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钴催化的对映选择性C-H活化/环化反应构建N-N轴手性骨架。

Cobalt-catalyzed atroposelective C-H activation/annulation to access N-N axially chiral frameworks.

作者信息

Li Tong, Shi Linlin, Wang Xinhai, Yang Chen, Yang Dandan, Song Mao-Ping, Niu Jun-Long

机构信息

College of Chemistry, Zhengzhou University, Zhengzhou, 450001, P. R. China.

出版信息

Nat Commun. 2023 Aug 29;14(1):5271. doi: 10.1038/s41467-023-40978-4.

Abstract

The N-N atropisomer, as an important and intriguing chiral system, was widely present in natural products, pharmaceutical lead compounds, and advanced material skeletons. The anisotropic structural characteristics caused by its special axial rotation have always been one of the challenges that chemists strive to overcome. Herein, we report an efficient method for the enantioselective synthesis of N-N axially chiral frameworks via a cobalt-catalyzed atroposelective C-H activation/annulation process. The reaction proceeds under mild conditions by using Co(OAc)·4HO as the catalyst with a chiral salicyl-oxazoline (Salox) ligand and O as an oxidant, affording a variety of N-N axially chiral products with high yields and enantioselectivities. This protocol provides an efficient approach for the facile construction of N-N atropisomers and further expands the range of of N-N axially chiral derivatives. Additionally, under the conditions of electrocatalysis, the desired N-N axially chiral products were also successfully achieved with good to excellent efficiencies and enantioselectivities.

摘要

N-N阻转异构体作为一种重要且引人关注的手性体系,广泛存在于天然产物、药物先导化合物及先进材料骨架中。其特殊的轴向旋转所导致的各向异性结构特征一直是化学家们努力攻克的挑战之一。在此,我们报道了一种通过钴催化的阻转选择性C-H活化/环化过程对N-N轴向手性骨架进行对映选择性合成的有效方法。该反应在温和条件下进行,使用Co(OAc)·4HO作为催化剂,手性水杨醛-恶唑啉(Salox)配体,O作为氧化剂,可高产率和对映选择性地得到多种N-N轴向手性产物。该方法为简便构建N-N阻转异构体提供了一种有效途径,并进一步拓展了N-N轴向手性衍生物的范围。此外,在电催化条件下,也成功以良好至优异的效率和对映选择性得到了所需的N-N轴向手性产物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca40/10465517/56de78cb68da/41467_2023_40978_Fig1_HTML.jpg

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