Alternating-Polarity Electrolysis Enables Efficient Enantioselective Semipinacol Rearrangement Using Sodium Chloride

High Resolution Image Download MS PowerPoint Slide Enantioselective chlorination using sustainable chloride sources has long been a pursuit in organic synthesis. Moving away from stoichiometric, corrosive, and costly electrophilic reagents, we report the use of NaCl as a green chlorine source for the enantioselective chlorination of organic molecules without the need for chemical oxidants. By leveraging electrochemical in situ oxidation, we demonstrate the first electricity-driven enantioselective semipinacol rearrangement. Central to this approach is a dual-organocatalyst phase-transfer system that synergistically manages both phase transfer and enantiomeric induction. Notably, the implementation of alternating current (AC) proved essential in preventing catalyst deposition on the electrode surface, enabling high efficiency at a synthetically useful scale. This work represents a rare application of AC in asymmetric electrosynthesis and its inaugural use in organocatalysis. A variety of cyclic and functionalized ketones bearing all-carbon quaternary stereocenters were synthesized with high enantioselectivity and excellent functional group compatibility. Detailed mechanistic insights supported by control experiments and cyclic voltammetry as well as DFT calculation further elucidate the catalytic cycle. This protocol establishes a practical platform for future enantioselective chlorination processes using sustainable chloride sources.