Ru(II)-Catalyzed C-H Sulfonamidation of the Medicinally Relevant Benzodiazepine Scaffolds.

A late-stage, efficient C-H functionalization of medicinally relevant 1,4-benzodiazepines for direct C-H sulfonamidation has been developed via Ru-catalyzed C-H activation. Tosyl azide (TsN3) serves as a bench-stable sulfonamidating reagent. The sulfonamidated product is further converted to an aminated product through chemoselective hydrolysis of the sulfonamide bond. In mechanistic studies, a ruthenacycle (BDZ-Ru-Cl) has been synthesized and characterized by NMR spectroscopy and SC-XRD. Additionally, a novel intermediate, Int-C (a six-membered N-SO2Ar-inserted species), was synthesized from BDZ-Ru-Cl, providing further support for the proposed mechanistic pathway. Density functional theory (DFT) studies were also conducted to gain deeper mechanistic insight and to validate the developed protocol.