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

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. Getting in key: A soft Lewis acid/hard Brønsted base cooperative catalyst allows for efficient stereoselectives coupling of N-alkylidene-α-aminoacetonitrile and aliphatic ketimines to access vicinal diamines bearing consecutive tetra- and trisubstituted stereogenic centers. The use of a soft Lewis basic thiophosphinoyl group on the ketimines is key to promoting the reaction with as little as 3 mol % catalyst loading.