2-(Cyanomethyl)benzimidazole Derivatives as 1,3-Dicarbonyl Analogues for a Kinetically Controlled Diastereo- and Enantioselective Mannich-Type Reaction Catalyzed by Chiral Phosphoric Acid.

An asymmetric Mannich-type reaction of -protected 2-(cyanomethyl)benzimidazoles with -benzoyl imines was developed by using chiral phosphoric acid as a chiral Brønsted acid catalyst. Products having vicinal trisubstituted carbon stereogenic centers were formed in a highly diastereo- and enantioselective manner, even though one of the stereogenic centers had an active methine proton. Comprehensive control experiments revealed that high stereoselectivity was achieved through a kinetically controlled process.