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.

Carbene-catalyzed dynamic kinetic resolutions and cycloaddition reactions via acylazolium intermediates

“…Our group reported an NHC-catalyzed DKR and acylation of hydroxyphthalides in 2019 (Scheme 1.31a). 45 The reaction gave a series of enantiomerically enriched phthalides in high yields and excellent optical purities (up to 96% yield, 99: We design a chiral NHC-catalyzed dynamic kinetic resolution of α-aryloxycarboxylic esters through transesterification reaction, which allows the isolation of α-aryloxycarboxylic esters in high optical purities. In addition, isoxazolidin-5-ones are valuable motifs frequently found in bioactive compounds and they have emerged as crucial chiral building blocks that are readily converted into the corresponding amino alcohols and β-amino acids.…”