3637. (269) Navarro, E.; Alonso, S. J.; Trujillo, J.; Jorge, E.; Pérez, C. J. Nat. Prod. 2001, 64, 134. (270) Kraus, G. A.; Kim, I. Org. Lett. 2003, 5, 1191. (271) Lu, H.; Liu, G.-T. Planta Med. 1992, 58, 311. (272) (a) Sun, M.; Zhao, C.; Gfesser, G. A.; Thiffault, C.; Miller, T. R.; Marsh, K.; Wetter, J.; Curtis, M.; Faghih, R.; Esbenshade, T. A.; Hancock, A. A.; Cowart, M. J. Med. Chem. 2005, 48, 6482. (b) Inoue, M.; Carson, M. W.; Frontier, A. J.; Danishefsky, S. J. J. Am. Chem. Soc. 2001, 123, 1878. (273) Chen, Y.; Chen, S.; Lu, X.; Cheng, H.; Ou, Y.; Cheng, H.; Zhou, G.-C. Bioorg. Med. Chem. Lett. 2009, 19, 1851. (274) Oter, O.; Ertekin, K.; Kirilmis, C.; Koca, M.; Ahmedzade, M. Sens. Actuators, B 2007, 122, 450. (275) Karatas, F.; Koca, M.; Kara, H.; Servi, S. Eur. J. Med. Chem. 2006, 41, 664. (276) Habermann, J.; Ley, S. V.; Smits, R. J. Chem. Soc., Perkin Trans. 1 1999, 2421. (277) (a) Yue, D.; Yao, T.; Larock, R. C. J. Org. Chem. 2005, 70, 10292. (b) Churruca, F.; SanMartin, R.; Tellitu, I.; Domínguez, E. Eur. J. Org. Chem. 2005, 12, 2481. (c) Dudley, M. E.; Morshed, M. M.; Hossain, M. M. Synthesis 2006, 1711. (d) Rosa, C. D.; Kneeteman, M. N.; Mancini, P. M. E. Tetrahedron Lett. 2005, 46, 8711. (e) Ma, D.; Cai, Q.; Xie, X. Synlett 2005, 1767. (f) Liao, Y.; Smith, J.; Fathi, R.; Yang, Z. Org. Lett. 2005, 7, 2707. (g) Chen, C.; Dormer, P. G. J. Org. Chem. 2005, 70, 6964. (h) Bellur, E.; Langer, P. J. Org. Chem. 2005, 70, 7686. (i) Rasool, N.; Rashid, M. A.; Reinke, H.; Fischer, C.; Langer, P. Tetrahedron 2007, 63, 11626. (j) Huang, X.-C.; Liu, Y.-L.; Liang, Y.; Pi, S.-F.; Wang, F.; Li, J.-H. Org. Lett. 2008, 10, 1525. (k) Liang, Y.; Tang, S.; Zhang, X.-D.; Mao, L.-Q.; Xie, Y.-X.; Li, J.-H. Org. Lett. 2006, 8, 3017. (l) Li, J.-H.; Li, J.-L.; Wang, D.-P.; Pi, S.-F.; Xie, Y.-X.; Zhang, M.-B.; Hu, X.-C. J. Org. Chem. 2007, 72, 2053. (m) Liao, Y.; Reitman, M.; Zhang, Y.; Fathi, R.; Yang, Z. Org. Lett. 2002, 4, 2607. (n) Cheng, X.-M.; Liu, X.-W. J. Comb. Chem. 2007, 9, 906. (o) Routledge, A.; Abell, C.; Balasubramanian, S. Synlett 1997, 61. (p) Du, X.; Armstrong, R. W. J. Org. Chem. 1997, 62, 5678. (q) Hosokawa, T.; Murahashi, S.-I. Acc. Chem. Res. 1990, 23, 49. (278) Teles, H. L.; Hemerly, J. P.; Pauletti, P. M.; Pandolfi, J. R. C.; Araújo, A. R.; Valentini, S. R.; Young, M. C. M.; Bolzani, V.; Da, S.; Silva, D. H. S. Nat. Prod. Res. 2005, 19, 319. (279) Serra, M. F.; Diaz, B. L.; Barreto, E.; Pereira, A. P. B.; Lima, M. C. R.; Barbosa-Filho, J. M.; Cordeiro, R. S. B.; Martins, M. A.; De Silva, P. M. R. Planta Med. 1997, 63, 207. (280) Hoang, V. D.; Tan, G. T.; Zhang, H.-J.; Tamez, P. A.; Van Hung, N.; Cuong, N. M.; Soejarto, D. D.; Fong, H. H. S.; Pezzuto, J. M. Phytochemistry 2002, 59, 325. (281) MacRae, W. D.; Towers, G. H. N. Phytochemistry 1984, 23, 1207. (282) Brown, R. C. D.; Bataille, C. J. R.; Bruton, G.; Hinks, J. D.; Swain, N. A. J. Org. Chem. 2001, 66, 6719. (283) Iwakami, S.; Wu, J.-B.; Ebizuka, Y.; Sankawa, U. Chem. Pharm. Bull. 1992, 40, 1196. (284) Ichikawa, K.; Kinoshita, T.; Nishibe, S.; Sankawa, U. Chem. Pharm. Bull. 1986, 34, 3514. (285) Nikaido, T.; Ohmoto, T.; Kinoshita, T.; Sankawa, U.; Nishibe, S.; Hisada, S. Chem. Pharm. Bull. 1981, 29, 3586. (286) Plante, G. E.; Prevost, C.; Chainey, A.; Braquet, P.; Sirois, P. Am. J. Physiol. 1987, 253, R375. (287) Bernard, C.-B.; Arnason, J. T.; Philogène, B. J. R.; Lam, J.; Waddell, T. Phytochemistry 1989, 28, 1373. (288) (a) Brown, R. C. D.; Bataille, C. J. R.; Hinks, J. D. Tetrahedron Lett. 2001, 42, 473. (b) Ogiku, T.; Yoshida, S. I.; Ohmizu, H.; Iwasaki, BT


Chemical Reviews

Review

T. J. Org. Chem. 1995, 60, 1148. (c) Yoda, H.; Kimura, K.; Takabe, K. Synlett 2001, 400. (d) Aldous, D. J.; Dalençon, A. J.; Steel, P. G. Org. Lett. 2002, 4, 1159. (e) Roy, S. C.; Rana, K. K.; Guin, C. J. Org. Chem. 2002, 67, 3242. (f) Pelter, A.; Ward, R. S.; Watson, D. J.; Jack, I. R. J. Chem. Soc., Perkin Trans. 1 1982, 183. (g) Takano, S.; Ohkawa, T.; Tamori, S.; Satoh, S.; Ogasawara, K. J. Chem. Soc., Chem. Commun. 1988, 189. (h) Orito, K.; Yorita, K.; Suginome, H. Tetrahedron Lett. 1991, 32, 5999. (i) Suginome, H.; Ishikawa, M.; Yorita, K.; Shimoyama, N.; Sasaki, T.; Orito, K. J. Org. Chem. 1995, 60, 3052. (j) Samizu, K.; Ogasawara, K. Chem. Lett. 1995, 543. (k) Beroza, M.; Schechter, M. S. J. Am. Chem. Soc. 1956, 78, 1242. (l) Aldous, D. J.; Dalencon, A. J.; Steel, P. G. J. Org. Chem. 2003, 68, 9159. (m) Banerjee, B.; Roy, S. C. Synthesis 2005, 2913. (289) Talinli, N.; Karliga, B. J. Heterocycl. Chem. 2004, 41, 205. (290) Chen, C.-X.; Liu, L.; Yang, D.-P.; Wang, D.; Chen, Y.-J. Synlett 2005, 2047. (291) Mosslemin, M. H.; Anary-Abbasinejad, M.; Fazli Nia, A.; Bakhtiari, S.; Anaraki-Ardakani, H. J. Chem. Res. 2009, 599. (292) Shchepin, V. V.; Fotin, D. V.; Nedugov, A. N.; Fotin, V. V. Russ. J. Org. Chem. 2002, 38, 256. (293) Fujimaki, T.; Nagase, H.; Yamaguchi, R.; Kawai, K.-I.; Otomasu, H. Chem. Pharm. Bull. 1985, 33, 2663. (294) Bailey, A. S.; Ledger, A. P.; Perkins, N. R. D. J. Chem. Soc. (C) 1967, 323. (295) Kadhim, S. A.; Bowlin, T. L.; Waud, W. R.; Angers, E. G.; Bibeau, L.; DeMuys, J.-M.; Bednarski, K.; Cimpoia, A.; Attardo, G. Cancer Res. 1997, 57, 4803. (296) Bednarski, K.; Dixit, D. M.; Wang, W.; Evans, C. A.; Jin, H.; Yuen, L.; Mansour, T. S. Bioorg. Med. Chem. Lett. 1994, 4, 2667. (297) Vlahakis, J. Z.; Kinobe, R. T.; Bowers, R. J.; Brien, J. F.; Nakatsu, K.; Szarek, W. A. J. Med. Chem. 2006, 49, 4437. (298) (a) Colobert, F.; Obringer, M.; Solladié, G. Eur. J. Org. Chem. 2006, 1455. (b) Williams, D. B. G.; Caddy, J.; Blann, K. Carbohydr. Res. 2005, 340, 1301. (c) Kim, H. O.; Schinazi, R. F.; Shanmuganathan, K.; Jeong, L. S.; Beach, J. W.; Nampalli, S.; Cannon, D. L.; Chu, C. K. J. Med. Chem. 1993, 36, 519. (d) Choi, W.B.; Wilson, L. J.; Yeola, S.; Liotta, D. C. J. Am. Chem. Soc. 1991, 113, 9377. (299) Clerici, A.; Porta, O. J. Org. Chem. 1989, 54, 3872. (300) Lu, C.-D.; Chen, Z.-Y.; Liu, H.; Hu, W.-H.; Mi, A.-Q. Org. Lett. 2004, 6, 3071 and references cited therein.. (301) (a) Mo, J.; Xiao, J. Angew. Chem., Int. Ed. 2006, 45, 4152. (b) Arefalk, A.; Larhed, M.; Hallberg, A. J. Org. Chem. 2005, 70, 938. (302) (a) Gopinath, R.; Haque, S. J.; Patel, B. K. J. Org. Chem. 2002, 67, 5842. (b) Ono, F.; Takenaka, H.; Fujikawa, T.; Mori, M.; Sato, T. Synthesis 2009, 1318. (c) Yu, J.; Zhang, C. Synthesis 2009, 2324. (303) Shao, Q.; Li, C. Synlett 2008, 2412. (304) Shao, Q.; Shi, W.; Li, C. Synthesis 2008, 3925. (305) Manning, D. T.; Stansbury, H. A., Jr. J. Org. Chem. 1961, 26, 3755. (306) (a) Roncali, J. Chem. Rev. 1992, 92, 711. (b) Roncali, J. Chem. Rev. 1997, 97, 173. (c) Miller, L. L.; Mann, K. R. Acc. Chem. Res. 1996, 29, 417. (307) Larsen, J.; Bechgaard, K. Acta Chem. Scand. 1996, 50, 71. (308) Müller, M.; Mauermann-Düll, H.; Wagner, M.; Enkelmann, V.; Müllen, K. Angew. Chem., Int. Ed. 1995, 34, 1583. (309) (a) Tsuji, K.; Nakamura, K.; Ogino, T.; Konishi, N.; Tojo, T.; Ochi, T.; Seki, N.; Matsuo, M. Chem. Pharm. Bull. 1998, 46, 279. (b) Becker, F. F.; Mukhopadhyay, C.; Hackfeld, L.; Banik, I.; Banik, B. K. Bioorg. Med. Chem. 2000, 8, 2693. (310) (a) Huynh, W. U.; Dittmer, J. J.; Alivisatos, A. P. Science 2002, 295, 2425. (b) Li, G.; Shrotriya, V.; Huang, J.; Yao, Y.; Moriarty, T.; Emery, K.; Yang, Y. Nat. Mater. 2005, 4, 864. (311) Schopf, G.; Koßmehl, G. Adv. Polym. Sci. 1997, 129, 1. (312) (a) Kiani, M. S.; Mitchell, G. R. Synth. Met. 1992, 46, 293. (b) Dimitrakopoulos, C. D.; Malenfant, P. R. L. Adv. Mater. 2002, 14, 99. (313) (a) Morrison, J. J.; Murray, M. M.; Li, X. C.; Holmes, A. B.; Morratti, S. C.; Friend, R. H.; Sirringhaus, H. Synth. Met. 1999, 102,

987. (b) Li, X.-C.; Sirringhaus, H.; Garnier, F.; Holmes, A. B.; Moratti, S. C.; Feeder, N.; Clegg, W.; Teat, S. J.; Friend, R. H. J. Am. Chem. Soc. 1998, 120, 2206. (314) Greenham, N. C.; Moratti, S. C.; Bradley, D. D. C.; Friend, R. H.; Holmes, A. B. Nature 1993, 365, 628. (315) (a) De Francesco, R.; Migliaccio, G. Nature 2005, 436, 953. (b) Chauvette, R. R.; Flynn, E. H.; Jackson, B. G.; Lavagnino, E. R.; Morin, R. B.; Mueller, R. A.; Pioch, R. P.; Roeske, R. W.; Ryan, C. W.; Spencer, J. L.; Van Heyningen, E. J. Am. Chem. Soc. 1962, 84, 3401. (316) (a) Pinto, I. L.; Jarvest, R. L.; Serafinowska, H. T. Tetrahedron Lett. 2000, 41, 1597. (b) Holmes, J. M.; Lee, G. C. M.; Wijono, M.; Weinkam, R.; Wheeler, L. A.; Garst, M. E. J. Med. Chem. 1994, 37, 1646. (317) (a) Campaigne, E. In Comprehensive Heterocyclic Chemistry; Katritzky, A. R., Rees, C. W., Eds.; Elsevier: Oxford, U.K., 1984; Vol. 4, pp 863−934. (b) Gronowitz, S. Thiophene and its Derivatives; Gronowitz, S., Ed.; John Wiley and Sons: New York, 1985; Part 1, pp 42−59. (c) Snieckus, V. Chem. Rev. 1990, 90, 879. (d) Revelant, G.; Dunand, S.; Hesse, S.; Kirsch, G. Synthesis 2011, 2935. (e) Wang, T.; Huang, X.-G.; Liu, J.; Li, B.; Wu, J.-J.; Chen, K.-X.; Zhu, W.-L.; Xu, X.Y.; Zeng, B.-B. Synlett 2010, 1351. (f) Matloubi Moghaddam, F.; Zali Bionee, H. Tetrahedron 2004, 60, 6085. (g) You, W.; Yan, X.; Liao, Q.; Xi, C. Org. Lett. 2010, 12, 3930. (h) Nandi, G. C.; Samai, S.; Singh, M. S. J. Org. Chem. 2011, 76, 8009. (i) Minetto, G.; Raveglia, L. F.; Sega, A.; Taddei, M. Eur. J. Org. Chem. 2005, 5277. (j) Kaleta, Z.; Makowski, B. T.; Soos, T.; Dembinski, R. Org. Lett. 2006, 8, 1625. (318) Mac Dowell, D. W. H.; Patrick, T. B. J. Org. Chem. 1967, 32, 2441. (319) Miyahara, Y.; Inazu, T.; Yoshino, T. Bull. Chem. Soc. Jpn. 1980, 53, 1187. (320) Yin, G.; Wang, Z.; Chen, A.; Gao, M.; Wu, A.; Pan, Y. J. Org. Chem. 2008, 73, 3377. (321) (a) Epple, R.; Russo, R.; Azimioara, M.; Cow, C.; Xie, Y.; Wang, X.; Wityak, J.; Karanewsky, D.; Gerken, A.; Iskandar, M.; Saez, E.; Seidel, H. M.; Tian, S.-S. Bioorg. Med. Chem. Lett. 2006, 16, 4376. (b) Karthikeyan, K.; Veenus Seelan, T.; Lalitha, K. G.; Perumal, P. T. Bioorg. Med. Chem. Lett. 2009, 19, 3370. (c) Koufaki, M.; Tsatsaroni, A.; Alexi, X.; Guerrand, H.; Zerva, S.; Alexis, M. N. Bioorg. Med. Chem. 2011, 19, 4841. (322) Lee, Y.-G.; Koyama, Y.; Yonekawa, M.; Takata, T. Macromolecules 2009, 42, 7709. (323) (a) Brown, D. H.; Styring, P. Liq. Cryst. 2003, 30, 23. (b) Gallardo, H.; Zucco, C.; Da Silva, L. Mol. Cryst. Liq. Cryst. 2002, 373, 181. (c) Bartulin, J.; Martinez, R.; Gallardo, H.; Muller, J.; Taylor, T. R. Mol. Cryst. Liq. Cryst. 1993, 225, 175. (d) Barbera, J.; Cativiela, C.; Serrano, J. L.; Zurbano, M. M. Liq. Cryst. 1992, 11, 887. (324) Frolund, B.; Jorgensen, A. T.; Tagmose, L.; Stensbol, T. B.; Vestergaard, H. T.; Engblom, C.; Kristiansen, U.; Sanchez, C.; Krogsgaard-Larsen, P.; Liljefors, T. J. Med. Chem. 2002, 45, 2454. (325) (a) Daidone, G.; Raffa, D.; Maggio, B.; Plescia, F.; Cutuli, V. M. C.; Mangano, N. G.; Caruso, A. Arch. Pharm. 1999, 332, 50. (b) Mishra, A.; Jain, S. K.; Asthana, J. G. Orient. J. Chem. 1998, 14, 151. (326) Kang, Y. K.; Shin, K. J.; Yoo, K. H.; Seo, K. J.; Hong, C. Y.; Lee, C.-S.; Park, S. Y.; Kim, D. J.; Park, S. W. Bioorg. Med. Chem. Lett. 2000, 10, 95. (327) Ko, D.-H.; Maponya, M. F.; Khalil, M. A.; Oriaku, E. T.; You, Z.; Lee. J. Med. Chem. Res. 1998, 8, 313. (328) Conti, P.; Dallanoce, C.; Amici, M. D.; Micheli, C. D.; Klotz, K.-N. Bioorg. Med. Chem. 1998, 6, 401. (329) Talley, J. J.; Brown, D. L.; Carter, J. S.; Graneto, M. J.; Koboldt, C. M.; Masferrer, J. L.; Perkins, W. E.; Rogers, R. S.; Shaffer, A. F.; Zhang, Y. Y.; Zweifel, B. S.; Seibert, K. J. Med. Chem. 2000, 43, 775. (330) Giovannoni, M. P.; Vergelli, C.; Ghelardini, C.; Galeotti, N.; Bartolini, A.; Kal Piaz, V. J. Med. Chem. 2003, 46, 1055. (331) Li, W.-T.; Hwang, D.-R.; Chen, C.-P.; Shen, C.-W.; Huang, C.L.; Chen, T.-W.; Lin, C.-H.; Chang, Y.-L.; Chang, Y.-Y.; Lo, Y.-K.; Tseng, H.-Y.; Lin, C.-C.; Song, J.-S.; Chen, H.-C.; Chen, S.-J.; Wu, S.H.; Chen, C.-T. J. Med. Chem. 2003, 46, 1706. BU


Chemical Reviews

Review

(332) (a) Curran, D. P. J. Am. Chem. Soc. 1983, 105, 5826. (b) Andersen, S. H.; Sharma, K. K.; Torssell, K. B. G. Tetrahedron 1983, 39, 2241. (c) Baraldi, P. G.; Barco, A.; Benetti, S.; Manfredini, S.; Simoni, D. Synthesis 1987, 276. (d) Bode, J. W.; Carreira, E. M. Org. Lett. 2001, 3, 1587. (e) Kozikowski, A. P.; Chen, Y. Y. J. Org. Chem. 1981, 46, 5248. (f) Müller, I.; Jäger, V. Tetrahedron Lett. 1982, 23, 4777. (g) Jager, V.; Grund, H. Angew. Chem., Int. Ed. 1976, 15, 50. (h) Lee, S. Y.; Lee, B. S.; Lee, C.-W.; Oh, D. Y. J. Org. Chem. 2000, 65, 256. (i) Yashiro, A.; Nishida, Y.; Kobayashi, K.; Ohno, M. Synlett 2000, 361. (333) (a) Desai, J. T.; Desai, C. K.; Desai, K. R. J. Iran. Chem. Soc. 2008, 5, 67. (b) Cuadrado, P.; González-Nogal, A. M.; Valero, R. Tetrahedron 2002, 58, 4975. (c) Vicentini, C. B.; Veronese, A. C.; Poli, T.; Guarneri, M.; Giori, P.; Ferretti, V. J. Hetercycl. Chem. 1990, 27, 1481. (d) He, Y.; Lin, N.-H. Synthesis 1994, 989. (e) Denmark, S. E.; Kallemeyn, J. M. J. Org. Chem. 2005, 70, 2839. (f) Jaeger, V.; Colinas, P. A. In Synthetic Applications of 1,3-Dipolar Cycloaddition Chemistry Toward Heterocycles and Natural Products; Padwa, A., Pearson, W. H., Eds.; Chemistry of Heterocyclic Compounds; Wiley: Hoboken, NJ, 2002; Vol. 59, pp 361−472. (g) Himo, F.; Lovell, T.; Hilgraf, R.; Rostovtsev, V. V.; Noodleman, L.; Sharpless, K. B.; Fokin, V. V. J. Am. Chem. Soc. 2005, 127, 210. (h) Hansen, T. V.; Wu, P.; Fokin, V. V. J. Org. Chem. 2005, 70, 7761. (i) Grecian, S.; Fokin, V. V. Angew. Chem., Int. Ed. 2008, 47, 8285. (j) Waldo, J. P.; Larock, R. C. J. Org. Chem. 2007, 72, 9643. (k) Katritzky, A. R.; Wang, M.; Zhang, S.; Voronkov, M. V. J. Org. Chem. 2001, 66, 6787. (l) Rosa, F. A.; Machado, P.; Bonacorso, H. G.; Zanatta, N.; Martins, M. A. P. J. Heterocycl. Chem. 2008, 45, 879. (m) Kidwai, M.; Kukreja, S.; Thakur, R. Lett. Org. Chem. 2006, 3, 135. (n) Xu, J. P.; Hamme, A. T., II Synlett 2008, 919. (o) Bourbeau, M. P.; Rider, J. T. Org. Lett. 2006, 8, 3679. (p) Wang, K.; Xiang, D.; Liu, J.; Pan, W.; Dong, D. Org. Lett. 2008, 10, 1691. (q) Bandiera, T.; Grünanger, P.; Albini, F. M. J. Heterocycl. Chem. 1992, 29, 1423. (334) Juhász-Tóth, É.; Patonay, T. Eur. J. Org. Chem. 2002, 3055. (335) Patonay, T.; Micskei, K.; Juhász-Tóth, É.; Fekete, S.; PardiTóth, V. Cs. ARKIVOC 2009, vi, 270. (336) (a) Ghosh, A. K.; Mathivanan, P.; Cappiello, J. Tetrahedron: Asymmetry 1998, 9, 1. (b) Gómez, M.; Muller, G.; Rocamora, M. Coord. Chem. Rev. 1999, 193, 769. (c) Johnson, J. S.; Evans, D. A. Acc. Chem. Res. 2000, 33, 325. (d) Fache, F.; Schulz, E.; Tommasino, M. L.; Lemaire, M. Chem. Rev. 2000, 100, 2159. (e) Jørgensen, K. A.; Johannsen, M.; Yao, S.; Audrain, H.; Thurhauge, J. Acc. Chem. Res. 1999, 32, 605. (f) McManus, H. A.; Guiry, P. J. Chem. Rev. 2004, 104, 4151. (337) (a) Wipf, P.; Venkatraman, S. J. Org. Chem. 1995, 60, 7224. (b) Ousmer, M.; Braun, N. A.; Ciufolini, M. A. Org. Lett. 2001, 5, 765. (338) Green, T. W.; Wutz, P. G. M. Protecting Groups in Organic Synthesis, 2nd ed.; John Wiley and Sons: New York, 1991. (339) (a) Wipf, P.; Fritch, P. C.; Geib, S. J.; Sefler, A. M. J. Am. Chem. Soc. 1998, 120, 4105. (b) Deng, S.; Taunton, J. J. Am. Chem. Soc. 2002, 124, 916. (c) Onishi, H. R.; Pelak, B. A.; Gerckens, L. S.; Silver, L. L.; Kahan, F. M.; Chen, M.-H.; Patchett, A. A.; Galloway, S. M.; Hyland, S. A.; Anderson, M. S.; Raetz, C. R. H. Science 1996, 274, 980. (d) Prinsep, M. R.; Moore, R. E.; Levine, I. A.; Patterson, G. M. L. J. Nat. Prod. 1992, 55, 140. (e) You, S.-L.; Kelly, J. W. Chem.Eur. J. 2004, 10, 71. (f) Momose, Y.; Maekawa, T.; Yamano, T.; Kawada, M.; Odaka, H.; Ikeda, H.; Sohda, T. J. Med. Chem. 2002, 45, 1518. (g) Schnur, R. C.; Sarges, R.; Peterson, M. J. J. Med. Chem. 1982, 25, 1451. (h) Pothuluri, J. V.; Freeman, J. P.; Heinze, T. M.; Beger, R. D.; Cerniglia, C. E. J. Agric. Food Chem. 2000, 48, 6138. (340) (a) Williams, R. M.; Glinka, T.; Flanagan, M. E.; Gallegos, R.; Coffman, H.; Pei, D. J. Am. Chem. Soc. 1992, 114, 733. (b) Tomita, F.; Takahashi, K.; Tamaoki, T. J. Antibiot. 1984, 37, 1268. (341) (a) Denmark, S. E.; Nakajima, N.; Nicaise, O. J.-C.; Faucher, A.-M.; Edwards, J. P. J. Org. Chem. 1995, 60, 4884. (b) Wipf, P.; Venkatraman, S. Tetrahedron Lett. 1996, 37, 4659. (c) Pirrung, M. C.; Tumey, L. N. J. Comb. Chem. 2000, 2, 675. (d) Wuts, P. G. M.; Northuis, J. M.; Kwan, T. A. J. Org. Chem. 2000, 65, 9223. (e) Rajaram, S.; Sigman, M. S. Org. Lett. 2002, 4, 3399. (f) Michaelis, D. J.; Ischay,

