Chiral Bicyclic Imidazole‐Catalyzed Acylative Dynamic Kinetic Resolution for the Synthesis of Chiral Phthalidyl Esters. Issue 3 (17th November 2020)

• Record Type: Journal Article
• Authors: Zhou, Muxing; Gridneva, Tatiana; Zhang, Zhenfeng; He, Ende; Liu, Yangang; Zhang, Wanbin
• Is Part Of: Angewandte Chemie international edition. Volume 60:Issue 3(2021)
• Page Start: 1641
• Page End: 1645
• Publication Date: 2020-11-17
• Subjects: bicyclic imidazole -- dynamic kinetic resolution -- enantioselective acylation -- organocatalyst -- phthalidyl ester prodrugs; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202012445
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: 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. Abstract : Utilizing a chiral bicyclic imidazole organocatalyst and adopting a continuous injection process, the acylative dynamic kinetic resolution of 3‐hydroxyphthalides has been implemented for the synthesis of a wide range of phthalidyl esters in high yields and with excellent enantioselectivities (up to 99 % ee ). Computational studies suggest a general base catalytic mechanism and a CH‐π interaction‐dominated stereocontrol mode.