Enantioselective Synthesis of Cα-Tetrasubstituted N-Hydroxyl-α-amino Nitriles via Cyanation of Ketonitrones Using Me2(CH2Cl)SiCN

Here, we report an unprecedented catalytic enantioselective cyanation of ketonitrones enabled by the bifunctional cyanating reagent Me-2(CH2Cl)SiCN. This approach allows facile access to optically active N-hydroxyl-alpha-amino nitriles that are of high synthetic value but difficult to acquire by other methods. The use of bifunctional cyanating reagent Me-2(CH2Cl)SiCN not only achieves an enantioselectivity higher than that with TMSCN but also enables various diversification reactions of the resulting silylated adducts. This represents the first enantioselective catalytic nucleophilic addition reaction of unactivated ketone-derived nitrones, exhibiting the potential of such tetrasubstituted C.N bonds for asymmetric synthesis of N-hydroxy alpha-amino acids and other N-hydroxy tertiary amines.

Automated summary

This study describes an unprecedented catalytic enantioselective cyanation of ketonitrones using a bifunctional cyanating reagent, Me-2(CH2Cl)SiCN, leading to the synthesis of optically active N-hydroxyl-alpha-amino nitriles. The use of this reagent not only achieves high enantioselectivity but also allows for diversification reactions of the resulting silylated adducts. Additionally, this work highlights the potential of tetrasubstituted C.N bonds for asymmetric synthesis of N-hydroxy alpha-amino acids and other N-hydroxy tertiary amines.