Convergent synthesis of thiodiazole dioxides from simple ketones and amines through an unusual nitrogen-migration mechanism

We report the modular preparation of dihydro-1,2,5-thiodiazole dioxide heterocycles starting from methyl ketones and primary amines. This one-pot, three-component coupling employs 2,3-dimethylimidazole-1-sulfonyl azide triflate as a coupling reagent and oxidant. The transformation is scalable and various ketones and amines can be used, yielding thiodiazole dioxide products in up to 89% yield. In addition, 15N- and 13C-labeling studies suggest a mechanism involving a 1,2-nitrogen migration. Together with the mechanistic studies, DFT calculations provide insight into the reaction pathway and set the stage for further exploration of the mechanistic nuances of reactions that use sulfamoyl azides. In combination with the demonstrated modularity of the approach reported herein, the derivatization of the thiodiazole dioxide products highlights the potential of this methodology to rapidly access diverse chemical structures. A modular approach to dihydro-1,2,5-thiodiazole dioxide heterocycles is reported. Mechanistic and computational studies support an unusual 1,2 nitrogen migration mechanism for this transformation.

Automated summary

A modular approach to dihydro-1,2,5-thiodiazole dioxide heterocycles is reported. Mechanistic and computational studies support an unusual 1,2 nitrogen migration mechanism for this transformation.