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Chiral Bicyclic Imidazole‐Catalyzed Acylative Dynamic Kinetic Resolution for the Synthesis of Chiral Phthalidyl Esters
Author(s) -
Zhou Muxing,
Gridneva Tatiana,
Zhang Zhenfeng,
He Ende,
Liu Yangang,
Zhang Wanbin
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202012445
Subject(s) - kinetic resolution , chemistry , enantioselective synthesis , bicyclic molecule , nucleophile , catalysis , imidazole , acylation , combinatorial chemistry , substrate (aquarium) , stereochemistry , organic chemistry , oceanography , geology
Utilizing a chiral bicyclic imidazole organocatalyst and adopting a continuous injection process, an alternative route has been developed for the efficient synthesis of chiral phthalidyl ester prodrugs via dynamic kinetic resolution of 3‐hydroxyphthalides through enantioselective acylation (up to 99 % ee ). The computational studies suggest a general base catalytic mechanism differing from the widely accepted nucleophilic catalytic mechanism. The structure analysis of the key transition states shows that the CH‐π interactions and not the previously considered cation/π‐π interactions between the catalyst and substrate is the dominant factor giving rise to the observed stereocontrol.