Rational Design of Bifunctional Imidazoles as Acyl Transfer Catalysts: Dynamic Kinetic Resolution of 5-Hydroxy-furanones/3-Hydroxy-phthalides

Abstract

A new class of chiral bifunctional imidazole catalysts has been designed and synthesized, utilizing economical amino alcohols as precursors, significantly expanding the diversity of N-1 position catalysts. These catalysts exhibit excellent substrate activation and stereoselectivity control and have been successfully employed in the asymmetric acylation of 5-hydroxy-furanones/3-hydroxy-phthalides through dynamic kinetic resolution, producing a series of chiral furanone and phthalide analogues featuring a quaternary stereocenter. This asymmetric acylation reaction exhibits excellent reactivity and enantioselectivity, has a wide range of applicability, requires a low catalyst loading, and can be readily converted into valuable building blocks. Moreover, DFT calculations revealed the detailed reaction mechanism and demonstrated that the weak N–H···O and C–H···O interactions between the catalyst and substrate are the key factors affecting the stereoselectivity.