Approaches to the Synthesis of Highly Substituted Aromatic and Fused Rings: Metal-Catalysed versus Thermal Cyclisation

A domino reaction has been used for the construction of lactonamycin derivatives. This research led to a comparison study between palladium-mediated cascade cyclisations and thermal alkyne [2+2+2] cyclisations. A palladium-mediated cyclisation of alkenyl bromides with alkynes and furans has been shown to furnish highly substituted aromatic rings. Penta- and hexasubstituted aromatic rings have also been prepared by the thermolysis of suitably substituted alkynes under microwave conditions. Tetrasubstituted pyridines can also be prepared using nitriles instead of alkynes. This work will provide a new and interesting array of drug templates; mechanistic details are discussed for both reaction series.