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.
Funding
Reactions of Arynes and Other Reactive Intermediates | Funder: National Science Foundation | Grant ID: CHE-2055055
History
Citation
Su, S., Zhang, Y., Liu, P., Wink, D. J.Lee, D. (2023). Intramolecular Carboxyamidation of Alkyne‐Tethered O‐Acylhydroxamates through Formation of Fe(III)‐Nitrenoids. Chemistry - A European Journal, e202303428-. https://doi.org/10.1002/chem.202303428