M. A.; Yoon, T. P. J. Am. Chem. Soc. 2008, 130, 6610. (g) Michaelis, D. J.; Williamson, K. S.; Yoon, T. P. Tetrahedron 2009, 65, 5118. (h) Trost, B. M.; Jiang, C. J. Am. Chem. Soc. 2001, 123, 12907. (i) Shim, J.-G.; Yamamoto, Y. Heterocycles 2000, 52, 885. (j) Shim, J.G.; Yamamoto, Y. Tetrahedron Lett. 1999, 40, 1053. (k) Shaghafi, M. B.; Grote, R. E.; Jarvo, E. R. Org. Lett. 2011, 13, 5188. (l) Bergmann, E. D. Chem. Rev. 1953, 53, 309. (m) Ward, A. F.; Wolfe, J. P. Org. Lett. 2011, 13, 4728. (n) Wipf, P.; Miller, C. P. Tetrahedron Lett. 1992, 33, 907. (o) Sakakura, A.; Kondo, R.; Ishihara, K. Org. Lett. 2005, 7, 1971. (p) Chaudhry, P.; Schoenen, F.; Neuenswander, B.; Lushington, G. H.; Aubé, J. J. Comb. Chem. 2007, 9, 473 and references cited therein. (342) Choi, I.-Y.; Lee, H. G.; Chung, K.-H. J. Org. Chem. 2001, 66, 2484. (343) (a) Agami, C.; Couty, F.; Lequesne, C. Tetrahedron 1995, 51, 4043. (b) Agami, C.; Couty, F.; Lequesne, C. Tetrahedron Lett. 1994, 35, 3309. (344) Ukaji, Y.; Yamamoto, K.; Fukui, M.; Fujisawa, T. Tetrahedron Lett. 1991, 32, 2919. (345) García-Valverde, M.; Macho, S.; Marcaccini, S.; Rodríguez, T.; Rojo, J.; Torroba, T. Synlett 2008, 33. (346) Belgodere, E.; Bossio, R.; Parrini, V.; Pepino, R. J. Heterocycl. Chem. 1977, 14, 997. (347) Belgodere, E.; Bossio, R.; Parrini, V.; Pepino, R. J. Heterocycl. Chem. 1977, 14, 957. (348) Ichiba, T.; Yoshida, W. Y.; Scheuer, P. J.; Higa, T.; Gravalos, D. G. J. Am. Chem. Soc. 1991, 113, 3173. (349) D’Ambrosio, M.; Guerriero, A.; Pietra, F.; Debitus, C. Helv. Chim. Acta 1996, 79, 51. (350) Brown, P.; Davies, D. T.; O’Hanlon, P. J.; Wilson, J. M. J. Med. Chem. 1996, 39, 446. (351) Hopkins, C. D.; Wipf, P. Nat. Prod. Rep. 2009, 26, 585. (352) Kean, W. F. Curr. Med. Res. Opin. 2004, 20, 1275. (353) Schlessinger, R. H.; Li, Y.-J. J. Am. Chem. Soc. 1996, 118, 3301. (354) Also known as virginiamycin M1: Delpierre, G. R.; Eastwood, F. W.; Gream, G. E.; Kingston, D. G. I.; Sarin, P. S.; Todd, L.; Williams, D. H. Tetrahedron Lett. 1966, 7, 369. (355) Looker, A. R.; Littler, B. J.; Blythe, T. A.; Snoonian, J. R.; Ansell, G. K.; Jones, A. D.; Nyce, P.; Chen, M.; Neubert, B. J. Org. Process Res. Dev. 2008, 12, 666. (356) (a) Jin, Z. Nat. Prod. Rep. 2006, 23, 464. (b) Jin, Z. Nat. Prod. Rep. 2009, 26, 382. (357) (a) Phillips, A. J.; Uto, Y.; Wipf, P.; Reno, M. J.; Williams, D. R. Org. Lett. 2000, 2, 1165. (b) Wipf, P.; Miller, C. P. Tetrahedron Lett. 1992, 33, 907. (c) Yokokawa, F.; Shioiri, T. Tetrahedron Lett. 2002, 43, 8679. (d) Sakakura, A.; Kondo, R.; Ishihara, K. Org. Lett. 2005, 7, 1971. (e) Xu, Q.; Li, Z. Tetrahedron Lett. 2009, 50, 6838. (f) Wuts, P. G. M.; Northuis, J. M.; Kwan, T. A. J. Org. Chem. 2000, 65, 9223. (g) Lafargue, P.; Guenot, P.; Lellouche, J.-P. Heterocycles 1995, 41, 947. (358) (a) Yamamoto, K.; Chen, Y. G.; Buono, F. G. Org. Lett. 2005, 7, 4673. (b) Aoyama, T.; Sonoda, N.; Yamauchi, M.; Toriyama, K.; Anzai, M.; Ando, A.; Shioiri, T. Synlett 1998, 35. (c) Tavares, F.; Meyers, A. I. Tetrahedron Lett. 1994, 35, 6803. (d) Barrish, J. C.; Singh, J.; Spergel, S. H.; Han, W.-C.; Kissick, T. P.; Kronenthal, D. R.; Mueller, R. H. J. Org. Chem. 1993, 58, 4494. (e) McGarvey, G. J.; Wilson, K. J.; Shanholtz, C. E. Tetrahedron Lett. 1992, 33, 2641. (359) (a) Wipf, P.; Graham, T. H. J. Org. Chem. 2001, 66, 3242. (b) Cai, X.-H.; Yang, H.-J.; Zhang, G.-L. Synthesis 2005, 1569. (c) Brain, C. T.; Paul, J. M. Synlett 1999, 1642. (d) Pulici, M.; Quartieri, F.; Felder, E. R. J. Comb. Chem. 2005, 7, 463. (e) Williams, D. R.; Fu, L. Org. Lett. 2010, 12, 808. (f) Ackermann, L.; Barfüsser, S.; Pospech, J. Org. Lett. 2010, 12, 724. (g) Lee, K.; Counceller, C. M.; Stambuli, J. P. Org. Lett. 2009, 11, 1457. (h) dos Santos, A.; Kaïm, L. E.; Grimaud, L.; Ronsseray, C. Chem. Commun. 2009, 3907. (i) Verrer, C.; Hoarau, C.; Marsais, F. Org. Biomol. Chem. 2009, 7, 647. (j) Flegeau, E. F.; Popkin, M. E.; Greaney, M. F. Org. Lett. 2008, 10, 2717. (k) Riedrich, M.; Harkal, S.; Arndt, H.-D. Angew. Chem., Int. Ed. 2007, 46, 2701. (l) Martín, R.; Cuenca, A.; Buchwald, S. L. Org. Lett. 2007, 9, 5521. (m) Flegeau, E. F.; Popkin, M. E.; Greaney, M. F. Org. BV


Chemical Reviews

Review

Lett. 2006, 8, 2495. (n) Keni, M.; Tepe, J. J. J. Org. Chem. 2005, 70, 4211. (o) Coqueron, P.-Y.; Didier, C.; Ciufolini, M. A. Angew. Chem., Int. Ed. 2003, 42, 1411. (p) Palmer, D. C.; Venkatraman, S. In Oxazoles: Synthesis, Reactivity and Spectroscopy; Palmer, D. C., Ed.; John Wiley & Sons Inc.: Hoboken, NJ, 2003; Part A. (q) Singh, J.; Gordon, T. D.; Earley, W. G.; Morgan, B. A. Tetrahedron Lett. 1993, 34, 211. (360) Belyuga, A. G.; Brovarets, V. S.; Drach, B. S. Russ. J. Gen. Chem. 2005, 75, 523. (361) (a) Roy, R. S.; Gehring, A. M.; Milne, J. C.; Belshaw, P. J.; Walsh, C. T. Nat. Prod. Rep. 1999, 16, 249. (b) Luesch, H.; Yoshida, W. Y.; Moore, R. E.; Paul, V. J.; Corbett, T. H. J. Am. Chem. Soc. 2001, 123, 5418. (c) Luesch, H.; Yoshida, W. Y.; Moore, R. E.; Paul, V. J. Bioorg. Med. Chem. 2002, 10, 1973. (362) Negwer, M. Organic-Chemical Drugs and Their Synonyms: An International Survey, 7th ed.; Akademie, VCH: New York, 1994. (363) (a) Šubr, V.; Ulbrich, K. React. Funct. Polym. 2006, 66, 1525. (b) Rostom, S. A. F.; El-Ashmawy, I. M.; Abd El Razik, H. A.; Badr, M. H.; Ashour, H. M. A. Bioorg. Med. Chem. 2009, 17, 882. (c) Nagao, Y.; Nishijima, H.; Iimori, H.; Ushirogochi, H.; Sano, S.; Shiro, M. J. Organomet. Chem. 2000, 611, 172. (d) Abdullah, M. N.; Arrasate, S.; Lete, E.; Sotomayor, N. Tetrahedron 2008, 64, 1323. (364) (a) Cosp, A.; Llácer, E.; Romea, P.; Urpí, F. Tetrahedron Lett. 2006, 47, 5819. (b) Baiget, J.; Cosp, A.; Gálvez, E.; Gómez-Pinal, L.; Romea, P.; Urpí, F. Tetrahedron 2008, 64, 5637. (c) Yang, J.-H.; Yang, G.-C.; Lu, C.-F.; Chen, Z.-X. Tetrahedron: Asymmetry 2008, 19, 2164. (365) (a) Kedrowski, B. L.; Heathcock, C. H. Heterocycles 2002, 58, 601. (b) Raman, P.; Razavi, H.; Kelly, J. W. Org. Lett. 2000, 2, 3289. (c) Ino, A.; Murabayashi, A. Tetrahedron 1999, 55, 10271. (d) Charette, A. B.; Chua, P. J. Org. Chem. 1998, 63, 908. (e) North, M.; Pattenden, G. Tetrahedron 1990, 46, 8267. (f) Chen, J.; Forsyth, C. J. Org. Lett. 2003, 5, 1281. (g) Fukuyama, T.; Xu, L. J. Am. Chem. Soc. 1993, 115, 8449. (h) Walker, M. A.; Heathcock, C. H. J. Org. Chem. 1992, 57, 5566. (i) Zarantonello, P.; Leslie, C. P.; Ferritto, R.; Kazmierski, W. M. Bioorg. Med. Chem. Lett. 2002, 12, 561. (j) Liu, B.; Davis, R.; Joshi, B.; Reynolds, D. W. J. Org. Chem. 2002, 67, 4595. (k) Larksarp, C.; Sellier, O.; Alper, H. J. Org. Chem. 2001, 66, 3502 and references cited therein. (l) Boyce, R. J.; Mulqueen, G. C.; Pattenden, G. Tetrahedron Lett. 1994, 35, 5705. (m) Busacca, C. A.; Dong, Y.; Spinelli, E. M. Tetrahedron Lett. 1996, 37, 2935. (n) Boden, C. D. J.; Pattenden, G.; Ye, T. Synlett 1995, 417. (o) Wipf, P.; Miller, C. P. Tetrahedron Lett. 1992, 33, 6267. (p) Wipf, P.; Fritch, P. C. Tetrahedron Lett. 1994, 35, 5397. (q) Xu, Z.; Ye, T. Tetrahedron: Asymmetry 2005, 16, 1905. (366) Agami, C.; Couty, F.; Prince, B.; Venier, O. Tetrahedron Lett. 1993, 34, 7061. (367) Pinho e Melo, T. M. V. D.; Soares, M. I. L.; d’A. Rocha Gonsalves, A. M.; Paixão, J. A.; Beja, A. M.; Silva, M. R.; da Veiga, L. A.; Pessoa, J. C. J. Org. Chem. 2002, 67, 4045. (368) Pearson, N. D.; Smale, T. C.; Southgate, R. Tetrahedron Lett. 1995, 36, 4493. (369) (a) Masquelin, T.; Obrecht, D. Tetrahedron 2001, 57, 153. (b) Zabriskie, T. M.; Mayne, C. L.; Ireland, C. M. J. Am. Chem. Soc. 1988, 110, 7919. (c) Crews, P.; Kakou, Y.; Quinoa, E. J. Am. Chem. Soc. 1988, 110, 4365. (d) Rosowsky, A.; Mota, C. E.; Wright, J. E.; Freisheim, J. H.; Heusner, J. J.; McCormack, J. J.; Queener, S. F. J. Med. Chem. 1993, 36, 3103. (e) Hutchinson, I.; Stevens, M. F. G.; Westwell, A. D. Tetrahedron Lett. 2000, 41, 425. (370) (a) Hirai, K.; Sugimoto, H.; Ishiba, T. J. Org. Chem. 1980, 45, 253. (b) Yang, B. V.; Weinstein, D. S.; Doweyko, L. M.; Gong, H.; Vaccaro, W.; Huynh, T.; Xiao, H.-Y.; Doweyko, A. M.; McKay, L.; Holloway, D. A.; Somerville, J. E.; Habte, S.; Cunningham, M.; McMahon, M.; Townsend, R.; Shuster, D.; Dodd, J. H.; Nadler, S. G.; Barrish, J. C. J. Med. Chem. 2010, 53, 8241. (371) Andreani, A.; Rambaldi, M.; Leoni, A.; Locatelli, A.; Andreani, F.; Gehret, J. C. Pharm. Acta Helv. 1996, 71, 247. (372) (a) Andreani, A.; Burnelli, S.; Granaiola, M.; Leoni, A.; Locatelli, A.; Morigi, R.; Rambaldi, M.; Varoli, L.; Calonghi, N.; Cappadone, C.; Farruggia, G.; Zini, M.; Stefanelli, C.; Masotti, L.;

Radin, N. S.; Shoemaker, R. H. J. Med. Chem. 2008, 51, 809. (b) Andreani, A.; Granaiola, M.; Leoni, A.; Locatelli, A.; Morigi, R.; Rambaldi, M.; Lenaz, G.; Fato, R.; Bergamini, C.; Farruggia, G. J. Med. Chem. 2005, 48, 3085. (c) Andreani, A.; Granaiola, M.; Leoni, A.; Locatelli, A.; Morigi, R.; Rambaldi, M.; Garaliene, V.; Welsh, W.; Arora, S.; Farruggia, G.; Masotti, L. J. Med. Chem. 2005, 48, 5604. (373) Budriesi, R.; Ioan, P.; Locatelli, A.; Cosconati, S.; Leoni, A.; Ugenti, M. P.; Andreani, A.; Di Toro, R.; Bedini, A.; Spampinato, S.; Marinelli, L.; Novellino, E.; Chiarini, A. J. Med. Chem. 2008, 51, 1592. (374) Crute, J. J.; Grygon, C. A.; Hargrave, K. D.; Simoneau, B.; Faucher, A.-M.; Bolger, G.; Kibler, P.; Liuzzi, M.; Cordingley, M. G. Nat. Med. 2002, 8, 386. (375) Borelli, C.; Schaller, M.; Niewerth, M.; Nocker, K.; Baasner, B.; Berg, D.; Tiemann, R.; Tietjen, K.; Fugmann, B.; Lang-Fugmann, S.; Korting, H. C. Chemotherapy 2008, 54, 245. (376) Gallardo-Godoy, A.; Gever, J.; Fife, K. L.; Silber, B. M.; Prusiner, S. B.; Renslo, A. R. J. Med. Chem. 2011, 54, 1010. (377) Kane, J. L., Jr.; Hirth, B. H.; Liang, B.; Gourlie, B. B.; Nahill, S.; Barsomian, G. Bioorg. Med. Chem. Lett. 2003, 13, 4463. (378) Mori, A.; Sekiguchi, A.; Masui, K.; Shimada, T.; Horie, M.; Osakada, K.; Kawamoto, M.; Ikeda, T. J. Am. Chem. Soc. 2003, 125, 1700. (379) Dölling, K.; Zaschke, H.; Schubert, H. J. Prakt. Chem. 1979, 321, 643. (380) (a) Tanaka, K.; Nomura, H.; Oda, H.; Yoshida, S.; Mitsuhashi, K. J. Heterocycl. Chem. 1991, 28, 907. (b) Ohkubo, M.; Kuno, A.; Nakanishi, I.; Takasuci, H. Chem. Pharm. Bull. 1995, 43, 1497. (c) Moriarty, R. M.; Vaid, B. K.; Duncan, M. P.; Levy, S. G.; Prakash, O.; Goyal, S. Synthesis 1992, 845. (d) Varma, R. S.; Kumar, D.; Liesen, P. J. J. Chem. Soc., Perkin Trans. 1 1998, 4093. (e) Wipf, P.; Venkatraman, S. J. Org. Chem. 1996, 61, 8004. (f) Zaleska, B.; Ciez, D.; Falk, H. Monatsh. Chem. 1996, 127, 1251. (g) Kim, H.-S.; Kwon, I.-C.; Kim, O.-H. J. Heterocycl. Chem. 1995, 32, 937. (h) Coen, S.; Ragonnet, B.; Vieillescazes, C.; Roggero, J.-P. Heterocycles 1985, 23, 1225. (i) Yoshimatsu, M.; Yamamoto, T.; Sawa, A.; Kato, T.; Tanabe, G.; Muraoka, O. Org. Lett. 2009, 11, 2952. (j) Sanz-Cervera, J. F.; Blasco, R.; Piera, J.; Cynamon, M.; Ibáñez, I.; Murguía, M.; Fustero, S. J. Org. Chem. 2009, 74, 8988. (k) Kaleta, Z.; Makowski, B. T.; Soos, T.; Dembinski, R. Org. Lett. 2006, 8, 1625. (l) Narender, M.; Reddy, M. S.; Kumar, V. P.; Srinivas, B.; Sridhar, R.; Nageswar, Y. V. D.; Rao, K. R. Synthesis 2007, 3469. (m) Conover, L. H.; Tarbell, D. S. J. Am. Chem. Soc. 1950, 72, 5221. (n) Castagnolo, D.; Pagano, M.; Bernardini, M.; Botta, M. Synlett 2009, 2093. (o) Dondoni, A.; Merino, P. In Comprehensive Heterocyclic Chemistry II; Katrizky, A. R., ReesC., W., Scriven, E. F. V., Eds.; Elsevier Science: Oxford, U.K., 1996; Vol. 3, pp 373−474. (381) (a) Hutchinson, I.; Chua, M.-S.; Browne, H. L.; Trapani, V.; Bradshaw, T. D.; Westwell, A. D.; Stevens, M. F. G. J. Med. Chem. 2001, 44, 1446. (b) Yoshida, M.; Hayakawa, I.; Hayashi, N.; Agatsuma, T.; Oda, Y.; Tanzawa, F.; Iwasaki, S.; Koyama, K.; Furukawa, H.; Kurakata, S.; Sugano, Y. Bioorg. Med. Chem. Lett. 2005, 15, 3328. (382) Palmer, P. J.; Trigg, R. B.; Warrington, J. V. J. Med. Chem. 1971, 14, 248. (383) Walczyński, K.; Zuiderveld, O. P.; Timmerman, H. Eur. J. Med. Chem. 2005, 40, 15. (384) (a) Tale, R. H. Org. Lett. 2002, 4, 1641. (b) Abbotto, A.; Bradamante, S.; Facchetti, A.; Pagani, G. A. J. Org. Chem. 2002, 67, 5753. (c) Rudrawar, S.; Kondaskar, A.; Chakraborti, A. K. Synthesis 2005, 15, 2521. (d) Benedí, C.; Bravo, F.; Uriz, P.; Fernández, E.; Claver, C.; Castillón, S. Tetrahedron Lett. 2003, 44, 6073. (e) Joyce, L. L.; Evindar, G.; Batey, R. A. Chem. Commun. 2004, 446. (f) Evindar, G.; Batey, R. A. J. Org. Chem. 2006, 71, 1802. (g) Foreman, M. S. J.; Woollins, J. D. J. Chem. Soc., Dalton Trans. 2000, 1533. (h) Seijas, J. A.; Vázquez-Tato, M. P.; Carballido-Reboredo, M. R.; Crecente-Campo, J.; Romar-López, L. Synlett 2007, 313. (i) Bahrami, K.; Khodaei, M. M.; Naali, F. J. Org. Chem. 2008, 73, 6835. (j) Ryabukhin, S. V.; Plaskon, A. S.; Volochnyuk, D. M.; Tolmachev, A. A. Synthesis 2006, 3715. (k) Bose, D. S.; Idrees, M. J. Org. Chem. 2006, 71, 8261. (l) Wang, F.; Cai, S.; Wang, Z.; Xi, C. Org. Lett. 2011, 13, 3202. BW


