Double Asymmetric Induction in Organocatalyzed Aldol Reactions: Total Synthesis of (+)-2-epi-Hyacinthacine A(2) and (-)-3-epi-Hyacinthacine A(1)

Abstract

The stereodivergent synthesis of two hyacinthacine analogues, which relies on an organocatalyzed aldol addition, is described. The aldol addition of dioxanone to an -N-carbobenzyloxy-substituted chiral aldehyde, promoted by both (R)- and (S)-proline, proceeds in reasonable yields with acceptable diastereomeric ratios. The success of the reaction may be due to the use of an acyclic aldehyde acceptor, which allows reagent control of the stereochemical outcome of the key aldolization step in both the matched and mismatched cases.