Synthetic Transformations through AlkynoxyâPalladium Interactions

Article pubs.acs.org/accounts

Synthetic Transformations through Alkynoxy−Palladium Interactions and C−H Activation Yasunori Minami* and Tamejiro Hiyama* Research and Development Initiative, Chuo University, Kasuga, Bunkyo-ku, Tokyo 112-8551, Japan CONSPECTUS: Organic synthesis based on straightforward transformations is essential for environmentally benign manufacturing for the invention of novel pharmaceuticals, agrochemicals, and organoelectronic materials in order to ultimately realize a sustainable society. Metal-catalyzed C−H bond-cleaving functionalization has become a promising method for achieving the above goal. For site-selective C−H bond cleavage, so-called directing groups, i.e., ligands attached to substrates, are employed. Commonly utilized directing groups are carbonyls, imines, carboxyls, amides, and pyridyls, which σ-donate electron pairs to metals. On the other hand, unsaturated substrates such as alkenes and alkynes, which participate largely as reactants in organic synthesis, are prepared readily by a wide variety of synthetic transformations and are also employed as reactants in organometallic chemistry. Moreover, such unsaturated groups form complexes with some metals by ligation of their p orbitals via donation and back-donation. However, the use of unsaturated bonds as directing groups has not been studied extensively. We have been involved in the development of methods for the cleavage of C−H bonds by means of transition-metal catalysts to achieve new carbon−carbon bond-forming reactions and incidentally came to focus on the alkynoxy group (−OCC−), which shows a ketene-like resonance structure. We expected the alkynoxy group to interact electrophilically with a low-valent transition-metal complex in order to cleave adjacent C−H bonds. In this Account, we summarize our recent achievements on C−H activation based on interactions of palladium with the alkynoxy group in alkynyl aryl ethers. The alkynoxy group plays two roles in the transformation: as a directing group for adjacent C−H bond activation and as an acceptor for the carbon and hydrogen fragments. A typical example is palladium-catalyzed ortho-C−H bond activation in alkynoxyarenes followed by sequential insertion/annulation with internal alkynes and the alkynoxy group to produce 2-methylidene-2H-1-benzopyrans. Mechanistic studies have shown that the presence of both oxygen and alkynyl moieties is essential for selective ortho-C−H bond activation and subsequent annulation. In addition to internal alkynes, norbornene, allenes, isocyanates, and ketenes produce the corresponding oxacycles. It is worthy of note that benzoxadinones formed by the reaction with isocyanates exhibit solid-state luminescence. In addition, 2-methylphenyl alkynyl ethers and 2alkynoxybiaryls undergo intramolecular annulation at the benzylic γ-position and aryl δ-position via C−H bond activation to give benzofurans and dibenzopyrans, respectively. The disclosed methods allow us to construct useful π-conjugated systems in a straightforward manner.

1. INTRODUCTION The addition reaction of carbonaceous nucleophiles to alkenes and alkynes is a simple and straightforward method for the construction of new carbon−carbon bonds and is utilized for the synthesis of multifunctionalized alkanes, alkenes, carbocycles, and polymers. Thus, this sort of addition reaction to unsaturated substrates is indispensable for the production of a wide variety of organic ingredients and functional chemicals in our future sustainable society. In contrast, unsaturated substrates also serve as ligands of metals through complexation of their π systems toward metal complexes.1 Hemilable ligands and chiral diene ligands are typical examples. Unsaturated substrates ligated by metals show electrophilic character and are thus able to react with various nucleophiles. Recently, ligationinduced site- and regioselective transformations have been realized2 and shown to have high synthetic potential. On the other hand, transition-metal-catalyzed carbon−hydrogen bond activations, i.e., oxidative addition of C−H bonds to metal © XXXX American Chemical Society

complexes and the concerted metalation/deprotonation (CMD) pathway, have been among the most important reactions in synthetic chemistry and environmentally friendly molecular transformations.3 For selective activation, σ-electrondonating functional groups such as pyridyl, acetyl, and amide are often utilized as directing groups for site-selective C−H activation. Recently, reactive directing groups such as methoxyamide have been suggested.4 On the other hand, alkenyl and alkynyl functional groups are much less established as directing groups, although some research groups have referred to C−H activation employing alkynyl, alkenyl, and thienyl groups (Scheme 1).5 We focused our attention on alkynyl ethers6 as highly polarized alkynes to invent novel C−H activation reactions. Since the triple bond of the alkynoxy group has a ketene-like Received: September 9, 2015

A

DOI: 10.1021/acs.accounts.5b00414 Acc. Chem. Res. XXXX, XXX, XXX−XXX

Article

Accounts of Chemical Research Scheme 1. Selected Examples of Unsaturated C−C Bond-Directing Groups

polarized resonance structure,7 we surmised that a low-valent nucleophilic transition-metal complex could be ligated by the oxygen-bonded alkynyl carbon via strong back-donation and may partly attack its α-carbon nucleophilically to give a zwitterionic metal species (Figure 1). We predicted that this

followed by insertion of the C−C triple bond of another molecule of 1a (Scheme 2).9 This result clearly demonstrated Scheme 2. Dimerization of Alkynyl Aryl Ethers

that the alkynoxy group properly acted as a reactive directing group for C−H activation and an addition acceptor. Perfect regioselectivity was accomplished by the bulky tert-butyldiphenylsilyl (TBDPS) group. With this observation in hand, we examined the crossannulation of alkynyl aryl ethers with other alkynes. p-Anisyl triisopropylsilylethynyl ether (1b) reacted with 1-octyne (3) in the presence of Pd(OAc)2, 1,1′-bis(diphenylphosphino)ferrocene (DPPF), and Zn. As a result, the 1,2-addition product 4 was produced regioselectively (Scheme 3),6j,9

Figure 1. Alkynyl ethers for reactive metal species.

polarized metal center may in turn cleave C−H bonds electrophilically. On the basis of this working hypothesis, we successfully demonstrated that the alkynoxy group plays two roles: as a potent directing group to activate C−H bonds with palladium complexes and as an addition acceptor to form cyclic products. In this Account, we summarize our invention of C−H bond activation reactions directed by the alkynoxy group. All of the reactions readily provide such oxacyclic compounds as chromenes, chromanes, and benzofurans8 with 100% atom economy. Deuterium-labeling experiments have provided a rough sketch of the reaction mechanism.

