Review pubs.acs.org/CR
Chiral Iron Catalysts for Asymmetric Synthesis Kovuru Gopalaiah* Department of Chemistry, University of Delhi, Delhi-110007, India Author Information Corresponding Author Notes Biography Acknowledgments Dedication References Note Added in Proof
1. INTRODUCTION Over the past few decades, asymmetric metal catalysis has become a major area in organic chemistry.1 This allows efficient access to a variety of important enantiomerically enriched molecules to meet the growing demands of both industry and academia.2 Asymmetric metal-catalytic reactions can produce large quantities of chiral products with a very high efficiency using small amounts of chiral metal catalysts. Much of the work in asymmetric metal catalysis has been performed using noble metals based on rhodium, palladium, ruthenium, and iridium complexes. However, the limited availability of these metals as well as their high price and considerable toxicity makes it desirable to search for clean, sustainable, and environmentally friendly alternatives. Therefore, chemists are focusing their attention on the use of first-row transition metals, especially iron and copper, which have their own obvious advantages and unique features. Iron is most abundant metal in Earth’s crust (∼4.7 wt %) after aluminum. The Earth’s core is believed to consist of mainly iron. Iron compounds are present in the soil, in the green plants and in hemoglobin (0.34% Fe). Iron is the most versatile metal in commerce. Iron is cheap, less toxic, and benign, shows variable oxidation states, and is amenable to ligation with nitrogen-, oxygen-, or phosphorus-based ligand sets. That the salts of iron function as good Lewis acids is an additional feature. Many iron salts and iron complexes are commercially available on a large scale or easy to synthesize. Iron is present in many oxidative enzymes (oxidases) such as cytochrome P-450, nitrogenase and methane monooxygenase, which perform some of the most difficult chemical transformations with admirable ease.3 The desire to emulate ironcatalyzed biological processes in vitro constitutes one important source of inspiration for the iron chemistry. Iron catalysis was brought into focus by Reppe in 1949,4 who used iron pentacarbonyl (discovered in 1891)5 for the hydroaminomethylation of olefins. Other important landmark discoveries in iron chemistry are ferrocene (1951)6 and Collman reagent Na2Fe(CO)4 (1959).7 Since then, there has been great progress in the design and use of iron catalysts in organic synthesis. An
CONTENTS 1. Introduction 2. Oxygen Transfer/Iron-Oxo and Related Species 2.1. Epoxidation 2.1.1. Porphyrin-Based Catalysts 2.1.2. Non-Porphyrin-Based Catalysts 2.2. Hydroxylation at Benzylic Carbon 2.3. cis-Dihydroxylation 2.4. Sulfide Oxidations 2.4.1. Porphyrin-Based Catalysts 2.4.2. Non-Porphyrin-Based Catalysts 3. Hydride Transfer/Iron Hydride and Related Species 3.1. Transfer Hydrogenation of Ketones 3.2. Hydrogenation and Transfer Hydrogenation of Imines 3.3. Hydrosilylation of Ketones 4. Activation of Lewis Basic Substrates/Iron Lewis Acids 4.1. Diels−Alder Reaction 4.2. 1,3-Dipolar Cycloadditions 4.3. Mukaiyama−Aldol Reaction 4.4. Mannich-Type Reaction 4.5. Michael, Sulfa-Michael, and Oxa-Michael Reactions 4.6. Friedel−Crafts-Type Reaction 4.7. Nazarov Cyclizations 5. Carbene Transfer/Iron-Carbene Species 5.1. Cyclopropanation 5.2. C−H Bond Functionalization of Indoles 5.3. O−H Bond Insertion Reactions 6. Nitrene Transfer/Iron-Nitrene Species 7. Carbanion Transfer/Organoiron Species 8. Miscellaneous 8.1. Oxidative Coupling of 2-Naphthols 8.2. Oxidative Kinetic Resolution of Secondary Alcohols 8.3. Oxyamination of Olefins 9. Conclusions © 2013 American Chemical Society
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Received: June 11, 2012 Published: March 5, 2013 3248
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excellent review article by Bolm et al. summarized the achievements in iron catalysis, in 2004.8 Subsequently, several reviews9 and books10 have been published on iron-catalyzed organic reactions. The next phase of development is the application of iron catalysis in asymmetric synthesis. There are significant developments in the design and use of chiral iron catalysts beginning with Groves discovery of catalytic asymmetric epoxidations with chiral iron-porphyrins in 1983.11 It is deemed useful to compile a general account at one place so that it will be useful to those interested in iron catalysis in asymmetric synthesis. The contents are organized on the basis of the mode of action of the catalyst and the type of catalytically active iron species. This review covers the literature up to mid 2012.
