Palladium-Catalyzed Defluorinative Alkylation of gem-Difluoroalkenes with Cyclopropanols: Stereoselective Synthesis of γ-Fluorinated γ,δ-Unsaturated Ketones

Lingyu Kong; Wenqing Ti; Aijun Lin; Hequan Yao; Yue Huang; Xuanyi Li

doi:10.1021/acs.orglett.4c01045

Palladium-Catalyzed Defluorinative Alkylation of gem-Difluoroalkenes with Cyclopropanols: Stereoselective Synthesis of γ-Fluorinated γ,δ-Unsaturated Ketones

Org Lett. 2024 May 3;26(17):3591-3596. doi: 10.1021/acs.orglett.4c01045. Epub 2024 Apr 25.

Authors

Lingyu Kong¹, Wenqing Ti², Aijun Lin², Hequan Yao¹, Yue Huang³, Xuanyi Li²

Affiliations

¹ Department of Medicinal Chemistry, China Pharmaceutical University, 639 Longmian Avenue, Nanjing, Jiangsu 210009, China.
² State Key Laboratory of Natural Medicines (SKLNM) and Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, Jiangsu 210009, China.
³ Department of Chemistry, School of Science, China Pharmaceutical University, Nanjing, Jiangsu 211098, China.

PMID: 38661127
DOI: 10.1021/acs.orglett.4c01045

Abstract

A palladium-catalyzed defluorinative alkylation of gem-difluoroalkenes with cyclopropyl alcohols was developed. A range of γ-fluorinated γ,δ-unsaturated ketones were constructed in good yields with excellent stereoselectivities. In addition, by base-mediated intramolecular nucleophilic vinylic substitution (S_NV), the products could be further transformed to 2,5-dimethylenetetrahydrofurans and analogues with excellent stereoselectivities.