Palladium-Catalyzed Regioselective Hydroaminocarbonylation of Alkynes to α,β-Unsaturated Primary Amides with Ammonium Chloride

• Published in: Journal of organic chemistry Vol. 83; no. 17; pp. 10134 - 10141
• Main Authors: Ji, Xiaolei, Gao, Bao, Zhou, Xibing, Liu, Zongjian, Huang, Hanmin
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 07.09.2018; Amer Chemical Soc
• Subjects: alkynes; amides; ammonium chloride; ammonium salts; catalysts; catalytic activity; chemical reactions; Chemistry; Chemistry, Organic; drugs; moieties; organic chemistry; palladium; Physical Sciences; polymers; regioselectivity; Science & Technology; ALKENES; AROMATIC AMIDE; INTRAMOLECULAR HYDROAMINOCARBONYLATION; CARBONYLATION REACTIONS; CARBON-MONOXIDE; AMINES; EFFICIENT SYNTHESIS; OLEFINS; RADICAL POLYMERIZATION; AMINOCARBONYLATION
• ISSN: 0022-3263; 1520-6904; 1520-6904
• DOI: 10.1021/acs.joc.8b01405

α,β-Unsaturated primary amides have found numerous applications in drug development, organic materials, and polymer sciences. However, the catalytic synthesis of α,β-unsaturated primary amides via carbonylation of alkynes has long been an elusive endeavor. Here, we report a novel palladium-catalyzed hydroaminocarbonylation of alkynes with NH4Cl as the amine source, enabling the highly chemo- and regioselective synthesis of α,β-unsaturated primary amides. A variety of alkynes, including aromatic alkynes, aliphatic alkynes, terminal alkynes, internal alkynes, as well as diynes with various functional groups, react well. The method turns the parasitic noncoordination ability of ammonium salts into a strategic advantage, enabling the gram-scale reaction to be performed in the presence of 0.05 mol % of catalyst with excellent selectivity