Figure 1. Groves−Myers chiral iron-porphyrins for enantioselective epoxidation of olefins.11
Table 1. Catalytic Asymmetric Epoxidations with Iron− Porphyrin 1a
2. OXYGEN TRANSFER/IRON-OXO AND RELATED SPECIES Cytochromes are redox enzymes, distributed widely in all living cells. They are conjugated proteins having an iron-porphyrin as prosthetic group. Cytochrome c and cytochrome P-450 are the most extensively studied oxidases. They bring about a wide range of stereoselective transformations, such as epoxidations, hydroxylations and others. There have been several attempts to design synthetic iron-porphyrins modeling the oxygen transfer reactions of cytochrome P-450 family of heme enzymes.12,13 Looking at the substantial success achieved in the design and application of metallosalens for catalytic asymmetric oxidations,14 many realized the need for sustained researches on catalyst design related to porphyrin core. Groves and coworkers are the pioneers in this area who initiated chiral ironporphyrin catalysts for a variety of selective oxidations.11,15 The desirable features of the metalloporphyrins are (i) rigid macrocyclic core, (ii) the alterable periphery in many geometries, and (iii) good stability of the catalyst toward oxidative processes. Over the last two decades, a large number of different complex structures have been designed and synthesized with the hope of achieving high ee values and high turnover number (TON). However, the synthesis of chiral porphyrin ligands is beset with practical difficulties.16 In view of this, the development of alternative catalytic systems (nonporphyrin-based catalysts), which may have a greater scope and applicability are also being actively pursued over the past decade. This section describes the advances made in asymmetric epoxidations, hydroxylation of benzylic compounds, cisdihydroxylation and sulfide oxidations using synthetic chiral iron catalysts to activate oxygen and transfer it to a substrate.
Reactions were performed in CH2Cl2 with 31.5 μmol of 1, 795 μmol of iodosylbenzene, and 2.6 mmol of olefin, at −8 °C for 3−4 h. b Phenylacetaldehyde was formed in 16% yield. a
Table 2. Catalytic Asymmetric Epoxidations with Iron− Porphyrin 2a
a Reactions were performed in toluene with 31.5 μmol of 2, 795 μmol of iodosylmesitylene and 2.6 mmol of olefin, at 0 °C for 12 h. bAt −23 °C; 7.5% p-chlorophenylacetaldehyde was also formed.
1,1′-binaphthyl-2-carboxamido]phenyl)porphyrin (2) iron complexes (Figure 1) were found to bring about asymmetric induction in the presence of either iodosylbenzene or iodosylmesitylene as the oxygen donors. Enantioselectivities up to 51% and TON of about 100 were achieved (Tables 1 and 2). Besides epoxides, aldehydes were formed as byproducts. The aldehyde formation is believed to be independent and not as a result of rearrangement of the epoxide. Although the ee values obtained with these catalysts are moderate (9−51%), Groves and Myers discovery disclosed a new approach and propelled active research in this area. The proposed mechanism of this epoxidation is summarized in Figure 2. It involves the initial formation of a reactive iron− oxo intermediate 3 from iron-porphyrin complex and iodosylarene. Olefin approaches the reactive oxoiron group
2.1. Epoxidation
Many chiral iron catalysts have been developed for epoxidation. For the purpose of this review, these catalytic systems are conveniently divided into two classes: porphyrin-based catalysts and non-porphyrin-based catalysts. The former class is further subdivided into three types in which the chiral auxiliary is linked through (i) amide bonds, (ii) ether bonds, and (iii) C− C bonds. 2.1.1. Porphyrin-Based Catalysts. 2.1.1.1. Chiral Auxiliaries Linked to Porphyrin via Amide Bonds. The first example of asymmetric epoxidation of olefins catalyzed by a synthetic iron-porphyrin complex was described by Groves and Myers, in 1983.11 The αβαβ-tetrakis(o-(R)-hydratropamidophenyl)porphyrin (1) and αβαβ-tetrakis(o-[(S)-2′-carboxymethyl3249
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Table 3. Catalytic Asymmetric Epoxidations with Vaulted Binaphthyl Iron-Porphyrin 5 (M = FeCl)a
Figure 2. Proposed catalytic pathway for the epoxidation of olefins by 1 and 2 complexes.
a
Reactions were performed in toluene with a ratio of catalyst/ iodosylbenzene/olefin = 1:100:1000, at 0 °C for 2 h. b20 °C. c−15 °C.
