Niu Shengtong, Zhang Hao, Xu Weici, Bagdi Prasanta Ray, Zhang Guoxiang, Liu Jinggong, Yang Shuang, Fang Xinqiang
State Key Laboratory of Structural Chemistry, and Key Laboratory of Coal to Ethylene Glycol and Its Related Technology, Center for Excellence in Molecular Synthesis, Fujian Institute of Research on the Structure of Matter, University of Chinese Academy of Sciences, Fuzhou, China.
Orthopedics Department, Guangdong Provincial Hospital of Traditional Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
Nat Commun. 2021 Jun 18;12(1):3735. doi: 10.1038/s41467-021-23990-4.
Contemporary asymmetric catalysis faces huge challenges when prochiral substrates bear electronically and sterically unbiased substituents and when substrates show low reactivities. One of the inherent limitations of chiral catalysts and ligands is their incapability in recognizing prochiral substrates bearing similar groups. This has rendered many enantiopure substances bearing several similar substituents inaccessible. Here we report the rationale, scope, and applications of the strategy of kinetic resolution of auxiliary adjacent alcohols (KRA*) that can be used to solve the above troubles. Using this method, a large variety of optically enriched tertiary alcohols, epoxides, esters, ketones, hydroxy ketones, epoxy ketones, β-ketoesters, and tetrasubstituted methane analogs with two, three, and four spatially and electronically similar groups can be readily obtained (totally 96 examples). At the current stage, the strategy serves as the optimal solution that can complement the inability caused by direct asymmetric catalysis in getting chiral molecules with challenging fully substituted stereocenters.
当代不对称催化在面对前手性底物带有电子和空间上无偏向性的取代基以及底物显示出低反应活性时面临巨大挑战。手性催化剂和配体的一个固有局限性在于它们无法识别带有相似基团的前手性底物。这使得许多带有几个相似取代基的对映体纯物质难以获得。在此，我们报道了辅助邻位醇的动力学拆分策略（KRA*）的原理、范围及应用，该策略可用于解决上述问题。使用这种方法，可以很容易地获得各种各样具有光学活性的叔醇、环氧化物、酯、酮、羟基酮、环氧酮、β - 酮酯以及具有两个、三个和四个空间和电子上相似基团的四取代甲烷类似物（共96个实例）。在当前阶段，该策略是一种最优解决方案，可弥补直接不对称催化在获得具有挑战性的全取代立体中心的手性分子方面的不足。
