Copper Catalysis, Alkali Acceleration, Oxygen As Oxidant Direct Oxidation Of C-H Bond Into Stupid Acyl, Isatin And Quinoxaline

Benzil derivatives are a class of attractive organic molecules due to their rich applications across many fields of science. For example, they are common photoinitiators in polymer chemistry, and they are versatile building blocks in organic synthesis to yield various biologically active heterocyclic compounds, such as imidazole, triazine and quinoxaline. In addition, recently benzil derivatives have been demonstrated to be potent inhibitor of human carboxylesterases (CE). Therefore, efficient synthesis of benzil derivatives has drawn significant attention. Classically, benzil can be prepared via benzoins condensation followed by oxidation of the obtained a-hydroxycarbonyl. Obviously, the method is efficient for the preparation of symmetric benzils but difficult to synthesize unsymmetrical benzils owing to lack of regiochemical control in the cross-benzoin reaction of two different aldehydes. The synthesis of unsymmetrical benzils generally undergoes the oxidation of diarylalkynes, diarylalkenes, hydrobenzoins, deoxybenzoins and others. Although these methods have proved their efficiency in benzils synthesis, they suffered from several drawbacks, such as (1) high catalyst loading (≥15 mol%); (2) harsh reaction conditions (e.g.100 ℃); (3) low yield for some cases. Among these oxidative methods, catalytic oxidation of deoxybenzoins to benzils with air or oxygen as the oxidant is an intriguing protocol because of the environmental and economic concerns.We describe herein an efficient and general copper (Ⅱ)-catalyzed base-accelerated oxidation of C-H Bond to synthesize benzils and isatins. With similar oxidation system an efficient one-pot procedure for the synthesis of quinoxaline derivatives was realized. The two protocols feature using molecular oxygen as terminal oxidant, low catalyst loading (5 mol%), wide substrate scope and high functional-group tolerance. Tentative mechanistic studies suggest that the oxidation reaction is likely to proceed by a radical process. Further mechanistic studies and applications of the approaches are in progress.