Catalytic Asymmetric Oxidative Coupling between C(sp3)–H Bonds and Carboxylic Acids

Abstract

The direct enantioselective functionalization of C(sp³)–H bonds in organic molecules could fundamentally transform the synthesis of chiral molecules. In particular, the enantioselective oxidation of these bonds would dramatically change the production methods of chiral alcohols and esters, which are prevalent in natural products, pharmaceuticals, and fine chemicals. Remarkable advances have been made in the enantioselective construction of carbon–carbon and carbon–nitrogen bonds through the C(sp³)–H bond functionalization. However, the direct enantioselective formation of carbon–oxygen bonds from C(sp³)–H bonds remains a considerable challenge. We herein report a highly enantioselective C(sp³)–H bond oxidative coupling with carboxylic acids. The method applies to allylic and propargylic C–H bonds and employs various carboxylic acids as oxygenating agents. The method successfully synthesized a range of chiral esters directly from readily available alkenes and alkynes, greatly simplifying the synthesis of chiral esters and related alcohols.