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. An asymmetric oxidative cross‐coupling strategy that combines the non‐natural catalytic activity of lipase with organic electrosynthesis was developed. This unprecedented protocol demonstrates that hydrolase catalysis is compatible with electrosynthesis.