Oxidative Coupling of 4‐Hydroxycoumarins with Quinoxalin‐2(1<i>H</i>)‐ones Induced by Visible Light under Aerobic Conditions
Loris Laze, P. Romero, Irene Bosque, José C. González‐Gómez
Abstract
Abstract 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(1 H )‐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.