Scheme 3. Reaction of Alkynyl Aryl Ethers with 1-Octyne

2. REACTION OF ARYL SILYLETHYNYL ETHERS WITH ALKYNES Initially, a solution of aryl silylethynyl ether 1 in toluene was heated in the presence of Pd(OAc)2, tricyclohexylphosphine (PCy3), and Zn as a reductant for the production of the palladium(0) catalyst. Starting with p-anisyl tert-butyldiphenylsilylethynyl ether (1a), the dimeric product 2a was produced regioselectively and was ascribed to ortho-C−H activation

suggesting that the terminal alkyne interacted with the palladium catalyst faster than the expected alkynoxy-groupdirected C−H activation. Accordingly, we chose an internal alkyne, 4-octyne (5a), as the annulation partner. Under the catalytic conditions for the dimerization of 1, successful crossannulation took place to give 6a in 86% isolated yield (Scheme 4).9,10 The annulation was equally effected by the palladium(0) B


Article

Accounts of Chemical Research Scheme 4. Reaction of p-Anisyl Triisopropylsilylethynyl Ether with 4-Octyne

ethers, activation at the less-hindered C−H bond was favored to form the products (6d and 6e). On the other hand, a 3fluorinated substrate reacted via C2−H bond cleavage to give 6f, probably as a result of the ortho-fluorine effect.11 Such sterically biased alkynes 5 reacted regioselectively, giving the corresponding chromene derivatives. For example, the reaction of 1b with 4,4-dimethyl-2-pentyne gave the annulation product 6i containing a tert-butyl group at C3 and a methyl group at C4. 1-Phenyl-1-propyne produced 6j having methyl and phenyl groups at C3 and C4, respectively. The reaction of 1,4bis(alkynoxy)benzene with tolan provided a double annulation product, dioxatricycle 6l. The deuterium-labeled substrate 1c-d5 provided 6m-d5, which contained deuterium at the 2-methylidene carbon (Scheme 6a). A crossover experiment using 1b and 1c-d5 demonstrated that both annulation products contained deuterium at the 2-methylidene carbon whereas no H/D scrambling was observed at C8 in either product (Scheme 6b). These results suggest that the palladium(0) complex selectively activates the ortho-C−H bond in the alkynyl aryl ether irreversibly and that the ortho-hydrogen may be transferred to the alkenyl position in either an intra- or intermolecular manner. A proposed mechanism is suggested in Scheme 7. The orthoC−H activation through oxidative addition to the palladium

complex Pd(PCy3)2. Thus, the catalytic system of Pd(OAc)2/ PCy3/Zn was considered to involve reduction of Pd(OAc)2 by Zn to give Pd(0) and Zn(OAc)2. The coproduced Zn(II) salt definitely promoted the annulation, as evidenced by the fact that the annulation reaction, catalyzed by Pd(PCy3 ) 2, proceeded faster in the presence of Zn(OAc)2. It is worthy of note that neither 1,4-dimethoxybenzene nor benzyl alkynes showed this C−H activation/cyclization upon reaction with internal alkynes. Under the conditions with Pd(OAc)2, PCy3, and Zn, various alkynyl aryl ethers and internal alkynes were applied to the annulation (Scheme 5). With meta-substituted alkynyl aryl

Scheme 5. Scope of the Reaction of Alkynyl Aryl Ethers with Internal Alkynes

C


Article

Accounts of Chemical Research

3. SEQUENTIAL INSERTION/ANNULATION OF ARYL ETHYNYL ETHERS WITH VARIOUS DOUBLE-BOND COMPOUNDS

Scheme 6. Deuterium-Labeling Experiments: (a) Reaction Using D-Labeled Substrate; (b) Crossover Experiment

Reaction with Bicycloalkenes

We next applied various alkenes to the reaction with alkynyl aryl ethers and found that the reaction of 1c with norbornadiene (7) proceeded in the presence of Pd(PCy3)2 and Zn to give 2-methylidenechromane 8 (Scheme 8).9,15 We Scheme 8. Annulation with Norbornadiene

assume that a catalytic amount of Zn metal prevented deactivation of the palladium catalyst; during the reaction, once-generated Pd(II) species were reduced to the active Pd(0) form.

Scheme 7. Proposed Mechanism for Annulation with Internal Alkynes

Reaction with Allenes: Formation of Condensed Tetracycles

We turned our attention to the annulation of alkynyl aryl ethers with allenes as cumulative double-bond acceptors.16 Our eventual goal was a possible straightforward synthesis of 1,2bis(methylidene) cycles, which are useful building blocks for the construction of polycondensed carbocycles by means of the Diels−Alder reaction.17 Thus, we examined the reaction of 1d with cyclohexylallene (9a) under conditions employing Pd(OAc)2, PCy3, and Zn and successfully obtained 2,3-bis(methylidene)chromane 10a via perfect regioselective insertion of the internal double bond of the allene (Scheme 9).18 The Scheme 9. Annulation with Cyclohexylallene Followed by a Diels−Alder Reaction

complex is triggered by the initial formation of a zwitterionic form that may be converted into a palladacycle by attack of the ortho-carbon on the palladium center or oxidative addition of the ortho-C−H bond to the cationic palladium center.12,13 Next, a 1,2-hydrogen shift or elimination of the silylethynoxy group from the palladium center accomplishes the oxidative addition to furnish the corresponding Ar−Pd−H complex. Following sequential insertion of internal alkyne 5 and reductive elimination, the final product 6 and the palladium(0) complex are formed. This mechanism was supported by theoretical studies suggesting back-donation from Pd(0) to the CC bond of the alkynoxy group, which supports the proposed C−H activation pathway.14 Zn(OAc)2 may promote this back-donation through ligation by the silylethynyl carbon, enhancing the reaction rate. It should be noted that appropriate bulky ligands and substituents on the alkynyl carbon are required for successful cross-annulation without generation of 2, probably because of steric repulsion. This combination is essential in the following annulations also; inhibition of the formation of dimer 2 is the underlying problem in all of the reactions using 1.

cyclohexyl group was located at C4 in 10a. This annulation was accomplished by a palladium(0) catalyst through a reaction mechanism similar to that for the annulation with alkynes. The 2,3-exo-bis(methylidene) moiety in the product readily underwent the Diels−Alder reaction with N-(p-bromophenyl)maleimide (11a) to form condensed tetracycle 12a. The structure of 12a clearly shows that the Diels−Alder reaction proceeded from the endo direction according to the endo rule and as a result of the steric repulsion between the cyclohexyl D


