Studies towards a total synthesis of Hippeastrine

Helary, Johanna Myriam (2015) Studies towards a total synthesis of Hippeastrine. Doctoral thesis, University of East Anglia.

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    Tricarbonyl(ŋ5 -carboxylic acid methyl ester)iron(1+) hexafluorophosphate(1−) (97) was easily prepared in a moderate yield by a tandem Wittig-Michael addition using (3-methoxycarbonylallyl)triphenylphosphonium bromide (94). The resulting cyclohexa-1,3-dienecarboxylic acid methyl ester (95) was complexed with Fe2(CO)9 to obtain tricarbonyl(cyclohexa-1,3-dienecarboxylic acid methyl ester)iron(0) (96) was converted into the highly electrophilic tricarbonyl(ŋ5 -carboxylic acid methyl ester)iron(1+) hexafluorophosphate(1−) by hydride abstraction using triphenylcarbenium hexafluorophosphate (97).
    4-Bromo-1,2-(methylenedioxy)benzene (132), 6-bromopiperonylic acid (98) and 2-bromo-5-methoxy benzoic acid (140) were converted into aryllithium reagents through lithiumbromide exchange by treatment with n-butyllithium. Lithiation and deuteration of 6-bromopiperonylic acid (98) , 2-bromobenzoic acid (136) and of 2-bromo-5-methoxybenzoic
    acid (140) were investigated by using various reagents such as n-butyllithium, LiHMDS and NaH to find the best route for the arylation of 98 to go onwards our target (+/−)-hippeastrine (107 and 108).
    Tricarbonyl[ŋ4-1-methyl ester-5-(3',4'-methylenedioxy)phenylcyclohexa- 1,3-diene]iron(0) (134) was prepared by preparing the aryllithium reagent 132 by lithium-bromide exchange and converting it into an organocuprate nucleophile with copper(I) bromide. Arylation with the cation 97 resulted in the formation of the complex 134. Tricarbonyl[ŋ4 -1-methyl ester-5-
    (3',4'-methylenedioxy-6'-carboxyphenyl)cyclohexa- 1,3-diene]iron(0) (99) was synthesised in the same way as complex (134), using the lithiated 6-bromopiperonylic acid (98) as the reagent. The structures of the compounds were determined by IR, 1HNMR, 13C-NMR spectroscopy and mass spectrometry.

    Item Type: Thesis (Doctoral)
    Faculty \ School: Faculty of Science > School of Chemistry
    Depositing User: Brian Watkins
    Date Deposited: 10 Mar 2016 12:45
    Last Modified: 10 Mar 2016 12:45

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