近日，中国厦门大学化学化工学院教授周波及其研究小组揭示了酸催化羧酸与胺和醇的氨基选择性偶联反应。该研究于2025年3月20日发表于国际一流学术期刊《德国应用化学》杂志上。

这里研究组报道了一个手性Br以酰胺为偶联剂，苯甲酸（CBA）催化羧酸与胺和醇的氨基选择性偶联。新的对映控制包括CBA催化的酯加成，通过分子间酰胺化和分子内大内酯化，可以直接构建具有高对映选择性的轴手性和平面手性酯。多种药用相关羧酸可以通过这种方法进行直接的后期修饰。重要的是，该反应代表了羧酸与胺的第一次atroo选择性偶联，以及羧酸与醇的第一次化学催化atroo选择性偶联。所得的atrosom异构骨架可以很容易地衍生为手性配体和不对称催化的催化剂。

据悉，羧酸是一种易得的化学物质，在化学相关领域有着广泛的应用，它们与胺和醇的偶联是有机合成的一个基本转变。然而，羧酸的催化对映选择性偶联仍然存在，特别是在对映选择性反应中。

附：英文原文

Title: Brønsted Acid-Catalyzed Atroposelective Coupling of Carboxylic Acids with Amines and Alcohols via Ynamide Mediation

Author: Hua-Hong Chen, Jia-Tian Jiang, Ye-Nan Yang, Long-Wu Ye, Bo Zhou

Issue&Volume: 2025-03-20

Abstract: Carboxylic acids are readily available chemicals with broad applications in chemistry-related areas, and their coupling with amines and alcohols is a fundamental transformation in organic synthesis. However, the catalytic enantioselective coupling of carboxylic acids remains elusive, especially for the atroposelective reaction. Here we report a chiral Brnsted acid (CBA)-catalyzed atroposelective coupling of carboxylic acids with amines and alcohols using ynamides as coupling reagents. The novel enantiocontrol involving CBA-catalyzed ester addition enables the straightforward construction of axially chiral amides and planar-chiral esters with high enantioselectivities through atroposelective intermolecular amidation and intramolecular macrolactonization. Diverse medicinally relevant carboxylic acids can undergo direct late-stage modification by this method. Importantly, this reaction represents the first atroposelective coupling of carboxylic acids with amines, as well as the first chemocatalytic atroposelective coupling of carboxylic acids with alcohols. The resulting atropisomeric skeletons can be readily derivatized to chiral ligands and catalysts for asymmetric catalysis.

DOI: 10.1002/anie.202505167

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202505167