Ni(0)-Catalyzed Efficient, Regioselective Synthesis of Dibenzo[b,e]oxepines and Dibenzo[c,f][1,2]oxathiepine 6,6-Dioxides: Mechanistic Study by DFT Calculation and Docking Interactions.

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