Cu(i)-catalyzed Michael addition of ketiminoesters to β-trifluoromethyl β,β-disubstituted enones: rapid access to 1-pyrrolines bearing a quaternary all-carbon stereocenter

Abstract

A highly chemo-, diastereo-, and enantioselective Cu(I)/(S,S)-ⁱPr-FOXAP-catalyzed Michael addition of ketiminoester to β-trifluoromethyl β,β-disubstituted enones was developed. This method provides facile access to highly functionalized 1-pyrrolines bearing two contiguous stereocenters, including a trifluoromethylated all-carbon quaternary stereocenter, via one-pot hydrolytic cyclization (up to >20 : 1 cr, > 20 : 1 dr, and 98% ee). The addition of trace amounts of water to the direct 1,3-dipolar cycloaddition is crucial for obtaining 1-pyrrolines with high chemoselectivities rather than pyrrolidines.