Chemical Reviews

Review

(m) Joyce, L. L.; Batey, R. A. Org. Lett. 2009, 11, 2792. (n) Bose, D. S.; Idrees, M.; Srikanth, B. Synthesis 2007, 819. (o) Itoh, T.; Mase, T. Org. Lett. 2007, 9, 3687. (385) Kolos, N, N.; Zamigaylo, L. L.; Musatov, V. I. Chem. Heterocycl. Compd. 2009, 45, 970. (386) Yang, X.-L.; Xu, C.-M.; Lin, S.-M.; Chen, J.-X.; Ding, J.-C.; Wu, H.-Y.; Su, W.-K. J. Braz. Chem. Soc. 2010, 21, 37. (387) Hyvl, J.; Srogl, J. Eur. J. Org. Chem. 2010, 2849. (388) (a) Pan, K.; Scott, M. K.; Lee, D. H. S.; Fitzpatrick, L. J.; Crooke, J. J.; Rivero, R. A.; Rosenthal, D. I.; Vaidya, A. H.; Zhao, B.; Reitz, A. B. Bioorg. Med. Chem. 2003, 11, 185. (b) Jung, K.-Y.; Kim, S.K.; Gao, Z.-G.; Gross, A. S.; Melman, N.; Jacobson, K. A.; Kim, Y.-C. Bioorg. Med. Chem. 2004, 12, 613. (c) Leung-Toung, R.; Wodzinska, J.; Li, W.; Lowrie, J.; Kukreja, R.; Desilets, D.; Karimian, K.; Tam, T. F. Bioorg. Med. Chem. 2003, 11, 5529. (389) Zhan, P.; Liu, X.; Cao, Y.; Wang, Y.; Pannecouque, C.; Clercq, E. D. Bioorg. Med. Chem. Lett. 2008, 18, 5368. (390) (a) Mullican, M. D.; Wilson, M. W.; Conner, D. T.; Kostlan, C. R.; Schrier, D. J.; Dyer, R. D. J. Med. Chem. 1993, 36, 1090. (b) Song, Y.; Connor, D. T.; Sercel, A. D.; Sorenson, R. J.; Doubleday, R.; Unangst, P. C.; Roth, B. D.; Beylin, V. G.; Gilbertsen, R. B.; Chan, K.; Schrier, D. J.; Guglietta, A.; Bornemeier, D. A.; Dyer, R. D. J. Med. Chem. 1999, 42, 1161. (391) (a) Chou, J.-Y.; Lai, S.-Y.; Pan, S.-L.; Jow, G.-M.; Chern, J.-W.; Guh, J.-H. Biochem. Pharmacol. 2003, 66, 115. (b) Miyamoto, K.; Koshiura, R.; Mori, M.; Yokoi, H.; Mori, C.; Hasegawa, T.; Takatori, K. Chem. Pharm. Bull. 1985, 33, 5126. (392) Oruç, E. E.; Rollas, S.; Kandemirli, F.; Shvets, N.; Dimoglo, A. S. J. Med. Chem. 2004, 47, 6760. (393) (a) Chapleo, C. B.; Myers, M.; Myers, P. L.; Saville, J. F.; Smith, A. C. B.; Stillings, M. R.; Tulloch, I. F.; Walter, D. S.; Welbourn, A. P. J. Med. Chem. 1986, 29, 2273. (b) Chapleo, C. B.; Myers, P. L.; Smith, A. C. B.; Stillings, M. R.; Tulloch, I. F.; Walter, D. S. J. Med. Chem. 1988, 31, 7. (394) Turner, S.; Myers, M.; Gadie, B.; Nelson, A. J.; Pape, R.; Saville, J. F.; Doxey, J. C.; Berridge, T. L. J. Med. Chem. 1988, 31, 902. (395) (a) Severinsen, R.; Kilburn, J. P.; Lau, J. F. Tetrahedron 2005, 61, 5565. (b) Baxendale, I. R.; Ley, S. V.; Martinelli, M. Tetrahedron 2005, 61, 5323. (c) Kilburn, J. P.; Lau, J.; Jones, R. C. F. Tetrahedron Lett. 2003, 44, 7825. (396) (a) Hultén, J.; Bonham, N. M.; Nillroth, U.; Hansson, T.; Zuccarello, G.; Bouzide, A.; Åqvist, J.; Classon, B.; Danielson, U. H.; Karlén, A.; Kvarnström, I.; Samuelsson, B.; Hallberg, A. J. Med. Chem. 1997, 40, 885. (b) Bäckbro, K.; Löwgren, S.; Ö sterlund, K.; Atepo, J.; Unge, T.; Hultén, J.; Bonham, N. M.; Schaal, W.; Karlén, A.; Hallberg, A. J. Med. Chem. 1997, 40, 898. (397) Lee, C.-H.; Korp, J. D.; Kohn, H. J. Org. Chem. 1989, 54, 3077. (398) Werber, G.; Buccheri, F.; Marino, M. L. J. Heterocycl. Chem. 1975, 12, 581. (399) Werber, G.; Buccheri, F.; Vivona, N.; Gentile, M. J. Heterocycl. Chem. 1977, 14, 1433. (400) (a) Ramirez, F.; Patwardhan, A. V.; Smith, C. P. J. Org. Chem. 1965, 30, 2575. (b) Ramirez, F.; Patwardhan, A. V.; Smith, C. P. J. Org. Chem. 1966, 31, 474. (401) Rubiralta, M.; Giralt, E.; Diez, E. Piperidine, Structure, Preparation, Reactivity and Synthetic Applications of Piperidine and Its Derivatives; Elsevier: Amsterdam, 1991. (402) (a) Aridoss, G.; Amirthaganesan, S.; Jeong, Y. T. Bioorg. Med. Chem. Lett. 2010, 20, 2242. (b) Ishida, J.; Hattori, K.; Yamamoto, H.; Iwashita, A.; Mihara, K.; Matsuoka, N. Bioorg. Med. Chem. Lett. 2005, 15, 4221. (c) Suleman, N. K.; Flores, J.; Tanko, J. M.; Isin, E. M.; Castagnoli, N., Jr. Bioorg. Med. Chem. 2008, 16, 8557. (d) Wimalasena, D. S.; Perera, R. P.; Heyen, B. J.; Balasooriya, I. S.; Wimalasena, K. J. Med. Chem. 2008, 51, 760. (e) Roberts, E.; Sançon, J. P.; Sweeney, J. B.; Workman, J. A. Org. Lett. 2003, 5, 4775. (f) Rodinovskaya, L. A.; Shestopalov, A. M.; Chunikhin, K. S. Tetrahedron 2002, 58, 4273. (403) (a) Tsukamoto, H.; Kondo, Y. Angew. Chem., Int. Ed. 2008, 47, 4851. (b) Spiegel, D. A.; Schroeder, F. C.; Duvall, J. R.; Schreiber, S. L. J. Am. Chem. Soc. 2006, 128, 14766. (c) Ramachandran, P. V.;

Burghardt, T. E.; Bland-Berry, L. J. Org. Chem. 2005, 70, 7911. (d) Zhu, X.-F.; Lan, J.; Kwon, O. J. Am. Chem. Soc. 2003, 125, 4716. (e) Legault, C.; Charette, A. B. J. Am. Chem. Soc. 2003, 125, 6360. (f) Kita, Y.; Maekawa, H.; Yamasaki, Y.; Nishiguchi, I. Tetrahedron 2001, 57, 2095. (g) Caplan, J. F.; Sutherland, A.; Vederas, J. C. J. Chem. Soc., Perkin Trans. 1 2001, 2217. (h) Harrison, T. J.; Dake, G. R. J. Org. Chem. 2005, 70, 10872. (i) Han, R.-G.; Wang, Y.; Li, Y.-Y.; Xu, P.-F. Adv. Synth. Catal. 2008, 350, 1474. (j) Zanatta, N.; Fernandes, L.; da, S.; Nachtigall, F. M.; Coelho, H. S.; Amaral, S. S.; Flores, A. F. C.; Bonacorso, H. G.; Martins, M. A. P. Eur. J. Org. Chem. 2009, 1435. (k) Sperger, C. A.; Mayer, P.; Wanner, K. T. Tetrahedron 2009, 65, 10463. (l) Aridoss, G.; Amirthaganesan, S.; Jeong, Y. T. Bioorg. Med. Chem. Lett. 2010, 20, 2242. (m) Misra, M.; Pandey, S. K.; Pandey, V. P.; Pandey, J.; Tripathi, R.; Tripathi, R. P. Bioorg. Med. Chem. 2009, 17, 625. (n) Khan, A. T.; Parvin, T.; Choudhury, L. H. J. Org. Chem. 2008, 73, 8398. (o) Khan, A. T.; Khan, M. M.; Bannuru, K. K. R. Tetrahedron 2010, 66, 7762. (404) (a) Boger, D. L.; Weinreb, S. M. Hetero Diels-Alder Methodology in Organic Synthesis; Academic: Orlando, 1987. (b) Weinreb, S. M. Acc. Chem. Res. 1985, 18, 16. (c) Birkinshaw, T. N.; Tabor, A. B.; Holmes, A. B.; Kaye, P.; Mayne, P. M.; Raithby, P. R. J. Chem. Soc., Chem. Commun. 1988, 1599. (405) Kobayashi, S.; Ishitani, H.; Nagayama, S. Chem. Lett. 1995, 423. (406) Kobayashi, S.; Ishitani, H.; Nagayama, S. Synthesis 1995, 1195. (407) Sasaki, T.; Ishibashi, Y.; Ohno, M. Chem. Lett. 1983, 12, 863. (408) Zhang, W.; Xie, W.; Fang, J.; Wang, P. G. Tetrahedron Lett. 1999, 40, 7929. (409) Chou, S.-S. P.; Hung, C.-C. Synth. Commun. 2001, 31, 1097. (410) Chou, S.-S. P.; Chen, K.-W. Synth. Commun. 2004, 34, 4573. (411) Lucchini, V.; Prato, M.; Scorrano, G.; Tecilla, P. J. Org. Chem. 1988, 53, 2251. (412) Lucchini, V.; Prato, M.; Quintily, U.; Scorrano, G. J. Chem. Soc., Chem. Commun. 1984, 48. (413) (a) Zhang, J. J.; Chang, C. W. T. J. Org. Chem. 2009, 74, 4414. (b) Cocco, M. T.; Congiu, C.; Lilliu, V.; Onnis, V. Eur. J. Med. Chem. 2005, 40, 1365. (c) Guo, K.; Mutter, R.; Heal, W.; Reddy, T. R. K.; Cope, H.; Pratt, S.; Thompson, M. J.; Chen, B. N. Eur. J. Med. Chem. 2008, 43, 93. (d) Ma, X.; Gang, D. R. Nat. Prod. Rep. 2004, 21, 752. (414) Fredholm, B. B.; Ijzerman, A. P.; Jacobson, K. A.; Klotz, K.-N.; Linden, J. Pharmacol. Rev. 2001, 53, 527. (415) Levy, S. B.; Alekshun, M. N.; Podlogar, B. L.; Ohemeng, K.; Verma, A. K.; Warchol, T.; Bhatia, B.; Boowser, T.; Grier, M. U.S. Pat. Appl., US2005124678, A1, 2005. (416) Khadikar, B.; Borkat, S. Synth. Commun. 1998, 28, 207. (417) Harada, H.; Watanuki, S.; Takuwa, T.; Kawaguchi, K.; Okazaki, T.; Hirano, Y.; Saitoh, C. PCT Int. Appl., WO2002006237 Al, 2002. (418) Chang, L. C. W.; Von Frijtag Drabbe Künzel, J. K.; MulderKrieger, T.; Spanjersberg, R. F.; Roerink, S. F.; van den Hout, G.; Beukers, M. W.; Brussee, J.; Ijzerman, A. P. J. Med. Chem. 2005, 48, 2045. (419) Beukers, M. W.; Chang, L. C. W.; Von Frijtag Drabbe Künzel, J. K.; Mulder-Krieger, T.; Spanjersberg, R. F.; Brussee, J.; Ijzerman, A. P. J. Med. Chem. 2004, 47, 3707. (420) (a) Newkome, G. R.; Patri, A. K.; Holder, E.; Schubert, U. S. Eur. J. Org. Chem. 2004, 235. (b) Wang, P.; Moorefield, C. N.; Newkome, G. R. Angew. Chem., Int. Ed. 2005, 44, 1679. (c) Newkome, G. R.; Wang, P. C.; Moorefield, N.; Cho, T. J.; Mohapatra, P. P.; Li, S.; Hwang, S.-H.; Lukoyanova, O.; Echegoyen, L.; Palagallo, J. A.; Iancu, V.; Hla, S.-W. Science 2006, 312, 1782. (421) (a) Fletcher, M. D.; Hurst, T. E.; Miles, T. J.; Moody, C. J. Tetrahedron 2006, 62, 5454. (b) Evdokimov, N. M.; Magedov, I. V.; Kireev, A. S.; Kornienko, A. Org. Lett. 2006, 8, 899. (c) Movassaghi, M.; Hill, M. D. J. Am. Chem. Soc. 2006, 128, 4592. (d) Tanaka, K.; Mori, H.; Yamamoto, M.; Katsumara, S. J. Org. Chem. 2001, 66, 3099. (e) Renslo, A. R.; Danheiser, R. L. J. Org. Chem. 1998, 63, 7840. (f) Hill, M. D. Chem.Eur. J. 2010, 16, 12052. (g) Lipson, V. V.; Gorobets, N. Y. Mol. Diversity 2009, 13, 399. (h) Varela, J. A.; Saá, C. Chem. Rev. 2003, 103, 3787. BX


Chemical Reviews

Review

(422) (a) Wang, B.; Hu, Y.; Hu, H. Synth. Commun. 1999, 29, 4193. (b) Anniyappam, M.; Muralidharan, D.; Perumal, P. T. Tetrahedron 2002, 58, 5069. (c) Heravi, M. M.; Derikvand, F.; Hassan-Pour, S.; Bakhtiari, K.; Bamoharram, F. F.; Oskooie, H. A. Bioorg. Med. Chem. Lett. 2007, 17, 3305. (d) Bagley, M. C.; Lubinu, M. C. Synthesis 2006, 1283. (e) Shahabi, D.; Amrollahi, M. A.; Jafari, A. A. J. Iran. Chem. Soc. 2011, 8, 1052. (f) Hashemi, M. M.; Ahmadi Beni, Y.; Ghafuri, H. Monatsh. Chem. 2003, 134, 107. (423) (a) Evdokimov., N. M.; Magedov, I. V.; Kireev, A. S.; Kornienko, A. Org. Lett. 2006, 8, 899. (b) Ranu, B. C.; Jana, R.; Sowmiah, S. J. Org. Chem. 2007, 72, 3152. (c) Evdokimov, N. M.; Kireev, A. S.; Yakovenko, A. A.; Antipin, M. Y.; Magedov, I. V.; Kornienko, A. J. Org. Chem. 2007, 72, 3443. (d) Guo, K.; Thompson, M. J.; Reddy, T. R. K.; Mutter, R.; Chen, B. Tetrahedron 2007, 63, 5300. (e) Mamgain, R.; Singh, R.; Rawat, D. S. J. Heterocycl. Chem. 2009, 46, 69. (f) Guo, K.; Thompson, M. J.; Chen, B. J. Org. Chem. 2009, 74, 6999. (g) Das, B.; Ravikanth, B.; Kumar, A. S.; Kanth, B. S. J. Heterocycl. Chem. 2009, 46, 1208. (h) Shinde, P. V.; Sonar, S. S.; Shingate, B. B.; Shingare, M. S. Tetrahedron Lett. 2010, 51, 1309. (424) (a) Mukhopadhyay, C.; Tapaswi, P. K.; Butcher, R. J. Tetrahedron Lett. 2010, 51, 1797. (b) Nagarapu, L.; Aneesa; Peddiraju, R.; Apuri, S. Catal. Commun. 2007, 8, 1973. (c) Smith, C. B.; Raston, C. L.; Sobolev, A. N. Green Chem. 2005, 7, 650. (d) Adib, M.; Tahermansouri, H.; Koloogani, S. A.; Mohammadi, B.; Bijanzadeh, H. R. Tetrahedron Lett. 2006, 47, 5957. (425) (a) Xiong, X.; Bagley, M. C.; Chapaneri, K. Tetrahedron Lett. 2004, 45, 6121. (b) Bagley, M. C.; Lunn, R.; Xiong, X. Tetrahedron Lett. 2002, 43, 8331. (426) Diring, S.; Retailleau, P.; Ziessel, R. Tetrahedron Lett. 2007, 48, 8069. (427) Pabst, G. R.; Sauer, J. Tetrahedron Lett. 1998, 39, 6687. (428) Pabst, G. R.; Sauer, J. Tetrahedron Lett. 1998, 39, 8817. (429) (a) Kozhevnikov, V. N.; Kozhevnikov, D. N.; Shabunina, O. V.; Rusinov, V. L.; Chupakhin, O. N. Tetrahedron Lett. 2005, 46, 1791. (b) Kozhevnikov, V. N.; Shabunina, O. V.; Kopchuk, D. S.; Ustinova, M. M.; König, B.; Kozhevnikov, D. N. Tetrahedron 2008, 64, 8963. (430) Sagi, M.; Amano, M.; Konno, S.; Yamanaka, H. Heterocycles 1989, 29, 2249. (431) Hajbi, Y.; Suzenet, F.; Khouili, M.; Lazar, S.; Guillaumet, G. Tetrahedron 2007, 63, 8286. (432) Taylor, E. C.; Macor, J. E. Tetrahedron Lett. 1986, 27, 431. (433) Taylor, E. C.; Macor, J. E.; French, L. G. J. Org. Chem. 1991, 56, 1807. (434) Lahue, B. R.; Lo, S.-M.; Wan, Z.-K.; Woo, G. H. C.; Snyder, J. K. J. Org. Chem. 2004, 69, 7171. (435) (a) Michael, J. P. Nat. Prod. Rep. 2008, 25, 166. (b) Bazin, M.; Kuhn, C. J. Comb. Chem. 2005, 7, 302. (c) Michael, J. P. Nat. Prod. Rep. 2004, 21, 650. (d) Michael, J. P. Nat. Prod. Rep. 2007, 24, 223. (436) (a) Chen, Y.-L.; Fang, K.-C.; Sheu, J.-Y.; Hsu, S.-L.; Tzeng, C.C. J. Med. Chem. 2001, 44, 2374. (b) Chauhan, P. M. S.; Srivastava, S. K. Curr. Med. Chem. 2001, 8, 1535. (c) Asolkar, R. N.; Schröder, D.; Heckmann, R.; Lang, S.; Wagner-Döbler, I.; Laatsch, H. J. Antibiot. 2004, 57, 17. (d) Jacquemond-Collet, I.; Benoit-Vical, F.; Valentin, M.; Stanislas, A.; Mallié, E.; Fourasté, I. Planta Med. 2002, 68, 68. (e) Ferrarini, P. L.; Mori, C.; Badawneh, M.; Calderone, V.; Greco, R.; Manera, C.; Martinelli, A.; Nieri, P.; Saccomanni, G. Eur. J. Med. Chem. 2000, 35, 815. (f) Roma, G.; Braccio, M. D.; Grossi, G.; Mattioli, F.; Ghia, M. Eur. J. Med. Chem. 2000, 35, 1021. (g) Dua, V. K.; Sinha, S. N.; Biswas, S.; Valecha, N.; Puri, S. K.; Sharma, V. P. Bioorg. Med. Chem. Lett. 2002, 12, 3587. (h) Gallo, S.; Atifi, S.; Mahamoud, A.; Santelli-Rouvier, C.; Wolfárt, K.; Molnar, J.; Barbe, J. Eur. J. Med. Chem. 2003, 38, 19. (i) Strekowski, L.; Say, M.; Henary, M.; Ruiz, P.; Manzel, L.; Macfarlane, D. E.; Bojarski, A. J. J. Med. Chem. 2003, 46, 1242. (j) Ries, U. J.; Priepke, H. W. M.; Hauel, N. H.; Haaksma, E. E. J.; Stassen, J. M.; Wienen, W.; Nar, H. Bioorg. Med. Chem. Lett. 2003, 13, 2291. (k) Bi, Y.; Stoy, P.; Adam, L.; He, B.; Krupinski, J.; Normandin, D.; Pongrac, R.; Seliger, L.; Watson, A.; Macor, J. E. Bioorg. Med. Chem. Lett. 2004, 14, 1577. (l) Sawada, Y.; Kayakiri, H.; Abe, Y.; Imai, K.; Mizutani, T.; Inamura, N.; Asano, M.; Aramori, I.;

