Research group of Professor Wan Xiaobing of Suzhou University: synthesis of oxalate through visible light catalysis of free radical process of diazo and oxygen

The author of this paper: maleic acid esters are widely found in natural products and drug molecules The traditional synthesis method of oxalate is mainly condensation reaction of oxalic acid and its derivatives with alcohol In the presence of alcohols, ozonation of alkenes or alkynes is also an effective way to synthesize oxalate Other synthesis methods of oxalate include dimerization of formate, oxidative cleavage of ketoacids, etc Generally speaking, most of the current synthesis methods of oxalate depend on the ion process Up to now, there is no report on the synthesis of asymmetric oxalates by free radical process In recent years, the organic reactions catalyzed by visible light have achieved fruitful results, among which the reactions using visible light as energy source, oxygen as oxidant or oxygen source are undoubtedly an ideal reaction Recently, Professor Wan Xiaobing's research group of Suzhou University realized the synthesis of oxalate with Eosin Y as photocatalyst, oxygen as oxidant and oxygen source The related research work was published on the recent organic letters (DOI: 10.1021 / ACS Org lett 8b02487) Figure 1 Synthesis method of oxalate ester (source: Organic letters) Firstly, after a large number of conditions screening, the author uses Eosin Y as photocatalyst, 12W green LED lamp as light source, DMF as solvent, and stirs all raw materials for 36 hours in oxygen atmosphere and room temperature The reaction can yield oxalate ester product 3 in a higher yield Under these conditions, the author investigated the substrate range of 1 (Fig 2) The results show that the yield of O -, M - and P-rings with different substituents is medium or higher A good yield of 2-phenyl-2-bromoacetophenone and 2-bromoacetophenone was also obtained Figure 2 Substrate expansion of α - bromoketones (source: Organic letters) Then, the scope of diazo compounds was expanded The experimental results show that the conventional alkane diazo esters can obtain high yield When the diazo ester contains olefins, alkynes and heterocycles in its structure, the yield of oxalate is also high Even the substrate with benzene ring can get oxalate in medium yield Fig 3 A series of experiments were designed by the authors to elucidate the mechanism of the reaction (Fig 4, 5) Through the fluorescence quenching experiment, it is confirmed that the excited photocatalyst is quenched by 1A; through the control experiment and heavy water labeling experiment, it is confirmed that the oxygen in the product molecule comes from oxygen, not water; compound 5 is put into the reaction instead of 1a, and there is no product 3a in the reaction, so it is possible to exclude 5 as the reaction intermediate Figure 4 Fluorescence quenching experiments of 1a and 2A (source: Organic letters) Figure 5 Mechanism verification experiment (source: Organic letters) based on the above experimental results and literature reports, the author proposed the possible mechanism of the reaction (Figure 6) Firstly, the photocatalyst absorbs visible light and generates an excited photocatalyst, and then generates a radical intermediate a through a single electron transfer process with 1 A; a is captured by oxygen to generate superoxide radical B, and B is further converted to hydrogen peroxide intermediate C; C is easily split to generate free radical D; then free radical D and diazo compound 2A After free radical addition, nitrogen is removed and free radical intermediate e is generated Through the process similar to a to D, e is successively converted into intermediates F, G and h finally, h is oxidized to target product 3a, and the excited photocatalyst is reduced back to the ground photocatalyst Figure 6 Possible catalytic cycles (source: Organic letters) The research results were published on organic letters Ma Meihua, a postgraduate of Suzhou University, was the first author of the paper Review of previous reports: Professor Wan Xiaobing's research group of Suzhou University: application of sulfonamide capture secondary amide ylide strategy to synthesis of n-sulfonamidine derivatives