Ni(0)-Catalyzed\nEfficient, Regioselective Synthesis\nof Dibenzo[<i>b</i>,<i>e</i>]oxepines and Dibenzo[<i>c</i>,<i>f</i>][1,2]oxathiepine 6,6-Dioxides: Mechanistic\nStudy by DFT Calculation and Docking

Herein, a nickel-catalyzed divergent reductive-Heck reaction\nof\n1-bromo-2-((2-(aryl/alkyl ethynyl)phenoxy)methyl)benzene and 2-(aryl/alkyl\nethynyl)phenyl 2-bromobenzenesulfonate derivatives has been demonstrated\nthrough the regulation of reducing agents and solvent systems. This\nscalable protocol offers regio- and stereoselective access to functionalized\ndibenzo[<i>b</i>,<i>e</i>]oxepine and dibenzo[<i>c</i>,<i>f</i>][1,2]oxathiepine 6,6-dioxide scaffolds\nin high to excellent yields under a mild set of reaction conditions.\nThis methodology offers a predictable route for the synthesis of medium\nring oxygen heterocycles and demonstrates wide substrate scope and\noutstanding tolerance to various functional groups like hydroxyl and,\nof course, practical instance via the synthesis of doxepin and nordoxepin\nmolecules. We validate the experimentally proposed reaction mechanism\nusing the density functional theory method. Further, molecular docking\ninteractions were investigated accommodating some of our synthesized\nmolecules.