Catalytic Enantioselective Conjugate Alkynylation of α,β-Unsaturated 1,1,1-Trifluoromethyl Ketones with Terminal Alkynes

The first catalytic enantioselective conjugate alkynylation of alpha,beta-unsaturated 1,1,1-trifluoromethyl ketones has been carried out. Terminal alkynes and 1,3-diynes were treated with trifluoromethyl ketones in the presence of a low catalytic load of a Cu-I-MeOBIPHEP complex (2.5 mol%) and triethylamine (10 mol%) to give the corresponding trifluoromethyl ketones bearing a propargylic stereogenic center at the beta position with good yields and excellent enantiomeric excesses in most of the cases. No 1,2-addition products were formed under the reaction conditions. The procedure showed broad substrate scope for alkyne, diyne, and enone. A rationale for the observed stereochemistry has been provided. Finally, the potential application of the reaction products in the synthesis of chiral tetrahydrofurans bearing a trifluoromethylated quaternary stereocenter has been devised.