Hatori, C.; Katayama, A.; Oku, T.; Tanaka, H. J. Med. Chem. 2004, 47, 1617. (437) (a) Yearick, K.; Ekoue-Kovi, K.; Iwaniuk, D. P.; Natarajan, J. K.; Alumasa, J.; de Dios, A. C.; Roepe, P. D.; Wolf, C. J. Med. Chem. 2008, 51, 1995. (b) Ramesh, E.; Manian, R. D. R. S.; Raghunathan, R.; Sainath, S.; Raghunathan, M. Bioorg. Med. Chem. 2009, 17, 660. (438) Gholap, A. R.; Toti, K. S.; Shirazi, F.; Kumari, R.; Bhat, M. K.; Deshpande, M. V.; Srinivasan, K. V. Bioorg. Med. Chem. 2007, 15, 6705. (439) Smith, H. C.; Cavanaugh, C. K.; Friz, J. L.; Thompson, C. S.; Saggers, J. A.; Michelotti, E. L.; Garcia, J.; Tice, C. M. Bioorg. Med. Chem. Lett. 2003, 13, 1943. (440) (a) Samosorn, S.; Bremner, J. B.; Ball, A.; Lewis, K. Bioorg. Med. Chem. 2006, 14, 857. (b) Foley, M.; Tilley, L. Pharmacol. Ther. 1998, 79, 55. (c) Gupta, M. K.; Prabhakar, Y. S. Eur. J. Med. Chem. 2008, 43, 2751. (441) Dorey, G.; Lockhart, B.; Lestage, P.; Casara, P. Bioorg. Med. Chem. Lett. 2000, 10, 935. (442) (a) Beadle, C. D.; Boot, J.; Camp, N. P.; Dezutter, N.; Findlay, J.; Hayhurst, L.; Masters, J. J.; Penariol, R.; Walter, M. W. Bioorg. Med. Chem. Lett. 2005, 15, 4432. (b) Berenguer, I.; El Aouad, N.; Andujar, S.; Romero, V.; Suvire, F.; Freret, T.; Bermejo, A.; Ivorra, M. D.; Enriz, R. D.; Boulouard, M.; Cabedo, N.; Cortes, D. Bioorg. Med. Chem. 2009, 17, 4968. (443) (a) Di Fabio, R.; Alvaro, G.; Bertani, B.; Donati, D.; Pizzi, D. M.; Gentile, G.; Pentassuglia, G.; Giacobbe, S.; Spada, S.; Ratti, E.; Corsi, M.; Quartaroli, M.; Barnaby, R. J.; Vitulli, G. Bioorg. Med. Chem. Lett. 2007, 17, 1176. (b) Barbay, J. K.; Gong, Y.; Buntinx, M.; Li, J.; Claes, C.; Hornby, P. J.; Van Lommen, G.; VanWauwe, J.; He, W. Bioorg. Med. Chem. Lett. 2008, 18, 2544. (c) Chen, M.-H.; Fitzgerald, P.; Singh, S. B.; O’Neill, E. A.; Schwartz, C. D.; Thompson, C. M.; O’Keefe, S. J.; Zaller, D. M.; Doherty, J. B. Bioorg. Med. Chem. Lett. 2008, 18, 2222. (444) Parmenon, C.; Guillard, J.; Caignard, D.-H.; Hennuyer, N.; Staels, B.; Audinot-Bouchez, V.; Boutin, J.-A.; Dacquet, C.; Ktorza, A.; Viaud-Massuard, M.-C. Bioorg. Med. Chem. Lett. 2008, 18, 1617. (445) (a) Weinreb, S. M. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, U.K., 1991; Vol. 5, p 401. (b) Babu, G.; Perumal, P. T. Aldrichimica Acta 2000, 33, 16. (c) Stevenson, P. J.; Nieuwenhuyzen, M.; Osborne, D. Chem. Commun. 2002, 444. (d) Sundararajan, G.; Prabagaran, N.; Varghese, B. Org. Lett. 2001, 3, 1973. (e) Xia, C.; Heng, L.; Ma, D. Tetrahedron Lett. 2002, 43, 9405. (f) Katritzky, A. R.; Belyakov, S. A. Aldrichimica Acta 1998, 31, 35. (g) Fache, F. Synlett 2004, 2827. (h) Fujita, K.-i.; Kitatsuji, C.; Furukawa, S.; Yamaguchi, R. Tetrahedron Lett. 2004, 45, 3215. (i) Lu, S.-M.; Wang, Y.-Q.; Han, X.-W.; Zhou, Y.G. Angew. Chem., Int. Ed. 2006, 45, 2260. (j) Rueping, M.; Antonchick, A. P.; Theissmann, T. Angew. Chem., Int. Ed. 2006, 45, 3683. (k) Wang, C.; Li, C.; Wu, X.; Pettman, A.; Xiao, J. Angew. Chem., Int. Ed. 2009, 48, 6524. (l) Buonora, P.; Olsen, J.-C.; Oh, T. Tetrahedron 2001, 57, 6099. (m) Talukdar, S.; Chen, C.-T.; Fang, J.-M. J. Org. Chem. 2000, 65, 3148. (n) Theeraladanon, C.; Arisawa, M.; Nishida, A.; Nakagawa, M. Tetrahedron 2004, 60, 3017 and references cited therein. (o) Akiyama, T.; Morita, H.; Fuchibe, K. J. Am. Chem. Soc. 2006, 128, 13070. (p) Liu, H.; Dagousset, G.; Masson, G.; Retailleau, P.; Zhu, J. J. Am. Chem. Soc. 2008, 131, 4598. (q) He, L.; Bekkaye, M.; Retailleau, P.; Masson, G. Org. Lett. 2012, 14, 3158. (r) Dagousset, G.; Zhu, J.; Masson, G. J. Am. Chem. Soc. 2011, 133, 14804. (s) Martínez, R.; Ramón, D. J.; Yus, M. J. Org. Chem. 2008, 73, 9778. (t) Palimkar, S. S.; Siddiqui, S. A.; Daniel, T.; Lahoti, R. J.; Srinivasan, K. V. J. Org. Chem. 2003, 68, 9371. (u) Dormer, P. G.; Eng, K. K.; Farr, R. N.; Humphrey, G. H.; McWilliams, J. C.; Reider, P. J.; Sager, J. W.; Volante, R. P. J. Org. Chem. 2003, 68, 467. (v) Patil, N. T.; Raut, V. S. J. Org. Chem. 2010, 75, 6961. (w) Korivi, R. P.; Cheng, C.-H. J. Org. Chem. 2006, 71, 7079. (x) Volochnyuk, D. M.; Ryabukhin, S. V.; Plaskon, A. S.; Dmytriv, U. Y.; Grygorenko, O. O.; Mykhailiuk, P. K.; Krotko, D. G.; Pushechnikov, A.; Tolmachev, A. A. J. Comb. Chem. 2010, 12, 510. (y) Bergstrom, F. W. Chem. Rev. 1944, 35, 77. BY


Chemical Reviews

Review

(j) Czarnocki, S. J.; Wojtasiewicz, K.; Józw ́ iak, A. P.; Maurin, J. K.; Czarnocki, Z.; Drabowicz, J. Tetrahedron 2008, 64, 3176. (k) Shankaraiah, N.; da Silva, W. A.; Andrade, C. K. Z.; Santos, L. S. Tetrahedron Lett. 2008, 49, 4289. (465) (a) Cox, E. D.; Cook, J. M. Chem. Rev. 1995, 95, 1797 and references cited therein. (b) Royer, J.; Bonin, M.; Micouin, L. Chem. Rev. 2004, 104, 2311. (c) Nakagawa, M. J. Heterocycl. Chem. 2000, 37, 567. (d) Vinu, A.; Kalita, P.; Samie, L.; Chari, M. A.; Pal, R.; Subba Reddy, B. V. Tetrahedron Lett. 2010, 51, 702. (e) Semenov, B. B.; Novikov, K. A.; Spitsin, A. N.; Azev, V. N.; Kachala, V. V. Chem. Nat. Compd. 2004, 40, 585. (f) Herrera, R. P.; Sgarzani, V.; Bernardi, L.; Ricci, A. Angew. Chem., Int. Ed. 2005, 44, 6576. (g) Semenov, B. B.; Novikov, K. A.; Smushkevich, Yu. I.; Azev, V. N.; Kachala, V. V. Chem. Heterocycl. Compd. 2005, 41, 1273. (h) Kuwada, T.; Fukui, M.; Hata, T.; Choshi, T.; Nobuhiro, J.; Ono, Y.; Hibino, S. Chem. Pharm. Bull. 2003, 51, 20. (i) Choshi, T.; Kuwada, T.; Fukui, M.; Matsuya, Y.; Sugino, E.; Hibino, S. Chem. Pharm. Bull. 2000, 48, 108. (j) Kuwada, T.; Fukui, M.; Hirayama, M.; Nobuhiro, J.; Choshi, T.; Hibino, S. Heterocycles 2002, 58, 325. (k) Dantale, S. W.; Söderberg, B. C. G. Tetrahedron 2003, 59, 5507. (l) Baruah, B.; Dasu, K.; Vaitilingam, B.; Mamnoor, P.; Venkata, P. P.; Rajagopal, S.; Yeleswarapu, K. R. Bioorg. Med. Chem. 2004, 12, 1991. (m) Iwadate, M.; Yamashita, T.; Tokuyama, H.; Fukuyama, T. Heterocycles 2005, 66, 241. (n) Zhou, H.; Liao, X.; Cook, J. M. Org. Lett. 2004, 6, 249. (o) Liu, C.; Masuno, M. N.; Mac Millan, J. B.; Molinski, T. F. Angew. Chem., Int. Ed. 2004, 43, 5951. (p) Yu, J.; Wearing, X. Z.; Cook, J. M. J. Org. Chem. 2005, 70, 3963. (q) Zhang, H.; Larock, R. C. J. Org. Chem. 2002, 67, 7048. (r) Ding, S.; Shi, Z.; Jiao, N. Org. Lett. 2010, 12, 1540. (s) Zhang, H.; Larock, R. C. Org. Lett. 2001, 3, 3083. (466) Yang, M.-L.; Kuo, P.-C.; Damu, A. G.; Chang, R.-J.; Chiou, W.F.; Wu, T.-S. Tetrahedron 2006, 62, 10900. (467) Kulkarni, A.; Abid, M.; Török, B.; Huang, X. Tetrahedron Lett. 2009, 50, 1791. (468) Molina, P.; Fresneda, P. M.; García-Zafra, S.; Almendros, P. Tetrahedron Lett. 1994, 35, 8851. (469) Benson, S. C.; Gross, J. L.; Snyder, J. K. J. Org. Chem. 1990, 55, 3257. (470) Benson, S. C.; Li, J.-H.; Snyder, J. K. J. Org. Chem. 1992, 57, 5285. (471) (a) Rohet, F.; Rubat, C.; Coudert, P.; Couquelet, J. Bioorg. Med. Chem. 1997, 5, 655. (b) Tucker, J. A.; Allwine, D. A.; Grega, K. C.; Barbachyn, M. R.; Klock, J. L.; Adamski, J. L.; Brickner, S. J.; Hutchinson, D. K.; Ford, C. W.; Zurenko, G. E.; Conradi, R. A.; Burton, P. S.; Jensen, R. M. J. Med. Chem. 1998, 41, 3727. (c) Tamayo, N.; Liao, L.; Goldberg, M.; Powers, D.; Tudor, Y.-Y.; Yu, V.; Wong, L. M.; Henkle, B.; Middleton, S.; Syed, R.; Harvey, T.; Jang, G.; Hungate, R.; Dominguez, C. Bioorg. Med. Chem. Lett. 2005, 15, 2409. (472) (a) Heinisch, G.; Kopelent-Franck, H. In Progress in Medicinal Chemistry; Ellis, G. P., Luscombe, D. K., Eds; Elsevier: Amsterdam, 1992; Vol. 29; pp 141−183. (b) Contreras, J.-M.; Rival, Y. M.; Chayer, S.; Bourguignon, J.-J.; Wermuth, C. G. J. Med. Chem. 1999, 42, 730. (c) Wermuth, C. G.; Schlewer, G.; Bourguignon, J.-J.; Maghioros, G.; Bouchet, M.-J.; Moire, C.; Kan, J.-P.; Worms, P.; Biziere, K. J. Med. Chem. 1989, 32, 528. (d) Tišler, M.; Stanovnik, B. Adv. Heterocycl. Chem. 1990, 49, 385. (e) Melikian, A.; Schlewer, G.; Chambon, J. P.; Wermuth, C. G. J. Med. Chem. 1992, 35, 4092. (f) Gelain, A. J. Heterocycl. Chem. 2005, 42, 395. (473) (a) Coates, W. J. Pyridazines and their Benzo Derivatives. In Comprehensive Heterocyclic Chemistry II; Katritzky, A. R., Rees, C. W., Scriven, E. F. V., Eds.; Pergamon: Oxford, U.K., 1996; Vol. 6, pp 1−91. (b) Kolar, P.; Tišler, M. Adv. Heterocycl. Chem. 1999, 75, 167. (c) Mátyus, P.; Maes, B. U. W.; Riedl, Z.; Hajós, G.; Lemière, G. L. F.; Tapolcsányi, P.; Monsieurs, K.; Eliás, O.; Dommisse, R. A.; Krajsovszky, G. Synlett 2004, 1123. (d) Groziak, M. P. In Progress in Heterocyclic Chemistry; Gribble, G. W., Joule, J. A., Eds.; Elsevier: Amsterdam, 2005; Vol. 17, pp 304−336. (e) Naud, S.; Pipelier, M.; Viault, G.; Adjou, A.; Huet, F.; Legoupy, S.; Aubertin, A.-M.; Evain, M.; Dubreuil, D. Eur. J. Org. Chem. 2007, 3296.

(446) Magesh, C. J.; Makesh, S. V.; Perumal, P. T. Bioorg. Med. Chem. Lett. 2004, 14, 2035. (447) Nagarajan, R.; Chitra, S.; Perumal, P. T. Tetrahedron 2001, 57, 3419. (448) Kumar, R. S.; Nagarajan, R.; Perumal, P. T. Synthesis 2004, 949. (449) Kobayashi, S.; Nagayama, S. J. Org. Chem. 1996, 61, 2256. (450) Alonso, D. A.; Bertilsson, S. K.; Johnsson, S. Y.; Nordin, S. J. M.; Södergren, M. J.; Andersson, P. G. J. Org. Chem. 1999, 64, 2276. (451) Tarantin, A. V.; Glushkov, V. A.; Suponitskii, K. Y.; Kudryashov, A. A.; Maiorova, O. A.; Tolstikov, A. G. Russ. J. Org. Chem. 2010, 46, 1479. (452) Saggiomo, A. J.; Kano, S.; Kikuchi, T.; Okubo, K.; Shinbo, M. J. Med. Chem. 1972, 15, 989. (453) Ziegler, E.; Kappe, Th.; Foraita, H. G. Monatsh. Chem. 1966, 97, 409. (454) (a) Croisy-Delcey, M.; Croisy, A.; Carrez, D.; Huel, C.; Chiaroni, A.; Ducrot, P.; Bisagni, E.; Jin, L.; Leclercq, G. Bioorg. Med. Chem. 2000, 8, 2629. (b) Kohlhagen, G.; Paull, K. D.; Cushman, M.; Nagafuji, P.; Pommier, Y. Mol. Pharmacol. 1998, 54, 50. (455) Bentley, K. W. The Isoquinoline Alkaloids; Harwood Academic Publishers: Australia, 1998; Vol. 1. (456) (a) Dai, G.; Larock, R. C. J. Org. Chem. 2002, 67, 7042. (b) Huang, Q.; Hunter, J. A.; Larock, R. C. J. Org. Chem. 2002, 67, 3437 and references therein. (c) Roesch, K. R.; Larock, R. C. J. Org. Chem. 2002, 67, 86. (d) Dai, G.; Larock, R. C. Org. Lett. 2001, 3, 4035. (e) Vanden Eynden, M. J.; Kunchithapatham, K.; Stambuli, J. P. J. Org. Chem. 2010, 75, 8542. (f) Yokoyama, A.; Ohwada, T.; Shudo, K. J. Org. Chem. 1999, 64, 611. (g) Kane, T. R.; Ly, C. Q.; Kelly, D. E.; Dener, J. M. J. Comb. Chem. 2004, 6, 564. (h) Larsen, R. D.; Reamer, R. A.; Corley, E. G.; Davis, P.; Grabowski, E. J. J.; Reider, P. J.; Shinkai, I. J. Org. Chem. 1991, 56, 6034. (i) Awuah, E.; Capretta, A. J. Org. Chem. 2010, 75, 5627. (j) Wang, B.; Lu, B.; Jiang, Y.; Zhang, Y.; Ma, D. Org. Lett. 2008, 10, 2761. (k) Niu, Y.-N.; Yan, Z.-Y.; Gao, G.-L.; Wang, H.-L.; Shu, X.-Z.; Ji, K.-G.; Liang, Y.-M. J. Org. Chem. 2009, 74, 2893. (l) Fischer, D.; Tomeba, H.; Pahadi, N. K.; Patil, N. T.; Huo, Z.; Yamamoto, Y. J. Am. Chem. Soc. 2008, 130, 15720. (457) Nimgirawath, S.; Kaewket, S. J. Sci. Soc. Thailand 1982, 8, 167. (458) Gilchrist, T. L.; d’A. Rocha Gonsalves, A. M.; Pinho e Melo, T. M. V. D. Tetrahedron Lett. 1993, 34, 4097. (459) (a) Ulven, T.; Kostenis, E. J. Med. Chem. 2005, 48, 897. (b) Schott, Y.; Decker, M.; Rommelspacher, H.; Lehmann, J. Bioorg. Med. Chem. Lett. 2006, 16, 5840. (c) Bentley, K. W. Nat. Prod. Rep. 2001, 18, 148. (460) (a) Formagio, A. S. N.; Tonin, L. T. D.; Foglio, M. A.; Madjarof, C.; de Carvalho, J. E.; da Costa, W. F.; Cardoso, F. P.; Sarragiotto, M. H. Bioorg. Med. Chem. 2008, 16, 9660. (b) Savariz, F. C.; Formagio, A. S. N.; Barbosa, V. A.; Foglio, M. A.; de Carvalho, J. E.; Duarte, M. C. T.; Filho, B. P. D.; Sarragiotto, M. H. J. Braz. Chem. Soc. 2010, 21, 288. (461) Tang, J.-G.; Liu, H.; Zhou, Z.-Y.; Liu, J.-K. Synth. Commun. 2010, 40, 1411 and references cited therein.. (462) (a) Herraiz, T.; Galisteo, J.; Chamorro, C. J. Agric. Food Chem. 2003, 51, 2168. (b) Herraiz, T.; Galisteo, J. J. Agric. Food Chem. 2003, 51, 7156. (c) Bi, W.; Bi, L.; Cai, J.; Liu, S.; Peng, S.; Fischer, N. O.; Tok, J. B.-H.; Wang, G. Bioorg. Med. Chem. Lett. 2006, 16, 4523. (463) (a) Ishida, J.; Wang, H.-K.; Bastow, K. F.; Hu, C.-Q.; Lee, K.H. Bioorg. Med. Chem. Lett. 1999, 9, 3319. (b) Ishida, J.; Wang, H.-K.; Oyama, M.; Cosentino, M. L.; Hu, C. Q.; Lee, K.-H. J. Nat. Prod. 2001, 64, 958. (464) (a) Liu, C.; Masuno, M. N.; MacMillan, J. B.; Molinski, T. F. Angew. Chem., Int. Ed. 2004, 43, 5951. (b) Yamashita, T.; Kawai, N.; Tokuyama, H.; Fukuyama, T. J. Am. Chem. Soc. 2005, 127, 15038. (c) Yu, J.; Wearing, X. Z.; Cook, J. M. J. Org. Chem. 2005, 70, 3963. (d) Zhou, H.; Liao, X.; Yin, W.; Ma, J.; Cook, J. M. J. Org. Chem. 2006, 71, 251. (e) Ma, J.; Yin, W.; Zhou, H.; Cook, J. M. Org. Lett. 2007, 9, 3491. (f) Mergott, D. J.; Zuend, S. J.; Jacobsen, E. N. Org. Lett. 2008, 10, 745. (g) Martin, S. F.; Chen, K. X.; Eary, C. T. Org. Lett. 1999, 1, 79. (h) Neipp, C. E.; Martin, S. F. J. Org. Chem. 2003, 68, 8867. (i) Ohba, M.; Natsutani, I.; Sakuma, T. Tetrahedron 2007, 63, 10337. BZ


Chemical Reviews

Review

(494) (a) Kappe, C. O. Eur. J. Med. Chem. 2000, 35, 1043. (b) Singh, K.; Arora, D.; Singh, K.; Singh, S. Mini-Rev. Med. Chem. 2009, 9, 95. (495) Vanelle, P.; Maldonado, J.; Crozet, M. P.; Senouki, K.; Delmas, F.; Gasquet, M.; Timon-David, P. Eur. J. Med. Chem. 1991, 26, 709. (496) Bisceglia, J. Á .; García, M. B.; Massa, R.; Magri, M. L.; Zani, M.; Gutkind, G. O.; Orelli, L. R. J. Heterocycl. Chem. 2004, 41, 85. (497) Atwal, K. S.; Swanson, B. N.; Unger, S. E.; Floyd, D. M.; Moreland, S.; Hedberg, A.; O’Reilly, B. C. J. Med. Chem. 1991, 34, 806. (498) (a) Mayer, T. U.; Kapoor, T. M.; Haggarty, S. J.; King, R. W.; Schreiber, S. L.; Mitchison, T. J. Science 1999, 286, 971. (b) Maliga, Z.; Kapoor, T. M.; Mitchison, T. J. Chem. Biol. 2002, 9, 989. (c) DeBonis, S.; Simorre, J.-P.; Crevel, I.; Lebeau, L.; Skoufias, D. A.; Blangy, A.; Ebel, C.; Gans, P.; Cross, R.; Hackney, D. D.; Wade, R. H.; Kozielski, F. Biochemistry 2003, 42, 338. (499) Barrow, J. C.; Nantermet, P. G.; Selnick, H. G.; Glass, K. L.; Rittle, K. E.; Gilbert, K. F.; Steele, T. G.; Homnick, C. F.; Freidinger, R. M.; Ransom, R. W.; Kling, P.; Reiss, D.; Broten, T. P.; Schorn, T. W.; Chang, R. S. L.; O’Malley, S. S.; Olah, T. V.; Ellis, J. D.; Barrish, A.; Kassahun, K.; Leppert, P.; Nagarathnam, D.; Forray, C. J. Med. Chem. 2000, 43, 2703. (500) Deres, K.; Schröder, C. H.; Paessens, A.; Goldmann, S.; Hacker, H. J.; Weber, O.; Krämer, T.; Niewöhner, U.; Pleiss, U.; Stoltefuss, J.; Graef, E.; Koletzki, D.; Masantschek, R. N. A.; Reimann, A.; Jaeger, R.; Groβ, R.; Beckermann, B.; Schlemmer, K.-H.; Haebich, D.; Rübsamen-Waigmann, H. Science 2003, 299, 893. (501) (a) Suzuki, T.; Kubota, T.; Kobayashi, J. Bioorg. Med. Chem. Lett. 2011, 21, 4220. (b) Guggisberg, A.; Drandarov, K.; Hesse, M. Helv. Chim. Acta 2000, 83, 3035. (c) Drandarov, K.; Guggisberg, A.; Hesse, M. Helv. Chim. Acta 1999, 82, 229. (502) (a) Chantrapromma, K.; Ganem, B. Tetrahedron Lett. 1981, 22, 23. (b) Perillo, I. A.; García, M. B.; Bisceglia, J. Á .; Orelli, L. R. J. Heterocycl. Chem. 2002, 39, 655. (c) Katritzky, A. R.; Singh, S. K.; He, H.-Y. J. Org. Chem. 2002, 67, 3115. (d) Mayr, M.; Wurst, K.; Ongania, K.-H.; Buchmeiser, M. R. Chem.Eur. J. 2004, 10, 1256. (e) Díaz, J. E.; Bisceglia, J. Á .; Mollo, M. C.; Orelli, L. R. Tetrahedron Lett. 2011, 52, 1895. (f) Wei, H.-L.; Yan, Z.-Y.; Niu, Y.-N.; Li, G.-Q.; Liang, Y.-M. J. Org. Chem. 2007, 72, 8600. (g) Axenrod, T.; Sun, J.; Das, K. K.; Dave, P. R.; Forohar, F.; Kaselj, M.; Trivedi, N. J.; Gilardi, R. D.; Flippen-Anderson, J. L. J. Org. Chem. 2000, 65, 1200. (h) Tingley, R.; Peori, M. B.; Church, R.; Vaughan, K. Can. J. Chem. 2005, 83, 1799. (503) (a) Dallinger, D.; Kappe, C. O. Pure Appl. Chem. 2005, 77, 155. (b) Singh, K.; Singh, S.; Mahajan, A. J. Org. Chem. 2005, 70, 6114. (c) Matloobi, M.; Kappe, C. O. J. Comb. Chem. 2007, 9, 275. (d) Salehi, P.; Dabiri, M.; Khosropour, A. R.; Roozbehniya, P. J. Iran. Chem. Soc. 2006, 3, 98. (e) Pourjavadi, A.; Salimi, H.; Barzegar, S.; Eftekhari-Sis, B. Acta Chim. Slov. 2007, 54, 140. (504) Mibu, N.; Yukawa, M.; Kashige, N.; Iwase, Y.; Goto, Y.; Miake, F.; Yamaguchi, T.; Ito, S.; Sumoto, K. Chem. Pharm. Bull. 2003, 51, 27. (505) Hepperle, M.; Eckert, J.; Gala, D. Tetrahedron Lett. 1999, 40, 5655. (506) Giannangeli, M.; Cazzolla, N.; Luparini, M. R.; Magnani, M.; Mabilia, M.; Picconi, G.; Tomaselli, M.; Baiocchi, L. J. Med. Chem. 1999, 42, 336. (507) Chambers, M. S.; Street, L. J.; Goodacre, S.; Hobbs, S. C.; Hunt, P.; Jelly, R. A.; Matassa, V. G.; Reeve, A. J.; Sternfeld, F.; Beer, M. S.; Stanton, J. S.; Rathbone, d.; Watt, A. P.; MacLeod, A. M. J. Med. Chem. 1999, 42, 691. (508) Alexopoulos, K.; Fatseas, P.; Melissari, E.; Vlahakos, D.; Smith, J.; Mavromoustakos, T.; Saifeddine, M.; Moore, G.; Hollenberg, M.; Matsoukas, J. Bioorg. Med. Chem. 1999, 7, 1033. (509) Sugihara, H.; Fukushi, H.; Miyawaki, T.; Imai, Y.; Terashita, Z.i.; Kawamura, M.; Fujisawa, Y.; Kita, S. J. Med. Chem. 1998, 41, 489. (510) (a) Manetti, D.; Ghelardini, C.; Bartolini, A.; Bellucci, C.; Dei, S.; Galeotti, N.; Gualtieri, F.; Romanelli, M. N.; Scapecchi, S.; Teodori, E. J. Med. Chem. 2000, 43, 1969. (b) Manetti, D.; Ghelardini, C.; Bartolini, A.; Dei, S.; Galeotti, N.; Gualtieri, F.; Romanelli, M. N.; Teodori, E. J. Med. Chem. 2000, 43, 4499.

