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

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

α,β-不饱和一级酰胺（α,β-Unsaturated primary amides）在药物开发、有机材料及高分子科学领域已有诸多应用。然而，通过炔烃羰基化反应催化合成α,β-不饱和一级酰胺，长期以来始终是一项难以攻克的研究课题。本文报道了一种新型钯催化的炔烃氢氨基羰基化反应（hydroaminocarbonylation），以氯化铵（NH4Cl）作为胺源，可实现α,β-不饱和一级酰胺的高化学选择性与区域选择性合成。多种炔烃均可良好适用于该反应，包括芳香炔烃、脂肪族炔烃、末端炔烃、内炔烃以及带有各类官能团的二炔。该方法将铵盐原本不具备配位能力的劣势转化为策略性优势，可在催化剂负载量为0.05 mol%的条件下开展克级规模反应，且具备优异的选择性。