Synthesis of Novel and Complex Molecules through Selective Coupling

The project has three distinct but related Aims: 1. To achieve a mechanistic understanding of the selective coupling of the two isomeric 1,2- dichloroethylenes and of trichloroethylene by computational means. The results will inform the choice of catalysts for experimental studies and will be implemented for the other two Aims. Disagreements in the literature about the regioselectivity of the coupling of trichloroethylene will be resolved by experimental studies in conjunction with theoretical work. 2. We will use sequential and selective Suzuki coupling of both cis-1,2-dichloroethylene and of trichloroethylene to synthesise, first, cis-stilbenes and triarylethylenes with a diverse range of substitution patterns. Then these will undergo oxidative cyclisation to phenanthrenes. This methodology will be extended to the synthesis of picenes by employing an extended coupling startegy followed by tandem cyclisation. In all cases, we will include a diverse set of substitution patterns on the molecules. We will include synthesis of the scarcely known aza-picenes and othert heteropicenes. In parallel, we will develop a novel route to picenes using the Bergman cyclisation and a route to corranulene using the hexadehydro-Diels-Alder reaction. Both of these routes rely on the selective coupling of chloroethylenes. The library of molecules thus produced will be submitted for preliminary testing of materials properties. 3. Using the same selective coupling methodology, we will synthesise two families of natural products: phenanthroizidines and onydecalins. For the phenathroizidines, we will draw upon the understanding of triarylethylene and phenanthrene synthesis of Aim 2, as well as developing methods for cyclisation, asymmetric hydrogenation and asymmetric hydroamination. For the synthesis of the onydecalins, after the selective coupling chemistry, we will employ an intramolecular Diels-Alder reaction, building upon our earlier synthesis of allahabadolactone. The library of molecules thus produced will be submitted for preliminary testing of biomedical properties.