Asymmetric Hydrocyanation of N-Phosphinoyl Aldimines with Acetone Cyanohydrin by Cooperative Lewis Acid/Onium Salt/Brønsted Base Catalysis

Abstract

α-Amino acids are of fundamental importance for life. Both natural and artificial α-amino acids also play a crucial role for pharmaceutical purposes. The catalytic asymmetric Strecker reaction still provides one of the most attractive strategies to prepare scalemic α-amino acids. Here we disclose a new concept for Strecker reactions, in which an achiral Brønsted base cooperates with a Lewis acid and an aprotic ammonium salt, which are both arranged in the same chiral catalyst entity. The described method could successfully address various long-standing practical issues of this reaction type. The major practical advantages are that (1) the N-protecting group is readily removable, (2) acetone cyanohydrin is attractive as cyanation reagent in terms of atom economy and cost efficiency, (3) an excess of the cyanation reagent is not necessary, (4) the new method does not require additives and (5) is performed at ambient temperature.