Figure 3. “Vaulted binaphthyl” porphyrin. Figure 4. Basket-handle (6) and picket (7, 8) iron-porphyrins.
from the side and parallel to the plane of the porphyrin ring as indicated in 4. Groves and Viski prepared porphyrin 5 (M = 2H) from αβαβ-tetrakis(2′-aminophenyl)porphyrin and (R)-(+)-2,2′-dimethoxy-1,1′-bis-6-naphthoylchloride, and the corresponding chloroiron(III) complex (Figure 3).15b They called it as “vaulted binaphthyl” iron-porphyrin and analyzed its structure and utility as a catalyst in asymmetric synthesis. Treatment of various olefins with 5 (M = FeCl) and iodosylbenzene as oxidant, afforded the corresponding epoxides in 30−72% ee (Table 3). The catalyst could be recovered and recycled up to five iterations to obtain the same results. In these reactions, variable amounts of ketones and aldehydes were also formed. Since Groves’s first report, many research groups developed novel chiral porphyrin iron complexes for the asymmetric epoxidation of olefins. Mansuy and co-workers synthesized “basket-handle” iron-porphyrin 6 bearing L-phenylalanine residues, and “picket” iron-porphyrins 7 and 8 bearing the same amino acid (Figure 4).17 These iron complexes were evaluated for the asymmetric epoxidation of p-chlorostyrene in the presence of iodosylbenzene. The iron-porphyrin 6 gave 50% ee of the (R)-epoxide, whereas 7 and 8 led to 12% and 21% ee, respectively, of the (S)-epoxide. The highest enantioselectivity with 6 could be ascribed to the more rigid conformation of the amino acids in close proximity to the iron center. Catalyst 6 favors the approach of the alkene to the FeO
Figure 5. L-Prolinoyl bis-strapped iron-porphyrins.
reactive site from the Re face, leading to the formation of (R)product predominantly. The asymmetric epoxidation of p-chlorostyrene and 1,2dihydronaphthalene using two different series of bis-strapped 3250
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chiral iron-porphyrins, such as αβαβ-9 and α2β2-10 derived from L-prolinoyl residues (Figure 5), were reported by Boitrel
Figure 6. L-Prolinoyl picket-fence iron-porphyrins.
et al.18 The αβαβ geometry did not induce any good enantioselectivity, whereas the α2β2 atropisomers gave ee values
Figure 8. Bis(binaphthyl) porphyrin 13 (M = 2H) and the quinonetype catalyst 14 (M = FeCl).
Table 4. Asymmetric Epoxidation of Olefins Catalyzed by Iron-Porphyrin 13 (M = FeCl)a
Figure 7. “BINOL-capped” iron-porphyrin.
