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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.

A novel chiral nucleophilic organocatalyst easily synthesized from simple starting materials bearing a 5,6,7,8-tetrahydroimidazo[1,2-a]pyridine skeleton has been developed and successfully applied in the direct enantioselective C-acylation of 3-substituted benzofuranones. Its catalytic efficiency was shown to be comparable to that of the previously reported chiral 6,7-dihydro-5H-pyrrolo[1,2-a]imidazole catalyst. A wide range of 3,3-disubstituted benzofuranones, possessing a quaternary stereocenter, were synthesized with high yields and enantioselectivities.