Asymmetric Csp 3 –Csp 3 Bond Formation via Ni-Catalyzed Regio- and Enantioselective Hydroalkylation of Linear 1,3-Diene through Carbonyl Umpolung

作者：Ruofei Cheng, Kangbao Zhong, Xue‐Qiang Chu, Yu Lan, Chao‐Jun Li · 发表于：ACS Catalysis · 年份：2024 · DOI：10.1021/acscatal.4c05759 · 被引用次数：13 · 研究领域：Asymmetric Hydrogenation and Catalysis、Catalytic C–H Functionalization Methods、Asymmetric Synthesis and Catalysis

Asymmetric Csp 3 –Csp 3 bond formation has been a grand pursuit in synthetic chemistry. The regioselective and enantioselective hydroalkylation of 1,3-diene has emerged as an appealing approach for constructing chiral allylic Csp 3 –Csp 3 bonds. However, this method is presently confined to the use of stabilized Csp 3 nucleophilic substrates. Herein, we present a nickel-catalyzed asymmetric hydroalkylation of 1,3-dienes with simple unstabilized alkyl carbanion enabled by naturally abundant carbonyls’ umpolung under mild reaction conditions. A range of simple alkylated chiral allylic compounds were generated in good to high yields (up to 96%), with an enantiomeric ratio (er) of up to 98:2 to form the Csp 3 –Csp 3 bond. The protocol is applicable to heterocycles, polyenes, and unsaturated hydrazones as well as late-stage functionalization of various complex pharmaceuticals. Density functional theory calculations elucidated the mechanism and enantioselectivity of the reaction. An enantiocontrol model is also proposed, emphasizing the crucial role of a chiral NHC ligand in facilitating this asymmetric reaction, as revealed by the two-layer two-dimensional (2D) contour maps.