Abstract

A sequential strategy to access 10,11-dihydro-5H-dibenzo[b,e][1,4]diazepinones (DBDAPs) is disclosed in this article through a palladium and copper-catalyzed amination (Buchwald–Hartwig (B–H) or Chan–Lam (C–L)) followed by a palladium-catalyzed intramolecular aminocarbonylation with Mo(CO)₆ as CO surrogate (to avoid toxic CO handling) of readily available o-phenylenediamines and either 1,2-dibromobenzene or 2-bromophenylboronic acid. The 10,11-dihydro-5H-dibenzo[b,e][1,4]diazepinone could be synthezised in good yield using a sequential catalytic procedure, using both C–L and B–H approaches. Gratifingly, the use of the C–L reaction was more impressive, and afforded the dibenzodiazepinones in good yields (up to 45%; 2 steps) and much milder conditions using copper as the catalyst. The synthetic utility of this novel strategy was showcased by demonstrating a formal synthesis for the antipsychotic drug clozapine and to an anticancer triazole–DBDAP hybrid.

Beilstein J. Org. Chem. 2024, 20, 193–204. doi:10.3762/bjoc.20.19

摘要

本文公开了通过钯和铜催化胺化获得 10,11-二氢-5 H -二苯并[ b , e ][1,4]二氮杂酮 (DBDAP) 的连续策略（Buchwald-Hartwig (B-H ) 或 Chan–Lam (C–L))，然后用 Mo(CO) ₆作为 CO 替代物（以避免有毒的 CO 处理）对容易获得的邻苯二胺和 1,2-二溴苯或 2 进行钯催化的分子内氨基羰基化-溴苯硼酸。10,11-二氢-5H-二苯并[ b , e ][1,4]二氮杂酮可以使用C-L和B-H方法的连续催化程序以良好的产率合成。令人欣慰的是，C-L 反应的使用更令人印象深刻，并且使用铜作为催化剂，以良好的产率（高达 45%；2 个步骤）和更温和的条件提供了二苯并二氮杂酮。通过展示抗精神病药物氯氮平和抗癌三唑-DBDAP混合物的正式合成，展示了这种新策略的合成效用。

贝尔斯坦 J. 组织。化学。 2024, 20, 193–204。doi:10.3762/bjoc.20.19