not exceeding 31%. Furthermore, the atropisomers α4, α3β, α2β2, and αβαβ of chiral L-prolinoyl picket-fence ironporphyrins 11 (Figure 6) were evaluated for epoxidation.19,20 The αβαβ-atropisomer gave the best ee (34%) for the epoxide of 1,2-dihydronaphthalene. In 1992, Collman et al. developed “BINOL capped” ironporphyrin 12 (Figure 7) consisting of two chiral BINOL units linked in a macrocyclic ether above each face of the porphyrin.21 In contrast to the “vaulted binaphthyl”15b and “basket handle”17 porphyrins, which have only one chiral group above each face of the porphyrin, 12 has two chiral groups above each face. Catalyst 12 was used for the epoxidation of some mono- and disubstituted aromatic olefins. The enantioselectivities of disubstituted olefins, such as cis-βmethylstyrene and 1,2-dihydronaphthalene were low (21− 29%), while 2-vinylnaphthalene gave better results (63%). Collman’s group also prepared a C2-symmetric chiral porphyrin 13 (M = 2H) bearing binaphthyl handles (Figure 8), by condensation of 2,2′-dimethoxy-1,1′-binaphthyl-3,3′diacylchloride with α2β2-tetrakis(o-aminophenyl)porphyrin atropisomer.22 Using iron-porphyrin 13 (M = FeCl) as a catalyst, a series of styrene derivatives were converted to the corresponding epoxides in the presence of PhIO (Table 4). High enantioselectivities were obtained for styrene oxide (83% ee, entry 1), pentafluorostyrene oxide (88% ee, entry 2), and mchlorostyrene oxide (82% ee, entry 3). The catalyst 13 (M = FeCl) also induced excellent enantioselectivities for nonconjugated terminal olefins, such as 3,3-dimethylbutene and vinyltrimethylsilane (entries 7 and 8). A noteworthy feature of
a
Reactions were performed in CH2Cl2 with 13 (M = FeCl) (1.0 μmol), PhIO (0.10 mmol) and olefin (1.0 mmol) at rt. bThe absolute configuration was not determined
iron catalyst 13 is an exceptional activity. The complex 13 (M = FeCl) induces the epoxidation at a rate of 2400 turnovers per hour if iodosylbenzene is added portionwise to the reaction mixture. The authors believed that the oxidative demethylation of the binaphthyl strap occurs during the reaction to generate a quinone-like structure 14 (M = FeCl) (Figure 8), which may have a bearing on the enantioselectivity. 3251
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group tried to rationalize this interesting observation in terms of molecular modeling concepts. 2.1.1.2. Chiral Auxiliaries Linked to Porphyrin via Ether Bonds. Another class of C2-symmetric porphyrins 21a (M = 2H) and 21b (M = 2H) which have binaphthyl and bitetralin chiral auxiliaries linked by ethereal bonds on both faces, respectively, were synthesized by Maruyama et al. (Figure 12).27 They named these as “twin-coronet” porphyrins. The catalytic activity of 21a,b (M = FeCl) was checked for the epoxidation of a variety of styrene derivatives possessing electron-withdrawing and electron-donating groups (Table 7). The best results were achieved for the electron-deficient substrates (entries 2−6). 2-Nitrostyrene provided the high ee values up to 89% (entries 2 and 10). The bitetralin catalyst (R)21b (M = FeCl) was found to be superior to the binaphthyl catalyst with respect to enantioselection (entries 9 vs 1 and 10 vs 2). Besides epoxides, the corresponding arylacetaldehydes were concomitantly formed in small quantities. The proposed mechanism for the epoxide formation involves either concerted oxygen addition (path a) or an acyclic cationic intermediate formation via electron transfer followed by ionic collapse (route b and c) as shown in Scheme 2. Maruyama et al. also proposed transition state models to explain the chiral induction.27b Maruyama group further evaluated the effect of central metal ion in 21a using Fe and Mn, on the catalytic asymmetric epoxidation of simple olefins.28 These results revealed that the Mn porphyrin catalyst is superior than the iron one in terms of ee values of the resulting epoxides. The iron-porphyrin 22 bearing chiral acetylated glucose units linked to the ortho position of phenyl groups of TPP (TPP = 5,10,15,20-tetraphenylporphyrin) via ether bonds, was reported (Figure 13).29 The activity of this new catalyst was tested on pchlorostyrene. Although the yield of the epoxide was satisfactory, the asymmetric induction was very low (33% ee). In 2001, Lindsay-Smith et al. reported the synthesis of four porphyrins 23a−d (M = 2H) by mixed condensation of pyrrole, (R,R)-2,6-di(1-phenylbutoxy)benzaldehyde and pentafluorobenzaldehyde (Figure 14).30a The sterically crowded iron complex 23a (M = FeCl) possessing four dialkoxyphenyl units, was a poor epoxidation catalyst (16% ee).30b The introduction of smaller pentafluorophenyl groups in place of 2,6-di(1phenylbutoxy)phenyl, enhanced the catalyst reactivity, stability and selectivity. The best results for the epoxidation of styrene (99%, ee = 23%) and cis-hept-2-ene (65%, ee = 21%) were
