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

• Published in: European journal of organic chemistry Vol. 26; no. 6
• Main Authors: Laze, Loris, Romero, Paula, Bosque, Irene, Gonzalez‐Gomez, Jose C.
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 06.02.2023; Wiley Subscription Services, Inc
• Subjects: 4-hydroxycoumarins; Chemistry; Chemistry, Organic; Coumarin; Coupling (molecular); Cross coupling; Dehydrogenation; oxidative coupling; Oxidizing agents; photocatalysis; Physical Sciences; quinoxalin-2(1H)-ones; Room temperature; Science & Technology; sustainable chemistry; OXYGEN; 4-hydroxycoumarins; oxidative coupling; 4-HYDROXY-6-METHYL-2-PYRONE; CHEMISTRY; sustainable chemistry; photocatalysis; QUINOXALINES; DERIVATIVES; quinoxalin-2(1H)-ones
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.202201484

Direct and selective C(sp2)−H/C(sp2)−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 C3‐H/C3‐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 C4‐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. A green protocol was developed for the cross‐dehydrogenative coupling of quinoxalin‐2‐ones and 2‐hydroxycoumarin derivatives, only using the Fukuzumi photocatalyst and visible light to obtain hybrid drug‐like molecules in a single step.