Asymmetric Csp3-Csp3 Bond Formation via Ni-Catalyzed Regio- and Enantioselective Hydroalkylation of 1,3-Diene through Carbonyl Umpolung

The asymmetric Csp3-Csp3 bond formation has been a grand pursuit in synthetic chemistry. The regio- and enantionselective hydroalkylation of 1,3-diene has emerged as an appealing approach for constructing chiral allylic Csp3-Csp3 bonds. However, this method is presently confined to the use of stabilized Csp3 nucleophilic substrates. Herein, we present a nickel-catalyzed asymmetric hydroalkylation of 1,3-dienes with simple unstablized alkyl carbanion enabled by hydrazones umpolung under mild reaction conditions. A range of simple alkylated chiral allylic compounds were generated in good to excellent yields, with enantiomeric ratio (er) of up to 2:98 in forming the Csp3-Csp3 bond. The protocol is applicable to heterocycles, polyenes and unsaturated hydrazones, as well as amenable for late-stage functionalizations of various complex pharmaceuticals. Density functional theory calculations elucidate 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.