Nickel-Catalyzed Conversion of Amides to Carboxylic Acids

• DOI: 10.1021/acs.orglett.0c00885
• Publication Date: 2020-03-25T15:29:31Z
• Authors: Rachel R. Knapp; Ana S. Bulger; Neil K. Garg
• Keywords: Molecular Structure; Nickel; Hydrolysis; Carboxylic Acids; Amides; 01 natural sciences; Catalysis; 0104 chemical sciences

We report the conversion of amides to carboxylic acids using nonprecious metal catalysis. The methodology strategically employs a nickel-catalyzed esterification using 2-(trimethylsilyl)ethanol, followed by a fluoride-mediated deprotection in a single-pot operation. This approach circumvents catalyst poisoning observed in attempts to directly hydrolyze amides using nickel catalysis. The selectivity and mildness of this transformation are shown through competition experiments and the net-hydrolysis of a complex valine-derived substrate. This strategy addresses a limitation in the field with regard to functional groups accessible from amides using transition metal-catalyzed C-N bond activation and should prove useful in synthetic applications.