Synthesis of Benzo[b]azepines Carrying a Fluorinated Side Chain

Guangwei Wang describes the Ni-catalyzed synthesis of 2,3,4,5-tetrahydro-1H-benzo[b]azepine analogues.

A Nickel(II) Chloride and Tetrahydroxydiboron Cocatalyzed Facile Synthesis of Benzo[b]azepines with an Appended Fluorinated Side Chain: W. Lei, Y. Yang, M. Guo, W. Zhao, G. Wang
Synthesis 2023, DOI: 10.1055/a-2096-7045

Given the large number of fluorine-containing drugs and bioactive compounds, the development of novel strategies for accessing selectively fluorinated molecules – especially belonging to those classes of privileged heterocycles which are known to be biologically active, such as benzodiazepines – remains a priority for organic and medicinal chemists. Recently, the group of Professor Guangwei Wang from Tianjin University (P. R. of China) reported a versatile and efficient method for achieving the fluoroalkylative cyclization of suitably functionalized anilines to produce the corresponding benzo[b]azepines.

Professor Wang said: “A novel nickel(II) chloride and tetrahydroxydiboron co-catalyzed cascade reaction strategy has been developed for the rapid synthesis of 2,3,4,5-tetrahydro-1H-benzo[b]azepine analogues with an appended fluorinated side chain, which features simple and mild conditions, low cost, and a wide range of substrates. It is noteworthy that tetrahydroxydiboron plays a key role of initiating free radicals, opening up its new potential application as a green and economic radical initiator.”