Synthesis of α-Substituted β,γ-Unsaturated Cyclobutanecarboxamides via Palladium-Catalyzed Aminocarbonylation of Vinylcyclobutanols.

ABSTRACT: Vinylcyclobutanols are highly strained molecules that are prone to semipinacol rearrangement or ring-opening under catalytic conditions, challenging the synthesis of functionalized cyclobutane scaffolds. We report here a palladium-catalyzed aminocarbonylation of vinylcyclobutanols with amine hydrochlorides and CO. The reaction proceeds via in situ formation of conjugated dienes and π-allyl palladium intermediates, furnishing α-substituted β,γ-unsaturated cyclobutanecarboxamides. This method shows a broad substrate scope and excellent functional group tolerance while effectively suppressing rearrangement and ring-opening. It provides a concise, robust route to structurally diverse α-substituted β,γ-unsaturated cyclobutane derivatives bearing a quaternary carbon center.

SUBMITTER: Liu YK 

PROVIDER: S-EPMC12538587 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature