Enantioselective Organocatalytic 1,6-Addition of Azlactones to <i>para</i>-Quinone Methides: An Access to α,α-Disubstituted and β,β-Diaryl-α-amino acid Esters

Abstract

This work describes the first enantioselective 1,6-additions of azlactones to para-quinone methides. In the presence of a chiral phosphoric acid, 1,6-adducts were obtained in high yields (up to 96%) with excellent diastereoselectivities and enantioselectivities (all >20:1 diastereoselectivity ratio (dr), up to 99% enantiomeric excess (ee)). Importantly, the method offers a facile synthetic approach, not only to enantiopure α,α-disubstituted α-amino acid esters, but also to unnatural enantioenriched β,β-diaryl-α-amino acid esters bearing adjacent tertiary and quaternary stereogenic centers.