Triflate with cuprates

Likewise, alkynyliodonium tosylates can be coupled with dialkyl- and diphenyl cuprates 136 to afford the respective alkyl- and phenyl-substituted alkynes 137 (Scheme 56) [114]. An interesting example of this reaction involves the coupling of (trimethylsilyl)ethynyl iodonium triflate with cubyl cuprate generated in situ from iodocubane 138 [116]. 

Vinyllithiums cf. 13, 142).10 An improved route to vinyllithiums involves coupling of vinyl and aryl triflates with tributyl- or trimethylstannylcuprates of the formula (R3Sn)2Cu(CN)Li2, prepared from LDA, R,SnH, and CuCN in THF at -50° to -60°. The higher-order cuprates couple with vinyl and aryl triflates at -20° to provide a vinyltin intermediate. Work-up of the intermediate with AgOAc provides a vinyltin, with bromine a vinyl bromide, or with CF,COOH an aryltin. 

It should be noted that direct substitution of sulfonate or iodide derivatives at C6 is sensitive to steric hindrance. Kishi reported a failure in the substitution of a primary tosylate by vinyl cuprate in the synthesis of mycalamides where C4 had two geminal methyl substituents. An alternate five step route was developed to introduce the vinyl substituent [119]. Direct substitution of a primary triflate by an aryl Grignard reagent is a key step in the formal synthesis of (+)-apicularen A from D-glucal [194]. Displacement of a triflate with an alkynyllithium has also been used in the total synthesis of (+)-panaxacol [195]. 

It will be recalled that lactone-derived enol triflate 102 was expected to serve as a substrate for a Murai coupling37 with the mixed cuprate reagent derived from iodo ortho ester 103 (see Scheme 17c). If successful, this C-C bond forming process would accomplish the introduction of the remaining carbon atoms needed for the annulation of the seven-membered D-ring lactone. 

Asymmetric conjugate addition of dialkyl or diaryl zincs for the formation of all carbon quaternary chiral centres was demonstrated by the combination of the chiral 123 and Cu(OTf)2-C H (2.5 mol% each component). Yields of 94-98% and ee of up to 93% were observed in some cases. Interestingly, the reactions with dialkyl zincs proceed in the opposite enantioselective sense to the ones with diaryl zincs, which has been rationalised by coordination of the opposite enantiofaces of the prochiral enone in the alkyl- and aryl-cuprate intermediates, which precedes the C-C bond formation, and determines the configuration of the product. The copper enolate intermediates can also be trapped by TMS triflate or triflic anhydride giving directly the versatile chiral enolsilanes or enoltriflates that can be used in further transformations (Scheme 2.30) [110],... 

Scheme 2.28 Functionalized allenes obtained by 1,6-cuprate addition to acceptor-substituted enynes and regioselective enolate trapping with methyl triflate (77), aldehydes (78, 79), ketones (80) and silyl halides (81).

A route involving trapping the enolate as a silyl enol ether, subsequent transme-tallation to the corresponding lithium enolate and alkylation turned out to be more efficient (Scheme 18.41) [123]. Thus, treatment of 120 with the cuprate 124 and chlorotrimethylsilane furnished the silyl enol ether 125, which was then converted into the desired enprostil derivative 127 with 68% yield over both steps by reaction with methyllithium and the allenic triflate 126. 

Stannyl cuprates couple with vinyl halides or triflates [16c-d, 85], and a vinyl stannane produced this way has been used in the synthesis of 7-[( )-alkylidene]-cephalosporins [117]. Vinyl substitution reactions starting from dihydrofurans are... 

The introduction of the allylic silane moiety required for the intermolec-ular Hosomi-Sakurai reaction is depicted in Scheme 16. Following the formation of the enol triflate 97, a Stille coupling provided excess to the allylic alcohol 98 [51]. The allylic alcohol (98) was endowed with a phosphate leaving group for the subsequent allylic substitution. Utilizing a trimethylsilyl cuprate as nucleophile for the 5 2 reaction, the allylic phosphate was converted into the allylic silane 89. A useful substrate-induced diastereoselectivity in favour of (14i )-89 was encountered at small scale but decreased significantly upon up-scaling. 

Coupling with enol esters (7, 93). A new synthesis of an alkyl-substituted alkene involves coupling of a lithium dialkyl cuprate with an enol triflate,1 available from a ketone by reaction with triflic anhydride and 2,6-di-t-butylpyridine.2 A wide variety of organocuprates can be used and the geometry of the enolate is largely retained. Reported yields are in the range 60 100%. 

Solution Tlie first reaction leads under basic conditions to cyclization to epoxide 34. Replacement of the triflate group by a methyl group to give 35 is accomplished with the aid of a Gilman cuprate.11 The... 

Another phenoxide activating approach published by Buchwald et al. [18] is based on the reaction of cesium phenoxides with aryl bromides or iodides in the presence of catalytic amounts of copper(I) triflate and ethyl acetate in refluxing toluene (Scheme 3b). In certain cases equimolar amounts of 1-naphthoic acid have been added in order to increase the reactivity of the phenoxide. The authors assume the formation of a cuprate-like intermediate of the structure [(ArO)2Cu] Cs+ as the reactive species. In addition, diaryl ether formation between phenols and aryl halides has been achieved using a phosphazene base forming naked phenoxide in the presence of copper bromide in refluxing toluene or 1,4-dioxane [19]. 

Bicyclic enediynes were obtained from the Diels-Alder adducts of cyclopenta-diene or furan with bis phenyliodonium acetylene triflate and lithium alkynyl cuprates. In this case the reaction conditions were more demanding and yields less satisfactory. 

Recently, the direct transformation of allyl- 206272 and aryl tellurides 209273 into the corresponding organocopper species 207 and 210 by tellurium-copper exchange was described. The resulting allyl 207 or aryl cuprates 210 were captured by coupling with vinyl triflates 208272 or by 1,4-addition to enones 211,273 respectively (Scheme 112). 

R2Cu(CN)Li2 arene synthesis,16 Aryl triflates or nonaflates do not couple with R2CuLi, but they do couple with the mixed cuprates R2Cu(CN)Li2 to give alkylarenes in 40-95% yield. Substituents on the aromatic ring have little effect in the reaction. Example ... 

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