Enantioselective Aerobic Construction of C2‐Quaternary Indolin‐3‐ones by Gold/Chiral Amine Relay Catalysis

Abstract

This study describes an efficient and environmentally friendly strategy for the enantioselective synthesis of C2‐quaternary indolin‐3‐ones via a gold/L‐proline relay catalytic system using air as a sustainable oxidant. The reaction proceeds through a gold‐catalyzed cyclization of 2‐alkynyl arylazides to form a key 3H‐indol‐3‐one intermediates, followed by an L‐proline‐catalyzed asymmetric Mannich reaction with ketones. Under optimized conditions, the method affords a wide range of chiral 2,2‐disubstituted indolin‐3‐ones in moderate to good yields with excellent enantioselectivities (up to >99% ee) and diastereoselectivities. The scope of both azide and ketone substrates was extensively explored, demonstrating broad functional group tolerance. Isotope labeling experiments confirmed that the carbonyl oxygen on the indole ring originates from water or acetone. This strategy offers a green and practical approach to accessing enantioenriched C2‐quaternary indolin‐3‐ones.