Nickel‐Catalyzed Modular Four‐Component 1,3‐Alkylcarbonylation of σ Bonds in Bicyclo[1.1.0]butanes via Ring Strain Effect

Comprehensive Summary Transition‐metal‐catalyzed radical‐mediated four‐component carbonylation reactions offer a sustainable and efficient strategy for modular synthesis of complex carbonyl compounds from simple feedstocks. However, current studies have primarily focused on the alkylcarbonylation of π‐bonds in unsaturated hydrocarbons, including alkenes, alkynes and 1,3‐enynes. In this study, we report a nickel‐catalyzed 1,3‐alkylcarbonylation of σ‐bonds in bicyclo[1.1.0]butanes (BCBs) using CO as an economical carbonyl source. By leveraging steric hindrance and ring‐strain effects, the reaction of BCB‐tethered esters, activated alkyl bromides and arylboronic acids proceeded efficiently under nickel catalysis and ambient CO pressure, affording a series of aryl cyclobutyl ketones containing a quaternary carbon center. This protocol is characterized by mild reaction conditions, a broad substrate scope, and excellent functional group compatibility. Control experiments revealed that the steric profile of tertiary alkyl radicals is paramount for the chemoselectivity of this four‐component carbonylation cascade.