Carbenes heteroaryl

An interesting class ot covalent Inflates are vin l and ar>/ or heteroaryl Inflates Vinyl inflates are used for the direct solvolytic generation of vinyl cations and for the generation of unsaturated carbenes via the a-elimination process [66] A triflate ester of 2-hydroxypyridine can be used as a catalyst for the acylation of aromatic compounds with carboxylic acids [109] (equation 55)... 

Saito et al. <1995S87> described a new method for the synthesis of heterocycle-fused[c]thiophenes via reaction of aryl heteroaryl thioketones with the carbene precursors. Heteroaromatic thioketones A react with carbenoids generated from bis(arylsulfonyl)diazomethanes or phenyliodonium bis(phenylsulfonyl)methylides to give heterocycle-fused[f]thiophenes B. The reaction involves the ring closure of the intermediary thiocarbonyl ylides, followed by restorative aromatization via the elimination of a sulfenic acid (Equation 11). 

Fischer carbene complexes 639 can be coupled with 3-alkynyl-2-heteroaromatic carbaldehydes to form initially the alkenylcarbene complexes 640, which undergo CO insertion to give the ketene intermediates 641, which upon ring closure affords heteroaryl-fused 277-pyran-2-ones (Scheme 147) <2001TL777, 2002JOC4177>. 

Diastereoselective and enantioselective (see Enantio-selectivity) cyclopropanations of chiral alkenes can be achieved (Scheme 57). Unactivated alkenes usually do not participate in cyclopropanation reactions of Fischer carbenes. However, alkenyl- and heteroaryl-substituted group 6 alkoxy carbene complexes cyclopropanate unactivated alkenes in good yield (Scheme 58). ... 

R = aryl, heteroaryl, 3° alkyl, C(=0)-alkyl catalyst NaCN, KCN, thiazolium salt, NHC (A/-heterocyclic carbenes)... 

Catalysts generated from A-heterocyclic carbenes 23-25 (Figure 7) have been shown to efficiently catalyze the coupling of aryl and heteroaryl halides with indoles. Reactions conducted with the terf-butoxide base, which is typically used for the C—N coupling, did not occur, but reactions with NaOH as base occurred to high conversion85. Although 4-bromotoluene and bromobenzene reacted with numerous substituted indoles under these conditions, electron-rich and orf/zo-substituted aryl bromides reacted slowly and in low or moderate yields. 

A review has discussed the photochemical cyclization of a variety of aryl- and heteroaryl-prop-2-enoic acids. Irradiation (A,>340nm) of the cyclohexenone (119) in argon purged benzene solution affords the cyclized derivatives (120) as a 3 1 mixture of diastereoisomers. The formation of the cyclopropyl group arises via the carbene (121) and insertion into a C-H bond of a neighbouring methyl group. This carbene is formed, presumably, from the biradical (122) which arises by addition of the alkene to the excited state of the enone. Further evidence for the carbene intermediate comes from a reaction in methanol when the diastereo-isomeric mixture of the ethers (123) and (124) is obtained." ... 

The order of reactivities observed in S Ar displacement reactions often parallels the order of reactivity of aryl halides in oxidative additions to Pd(0). Likewise, the ease with which the oxidative addition occurs for heteroaryl halides can often be predicted on the basis of S Ar reactivity of a given substrate. In addition, a- and y-chloroheteroarenes are sufficiently activated for use in Pd-catalyzed reactions with a variety of different catalysts, whereas Pd-catalyzed reactions of unactivated aryl chlorides (e.g. chlorobenzene) typically require large, electron-rich phosphine or 7V-heterocychc carbene ligands [4]. 

However, a truly general method for electron-rich heterocycle arylation was not reported until 2007 [38], Electron-rich, bulky butyl-di-l-adamantylphosphine or /er/-buty I dicyclohexyl phosphine in combination with Pd(OAc)2 afforded the best results, and the former was chosen because of cost considerations. Interestingly, electron-rich AMieterocyclic carbene ligands that facilitate oxidative addition of aryl chlorides to low-valent transition metals are inefficient in heterocycle arylation. A number of structurally diverse electron-rich heterocycles are reactive (Scheme 3). Thiophene, benzothiophene, 1,2- and 1,3-oxazole derivatives, benzofuran, thiazoles, benzothiazole, 1-alkylimidazoles, 1-alky 1-1,2,4-triazoles, and caffeine can be arylated. Electron-rich, electron-poor, and heteroaryl chlorides can be used. 

Ducept and Marsden described a general synthesis of 5-ethoxy-2-substituted 4-(triethylsilyl)oxazoles 176 from the rhodium(II)octanoate-catalyzed diazo-transfer reaction of ethyl (triethylsilyl)diazoacetate 175 and nitriles (Scheme 1.48). The reaction conditions tolerate a wide variety of functional groups on the nitrile, including alkyl, aryl, heteroaryl, vinyl, carbonyl, sUyloxy, and dialkylamino. Desilylation of 176 with TBAF afforded the corresponding 2-alkyl(aryl)-5-ethoxy-oxazoles 177, which are normally inaccessible from diazoesters using conventional rhodium-carbene methodology. The authors noted that carbonyl groups in the 2 position of 176 are not compatible with TBAF deprotection. 

Patenden et al. [46] synthesized heterocyclic analogues of pulvinones 52-55 and of permethylated pulvinic acids 56, 57 which were found in higher fungi (Scheme 21). All compounds possessing lactonic structures were synthesized in the Horner-Wittig reaction using the corresponding heteroaryl aldehydes and 4-dimethoxy-phosphorylated lactone 58. The latter was obtained as the main product in the reaction between substituted maleic anhydrides 59 and sodium dimethyl phosphite via the postulated carbene. 

The use of transition-metal catalysts in the substitution of aryl halides by amines has been reviewed. There has also been a summary of the use of palladium catalysts in the reaction of aryl and heteroaryl halides with primary and secondary amines. It has been shown that the amination of aryl sulfamates by aliphatic amines may be achieved using a nickel catalyst with an A-heterocyclic carbene ligand. Suitable ligands for nickel and palladium in the catalysed amination reactions of aryl sulfamates and imidazolylsulfonates have been identified. " The palladium-catalysed reaction of aryl nonafluorobutanesulfonates with primary sulfonamides may yield substituted products such as (22). Kinetic data suggest that reductive elimination from the palladium intermediate is likely to be rate limiting. A-Arylmethanesulfonamides may also be formed from aryl bromides and chlorides using a palladium catalyst... 

Aryl carbene complexes with electron-donating or electron-withdrawing substituents in the ortho-, para-, or meta-positions participate in the DBR. The aryl group can also be naphthyl and heteroaryl such as furan, thiophene, pyrrole, pyrazole, and indole. Simple alkyl substituted vinyl carbene complexes have been extensively examined. The double bond can be in either a cyclic or an acyclic system. 

SCHEME 5.25 Coupling of a,P-unsaturated carbene Vlla/b with aUcynyl heteroaryl ketone 33 and DMAD. 

The Dotz reaction may employ heteroaryl substituted carbenes. The fiuyl carbene 8.58 gave thebenzofuran 8.59 (Scheme 8.19). The reaction may also be intramolecular, taking advantage of the acylation of the ate complex 8.60 to introduce the alkyne (Scheme 8.20). ... 

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