Synthetic Approaches to Lycopodine

Shroot, Braham (1967) Synthetic Approaches to Lycopodine. PhD thesis, University of Glasgow.

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The preparation of a series of substituted bicyclo-(3,3,1)nonane derivatives which possess the requisite functionality for rings B and D of lycopodine is described, culminating in the direct application of these results towards an attempt at a stereospecific synthesis of lycopodine. The model compounds were prepared by treatment of a suitably substituted cyclohexyl-beta-keto-ester with acrolein or methacrolein to furnish the corresponding substituted beta-(l-ethoxycarbonyl-2-oxocyclohexyl)-propionaldehyde. These keto-aldehydes were then treated with either hydrochloric acid or triethylamine to furnish the corresponding ethyl-epimeric, hydnoxybicyclo(3,3,1)nonan-9-one-1-carboxylates. Various unfruitful attempts to convert these ketols (and their derivative into the corresponding bicyclic-keto-olefin are described. In the event it was found that solvolysis of the axial p-toluenesulphonate esters in 10% aqueous acetic acid furnished the desired olefin in high yield. The difficulties encountered in the preparation of l-methoxycarbonyl-6-methoxy-2-tetralone are described, together with a complete spectral and chemical proof of the proposed structure. A Michael reaction between this beta-keto-ester and methacrolein then furnished two diastereoisomeric keto-aldehydes which on treatment with hydrochloric acid afforded four epimeric ketols. Buffered acetolysis of the corresponding p-toluenesulphonates then gave methyl-7-methyl-3'-methoxy-2,3-benzobicyclo(3,3,1)non-2,6-diene-9-one-1-carboxylate in good yield. Catalytic hydrogenation of this olefin over 5% palladium on carbon resulted in the equatorial methyl dihydro derivative, and reduction over 5% rhodium on carbon furnished the axial methyl dihyro derivative. These stereochemical assignments were made with the aid of nuclear magnetic resonance spectroscopy. Insertion of the nitrogen atom and the attempts to construct ring A are then reported. The reductive rearrangement of delta-enol-lactones to furnish the thermodynamically less stable axial bicyclic ketol, is discussed in the addendum. Further evidence in favour of the proposed mechanism is presented.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Organic chemistry
Date of Award: 1967
Depositing User: Enlighten Team
Unique ID: glathesis:1967-78447
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 30 Jan 2020 15:22
Last Modified: 30 Jan 2020 15:22

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