Merging the Non-Natural Catalytic Activity of Lipase and Electrosynthesis: Asymmetric Oxidative Cross-Coupling of Secondary Amines with Ketones

We describe the enantioselective oxidative cross-coupling of secondary amines with ketones by combining the non-natural catalytic activity of lipase with electrosynthesis. Various 2,2-disubstituted 3-carbonyl indoles with a stereogenic quaternary carbon center were synthesized from 2-substituted indoles in yields up to 78 % with good enantio- and diastereoselectivities (up to 96 : 4 e.r. and >20 : 1 d.r.). This unprecedented protocol demonstrated that hydrolase catalysis is compatible with electrosynthesis, and the reaction can be carried out in organic solvents with a broad substrate scope and good stereoselectivity. This work provides insights into enzymatic electrosynthesis.

Automated summary

The enantioselective oxidative cross-coupling of secondary amines with ketones was achieved by combining the catalytic activity of lipase with electrosynthesis. This novel protocol allowed for the synthesis of 2,2-disubstituted 3-carbonyl indoles with a stereogenic quaternary carbon center in high yields and good enantio- and diastereoselectivities. The compatibility of hydrolase catalysis with electrosynthesis was demonstrated, highlighting the potential and mechanism of enzymatic electrosynthesis.