(474) (a) Carboni, R. A.; Lindesey, R. V., Jr. J. Am. Chem. Soc. 1959, 81, 4342. (b) Sauer, J.; Heldmann, D. K.; Hetzenegger, J.; Krauthan, J.; Sichert, H.; Schuster, J. Eur. J. Org. Chem. 1998, 2885. (c) Yu, Z.-X.; Dang, Q.; Wu, Y.-D. J. Org. Chem. 2001, 66, 6029. (475) (a) Ö zer, G.; Saraçoğlu, N.; Balci, M. J. Org. Chem. 2003, 68, 7009. (b) González-Goméz, J. C.; Santana, L.; Uriarte, E. Tetrahedron 2005, 61, 4805. (c) Pippich, S.; Bartsch, H. Heterocycles 1996, 43, 1967. (d) Klindert, T.; Seitz, G. Synth. Commun. 1996, 26, 2587. (e) Boger, D. L. Chem. Rev. 1986, 86, 781. (f) Draper, T. L.; Bailey, T. R. J. Org. Chem. 1995, 60, 748. (g) Helm, M. D.; Moore, J. E.; Plant, A.; Harrity, J. P. A. Angew. Chem., Int. Ed. 2005, 44, 3889. (h) Yang, X.; Knochel, P. Org. Lett. 2006, 8, 1941. (i) Hamasaki, A.; Ducray, R.; Boger, D. L. J. Org. Chem. 2006, 71, 185. (j) Akiyama, T.; Morita, H.; Fuchibe, K. J. Am. Chem. Soc. 2006, 128, 13070. (k) Xie, H.; Zu, L.; Oueis, H. R.; Li, H.; Wang, J.; Wang, W. Org. Lett. 2008, 10, 1923. (l) Stehl, A.; Seitz, G.; Schulz, K. Tetrahedron 2002, 58, 1343. (m) Wallace, C. E.; Selegue, J. P.; Carrillo, A. Organometallics 1998, 17, 3390. (n) Cermola, F.; Iesce, M. R.; Buonerba, G. J. Org. Chem. 2005, 70, 6503. (476) Rimaz, M.; Khalafy, J. ARKIVOC 2010, ii, 110. (477) Ismail, K. A.; El-Tombary, A. A.; AboulWafa, O. M.; Omar, A.M. M. E.; El-Rewini, S. H. Arch. Pharm. 1996, 329, 433. (478) Marriner, G. A.; Garner, S. A.; Jang, H.-Y.; Krische, M. J. J. Org. Chem. 2004, 69, 1380. (479) Contreras, J.-M.; Rival, Y. M.; Chayer, S.; Bourguignon, J.-J.; Wermuth, C. G. J. Med. Chem. 1999, 42, 730. (480) Bourotte, M.; Pellegrini, N.; Schmitt, M.; Bourguignon, J.-J. Synlett 2003, 1482. (481) (a) Brown, D. J. In Comprehensive Heterocyclic Chemistry; Katritzky, A. R., Rees, C. W., Eds.; Pergamon Press, Oxford, U.K., 1984; Vol. 3, pp 57−155. (b) Hamilton, G. A. In Progress in Bioorganic Chemistry; Kaiser, E. T., Kezdy, F. J., Eds.; Wiley, New York, 1971, Vol. 1, p 83. (c) Dal Píaz, V.; Ciciani, G.; Giovannoni, M. Synthesis 1994, 669. (d) Wamhoff, H.; Dzenis, J.; Hirota, K. Adv. Heterocycl. Chem. 1992, 55, 129. (e) Mátyus, P. J. Heterocycl. Chem. 1998, 35, 1075. (f) Matyus, P.; Fuji, K.; Tanaka, K. Heterocycles 1993, 36, 1975. (482) Altomare, C.; Cellamare, S.; Summo, L.; Catto, M.; Carotti, A. J. Med. Chem. 1998, 41, 3812. (483) (a) Takeda, K.; Otha, T.; Shudo, K.; Okamoto, T.; Tsuji, T.; Kosuge, T. Chem. Pharm. Bull. 1977, 25, 2145. (b) Akimoto, H.; Kawai, A.; Nomura, H.; Nagao, M.; Kawachi, T.; Sugimura, T. Chem. Lett. 1977, 1061. (c) Murineddu, G.; Cignarella, G.; Chelucci, G.; Loriga, G.; Pinna, G. A. Chem. Pharm. Bull. 2002, 50, 754. (484) Ali, A.; Cablewski, T.; Francis, C. L.; Ganguly, A. K.; Sargent, R. M.; Sawutz, D. G.; Winzenberg, K. N. Bioorg. Med. Chem. Lett. 2011, 21, 4160. (485) Rashad, A. E.; Shamroukh, A. H.; Ali, M. A.; Abdel-Motti, F. M. Heteroat. Chem. 2007, 18, 274. (486) Abbady, M. S.; Radwan, S. M. Phosphorus, Sulfur Silicon Relat. Elem. 1994, 86, 203. (487) (a) Ujjinamatada, R. K.; Paulman, R. L.; Ptak, R. G.; Hosmane, R. S. Bioorg. Med. Chem. 2006, 14, 6359. (b) Pita, B.; Sotelo, E.; Suárez, M.; Raviña, E.; Ochoa, E.; Verdecia, Y.; Novoa, H.; Blaton, N.; de Ranter, C.; Peeters, O. M. Tetrahedron 2000, 56, 2473. (c) Potts, K. T.; Elliott, A. J. J. Org. Chem. 1973, 38, 1769. (d) Mallory, W. R.; Morrison, R. W., Jr.; Styles, V. L. J. Org. Chem. 1982, 47, 667. (488) Morrison, R. W., Jr.; Styles, V. L. J. Org. Chem. 1982, 47, 674. (489) Turbiak, A. J.; Kampf, J. W.; Showalter, H. D. H. Tetrahedron Lett. 2010, 51, 1326. (490) Rimaz, M.; Khalafy, J.; Noroozi Pesyan, N.; Prager, R. H. Aust. J. Chem. 2010, 63, 507. (491) Khalafy, J.; Rimaz, M.; Panahi, L.; Rabiei, H. Bull. Korean Chem. Soc. 2011, 32, 2428. (492) Braña, M. F.; Cacho, M.; García, M. L.; Mayoral, E. P.; López, B.; de Pascual-Teresa, B.; Ramos, A.; Acero, N.; Llinares, F.; MuñozMingarro, D.; Lozach, O.; Meijer, L. J. Med. Chem. 2005, 48, 6843. (493) (a) Atwal, K. S.; Rovnyak, G. C.; O’Reilly, B. C.; Schwartz, J. J. Org. Chem. 1989, 54, 5898. (b) Kappe, C. O.; Fabian, W. M. F.; Semones, M. A. Tetrahedron 1997, 53, 2803. CA


Chemical Reviews

Review

(529) (a) Brown, W. V.; Moore, B. P. Insect Biochem. 1979, 9, 451. (b) Oldham, N. J.; Morgan, E. D. J. Chem. Soc., Perkin Trans. 1 1993, 2713. (530) Hasegawa, M.; Katsumata, T.; Ito, Y.; Saigo, K.; Iitaka, Y. Macromolecules 1988, 21, 3134. (531) (a) Mikuriya, M.; Yoshioka, D.; Handa, M. Coord. Chem. Rev. 2006, 250, 2194. (b) Crutchley, R. J. Angew. Chem., Int. Ed. 2005, 44, 6452. (c) Takamizawa, S.; Kohbara, M.-a. Dalton Trans. 2007, 3640. (d) Caradoc-Davies, P. L.; Hanton, L. R.; Henderson, W. J. Chem. Soc., Dalton Trans. 2001, 2749. (532) (a) Guo, C.; Bhandaru, S.; Fuchs, P. L.; Boyd, M. R. J. Am. Chem. Soc. 1996, 118, 10672. (b) Taber, D. F.; DeMatteo, P. W.; Taluskie, K. V. J. Org. Chem. 2007, 72, 1492. (c) Palacios, F.; de Retana, A. M. O.; Gil, J. I.; de Munain, R. L. Org. Lett. 2002, 4, 2405. (d) Guram, A. S.; Jordan, R. F. J. Org. Chem. 1992, 57, 5994. (e) Liu, W.; Walker, J. A., II; Chen, J. J.; Wise, D. S.; Townsend, L. B. Tetrahedron Lett. 1996, 37, 5325. (f) Buron, F.; Plé, N.; Turck, A.; Queguiner, G. J. Org. Chem. 2005, 70, 2616. (g) Mamane, V.; Aubert, E.; Fort, Y. J. Org. Chem. 2007, 72, 7294. (h) Taber, D. F.; DeMatteo, P. W.; Taluskie, K. V. J. Org. Chem. 2007, 72, 1492. (i) Seggio, A.; Chevallier, F.; Vaultier, M.; Mongin, F. J. Org. Chem. 2007, 72, 6602. (j) Low, M. Y.; Parker, J. K.; Mottram, D. S. J. Agric. Food Chem. 2007, 55, 4087. (k) Aparicio, D.; Attanasi, O. A.; Filippone, P.; Ignacio, R.; Lillini, S.; Mantellini, F.; Palacios, F.; de los Santos, J. M. J. Org. Chem. 2006, 71, 5897. (l) Turck, A.; Plé, N.; Mongin, F.; Quéguiner, G. Tetrahedron 2001, 57, 4489. (m) Sato, N. Compr. Heterocycl. Chem. II 1996, 6, 233. (n) Sato, N. Sci. Synth. 2004, 16, 751 and references therein. (o) Smith, S. C.; Heathcock, C. H. J. Org. Chem. 1992, 57, 6379. (p) Heathcock, C. H.; Smith, S. C. J. Org. Chem. 1994, 59, 6828. (q) Pan, Y.; Merriman, R. L.; Tanzer, L. R.; Fuchs, P. L. Bioorg. Med. Chem. Lett. 1992, 2, 967. (533) Karpetsky, T. P.; White, E. H. J. Org. Chem. 1972, 37, 339. (534) Vogl, O.; Taylor, E. C. J. Am. Chem. Soc. 1959, 81, 2472. (535) Zhang, W.; Haight, A. R.; Ford, K. L.; Parekh, S. I. Synth. Commun. 2001, 31, 725. (536) Haight, A. R.; Bailey, A. E.; Baker, W. S.; Cain, M. H.; Copp, R. R.; DeMattei, J. A.; Ford, K. L.; Henry, R. F.; Hsu, M. C.; Keyes, R. F.; King, S. A.; McLaughlin, M. A.; Melcher, L. M.; Nadler, W. R.; Oliver, P. A.; Parekh, S. I.; Patel, H. H.; Seif, L. S.; Staeger, M. A.; Wayne, G. S.; Wittenberger, S. J.; Zhang, W. Org. Process Res. Dev. 2004, 8, 897. (537) Jaung, J.-Y.; Matsuoka, M.; Fukunishi, K. Dyes Pigm. 1998, 40, 73. (538) Taylor, E. C.; French, L. G. J. Org. Chem. 1989, 54, 1245. (539) (a) Seitz, L. E.; Suling, W. J.; Reynolds, R. C. J. Med. Chem. 2002, 45, 5604. (b) Bailly, C.; Echepare, S.; Gago, F.; Waring, M. AntiCancer Drug Des. 1999, 14, 291. (c) Raw, S. A.; Wilfred, C. D.; Taylor, R. J. K. Chem. Commun. 2003, 2286. (540) (a) Gazit, A.; App, H.; McMahon, G.; Chen, J.; Levitzki, A.; Bohmer, F. D. J. Med. Chem. 1996, 39, 2170. (b) Sehlstedt, U.; Aich, P.; Bergman, J.; Vallberg, H.; Nordén, B.; Gräslund, A. J. Mol. Biol. 1998, 278, 31. (541) Moore, P. R.; Evenson, A.; Luckey, T. D.; McCoy, E.; Elvehjem, C. A.; Hart, E. B. J. Biol. Chem. 1946, 165, 437. (542) (a) Carta, A.; Corona, P.; Loriga, M. Curr. Med. Chem. 2005, 12, 2259. (b) Carta, A.; Paglietti, G.; Nikookar, M. E. R.; Sanna, P.; Sechi, L.; Zanetti, S. Eur. J. Med. Chem. 2002, 37, 355. (c) Jaso, A.; Zarranz, B.; Aldana, I.; Monge, A. Eur. J. Med. Chem. 2003, 38, 791. (d) Das, U.; Pati, H. N.; Panda, A. K.; De Clercq, E.; Balzarini, J.; Molnár, J.; Baráth, Z.; Ocsovszki, I.; Kawase, M.; Zhou, L.; Sakagami, H.; Dimmock, J. R. Bioorg. Med. Chem. 2009, 17, 3909. (543) Dailey, S.; Feast, W. J.; Peace, R. J.; Sage, I. C.; Till, S.; Wood, E. L. J. Mater. Chem. 2001, 11, 2238. (544) Jonathan, L. S.; Hiromitsu, M.; Toshihisa, M.; Vincent, M. L.; Hiroyuki, F. Chem. Commun. 2002, 8, 862. (545) Sascha, O.; Rüdiger, F. Synlett 2004, 1509. (546) Kazunobu, T.; Ryusuke, T.; Tomohiro, O.; Shuichi, M. Chem. Commun. 2002, 3, 212. (547) More, S. V.; Sastry, M. N. V.; Yao, C.-F. Green Chem. 2006, 8, 91.

(511) Jinsmaa, Y.; Miyazaki, A.; Fujita, Y.; Li, T.; Fujisawa, Y.; Shiotani, K.; Tsuda, Y.; Yokoi, T.; Ambo, A.; Sasaki, Y.; Bryant, S. D.; Lazarus, L. H.; Okada, Y. J. Med. Chem. 2004, 47, 2599. (512) Heeres, J.; de Jonge, M. R.; Koymans, L. M. H.; Daeyaert, F. F. D.; Vinkers, M.; Van Aken, K. J. A.; Arnold, E.; Das, K.; Kilonda, A.; Hoornaert, G. J.; Compernolle, F.; Cegla, M.; Azzam, R. A.; Andries, K.; de Béthune, M.-P.; Azijn, H.; Pauwels, R.; Lewi, P. J.; Janssen, P. A. J. J. Med. Chem. 2005, 48, 1910. (513) DiMaio, J.; Belleau, B. J. Chem. Soc., Perkin Trans. 1 1989, 1687. (514) Kendrick, D. A.; Ryder, H.; Semple, G.; Szelke, M. Bioorg. Med. Chem. Lett. 1992, 2, 9. (515) (a) Askew, B. C.; McIntyre, C. J.; Hunt, C. A.; Claremon, D. A.; Gould, R. J.; Lynch, R. J.; Armstrong, D. J. Bioorg. Med. Chem. Lett. 1995, 5, 475. (b) Askew, B. C.; McIntyre, C. J.; Hunt, C. A.; Claremon, D. A.; Baldwin, J. J.; Anderson, P. S.; Gould, R. J.; Lynch, R. J.; Chang, C. C.-T.; Cook, J. J.; Lynch, J. J.; Holahan, M. A.; Sitko, G. R.; Stranieri, M. T. Bioorg. Med. Chem. Lett. 1997, 7, 1531. (516) Logan, M. E.; Goswami, R.; Tomczuk, B. E.; Venepalli, B. R. Annu. Rep. Med. Chem. 1991, 26, 43. (517) (a) Guercio, G.; Bacchi, S.; Goodyear, M.; Carangio, A.; Tinazzi, F.; Curti, S. Org. Process Res. Dev. 2008, 12, 1188. (b) Pollini, G. P.; Baricordi, N.; Benetti, S.; Risi, C. D.; Zanirato, V. Tetrahedron Lett. 2005, 46, 3699. (c) Seibel, J.; Brown, D.; Amour, A.; Macdonald, S. J.; Oldham, N. J.; Schofield, C. J. Bioorg. Med. Chem. Lett. 2003, 13, 387. (d) Rossen, K.; Sager, J.; DiMichele, L. M. Tetrahedron Lett. 1997, 38, 3183. (e) Hulme, C.; Cherrier, M.-P. Tetrahedron Lett. 1999, 40, 5295. (f) Kennedy, A. L.; Fryer, A. M.; Josey, J. A. Org. Lett. 2002, 4, 1167. (g) Hulme, C.; Gore, V. Curr. Med. Chem. 2003, 10, 51. (h) Nixey, T.; Kelly, M.; Hulme, C. Tetrahedron Lett. 2000, 41, 8729. (i) Mc Cullough, K. J. In Rodd’s Chemistry of Carbon Compounds; Elsevier Science: New York, 1989; pp 294−296. (j) Masaki, V. M.; Ohta, M. Bull. Chem. Soc. Jpn. 1963, 36, 922. (k) Martin, W. B.; Martell, A. E. J. Am. Chem. Soc. 1950, 72, 4301. (l) Dinsmore, C. J.; Zartman, C. B. Tetrahedron Lett. 2000, 41, 6309. (m) Taguchi, H.; Yokoi, T.; Tsukatani, M.; Okada, Y. Tetrahedron 1995, 51, 7361. (n) Taguchi, H.; Yokoi, T.; Kasuya, F.; Nishiyama, Y.; Fukui, M.; Okada, Y. J. Chem. Soc., Chem. Commun. 1994, 247. (518) Tripier, R.; Chuburu, F.; Le Baccon, M.; Handel, H. Tetrahedron 2003, 59, 4573. (519) Mukaiyama, H.; Nishimura, T.; Kobayashi, S.; Ozawa, T.; Kamada, N.; Komatsu, Y.; Kikuchi, S.; Oonota, H.; Kusama, H. Bioorg. Med. Chem. 2007, 15, 868. (520) Karmas, G.; Spoerri, P. E. J. Am. Chem. Soc. 1952, 20, 1580. (521) Mano, M.; Seo, T.; Imai, K.-I. Chem. Pharm. Bull. 1980, 28, 2720. (522) Faggi, C.; García-Valverde, M.; Marcaccini, S.; Pepino, R.; Pozo, M. C. Synthesis 2003, 1553. (523) Garg, N. K.; Sarpong, R.; Stoltz, B. M. J. Am. Chem. Soc. 2002, 124, 13179. (524) Bradbury, R. H.; Griffiths, D.; Kivett, J. E. Heterocycles 1990, 31, 1647. (525) (a) Jones, R. C. J. Am. Chem. Soc. 1949, 71, 78. (b) Sato, N. J. Heterocycl. Chem. 1978, 15, 665. (c) Singh, B.; Lesher, G. Y. Heterocycles 1990, 31, 2163. (526) (a) Asaki, T.; Hamamoto, T.; Sugiyama, Y.; Kuwano, K.; Kuwabara, K. Bioorg. Med. Chem. 2007, 15, 6692. (b) Corbett, J. W.; Rauckhorst, M. R.; Qian, F.; Hoffman, R. L.; Knauer, C. S.; Fitzgerald, L. W. Bioorg. Med. Chem. Lett. 2007, 17, 6250. (c) Buron, F.; Turck, A.; Plé, N.; Bischoff, L.; Marsais, F. Tetrahedron Lett. 2007, 48, 4327. (d) Buron, F.; Plé, N.; Turck, A.; Queguiner, G. J. Org. Chem. 2005, 70, 2616. (527) (a) Brophy, J. J.; Cavill, G. W. K. Heterocycles 1980, 14, 477. (b) Seeman, J. I.; Ennis, D. M.; Sector, H. V.; Clawson, L.; Palen, J. Chem. Senses 1989, 14, 395. (528) (a) Fales, H. M.; Blum, M. S.; Southwick, E. W.; Williams, D. L.; Roller, P. P.; Don, A. W. Tetrahedron 1988, 44, 5045. (b) Wheeler, J. W.; Avery, J.; Olubajo, O.; Shamim, M. T.; Storm, C. B.; Duffield, R. M. Tetrahedron 1982, 38, 1939. CB


