Organocopper compounds conjugate additions

CONJUGATE ADDITION OF ORGANOCOPPER REAGENTS TO a,p-UNSATURATED CARBONYL COMPOUNDS... 

As in the case of addition reactions of carbon nucleophiles to activated dienes (Section HA), organocopper compounds are the reagents of choice for regio- and stereoselective Michael additions to acceptor-substituted enynes. Substrates bearing an acceptor-substituted triple bond besides one or more conjugated double bonds react with organocuprates under 1,4-addition exclusively (equation 51)138-140 1,6-addition reactions which would provide allenes after electrophilic capture were not observed (cf. Section IV). 

While a large number of studies have been reported for conjugate addition and Sn2 alkylation reactions, the mechanisms of many important organocopper-promoted reactions have not been discussed. These include substitution on sp carbons, acylation with acyl halides [168], additions to carbonyl compounds, oxidative couplings [169], nucleophilic opening of electrophilic cyclopropanes [170], and the Kocienski reaction [171]. The chemistry of organocopper(II) species has rarely been studied experimentally [172-174], nor theoretically, save for some trapping experiments on the reaction of alkyl radicals with Cu(I) species in aqueous solution [175]. 

The synthetic application of organocopper compounds received a major impetus from the study of the catalytic effect of copper salts on reactions of Grignard reagents with y.,(i-unsaturated ketones.1 Whereas Grignard reagents normally add to conjugated enones to give the 1,2-addition product, the presence of catalytic amounts of Cu(I) results in... 

Regioselective alkylative opening of a,(1-epoxy ketone oxime [40] and tosylhydra-zones [41] with organocopper reagents is initiated by the generation of unsaturated azo compounds which undergo conjugate addition. 

The conjugate addition of organocopper reagents to polyalkenic carbonyl compounds presents an opportunity in which either 1,4-, 1,6- and sometimes 1,8-addition can occur. Much of the early woik in this area was conducted in the study of the reaction of a dienoate or dienone with an alkylcuprate or a catalytic copper/organomagnesium combination. The predominant mode of addition for the reaction of a dienoate and a copper-based organomagnesium reagent was found to be 1,6 not 1,4.72 If the opportunity of 1,8-addition was present, then this mode prevailed.73 However, a truly systematic study has not been carried out with the various reagents. 

You met organocopper reagents in Chapter 10 where you saw that they did conjugate additions to a,p-unsaturated carbonyl compounds. Other metals, such as cadmium or manganese, can also be used to make ketones from acid chlorides. 

Chemists soon showed that it was an easy matter to synthesize a related ester by a conjugate addition of an organocopper derivative (Chapter 10) and then the alkylation of an ester enolate (Chapter 26). The enolate reacts with Mel on the face opposite the propenyl side chain—a good example of stereochemical control with cyclic compounds (Chapter 33). 

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