Copper-mediated C-H Arylation Of Benzoxazole With Benzyl Sodium Thiosulfate

Among various C-heteroatom bond functionalizations, the activation of the C-S bond is extremely special and critical. First of all, sulfur atoms exist widely in natural products, pesticides, or proteins. Highly selective activation or functionalization of the C-S bond can accurately modify sulfur-containing molecules; however, sulfur atoms can bind to transition metals tightly, which makes them poisonous toward transition metal catalysts.Recently, some research results revealed that C-S bond was successfully activated to construct various C-C bonds when some sulfur-containing reagents were used to functionalize benzoxazole with palladium and/or cupper catalyst. Representative reagents include sulfonyl hydrazide, sulfonyl chloride, sulfonamide, sulfinate, thiol（phenol）, thioether, thiosulfate. From economic considerations, cheap and easy obtained raw materials are attractive to scientist. However, there are little or no reports at present for using benzyl sodium thiosulfate as new sulfur-containing materials to form new C-C bonds via C-S activation.In this thesis, an overview about the synthetic application of benzyl sodium thiosulfate and other sulfur-containing compounds was given firstly. And various synthetic methods of 2-aryl benzoxazoles were also listed at the same time. Then, base on the experimental results, we found a unique, alternative, convenient, and efficient method to access 2-aryl benzoxazoles using a copper-mediated oxidative desulfurization and decarbonylation approach（Scheme 1）.Generally, the C-H acylation of benzoxazole with benzyl sodium thiosulfate was performed smoothly in the presence of Na₂CO₃ as the base and imidazole as the additive, when the stoichiometric Cu BF₄ was employed in DMSO at 140 oC. The results showed clearly that the benzyl sodium thiosulfate was used as aryl resource in this reaction conditions. By using benzyl sodium thiosulfate instead of benzaldehyde or benzoyl chloride, a series of 2-arylbenzoxazole were obtained up to 92% yields. The benzyl sodium thiosulfates with electron-withdrawing or electron-releasing groups on the phenyl ring were well tolerated. Substrates both with strong electron-withdrawing groups gave better results than those possessing electron-donating groups. And steric effect exists in the reaction violently. All the obtained compounds were characterized by ¹H NMR, ¹³ C NMR.Finally, a possible mechanism was proposed according to the extensive experimental results（Scheme 2）.