武汉大学孔望清团队报道了镍催化可调环化和酰胺N-C键断裂引发的1，4酰基转移发散合成2-Benzazepine衍生物。相关研究成果发表在2022年4月6日出版的《德国应用化学》。

配体定向的发散合成可以通过简单地调节不同的配体，将常见的起始材料转化为不同的分子支架。该策略能够快速构建结构丰富的小分子集合，用于生物评估，并揭示催化转化的新模式，代表了合成化学中最受欢迎的挑战之一。

该文中，研究人员报告了一种镍催化配体控制的可调环化/交叉偶联，用于发散合成具有重要药理意义的2-benzazepine框架。双齿配体促进芳基卤化物与酰胺羰基的亲核加成，然后进行1,4-酰基转移和交叉偶联，以获得-benzazepin-5-ones和benzo[c]pyrano[2,3-e]azepines。三齿配体促进选择性7-内环化/交叉偶联以获得2-benzazepin-3-ones。

该方案在温和的反应条件下进行操作，具有不同的环化模式，可通过配体骨架轻松调节。

附：英文原文

Title: Ni-Catalyzed Divergent Synthesis of 2-Benzazepine Derivatives via Tunable Cyclization and 1,4-Acyl Transfer Triggered by Amide N-C Bond Cleavage

Author: yuanyuan ping, Xiao Li, qi pan, Wangqing Kong

Issue&Volume: 2022-04-06

Abstract: Ligand-directed divergent synthesis can transform common starting materials into distinct molecular scaffolds by simple tuning different ligands. This strategy enables the rapid construction of structurally rich collection of small molecules for biological evaluation and reveals novel modes of catalytic transformation, representing one of the most sought-after challenges in synthetic chemistry. We herein report a Ni-catalyzed ligand-controlled tunable cyclization/cross-couplings for the divergent synthesis of pharmacologically important 2-benzazepine frameworks. The bidentate ligand facilitates the nucleophilic addition of the aryl halides to the amide carbonyl, followed by 1,4-acyl transfer and cross-coupling to obtain 2-benzazepin-5-ones and benzo[c]pyrano[2,3-e]azepines. The tridentate ligand promotes the selective 7-  endo  cyclization/cross-coupling to access to 2-benzazepin-3-ones. The protocol operates under mild reaction conditions with divergent cyclization patterns that can be easily modulated through the ligand backbone.

DOI: 10.1002/anie.202201574

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202201574