Synthesis of α-Chiral Ketones by Ni-Catalyzed Regio- and Enantioselective Hydroacylation of Alkenes with Acid Chlorides

Enantioenriched α-arylated dialkyl ketones are key substructures in bioactive and functional molecules.Thus, the development of catalytic protocols for efficient synthesis of such structures are among the longterm yet challenging tasks in catalysis and organic synthesis.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, intermolecular version remains underdeveloped.Herein, a Ni-catalyzed asymmetric hydroacylation of alkenes with acid chlorides has been developed for the first time, affording enantioenriched α-N-heteroarylated and α-arylated unsymmetric dialkyl ketones in excellent yields with exclusive regioselectivity and excellent enantioselectivity.Notably, the reaction features a three-component formal asymmetric hydroacylation of alkenes by earth-abundant-metal catalysis under mild conditions.Key to 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 is observed for the first time and allows for the asymmetric Csp2-Csp3 cross-coupling event with the control of chemo-, regio-and enantioselectivity.Enantioenriched α-arylated dialkyl ketones represent a privileged structural motif in natural products and pharmaceutical molecules, which also serve as important chiral precursors for the synthesis of other valueadded chiral targets (Scheme 1a) [1][2][3][4][5][6][7] .Given their ubiquity and usefulness, it is of great significance to develop straightforward and efficient synthetic protocols to produce unsymmetric dialkyl ketones with a α-stereogenic center from readily available starting materials.Conventional catalytic approaches towards