Lu Guang-Sheng, Ruan Zhong-Lei, Wang Yan, Lü Jin-Fang, Ye Jian-Liang, Huang Pei-Qiang
Department of Chemistry and Fujian Provincial Key Laboratory of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian, 361005, P. R. China.
Angew Chem Int Ed Engl. 2025 Mar 17;64(12):e202422742. doi: 10.1002/anie.202422742. Epub 2024 Dec 19.
Reported herein is a convenient and efficient method for one-pot, catalytic reductive amination, as well as the first multi-component tandem reductive amination-functionalization of bench-stable and readily available common carboxylic esters. This method is based on the cationic [Ir(COD)]BArF-catalyzed chemoselective hydrosilylation of esters, followed by one-pot acid-mediated amination and nucleophilic addition. The reaction was conducted under mild conditions at a very low catalyst loading (0.1 mol % of Ir), which could be further reduced to 0.001 mol %, as demonstrated by a reaction at a 15 g scale. The method is highly versatile, allowing the use of esters with or without α-protons for the N-mono-alkylation of primary and secondary amines to produce diverse secondary and tertiary amines, as well as α-branched/functionalized amines. The method is highly chemoselective and tolerates a variety of functional groups such as bromo, trifluoromethyl, ester, and cyano groups. The value of the method was demonstrated by the one-step catalytic synthesis of two bio-relevant N-mono-methyl α-amino esters and the antiparkinsonian agent piribedil, as well as by the use of two shorter chain triglycerides as alkylating feedstock.
本文报道了一种便捷高效的一锅法催化还原胺化方法，以及首例对稳定且易于获得的常见羧酸酯进行多组分串联还原胺化-官能化反应。该方法基于阳离子[Ir(COD)]BArF催化的酯的化学选择性硅氢化反应，随后进行一锅法酸介导的胺化反应和亲核加成反应。反应在温和条件下进行，催化剂负载量极低（铱为0.1 mol%），15 g规模的反应表明该负载量可进一步降至0.001 mol%。该方法具有高度通用性，允许使用含或不含α-质子的酯对伯胺和仲胺进行N-单烷基化反应，以制备多种仲胺和叔胺，以及α-支链/官能化胺。该方法具有高度的化学选择性，能耐受多种官能团，如溴、三氟甲基、酯基和氰基。通过一步催化合成两种与生物相关的N-单甲基α-氨基酯和抗帕金森病药物匹立哌唑，以及使用两种较短链的甘油三酯作为烷基化原料，证明了该方法的价值。