Article

Accounts of Chemical Research and N-aryl groups. The sequential annulation/Diels−Alder reaction could be carried out in a one-pot operation (Scheme 10).

regioselectivity in moderate yield. 21,22 With Zn(OAc) 2 cocatalyst, the reaction was accelerated and the yield of 14a increased (Scheme 12).23 Purification of 14a was easily

Scheme 10. One-Pot Annulation

Scheme 12. Reaction with Phenyl Isocyanate

Typical products are summarized in Scheme 11. The annulation of 2-(1-methoxycyclohexyl)ethynyl p-methoxyphenyl ether successfully proceeded to give 10c. Thus, the bulky carbonaceous group worked equally as well as the triisopropylsilyl (TIPS) group. The fact that 10d was solely produced demonstrates that the less-hindered C−H bond preferentially participated in the reaction. Functional groups such as the cyano group did not hamper the reaction. Internal and 1,1disubstituted allenes could be used to form corresponding cycles 10g and 10h. However low regioselectivity was observed in the latter case.

performed by preparative TLC followed by recrystallizations from CH2Cl2/hexane. The fact that the combination of Pd(OAc)2 and PCy3 is effective for the reaction with isocyanates clearly indicates that C−H bond activation is achieved by a CMD pathway.24 It should be noted that the regioselectivity observed herein is unique: previously reported insertions of isocyanates into C−H bonds exclusively favored insertion of the isocyanate CN bond into the C−H bond.25 Various aryl silylethynyl ethers and aryl isocyanates were applicable to the reaction. Examples are shown in Scheme 13. Diphenylamino and trifluoromethyl groups did not interfere with the reaction. Bulky o-methoxyphenyl and 2,6-diethylphenyl isocyanates gave the corresponding products, albeit in low yields, probably because of the steric hindrance for ligation of an isocyanate group to the palladium center. Benzoxazinones 14 exhibit solid-state luminescence upon irradiation with UV light (365 nm). X-ray crystallographic analysis of 14a revealed that the benzoxazinone ring is nearly planar and that the 4-phenyl group is twisted almost perpendicular to the benzoxazinone plane. The phenyl and bulky TIPS groups apparently prevent an intermolecular quenching process, favorably affecting the solid-state lumines-

Reaction with Isocyanates: Synthesis of Solid-State Emissive Materials

Solid luminescent materials play key roles in such optoelectronic devices as light-emitting diodes.19 As a parallel ongoing research program, we have been exploiting light-emissive organic materials. We were fortunate to discover that a benzoxazinone structure is formed by the annulation of alkynyl aryl ethers with isocyanates.20 Incidentally, we attempted the reaction of 1b with phenyl isocyanate (13a) in the presence of Pd(OAc) 2/PCy 3/Zn but observed no desired product. However, without Zn, product 14a was obtained with perfect

Scheme 11. Scope of the Formation of 2,3-Bis(methylidene)chromanes

E


Article

Accounts of Chemical Research Scheme 13. Scope of 2-Methylidene-2H-1,4-benzoxazin-3(4H)-one Synthesis

cence.19b The absorption spectra of 14 in cyclohexane show a weak band in the range from 300 to 340 nm, which is ascribed to an intramolecular charge transfer transition. The fluorescence maximum and quantum yield are controllable by variation of the substituents on the appropriate sites. Representative examples of their fluorescence maxima and quantum yields are shown in Table 1. In solid-state 14b (least

Scheme 14. Deuterium-Labeling Experiments: (a) Reaction Using D-Labeled Substrate; (b) Crossover Experiment

Table 1. Fluorescence Maxima and Quantum Yields 14b 14d 14h 14i

in cyclohexane powder in cyclohexane powder in cyclohexane powder in cyclohexane powder

λem max (nm)

Φf

461 452 494 522 453 428 430 468

0.02 0.24 0.02 0.05 0.10 0.78 0.33 0.33

substituted), an emission band (λem max = 452 nm) was observed with a quantum yield (Φf = 0.24) higher than that in cyclohexane solution (Φf = 0.02). The introduction of a diphenylamino group at C7 (14d) resulted in a longer maximum-emission wavelength (λem max = 522 nm) in the solid state compared with 14b, albeit with a lower quantum yield (Φf = 0.05). The 2-methoxyphenyl group at C4 (14h) provided the highest quantum yield (Φf = 0.78, powder) as a result of both electron-donating and steric effects. On the other hand, the 2,6diethylphenyl group (14i) increased the quantum yield in solution (Φf = 0.33). To gain insight into the C−H bond-cleaving event, we conducted the reaction of 1c-d5 with 13a to give 14b-d5 having a deuterium in the 2-methylidene moiety (Scheme 14a). A crossover experiment using 1b and 1c-d5 demonstrated that two deuterium atoms at the ortho position in 1c-d5 were transferred, and both annulation products contained deuterium

at the 2-methylidene and C8 (Scheme 14b). This fact suggests a reversible C−H bond-cleaving pathway, which is clearly different from the reaction with alkynes, thus supporting the CMD pathway. The reaction mechanism using 1c and 13a as representative substrates is described briefly in Scheme 15. The reversible C−H cleavage by the alkynoxy-ligated palladium species generates an aryl palladium complex, into which the isocyanate inserts. It is assumed that this step is particularly accelerated by the presence of Zn(OAc)2, possibly through coordination of an oxygen atom in the isocyanate to Zn(II) rather than silylethynyl carbon.26 The reason why the CMD pathway is proposed in this case is that the alkynoxy-ligated F


Article

Accounts of Chemical Research Scheme 15. Proposed Mechanism of the Reaction Using Isocyanates

absence of Zn, indicating that the benzylic C−H bond was cleaved via the CMD pathway instead of a difficult oxidative addition of the C(sp3)−H bond. However, the mechanistic details of this hydrobenzylation still remain to be clarified. The initial hydrobenzylation product 17 containing a silylated exo-methylidene structure turned out to be structurally labile and readily converted into various benzofurans. Acetic acid was added to the reaction mixture containing 17b to induce quick CC bond isomerization to give 18b (Scheme 18). Compound 17c generated in situ from triethylsilyl-

palladium coordinated by the isocyanate shows high electrophilicity to hamper the oxidative addition of the C−H bond. Reaction with Ketenes

Ethyl phenyl ketene (15) reacted with 1b regioselectively in the presence of Pd(OAc)2, PCy3, and Zn(OAc)2 to give 1benzopyran-3-one 16 (Scheme 16).22,27 The product 16, which is a carbon analogue of 14, hardly emitted luminescence (Φf < 0.01) in cyclohexane. Scheme 16. Annulation with Ethyl Phenyl Ketene

