Synthesis of 1,3-Benzodiazepines through [5 + 2] Annulation of <i>N</i>-Aryl Amidines with Propargylic Esters
Xia Song, Qianting Zhou, Jie Zhao, Yuqin Jiang, Xiaopeng Zhang, Xiaopeng Zhang, Xinying Zhang, Xinying Zhang, Xuesen Fan
Abstract
In this paper, an efficient synthesis of functionalized 1,3-benzodiazepines through an unprecedented [5 + 2] annulation of N-aryl amidines with propargylic esters is presented. The reactions proceed through Rh(III)-catalyzed C(sp2)−H alkenylation followed by annulation and deacetoxylation along with cascade C−H/N−H/C−O bond cleavage and C−C/C−N bond formation. Furthermore, the cytotoxicity of selected products against several human cancer cell lines was tested, which demonstrated their good potential for pharmaceutical applications.
Topics & Concepts
ChemistryAnnulationArylBenzazepinesMedicinal chemistryStereochemistryCombinatorial chemistryOrganic chemistryCatalysisAlkylCatalytic C–H Functionalization MethodsCatalytic Alkyne ReactionsSynthesis and pharmacology of benzodiazepine derivatives