Synthesis of sulfur heterocycles by C–H bond functionalization of disulfide intermediates

Abstract

Sulfur- and nitrogen-containing heterocycles are found in many natural products but also in most biologically active molecules used in the pharmaceutical and agrochemical industry. Among these molecules are substituted benzo[4,5]thiazolo[2,3-c][1,2,4]triazoles which exhibit a broad range of biological activities. Tricyclazole, a fungicide used to treat rice blast, belongs to this class of compounds. In this review we summarize the development of a new synthetic strategy to prepare benzo[4,5]thiazolo[2,3-c][1,2,4]triazole derivatives. The target compounds are conveniently obtained in a one pot-two step procedure from air stable para-methoxybenzyl protected 4-(2-mercaptophenyl)triazole derivatives which upon deprotection of the thiols undergo an oxidative cyclization to the corresponding tricyclic heteroarenes. Using this procedure, it is possible to obtain a variety of tricyclic heteroarenes which contain both electron-withdrawing and electron donating substituents as well as a wide range of synthetically useful groups, thus allowing biologically relevant groups to be introduced either before or after the heterocycle formation. Mechanistic investigations suggest that the oxidative cyclization proceeds via a disulfide intermediate.