Iron-Catalyzed Defluorinative Alkylation for Accessing Cyclic Acetal-gem-Difluoroalkenes
Xiao-Tong Wang1, Pui Ying Choy1, Chi Wai Cheung1
1State Key Laboratory of Synthetic Chemistry and Department of Chemistry, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
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.
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