Scheme 1. Enantioselective Epoxidation of Racemic Allylic Alcohols 15
The iron-porphyrin catalyst 13 (M = FeCl) was used for the asymmetric epoxidation of acyclic and cyclic racemic allyl alcohols 15 (Scheme 1, Table 5).23 Whereas one enantiomer of the allyl alcohol 15 was preferentially oxidized to give the threoor cis-epoxy alcohol 16 (up to 43% ee) as the main product (dr = 73:27 to >95:5), the other enantiomer of 15 is enriched (up to 31% ee). Some non-stereoselective allylic oxidation also takes place to give the enone 17 in variable amounts. The stereochemical outcome of this asymmetric oxidation is rationalized in terms of a synergistic interplay between the hydroxyl group directing effect and the steric interactions of the catalyst 13 (M = FeCl) and the substrate 15. A new family of iron-porphyrins 18 (Figure 9), prepared from Mosher’s acid chloride, 2,6-dinitro-4-tert-butylbenzaldehyde and pentafluorobenzaldehyde, were reported jointly by Rose group and Collman group in 1998.24 Using catalysts 18, the enantioselectivities of styrene oxide were very low (0−6%). In a followup report, Rose and co-workers described the synthesis of iron-porphyrin 19 (Figure 10) named as “seat” iron-porphyrin.25 The asymmetric induction by catalyst 19 for styrene oxide and pentafluorostyrene oxide were 59% and 85% ee, respectively. Rose et al. also developed a C2-symmetric bis(binaphthyl) porphyrin 20 (M = 2H) (Figure 11) whose strap differs from that of 13 (Figure 8) by only two CH2 groups, hoping that 20 would provide more access to the metal center than 13 and also would prevent any oxidative demethylation.26 This strategy proved to be correct as catalyst 20 (M = FeCl) epoxidized several styrene derivatives in high yields and with excellent enantioselectivities (81−97%, Table 6). Furthermore, the catalyst appeared very stable as the ee value remained close to 80% after 16000 turnovers at room temperature. An intriguing fact is that catalyst 13 (M = FeCl) forms (S)-epoxides while catalyst 20 (M = FeCl) generates the (R)-enantiomers. Rose’s
Table 5. Epoxidation of Various Allylic Alcohols 15 with Catalyst 13 (M = FeCl)
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Figure 9. “Mosher-picket” iron-porphyrins 18.
Figure 10. “Seat” iron-porphyrin.
obtained using 23c (M = FeCl) and 23b (M = FeCl) catalysts, respectively. The threitol iron-porphyrins 24a,b (Figure 15), which are derived from ketal-protected threitol-1,4-ditosylate and tetrakis(2,6-dihydroxyphenyl)porphyrin, were used as catalysts for the epoxidation of non-functionalized olefins under different reaction conditions.31 The enantioselectivities of epoxides were superior in aromatic solvents (44% ee in benzene or toluene for styrene oxide with 24a) compared to nonaromatic solvents (10−36% ee in CH3CN, CH2Cl2 and CCl4) suggesting that there should be specific association between aromatic molecules and metalloporphyrin in solution. At −20 °C, ee values were generally high and reached up to 73% for the 24bcatalyzed epoxidations (Table 8). Several attempts to improve the ee by inclusion of amine additives to the reaction mixture or altering the metal (Ru, Mn) in the porphyrin core were unsuccessful. In 2004, Higuchi and co-workers described an efficient synthesis of novel D4-symmetric chiral porphyrin 25 (M = 2H) that utilizes commercially available C2-symmetric diol as the chiral source (Figure 16).32 Epoxidation of styrene with catalyst 25 (M = FeBr) showed moderate enantioselectivity. The ee values were markedly increased by the introduction of electronwithdrawing groups on the aromatic ring of styrene (Table 9). Likewise, the electron-withdrawing groups on the aryl ring of 25 (X = tBuCO, Br; M = FeBr) also increased the enantioselectivity.33
Figure 11. Bis(binaphthyl) porphyrin 20 (M = 2H) bearing binaphthyl unit and CH2-groups in strap.
Table 6. Epoxidation of Styrene Derivatives with IronPorphyrin Catalyst 20 (M = FeCl)a
a Reactions were performed in CH2Cl2 at −5 °C. bReaction conditions: catalyst/PhIO/olefin = 1:100:1000. cReaction conditions: catalyst/PhIO/olefin = 1:1000:10 000.
