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

Zeng, Daning; Liu, Zihao; Huang, Guoce; Wang, You; Zhu, Shaolin · Nat Commun · 2024

basic_science · Level V

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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(sp<sup>3</sup>)-H/C(sp<sup>2</sup>)-F activation with high levels of regio-, stereo-, and enantiocontrol.