Novel developments of Palladium and radical mediated cyclisations

In this project cyclisation chemistry using palladium and radical methodologies has been developed. The aim was to compare palladium and radical mediated cyclisations. Initially small molecules containing amine and amide functional groups were synthesised to screen the methodology. Later the design of these molecules was changed to be based on the imidoyl functional group. A series of N-benzyl protected aliphatic amine and amides were synthesised in the hope (with the aim of cyclisation) that they could be cyclised using both palladium and radical conditions. When these examples failed, which was attributed to the strain of the cyclic molecules, alternative precursors were sought. Initially, the N-protecting group was changed to a tosyl-group. However, when this had no positive effect, the size of the precursor molecules were examined. Two alternative amine precursors were designed which would remove the strain element in the cyclised molecules. The lengthy synthesis of these two molecules was not favourable for the development of methodology. Although it appeared that the cyclisations were now occurring it did not prove favourable to carry on down this path. The final part of this research project utilises imines and imidoyl selenides as radical and palladium cyclisation precursors respectively. A series of aromatic imines and imidoyl selenides were synthesised. The irnines were synthesised from amino-biphenyl and a range of p-substituted benza1dehydes. The corresponding imidoyl selenides were synthesised from amino-biphenyl and a range of p-substituted benzoyl chlorides to give the amides which in tum were converted to the target molecules via the imidoyl chlorides. The successful cyclisations using both methodologies resulted in a series of phenanthridines. This success of these cyclisations led to further precursors being developed which included bisphenanthridine, alkyne, alkyl and heteroaromatic precursors. However, most of the cyclisations of these molecules proved problematic and require further development of methodology.