Carbene-Catalyzed Dynamic Kinetic Resolution and Asymmetric Acylation of Hydroxyphthalides and Related Natural Products

Abstract

A catalytic dynamic kinetic resolution and asymmetric acylation reaction of hydroxyphthalides is developed. The reaction involves formation of a carbene catalyst derived chiral acyl azolium intermediate that effectively differentiates the two enantiomers of racemic hydroxyphthalides. The method allows quick access to enantiomerically enriched phthalidyl esters with proven applications in medicine. It also enables asymmetric modification of natural products and other functional molecules that contain acetal/ketal groups, such as corollosporine and fimbricalyxlactone C.

Keywords: N-heterocyclic carbenes; chirality; kinetic resolution; natural products; organocatalysis.