Cuprate coupling

The formation of g-alkyl-a,g-unsaturated esters by reaction of lithium dialkylcuprates or Grignard reagents in the presence of copper(I) iodide, with g-phenylthio-, > g-acetoxy-g-chloro-, and g-phosphoryloxy-a,g-unsaturated esters has been reported. The principal advantage of the enol phosphate method is the ease and efficiency with which these compounds may be prepared from g-keto esters. A wide variety of cyclic and acyclic g-alkyl-a,g-unsaturated esters has been synthesized from the corresponding g-keto esters. However, the method is limited to primary dialkylcuprates. Acyclic g-keto esters afford (Zl-enol phosphates which undergo stereoselective substitution with lithium dialkylcuprates with predominant retention of stereochemistry (usually > 85-98i )). It is essential that the cuprate coupling reaction of the acyclic enol phosphates be carried out at lower temperatures (-47 to -9a°C) to achieve high stereoselectivity. When combined with they-... 

Stannyl cuprates couple widi vinyl halides or trlGales [16c-d, 85], and a vinyl stannane produced diis way has been used in die syntliesis of 7-[f )-alkylidetie]-cepbalosporlns [117]. Vinyl substitution reactions slariing Grom ddiydrofciraiis are... 

Dienes. 4 (Z)-Dialkenyl cuprates couple with alkenyl halides in the presence of Pd[P(C6H5)j]4 to form conjugated dienes in good yield, but with fair stereoselectivity. If 1 equivalent of zinc bromide (8, 86) is present, the configuration of the alkenyl halide is retained ( 99.5%). 

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. 

A variation involves an aryl cuprate coupled with a vinyl halide, leading eventually to the /3-methylenedihydrobenzo-furan complex (equation 103). Cyclization occurs spontaneously upon fluoride-induced removal of the silyl protecting... 

Two key differences in reactivity between vinyl- or aryl-liftiums and the corresponding R2CuLi species are firstly that the cuprates couple efficiently (and more rapidly than with alkyl halides) with both primary and secondary tosylates, which the lithiums do not, and secondly the general lack of... 

Cuprates couple efficiently with alkyl halides, as in the simple synthesis of n-undecane21 via the cuprate prepared from BuLi. When a Grignard reagent is involved, a Cu(I) compound is usually added in catalytic amounts for coupling with an alkyl halide. 

An even more efficient strategy might be based upon the utilization of the same chiral building block for all the asymmetric centers provided such a building block is readily available in enantiomerically pure form. The benzyl ether of 21 (see equation 10) is the intermediate in the cuprate coupling of 28... 

The fact that 31 is a four carbon chain in which every carbon bears a substituent, three of them oxygen and one a methyl group, suggests R,R-tartaric acid as a logical precursor (15.16). Scheme 4 outlines an extraordinarily efficient route from R,R-tartaric acid to 31 in an overall yield of 64%. Correlation of 31 via cuprate coupling and selective formation of the pivalate at the secondary alcohol gives 32 which was previously derived from 29. 

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