Chiral Radical-Polar Crossover Chromium Catalysis with Cyclopropanols

Abstract

Transition metal-catalyzed coupling reactions of cyclopropyl alcohols have proven to be a powerful strategy in organic synthesis and drug discovery. Despite this, the use of earth-abundant chromium catalysis to access chromium homoenolates has remained elusive. Here, we disclose an unprecedented enantioselective radical-polar crossover reaction enabled ONLY by visible-light-activated chiral chromium catalysis, which facilitates the three-component coupling of cyclopropanols, 1,3-dienes, and aldehydes. Mechanistically, the reaction proceeds through the formation of chromium homoenolates, which undergo photoexcitation to generate primary radical intermediates, and a low-valent chiral chromium species, which react with 1,3-dienes to form allylic chromium intermediates, which subsequently add to aldehydes, delivering chiral homoallylic alcohols with high efficiency. This method features a broad substrate scope and functional group tolerance and is supported by experimental and computational studies that delineate a radical-polar crossover mechanism underpinned by photoexcited chiral chromium catalysis.