Direct Catalytic Decarboxylative Amination of Aryl Acetic Acids. Issue 3 (5th December 2019)

• Record Type: Journal Article
• Authors: Kong, Duanyang; Moon, Patrick J.; Bsharat, Odey; Lundgren, Rylan J.
• Is Part Of: Angewandte Chemie international edition. Volume 59:Issue 3(2020)
• Page Start: 1313
• Page End: 1319
• Publication Date: 2019-12-05
• Subjects: amination -- chemoselectivity -- copper -- decarboxylation -- synthetic methods; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201912518
• Languages: English
• ISSNs: 1433-7851

Abstract

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 by oxidative catalysis. In 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. Reported here is a process for the direct chemoselective decarboxylative amination of electron‐poor arylacetates by 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. Abstract : The direct, chemoselective amination of aryl acetic acids is reported. The process enables late‐stage alkylation of drug targets without interference from other protic groups or electrophiles. Mechanistic studies support the generation of a benzylic nucleophile which is aminated in a Chan–Lam‐type redox pathway.