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Scheme 2. Proposed Mechanism for the Epoxidation of Styrene Derivatives Using “Twin-Coronet” Iron-Porphyrin Catalysts
Figure 12. “Twin-coronet” porphyrins.
Table 7. Epoxidation of Olefins Catalyzed by Twin-Coronet Iron-Porphyrins 21a,b (M = FeCl)a
Figure 13. Glucosyl iron-porphyrin αβαβ-atropisomer.
Reactions were performed in CH2Cl2 with 1 μmol of catalyst, 100 μmol of PhIO and 500 μmol of olefin, at 0 °C. b0.2 μmol of the catalyst was used. c0.6 μmol of the catalyst was used. a
Figure 14. 2,6-Dialkoxyphenylporphyrins 23.
2.1.1.3. Chiral Auxiliaries Linked to Porphyrin via C−C Bonds. The only one example under this class was reported by Salvadori and co-workers.34 They synthesized four atropisomers of meso-binaphthyl porphyrins 26 (M = 2H), as well as their corresponding chloroiron(III) complexes 26 (M = FeCl) (Figure 17). The ability of these catalysts was evaluated for the asymmetric epoxidation of styrene in the presence of PhIO. The α2β2-atropisomer of 26 (M = FeCl) was found to be the best catalyst, which gave (S)-styrene oxide in 47% yield and with 57% ee. 2.1.2. Non-Porphyrin-Based Catalysts. As mentioned earlier, numerous chiral porphyrin ligands and their iron coordination complexes have been reported for use in asymmetric epoxidation. It is necessary to point out the problems in the metalloporphyrin chemistry. First, the synthesis of porphyrin core requires pure starting materials.
Second, careful choice of reaction conditions during linkage of chiral auxiliary is critical. Third, extensive purification of the chiral porphyrin is essential. Fourth, the overall conversion is very low. The fifth, is the preparation of metal complexes and application of special methods for characterization. All the above and other difficulties are the deterrents to venture into metalloporphyrin chemistry. The oxidant is more often iodosylbenzene, which is not considered environmentally friendly. An equally good substitute for this is yet to be identified. The need to use oxidants, such as H2O2, NaOCl, tBuOOH, and air are advocated by many researchers. The stability of metalloporphyrins toward these oxidants is a factor to reckon with. The above considerations are the motivating forces to design non-porphyrin chiral iron catalytic systems not only for epoxidation but also for a wide range of reaction types. 3254
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Table 9. Epoxidation of Aromatic Olefins Catalyzed by IronPorphyrin 25 (M = FeBr)a
Figure 15. Ketal-protected threitol iron-porphyrins. Reactions were performed in toluene with 0.25 μmol of catalyst, 25 μmol of PhIO, and 250 μmol of substrate, at −20 °C for 3 h. bThe absolute configuration was not determined. a
Table 8. Epoxidation of Aromatic Olefins Catalyzed by Chiral Iron-Porphyrins 24a,b
Figure 17. Iron-porphyrins bearing 2′-methoxy-1,1′-binaphth-2-yl group.
chain was linked to a capping unit belonging to a heterocyclic moiety. In this manner, a library of ligands were generated. Scheme 3. Typical Catalytic System for the Epoxidation of trans-β-Methylstyrene with H2O2 Using Combinatorial Chemistry
a
Reaction conditions: catalyst:iodosylbenzene:substrate =1:10 000:100 000 in benzene for 3h. bIn toluene, under otherwise identical reaction conditions. cThe ee and yields refers to the cis-epoxides.
Figure 16. D4-symmetric chiral porphyrin 25 (M = 2H).
