STUDIES DIRECTED TOWARD THE TOTAL SYNTHESIS OF JOLKINOL D
Abstract
The Lathyranes are a class of diterpenes characterized by a tricyclic {10.3.0.0} pentadecane ring system generally containing two trans double bonds at the 3 and 10 positions. The ultimate goal of this research is the total synthesis of Jolkinol D by a synthetic route which could easily accomodate the rest of the Lathyranes. The synthetic scheme involves four major requirements: (1) A method for generating (alpha),(beta),(gamma)-functionalized cyclic enones; (2) The equivalent of a hydrolysis of a vinylsulfone; (3) An enolate-assisted fragmentation for synthesis of the macrocyclic ring; and (4) The preparation of the starting materials in optically active form. Enolate-assisted fragmentations to produce macrocyclic dienes have been studied previously. Resolution of the vinylsulfone precursor affords both enantiomers in equal amounts. For the sake of efficiency, methodology was developed to convert either enantiomer to the desired vinylsulfone. This enantioconvergent approach was applied as well to the synthesis of Prostaglandin E(,2) by Fuchs' coworker. Oxidation of (alpha)-sulfonyl carbanions (generated in situ from the addition of organometallic reagents to vinylsulfones) with a molybdenum peroxide-lithium diisopropylamide complex produced (alpha)-substituted ketones. Addition of a hydride reagent followed by oxidation of the resultant sulfone carbanion (the reductive-oxidative "hydrolysis" of a vinylsulfone) was not attempted. Previous vinylsulfone methodology allowed for the preparation of (alpha),(beta)-substituted cyclic enones. By utilizing epoxy vinylsulfones as triply charge-inverted ynone synthons this methodology was extended to allow for the enantiospecific incorporation of an alkyl moiety into the gamma position of an enone. Application of this strategy in the synthesis provided the intermediates for cyclization to the key tetracyclic ring structure required in the subsequent fragmentation reaction. This cyclization to date has shown only limited success.
Degree
Ph.D.
Subject Area
Organic chemistry
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