Internally Reuse Waste: Catalytic Asymmetric One‐Pot Strecker Reaction of Fluoroalkyl Ketones, Anilines and TMSCN by Sequential Catalysis

Abstract

We report a highly enantioselective one‐pot facile synthesis of fluorinated C α ‐ tetrasubstituted amino nitriles from α ‐fluoroalkyl α ‐aryl ketones, anilines, and TMSCN through a sequential p ‐TsOH catalyzed ketimine formation and chiral bifunctional tertiary amine mediated asymmetric Strecker reaction. This one‐pot approach has two important advantages. First, it greatly improves the overall yield of the synthesis of chiral C α ‐tetrasubstituted fluorinated aminonitriles from ketones, because the purification of α ‐fluorinated ketimines by column chromatography suffers from great yield loss. Second, it represents the first example of asymmetric tandem reactions that can simultaneously reuse the by‐product and catalyst from the upstream step as a promoter and an additive to improve the reactivity and enantioselectivity of the subsequent catalytic enantioselective reaction, respectively. It could utilize the by‐product H 2 O generated in‐situ from the ketimine formation step to activate TMSCN to form HCN, and concurrently reuse the remaining p ‐TsOH acid as an additive to improve enantioselectivity.