Cobalt(III)-Catalyzed Synthesis of Aminoisoquinolones and Amino-2-Pyridones via C–H Functionalization with Ynamides: A Combined Experimental and Computational Study
Year: 2026
Type: preprint
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.
Source: ChemRxiv
Authors: Yujie Cao, Justin D. DeBow, Elise Mach, Melody Wu, Veronica Carta, Kevin G. M. Kou
Institution: University of California, Riverside
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7214128756