Total Syntheses of All Four Stereoisomers of Piscidic AcidviaCatalytic Asymmetric Dihydroxylation of (Z)- and (E)-trisubstituted Olefins

Abstract

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 (carbomethoxymethylene)triphenylphosphorane gave (Z)- and (E)-trisubstituted olefins in a 3:1 ratio. After protecting the phenolic hydroxyl group as the tert-butyldimethylsilyl ether, the (Z)-olefin was subjected to asymmetric dihydroxylation by using the chiral ligand, dihydroquinidine 1,4-anthraquinonediyl diether, and the reaction proceeded with 89% e.e. Desilylation and subsequent alkaline hydrolysis gave (2S, 3R)-(+)-piscidic acid. The optical purity was increased to >99% e.e. by recrystallization. The use of dihydroquinine 1,4-anthraquinonediyl diether enable (2R, 3S)-(-)-piscidic acid to be obtained. In the asymmetric dihydroxylation of the (E)-olefin, phthalazine ligands (dihydroquinidine and dihydroquinine 1,4-phthalazinediyl diethers) gave high e.e. values. Via the same deprotection procedure, (2S, 3S)-(+)-3-epi-piscidic acid and (2R, 3R)-(-)-2-epi-piscidic acid were respectively obtained.