Synthesis of 7-Arylthiomethyl Dibenzo[<i>b</i>,<i>d</i>]azepines through Imidoylative Heck Cyclization and CPA-Catalyzed Thio-Michael Addition/Enantioselective Protonation
Weiming Hu, Xilong Wang, Yan Peng, Shuang Luo, Jiaji Zhao, Qiang Zhu
Abstract
A chiral phosphoric acid-catalyzed thio-Michael addition/enantioselective protonation has been developed for the first time. The reaction applies 7-methylene-6-aryl-7H-dibenzo[b,d]azepines, products of Pd-catalyzed imidoylative Heck cyclization, as Michael acceptors in reactions with a wide range of aryl thiols. Diversified 7-[(arylthio)methyl]-7H-dibenzo[b,d]azepines bearing a benzylic stereocenter and a thermodynamically regulated biaryl axis were produced with good to excellent enantioselectivity and 14–25:1 diastereoisomeric ratios.
Topics & Concepts
ChemistryEnantioselective synthesisStereocenterThio-ProtonationMichael reactionArylCatalysisMedicinal chemistryPhosphoric acidHeck reactionStereochemistryOrganic chemistryCombinatorial chemistryPalladiumIonAlkylSulfur-Based Synthesis TechniquesCatalytic C–H Functionalization MethodsAxial and Atropisomeric Chirality Synthesis