Synthesis of Heterocyclic Ring Systems via Intramolecular Diels-Alder Furan Reactions

Investigations into the use of the intramolecular Diels-Alder furan cycloaddition (IMDAF) reaction for synthesis of complex polycyclic compounds were carried out. Studies towards a synthesis of the core structure of the akuammiline alkaloid picrinine were commenced, in parallel with an investigation into the potential for asymmetric catalysis on model IMDAF substrates. IMDAF cycloadditions of ether and ester-containing substrates were attempted in the presence of Lewis acids and imidazolidinone catalysts. Substrates containing dienophiles bearing two electron-withdrawing groups underwent uncatalysed cyclisation readily, whereas unactivated substrates were unreactive even in the presence of catalysts. Studies were begun towards an alternative approach, where the reversible cycloaddition is coupled to an irreversible asymmetric transformation in a dynamic kinetic resolution process.

Copper-catalysed N-arylation of oxindole with 2-bromofuran delivered a potentially useful intermediate for the picrinine synthesis, containing diene and all necessary tether atoms for the cycloaddition. It was shown that under the reaction conditions, oxidation of the product to the corresponding isatin was a competing side reaction, an important observation for future optimisation of this reaction.