Rhodium- and Iridium-Catalyzed (Enantioselective) Fluoroamidation of gem-Difluoroalkenes via Chelation Assistance

The incorporation of fluorine atoms into organics often significantly improved the lipophilicity and metabolic stability of pharmaceuticals. Herein, two classes of fluoroamidation reactions of gem-difluoroalkenes are described. Rhodium-catalyzed asymmetric 1,2-fluoroamidation of 4,4-difluoro-3-butenamide proceeded in excellent enantioselectivity to give a CF3-containing diamide using CsF as a convenient fluoride source. On the other hand, the 1,4-fluoroamidation of gem-difluoro-1,3-dienes required iridium catalysis using AgF as a fluoride source under mild reaction conditions. In both cases, fluorometalation occurs as a key elementary step, with a metal-alkyl intermediate being stabilized by chelation or allyl formation as a driving force.