Scheme 18. Synthetic Transformations of 17

4. INTRAMOLECULAR INSERTION OF ARYL ETHYNYL ETHERS Hydrobenzylation for the Synthesis of Benzofurans

With the development of ortho-C−H activation of alkynyl aryl ethers, we subsequently exploited the possibility of C(sp3)−H bond activation. To our delight, we found that benzylic C−H bond activation followed by intramolecular insertion of the alkynoxy moiety takes place.28 For example, alkynyl o-tolyl ether 1e was converted to the hydrobenzylation product 17a in the presence of Pd(OAc)2/PCy3/Zn in toluene (1 M) at 90 °C. However, dimer 2b was the main product.29 To prevent the generation of 2b, lowering the concentration of the reaction mixture was highly effective, and 17a was produced in a yield of synthetic significance (Scheme 17).30 The reaction using 2,6xylyl TIPS-ethynyl ether (1f) gave 17b in the presence or

substituted 1g reacted with ethyl glyoxylate to form aldoltype product 19. When ethyl 3,3,3-trifluoro-2-oxopropanoate was used, the reaction of bulky TIPS-substituted 17b gave C3substituted benzofuran 20 by avoiding steric repulsion between the TIPS group and the oxopropanoate. Aerobic oxidation of the TIPS group in 17b formed 2-benzofuryl aldehyde 21. Representative results of the hydrobenzylation are listed in Scheme 19. After the intramolecular hydrobenzylation, all of the insertion products were treated with acetic acid to isolate 2(silylmethyl)benzofurans 18 without problems. A benzylic C− H bond was selectively activated in 2,6-diethylphenyl alkynyl ether to give adduct 18c. Ethyl, methoxy, and trifluoromethyl groups at the other ortho position did not affect the hydrobenzylation; only methyl C−H bonds were selectively activated to give 18d, 18e, and 18f, respectively. Aryl 1-alkynyl ethers whose propargylic position is substituted fully could be utilized in the hydrobenzylation. In particular, a diphenyl(methoxy)-substituted propynyl ether was converted to 2-ethenylbenzofuran derivatives. The reaction of 3-methoxy-3,3-diphenyl-1-propynyl 2,6-xylyl ether (1h) gave the normal insertion product 22, which was readily transformed into 2-(2,2-diphenylethenyl)benzofuran 23 via elimination of methanol by treatment with acetic acid (Scheme 20).31

Scheme 17. Palladium-Catalyzed Intramolecular Hydrobenzylation

G


Article

Accounts of Chemical Research Scheme 19. Scope of the Formation of Benzofurans via Hydrobenzylation/Isomerization

Scheme 20. Formation of a 2-Ethenylbenzofuran Derivative

Hydroarylation for the Synthesis of Dibenzopyrans

PdCl2 instead of Pd(OAc)2 was ineffective. Various biaryl substrates were used to form the corresponding cycles. Fluorine bound to an aryl ring did not interfere with the hydroarylation to form 24b. The reaction of 1-[2-(silylethynyloxy)phenyl]naphthalene also proceeded smoothly to give [4]oxahelicene 24c. Thiophenes can participate in this annulation to produce thienobenzopyrans. For example, 2-(3-thienyl)phenyl alkynyl ether gave thienobenzopyran 24e via selective C−H bond cleavage at C2 of the thiophene ring. This method allows us to synthesize condensed polyoxacyclic compounds. Double hydroarylation of bis(silylethynyloxy)terphenyl 25 proceeded readily to provide pentacyclic benzo[1,2-c:4,5-c′]bis([1]benzopyran) 26 (Scheme 22). The hydroarylation products could be converted into 6,6disubstituted dibenzopyrans (Scheme 23). Protodesilylation of 23a using hydrogen bromide in acetic acid gave 6methyldibenzo[b,d]pyrylium bromide (27), which was nucleophilically attacked at C6 by the cuprate reagent BuCu(CN)Li prepared from BuLi and CuCN to give 6-butylated 6methyldibenzopyran 28 (two steps). A mechanism for the hydroarylation is suggested in Scheme 24. The 2′-C−H bond is cleaved via a CMD pathway from both the alkynoxy- and twisted aryl-ligated acetoxypalladium complex to give an alkynoxy-ligated arylpalladium(II) complex. The alkynoxy moiety subsequently inserts into the aryl−Pd bond to form the vinylpalladium complex, which is hydrolyzed by generated acetic acid to give 23. A deuterium-labeling experiment supported the CMD pathway for the C−H cleavage. The reaction using 1l-d5 provided 24a-d7 having deuterium at the 6-methylidene carbon, C1, and C4 (48% D,

Condensed heterocycles have attracted considerable attention because of their biological and pharmacological activities and electronic/photophysical properties.32 We applied the alkynoxy-directed C−H activation reaction to the construction of a dibenzopyran structure.33 We examined the intramolecular hydroarylation of 2-triisopropylsilylethynyloxybiphenyl (1i) using various palladium catalysts and found that the conditions with Pd(OAc)2 (5 mol %) and PCy3 (5 mol %) in toluene (0.1 M) at 90 °C were optimal for the hydroarylation; 6-(Z)triisopropylsilylmethylidene-6H-dibenzo[b,d]pyran (24a) was obtained in 88% yield (Scheme 21).34 The use of Pd(dba)2 or Scheme 21. Intramolecular Hydroarylation of oAlkynoxybiaryls

Scheme 22. Double Hydroarylation

H


Article

Accounts of Chemical Research Scheme 23. Synthetic Transformation To Give a 6,6-Dialkyldibenzopyran

Scheme 24. Proposed Mechanism for the Hydroarylation

C−H and arylic C−H activations. All of the products showed high synthetic versatility for the construction of various oxacycles. Moreover, this novel strategy allows the planning of straightforward syntheses of functional organic materials. An attractive and challenging topic in this area is the discovery of practical C−H activation assisted by such simple unsaturated bonds as alkynes and alkenes. This approach will make it possible to synthesize a wide variety of useful ring structures in straightforward manners.

