Total syntheses of all four stereoisomers of piscidic acid via catalytic asymmetric dihydroxylation of (Z)- and (E)-trisubstituted olefins

All four stereoisomers of (2S, 3R)-(+)-piscidic acid were synthesized with high optical purity via Sharpless catalytic asymmetric dihydroxylation of ( Z)- and (E)-trisubstituted olefins in 6 steps from (4-hydroxyphenyl)pyruvic acid. The Wittig reaction of methyl (4-hydroxyphenyl)pyruvate with (carbom ethoxymethylene)triphenylphosphorane gave (Z)- and (E)-trisubstituted olefi ns in a 3:1 ratio. After protecting the phenolic hydroxyl group as the tert -butyl-dimethylsilyl ether, the (Z)-olefin was subjected to asymmetric dihy droxylation by using the chiral ligand, dihydroquinidine 1,4-anthraquinoned iyl diether, and the reaction proceeded with 89% e.e. Desilylation and subs equent alkaline hydrolysis gave (2S, SR) (+)-piscidic acid. The optical pur ity was increased to >99% e.e. by recrystallization. The use of dihydroquin ine 1,4-anthraquinonediyl diether enable (2R, 3S)-(-)-piscidic acid to be o btained. In the asymmetric dihydroxylation of the (E)-olefin, phthalazine l igands (dihydroquinidine and dihydroquinine 1,4-phthalazinediyl diethers) g ave high e.e. values. Via the same deprotection procedure, (2S, 3S)-(+)-3-e pi-piscidic acid and (2R, 3R)-(-)3-epi-piscidic acid were respectively obta ined.