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

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.