Nickel‐Catalyzed Esterification of Aliphatic Amides

• DOI: 10.1002/ange.201607856
• Publication Date: 2016-11-04T10:41:37Z
• Authors: Liana Hie; Emma L. Baker; Sarah M. Anthony; Jean‐Nicolas Desr...; Chris Senanayake; Neil K. Garg
• Keywords: Amide; Bond cleavage; Peptide bond; Stereocenter; Heteroatom

Recent studies have demonstrated that amides can be used in nickel-catalyzed reactions lead to cleavage of the amide C−N bond, with formation a C−C or C−heteroatom bond. However, general scope these methodologies has been restricted where carbonyl is directly attached an arene heteroarene. We now report esterification derived from aliphatic carboxylic acids. The transformation requires only slight excess alcohol nucleophile and tolerant heterocycles, substrates epimerizable stereocenters, sterically congested coupling partners. Moreover, series competition experiments establish selectivity principles will aid future synthetic design. These overcome critical limitation current Ni-catalyzed couplings are expected further stimulate use as building blocks bond processes.