Aerobic Oxidative C-S Bond Coupling Synthesis Of 3-Sulfenylindoles Catalyzed By KI/NaNO₂/AcOH

The construction of C-S bonds represents an important step in general organic synthesis as well as in the pharmaceutical industry and material science.Substituted indole derivatives are widespread in a large number of natural products and are extremely significant in medicinal chemistry.3-thioindoles have recently attracted considerable attention from both industry and academia due to their therapeutic value in a variety of diseases.This study develops environmentally friendly,economical and efficient methods for the sulfenylation of indoles with a variety of sulfenylation agents as the sulfur sources via oxidative C-S bond coupling.The KI/NaNO₂/AcOH/O₂ catalytic system was developed in the preparation of3-sulfenylindoles using Bunte salts as the sulfenylating agents.The cross-coupling of indole and sodium S-3-methoxyphenyl sulfothioate was chosen as the model reaction,the reaction conditions such as kinds of catalysts,the effect of solvents,the amount of catalysts,the reaction temperature and ratio of reactants were screened.Under the optimal reaction conditions,a number of indoles could sulfenylated with Bunte salts to generate 3-sulfenylindoles in good yields.We have further extended this strategy to show the sulfenylation reagents tolerance.For this purpose,we carried out the reactions of different aryl thiols and diaryl disulfides.It is noteworthy that aryl thiols and diaryl disulfides were well tolerated in this transformation,Especially,the sulfenylation of indoles with diaryl disulfides were completed in 2-3 h,which was shorter than that of indoles with aryl thiols,as well as indoles with Bunte salts.In conclusion,we have designed and successfully developed an efficient method for the 3-sulfenylation of indoles with different sulfenylating agents including Bunte salts,aryl thiols and diaryl disulfides via oxidative C-S bond coupling.