Ketones conjugate additions, organocuprates

There are two major reactions of organocuprates, and both give products reminiscent of a carbon nucleophile (1) reaction with alkyl halides and (2) conjugate addition with a,p-unsaturated ketones. Conjugate addition to a, 3-unsaturated ketones is promoted when ether is used as a solvent.381 The substitution reaction is promoted by the use of THF or ether-HMPA as a solvent. l As mentioned earlier, the mechanism of these reactions probably involves a one-electron transfer, although other mechanistic proposals are in the literature,but the synthetic result is that expected of a carbon nucleophile. 85 The general reactivity of organocuprates with electrophiles follows the order ... 

Outline two ways in which 4 methyl 2 octanone can be pre pared by conjugate addition of an organocuprate to an a p unsaturated ketone... 

Addition of RJCuLi to bridgehead enones.1 Ordinarily organocuprates do not react with a bridgehead halide. However, they can undergo conjugate addition to bridgehead enones generated in situ from p-bromo ketones with potassium t-butoxide or lithium 2,6-di-r-butyl-4-methylphenoxide (6,95). 

INT2, Scheme 10.7) undergoes further reaction (Li/Cu transmetalation) and generates a new organocuprate compound. (Note however that this difference could become more subtle since the product of conjugate addition (PD) might behave more like an a-cuprio(I) ketone complexed with a lithium cation [52] than a lithium enolate complexed with copper(I)). In neither reaction was any evidence of radical intermediates (i.e., SET) found by theoretical calculations [79]. 

Lithium organocuprates are reagents for cross-coupling, conjugate addition, epoxide opening, ketone synthesis and addition to acetylenes ... 

The mechanistic picture for addition of organocuprates to a,P-unsaturated carbonyl compounds is no less complex than that for substitution reactions. On the basis of current information, conjugate addition of lithiocuprates to a, P-unsaturated ketones and esters may proceed via a initial reversible copper(I)-olefin-lithium association, which then undergoes oxidative addition followed by reductive elimination. ... 

An interesting observation from organocuprate chemistry is that the initial step in 1,4-addition to enones may be electron transfer. Thus the relative reactivity of enones toward conjugate addition parallels their ease of reduction. One problem with any reaction between a ketone or aldehyde and a metal alkyl is deprotonation, when a hydrogens are present, to yield an enolate. Given the considerable basicity of metal alkyls, this side reaction should be anticipated. 

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