DMAP Catalyzed One-Pot Curtius Rearrangement Using 1,1-Dimethyl-2,2,2-trichloroethoxycarbonyl Azide

Abstract

We report our development of a controllable, basefree, one-pot Curtius rearrangement using 1,1-dimethyl-2,2,2trichloroethoxycarbonyl azide (DMTN 3 ) with 4-(dimethylamino)pyridine (DMAP) as a catalyst. The scope of this catalytic process covers a range of primary, secondary, and tertiary alkyl and aryl carboxylic acids that allow the efficient stereospecific construction of alkyl or aryl isocyanates. Examples are reported of late-stage decarboxylative isocyanation of natural products and drug molecules, the rapid synthesis of several drugs, and the utilization of in situ generated DMTN 3 . Detailed studies of the mechanism indicate that the reaction rate depends on the concentration of the DMAP catalyst, and this ensures that the reaction is a mild and controllable process.