title: Chiral synthesis of asymmetrically tetra-C-substituted cyclopentane derivatives by Diels-Alder addition of cyclopentadiene to unsaturated acyclic-sugar derivatives.
abstract: Optically pure, substituted cyclopentane derivatives of interest in synthesis of prostaglandin analogs have been obtained by stereocontrolled addition of cyclopentadiene to trans alpha,beta-unsaturated sugar derivatives. Methyl (E)-4,5,6,7-tetra-O-acetyl-2,3-dideoxy-D-arabino-hept-2-enonate (2), obtained by Wittig addition of Ph3PCHCO2Me to aldehydo-D-arabinose tetraacetate, reacted with cyclopentadiene in boiling toluene to give 40% of a crystalline, norbornene adduct (3) having the 5S-exo ester, 6S-endo sugar-chain configuration, as established by crystallography and by conversions into the known, crystalline (2S,3S)-bis(p-tolylsulfonyloxymethyl)bicyclo[2.2.1]heptane. Likewise, the L enantiomer (19) of 2 was converted into the crystalline enantiomer of 3; chromatographic resolution of the other Diels-Alder adducts from the reaction afforded lesser amounts of the other three possible isomeric adducts, which were characterized by appropriate conversions. The Ph3PCHCO2Me Wittig adduct (9) from 2,3:4,5-di-O-isopropylidene-aldehydo-D-arabinose with cyclopentadiene in hot toluene gave a crystalline mixture of the isomeric 5S,6S adducts (10 and 11), separable after deacetonation and acetylation as the already characterized product 3 and its 6S-endo ester, 5S-exo sugar-chain isomer. Likewise, the L enantiomer of the D dienophile 9 gave a crystalline mixture of 5R,6R adducts that were the enantiomers of 10 and 11. A reversed ratio of adducts resulted when the tetraacetylated L dienophile 19 reacted at 0 degrees with cyclopentadiene under AlCl3 catalysis, and 36% of the crystalline 5S-endo ester, 6S-exo sugar-chain adduct (23) was obtained. Hydroxylation-glycol cleavage of the double bond in 23, followed by reduction and acetylation, gave 65% of an optically pure cyclopentane derivative having five chiral centers of the same absolute configuration as in prostaglandin F1 alpha.
mesh_terms: D002241:Carbohydrates; D003517:Cyclopentanes / Q000138:chemical synthesis*; D011453:Prostaglandins / Q000138:chemical synthesis
chemical_list: D002241:Carbohydrates; D003517:Cyclopentanes; D011453:Prostaglandins; C004709:1,3-cyclopentadiene