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

Abstract

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.

Keywords

1,3-Alkylcarbonylation / Bicyclo[1.1.0]butanes / Nickel catalysis / Tertiary alkyl radical / Four-component carbonylation / σ bond cleavage / Aryl cyclobutyl ketone / Modular synthesis

RIGHTS & PERMISSIONS

2025 SIOC, CAS, Shanghai, & WILEY-VCH GmbH