Homocuprates

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. 

CH,)jSO cupratesThe carbanion of DMSO is a useful nontransfer-able ligand for homocuprates. These cuprates are readily prepared by sequential reaction of DMSO with BuLi, Cul, and RLi and undergo the usual reactions with complete retention of the CH3SOCH2 group. The (CH3)2SO cyanocuprates, [CH3SOCH2Cu(CN)R]Li2, are obtained by reaction of dimsyllithium with CuCN... 

A 1,2-metalate rearrangement of a higher order cuprate, known as a Kodenski rearrangement [64], was used as a key step in the synthesis of the marine antiinflammatory sesterterpenoid manoalide 95 (Scheme 9.20) [65]. Treatment of the alkenyl lithium 89 (prepared from the alkenylstannane 88 with s-BuLi in a diethyl ether-pentane mixture) with the homocuprate 91 (produced from iodoalkane 90) gave the iodoalkene 94 in 72% overall yield from 88. The reaction proceeds as fol-... 

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 reaction of dehydrolinalool acetate (274) with the homocuprate of olivetol bis(tetrahydropyranyl ether) (273) was expected to yield cannabichromene by analogy with the reaction with 3-acetoxy-3-methylbut-l-yne (79JCS(Pl)20l). However, the major product was 3,4-m-A1,2-tetrahydrocannabinol (275), which could readily be purified, thereby providing a valuable route to this substance. Its formation is thought to involve the generation of an allene which proceeds to the chroman via an allylic cation and trans addition to the isopropylidene group (Scheme 69). 

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. 

Mixed homocuprates.7 Mixed cuprates (1) in which the nontransferable ligand is an a-sulfonyl carbanion are easily prepared from dimethyl sulfone or methyl phenyl sulfone (equation I), and are effective for conjugate addition to enones and for a synthesis of ketones from acid chlorides. 

Lewis acid converts the homocuprate into a mixture of four components ... 

Aiylation with a homocuprate. A key step in a synthesis of the cannabis constituent 4 is the reaction of 1 with the homocuprate derived from olivetol dimethyl ether (2) hy regiospecific lithiation followed by reaction with CuBr. The cuprate does not react with 1 in the absence of a Lewis acid, but in the presence of BF, etherate (3.5 equiv.) ( —)-3 is obtained in 78% yield with high regio- and stereospecificity. The dihydrobromide of... 

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. 

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