Enantioselective Decarboxylative C(sp3)-C(sp3) Cross-Coupling of Aliphatic Redox-Active Esters with gem-Borazirconocene Alkanes

Jing Wang, Songlin Bai, Chao Yang and Xiangbing Qi

Asymmetric decarboxylative cross-couplings of carboxylic acids are powerful methods for synthesizing chiral building blocks essential in medicinal chemistry and material science. Despite their potential, creating versatile chiral alkylboron derivatives through asymmetric decarboxylative C(sp³)-C(sp³) cross-coupling from readily available primary aliphatic acids and mild organometallic reagents remains challenging. In this study, we present a visible light-induced Ni-catalyzed enantioconvergent C(sp³)-C(sp³) cross-coupling of unactivated primary aliphatic acid NHPI esters with gem-borazirconocene alkanes, producing a diverse array of valuable chiral alkylboron building blocks. The method boasts a broad substrate scope, high functional group tolerance, and the ability for late-stage modification of complex drug molecules and natural products with high enantioselectivity, showcasing its synthetic potential. Mechanistic investigations suggest a nickel-catalyzed enantioconvergent radical cross-coupling pathway, wherein the primary radical from a redox-active ester is generated through single-electron reduction with Zr^III species. This represents an unprecedented example of enantioselective radical C(sp³)-C(sp³) cross-coupling in the absence of photocatalysts.

DOI: 10.1021/jacs.4c09245