Homocuprate reagents

R Cu, or litliium or magnesium homocuprates RfCuM fM = Li, MgX), are fre-quently used, but a number of catalytic processes have also been developed. These processes nornnally utilize a catalytic amount of a copper salt CuY and a stoichiometric amount of an organometallic reagent R M IM = Li, MgX, ZnX, etc.). Hie leaving groups used include balides, esters, sulfonates, and epoxides, among others. 

The selective formation of 5-hydroxy-2,2-dimethylch romenes instead of the usual 7-hydroxy isomer has been accomplished with organocopper reagents <79JCS(Pl)201). Olivetol bis(tetrahydropyranyl ether) (61) is- selectively metallated at C-2 and the resulting homocuprate (62) reacts with 3-acetoxy-3-methylbut-l-yne to yield 5-hydroxy-2,2-dimethyl-7-pentylchroipene (63 Scheme 7). 

The combinations of chlorotrimethylsilane-hexamethylphosphoramide (HMPA) or chlorotrimethylsi-lane-4-(dimethylamino)pyridine (DMAP) are also powerful accelerants for copper(I)-catalyzed Grignard conjugate additions,33 and stoichiometric organocopper and homocuprate additions (Scheme 21 ).36 However, these reactions must be performed in tetrahydrofuran instead of ether.37 These procedures are noted for their high yields with stoichiometric quantities of Grignard reagents, excellent chemoselectivity and efficiency with a,3-unsaturated amides and esters and enals.58 Typically, additions to enals proceed via the S-trans conformers to afford stereo-defined silyl enol ethers for example, enals (122) and (124) give the ( )-silyl enol ether (123) and (Z)-silyl enol ether (125), respectively. 

Annelation, The Gilman ate reagents derived from acetone N,N-dimethyl-hydrazone, either the homocuprate derivative (7, 149) or the more recently developed phenylthio heterocuprate derivative, add in a conjugate fashion to ethyl 1-cyclohexene-1-carboxylate (1) to afford the keto ester (2, 60-70% yield) after hydrolysis of the N,N-dimethylhydrazone group. The keto ester 2 serves as a versatile intermediate tor the preparation of several complementary annelation products 4-8. 

Since only one of the organic groups of homocuprates is usually utilized, a non-trans-ferable group bonded to copper, such as RC C, 2-thienyl, PhS, r-BuO, R2N, Ph2P, or Me3SiCH2, is employed for the preparation of heterocuprate reagents. These cuprates are usually thermally more stable (less prone toward P-elimination of Cu-H), and a smaller excess of the reagent may be used. 

The organocopper reagents used for conjugate additions to enones are homocuprates, heterocuprates, higher-order cuprates, and Grignard reagents in the presence of catalytic amounts of copper salts (CuX). 

Enolates obtained from conjugate addition of either homocuprates or copper-catalyzed Grignard reagents undergo aldol condensation with aldehydes in the presence of ZnCl2 to give stereoisomeric mixtures of aldol products A ... 

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