Enantioselective radical α-enolation of esters via electrochemical chiral isothiourea catalysis

Carboxylic ester motifs are prevalent in biological, chemical and materials sciences, and the asymmetric α-functionalization of simple esters plays a crucial role in the field of organic synthesis. Here we present a versatile electricity-driven asymmetric Lewis base catalysis strategy for the oxidative radical cross-coupling of simple esters with silyl enol ethers. This approach integrates the electrochemical anodic oxidation process with chiral isothiourea catalysis, enabling a polarity inversion at the nucleophilic carbon of the enolate to trigger the formation of a chiral isothiourea-bound α-carbonyl radical species from a C1-ammonium enolate. The combination of asymmetric Lewis base catalysis and electrochemistry unlocks mild oxidative radical coupling reactions, achieving up to 98% enantiomeric excess and demonstrating broad substrate compatibility. This work underscores the synthetic potential of the approach and provides a platform for advancing asymmetric electrosynthesis. Strategies for asymmetric control in electrosynthesis involving radicals are sought after. Now asymmetric Lewis base catalysis is combined with electrochemistry, enabling the oxidative radical cross-coupling of esters with silyl enol ethers and affording γ-keto esters in high enantiomeric excess.