15% D, and 40% D, respectively) (Scheme 25A). The reaction of 1l in the presence of AcOD formed 24a-d4 having deuterium Scheme 25. Deuterium-Labeling Experiments: (A) Reaction Using D-Labeled Substrate; (B) Reaction of 1l in the Presence of AcOD

■

AUTHOR INFORMATION

Corresponding Authors

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

The authors declare no competing financial interest. Biographies Yasunori Minami received his Ph.D. from Osaka University under the supervision of Professor Nobuaki Kambe in 2010. He was also educated by Prof. John F. Hartwig in chemistry at University of Illinois at Urbana−Champaign as a visiting student in 2009. He then joined the Research and Development Initiative (RDI) at Chuo University as an Assistant Professor. His current research interests are synthetic organic chemistry using transition-metal catalysts and main-group element chemicals.

at four positions: the 6-methylidene carbon, C1, C4, and C10 derived from AcOD (Scheme 25B). These results clearly demonstrate that the C2′, C3, and C6 C−H bonds are cleaved reversibly via the CMD pathway.

Tamejiro Hiyama was appointed Associate Professor at Kyoto University in 1972 and completed his Ph.D. under the supervision of Professor Hitosi Nozaki at Kyoto University in 1975, after which he spent a postdoctoral year at Harvard University working for Professor Yoshito Kishi. In 1981 he started his own independent research at Sagami Chemical Research Center. In 1992 he moved to the Research Laboratory for Resources Utilization at Tokyo Institute of Technology as a Full Professor and then to the Graduate School of Engineering at Kyoto University in 1997. Since his retirement from Kyoto University in 2010, he has been at Chuo University as an RDI Professor. His research is based on the invention of novel synthetic methods for the synthesis of biologically active substances and functionalized materials such as liquid crystals and organic light-emitting materials.

5. CONCLUSION Oxacycles such as benzopyrans and benzofurans are common structures for biologically active natural products and recently have been the target structures of optoelectronics. Thus, the importance of these molecules is rapidly growing. It is easily conceivable that, if straightforward synthetic methods for various targets are invented, the chemistry of oxygen-containing molecules will undergo significant evolution. We have demonstrated that the discovery of a novel C−H activation strategy using alkynoxy directing groups and palladium catalysts led to invention of straightforward methods for the synthesis of benzofuran and benzopyran frameworks. The alkynoxy moiety plays a key role as a directing group for C−H activation, probably because of the strong interaction with palladium complexes via back-donation. Various six-membered oxacycles can be synthesized by the ortho-C−H activation of aryl ethynyl ethers followed by annulation with unsaturated partners. 2Methylidene-2,3-dihydrobenzofuran and 6-methylidene-6Hdibenzo[b,d]pyran derivatives are produced, possibly via benzyl

■

ACKNOWLEDGMENTS We are grateful to our colleagues for their contributions to the work described in this Account. T.H. appreciates financial support of Grants-in-Aid for Scientific Research (S) (21225005) from JSPS and ACT-C from JST. Y.M. is thankful for Grants-in-Aid from JSPS for Young Scientists (B) I


Article

Accounts of Chemical Research

G. Silver-Catalyzed Regio- and Stereoselective Addition of Carboxylic Acids to Ynol Ethers. J. Org. Chem. 2014, 79, 9179−9185. (j) Babu, M. H.; Dwivedi, V.; Kant, R.; Reddy, M. S. Palladium-Catalyzed Regioand Stereoselective Cross-Addition of Terminal Alkynes to Ynol Ethers and Synthesis of 1,4-Enyn-3-ones. Angew. Chem., Int. Ed. 2015, 54, 3783−3786. (7) (a) Tanaka, R.; Miller, S. I. Nucleophilic substitution at an acetylenic carbon: 1-alkoxy-2-phenylacetylenes from 1-chloro-2phenylacetylene. Tetrahedron Lett. 1971, 12, 1753−1756. (b) Tanaka, K.; Shiraishi, S.; Nakai, T.; Ishikawa, N. New applications of organofluorine reagents in organic synthesis. III. A convenient synthetic method for acetylenic ethers and thioethers. Tetrahedron Lett. 1978, 19, 3103−3106. (c) Stang, P. J.; Roberts, K. A. Generation and trapping of alkynolates from alkynyl tosylates: formation of siloxyalkynes and ketenes. J. Am. Chem. Soc. 1986, 108, 7125−7127. (8) (a) Fravel, B. W.; Nedolya, N. A. 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. 7, pp 701−726 and previous editions of this series. For recent examples, see: (b) Mandal, S.; Parida, K. N.; Samanta, S.; Moorthy, J. N. Influence of (2,3,4,5,6-Pentamethyl/phenyl)phenyl Scaffold: Stereoelectronic Control of the Persistence of o-Quinonoid Reactive Intermediates of Photochromic Chromenes. J. Org. Chem. 2011, 76, 7406−7414. (c) Mitsui, C.; Soeda, J.; Miwa, K.; Tsuji, H.; Takeya, J.; Nakamura, E. Naphtho[2,1-b:6,5-b′]difuran: A Versatile Motif Available for SolutionProcessed Single-Crystal Organic Field-Effect Transistors with High Hole Mobility. J. Am. Chem. Soc. 2012, 134, 5448−5451. (9) Minami, Y.; Shiraishi, Y.; Kodama, T.; Kanda, M.; Yamada, K.; Anami, T.; Hiyama, T. Alkynoxy-directed C−H Functionalizations: Palladium(0)-catalyzed Annulations of Alkynyl Aryl Ethers with Alkynes. Bull. Chem. Soc. Jpn. 2015, 88, 1388−1403. (10) Minami, Y.; Shiraishi, Y.; Yamada, K.; Hiyama, T. PalladiumCatalyzed Cycloaddition of Alkynyl Aryl Ethers with Internal Alkynes via Selective Ortho C−H Activation. J. Am. Chem. Soc. 2012, 134, 6124−6147. (11) (a) Clot, E.; Eisenstein, O.; Jasim, N.; Macgregor, S. A.; Mcgrady, J. E.; Perutz, R. N. C-F and C-H Bond Activation of Fluorobenzenes and Fluoropyridines at Transition Metal Centers: How Fluorine Tips the Scales. Acc. Chem. Res. 2011, 44, 333−348. (b) Clot, E.; Mégret, C.; Eisenstein, O.; Perutz, R. N. Exceptional Sensitivity of Metal−Aryl Bond Energies to ortho-Fluorine Substituents: Influence of the Metal, the Coordination Sphere, and the Spectator Ligands on M−C/H−C Bond Energy Correlations. J. Am. Chem. Soc. 2009, 131, 7817−7827. (c) Evans, M. E.; Burke, C. L.; Yaibuathes, S.; Clot, E.; Eisenstein, O.; Jones, W. D. Energetics of C-H Bond Activation of Fluorinated Aromatic Hydrocarbons Using a [Tp’Rh(CNneopentyl)] Complex. J. Am. Chem. Soc. 2009, 131, 13464−13473. (12) For the oxidative addition of ortho-C−H bonds in anisole to pincer-coordinated iridium complexes, see: Ben-Ari, E.; Cohen, R.; Gandelman, M.; Shimon, L. J. W.; Martin, J. M. L.; Milstein, D. ortho C−H Activation of Haloarenes and Anisole by an Electron-Rich Iridium(I) Complex: Mechanism and Origin of Regio- and Chemoselectivity. An Experimental and Theoretical Study. Organometallics 2006, 25, 3190−3210. (13) The addition of the 2-C−H bond in indenes to alkynes has been reported. See: (a) Tsukada, N.; Mitsuboshi, T.; Setoguchi, H.; Inoue, Y. Stereoselective cis-Addition of Aromatic C−H Bonds to Alkynes Catalyzed by Dinuclear Palladium Complexes. J. Am. Chem. Soc. 2003, 125, 12102−12103. (b) Tsukada, N.; Setoguchi, H.; Mitsuboshi, T.; Inoue, Y. Hydroalkenylation of Alkynes Catalyzed by Dinuclear Palladium Complexes via C−H Bond Activation. Chem. Lett. 2006, 35, 1164−1165. (14) Meng, Q.; Wang, F. Theoretical studies of palladium-catalyzed cycloaddition of alkynyl aryl ethers and alkynes. J. Mol. Model. 2014, 20, 2514. (15) For some examples of normal addition of C−H bonds to CC bonds in norbornenes, see: (a) Aufdenblatten, R.; Diezi, S.; Togni, A. Iridium(I)-Catalyzed Asymmetric Intermolecular Hydroarylation of

