Chiral phosphine-phosphite ligands in the enantioselective 1,4-addition of Grignard reagents to α,β-unsaturated carbonyl compounds

A library of chiral phosphine-phosphite ligands was evaluated in the Cu-catalyzed asymmetric 1,4-addition of Grignard reagents to cyclopentenone, cycloheptenone and 5,6-dihydro-2H-pyran-2-one. TADDOL-based ligands 1a and 1b with a bulky substituent at the ortho-position to the chiral phosphite moiety gave rise to the 1,4-addition products with high enantioselectivities (up to 93% ee). In addition to ethyl-MgBr (as a standard alkyl nucleophile) phenyl- and isopropenyl-MgBr could also be employed. In the case of cyclopentenone, the use of chlorotrimethylsilane as an additive led to improved regio- and enantioselectivities. (C) 2011 Elsevier Ltd. All rights reserved.