Total Synthesis of Natural Trisubstituted Lactones via Tungsten Alkynyl Complexes

• Main Authors: Ming-Jung Chen, 陳明榮
• Other Authors: Rai-Shung Liu
• Format: Others
• Language: zh-TW
• Published: 2000
• Online Access: http://ndltd.ncl.edu.tw/handle/59608762747124635647

博士 === 國立清華大學 === 化學系 === 88 === Several natural products are found to have α-methylene γ-butyrolactone skeleton. The pharmacological importance of these compounds has always been the driving force for their total synthesis. In the last several years we have also turned our attention towards the toolbox for the facile and stereocontrolled construction of functionalized butyrolactone skeleton. Such as Dr. Kesavaram Narkunan synthesize avenociolide and isoavenociolide; Dr. Chandrasekharam synthesize (-)-methylenolactocin; Dr. Liang, K. W. synthesize mitsugashiwalactone; Dr. Shiu, L. H. synthesize confertin isomer. The first part of thesis deals mainly with the chemistry involving tungsten-π-allyl complex. Replacement of carbonyl ligands by NOBF4 and NaI led to the formation of reactive allyl species and its reaction with aldehydes resulted in trans α-methylene γ-butyrolactones in high yields. The stereoselective formation of these lactones has been attributed to the involvement of chair like transition state. This methodology was extended for the construction of protolichesterinic acid, roccellaric acid and (+)-dihydrocanadensolide. In the second part of thesis describes the cycloalkenylation of tungsten-alkynol complexes. Treatment of tungsten-alkynols with organic aldehydes and BF3OEt2 followed by the oxidation of their resulting tungsten oxacarbenium salts led to α-alkylidene γ-butyrolactones. This methodology has also been effectively utilized for the construction of natural products like (+)-Antimycinon、NFX-2、(+)-Blastmycinolactol、(+)-Blastmycinon、 (+)-Litsenolide C2、(+)-Isodihydromahubanolide A、 (-)-3-epi-Blastmycinon、(-)-Epilitsenolide C2、Isodihydromahubanolide B、 (-)-(2R,3S,4S)-3-hydroxy-4-methyl-2-(1''-n-tetradecyl)-butanolide。