Towards the total synthesis of trichoether A

Abstract

This dissertation comprises two chapters. The first chapter is a short review that covers the different methodologies used to construct polyunsaturated motifs in polyene natural products. Mainly divided into two segments, direct olefination and cross-coupling reactions, the advantages and disadvantages of these reactions are reviewed and discussed in this chapter. The second chapter describes an approach towards the total asymmetric synthesis of Trichoether A which involves three stages – the construction of the triene aliphatic chain fragment, the trisubstituted benzyl fragment, and the different approaches employed in unifying these two fragments in a convergent synthesis. The synthesis of the triene aliphatic chain features an optimisation of the alkynylation in a tricarbonyliron-dienyne complex. In the development of this optimisation step, a different electrophile was introduced to not only enhance the yield of the reaction, but also created an opportunity to avert the use of any hydroxyl protecting groups during the synthesis of the triene aliphatic chain. A subsequent regiospecific hydrostannylation across the internal alkyne was established. Completion of the aliphatic chain then ensued via a Suzuki coupling and Sharpless asymmetric dihydroxylation. The synthesis of the benzyl fragment emphasised the strategic use of C-H activation to install the respective substituent groups. In the final stage of the total synthesis, several coupling strategies for the ether construction as the key step were pursued. Both SN2 and SN1 reactions were described for the etherification step, but other protocols such as the use of Quinone Methide and ketal fragmentation were explored as well. While the partial chiral ketal reduction could deliver the ether bond formation, a model study was carried out to elucidate the mechanistic pathway of the ketal fragmentation strategy.