Chemoselective Intramolecular Formal Insertion Reaction of Rh-Nitrenes into an Amide Bond Over C-H Insertion

The past few decades have witnessed extensive efforts to disclose the unique reactivity of metal-nitrenes, because they could be a powerful synthetic tool for introducing the amine functionality into unactivated chemical bonds. The reactivity of metal-nitrenes, however, is currently mainly confined to aziridination (an insertion into a C=C bond) and C-H amination (an insertion into a C-H bond). Nitrene insertion into an amide C-N bond, however, has not been reported so far. In this work we have developed a rhodium-catalyzed one-nitrogen insertion into amide C-N and sulfonamide S-N bonds. Experimental and theoretical analyses based on density functional theory indicate that the formal amide insertion proceeds via a rhodium-coordinated ammonium ylide formed between the nitrene and the amide nitrogen, followed by acyl group transfer concomitant with C-N bond cleavage. Mechanistic studies have allowed rationalization of the origin of the chemoselectivity observed between the C-H and amide insertion reactions. The methodology presented herein is the first example of an insertion of nitrene into amide bonds and provides facile access to unique diazacyclic systems with an N-N bond linkage.