Chemical Reviews

Review

(548) Patra, A. K.; Dhar, S.; Nethaji, M.; Chakravarty, A. R. Dalton Trans. 2005, 896. (549) O’Brien, D.; Weaver, M. S.; Lidzey, D. G.; Bradley, D. D. C. Appl. Phys. Lett. 1996, 69, 881. (550) (a) Schmitz, C.; Pösch, P.; Thelakkat, M.; Schmidt, H.-W.; Montali, A.; Feldman, K.; Smith, P.; Weder, C. Adv. Funct. Mater. 2001, 11, 41. (b) Cui, Y.; Zhang, X.; Jenekhe, S. A. Macromolecules 1999, 32, 3824. (c) Karastatiris, P.; Mikroyannidis, J. A.; Spiliopoulos, L. K. Macromolecules 2004, 37, 7867. (d) Kulkarni, A. P.; Zhu, Y.; Jenekhe, S. A. Macromolecules 2005, 38, 1553. (e) Huang, T.-H.; Whang, W.-T.; Shen, J. Y.; Wen, Y. S.; Lin, J. T.; Ke, T.-H.; Chen, L.Y.; Wu, C.-C. Adv. Funct. Mater. 2006, 16, 1449. (551) (a) Hassan, H. Y.; Khattab, S. N.; Bekhit, A. A.; Amer, A. Bioorg. Med. Chem. Lett. 2006, 16, 1753. (b) Thakuria, H.; Das, G. J. Chem. Sci. 2006, 118, 425. (c) Woo, G. H. C.; Snyder, J. K.; Wan, Z. K. Prog. Heterocycl. Chem. 2002, 14, 279. (d) Mizuno, T.; Wei, W. H.; Eller, L. R.; Sessler, J. L. J. Am. Chem. Soc. 2002, 124, 1134. (e) Crossley, J. C.; Johnston, L. A. Chem. Commun. 2002, 10, 1122. (f) Juncai, F.; Yang, L.; Qinghua, M.; Bin, L. Synth. Commun. 1998, 28, 193. (g) Barluenga, J.; Aznar, F.; Liz, R.; Cabal, M.-P. Synthesis 1985, 313. (h) Eicher, T.; Hauptmann, S. The Chemistry of Heterocycles; Thieme: New York, 1995; pp 417−422. (i) Petukhov, P. A.; Tkachev, A. V. Tetrahedron 1997, 53, 9761. (j) Brown, D. J. In The Chemistry of Heterocyclic Compounds; Taylor, E. C., Wipf, P., Eds.; John Wiley & Sons: Hoboken, NJ, 2004. (552) Ayaz, M.; Dietrich, J.; Hulme, C. Tetrahedron Lett. 2011, 52, 4821. (553) Banihashemi, A.; Amiri, M.; Haghighi, B. Iran. J. Polym. Sci. Technol. 1993, 2, 19. (554) Wrasidlo, W.; Augl, J. M. Macromolecules 1970, 3, 544. (555) Moreno, E.; Ancizu, S.; Pérez-Silanes, S.; Torres, E.; Aldana, I.; Monge, A. Eur. J. Med. Chem. 2010, 45, 4418. (556) (a) Gazit, A.; App, H.; McMahon, G.; Chen, J.; Levitzki, A.; Bohmer, F. D. J. Med. Chem. 1996, 39, 2170. (b) Angier, R. B. J. Org. Chem. 1963, 28, 1398. (c) de Revel, G.; Pripis-Nicolau, L.; Barbe, J.-C.; Bertrand, A. J. Sci. Food Agric. 2000, 80, 102. (d) Mohsenzadeh, F.; Aghapoor, K.; Darabi, H. R. J. Braz. Chem. Soc. 2007, 18, 297. (e) Saeed, A. A. H.; Ebraheem, E. K. J. Heterocycl. Chem. 1983, 20, 1739. (f) Taylor, E. C.; Perlman, K. L.; Sword, I. P.; Séquin-Frey, M.; Jacobi, P. A. J. Am. Chem. Soc. 1973, 95, 6407. (g) Ohta, A.; Akita, Y.; Hara, M. Chem. Pharm. Bull. 1979, 27, 2027. (h) Steinbach, L.; Becker, E. I. J. Am. Chem. Soc. 1954, 76, 5808. (i) Storm, C. B.; Shiman, R.; Kaufman, S. J. Org. Chem. 1971, 36, 3925. (j) Fuson, R. C.; Emerson, W. S.; Gray, H. W. J. Am. Chem. Soc. 1939, 61, 480. (k) Yadav, J. S.; Reddy, B. V. S.; Premalatha, K.; Shankar, K. S. Synthesis 2008, 3787. (l) Jones, R. G. J. Am. Chem. Soc. 1949, 71, 78. (m) Wang, K.; Shi, W.; Jia, J.; Chen, S.; Ma, H. Talanta 2009, 77, 1795. (n) Sugiura, S.; Inoue, S.; Kishi, Y.; Goto, T. Yakugaku Zasshi 1969, 89, 1646. (o) Yurugi, S.; Hieda, M. Yakugaku Zasshi 1972, 92, 1322. (p) Haddadin, M. J.; Bitar, H. E.; Issidorides, C. H. Heterocycles 1979, 12, 323. (q) El Sekily, M. A. Arab. J. Sci. Eng. 2008, 33A, 7. (557) (a) Miyashiro, J.; Woods, K. W.; Park, C. H.; Liu, X.; Shi, Y.; Johnson, E. F.; Bouska, J. J.; Olson, A. M.; Luo, Y.; Fry, E. H.; Giranda, V. L.; Penning, T. D. Bioorg. Med. Chem. Lett. 2009, 19, 4050. (b) Szabó, G.; Kiss, R.; Páyer-Lengyel, D.; Vukics, K.; Szikra, J.; Baki, A.; Molnár, L.; Fischer, J.; Keserű , G. M. Bioorg. Med. Chem. Lett. 2009, 19, 3471. (c) Grande, F.; Aiello, F.; De Grazia, O.; Brizzi, A.; Garofalo, A.; Neamati, N. Bioorg. Med. Chem. 2007, 15, 288. (d) Glennon, R. A.; Daoud, M. K.; Dukat, M.; Teitler, M.; Herrick-Davis, K.; Purohit, A.; Syed, H. Bioorg. Med. Chem. 2003, 11, 4449. (e) Parihar, H. S.; Kirschbaum, K. S. Bioorg. Med. Chem. Lett. 2002, 12, 2743. (f) Goya, P.; Paez, J. A.; Alkorta, I.; Carrasco, E.; Grau, M.; Anton, F.; Julia, S.; Martinez-Ripoll, M. J. Med. Chem. 1992, 35, 3977. (558) Maga, G.; Gemma, S.; Fattorusso, C.; Locatelli, G. A.; Butini, S.; Persico, M.; Kukreja, G.; Romano, M. P.; Chiasserini, L.; Savini, L.; Novellino, E.; Nacci, V.; Spadari, S.; Campiani, G. Biochemistry 2005, 44, 9637. (559) Guillon, J.; Grellier, P.; Labaied, M.; Sonnet, P.; Léger, J.-M.; Depréz-Poulain, R.; Forfar-Bares, I.; Dallemagne, P.; Lemaitre, N.;

Péhourq, F.; Rochette, J.; Sergheraert, C.; Jarry, C. J. Med. Chem. 2004, 47, 1997. (560) Campiani, G.; Aiello, F.; Fabbrini, F.; Morelli, E.; Ramunno, A.; Armaroli, S.; Nacci, V.; Garofalo, A.; Greco, G.; Novellino, E.; Maga, G.; Spadari, S.; Bergamini, A.; Ventura, A.; Bongiovanni, V.; Cappozi, M.; Bolacchi, F.; Marini, S.; Colleta, M.; Guiso, G.; Caccia, S. J. Med. Chem. 2001, 44, 305. (561) Desplat, V.; Geneste, A.; Begorre, M.-A.; Fabre, S. B.; Brajot, S.; Massip, S.; Thiolat, D.; Mossalayi, D.; Jarry, C.; Guillon, J. J. Enzyme Inhib. Med. Chem. 2008, 23, 648. (562) Seredenin, S. B.; Voronina, T. A.; Likhosherstov, A. M.; Peresada, V. P.; Molodavkin, G. M.; Halikas, J. A. U.S. Patent 5,378,846, 1995; Chem. Abstr. 1995, 123, 83350w. (563) Negoro, T.; Murata, M.; Ueda, S.; Fujitani, B.; Ono, Y.; Kuromiya, A.; Komiya, M.; Suzuki, K.; Matsumoto, J.-i. J. Med. Chem. 1998, 41, 4118. (564) (a) Khaled, M. A.; Morin, R. D.; Benington, F.; Daugherty, J. P. Cancer Chemother. Pharmacol. 1984, 13, 73. (b) Suster, D. C.; Tarnauceanu, E.; Ionescu, D.; Dobre, V.; Niculescu-Duvaz, I. J. Med. Chem. 1978, 21, 1162. (565) (a) Waring, P.; Armarego, W. L. F. Aust. J. Chem. 1985, 38, 629. (b) Russell, J. R.; Garner, C. D.; Joule, J. A. Synlett 1992, 711. (c) Evans, R. M.; Jones, P. G.; Palmer, P. J.; Stephens, F. F. J. Chem. Soc. 1956, 4106. (d) Taylor, E. C.; Vogl, O.; Cheng, C. C. J. Am. Chem. Soc. 1959, 81, 2442. (e) Pfleiderer, W. In Comprehensive Heterocyclic Chemistry; Katritzky, A. R., Rees, C. W., Eds.; Pergamon: Oxford, U.K., 1984; Vol. 3, Part 2B, p 263. (566) (a) Campillo, N.; García, C.; Goya, P.; Páez, J. A.; Carrasco, E.; Grau, M. J. Med. Chem. 1999, 42, 1698. (b) Alkorta, I.; Goya, P.; Páez, J. A.; Pfleiderer, W. Pteridines 1990, 2, 3. (567) Barlin, G. B. Aust. J. Chem. 1981, 34, 1361. (568) Lee, K.-H.; Huang, B.-R.; Chen, Y.-L.; Tzeng, C.-C. Heterocycles 1993, 36, 2577. (569) Palanki, M. S. S.; Dneprovskaia, E.; Doukas, J.; Fine, R. M.; Hood, J.; Kang, X.; Lohse, D.; Martin, M.; Noronha, G.; Soll, R. M.; Wrasidlo, W.; Yee, S.; Zhu, H. J. Med. Chem. 2007, 50, 4279. (570) Ma, F.; Lü, G.; Zhou, W.-F.; Wang, Q.-J.; Zhang, Y.-H.; Yao, Q. Z. Arch. Pharm. Chem. Life Sci. 2009, 342, 274. (571) Taghavi-Moghadam, S.; Pfleiderer, W. Tetrahedron Lett. 1997, 38, 6835. (572) Taylor, E. C.; Perlman, K. L.; Kim, Y.-H.; Sword, I. P.; Jacobi, P. A. J. Am. Chem. Soc. 1973, 95, 6413. (573) Singh, R.; Geetanjali. Russ. J. Org. Chem. 2006, 42, 136. (574) (a) Schmitz, W. D.; Brenner, A. B.; Bronson, J. J.; Ditta, J. L.; Griffin, C. R.; Li, Y.-W.; Lodge, N. J.; Molski, T. F.; Olson, R. E.; Zhuo, X.; Macor., J. E. Bioorg. Med. Chem. Lett. 2010, 20, 3579. (b) Sztanke, K.; Tuzimski, T.; Sztanke, M.; Rzymowska, J.; Pasternak., K. Bioorg. Med. Chem. 2011, 19, 5103. (c) Saad, H. A.; Moustafa, A. H. Molecules 2011, 16, 5682. (d) Abdel-Halim, A. M.; el-Gendy, Z.; Abdel-Rahman, R. M. Pharmazie 1995, 50, 726. (e) Bhatia, P. A.; Brooks, C. D. W.; Basha, A.; Ratajczyk, J. D.; Gunn, B. P.; Bouska, J. B.; Lanni, C.; Young, P. R.; Bell, R. L.; Carter, G. W. J. Med. Chem. 1996, 39, 3938. (575) (a) Camparini, A.; Celli, A. M.; Ponticelli, F.; Tedeschi, P. J. Heterocycl. Chem. 1978, 15, 1271. (b) Kammoun, M.; Khemakhem, A. M.; Hajjem, B. J. Fluorine Chem. 2000, 105, 83. (c) Collins, D. J.; Hughes, T. C.; Johnson, W. M. Aust. J. Chem. 1999, 52, 379. (d) Smodis, J.; Zupet, R.; Petric, A.; Stanovnik, B.; Tisler, M. Heterocycles 1990, 30, 393. (e) Collins, D. J.; Hugues, T. C.; Johnson, W. M. Aust. J. Chem. 1996, 49, 463. (576) (a) Lalezari, I. J. Org. Chem. 1968, 33, 4281. (b) Lalezari, I.; Shafiee, A.; Yalpani, M. Tetrahedron Lett. 1969, 10, 3059. (577) Lalezari, I.; Sharghi, N.; Shafiee, A.; Yalpani, M. J. Heterocycl. Chem. 1969, 6, 403. (578) Zelenin, K. N.; Kuznetsova, O. B.; Alekseev, V. V. Chem. Heterocycl. Compd. 1992, 28, 1211. (579) Alekseyev, V. V.; Lagoda, I. V.; Yakimovich, S. I.; Yegorova, M. B. Chem. Heterocycl. Compd. 2010, 46, 971. CC


Chemical Reviews

Review

(580) Neunhoeffer, H. In Comprehensive Heterocyclic Chemistry II; Katritzky, A. R., Rees, C. W., Scriven, E. F. V., Ed.; Pergamon: Oxford, U.K.. 1996; Vol. 6, pp 507−573. (581) (a) Seela, F.; He, Y. J. Org. Chem. 2003, 68, 367. (b) Seela, F.; Chittepu, P. J. Org. Chem. 2007, 72, 4358. (582) (a) Neunhoeffer, H. In Comprehensive Heterocyclic Chemistry; Katrizky, A. R., Rees, C. W., Eds.; Pergamon Press: Oxford, U.K., 1984; Vol. 3, pp 385−456. (b) El Ashry, E. S. H.; Rashed, N.; Taha, M.; Ramadan, E. Adv. Heterocycl. Chem. 1994, 59, 39. (583) (a) Creasey, W. A.; Fink, M. E.; Handschumacher, R. E.; Calabresi, P. Cancer Res. 1963, 23, 444. (b) Walters, T. R.; Aur, R. J. A.; Hernandez, K.; Vietti, T.; Pinkel, D. Cancer 1972, 29, 1057. (584) Sidwell, R. W.; Dixon, G. J.; Sellers, S. M.; Schabel, F. M., Jr. Appl. Microbiol. 1968, 16, 370. (585) Matolcsy, G. Acta Phytopathol. 1966, 1, 245. (586) (a) Taylor, E. C.; Pont, J. L. J. Org. Chem. 1987, 52, 4287. (b) Charushin, V. N.; van Veldhuizen, B.; van der Plas, H. C.; Stam, C. H. Tetrahedron 1989, 45, 6499. (587) Croot, P. L.; Hunter, K. A. Anal. Chim. Acta 2000, 406, 289. (588) (a) O’Rourke, M.; Lang, S. A., Jr.; Cohen, E. J. Med. Chem. 1977, 20, 723. (b) Konno, S.; Osawa, N.; Yamanaka, H.; Sanemitsu, Y.; Kawamura, S.; Sakaki, M. J. Agric. Food Chem. 1995, 43, 838. (589) Limanto, J.; Desmond, R. A.; Gauthier, D. R., Jr.; Devine, P. N.; Reamer, R. A.; Volante, R. P. Org. Lett. 2003, 5, 2271. (590) Matikainen, J. K. T.; Elo, H. O. Microchim. Acta 2004, 146, 49. (591) Correia, J. J. Org. Chem. 1978, 43, 3394. (592) Bruce, M. J.; McLean, G. A.; Royles, B. J. L.; Smith, D. M.; Standring, P. N. J. Chem. Soc., Perkin Trans. 1 1995, 1789. (593) Culbertson, B. M.; Parr, G. R. J. Heterocycl. Chem. 1967, 4, 422. (594) (a) Case, F. H. J. Heterocycl. Chem. 1973, 10, 353. (b) Konno, S.; Sagi, M.; Kimura, C.; Kikuchi, J.; Yamanaka, H.; Fujita, F.; Yamada, Y.; Adachi, M. Yakugaku Zasshi 1988, 108, 142. (c) Joshi, K. C.; Dubey, K.; Dandia, A. Heterocycles 1981, 16, 1545. (595) (a) Kgokong, J. L.; Smith, P. P.; Matsabisa, G. M. Bioorg. Med. Chem. 2005, 13, 2935. (b) Hunt, J. T.; Mitt, T.; Borzilleri, R.; GulloBrown, J.; Fargnoli, J.; Fink, B.; Han, W.-C.; Mortillo, S.; Vite, G.; Wautlet, B.; Wong, T.; Yu, C.; Zheng, X.; Bhide, R. J. Med. Chem. 2004, 47, 4054. (c) De Clercq, E. J. Med. Chem. 1986, 29, 1561. (d) Diana, P.; Barraja, P.; Lauria, A.; Montalbano, A.; Almerico, A. M.; Dattolo, G.; Cirrincione, G. Eur. J. Med. Chem. 2002, 37, 267. (e) Mulvihill, M. J.; Ji, Q.-S.; Werner, D.; Beck, P.; Cesario, C.; Cooke, A.; Cox, M.; Crew, A.; Dong, H.; Feng, L.; Foreman, K. W.; Mak, G.; Nigro, A.; O’Connor, M.; Saroglou, L.; Stolz, K. M.; Sujka, I.; Volk, B.; Weng, Q.; Wilkes, R. Bioorg. Med. Chem. Lett. 2007, 17, 1091. (f) Mulvihill, M. J.; Ji, Q.-S.; Coate, H. R.; Cooke, A.; Dong, H.; Feng, L.; Foreman, K.; Rosenfeld-Franklin, M.; Honda, A.; Mak, G.; Mulvihill, K. M.; Nigro, A. I.; O’Connor, M.; Pirrit, C.; Steinig, A. G.; Siu, K.; Stolz, K. M.; Sun, Y.; Tavares, P. A. R.; Yao, Y.; Gibson, N. W. Bioorg. Med. Chem. 2008, 16, 1359. (g) Da Settimo, F.; Primofiore, G.; Taliani, S.; Marini, A. M.; La Motta, C.; Novellino, E.; Greco, G.; Lavecchia, A.; Trincavelli, L.; Martini, C. J. Med. Chem. 2001, 44, 316. (h) Haning, H.; Niewöhner, U.; Schenke, T.; Es-Sayed, M.; Schmidt, G.; Lampe, T.; Bischoff, E. Bioorg. Med. Chem. Lett. 2002, 12, 865. (i) Dunn, P. J. Org. Process Res. Dev. 2005, 9, 88. (j) Sharma, N.; Kumar, Y.; Sahi, S.; Priyanka. Int. J. Pharmacy Pharm. Sci. 2010, 2 (Suppl 2), 118. (k) De Zwart, M.; Vollinga, R. C.; Beukers, M. W.; Sleegers, D. F.; Von Frijtag Drabbe Kunzel, J. K.; De Groote, M.; Ijzerman, A. P. Drug Dev. Res. 1999, 48, 95. (l) Peng, H.; Kumaravel, G.; Yao, G.; Sha, L. I.; Wang, J.; Van Vlijmen, H.; Bohnert, T.; Huang, C.; Vu, C. B.; Ensinger, C. L.; Chang, H.; Engber, T. M.; Whalley, E. T.; Petter, R. C. J. Med. Chem. 2004, 47, 6218. (m) Vu, C. B.; Peng, B. O.; Kumaravel, G.; Smits, G.; Jin, X.; Phadke, D.; Engber, T.; Huang, C.; Reilly, J.; Tam, S.; Grant, D.; Hetu, G.; Chen, L.; Zhang, J.; Petter, R. C. J. Med. Chem. 2004, 47, 4291. (596) (a) Charles, I.; Latham, D. W. S.; Hartley, D.; Oxford, A. W.; Scopes, D. I. C. J. Chem. Soc., Perkin Trans. 1 1980, 1139. (b) Riedl, Z.; Hajós, G.; Kövér, P.; Kollenz, G. ARKIVOC 2003, v, 62. (c) Hayashi, M.; Araki, A.; Maeba, I. Heterocycles 1992, 34, 569. (d) Patil, S. A.; Otter, B. A.; Klein, R. S. J. Heterocycl. Chem. 1994, 31, 781.

(e) Quintela, J. M.; Moreira, M. J.; Peinador, C. Tetrahedron 1996, 52, 3037. (f) Knutsen, L. J. S.; Judkins, B. D.; Newton, R. F.; Scopes, D. I. C.; Klinkert, G. J. Chem. Soc., Perkin Trans. 1 1985, 621. (g) Heim-Riether, A.; Healy, J. J. Org. Chem. 2005, 70, 7331. (h) Charles, I.; Latham, D. W. S.; Hartley, D.; Oxford, A. W.; Scopes, D. I. C. J. Chem. Soc., Perkin Trans. 1 1980, 1139. (i) Reich, M. F.; Fabio, P. F.; Lee, V. J.; Kuck, N. A.; Testa, R. T. J. Med. Chem. 1989, 32, 2474. (597) Attanasi, O. A.; De Crescentini, L.; Foresti, E.; Gatti, G.; Giorgi, R.; Perrulli, F. R.; Santeusanio, S. J. Chem. Soc., Perkin Trans. 1 1997, 1829. (598) Lalezari, I.; Levy, Y. J. Heterocycl. Chem. 1974, 11, 327. (599) Ueda, T.; Adachi, T.; Nagai, S.-I.; Sakakibara, J.; Murata, M. J. Heterocycl. Chem. 1988, 25, 791. (600) Hajós, G.; Riedl, Z.; Gács-Baitz, E.; Messmer, A. Tetrahedron 1992, 48, 8459. (601) (a) Abrams, J. N.; Babu, R. S.; Guo, H.; Le, D.; Le, J.; Osbourn, J. M.; O’Doherty, G. A. J. Org. Chem. 2008, 73, 1935. (b) Guo, H.; O’Doherty, G. A. Org. Lett. 2005, 7, 3921. (c) Zhou, M. Q.; O’Doherty, G. A. J. Org. Chem. 2007, 72, 2485. (d) Guo, H. B.; O’Doherty, G. A. J. Org. Chem. 2008, 73, 5211. (e) Leverett, C. A.; Cassidy, M. P.; Padwa, A. J. Org. Chem. 2006, 71, 8591. (f) Harris, J. M.; Padwa, A. J. Org. Chem. 2003, 68, 4371. (g) Griggs, N. D.; Phillips, A. J. Org. Lett. 2008, 10, 4955. (h) Henderson, J. A.; Jackson, K. L.; Phillips, A. J. Org. Lett. 2007, 9, 5299. (i) Babu, R. S.; O’Doherty, G. A. J. Carbohydr. Chem 2005, 24, 169. (j) Peng, X.; Li, A.; Lu, J.; Wang, Q.; Pan, X.; Chan, A. S. C. Tetrahedron 2002, 58, 6799. (k) Wender, P. A.; Bi, F. C.; Buschmann, N.; Gosselin, F.; Kan, C.; Kee, J.-M.; Ohmura, H. Org. Lett. 2006, 8, 5373. (l) Couladouros, E. A.; Strongilos, A. T. Angew. Chem., Int. Ed. 2002, 41, 3677. (m) Zhou, X.; Wu, W.; Liu, X.; Lee, C.-S. Org. Lett. 2008, 10, 5525. (n) Harris, J. M.; O’Doherty, G. A. Org. Lett. 2000, 2, 2983. (o) Yu, X.; O’Doherty, G. A. Org. Lett. 2008, 10, 4529. (602) (a) Laurence, B. R.; Pickett, J. A. J. Chem. Soc., Chem. Commun. 1982, 59. (b) Sato, M.; Nakashima, H.; Hanada, K.; Hayashi, M.; Honzumi, M.; Taniguchi, T.; Ogasawara, K. Tetrahedron Lett. 2001, 42, 2833. (c) Hinterding, K.; Singhanat, S.; Oberer, L. Tetrahedron Lett. 2001, 42, 8463. (d) Wu, Y.; Shen, X.; Tang, C.-J.; Chen, Z.-L.; Hu, Q.; Shi, W. J. Org. Chem. 2002, 11, 3802. (e) Yadav, J. S.; Reddy, P. M. K.; Reddy, P. V. Tetrahedron Lett. 2007, 48, 1037. (f) Chakraborty, T. K.; Tapadar, S. Tetrahedron Lett. 2003, 44, 2541. (g) Yamashita, Y.; Saito, S.; Ishitani, H.; Kobayashi, S. J. Am. Chem. Soc. 2003, 125, 3793. (h) Ali, A. M.; Mckeen, M. M.; Hamid, M.; Aun, Q. B.; Zauyah, Y.; Azimahtol, H. L. P.; Kawazu, K. Planta Med. 1997, 63, 81. (i) Falomir, E.; Murga, J.; Carda, M.; Marco, J. A. Tetrahedron Lett. 2003, 44, 539. (j) Chênevert, R.; Courchesne, G.; Caron, D. Tetrahedron: Asymmetry 2003, 14, 2567. (603) Smith, A. B., III; Fox, R. J.; Razler, T. M. Acc. Chem. Res. 2008, 41, 675. (604) Argoudelis, A. D.; Zieserl, J. F. Tetrahedron Lett. 1966, 18, 1969. (605) Yasui, K.; Tamura, Y.; Nakatani, T.; Kawada, K.; Ohtani, M. J. Org. Chem. 1995, 60, 7567. (606) (a) Dumontet, V.; Van Hung, N.; Adeline, M.-T.; Riche, C.; Chiaroni, A.; Sévenet, T.; Guéritte, F. J. Nat. Prod. 2004, 67, 858. (b) de Fátima, Â .; Kohn, L. K.; de Carvalho, J. E.; Pilli, R. A. Bioorg. Med. Chem. 2006, 14, 622. (607) Maria, A. O. M.; Donadel, O.; Wendel, G. H.; Guzman, J. A.; Guerreiro, E.; Giordano, O. S. Biol. Pharm. Bull. 2000, 23, 555. (608) de Fatima, Â .; Kohn, L. K.; Antônio, M. A.; de Carvalho, J. E.; Pilli, R. A. Bioorg. Med. Chem. 2004, 12, 5437. (609) Saeed, M.; IIg, T.; Schick, M.; Abbas, M.; Voelter, W. Tetrahedron Lett. 2001, 42, 7401. (610) (a) Du, H.; Zhang, X.; Wang, Z.; Bao, H.; You, T.; Ding, K. Eur. J. Org. Chem. 2008, 2248. (b) Jørgensen, K. A. Angew. Chem., Int. Ed. 2000, 39, 3558. (c) Du, H.; Long, J.; Hu, J.; Li, X.; Ding, K. Org. Lett. 2002, 4, 4349. (d) Maruoka, K.; Itoh, T.; Shirasaka, T.; Yamamoto, H. J. Am. Chem. Soc. 1988, 110, 310. (e) Doyle, M. P.; Phillips, I. M.; Hu, W. J. Am. Chem. Soc. 2001, 123, 5366. (f) Berkessel, CD


