Organocatalytic enantioconvergent α-substitution of sulfonium salts by nitrogen nucleophiles.

Chiral α-amino carbonyl compounds are essential building blocks in the synthesis of natural products and pharmaceuticals. Direct enantioconvergent nucleophilic substitution represents a powerful approach, but it has not been well established for the synthesis of α-amino ketones. Herein, we report a robust organocatalytic protocol with α-keto sulfonium salts. Utilizing a chiral phosphoric acid (CPA) in an aqueous/organic biphasic system, we achieved enantioconvergent substitution with free amines in high yields and excellent enantioselectivity. Mechanistic studies suggest that the CPA plays a dual role as both the source of chirality and a phase-transfer catalyst, facilitating the reaction via a dynamic kinetic resolution of a chiral sulfonium ion pair. This mild protocol was successfully extended to asymmetric azidation using a neutral hydrogen-bond-donor (HBD) catalyst.