Mechanism and Stereochemistry Reactions of organocopper reagents

1 mechanism , stereochemistry

1.1 substitution reactions
1.2 conjugate addition reactions
1.3 enantioselective variants

mechanism , stereochemistry
substitution reactions

the mechanism of nucleophilic substitution lower-order organocuprates depends in profound way on structure of substrate, organocuprate, , reaction conditions. evidence suggested direct sn2 displacement occurring; more recent results suggest invertive oxidative addition of copper(i) carbon-leaving group bond takes place, generating copper(iii) intermediate undergoes reductive elimination generate coupled product. both of these mechanisms predict inversion @ electrophilic carbon, observed in number of cases. on other hand, experiments radical traps , observation of racemization during substitution suggest radical mechanism.

(1)

conjugate addition reactions

the mechanistic picture of conjugate additions of organocuprates complex. significant amount of evidence has been gathered existence of initial complex between enone , organocuprate. carbocupration across carbon-carbon double bond may generate copper enolate, shown @ bottom of eq. (2). more likely, however, conjugate addition of organocuprate afford lithium enolate. subsequent reductive elimination , protonation leads product.

(2)

enantioselective variants

diastereoselective conjugate addition reactions of chiral organocuprates provide β-functionalized ketones in high yield , diastereoselectivity. disadvantage of these reactions requirement of full equivalent of enantiopure starting material.

(3)

more recently, catalytic enantioselective methods have been developed based on copper(i)-catalyzed conjugate addition of grignard reactions enones. proposed mechanism involves transmetalation grignard reagent copper, conjugate addition, , rate-determining reductive elimination (see analogous upper pathway in equation (2)).

(4)