摘要
We report a highly enantioselective one-pot facile synthesis of fluorinated Cα-tetrasubstituted amino nitriles from α-fluoroalkyl α-aryl keo tones, 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 Cα-tetrasubstituted fluorinated aminonitriles from ketones, because the purification of a-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_2O 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.
We report a highly enantioselective one-pot facile synthesis of fluorinated Cα-tetrasubstituted amino nitriles from α-fluoroalkyl α-aryl keo tones, 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 Cα-tetrasubstituted fluorinated aminonitriles from ketones, because the purification of a-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_2O 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.
基金
We thank the financial support from the National Natural Science Foundation of China （Nos. 21472049, 21725203）.