Chemical Reviews

Review

A.; Vogl, N. Eur. J. Org. Chem. 2006, 5029. (g) Aikawa, K.; Irie, R.; Katsuki, T. Tetrahedron 2001, 57, 845. (h) Merino, P.; MarquésLópez, E.; Tejero, T.; Herrera, R. P. Synthesis 2010, 1. (i) Huang, Y.; Unni, A. K.; Thadani, A. N.; Rawal, V. H. Nature 2003, 424, 146. (j) Anderson, C. D.; Dudding, T.; Gordillo, R.; Houk, K. N. Org. Lett. 2008, 10, 2749. (k) Unni, A. K.; Takenaka, N.; Yamamoto, H.; Rawal, V. H. J. Am. Chem. Soc. 2005, 127, 1336. (l) McManus, H. A.; Guiry, P. J. Chem. Rev. 2004, 104, 4151. (m) Huang, Y.; Rawal, V. H. Org. Lett. 2000, 2, 3321. (n) Anada, M.; Washio, T.; Shimada, N.; Kitagaki, S.; Nakajima, M.; Shiro, M.; Hashimoto, S. Angew. Chem., Int. Ed. 2004, 43, 2665. (o) Yamashita, Y.; Saito, S.; Ishitani, H.; Kobayashi, S. Org. Lett. 2002, 4, 1221. (p) Danishefsky, S. J. Aldrichimica Acta 1986, 19, 59. (q) Bednarski, M.; Danishefsky, S. J. Am. Chem. Soc. 1986, 108, 7060. (r) Dossetter, A. G.; Jamison, T. F.; Jacobsen, E. N. Angew. Chem., Int. Ed. 1999, 38, 2398. (611) Oi, S.; Terada, E.; Ohuchi, K.; Kato, T.; Tachibana, Y.; Inoue, Y. J. Org. Chem. 1999, 64, 8660. (612) (a) Luo, H.-K.; Khim, L. B.; Schumann, H.; Lim, C.; Jie, T. X.; Yang, H.-Y. Adv. Synth. Catal. 2007, 349, 1781. (b) Luo, H.-K.; Woo, Y.-L.; Schumann, H.; Jacob, C.; van Meurs, M.; Yang, H.-Y.; Tan, Y.-T. Adv. Synth. Catal. 2010, 352, 1356. (613) Becker, J. J.; Van Orden, L. J.; White, P. S.; Gagné, M. R. Org. Lett. 2002, 4, 727. (614) Tonoi, T.; Mikami, K. Tetrahedron Lett. 2005, 46, 6355. (615) (a) Shchepin, V. V.; Korzun, A. E.; Nedugov, A. N.; Sazhneva, Y. K.; Shurov, S. N. Russ. J. Org. Chem 2002, 38, 248. (b) Shchepin, V. V.; Korzun, A. E.; Sazhneva, Y. K.; Nedugov, A. N. Chem. Heterocycl. Compd. 2001, 37, 374. (616) Shchepin, V. V.; Kirillov, N. F.; Nedugov, A. N. Russ. J. Gen. Chem. 2003, 73, 1264. (617) (a) Aubele, D. L.; Wan, S.; Floreancig, P. E. Angew. Chem., Int. Ed. 2005, 44, 3485. (b) Chan, K.-P.; Ling, Y. H.; Loh, T.-P. Chem. Commun. 2007, 939. (c) Schmidt, M.; Ungvári, J.; Glöde, J.; Dobner, B.; Langner, A. Bioorg. Med. Chem. 2007, 15, 2283. (618) (a) Lumma, W. C.; Ma, O. H. J. Org. Chem. 1970, 35, 2391. (b) Adams, D. R.; Bhatnagar, S. P. Synthesis 1977, 661. (c) Arundale, E.; Mikeska, L. A. Chem. Rev. 1952, 51, 505. (d) El Gharbi, R.; Delmas, M.; Gaset, A. Synthesis 1981, 361. (e) Tateiwa, J.-I.; Hashimoto, K.; Yamauchi, T.; Uemura, S. Bull. Chem. Soc. Jpn. 1996, 69, 2361. (f) Bach, T.; Löbel, J. Synthesis 2002, 2521. (g) Gu, Y.; Karam, A.; Jérôme, F.; Barrault, J. Org. Lett. 2007, 9, 3145. (h) Piergentili, A.; Quaglia, W.; Giannella, M.; Del Bello, F.; Bruni, B.; Buccioni, M.; Carrieri, A.; Ciattini, S. Bioorg. Med. Chem. 2007, 15, 886. (619) Xianming, H.; Kellogg, R. M. Recl. Trav. Chim. Pays-Bas 1996, 115, 407. (620) Becerra-Martínez, E.; Velázquez-Ponce, P.; Sánchez-Aguilar, M. A.; Rodríguez-Hosteguín, A.; Joseph-Nathan, P.; Tamariza, J.; Zepeda, L. G. Tetrahedron: Asymmetry 2007, 18, 2727. (621) Griffiths, D. W.; Gutsche, C. D. J. Org. Chem. 1971, 36, 2184. (622) (a) Ingall, A. H. In Comprehensive Heterocyclic Chemistry II; McKillop, A., Ed.; Pergamon Press: Oxford, U.K., 1996; Vol. 5, pp 501−617. (b) Al Nakib, T.; Bezjak, V.; Meegan, M.; Chandy, R. Eur. J. Med. Chem. 1990, 25, 455. (c) Al Nakib, T.; Bezjak, V.; Rashid, S.; Fullam, B.; Meegan, M. Eur. J. Med. Chem. 1991, 26, 221. (d) van Vliet, L. A.; Rodenhuis, N.; Dijkstra, D.; Wikström, H.; Pugsley, T. A.; Serpa, K. A.; Meltzer, L. T.; Heffner, T. G.; Wise, L. D.; Lajiness, M. E.; Huff, R. M.; Svensson, K.; Sundell, S.; Lundmark, M. J. Med. Chem. 2000, 43, 2871. (623) (a) Yamamoto, K.; Yamazaki, S.; Osedo, H.; Murata, I. Angew. Chem., Int. Ed. 1986, 25, 635. (b) Yamamoto, K.; Yamazaki, S.; Murata, I.; Fukazawa, Y. J. Org. Chem. 1987, 52, 5239. (624) (a) Chen, C. H.; Reynolds, G. A. J. Org. Chem. 1980, 45, 2449. (b) Nakasuji, K.; Nakasuka, M.; Murata, I. J. Chem. Soc., Chem. Commun. 1981, 1143. (c) Chen, C. H.; Reynolds, G. A.; Luss, H. R.; Perlstein, J. H. J. Org. Chem. 1986, 51, 3282. (d) Fox, J. L.; Chen, C. H.; Luss, H. R. J. Org. Chem. 1986, 51, 3551. (625) (a) Schuler, B.; Sundermeyer, W. Tetrahedron Lett. 1989, 30, 4111. (b) Timoshenko, V. M.; Bouillon, J.-P.; Shermolovich, Y. G.; Portella, C. Tetrahedron Lett. 2002, 43, 5809. (c) Shermolovich, Y. G.;

Slusarenko, Y. I.; Timoshenko, V. M.; Rozhenko, A. B.; Markovski, L. N. J. Fluorine Chem. 1991, 55, 329. (d) Bouillon, J.-P.; Shermolovich, Y. G.; Portella, C. Tetrahedron Lett. 2001, 42, 2133. (e) Pfund, E.; Lequeux, T.; Vazeux, M.; Masson, S. Tetrahedron Lett. 2002, 43, 2033. (f) Morita, H.; Takeda, M.; Yoshimura, T.; Fujii, T.; Ono, S.; Shimasaki, C. J. Org. Chem. 1999, 64, 6730. (626) Capperucci, A.; Degl’Innocenti, A.; Ricci, A.; Mordini, A.; Reginato, G. J. Org. Chem. 1991, 56, 7323. (627) Turgut, Z.; Pelit, E.; Koyeu, A. Molecules 2007, 12, 345. (628) (a) Kurz, T. Tetrahedron 2005, 61, 3091. (b) Lesher, G. Y.; Surrey, A. R. J. Am. Chem. Soc. 1955, 77, 636. (629) Adib, M.; Sheibani, E.; Mostofi, M.; Ghanbary, K.; Bijanzadeh, H. R. Tetrahedron 2006, 62, 3435. (630) (a) de Poël, H. V.; Guillaumet, G.; Viaud-Massuard, M.-C. Tetrahedron Lett. 2002, 43, 1205. (b) Remillard, S.; Rebhun, L. I.; Howie, G. A.; Kupchan, S. M. Science 1975, 189, 1002. (631) Cocuzza, A. J.; Chidester, D. R.; Cordova, B. C.; Jeffrey, S.; Parsons, R. L.; Bacheler, L. T.; Erickson-Viitanen, S.; Trainor, G. L.; Ko, S. S. Bioorg. Med. Chem. Lett. 2001, 11, 1177. (632) Kajino, M.; Shibouta, Y.; Nishikawa, K.; Meguro, K. Chem. Pharm. Bull. 1991, 11, 2896. (633) (a) Sasaki, K.; Kusakabe, Y.; Esumi, S. J. Antibiot. 1972, 25, 151. (b) Kusakabe, Y.; Nagatsu, J.; Shibuya, M.; Kawaguchi, O.; Hirose, C.; Shirato, S. J. Antibiot. 1972, 25, 44. (c) Kupchan, S. M.; Komoda, Y.; Court, W. A.; Thomas, G. J.; Smith, R. M.; Karim, A.; Gilmore, C. J.; Haltiwanger, R. C.; Bryan, R. F. J. Am. Chem. Soc. 1972, 94, 1354. (634) Buckman, B. O.; Mohan, R.; Koovakkat, S.; Liang, A.; Trinh, L.; Morrissey, M. M. Bioorg. Med. Chem. Lett. 1998, 8, 2235. (635) Mosher, H. S.; Frankel, M. B.; Gregory, M. J. Am. Chem. Soc. 1953, 75, 5326. (636) Katsura, Y.; Nishino, S.; Takasugi, H. Chem. Pharm. Bull. 1991, 11, 2937. (637) Kerdesky, F. A. J. Tetrahedron Lett. 2005, 46, 1711. (638) Ritter, J. J.; Tillmanns, E. J. J. Org. Chem. 1957, 22, 839. (639) Katritzky, A. R.; Shcherbakova, I. V.; Tack, R. D.; Dai, X. Q. Tetrahedron 1993, 49, 3907. (640) Wipf, P.; Hayes, G. B. Tetrahedron 1998, 54, 6987. (641) Eckstein, Z.; Urbanski, T. Adv. Heterocycl. Chem. 1963, 2, 311. (642) Schmidt, R. R.; Schwille, D.; Sommer, U. Justus Liebigs Ann. Chem. 1969, 723, 111. (643) (a) Mathew, B. P.; Nath, M. J. Heterocycl. Chem. 2009, 46, 1003. (b) Kategaonkar, A. H.; Sonar, S. S.; Pokalwar, R. U.; Kategaonkar, A. H.; Shingate, B. B.; Shingare, M. S. Bull. Korean Chem. Soc. 2010, 31, 1657. (c) Sadaphal, S. A.; Sonar, S. S.; Shingate, B. B.; Shingare, M. S. Green Chem. Lett. Rev. 2010, 3, 213. (d) Tumtin, S.; Phucho, I. T.; Nongpiur, A.; Nongrum, R.; Vishwakarma, J. N.; Myrboh, B.; Nongkhlaw, R. L. J. Heterocycl. Chem. 2010, 47, 125. (e) Shinde, P. V.; Sonar, S. S.; Shingate, B. B.; Shingare, M. S. Tetrahedron Lett. 2010, 51, 1309. (f) Niralwad, K. S.; Shingate, B. B.; Shingare, M. S. Tetrahedron Lett. 2010, 51, 3616. (644) Ko, K.-Y.; Park, J.-Y. Tetrahedron Lett. 1997, 38, 407. (645) Ko, K.-Y.; Yun, H. Heterocycles 2010, 81, 2351. (646) (a) He, X.-C.; Eliel, E. L. Tetrahedron 1987, 43, 4979. (b) Eliel, E. L.; He, X.-C. J. Org. Chem. 1990, 55, 2114. (647) Choi, I.-Y.; Son, J.-Y.; Chung, K.-H. Bull. Korean Chem. Soc. 1999, 20, 484. (648) Horii, Z.-I.; Inoi, T.; Kim, S.-W.; Tamura, Y.; Suzuki, A.; Matsumoto, H. Chem. Pharm. Bull. 1965, 13, 1151. (649) (a) Berg, S.; Larsson, L.-G.; Rényi, L.; Ross, S. B.; Thorberg, S.O.; Thorell-Svantesson, G. J. Med. Chem. 1998, 41, 1934. (b) Letavic, M. A.; Keith, J. M.; Ly, K. S.; Bonaventure, P.; Feinstein, M. A.; Lord, B.; Miller, K. L.; Motley, S. T.; Nepomuceno, D.; Sutton, S. W.; Carruthers, N. I. Bioorg. Med. Chem. Lett. 2008, 18, 5796. (650) Verma, M.; Gujrati, V. R.; Sharma, M.; Saxena, A. K.; Bhalla, T. N.; Sinha, J. N.; Bhargava, K. P.; Shanker, K. Pharmacol. Res. Commun. 1984, 16, 9. (651) (a) Wong, E. H. F.; Sonders, M. S.; Amara, S. G.; Tinholt, P. M.; Piercey, M. F. P.; Hoffmann, W. P.; Hyslop, D. K.; Franklin, S.; CE


Chemical Reviews

Review

Porsolt, R. D.; Bonsignori, A.; Carfagna, N.; McArthur, R. A. Biol. Psychiatry 2000, 47, 818. (b) Hajós, M.; Fleishaker, J. C.; FilipiakReisner, J. K.; Brown, M. T.; Wong, E. H. F. CNS Drug Rev. 2004, 10, 23. (652) D’Arrigo, P.; Lattanzio, M.; Fantoni, G. P.; Servi, S. Tetrahedron: Asymmetry 1998, 9, 4021. (653) (a) Brenner, E.; Baldwin, R. M.; Tamagnan, G. Org. Lett. 2005, 7, 937. (b) Wirz, B.; Walther, W. Tetrahedron: Asymmetry 1992, 3, 1049. (c) Kojima, T.; Niigata, K.; Fujikura, T.; Tachikawa, S.; Nozaki, Y.; Kagami, S.; Takahashi, K. Chem. Pharm. Bull. 1985, 33, 3766. (654) (a) Nozulak, J.; Vigouret, J. M.; Jaton, A. L.; Hofmann, A.; Dravid, A. R.; Weber, H. P.; Kalkman, H.; Walkinshaw, M. D. J. Med. Chem. 1992, 35, 480. (b) Somei, M.; Aoki, K.; Nagaham, Y.; Nakagawa, K. Heterocycles 1995, 41, 5. (c) Nishi, T.; Ishibashi, K.; Takemoto, T.; Nakajima, K.; Fukazawa, T.; Iio, Y.; Itoh, K.; Mukayama, O.; Yamaguchi, T. Biorg. Med. Chem. Lett. 2000, 10, 1665. (d) Lanman, B. A.; Myers, A. G. Org. Lett. 2004, 6, 1045. (e) Fustero, S.; Jimenez, D.; Moscardó, J.; Catalàn, S.; Del Pozo, C. Org. Lett. 2007, 9, 5283. (655) Grotenbreg, G. M.; Christina, A. E.; Buizert, A. E. M.; Van der Marel, G. A.; Overkleeft, H. S.; Overhand, M. J. Org. Chem. 2004, 69, 8331. (656) Berrée, F.; Debache, A.; Marsac, Y.; Carboni, B. Tetrahedron Lett. 2001, 42, 3591. (657) Sheradsky, T.; Silcoff, E. R. J. Heterocycl. Chem. 1996, 33, 1271. (658) Polyak, F.; Dorofeeva, T.; Zelchans, G.; Shustov, G. Tetrahedron Lett. 1996, 37, 8223. (659) (a) Zhao, M. M.; McNamara, J. M.; Ho, G.-J.; Emerson, K. M.; Song, Z. J.; Tschaen, D. M.; Brands, K. M. J.; Dolling, U.-H.; Grabowski, E. J. J.; Reider, P. J.; Cottrell, I. F.; Ashwood, M. S.; Bishop, B. C. J. Org. Chem. 2002, 67, 6743. (b) Ashwood, M. S.; Bishop, B. C.; Cottrell, I. F. U.K. Patent 2,341,386, 2000; U.S. Patent 6,046,325, 2000. (660) Gualandi, A.; Manoni, F.; Monari, M.; Savoia, D. Tetrahedron 2010, 66, 715. (661) Pedrosa, R.; Andrés, C.; Mendiguchía, P.; Nieto, J. J. Org. Chem. 2006, 71, 8854. (662) (a) Eliel, E. L.; He, X.-C. Tetrahedron 1987, 43, 4979. (b) Eliel, E. L.; He, X.-C. J. Org. Chem. 1990, 55, 2114. (663) (a) Sano, H.; Noguchi, T.; Miyajima, A.; Hashimoto, Y.; Miyachi, H. Bioorg. Med. Chem. Lett. 2006, 16, 3068. (b) Perregaard, J.; Arnt, J.; Boegesoe, K. P.; Hyttel, J.; Sanchez, C. J. Med. Chem. 1992, 35, 1092. (c) Cole, D. C.; Ellingboe, J. W.; Lennox, W. J.; Mazandarani, H.; Smith, D. L.; Stock, J. R.; Zhang, G.; Zhou, P.; Schechter, L. E. Bioorg. Med. Chem. Lett. 2005, 15, 379. (d) Li, Q.; Li, T.; Woods, K. W.; Gu, W.-Z.; Cohen, J.; Stoll, V. S.; Galicia, T.; Hutchins, C.; Frost, D.; Rosenberg, S. H.; Sham, H. L. Bioorg. Med. Chem. Lett. 2005, 15, 2918. (e) Xu, H.; Liu, W.-Q.; Fan, L.-L.; Chen, Y.; Yang, L.-M.; Lv, L.; Zheng, Y.-T. Chem. Pharm. Bull. 2008, 56, 720. (664) (a) Padwa, A.; Eisenbarth, P. Tetrahedron 1985, 41, 283. (b) Tiecco, M.; Testaferri, L.; Marini, F. Tetrahedron 1996, 52, 11841. (c) Job, A.; Janeck, C. F.; Bettray, W.; Peters, R.; Enders, D. Tetrahedron 2002, 58, 2253. (665) Smalley, R. K. In Comprehensive Heterocyclic Chemistry II; Boulton, A. J., Ed.; Elsevier: Oxford, U.K., 1996; Vol. 6, pp 681−694. (666) Amitina, S. A.; Grigoŕev, I. A.; Mamatyuk, V. I.; Tikhonov, A. Y. Russ. Chem. Bull. 2007, 56, 1190. (667) Gupta, R. R., Ed. Phenothiazines and 1,4-Benzothiazines− Chemical and Biomedical Aspects, Elsevier, Amsterdam, 1988. (668) Schwarz, M. K.; Tumelty, D.; Gallop, M. A. J. Org. Chem. 1999, 64, 2219. (669) Castro, A.; Abasolo, M. I.; Gil, C.; Segarra, V.; Martinez, A. Eur. J. Med. Chem. 2001, 36, 333. (670) Kuroita, T.; Marubayashi, N.; Sano, M.; Kanzaki, K.; Inaba, K.; Kawakita, T. Chem. Pharm. Bull. 1996, 44, 2051. (671) King, D. J.; Wager, E. J. Psychopharmacol. 1998, 12, 283. (672) Petts, H. V.; Pleuvry, B. J. Br. J. Anaesthesiol. 1983, 55, 437. (673) Yamamoto, T.; Hori, M.; Watanabe, I.; Harada, K.; Ikeda, S.; Ohtaka, H. Chem. Pharm. Bull. 2000, 48, 843.

