Intramolecular Carboxyamidation of Alkyne‐Tethered O‐Acylhydroxamates through Formation of Fe(III)‐Nitrenoids

Abstract

We developed intramolecular carboxyamidations of alkyne‐tethered O‐acylhydroxamates followed by either thermally induced spontaneous or 4‐(dimethylamino)pyridine‐catalyzed O→O or O→N acyl group migration. Under iron‐catalyzed conditions, the carboxyamidation products were generated in high yield from both Z‐alkene and arene‐tethered substrates. DFT calculations indicate that the iron‐catalyzed carboxyamidation proceeds via a stepwise mechanism involving iron‐imidyl radical cyclization followed by intramolecular acyloxy transfer from the iron center to the alkenyl radical center to furnish the cis‐carboxyamidation product. Upon treatment with 4‐(dimethylamino)pyridine, the Z‐alkene‐tethered carboxyamidation products underwent selective O→O acyl migration to generate 2‐acyloxy‐5‐acyl pyrroles. Thermal O→N acyl migration occurs during carboxyamidation if the Z‐alkene linker contains an alkyl or an aryl substituent at the β‐position of the carbonyl group. On the other hand, the arene linker‐containing compounds selectively undergo O→N acyl migration to generate N‐acyl‐3‐acylisoindolinones, and the corresponding O→O acyl migration forming isoindole derivatives was not observed.