Vinyl Carbanions. Part 36.. Synthesis of 3‐deoxy‐D‐manno‐2‐octulosonic acid (KDO) and derivatives

The β‐ C ‐lithiated acrylamide 3A has been proven to be an ideal pyruvate β‐carbanion equivalent useful in a highly diastereoselective KDO synthesis. The starting material 3 was prepared from pyruvate diethyl acetal in four convenient steps. Direct lithiation with 2 equiv. of LDA generated the dilithiated species 3A quantitatively. Reaction with 2,3:4,5‐di‐ O ‐isopropylidene‐ D ‐arabinose ( 11 ) was highly D ‐ manno ‐selective. The product 12 was obtained readily from the reaction mixture via crystallization. Ring closure to the butenolide 13 , subsequent PhS‐group removal with Bu 3 SnH and pyridinium bromide, and hydrogenolytic debenzylation afforded the known butenolide 19 ; this KDO precursor gives KDO in two convenient steps. Butenolide 19 was also transformed via two high‐yielding steps into the 4,5:7,8‐di‐ O ‐cyclohexylidene‐KDO derivative 22 , a valuable starting material for KDO α‐glycoside syntheses.