New and efficient strategies in stereoselective heterocycle synthesis.

This thesis describes the development and the application of three different [3+3]
annelation strategies for the formation of functionalised piperidines. Initially, the
scope of the [3+3] cycloaddition reaction of Pd-trimethylenemethane and
aziridines towards functionalised piperidines was investigated for its application
to silyl ether substituted aziridines. These substrates appeared to be very
challenging, undergoing the cycloaddition only under very rigorous conditions.
Since this methodology was not trivial to repeat, a two-step strategy was explored
that involved the addition of a Grignard reagent to the aziridines followed by ringclosure
to the corresponding piperidines. These two procedures were found to be
enantiospecific, providing good routes for the synthesis of enantiopure
piperidines. The functionalisation of the exo-alkene group of these piperidines
was also investigated with particular regard to the reaction diastereoselectivity. A
third [3+3] annelation reaction towards the synthesis of the piperidine core has
also been employed, which invoked the addition of the Bilchi Grignard reagent to
the enantiopure silyl ether substituted aziridine (R)-139 to provide the
corresponding acetal 263 in good yield. Acid catalysed cyclisation of the acetal
produced the corresponding enantiopure tetrahydropyridine 264. The last section
of this work focused on the applicability of these methods for the synthesis of
natural products and highlights our attempts towards the synthesis of quinolizidine
alkaloid (-)217A.