Fine-tuning the chemo- and regioselective alkylation of 1,4-benzodiazepines: further applications of the Mitsunobu reaction

Abstract

The reaction of 1,4-benzodiazepines with primary and secondary alkyl bromides/iodides can lead to a mixture of N- and O-alkylations of both the anilide and benzamide functions. We have developed conditions that demonstrate the degree of N- and O-alkylation, exclusively at the anilide function, can be controlled by the Mitsunobu reaction under mild conditions. More generally, the Mitsunobu reaction has now been successfully extended to encompass activated, heterocyclic anilide pro-nucleophiles.