郑州大学梅光建团队报道了轴向手性C2芳基吡咯衍生氨基醇的合理设计与阿托品选择性合成。相关研究成果发表在2022年6月21日出版的《德国应用化学》。
轴向手性二芳基二醇BINOLs在不对称催化中取得了巨大的成功。相比之下，轴向手性二芳基氨基醇，如NOBIN，则远未得到开发。
该文中，研究人员基于轴向手性C2芳基吡咯框架，合理设计了一种多用途的C1对称双芳基氨基醇支架1-（1-氨基吡咯-2-基）萘-2-醇（NPNOL）。对于其对映选择性合成，建立了手性磷酸催化的1,3-二羰基化合物与偶氮烯烃的不对称Attanasi反应。通过使用这种实用的方法，可以很容易地以高产量和优异的阿托品选择性制备各种NPNOLs（38个实例，高达89%的产量和99%的ee）。
DFT计算揭示了反应机理和对映选择性的来源。NPNOL衍生产物很容易转化为有机催化剂/配体，并在不对称催化反应中得到初步应用，这表明NPNOL具有广阔的应用前景。
附：英文原文
Title: The Rational Design and Atroposelective Synthesis of Axially Chiral C2-Arylpyrrole-Derived Amino Alcohols
Author: Tian-Jiao Han, Zheng-Xu Zhang, Min-Can Wang, Li-Ping Xu, Guang-Jian Mei
Issue&Volume: 2022-06-21
Abstract: Axially chiral biaryl diol BINOLs have achieved great success in asymmetric catalysis. By contrast, axially chiral biaryl amino alcohols, such as NOBIN, are far less developed. Herein, we have rationally designed a versatile C 1 -symmetric biaryl amino alcohol scaffold 1-(1-amino-pyrrol-2-yl)naphthalen-2-ol (NPNOL) on the basis of axially chiral C2-arylpyrrole framework. For its enantioselective synthesis, the chiral phosphoric acid-catalyzed asymmetric Attanasi reaction between 1,3-dicarbonyl compounds and azoalkenes had been established. By using this practical method, a wide range of NPNOLs were readily prepared in high yields and excellent atroposelectivities (38 examples, up to 89% yield and 99% ee ). DFT calculations were performed to reveal the reaction mechanism and the origins of the enantioselectivity. The easy transformations of NPNOL-derived products into organo-catalysts/ligands and their preliminary applications in asymmetric catalytic reactions demonstrated the promising utility of NPNOL.
DOI: 10.1002/anie.202207517
Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202207517