These ligands were complexed with metal ions to form metal− ligand catalysts. Thus, a total of 5760 metal−ligand combinations were screened for epoxidation of trans-βmethylstyrene using 30% H2O2 as the oxidant. In this manner, three iron/ligand catalysts were identified. A typical example illustrating the above approach is shown in Scheme 3. The tris(D,D-dicampholylmethanato) iron(III) complex, Fe(dcm)3 (27) shown in Figure 18 is another example of nonporphyrin catalyst.36 The activity of the new catalyst was tested
Francis and Jacobsen sought to apply combinatorial chemistry to aid the process of discovering new efficient catalytic systems.35 This is the first paradigm shift from the classical approach. A number of metal−ligand combinations were synthesized. The ligands were prepared from chiral amino acids containing a variety of donor side chains, and these amino acids were coupled to aminomethyl polystyrene by usual peptide coupling techniques. The other end of the peptide 3255
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Table 11. Epoxidation of Alkenes Using Diiron Catalyst 30a
Figure 18. Chiral β-diketone iron(III) complex 27. a Reaction conditions: Alkene (0.9 M) in CH2Cl2. bReaction conditions: Alkene (0.9 M) in CH3CN cReaction conditions: Catalyst 0.2 mol % and 32% peracetic acid (1.15 equiv) added at 0 °C at once; reaction time 2 min.
first on styrene using molecular oxygen (atmosphere pressure) at 30 °C in 1,2-dichloroethane. Under these conditions there Table 10. Asymmetric Epoxidation of Styrene Derivatives 28 with Catalyst 27
(μ-oxo-diferric complex) 30. This catalyst was found to epoxidize alkenes readily in the presence of peracetic acid (Table 11). The unsymmetrical alkenes were converted into their epoxides with enantioselectivities ranging from 15 to 63%, while symmetrical alkene, for example, trans-stilbene was transformed to racemic mixture. The use of oxidants other than peracetic acid, such as H2O2, alkyl peroxides, m-CPBA did not lead to epoxide. The efficiency of the catalyst is said to be high in the case of trans-β-methylstyrene (TON up to 850). All oxidations require the diferric complex (dinuclearity with respect to iron) rather than mononuclear complex. The method may be good for terminal and electron-deficient alkenes.
was collateral conversion of styrene to benzaldehyde besides styrene oxide. This side reaction could be controlled by the addition of sacrificial reductant such as 2-ethylbutyraldehyde, Figure 20. Chiral amine ligands used by Beller et al. for the epoxidation of aromatic alkenes.38,39
Benzaldehyde, phenylacetaldehyde and also benzoic acid are minor byproducts in this oxidation process. Beller and co-workers developed simple catalytic systems using commercially available enantiopure 1,2-diphenylethylenediamine.38,39 The diamine was monosulfonylated to obtain one set of ligands (S,S)-31a−c (Figure 20) and the other free amine group was benzylated to get another set of ligands (S,S)32a−c. These chiral ligands were complexed with ferric chloride and pyridine-2,6-dicarboxylic acid (Pydic) as a coligand. The epoxidations were carried out with 30% H2O2 at room temperature. Preliminary screening using ligands 31a−c and 32a−c on trans-stilbene as a model reaction indicated that the N-benzylN′-sulfonylated ligand 32a is the best one (87%, ee = 42%). A striking observation is that ligands 31a−c gave (2S,3S)-epoxide while the ligands 32a−c produced (2R,3R)-epoxide. The scope of the Fe(III)/32a/Pydic catalytic system was explored for epoxidation of different aromatic olefins (Table 12). The para-substituted trans-stilbenes gave the best enantioselectivities than the analogous ortho- or meta-
Figure 19. Chiral diferric μ-oxo complex 30.
which was the best among several aldehydes tested. In this way, a variety of styrene derivatives 28 were epoxidized in moderate to high yields and enantioselectivities up to 92% (Table 10). Ménage and co-workers prepared a chiral ligand bisPB (bis(4,5-pinene-2,2′-bipyridine)) containing a bipyridyl core (Figure 19).37 The ligand bisPB on mixing with appropriate amount of ferric perchlorate hexahydrate in acetonitrile gave the colored iron complex whose structure was established as [Fe2O(bisPB)4(H2O)2](ClO4)4 and named as diiron catalyst 3256
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Table 12. Fe(III)/32a/Pydic-Catalyzed Asymmetric Epoxidation of Aromatic Alkenesa
Scheme 4. Proposed Mechanistic Pathway to Explain the Enantioselectivity of Fe(III)/31/Pydic- and Fe(III)/32/ Pydic-Catalyzed Epoxidations
a
H2O2 (8 equiv), Pydic (20 mol %), FeCl3.6H2O (20 mol %), and 32a (48 mol %). bReaction at 10 °C.
