Title:
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Novel Ketone Catalysts for Asymmetric Epoxidation of Alkenes
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Chiral non-racemic ketones have been shown to be powerful promoters of
asymmetric induction in epoxidation reactions with alkenes in the presence of
Oxone®. However, the catalyst structural features are specific for the class of olefins
used as substrates. Up to date, excellent results have been achieved for trans- and trisubstituted
alkenes, while terminal alkenes still represent one of the most challenging
areas. Much work needs to be done in developing suitable catalysts to lead to high
enantioselectivities.
Previous work in ArmstrongÂ’s group identified ketone catalysts based on
oxabicyclo[3.2.1]octan-3-ones and on the N-carboethoxytropinone skeleton, which
performed very well in enantioselective epoxidation of trans- substituted olefins (up
to 93% ee for E-stilbene). This thesis describes the synthesis and the efficiency
towards alkene epoxidations of novel a,a-disubstituted ketones based on the Ncarboethoxytropinone
scaffold. In particular, encouraged by the positive results
achieved by ShiÂ’s group for terminal alkenes, several spiro-motifs a to the carbonyl
have been investigated. A slight improvement was observed towards the challenging
terminal olefins compared to the monosubstituted ketone analogues, whilst very high
ee were maintained for trans- substituted alkenes. However, to our surprise, only
minor changes in enantioselectivity were observed from modifications of the steric
and electronic properties of this spiro-motif in the ketone catalyst. Further axial or
equatorial a functionalisation was explored as a possible strategy to increase
enantioselectivity towards terminal and 1,1-disubstituted alkenes. Indeed, significant
improvements were achieved in enantioselective epoxidation of styrene (up to 50%
ee) and a-methyl styrene (up to 39% ee).
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