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Rh(III) Catalyzed Redox-Neutral C–H Activation/[5 + 2] Annulation of Aroyl Hydrazides and Sulfoxonium Ylides: Synthesis of Benzodiazepinones

Pothapragada S. K. Prabhakar Ganesh, Perumal Muthuraja, Purushothaman Gopinath

2023Organic Letters15 citationsDOI

Abstract

We herein report the Rh(III) catalyzed redox-neutral C-H activation/[5 + 2] annulation of aroyl hydrazides with sulfoxonium ylides as safe carbene precursors. The reaction shows excellent functional group tolerance, broad substrate scope, and scalability. We demonstrated the synthetic utility of the protocol via the synthesis of various diazepam drug analogues, late-stage functionalization of probenecid drug, and large scale synthesis. Finally, kinetic studies revealed C-H activation as the rate-determining step.

Topics & Concepts

ChemistryAnnulationCatalysisCombinatorial chemistryCarbeneRedoxFunctional groupStereochemistryMedicinal chemistryOrganic chemistryPolymerCatalytic C–H Functionalization MethodsCyclopropane Reaction MechanismsCatalytic Cross-Coupling Reactions
Rh(III) Catalyzed Redox-Neutral C–H Activation/[5 + 2] Annulation of Aroyl Hydrazides and Sulfoxonium Ylides: Synthesis of Benzodiazepinones | Litcius