Oxidative Coupling of 4-Hydroxycoumarins with Quinoxalin-2(1H)-ones Induced by Visible Light under Aerobic Conditions

Direct and selective C(sp(2))-H/C(sp(2))-H cross-dehydrogenative coupling has become a promising strategy to increase molecular complexity with a high atom economy. This study describes an efficient and straightforward protocol for the regioselective C-3-H/C-3-H cross-coupling of 4-hydroxycoumarin derivatives with quinoxalin-2(1H)-ones, including late-stage modification of natural drugs, promoted by visible light under aerobic conditions at room temperature. With this approach, a wide range of hybrid drug-like molecules were prepared, using air as the terminal oxidant. Remarkably, the C-4-OH group at the coumarin ring is essential for the reaction and has been used as a handle for diverse functionalizations of the final products. Moreover, sunlight can promote the reaction under very mild and sustainable conditions, even on a gram scale. Qualitative and semi-quantitative tools were used to demonstrate the greenness advance of this methodology over previously reported ones. Several experiments were conducted to propose a plausible mechanism for this transformation.

Automated summary

This study presents an efficient method for the regioselective C-3-H/C-3-H cross-coupling of 4-hydroxycoumarin derivatives with quinoxalin-2(1H)-ones, using visible light and air as the terminal oxidant. The reaction is promoted by sunlight under mild and sustainable conditions, and the C-4-OH group at the coumarin ring is essential for the reaction and allows for diversified functionalizations of the final products. The greenness of this methodology over previous ones is demonstrated through qualitative and semi-quantitative analysis, and a plausible mechanism for this transformation is proposed through various experiments.