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Conjugate Addition Coupled with Enolate Oxidation in the Total Synthesis of Natural Polyphenols
Mašek, Tomáš ; Jahn, Ullrich (advisor) ; Pospíšil, Jiří (referee) ; Švenda, Jakub (referee)
1 ABSTRACT This thesis describes the development of the concept of C-C bond forming conjugate addition/oxidative cyclisation reactions and their application in the total synthesis of natural polyphenols. The first part deals with the development of methodology for conjugate addition of main- group organometallic reagents to unsaturated carbonyl compounds coupled with in situ single electron transfer oxidation. The resulting radical undergoes stereoselective cyclisation, that can be followed by a second SET oxidation, leading to further cationic cyclisation. This methodology is ideally suited for the synthesis of furoindane stilbenolignans (FIS), a neglected and structurally distinct class of natural polyphenols. Using this process, racemic synthesis of a derivative of kompasinol A was achieved, confirming the relative configuration of FISs. In an effort to develop asymmetric route to FISs, an unprecedented direct conjugate addition of aryllithiums to ylidenemalonates mediated by diethers and diamines was discovered, leading to asymmetric synthesis of gnetifolin F and 11- deoxykompasinol A. Based on X-ray evidence, a related annulation methodology consisting of direct conjugate addition/epoxide opening was shown to result in bridged lactones, instead of isomeric FISs. This finding led to an approach for the...
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Tandem Anionic Sigmatropic Rearrangement/Radical Reactions and Their Application Toward the Total Synthesis of Natural Products
Šimek, Michal ; Jahn, Ullrich (advisor) ; Urban, Milan (referee) ; Švenda, Jakub (referee)
The thesis describes the development of unprecedented tandem reactions merging anionic oxy-Cope rearrangement with single-electron transfer oxidation of thus generated metal enolates by ferrocenium hexafluorophosphate. The formed α-carbonyl radicals were utilized in oxygenation reactions by coupling them with persistent radical TEMPO, furnishing rearranged α-aminoxy carbonyl compounds. Suitable reaction conditions and factors influencing the rearrangement aptitudes were determined. The obtained polyfunctional products proved versatile in diversifications by polar reactions producing diverse scaffolds. Furthermore, rearranged α-aminoxy carbonyls with a double bond located in the δ-position of the carbonyl group are applicable in all-carbon 5-endo-trig radical cyclizations governed by the persistent radical effect. Despite the low kinetic rate, this rare cyclization mode furnished a number of substituted cyclopentanes. The reaction scope, including competitive cyclization modes, was studied. The developed methodology was utilized as a key reaction step to synthesize appropriately substituted cyclopentane core in a divergent approach to meroterpenoid fungal metabolites isolated from Ganoderma applanatum. The accomplished synthesis of applanatumols V and W and their epimers enabled the correction of...
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