Asymmetric Sulfa-Michael/Mannich Cascade Reaction of β,γ-Unsaturated α-Keto Esters for the Construction of γ-Mercapto-γ-amino-α-keto Esters Bearing Multiple Chiral Centers

Enantioselective three-component sulfa-Michael/Mannich cascade reaction of β,γ-unsaturated α-keto esters has been developed under the catalysis of a chiral multifunctional organocatalyst. A methodology to access various functionalized γ-thio-γ-amino-α-keto esters bearing three consecutive stereocenters in high yields and enantioselectivities (up to 98% yield, 99:1 dr, and >99% ee) has been established. Synthetic utility of this protocol is demonstrated by the gram-scale experiment and functional transformation to construct α-azetidine acid derivatives.