(25870747) and the Asahi Glass Foundation. Particularly we thank Profs. Makoto Yamashita, Katsunori Suzuki, Masaaki Haga, and Hiroaki Ozawa for kind assistance with measurements of physical data.

■

REFERENCES

(1) Johnson, J. B.; Rovis, T. More than Bystanders: The Effect of Olefins on Transition-Metal-Catalyzed Cross-Coupling Reactions. Angew. Chem., Int. Ed. 2008, 47, 840−871. (2) For examples, see: (a) Kawasaki, Y.; Ishikawa, Y.; Igawa, K.; Tomooka, K. Directing Group-Controlled Hydrosilylation: Regioselective Functionalization of Alkyne. J. Am. Chem. Soc. 2011, 133, 20712−20715. (b) Zhu, C.; Yang, B.; Jiang, T.; Bäckvall, J.-E. OlefinDirected Palladium-Catalyzed Regio- and Stereoselective Oxidative Arylation of Allenes. Angew. Chem., Int. Ed. 2015, 54, 9066−9069. (3) (a) C−H Activation; Yu, J.-Q., Shi, Z., Eds.; Springer: Berlin, 2010. (b) Alkane C−H Activation by Single-Site Metal Catalysis; Pérez, P. J., Ed.; Springer: Berlin, 2012. (4) For a review, see: Chen, Z.; Wang, B.; Zhang, J.; Yu, W.; Liu, Z.; Zhang, Y. Transition metal-catalyzed C−H bond functionalizations by the use of diverse directing groups. Org. Chem. Front. 2015, 2, 1107− 1295. (5) (a) Gandeepan, P.; Cheng, C.-H. Transition-Metal-Catalyzed πBond-Assisted C−H Bond Functionalization: An Emerging Trend in Organic Synthesis. Chem. - Asian J. 2015, 10, 824−838. For selected examples of unsaturated C−C bonds acting as directing groups to cleave C−H bonds, see: (b) Takeuchi, R.; Yasue, H. Rhodium complex-catalyzed desilylative cyclocarbonylation of 1-aryl-2(trimethylsilyl)acetylenes: a new route to 2,3-dihydro-1H-inden-1ones. J. Org. Chem. 1993, 58, 5386−5392. (c) Chernyak, N.; Gevorgyan, V. Exclusive 5-exo-dig Hydroarylation of o-Alkynyl Biaryls Proceeding via C−H Activation Pathway. J. Am. Chem. Soc. 2008, 130, 5636−5637. (d) Tobisu, M.; Hyodo, I.; Onoe, M.; Chatani, N. Rhodium-catalyzed anomalous dimerization of styrenes involving the cleavage of the ortho C−H bond. Chem. Commun. 2008, 44, 6013− 6015. (e) Gandeepan, P.; Cheng, C.-H. Allylic Carbon−Carbon Double Bond Directed Pd-Catalyzed Oxidative ortho-Olefination of Arenes. J. Am. Chem. Soc. 2012, 134, 5738−5741. (f) Iitsuka, T.; Hirano, K.; Satoh, T.; Miura, M. Rhodium-Catalyzed Annulative Coupling of 3-Phenylthiophenes with Alkynes Involving Double C-H Bond Cleavages. Chem. - Eur. J. 2014, 20, 385−389. (6) For recent examples of reactions using alkynyl ethers, see: (a) Hashmi, A. S. K.; Rudolph, M.; Huck, J.; Frey, W.; Bats, J. W.; Hamzić, M. Gold Catalysis: Switching the Pathway of the Furan-Yne Cyclization. Angew. Chem., Int. Ed. 2009, 48, 5848−5848. (b) Miyauchi, Y.; Kobayashi, M.; Tanaka, K. Rhodium-Catalyzed Intermolecular [2 + 2+2] Cross-Trimerization of Aryl Ethynyl Ethers and Carbonyl Compounds to Produce Dienyl Esters. Angew. Chem., Int. Ed. 2011, 50, 10922−10926. (c) Zhao, W.; Wang, Z.; Sun, J. Synthesis of EightMembered Lactones: Intermolecular [6 + 2] Cyclization of Amphoteric Molecules with Siloxy Alkynes. Angew. Chem., Int. Ed. 2012, 51, 6209−6213. (d) Cabrera-Pardo, J. R.; Chai, D. I.; Liu, S.; Mrksich, M.; Kozmin, S. A. Label-assisted mass spectrometry for the acceleration of reaction discovery and optimization. Nat. Chem. 2013, 5, 423−427. (e) Bai, Y.; Yin, J.; Kong, W.; Mao, M.; Zhu, G. Pdcatalyzed addition of boronic acids to ynol ethers: a highly regio- and stereoselective synthesis of trisubstituted vinyl ethers. Chem. Commun. 2013, 49, 7650−7652. (f) Graf, K.; Rühl, C. L.; Rudolph, M.; Rominger, F.; Hashmi, A. S. K. Metal-Free Oxidative Cyclization of Alkynyl Aryl Ethers to Benzofuranones. Angew. Chem., Int. Ed. 2013, 52, 12727−12731. (g) Cui, W.; Yin, J.; Zheng, R.; Cheng, C.; Bai, Y.; Zhu, G. Palladium-Catalyzed Hydroarylation, Hydroalkenylation, and Hydrobenzylation of Ynol Ethers with Organohalides: A Regio- and Stereoselective Entry to α,β- and β,β-Disubstituted Alkenyl Ethers. J. Org. Chem. 2014, 79, 3487−3493. (h) Alford, J. S.; Davies, H. M. L. Mild Aminoacylation of Indoles and Pyrroles through a ThreeComponent Reaction with Ynol Ethers and Sulfonyl Azides. J. Am. Chem. Soc. 2014, 136, 10266−10269. (i) Yin, J.; Bai, Y.; Mao, M.; Zhu, J


