jo9b02013_si_001.pdf (2.81 MB)
Metal-Free Transamidation of Secondary Amides by N–C Cleavage
journal contribution
posted on 2019-09-09, 11:34 authored by Md. Mahbubur Rahman, Guangchen Li, Michal SzostakTransamidation
reactions represent a fundamental chemical process
involving conversion of one amide functional group into another. Herein,
we report a facile, highly chemoselective method for transamidation
of N-tert-butoxycarbonylation (N-Boc)
activated secondary amides that proceeds under exceedingly mild conditions
in the absence of any additives. Because this reaction is performed
in the absence of metals, oxidants, or reductants, the reaction tolerates
a large number of useful functionalities. The reaction is compatible
with diverse amides and nucleophilic amines, affording the transamidation
products in excellent yields through direct nucleophilic addition
to the amide bond. The utility of this methodology is highlighted
in the synthesis of Tigan, a commercial antiemetic, directly from
the amide bond. We expect that this new metal-free transamidation
will have broad implications for the development of new transformations
involving direct nucleophilic addition to the amide bond as a key
step.