A Straightforward Approach for the Stereoselective Synthesis of (<i>E</i>)‐2‐Aryl/vinylmethylidene‐1,4‐benzodiazepines and ‐1,4‐benzodiazepin‐5‐ones through Palladium/Charcoal‐Catalyzed Reactions

Abstract

Abstract A facile and general method for the stereoselective synthesis of ( E )‐2‐aryl‐ (or vinyl)methylidene‐1,4‐benzodiazepin‐5‐ones has been developed by means of palladium/charcoal‐catalyzed reactions between aryl (or vinyl) halides/triflates and 2‐aminotosyl (or nosyl/brosyl/mesyl)‐ N ‐alkyl‐ N ‐(prop‐2‐ynyl)benzamides. Replacing the benzamide unit in the latter substrate by its benzylamine analogue and subsequent reaction with aryl iodides under the same reaction conditions resulted in the formation of ( E )‐2‐aryl‐ (or vinyl)methylidene‐1,4‐benzodiazepines. The reaction mechanism involves trans ‐aminopalladation as a key step during cyclization (7‐ exo ‐ dig ) ensuring exclusive ( E )‐stereochemistry of the products. The method is fast, operationally simple, totally regio‐ and stereoselective, and uses readily available substrates with varied structures and low cost Pd/C instead of costly palladium as catalyst. Furthermore, simple base‐induced isomerization of the exocyclic double bond of the 1,4‐benzodiazepin‐5‐one products yielded their endocyclic isomers. magnified image