Formal Synthesis of 3-Deoxy-d-manno-2-Octulosonic Acid (KDO) via a Highly Double-Stereoselective Hetero Diels−Alder Reaction Directed by a (Salen)CoII Catalyst and Chiral Diene

Abstract

This paper presents a formal total synthesis of 3-deoxy-D-manno-2-octulosonic acid (KDO) based on a highly double-stereoselective hetero Diels-Alder reaction between an electron-rich diene and ethyl glyoxylate catalyzed by (Salen)Co(II) complex, a new catalyst for Diels-Alder reactions. A facial specific hydroboration followed by oxidative workup leads to a diol system with the trans-diequatorial arrangement of hydroxyl groups at the C-4 and C-5. Inversion of the configuration of the C-5 hydroxyl group in 12 and then ketal formation afford the desired target diisopropylidene-2-deoxy-KDO methyl ester (18), which can be converted to KDO according to the literature procedure.