Catalytic asymmetric mannich-type reaction of N-alkylidene-α-aminoacetonitrile with ketimines

Abstract

Optically active vicinal diamines are versatile chiral building blocks in organic synthesis. A soft Lewis acid/hard Brønsted base cooperative catalyst allows for an efficient stereoselective coupling of N-alkylidene-α-aminoacetonitrile and ketimines to access this class of compounds bearing consecutive tetra- and trisubstituted stereogenic centers. The strategic use of a soft Lewis basic thiophosphinoyl group for ketimines is the key to promoting the reaction, and aliphatic ketimines serve as suitable substrates with as little as 3 mol % catalyst loading.

Keywords: Mannich reaction; asymmetric catalysis; copper; ketimines; nitriles.