Catalytic Asymmetric Reactions of Alkyl Alkynyl Ketimines: A Versatile Approach to Chiral α-Trialkyl Amines

Abstract

Chiral α-tertiary amine motifs exist in a variety of drugs and bioactive natural products. Therefore, considerable efforts have been devoted to the synthesis of chiral α-tertiary amines. Although chiral α-trialkyl amines are structurally most diverse and synthetically most important among α-tertiary amines, catalytic asymmetric methods toward these chiral amines remain extremely limited. Here, we report a new method for the catalytic asymmetric synthesis of chiral α-tertiary propargyl amines, which was realized by a chiral ammonium salt-catalyzed reaction of alkynyl ketimines with enals and enones. This reaction exhibited broad substrate tolerance with respect to variations on both alkynyl ketimines and enals, producing a diverse range of chiral α,α-dialkyl propargyl amines with either α- or α,β-stereocenters. Additionally, these chiral amines could be readily transformed into chiral α-trialkyl amines, which were especially challenging to synthesize by existing methods. We anticipate that this method could provide a broadly useful approach for the asymmetric synthesis of chiral α-tertiary amines.