Tetrafluoropyridazíne: a scaffold for the synthesis of highly functionalised heterocycles

Abstract

There is a great desire for the synthesis of new heteroaromatic compounds, which have a range of applications from pharmaceuticals to materials. These industries require large numbers of heterocyclic derivatives for their screening programmes, however many common routes for the synthesis of aromatic heterocycles do not allow for the flexible introduction of a diverse range of substituents. Our approach involves the use of tetrafluoropyridazine as a scaffold for the synthesis of a diverse range of heteroaromatic systems. Perfluorinated heteroaromatic compounds, such as tetrafluoropyridazíne, are highly reactive towards displacements by nucleophilic species. Sequential nucleophilic aromatic substitution reactions of 4,5,6- trifluoropyridazin-3(2H) one have been studied and a range of polysubstituted systems synthesised. Similarly, reactions of tetrafluoropyridazine with dinucleophiles have been utilised to yield ring-fijsed products, many of which are rare heterocyclic substructures. This approach has allowed the synthesis of a small library of compounds based on the pyridazine ring system with moderate skeletal and substituent diversity. The synthesis of some non-halogenated products by displacement of all ring fluorine atoms has also been reported.