Nickel‐Catalyzed Esterification of Aliphatic Amides |
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| Authors: | Liana Hie Emma L Baker Sarah M Anthony Dr Jean‐Nicolas Desrosiers Dr Chris Senanayake Prof Dr Neil K Garg |
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| Affiliation: | 1. http://garg.chem.ucla.edu;2. Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA, USA;3. Department of Chemical Development US, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA |
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| Abstract: | 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. |
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| Keywords: | aliphatic amides cross-coupling esterification homogeneous catalysis nickel |
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