A Concise Organocatalytic Synthesis of 3‐Deoxy‐2‐ulosonic Acids through Cinchona‐Alkaloid‐Promoted Aldol Reactions of Pyruvate

Abstract

Direct cross‐aldol reactions of a pyruvate ester with chiral aldehydes, mediated by purely organic catalysts, is described as a crucial step in the synthesis of ulosonic acids. Cinchona alkaloids containing a tertiary amine group efficiently promote direct aldol reactions of a sterically hindered pyruvate ester with various sugar aldehydes. The pyruvic acid ester can be directly used as chemical equivalent of PEP (phosphoenolpyruvate) in imitation of the synthetic principle used in nature. The appropriate combination of a chiral aldehyde with a chiral catalyst allows the flexible preparation of anti‐ or syn‐configured aldols, as desired. As a result, concise syntheses of diverse six‐, seven‐, eight‐, and nine‐carbon ulosonic acid esters are described, by using a biomimetic three‐carbon chain elongation of various sugar aldehydes. Consequently, short and practical syntheses of several ulosonic acids, including three important naturally occurring sugars – 3‐deoxy‐d‐erythro‐hex‐2‐ulosonic acid (KDG), 3‐deoxy‐d‐manno‐oct‐2‐ulosonic acid (KDO), and the rare 3‐deoxyglucosone (3DG), in good overall yields are presented.