Angewandte Chemie | 2019
Direct Catalytic Decarboxylative Amination of Aryl Acetic Acids.
Abstract
The decarboxylative coupling of a carboxylic acid with an amine nucleophile provides an alternative to the substitution of traditional organohalide coupling partners. Benzoic and alkynyl acids may be directly aminated via oxidative catalysis. By contrast, methods for intermolecular alkyl carboxylic acid to amine conversion, including amidate rearrangements and photoredox-promoted approaches, require stoichiometric activation of the acid unit to generate isocyanate or radical intermediates. We report a process for the direct chemoselective decarboxylative amination of electron-poor arylacetates via oxidative Cu catalysis. The reaction proceeds at (or near) room temperature, uses native carboxylic acid starting materials, and is compatible with protic, electrophilic, and other potentially complicating functionality. Mechanistic studies support a pathway in which ionic decarboxylation of the acid generates a benzylic nucleophile which is aminated in a Chan-Evans-Lam type process.