Highly enantioselective Cu(i)–Tol-BINAP-catalyzed asymmetric conjugate addition of Grignard reagents to α,β-unsaturated esters

Chemical Communications Pub Date: 2010-10-29 DOI: 10.1039/C0CC03211E

Abstract

The copper-catalyzed conjugate addition (CA) of organometallic reagents to α,β-unsaturated carbonyl compounds is one of the most versatile synthetic methods for the construction of C–C bonds. Interestingly, the application of Grignard reagents, which are among the most widely used of organometallic compounds, in asymmetric conjugate addition (CA) reactions has received less attention. Therefore, our group and others have been exploring better catalytic systems to effect the asymmetric 1,4-conjugate addition of Grignard reagents to α,β-unsaturated esters. It is only in the past decade that significant breakthroughs have been made in this field. In our studies, we found that CuI–Tol-BINAP could catalyze the asymmetric conjugate addition (CA) reactions of Grignard reagents, including the addition of MeMgBr to α,β-unsaturated esters to afford the β-methylated esters in good yields with excellent regio- and enantioselectivities. Both enantiomers of the products could be obtained by either using the enantiomers of the chiral Tol-BINAP or by using the geometrical isomer of the starting material. This method is also suitable for other Michael acceptors. In this article, we describe the development of the asymmetric Cu(I)–Tol-BINAP catalyzed 1,4-conjugate addition of Grignard reagents to α,β-unsaturated esters and applications of this chemistry. This method provides a convenient method to synthesize β-alkyl esters with high enantioselectivity or diastereoselectivity using CuI and the inexpensive chiral ligand, Tol-BINAP.

Graphical abstract: Highly enantioselective Cu(i)–Tol-BINAP-catalyzed asymmetric conjugate addition of Grignard reagents to α,β-unsaturated esters
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