Article

Accounts of Chemical Research Norbornene with Benzamide. Monatsh. Chem. 2000, 131, 1345−1350. (b) Kuninobu, Y.; Matsuki, T.; Takai, K. Rhenium-Catalyzed Regioselective Alkylation of Phenols. J. Am. Chem. Soc. 2009, 131, 9914−9915. (c) Oyamada, J.; Hou, Z. Regioselective C−H Alkylation of Anisoles with Olefins Catalyzed by Cationic Half-Sandwich Rare Earth Alkyl Complexes. Angew. Chem., Int. Ed. 2012, 51, 12828− 12832. (d) Sevov, C. S.; Hartwig, J. F. Iridium-Catalyzed Intermolecular Asymmetric Hydroheteroarylation of Bicycloalkenes. J. Am. Chem. Soc. 2013, 135, 2116−2119. (16) For examples of the insertion/allylation of allenes into C−H bonds, see: (a) Zhang, Y. J.; Skucas, E.; Krische, M. J. Direct Prenylation of Aromatic and α,β-Unsaturated Carboxamides via Iridium-Catalyzed C-H Oxidative Addition-Allene Insertion. Org. Lett. 2009, 11, 4248−4250. (b) Zeng, R.; Fu, C.; Ma, S. Highly Selective Mild Stepwise Allylation of N-Methoxybenzamides with Allenes. J. Am. Chem. Soc. 2012, 134, 9597−9600. (c) Ye, B.; Cramer, N. A Tunable Class of Chiral Cp Ligands for Enantioselective Rhodium(III)-Catalyzed C−H Allylations of Benzamides. J. Am. Chem. Soc. 2013, 135, 636−639. (17) (a) Nicolaou, K. C.; Chen, J. S.; Edmonds, D. J.; Estrada, A. A. Recent Advances in the Chemistry and Biology of Naturally Occurring Antibiotics. Angew. Chem., Int. Ed. 2009, 48, 660−719. (b) Nawrat, C. C.; Moody, C. J. Quinones as Dienophiles in the Diels-Alder Reaction: History and Applications in Total Synthesis. Angew. Chem., Int. Ed. 2014, 53, 2056−2077. (c) Eschenbrenner-Lux, V.; Kumar, K.; Waldmann, H. The Asymmetric Hetero-Diels-Alder Reaction in the Syntheses of Biologically Relevant Compounds. Angew. Chem., Int. Ed. 2014, 53, 11146−11157. (18) Minami, Y.; Kanda, M.; Hiyama, T. Palladium-catalyzed Cycloaddition of Alkynyl Aryl Ethers to Allenes to Form a 2,3Bismethylidene-2,3-dihydro-4H-1-benzopyran Framework. Chem. Lett. 2014, 43, 181−183. (19) (a) Shimizu, M.; Hiyama, T. Organic Fluorophores Exhibiting Highly Efficient Photoluminescence in the Solid State. Chem. - Asian J. 2010, 5, 1516−1531. (b) Hong, Y.; Lam, J. W. Y.; Tang, B. Z. Aggregation-induced emission. Chem. Soc. Rev. 2011, 40, 5361−5388. (20) 1,4-Benzoxazin-2-one exhibits luminescence in solution. See: (a) Azuma, K.; Suzuki, S.; Uchiyama, S.; Kajiro, T.; Santa, T.; Imai, K. A study of the relationship between the chemical structures and the fluorescence quantum yields of coumarins, quinoxalinones and benzoxazinones for the development of sensitive fluorescent derivatization reagents. Photochem. Photobiol. Sci. 2003, 2, 443−449. (b) Lemp, E.; Cãnete, A.; Günther, G.; Pizarro, N.; Zanocco, A. L. Photosensitized generation of singlet molecular oxygen by aryloxazinones. J. Photochem. Photobiol., A 2008, 199, 345−352. (21) Minami, Y.; Kanda, M.; Hiyama, T. Palladium-catalyzed Cycloaddition of Aryl Silylethynyl Ethers with Isocyanates via o-C− H Cleavage. Chem. Lett. 2014, 43, 1408−1410. (22) Minami, Y.; Kanda, M.; Sakai, M.; Hiyama, T. PalladiumCatalyzed Annulation of Alkynyl Aryl Ethers with Isocyanates through o-C-H Cleavage. Synthesis of Solid-state Emissive 2-Methylidene-2H1,4-benzoxazin-3(4H)-ones. Tetrahedron 2015, 71, 4522−4534. (23) It seems that a tetranuclear zinc cluster derived from Zn(OAc)2 is effective. See: (a) Auger, V.; Robin, I. A basic zinc acetate analogous to beryllium acetate. C. R. Hebd. Seances Acad. Sci. 1924, 178, 1546− 1548. (b) Besson, J.; Hardt, H. D. Z. Z. Zur Kenntnis der fettsauren Salze des Berylliums. Z. Anorg. Allg. Chem. 1954, 277, 188−200. (c) Koyama, H.; Saito, Y. The Crystal Structure of Zinc Oxyacetate, Zn4O(CH3COO)6. Bull. Chem. Soc. Jpn. 1954, 27, 112−114. (24) Lapointe, D.; Fagnou, K. Overview of the Mechanistic Work on the Concerted Metallation−Deprotonation Pathway. Chem. Lett. 2010, 39, 1118−1126. (25) For selected examples of the insertion of isocyanates into C−H bonds, see: (a) Kuninobu, Y.; Tokunaga, Y.; Kawata, A.; Takai, K. Insertion of Polar and Nonpolar Unsaturated Molecules into Carbon− Rhenium Bonds Generated by C−H Bond Activation: Synthesis of Phthalimidine and Indene Derivatives. J. Am. Chem. Soc. 2006, 128, 202−209. (b) Hesp, K. D.; Bergman, R. G.; Ellman, J. A. Expedient Synthesis of N-Acyl Anthranilamides and β-Enamine Amides by the

