Electricity-driven asymmetric Lewis acid catalysis

Abstract

Catalytic asymmetric electrosynthesis combines the unique features of an electrochemical addition or removal of electrons with the catalytic asymmetric synthesis of enantioenriched molecules. However, identifying suitable catalysts that are compatible with electrochemical conditions and provide a high stereocontrol is a formidable challenge. Here we introduce a versatile electricity-driven chiral Lewis acid catalysis for the oxidative cross-coupling of 2-acyl imidazoles with silyl enol ethers. Powered by an electric current, this work provides a sustainable avenue to synthetically useful non-racemic 1,4-dicarbonyls, which include products that bear all-carbon quaternary stereocentres. A chiral-at-metal rhodium catalyst activates a substrate towards anodic oxidation by raising the highest occupied molecular orbital on enolate formation, which enables mild redox conditions, high chemo- and enantioselectivities (up to >99% enantiomeric excess) and a broad substrate scope. This work demonstrates the potential of combining asymmetric Lewis acid catalysis with electrochemistry and we anticipate that it will spur the further development of catalytic asymmetric electrosynthesis. The use of electrochemistry in asymmetric catalysis can prove challenging, not least due to the difficulty of achieving chemo- and stereoselectivity in combination with very reactive electrochemically generated intermediates. Here, catalytic asymmetric electrosynthesis is reported for the synthesis of 1,4-dicarbonyl compounds with high enantiomeric excess, including compounds with all-carbon quaternary stereocentres. The chiral-at-metal catalyst activates the substrate towards anodic oxidation in addition to controlling the enantioselectivity of the process.