substituted compounds, presumably on steric grounds. Thus, high enantioselectivities (up to 97%) were obtained with sterically bulky 4,4′-disubstituted trans-stilbenes (entries 4, 7 and 8). Authors extended the use of Fe(III)/32a/Pydic catalytic system for the asymmetric epoxidation of more commonly encountered styrene and stilbene derivatives.39 The enantioselectivities are lower for small alkenes such as the styrenes (ee = 8−48%). Beller et al. speculated on the possible mechanism of epoxidation.39 They presumed that initially formed [Fe(III)(L*)2(Pydic)] may react with H2O2 to generate [Fe(III)(L*)2(OOH)(Pydic)]. Homolysis or heterolysis of such a species could generate the reactive FeIVO and FeVO species. The epoxidation reaction appears to proceed via radical intermediates as shown in Scheme 4. It is further assumed that a top-on approach of the alkene is preferred over the side-on approach. Kwong and co-workers described the synthesis of a novel chiral sexipyridine ligand 33 (Figure 21a) and the use of its iron complex for alkene epoxidation with H2O2.40 Treatment of 33 with FeCl2 in 1:2 molar ratio afforded the binuclear species [Fe2O(33)Cl4], which was isolated as air stable solid and was characterized by elemental analysis and ESI-MS. The proposed structure of the binuclear complex 34 is shown in Figure 21b. Catalyst 34 induced low enantioselectivities (31−43%) for the terminal alkene and 1,2-disubstituted alkene epoxides (Table 13).
Figure 21. (a) Chiral sexipyridine ligand and (b) proposed structure of [Fe2O(33)Cl4].
Table 13. Asymmetric Epoxidation of Alkenes Catalyzed by Complex 34
Recently, Nishikawa and Yamamoto studied the asymmetric epoxidation of acyclic β,β-disubstituted enones.41 They 3257
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Scheme 5. Asymmetric Epoxidation with a Nonactivated Olefin and a Competitive Experiment Using Electron-Rich and Electron-Deficient Olefins
Figure 22. Phenanthroline ligand bearing binaphthyl unit.
screened various oxidants and different catalysts consisting of iron salts and phenanthroline ligands attached to binaphthyl moieties. The oxidant peracetic acid was found to be very crucial for epoxidation. The best results were obtained with ligand 35 (Figure 22) and Fe(OTf)2. A study of the ligand/ metal ratios indicated that an iron complex coordinated by two phenanthroline ligands induces high enantioselectivity. However, the relationship between the iron/ligand complex formation and the enantioselectivities, as well as the actual
The authors proposed that epoxide formation proceeds via a concerted pathway.
Table 14. Epoxidation of β,β-Disubstituted Enones 36 with Fe(OTf)2/35 Catalyst
Table 15. Asymmetric Epoxidation of α,β-Enones 41 Catalyzed by Iron Complex 40
structure of the catalyst in the reaction medium remains unclear. Applying the optimal catalyst Fe(OTf)2/35, several β,βdisubstituted enones 36 were oxidized with peracetic acid to obtain α,β-epoxyketones 37 in good yields with excellent enantioselectivity (90−92% ee, Table 14). An electron-rich olefin such as trans-α-methylstilbene was also oxidized using Fe(OTf)2/35 catalyst, to the corresponding epoxide with good enantioselectivity (Scheme 5, eq 1). Furthermore, an intermolecular competition reaction between electron-rich alkene 38 and electron-deficient alkene 36a (Scheme 5, eq 2) showed the formation of a 2.4:1 ratio of 39 and 37a with comparable enantioselectivities, implying the electrophilic nature of the active oxidant. It should be noted that only one diastereomer of the epoxide was formed in all the reactions.
a The quantities of catalyst and reagents specified here are with respect to 0.25 mmol of substrate. bPeracetic acid (1.2 equiv) was used.
In the same context, Sun et al. developed chiral iron(II) complex 40 (N4-type ligand) for the epoxidation of α,β-enones 41 using hydrogen peroxide or peracetic acid as oxidant (Table 15).42 The epoxyketones 42 were obtained in moderate to good yields and 74−87% ee. The method appears to be applicable only to α,β-enones. 3258
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although the chiral ligand of 43 is tridentate while the porphyrin core is tetradentate. The advantages of this catalytic system are the low catalyst loading (1 mol %), short reaction time (
