Ru(II)-Catalyzed C-H Sulfonamidation of the Medicinally Relevant Benzodiazepine Scaffolds
Shourabh Rav1, Shiv Shankar Gupta1, Sarthi1,2
1C-H Activation & Phytochemistry Lab, Chemical Technology Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur176061, India.
Abstract:
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.
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