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.

Graphical Abstract

Keywords:

• Sulfur heterocycles
• oxidative cyclization
• C–H functionalization
• heteroarenes
• disulfides

Additional information

Funding

Acknowledgment is made to the donors of the American Chemical Society Petroleum Research Fund for support of this research (ACS PRF Doctoral New Investigator (DNI) Research Grant; proposal number: 58507 DNI-1).