Cobalt(III)-Catalyzed Synthesis of Aminoisoquinolones and Amino-2-Pyridones via C–H Functionalization with Ynamides: A Combined Experimental and Computational Study
Abstract
Carbon–hydrogen (C–H) functionalization methodologies typically rely on electron-poor π-systems, whereas the engagement of electron-rich counterparts remains underdeveloped. Herein, we report the first cobalt-catalyzed, site- and regioselective C–H functionalization of O-phenyl hydroxamic acids with electron-rich ynamides to afford aminoisoquinolones and 2-pyridones. Combined experimental and computational mechanistic studies reveal a pathway governed by Curtin–Hammett kinetics, featuring reversible concerted metalation deprotonation, irreversible selectivitydetermining migratory insertion, and turnover-limiting C–N reductive elimination. The transformation proceeds via divergent pathways, wherein the major 4-aminoisoquinolone is generated through a Co(III) cycle and the minor 3aminoisoquinolone transits a Co(III)/Co(I) redox manifold. Furthermore, high-valent Co(V) nitrenoids, which are frequently invoked in related reactions, are ruled out as catalytic intermediates.
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BibTeX
@misc{cao2026cobaltiiicatalyzed,
title = {{Cobalt(III)-Catalyzed Synthesis of Aminoisoquinolones and Amino-2-Pyridones via C–H Functionalization with Ynamides: A Combined Experimental and Computational Study}},
author = {Yujie Cao and Justin D. DeBow and Elise Mach and Melody Wu and Veronica Carta and Kevin G. M. Kou},
howpublished = {ChemRxiv},
year = {2026},
month = sep,
doi = {10.26434/chemrxiv.15009358/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009358/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Cobalt(III)-Catalyzed Synthesis of Aminoisoquinolones and Amino-2-Pyridones via C–H Functionalization with Ynamides: A Combined Experimental and Computational Study
AU - Yujie Cao
AU - Justin D. DeBow
AU - Elise Mach
AU - Melody Wu
AU - Veronica Carta
AU - Kevin G. M. Kou
PY - 2026
DA - 2026/09/23
PB - ChemRxiv
DO - 10.26434/chemrxiv.15009358/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009358/v1
AB - Carbon–hydrogen (C–H) functionalization methodologies typically rely on electron-poor π-systems, whereas the engagement of electron-rich counterparts remains underdeveloped. Herein, we report the first cobalt-catalyzed, site- and regioselective C–H functionalization of O-phenyl hydroxamic acids with electron-rich ynamides to afford aminoisoquinolones and 2-pyridones. Combined experimental and computational mechanistic studies reveal a pathway governed by Curtin–Hammett kinetics, featuring reversible concerted metalation deprotonation, irreversible selectivitydetermining migratory insertion, and turnover-limiting C–N reductive elimination. The transformation proceeds via divergent pathways, wherein the major 4-aminoisoquinolone is generated through a Co(III) cycle and the minor 3aminoisoquinolone transits a Co(III)/Co(I) redox manifold. Furthermore, high-valent Co(V) nitrenoids, which are frequently invoked in related reactions, are ruled out as catalytic intermediates.
ER -