Retro-Diels-Alder routes to 4,5 disubstituted cyclopentenones

Master Thesis


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University of Cape Town

Investigation into the synthesis of 4,5-disubstituted cyclopentenones was conducted in light of recent interest on cyclopentenone prostaglandins (PGs) as a new class of anti-viral and anti-inflammatory agents. The strategy involved conjugate addition of various organocuprates to tricyclodecadienone derived from dicyclopentadiene and gave 5-exo-substituted tricyclodecadienones. Attempts to alkylate the kinetic lithium, copper and quaternary ammonium enolates generated from 5-exo-substituted tricyclodecadienones with alkylhalides were unsuccessful. Even in the presence of strong cation solvating hexamethylphosphoramide (HMPA) (±30% co-solvent), lithium enolates proved inert. However, trapping the magnesium enolate generated from the 1, 4-addition of n-butylmagnesium bromide to tricyclodecadienone with aldehydes yielded β-ketols of syn and anti-relative configuration. Due to their labile nature, the β-ketols were dehydrated to their corresponding stable enones. Achiral retro-Diets-Alder reactions were first attempted on 5-exo-substituted tricyclodecadienones using several Lewis-acid catalysts. 4-Substituted-2 cyclopentenones were isolated in good yield and no double bond rearrangement or decomposition was observed. Similar results were also obtained with the dienones generated from dehydration of β-ketols to give αα',ββ'-unsaturated cyclopentadienones in good yield. The synthesis of enantiomerically pure 4- Substituted cyclopentenones and 4- butyl-5-butylidene-cyclopent-2-enone via chiral Lewis-acid catalysed asymmetric retro-Diets-Alder reactions were unsuccessful. Chiral Lewis-acids were prepared in situ from selected Lewis-acids and chiral ligands containing the diol functionality namely BINOL and the TADDOLs.

Includes bibliographical references ( leaves 78-81)