Rh(III)-Catalyzed Amidation of Aryl and Vinyl C−H Bonds with Isocyanates. J. Am. Chem. Soc. 2011, 133, 11430−11433. (c) Sueki, S.; Guo, Y.; Kanai, M.; Kuninobu, Y. Rhenium-Catalyzed Synthesis of 3Imino-1-isoindolinones by C−H Bond Activation: Application to the Synthesis of Polyimide Derivatives. Angew. Chem., Int. Ed. 2013, 52, 11879−11883. (26) (a) Pestemer, M.; Lauerer, D. IR-Spektroskopischer Nachweis der Anlagerung katalytisch wirksamer Elektronendonatoren und -acceptoren an Moleküle mit polaren Mehrfachbindungen. Angew. Chem. 1960, 72, 612−618. (b) Horder, J. R.; Lappert, M. F. Chloroboration and allied reactions of unsaturated compounds. Part VIII. Insertion of isocyanates and isothiocyanates into Al−Et and Al− Br bonds. J. Chem. Soc. A 1968, 2004−2008. (c) Sun, J.-L.; Liu, H.; Yin, H.-M.; Han, K.-L.; Yang, S. Photodissociation of Solvated Metal Cation Complexes Mg+(OCNC2H5)n (n = 1−3). J. Phys. Chem. A 2004, 108, 3947−3954. (27) Insertion of ketenes into C(sp)−H bonds has been reported. See: Ogata, K.; Ohashi, I.; Fukuzawa, S. Rhodium-Catalyzed ThreeComponent Reaction between Silylacetylene and Two Ketenes Leading to 1,3-Enynes Bearing a Carboxylic Ester Group via Double Insertion of Ketenes. Org. Lett. 2012, 14, 4214−4217. (28) Metal-mediated intramolecular anti-insertion of alkynes into benzylic C−H bonds has been reported. See: (a) Bajracharya, G. B.; Pahadi, N. K.; Gridnev, I. D.; Yamamoto, Y. PtBr2-Catalyzed Transformation of Allyl(o-ethynylaryl)carbinol Derivatives into Functionalized Indenes. Formal sp3 C-H Bond Activation. J. Org. Chem. 2006, 71, 6204−6210. (b) Tobisu, M.; Nakai, H.; Chatani, N. Platinum and Ruthenium Chloride-Catalyzed Cycloisomerization of 1Alkyl-2-ethynylbenzenes: Interception of π-Activated Alkynes with a Benzylic C−H Bond. J. Org. Chem. 2009, 74, 5471−5475. (c) Yang, S.; Li, Z.; Jian, X.; He, C. Platinum(II)-Catalyzed Intramolecular Cyclization of o-Substituted Aryl Alkynes through sp3 C−H Activation. Angew. Chem., Int. Ed. 2009, 48, 3999−4001. For an example of the insertion of an alkene into a benzylic C−H bond, see ref 15c. (29) Minami, Y.; Yamada, K.; Hiyama, T. Palladium-Catalyzed Hydrobenzylation of ortho-Tolyl Alkynyl Ethers by Benzylic C−H Activation: Remarkable Alkynoxy-Directing Effect. Angew. Chem., Int. Ed. 2013, 52, 10611−10615. (30) Similar selectivity for benzylic C−H cleavage has been reported. See: Crespo, M.; Anderson, C. M.; Kfoury, N.; Font-Bardia, M.; Calvet, T. Organometallics 2012, 31, 4401−4404. (31) Ukhin, L. Y.; Belousova, L. V.; Orlova, Z. I.; Korobov, M. S.; Borodkin, G. S. Dehydration Rearrangements of Derivatives of Methylenedihydrobenzofuran - a New Path to Substituted Benzofurans. Chem. Heterocycl. Compd. 2002, 38, 1174−1179. (32) Comprehensive Heterocyclic Chemistry III, Volume 3; Katritzky, A. R., Ramsden, C. A., Scriven, E. F. V., Taylor, R. J. K., Eds.; Elsevier: Oxford, U.K., 2008 and previous editions of this series. (33) (a) Zhi, L.; Tegley, C. M.; Pio, B.; Edwards, J. P.; Jones, T. K.; Marschke, K. B.; Mais, D. E.; Risek, B.; Schrader, W. T. Synthesis and Biological Activity of 5-Methylidene 1,2-Dihydrochromeno[3,4-f ]quinoline Derivatives as Progesterone Receptor Modulators. Bioorg. Med. Chem. Lett. 2003, 13, 2071−2074. (b) Zhi, L.; Tegley, C. M.; Pio, B.; Edwards, J. P.; Motamedi, M.; Jones, T. K.; Marschke, K. B.; Mais, D. E.; Risek, B.; Schrader, W. T. 5-Benzylidene-1,2-dihydrochromeno[3,4-f ]quinolines as Selective Progesterone Receptor Modulators. J. Med. Chem. 2003, 46, 4104−4112. (c) Hong, L. P. T.; White, J. M.; Donner, C. D. Synthesis and X-Ray Crystal Structure of Cynandione B Analogues. Aust. J. Chem. 2012, 65, 58−64. (d) Shi, Y.; Wan, P. Photocyclization of a 1,1′-bisnaphthalene: planarization of a highly twisted biaryl system after excited state ArOH dissociation. Chem. Commun. 1997, 33, 273−274. (34) Minami, Y.; Anami, T.; Hiyama, T. Palladium-catalyzed Annulation of 2-Substituted Silylethynyloxybiaryls through δ-C−H Activation. Chem. Lett. 2014, 43, 1791−1793.

K


Synthetic Transformations through AlkynoxyâPalladium Interactions

Recommend Documents

Synthetic Transformations through AlkynoxyâPalladium Interactions