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

Abstract

AbstractThe incorporation of fluorine atoms in organics improves their bioactivity and lipophilicity. Catalytic functionalization of gem‐difluorodienes represents one of the most straightforward approaches to access fluorinated alkenes. In contrast to the regular 1,3‐dienes that undergo diverse asymmetric di/hydrofunctionalizations, the regio‐ and enantioselective oxyamination of gem‐difluorodienes remains untouched. Herein, we report asymmetric 1,4‐oxyamination of gem‐difluorodiene by chiral rhodium‐catalyzed three‐component coupling with readily available carboxylic acid and dioxazolone, affording gem‐difluorinated 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.