(674) (a) Gupta, R. R.; Saraswat, V.; Gupta, V.; Rajoria, C. M.; Gupta, A.; Jain, M. J. Heterocycl. Chem. 1993, 30, 803. (b) Trifilenkov, A. S.; Kobak, V. V.; Salina, M. A.; Kusovkova, J. A.; Ilyin, A. P.; Khvat, A. V.; Tkachenko, S. E.; Ivachtchenko, A. V. J. Comb. Chem. 2006, 8, 469. (c) Sanghvi, A. S.; Dabholkar, V. V. Indian J. Heterocycl. Chem. 2006, 16, 105. (d) Dabholkar, V. V.; Ansari, F. Y. Indian J. Chem. 2008, 47B, 1759. (675) Reliquet, A.; Besbes, R.; Reliquet, F.; Meslin, J. C. Synthesis 1991, 543. (676) MacKenzie, N. E.; Thomson, R. H.; Greenhalgh, C. W. J. Chem. Soc., Perkin Trans. 1 1980, 2923. (677) (a) Mannhold, R. Med. Res. Rev. 2004, 24, 213. (b) Braghiroli, D.; Puia, G.; Cannazza, G.; Tait, A.; Parenti, C.; Losi, G.; Baraldi, M. J. Med. Chem. 2002, 45, 2355. (c) Bliss, T. V. P.; Collingridge, G. L. Nature 1993, 361, 31. (d) Arranz, M. E.; Díaz, J. A.; Ingate, S. T.; Witvrouw, M.; Pannecouque, C.; Balzarini, J.; De Clercq, E.; Vega, S. Bioorg. Med. Chem. 1999, 7, 2811. (e) Martinez, A.; Gil, C.; Abasolo, M. I.; Castro, A.; Bruno, A. M.; Perez, C.; Prieto, C.; Otero, J. J. Med. Chem. 2000, 43, 3218. (f) Tait, A.; Luppi, A.; Cermelli, C. J. Heterocycl. Chem. 2004, 41, 747. (g) Martínez, A.; Castro, A.; Gil, C.; Miralpeix, M.; Segarra, V.; Doménech, T.; Beleta, J.; Palacios, J. M.; Ryder, H.; Miró, X.; Bonet, C.; Casacuberta, J. M.; Azorín, F.; Piña, B.; Puigdoménech, P. J. Med. Chem. 2000, 43, 683. (h) Castro, A.; Abasolo, M. I.; Gil, C.; Segarra, V.; Martienz, A. Eur. J. Med. Chem. 2001, 36, 333. (i) de Tullio, P.; Dupont, L.; Francotte, P.; Counerotte, S.; Lebrun, P.; Pirotte, B. J. Med. Chem. 2006, 49, 6779. (678) (a) de Tullio, P.; Becker, B.; Boverie, S.; Dabrowski, M.; Wahl, P.; Antoine, M.-H.; Somers, F.; Sebille, S.; Ouedraogo, R.; Hansen, J. B.; Lebrun, P.; Pirotte, B. J. Med. Chem. 2003, 46, 3342. (b) Boverie, S.; Antoine, M.-H.; Somers, F.; Becker, B.; Sebille, S.; Ouedraogo, R.; Counerotte, S.; Pirotte, B.; Lebrun, P.; de Tullio, P. J. Med. Chem. 2005, 48, 3492. (c) de Tullio, P.; Boverie, S.; Becker, B.; Antoine, M.H.; Nguyen, Q.-A.; Francotte, P.; Counerotte, S.; Sebille, S.; Pirotte, B.; Lebrun, P. J. Med. Chem. 2005, 48, 4990. (d) Deng, Y.; Xu, R.; Ye, Y. J. Chin. Pharm. Sci. 2000, 9, 116. (e) Kamal, A.; Reddy, K. S.; Ahmed, S. K.; Khan, M. N. A.; Sinha, R. K.; Yadav, J. S.; Arora, S. K. Bioorg. Med. Chem. 2006, 14, 650. (679) Topliss, J. G.; Sherlock, M. H.; Clarke, F. H.; Daly, M. C.; Pettersen, B. W.; Lipski, J.; Sperber, N. J. Org. Chem. 1961, 26, 3842. (680) Grivas, J. C. J. Org. Chem. 1976, 41, 1325. (681) (a) Sharaf, M. H. M., Jr.; Schiff, P. L.; Tackie, A. N.; Phoebe, C. H., Jr.; Davis, A. O.; Andrews, C. W.; Crouch, R. C.; Martin, G. E. J. Hetereocycl. Chem. 1995, 32, 1631. (b) Maelicke, A.; Albuquerque, E. X. Drug Discovery Today 1996, 1, 53. (682) (a) Kogen, H.; Toda, N.; Tago, K.; Marumoto, S.; Takami, K.; Ori, M.; Yamada, N.; Koyama, K.; Naruto, S.; Abe, K.; Yamazaki, R.; Hara, T.; Aoyagi, A.; Abe, Y.; Kaneko, T. Org. Lett. 2002, 4, 3359. (b) Dalence-Guzmán, M. F.; Berglund, M.; Skogvall, S.; Sterner, O. Bioorg. Med. Chem. 2008, 16, 2499. (c) Berglund, M.; DalenceGuzmán, M. F.; Skogvall, S.; Sterner, O. Bioorg. Med. Chem. 2008, 16, 2513. (d) Ishibashi, H.; Kobayashi, T.; Nakashima, S.; Tamura, O. J. Org. Chem. 2000, 65, 9022. (e) Schäfer, S.; Steioff, K.; Linz, W.; Bleich, M.; Busch, A. E.; Löhn, M. Eur. J. Pharmacol. 2004, 484, 361. (f) Gentles, R. G.; Middlemiss, D.; Proctor, G. R.; Sneddon, A. H. J. Chem. Soc., Perkin Trans. 1 1991, 1423. (g) Clark, M. T.; Chang, J.; Navran, S. S.; Akbar, H.; Mukhopadhyay, A.; Amin, H.; Feller, D. R.; Miller, D. D. J. Med. Chem. 1986, 29, 181. (h) Banwell, M. G.; Kokas, O. J.; Willis, A. C. Org. Lett. 2007, 9, 3503. (i) Mach, U. R.; Hackling, A. E.; Perachon, S.; Ferry, S.; Wermuth, C. G.; Schwartz, J.-C.; Sokoloff, P.; Stark, H. ChemBioChem 2004, 5, 508. (j) Sha, C.-K.; Hong, A.-W.; Huang, C.-M. Org. Lett. 2001, 3, 2177. (k) Guillou, C.; Beunard, J.-L.; Gras, E.; Thal, C. Angew. Chem., Int. Ed. 2001, 40, 4745. (683) (a) Lohse, O.; Beutler, U.; Fünfschilling, P.; Furet, P.; France, J.; Kaufmann, D.; Penn, G.; Zaugg, W. Tetrahedron Lett. 2001, 42, 385. (b) Carril, M.; SanMartin, R.; Churruca, F.; Tellitu, I.; Domínguez, E. Org. Lett. 2005, 7, 4787. (c) Carril, M.; SanMartin, R.; Domínguez, E.; Tellitu, I. Tetrahedron 2006, 63, 690. (d) Fuenfschilling, P. C.; Zaugg, W.; Beutler, U.; Kaufmann, D.; Lohse, O.; Mutz, J.-P.; Onken, U.; Reber, J.-L.; Shenton, D. Org. Process Res. Dev. 2005, 9, 272. CF


Chemical Reviews

Review

1994, 31, 61. (g) Archer, G. A.; Sternbach, L. H. Chem. Rev. 1968, 68, 747. (h) Insuasty, B.; Ramos, M.; Moreno, R.; Quiroga, J.; Sánchez, A.; Nogueras, M.; Hanold, N.; Meier, H. J. Heterocycl. Chem. 1995, 32, 1229. (i) Broggini, G.; Molteni, G.; Terraneo, A.; Zecchi, G. Tetrahedron 1999, 55, 14803. (j) Santagada, V.; Perissutti, E.; Fiorino, F.; Vivenzio, B.; Caliendo, G. Tetrahedron Lett. 2001, 42, 2397. (k) Anwar, B.; Grimsey, P.; Hemming, K.; Krajniewski, M.; Loukou, C. Tetrahedron Lett. 2000, 41, 10107. (l) White, J. D.; Haefliger, W. E.; Dimsdale, M. J. Tetrahedron 1970, 26, 233. (693) Sañudo, M.; García-Valverde, M.; Marcaccini, S.; Delgado, J. J.; Rojo, J.; Torroba, T. J. Org. Chem. 2009, 74, 2189. (694) Lecinska, P.; Corres, N.; Moreno, D.; García-Valverde, M.; Marcaccini, S.; Torroba, T. Tetrahedron 2010, 66, 6783. (695) Tolkunov, A. S.; Bogza, S. L. Chem. Heterocycl. Compd. 2010, 46, 711. (696) (a) Grinsteiner, T. J.; Kishi, Y. Tetrahedron Lett. 1994, 45, 8333. (b) Grinsteiner, T. J.; Kishi, Y. Tetrahedron Lett. 1994, 45, 8337. (697) (a) Bajaj, K.; Archana, Kumar, A. Eur. J. Med. Chem. 2004, 39, 369. (b) Audouze, K.; Nielsen, E. Ø.; Peters, D. J. Med. Chem. 2004, 47, 3089. (c) Allaway, C. L.; Daly, M.; Nieuwenhuyzen, M.; Saunders, G. C. J. Fluorine Chem. 2002, 115, 91. (d) Ott, I.; Kircher, B.; Heinisch, G.; Matuszczak, B. J. Med. Chem. 2004, 47, 4627. (698) (a) Clark, S. M.; Osborn, H. M. I. Tetrahedron: Asymmetry 2004, 15, 3643. (b) Xu, J.-F.; Huang, X. J. Comb. Chem. 2009, 11, 938. (c) Das, S. K.; Srivastava, A. K.; Panda, G. Tetrahedron Lett. 2010, 51, 1483. (d) Räcker, R.; Döring, K.; Reiser, O. J. Org. Chem. 2000, 65, 6932. (e) Sharma, G.; Park, J. Y.; Park, M. S. Bioorg. Med. Chem. Lett. 2008, 18, 3188. (699) (a) Choi, M.-S.; Yamazaki, T.; Yamazaki, I.; Aida, T. Angew. Chem., Int. Ed. 2004, 43, 150. (b) Aratani, N.; Kim, D.; Osuka, A. Acc. Chem. Res. 2009, 42, 1922. (c) Faiz, J. A.; Heitz, V.; Sauvage, J.-P. Chem. Soc. Rev. 2009, 38, 422. (d) Gust, D.; Moore, T. A.; Moore, A. L. Acc. Chem. Res. 2001, 34, 40. (e) Benniston, A. C.; Harriman, A.; Li, P. J. Am. Chem. Soc. 2010, 132, 26. (f) Kuciauskas, D.; Liddell, P. A.; Lin, S.; Johnson, T. E.; Weghorn, S. J.; Lindsey, J. S.; Moore, A. L.; Moore, T. A.; Gust, D. J. Am. Chem. Soc. 1999, 121, 8604. (g) Balaban, T. S. Acc. Chem. Res. 2005, 38, 612. (700) (a) Jurow, M.; Schuckman, A. E.; Batteas, J. D.; Drain, C. M. Coord. Chem. Rev. 2010, 254, 2297. (b) Otsuki, J. Coord. Chem. Rev. 2010, 254, 2311. (c) Drain, C. M.; Varotto, A.; Radivojevic, I. Chem. Rev. 2009, 109, 1630. (d) Beletskaya, I.; Tyurin, V. S.; Tsivadze, A. Y.; Guilard, R.; Stern, C. Chem. Rev. 2009, 109, 1659. (e) Liddell, P. A.; Kodis, G.; Moore, A. L.; Moore, T. A.; Gust, D. J. Am. Chem. Soc. 2002, 124, 7668. (f) Waskitoaji, W.; Hyakutake, T.; Kato, J.; Watanabe, M.; Nishide, H. Chem. Lett. 2009, 38, 1164. (701) (a) Peng, X.; Nakamura, Y.; Aratani, N.; Kim, D.; Osuka, A. Tetrahedron Lett. 2004, 45, 4981. (b) Wagner, R. W.; Lindsey, J. S.; Seth, J.; Palaniappan, V.; Bocian, D. F. J. Am. Chem. Soc. 1996, 118, 3996. (702) (a) Campbell, W. M.; Burrell, A. K.; Officer, D. L.; Jolley, K. W. Coord. Chem. Rev. 2004, 248, 1363. (b) Xiang, N.; Liu, Y.; Zhou, W.; Huang, H.; Guo, X.; Tan, Z.; Zhao, B.; Shen, P.; Tan, S. Eur. Polym. J. 2010, 46, 1084. (703) (a) Montes, V. A.; Pérez-Bolívar, C.; Agarwal, N.; Shinar, J.; Anzenbacher, P., Jr. J. Am. Chem. Soc. 2006, 128, 12436. (b) Wang, X.; Wang, H.; Yang, Y.; He, Y.; Zhang, L.; Li, Y.; Li, X. Macromolecules 2010, 43, 709. (704) Poon, C.-T.; Zhao, S.; Wong, W.-K.; Kwong, D. W. J. Tetrahedron Lett. 2010, 51, 664. (705) (a) Swamy, N.; James, D. A.; Mhor, S. C.; Hanson, R. N.; Ray, R. Bioorg. Med. Chem. 2002, 10, 3237. (b) Chaleix, V.; Sol, V.; Krausz, P. Tetrahedron Lett. 2011, 52, 2977. (c) Sol, V.; Lamarche, F.; Enache, M.; Garcia, G.; Granet, R.; Guilloton, M.; Blais, J. C.; Krausz, P. Bioorg. Med. Chem. 2006, 14, 1364. (d) Schneider, R.; Schmitt, F.; Frochot, C.; Fort, Y.; Lourette, N.; Guillemin, F.; Müller, J.-F.; Barberi-Heyob, M. Bioorg. Med. Chem. 2005, 12, 2799. (e) Ethirajan, M.; Chen, Y.; Joshi, P.; Pandey, R. K. Chem. Soc. Rev. 2011, 40, 340. (706) (a) Goldberg, I. Chem. Commun. 2005, 1243. (b) Goldberg, I. CrystEngComm 2008, 10, 637. (c) Suslick, K. S.; Bhyrappa, P.; Chou,

(e) Kaufmann, D.; Füenfschilling, P. C.; Beutler, U.; Hoehn, P.; Lohse, O.; Zaugg, W. Tetrahedron Lett. 2004, 45, 5275. (f) Sakya, S. M.; Flick, A. C.; Coe, J. W.; Gray, D. L.; Liang, S.; Ferri, F.; Van Den Berg, M.; Pouwer, K. Tetrahedron Lett. 2012, 53, 723. (g) Pearson, W. H.; Aponick, A.; Dietz, A. L. J. Org. Chem. 2006, 71, 3533. (h) Pearson, W. H.; Aponick, A. Org. Lett. 2001, 3, 1327. (i) Lee, H. K.; Im, J, H.; Jung, S. H. Tetrahedron 2007, 63, 3321. (j) Vieira, T. O.; Alper, H. Org. Lett. 2008, 10, 485. (k) Basavaiah, D.; Satyanarayana, T. Chem. Commun. 2004, 32. (k) Nyerges, M.; Virányi, A.; Pintér, Á .; Tő ke, L. Tetrahedron Lett. 2003, 44, 793. (l) Kamimura, A.; Taguchi, Y.; Omata, Y.; Hagihara, M. J. Org. Chem. 2003, 68, 4996. (m) Katritzky, A. R.; Maimait, R.; Xu, Y.-J.; Akhmedova, R. G. Synthesis 2002, 601. (n) Martins, J. C.; Rompaey, K. V.; Wittmann, G.; Tömböly, C.; Tóth, G.; De Kimpe, N.; Tourwé, D. J. Org. Chem. 2001, 66, 2884. (o) Griesbeck, A. G.; Mauder, H. Angew. Chem., Int. Ed. 1992, 31, 73. (p) Fuerstner, A.; Guth, O.; Dueffels, A.; Seidel, G.; Liebl, M.; Gabor, B.; Mynott, R. Chem.Eur. J. 2001, 7, 4811. (q) Wipf, P.; Rector, S.; Takahashi, H. J. Am. Chem. Soc. 2002, 124, 14848. (r) Hunt, J. C. A.; Laurent, P.; Moody, C. J. J. Chem. Soc., Perkin Trans. 1 2002, 2378. (684) Pedrosa, R.; Andrés, C.; Gutiérrez-Loriente, A.; Nieto, J. Eur. J. Org. Chem. 2005, 2449. (685) (a) Evans, B. E.; Rittle, K. E.; Bock, M. G.; DiPardo, R. M.; Freidinger, R. M.; Whitter, W. L.; Lundell, G. F.; Veber, D. F.; Anderson, P. S.; Chang, R. S. L.; Lotti, V. J.; Cerino, D. J.; Chen, T. B.; Kling, P. J.; Kunkel, K. A.; Springer, J. P.; Hirschfield, J. J. Med. Chem. 1988, 31, 2235. (b) Herrero, S.; García-López, M. T.; Herranz, R. J. Org. Chem. 2003, 68, 4582. (686) (a) Showell, G. A.; Bourrain, S.; Neduvelil, J. G.; Fletcher, S. R.; Baker, R.; Watt, A. P.; Fletcher, A. E.; Freedman, S. B.; Kemp, J. A.; Marshall, G. R.; Patel, S.; Smith, A. J.; Matassa, V. G. J. Med. Chem. 1994, 37, 719. (b) Wright, W. B., Jr.; Brabander, H. J.; Greenblatt, E. N.; Day, I. P.; Hardy, R. A., Jr. J. Med. Chem. 1978, 21, 1087. (c) Boojamra, C. G.; Burow, K. M.; Thompson, L. A.; Ellman, J. A. J. Org. Chem. 1997, 62, 1240. (d) Webb, R. R., II; Barker, P. L.; Baier, M.; Reynolds, M. E.; Robarge, K. D.; Blackburn, B. K.; Tischler, M. H.; Weese, K. J. Tetrahedron Lett. 1994, 35, 2113. (e) Iden, H. S.; Lubell, W. D. J. Org. Chem. 2007, 72, 8980. (f) Iden, H. S.; Lubell, W. D. J. Comb. Chem. 2008, 10, 691. (687) (a) Thomas, A. W. Bioorg. Med. Chem. Lett. 2002, 12, 1881. (b) Schutz, H. Benzodiazepines; Springer: Heidelberg, Germany, 1982. (688) (a) Thurston, D. E.; Bose, D. S. Chem. Rev. 1994, 94, 433. (b) Wilkinson, G. P.; Taylor, J. P.; Shnyder, S.; Cooper, P.; Howard, P. W.; Thurston, D. E.; Jenkins, T. C.; Loadman, P. M. Invest. New Drugs 2004, 22, 231. (689) Nallan, L.; Bauer, K. D.; Bendale, P.; Rivas, K.; Yokoyama, K.; Hornéy, C. P.; Pendyala, P. R.; Floyd, D.; Lombardo, L. J.; Williams, D. K.; Hamilton, A.; Sebti, S.; Windsor, W. T.; Weber, P. C.; Buckner, F. S.; Chakrabarti, D.; Gelb, M. H.; Van Voorhis, W. C. J. Med. Chem. 2005, 48, 3704. (690) Kukla, M. J.; Breslin, H. J.; Diamond, C. J.; Grous, P. P.; Ho, C. Y.; Miranda, M.; Rodgers, J. D.; Sherrill, R. G.; De Clercq, E.; Pauwels, R.; Andries, K.; Moens, L. J.; Janssen, M. A. C.; Janssen, P. A. J. J. Med. Chem. 1991, 34, 3187. (691) (a) Hunt, J. T.; Ding, C. Z.; Batorsky, R.; Bednarz, M.; Bhide, R.; Cho, Y.; Chong, S.; Chao, S.; Gullo-Brown, J.; Guo, P.; Kim, S. H.; Lee, F. Y. F.; Leftheris, K.; Miller, A.; Mitt, T.; Patel, M.; Penhallow, B. A.; Ricca, C.; Rose, W. C.; Schmidt, R.; Slusarchyk, W. A.; Vite, G.; Manne, V. J. Med. Chem. 2000, 43, 3587. (b) Dourlat, J.; Liu, W.-Q.; Gresh, N.; Garbay, C. Bioorg. Med. Chem. Lett. 2007, 17, 2527. (692) (a) Fenster, E.; Smith, B. T.; Gracias, V.; Milligan, G. L.; Aubé, J. J. Org. Chem. 2008, 73, 201. (b) Fenster, E.; Rayabarapu, D. K.; Zhang, M.; Mukherjee, S.; Hill, D.; Neuenswander, B.; Schoenen, F.; Hanson, P. R.; Aubé, J. J. Comb. Chem. 2008, 10, 230. (c) Wlodarczyk, N.; Gilleron, P.; Millet, R.; Houssin, R.; Hénichart, J.-P. Tetrahedron Lett. 2007, 48, 2583. (d) Song, L.; Chen, X.; Zhang, S.; Zhang, H.; Li, P.; Luo, G.; Liu, W.; Duan, W.; Wang, W. Org. Lett. 2008, 10, 5489. (e) Gellerman, G.; Hazan, E.; Kovaliov, M.; Albeck, A.; Shatzmiler, S. Tetrahedron 2009, 65, 1389. (f) Insuasty, B.; Ramos, M.; Quiroga, J.; Sánchez, A.; Nogueras, M.; Hanold, N.; Meier, H. J. Heterocycl. Chem. CG


Chemical Reviews

Review

J.-H.; Kosal, M. E.; Nakagaki, S.; Smithenry, D. W.; Wilson, S. R. Acc. Chem. Res. 2005, 38, 283. (d) Hosseini, M. W. Acc. Chem. Res. 2005, 38, 313. (e) Cuesta, L.; Sessler, J. L. Chem. Soc. Rev. 2009, 38, 2716. (f) Matano, Y.; Imahori, H. Acc. Chem. Res. 2009, 42, 1193. (707) (a) Pasternack, R. F.; Gibbs, E. J.; Villafranca, J. J. Biochemistry 1938, 22, 2406. (b) D’Urso, A.; Mammana, A.; Balaz, M.; Holmes, A. E.; Berova, N.; Lauceri, R.; Purrello, R. J. Am. Chem. Soc. 2009, 131, 2046. (708) (a) Wagner, R. W.; Lawrence, D. S.; Lindsey, J. S. Tetrahedron Lett. 1987, 28, 3069. (b) Lindsey, J. S.; Schreiman, I. C.; Hsu, H. C.; Kearney, P. C.; Marguerettaz, A. M. J. Org. Chem. 1987, 52, 827. (c) Dogutan, D. K.; Ptaszek, M.; Lindsey, J. S. J. Org. Chem. 2008, 73, 6187. (d) Lindsey, J. S. Acc. Chem. Res. 2010, 43, 300. (e) Milgrom, L. R. J. Chem. Soc., Perkin Trans. 1 1984, 1483. (f) Harmjanz, M.; Božidarević, I.; Scott, M. J. Org. Lett. 2001, 3, 2281. (g) Robinsohn, A. E.; Buldain, G. Y. J. Heterocycl. Chem. 1995, 32, 1567. (709) Nishino, N.; Wagner, R. W.; Lindsey, J. S. J. Org. Chem. 1996, 61, 7534. (710) Ivonin, S. P.; Lapandin, A. V.; Anishchenko, A. A.; Shtamburg, V. G. Synth. Commun. 2004, 34, 451. (711) Ivonin, S. P.; Mazepa, A. V.; Lapandin, A. V. Chem. Heterocycl. Compd. 2006, 42, 451. (712) (a) Liang, X.; Sadler, P. J. Chem. Soc. Rev. 2004, 33, 246. (b) Delgado, R.; Félix, V.; Lima, L. M. P.; Price, D. W. Dalton Trans. 2007, 2734. (c) Casero, R. A., Jr.; Woster, P. M. J. Med. Chem. 2009, 52, 4551. (713) Suchý, M.; Hudson, R. H. E. Eur. J. Org. Chem. 2008, 4847. (714) (a) Caravan, P. Chem. Soc. Rev. 2006, 35, 512. (b) Aime, S.; Crich, S. G.; Gianolio, E.; Giovenzana, G. B.; Tei, L.; Terreno, E. Coord. Chem. Rev. 2006, 250, 1562. (c) De León-Rodríguez, L. M.; Kovacs, Z. Bioconjugate Chem. 2008, 19, 391. (d) Lauffer, R. B. Chem. Rev. 1987, 87, 901. (715) (a) Liu, S. Adv. Drug Delivery Rev. 2008, 60, 1347. (b) Tanaka, K.; Fukase, K. Org. Biomol. Chem. 2008, 6, 815. (716) (a) Aime, S.; Botta, M.; Parker, D.; Williams, J. A. G. J. Chem. Soc., Dalton Trans. 1996, 17. (b) Parker, D.; Williams, J. A. G. J. Chem. Soc., Perkin Trans. 2 1995, 1305. (717) (a) Gunnlaugsson, T.; Leonard, J. P. Chem. Commun. 2005, 3114. (b) Bünzli, J.-C. G.; Piguet, C. Chem. Soc. Rev. 2005, 34, 1048. (718) Reichenbach-Klinke, R.; König, B. J. Chem. Soc., Dalton Trans. 2002, 121. (719) De Clercq, E. Nat. Rev. Drug Discovery 2003, 2, 581. (720) (a) Macrocycle Synthesis: A Practical Approach, Parker, D., Ed.; Oxford University Press: Oxford, U.K., 1996. (b) Renn, O.; Meares, C. F. Bioconjugate Chem. 1992, 3, 563. (c) Takenouchi, K.; Tabe, M.; Watanabe, K.; Hazato, A.; Kato, Y.; Shionoya, M.; Koike, T.; Kimura, E. J. Org. Chem. 1993, 58, 6895. (d) Gilbert, M. L.; Brown, G. M.; Elbert, J. E.; Sachleben, R. A. Tetrahedron Lett. 1993, 34, 5531. (e) Ansari, M. H.; Ahmad, M.; Dicke, K. A. Bioorg. Med. Chem. Lett. 1993, 3, 1067. (721) Edlin, C. D.; Faulkner, S.; Parker, D.; Wilkinson, M. P. Chem. Commun. 1996, 1249. (722) Obijalska, E.; Mlostoń, G.; Linden, A.; Heimgartner, H. Helv. Chim. Acta 2010, 93, 1725.

CH


Arylglyoxals in Synthesis of Heterocyclic Compounds - ACS Publications

Recommend Documents