[PDF] Copper- Catalyzed Asymmetric Synthesis by Alexakis, Krause and Woodward

Copper- Catalyzed Asymmetric Synthesis by Alexakis, Krause and Woodward : Content: 12.2 Conjugate Addition: Asymmetric copper-catalyzed conjugate addition reaction is a versatile and a very useful organic transformation. Progress in this area has been covered inseveral reviews [14–23]. The mechanism for nonstabilized nucleophiles (e.g.,RMgX, ZnR2, AlR3) is thought to share much of the characteristics from the stoichiometric versions involving lithium organocuprates [24]. The general

catalytic cycle involves a transmetallation of the nucleophile to CuI with the

stoichiometric metal staying associated and functioning as a Lewis acid in the

following steps: formation of a π-complex with the enone and either an

oxidative addition (to a σ-complex) followed by reductive elimination or a

carbocupration (1,2-migratory insertion) with subsequent rearrangement to

reform the copper catalyst (Scheme 12.2). Cu(I) is thought to be the active

catalyst although Cu(II)-salts are the most commonly used precatalysts

because they are less hygroscopic and air sensitive. NMR and EPR (electron

paramagnetic resonance) studies support the theory of in situ reduction of

Cu(II) to Cu(I) [25].