Enantioselective Oxidative Multi-Functionalization of Terminal Alkynes with Nitrones and Alcohols for Expeditious Assembly of Chiral alpha-Alkoxy-beta-amino-ketones

Catalytic oxidative functionalization of alkynes has emerged as an effective method in synthetic chemistry in recent decades. However, enantioselective transformations via metal carbene intermediates are quite rare due to the lack of robust chiral catalysts, especially in the intermolecular versions. Herein, we report the first asymmetric three-component reaction of commercially available alkynes with nitrones and alcohols, which affords alpha-alkoxy-beta-amino-ketones in good yields with high to excellent enantioselectivity using combined catalysis by an achiral gold complex and a chiral spiro phosphoric acid (CPA). Mechanistically, this atom-economic reaction involves a catalytic alkyne oxidation/ylide formation/Mannich-type addition sequence that uses nitrone as the oxidant and the leaving fragment imine as the electrophile, providing a novel method for multi-functionalization of commercially available terminal alkynes.

Automated summary

An asymmetric three-component reaction method has been reported to synthesize alpha-alkoxy-beta-amino-ketones with high yields and excellent enantioselectivity. This atom-economic reaction involves catalytic alkyne oxidation, ylide formation, and Mannich-type addition sequence.