Synthesis of α-(Hetero)aryl Ketones by Ni-Catalyzed Regio- and Enantioselective Hydroacylation of Alkenes with Acid Chlorides

Abstract Enantioenriched α-arylated dialkyl ketones are key substructures in bioactive and functional molecules. Thus, the development of catalytic protocols for the efficient synthesis of such structures is among the long-term yet challenging tasks in catalysis and organic synthesis. The catalytic asymmetric hydroacylation of alkenes represents one of the most ideal and straightforward methods to access α-chiral ketones from readily available and cost-effective starting materials. However, most efforts focused on intramolecular asymmetric hydroacylation of alkenes at elevated temperatures, and the intermolecular version remains underdeveloped. Herein, a Ni-catalyzed asymmetric hydroacylation of alkenes with acid chlorides has been developed, affording enantioenriched α-N-heteroarylated and α-arylated unsymmetric dialkyl ketones in good yields with exclusive regioselectivity and good levels of enantioselectivity. Notably, the reaction features a three-component formal asymmetric hydroacylation of alkenes by earth-abundant metal catalysis under mild conditions. The key to the success of this reaction is the nontrivial selective hydrometalation of alkenes in the absence of a directing group over more polarized and more reactive acid chlorides, which allows for the asymmetric Csp2−Csp3 cross-coupling event with the control of chemo-, regio-, and enantioselectivity.