Work

Regio-, stereo-, and enantioselective ipso- and migratory defluorinative olefin cross-coupling to access highly functionalized monofluoroalkenes

Year: 2024

Type: article

Abstract: Monofluoroalkenes serve as nonhydrolyzable mimetics of amides and are frequently encountered in drug candidates. Herein we report a regio-, enantio-, and stereoselective NiH-catalyzed ipso- and migratory defluorinative olefin cross-coupling employing readily available olefins and gem-difluoroalkenes under mild conditions. This approach enables the efficient synthesis of a broad array of structurally diverse monofluoroalkenes bearing a tertiary allylic stereogenic center. Mechanistically, the challenging migratory defluorinative olefin cross-coupling process is successfully realized through a ligand relay catalytic strategy, enabling the formal C(sp3)–H/C(sp2)–F activation with high levels of regio-, stereo-, and enantiocontrol. Monofluoroalkenes serve as nonhydrolyzable mimetics of amides and are frequently encountered in drug candidates. Herein, the authors report a regio-, enantio-, and stereoselective NiH-catalyzed ipso- and migratory defluorinative olefin cross-coupling employing readily available olefins and gem-difluoroalkenes under mild conditions.

Source: Nature Communications

DOI: 10.1038/s41467-024-52054-6

Authors: Daning Zeng, Zihao Liu, Guoce Huang, You Wang, Shaolin Zhu

Institutions: Nanjing University, Shanghai Jiao Tong University, Henan Normal University

Language: English

Topic: Fluorine in Organic Chemistry

Subfield: Pharmaceutical Science

Field: Pharmacology, Toxicology and Pharmaceutics

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $6,790