Iron-Catalyzed Defluorinative Alkylation for Accessing Cyclic Acetal– gem -Difluoroalkenes

Abstract

Cyclic acetals and gem-difluoroalkenes are proven structural motifs in medicinal chemistry, yet their modular incorporation into a densely functionalized hybrid architecture remains an uncharted frontier. Herein, we disclose an Fe-catalyzed reductive defluorinative cross-coupling between trifluoromethyl alkenes and 1,3-dioxolanyl- or 1,3-dioxepanyl-substituted alkyl iodides, enabling the rapid assembly of five- or seven-membered cyclic acetal-embodied fluorinated scaffolds, respectively. This protocol enriches defluorinative coupling versatility and offers streamlined access to structurally diverse pharmaceutically relevant scaffolds.