Chemistry of pyruvate enolates : anti-selective direct aldol reactions of pyruvate ester with sugar aldehydes promoted by a dinuclear zinc catalyst

A chiral dinuclear zinc complex can effectively catalyse the direct aldol reactions of pyruvic acid ester with various chiral sugar aldehydes, thus functionally mimicking the pyruvate-dependent type II aldolases. Application of sterically hindered aryl esters allows for the elusive aldol reaction of the pyruvate donor with controlled anti-selectivity en route to the short and efficient synthesis of 3-deoxy-2-ulosonic acids. Pyruvic acid ester is here used as a chemical equivalent of phosphoenol pyruvate (PEP) in imitation of the synthetic principle used in nature. The presented biomimetic methodologies use enol formation for the highly efficient and flexible formation of various C6–C9 ulosonic acids. Particularly, efficient and concise syntheses of 3-deoxy-D-erythro-hex-2-ulosonic acid (KDG, overall 50% yield), 3-deoxy-D-ribo-hept-2-ulosonic acid (DRH, overall 53% yield) and 3-deoxy-D-glycero-D-talo-non-2-ulosonic acid (4-epi-KDN, overall 78% yield) are described. This direct efficient application of pyruvic esters does not require additional demasking steps and thus surpassess previously methodologies utilising masked pyruvic synthons such 2-acetylthiazole and pyruvic aldehyde dimethyl acetal.