Catalytic enantioselective conjugate addition with Grignard reagents

Abstract

In this Account, recent advances in catalytic asymmetric conjugate addition of Grignard reagents are discussed. Synthetic methodology to perform highly enantioselective Cu-catalyzed conjugate addition of Grignard reagents to cyclic enones with ee's up to 96% was reported in 2004 from our laboratories. Excellent levels of stereocontrol were achieved with Cu(I) halides, alkylmagnesium bromides, and commercially available chiral ferrocenyl diphosphines. Studies carried out during the last 2 years demonstrated that these Cu-catalysts are very effective for the enantioselective conjugate addition of Grignard reagents to acyclic enones, alpha,beta-unsaturated esters, and thioesters. On the basis of this methodology, a diastereo- and enantioselective iterative route to deoxypropionate units was developed and applied to the synthesis of natural products. Finally, we summarize our recently conducted mechanistic investigations and the application of this catalytic system to the enantioselective SN2' substitution reactions of allylic bromides with Grignard reagents.