Access to enantioenriched compounds bearing challenging tetrasubstituted stereocenters via kinetic resolution of auxiliary adjacent alcohols

• Published in: Nature communications Vol. 12; no. 1; p. 3735
• Main Authors: Niu, Shengtong, Zhang, Hao, Xu, Weici, Bagdi, Prasanta Ray, Zhang, Guoxiang, Liu, Jinggong, Yang, Shuang, Fang, Xinqiang
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18-06-2021; Nature Publishing Group; Nature Portfolio
• Subjects: 49/47; 639/638/403; 639/638/77/883; Alcohol; Alcohols; Asymmetry; Catalysis; Catalysts; Epoxides; Esters; Humanities and Social Sciences; Ketoesters; Ketones; Ligands; multidisciplinary; Science; Science (multidisciplinary); Substrates
• ISSN: 2041-1723; 2041-1723
• 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.
A large number of enantiopure substances, such as those with tetrasubstituted carbon centres bearing several similar substituents, are inaccessible due to the incapability of chiral catalysts/ligands to recognize those substrates. Here, the authors develop kinetic resolution of auxiliary adjacent alcohols (KRA*) strategy to access various optically enriched compounds with two, three or four spatially and electronically similar groups.