Ni-Catalyzed Adaptive Migration: Asymmetric Cross-Hydrocarbonylation of Unactivated Alkenes to Access Enantioenriched α-Arylated Ketones

Abstract Transition-metal-catalyzed regio- and enantioselective cross-coupling of alkyl metallic species has emerged as a cornerstone in modern organic synthesis, which enables the highly precise formation of carbon–carbon and carbon–heteroatom bonds and thereby facilitating the efficient synthesis of structurally complex and functionally important organic molecules. However, the selective generation and application of diverse alkyl metal intermediates from a single precursor under identical reaction conditions remain unexplored and represents an unsolved challenge. Herein, a new reaction mode enabled by nickel-catalyzed adaptive migration of one alkyl metallic intermediate to form both thermodynamic and kinetic favored alkyl metallic intermediates has been established, which could undergo asymmetric cross-hydrocarbonylation to synthesize enantioenriched α-arylated ketones. This strategy enables an identical alkene serves as the precursor for two distinct alkyl metal intermediates through adaptive migration, offering one of the most direct and efficient approaches to access enantioenriched α-arylated ketones. Moreover, the adaptive migration strategy could be applied to two different alkenes, in which alkene sorting enables one alkene corresponds to generate thermodynamic favored alkyl nickel intermediate, while the other alkene corresponds to generate kinetic favored alkyl nickel intermediate.