Nickel-Catalyzed Esterification of Aliphatic Amides

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