近日，长沙理工大学罗维纬团队研究了有机催化芳基化反应中异恶唑衍生氨基醇的atropo选择性合成。2025年7月10日出版的《中国化学》杂志发表了这项成果。

研究组通过非线性效应和控制实验等初步机理研究，阐明了反应机理和激活方式。该方法不仅为构建五原子异恶唑支架提供了有效的方法，而且扩展了轴手性氨基醇家族。

手性磷酸催化剂通过加速对映选择性催化反应的动力学，有效地竞争甚至抑制未催化的外消旋背景反应，从而实现5-氨基异恶唑和醌的atroopselective芳基化。在这种策略下，研究组合成了大量的轴向手性异恶唑衍生的氨基醇，收率一般很高，对映选择性很好。该方法反应条件温和，官能团相容性广，可扩展性好。X射线晶体学和热外消旋实验揭示了六元OH···O氢键稳定构型，在质子和非质子溶剂中表现出明显不同的外消旋势垒。

附：英文原文

Title: Atroposelective Synthesis of Isoxazole-Derived Amino Alcohols via Organocatalytic Arylation Reaction

Author: Liang Liu, Hui Wang, Ting Han, Wenkun Luo, Chao Liu, Jun Zhou, Weiwei Luo

Issue&Volume: 2025-07-10

Abstract: The chiral phosphoric acid catalyst enables the atroposelective arylation of 5-aminoisoxazoles and quinones by accelerating the kinetics of the enantioselective catalytic reaction, effectively outcompeting and even suppressing the uncatalyzed racemic background reaction. In this strategy, a large panel of axially chiral isoxazole-derived amino alcohols was synthesized with generally high yields and excellent enantioselectivities. The method features mild reaction conditions, broad functional group compatibility and good scalability. X-ray crystallography and thermal racemization experiments revealed the important role of six-membered intramolecular OH···O hydrogen bonding in stabilizing the configurations, which exhibit markedly different racemization barriers in protic and aprotic solvents. Moreover, preliminary mechanistic studies, including nonlinear effects and control experiments were conducted to elucidate the reaction mechanism and activation mode. This approach not only provides an efficient method for constructing pentatomic isoxazole scaffolds, but also expands the family of axially chiral amino alcohols.

DOI: 10.1002/cjoc.70173

Source: https://onlinelibrary.wiley.com/doi/10.1002/cjoc.70173