The development of an in situ Shapiro-Suzuki reaction and its application to the synthesis of monoterpenylmagnolol

The first chapter of this dissertation is a general introduction to multistep reactions, of which the in situ Shapiro-Suzuki is a part. It represents an attempt to define and classify such multistep reactions into in situ or one-pot, simple tandem, domino, cascade, and concurrent reactions.;The third chapter describes the application of the in situ Shapiro-Suzuki reaction to an approach towards monoterpenylmagnolol. The first part of this chapter deals with the synthesis of the biphenol fragment of monoterpenylmagnolol. Several approaches were investigated, including cobalt mediated couplings and Claisen-Cope reactions. In addition, two new biphenyls were prepared in which protecting groups for the phenols were used as ortho-lithiation directors. Bis(methoxymethyl) protected biphenol, a 6,6-dimethyldibenzo[d,f]dioxepine and a 6-ethoxydibenzo[d,f]dioxepine were synthesised and used in lithiation experiments. The selective lithiation of 2,2'-bis(methoxymethoxy)biphenyl and 6,6-dimethyldibenzo[d,f]dioxepine was optimised in order to synthesise the corresponding monoiodides. The two alternative biphenol fragments were also functionalised in the para -position and the results are discussed. The second part of chapter three focuses on the synthesis of an advanced intermediate towards monoterpenylmagnolol using the in situ Shapiro-Suzuki reaction developed in chapter two. Attempts to migrate the double bond of these intermediates were unsuccessful. However, during these attempts an interesting allylic oxidation product from the reaction of dimethyldioxirane with the in situ Shapiro-Suzuki intermediates was identified.;The second chapter focuses on the development of the in situ Shapiro-Suzuki reaction. For both reactions to proceed on most substrates, the Shapiro reaction has to be carried out in a TMEDA/hexanes mixture. The hexanes have to be replaced with toluene for the Suzuki reaction to proceed in good yield. The combination of the two reactions gives yields between 50 and 60%, which was demonstrated on a number of substrates. It was attempted to optimise the reaction by reducing the number of by-products by finding the best catalyst. Palladium acetate/triphenylphosphine has been found to be the catalyst that is most active and most specific with respect to the product. The identification of the by-products showed a very unexpected coupling product that was found to originate from a palladium catalysed coupling between an arylsulfinate salt and the organolialide. An investigation into the effect of TMEDA and triisopropylbenzenesulfinic acid onto the coupling showed that TMEDA is a strong inhibitor of the Suzuki coupling.