Asymmetric Reductive Amination/Ring-Closing Cascade: Direct Synthesis of Enantioenriched Biaryl-Bridged NH Lactams
Yao Zhang, Yunqi Liu, Le’an Hu, Xumu Zhang, Qin Yin
Abstract
We report here a Ru-catalyzed enantioselective synthesis of biaryl-bridged NH lactams through asymmetric reductive amination and a spontaneous ring-closing cascade from keto esters and NH4OAc with H2 as reductant. The reaction features broad substrate generality and high enantioselectivities (up to >99% ee). To showcase the practical utility, a highly enantioselective synthesis of 5-ethylindolobenzazepinone C, a promising antimitotic agent, has been rapidly completed. Furthermore, the amide group in the products enables versatile elaborations through directed C–H functionalization.
Topics & Concepts
ChemistryReductive aminationCascadeAminationCombinatorial chemistryRing (chemistry)StereochemistryClosing (real estate)LactamOrganic chemistryCatalysisChromatographyLawPolitical scienceAsymmetric Hydrogenation and CatalysisCatalytic C–H Functionalization MethodsAsymmetric Synthesis and Catalysis