Development and Scale-Up of a Direct Asymmetric Reductive Amination with Ammonia
Alison Campbell Brewer, J. Craig Ruble, H. George Vandeveer, Scott A. Frank, C. Richard Nevill
Abstract
Direct asymmetric reductive amination represents an efficient means of converting ketones to α-chiral primary amines, but reported examples are very limited. We describe the development of two sets of Ru-catalyzed conditions for the direct conversion of an aryl methyl ketone to a pharmaceutically relevant chiral primary amine. In the presence of NH3, NH4Cl, and H2, a readily available dtbm-Segphos ruthenium catalyst can be used to prepare the desired chiral primary amine with >93% ee on multikilogram scale.
Topics & Concepts
Reductive aminationAmine gas treatingAminationRutheniumPrimary (astronomy)ChemistryCatalysisKetoneAmmoniaCombinatorial chemistryArylOrganic chemistryPhysicsAstronomyAlkylAsymmetric Hydrogenation and CatalysisSynthesis and Catalytic ReactionsCatalytic C–H Functionalization Methods