Rhodium-Catalyzed Enantioselective 1,4-Oxyamination of Conjugated gem-Difluorodienes via Coupling with Carboxylic Acids and Dioxazolones.

Abstract

The incorporation of fluorine atoms in organics conduces to improvement of their bioactivity and lipophilicity. Catalytic functionalization of gem-difluorodienes represents one of the most straightforward approaches to access fluorinated alkenes. However, the regio- and enantioselective oxyamination of gem-difluorodienes remains untouched. Herein, we report asymmetric 1,4-oxyamination of gem-difluorodiene via chiral rhodium-catalyzed three-component coupling with readily available carboxylic acid and dioxazolone to forge a gem-difluorinated and enantioenriched 1,4-amino alcohol derivatives. Our asymmetric protocol exhibits high 1,4-regio- and enantioselectivity with utility in the late-stage modification of pharmaceuticals and natural products. Stoichiometric experiments provide evidences for the π-allylrhodium pathway. Related oxyamination was also realized when trifluoroethanol was used as an oxygen nucleophile.