One-pot synthesis of benzo[b][1,4]diazepines via the carbonylative Sonogashira reaction and aza-Michael addition cyclocondensation

Benzodiazepines are essential structural motifs commonly found in biologically active compounds and pharmaceutical agents. General and step-economical methods for the direct synthesis of benzodiazepines from simple and easily accessible starting materials remain a continuous challenge for synthetic chemists. Herein, a highly efficient synthetic method for benzodiazepine has been reported, which involves a ppm-level Pd-catalysed carbonylative coupling of iodobenzene with terminal alkynes to afford 1,3-ynones as key intermediates and a subsequent Cp2TiCl2/m-phthalic acid/ethanol-catalysed cyclo-condensation in one-pot conditions. The new approach proceeds with a broad substrate scope under mild reaction conditions, providing benzo[b][1,4]diazepines in up to 90% yield.

Automated summary

Benzodiazepines are commonly found in biologically active compounds and pharmaceutical agents. Direct synthesis of these compounds from simple and easily accessible starting materials has been a challenge in synthetic chemistry. In this study, a highly efficient synthetic method for benzodiazepines was developed, involving a multi-step reaction sequence and specific catalysts, to achieve the synthesis under mild conditions.