Ring Opening of Dihydro-2-pyridones and Intramolecular Diels−Alder Reactions.Chiral Synthesis of Indolizidines 209D and 167B via Asymmetric Oxidation of Sulfides and Sulfoxides.

• Main Authors: Wu, Chien-Jung, 吳建忠
• Other Authors: Chou, Shang-Shing
• Format: Others
• Language: zh-TW
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/02531194856456045441

博士 === 輔仁大學 === 化學系 === 100 === (一) A new ring-opening reaction of 5,6-dihydro-2-pyridones was discovered. 5,6-Dihydro-2-pyridones (1, 11) were converted to the corresponding dienoic amides (2, 12) by reaction with sodium hydride at room temperature. N-allylation of compounds 2 and 12 followed by intramolecular Diels－Alder (IMDA) reaction provided the cis-fused hexahydro-1-indolones 9 and 14, respectively. Treatment of compounds 9 and 14 with DBU in refluxing ethyl acetate gave the conjugated products 10 and 15, which upon N-detosylation and N-substitution were further transformed to the amides 16－19. The phenylthio group of compounds 9, 10, 14 and 15 were oxidized to the corresponding sulfone derivatives 20－23. The phenylthio group of compound 15 was also substituted by a methyl group to give product 24. (二) We found that asymmetric oxidation of racemic phenylthio compounds led to the synthesis of chiral sulfoxide and chiral sulfone derivatives, which were further converted to the natural products indolizidines (－)-209D, (＋)-209D, (－)-167B and (＋)-167B. First, (±)-7-(phenylthio)-2,3,8,8a-tetrahydroindolizin-5(1H)-one (25) was converted to (±)-cis-7-(phenylthio)-5-hexyl-1,2,3,5,8,8a-hexahydro- indolizine (26) by reaction with C6H13MgBr and NaBH4. Compound 26 was treated with excess Ra-Ni to cleave the phenylthio group and reduce the doubled bond to give indolizidine (±)-209D. The nitrogen atom of compound 26 was protonated by sulfuric acid and then oxidized by m-CPBA to give two diastereomeric sulfoxides (±)-31a and (±)-31b. Compound 26 was treated with p-toluenesulfonic acid and was then oxidized to chiral sulfoxide (－)-31a and chiral sulfone (＋)-32 using 6 equivalents of chiral oxidants (Ti(O-i-Pr)4/(－)-DET/t-BuOOH = 7 : 28 : 6). Compounds (－)-31a and (＋)-32 were further converted to the indolizidine natural products (－)-209D and (＋)-209D, respectively. Using C3H7MgBr to react with compound 26 led to (±)-cis-7-(phenylthio)-5-propyl-1,2,3,5,8,8a-hexahydroindolizine (33), which was similarly converted to indolizidines (－)-167B and (＋)-167B.