A practical catalytic reductive amination of carboxylic acids
Emma L. Stoll, Thomas Tongue, Keith G. Andrews, Damien Valette, David J. Hirst, Ross M. Denton
Abstract
-catalyzed amide reduction. The reaction is applicable to a wide range of amines and carboxylic acids and has been demonstrated on a large scale (305 mmol of amine). The rate differential between the reduction of tertiary and secondary amide intermediates is exemplified in a convergent synthesis of the antiretroviral medicine maraviroc. Mechanistic studies demonstrate that a residual 0.5 equivalents of carboxylic acid from the amidation step is responsible for the generation of silane reductants with augmented reactivity, which allow secondary amides, previously unreactive in zinc/phenylsilane systems, to be reduced.
Topics & Concepts
Reductive aminationAminationCatalysisChemistryCombinatorial chemistryOrganic chemistryAsymmetric Hydrogenation and CatalysisChemical Synthesis and AnalysisAdvanced Synthetic Organic Chemistry