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Thiourea-Assisted Chiral Bicyclic Imidazole Organocatalysts: Design, Synthesis, and Application in Asymmetric Acylative Desymmetrization of Bisphenols for the Construction of P-Stereocenters

Chenglong Hu, Xuyang Tang, Baochi Zhang, Zhenfeng Zhang, Wei‐Ping Deng, Wanbin Zhang

2023ACS Catalysis22 citationsDOI

Abstract

Thiourea-assisted chiral bicyclic imidazole organocatalysts were designed, synthesized, and successfully applied in the asymmetric acylative desymmetrization of P-prochiral bisphenols. Under mild conditions, the P-stereogenic products were obtained in high yields (up to 99% yield) and with high enantioselectivities (up to 99% ee). Most importantly, the reaction could also achieve satisfactory results under 1 mol % catalyst loadings. Mechanistic studies showed that the synergistic effect including the covalent activation of the acyl group by the nucleophilic imidazole and the noncovalent H-bonding and π-interaction between the catalyst and substrate was crucial for the efficient construction of P-stereocenters.

Topics & Concepts

DesymmetrizationStereocenterEnantioselective synthesisImidazoleChemistryBicyclic moleculeNucleophileThioureaOrganocatalysisCatalysisNitroaldol reactionOrganic chemistryCombinatorial chemistryStereochemistryAsymmetric Synthesis and CatalysisAsymmetric Hydrogenation and CatalysisSynthetic Organic Chemistry Methods
Thiourea-Assisted Chiral Bicyclic Imidazole Organocatalysts: Design, Synthesis, and Application in Asymmetric Acylative Desymmetrization of Bisphenols for the Construction of P-Stereocenters | Litcius