Studies on the stereocontrolled synthesis of medium ring compounds.

Several approaches towards the synthesis of an acyclic molecule possessing one chiral centre along with suitable functionality to enable cyclisation to a medium ring were investigated. The intramolecular cyclisation reaction would create a second chiral centre so that two diastereoisomeric products would be possible. Potential cyclisation reactions appeared to include allysilane-aldehyde and allyl tin-aldehyde cyclisations. The first route attempted involved the coupling of an oxygen protected w-hydroxy-aldehyde with 3,3-diethoxy-2-bromopropene via a Grignard reaction or an alkyl lithium reaction, to generate the first chiral centre. A slight variation was also investigated. In this second case the key reaction to form the first chiral centre was the reaction of an oxygen protected w-hydroxy-a-bromoalkane with 2-(trimethylsilyl)methyl-2-propenal via a Grignard reaction. A third approach to the key reaction to introduce the first chiral centre involved the reaction of 2-bromo-3-(trimethylsilyl)propene with an oxygen protected w-hydroxy-aldehyde via Grignard reaction. The products of this reaction then underwent further reactions to generate acyclic molecules containing both allylsilane and aldehyde functionality mediated intramolecular allylsilane-aldehyde cyclisations were then performed. The reaction did not appear to be very stereoselective for the simple molecules which were investigated, as in all cases the diastereoisomer ratios were approximately 1:1. In an attempt to synthesise heterocyclic medium rings an intramolecular acetal initiated allylsilane cyclisation in the presence of Lewis Acid was investigated. It appeared that with the tetrahydropyranyl ethers which were investigated, deprotection of the alcohol group occurred with loss of Thp in preference to breaking of the alternative C-O bond which would have led to cyclisation and the formation of medium ring ethers.