A novel cyclization in the construction of fused rings

Abstract

The discovery of the novel thermal cyclization of enediyne molecules within the Parsons group during studies directed towards the total synthesis of lactonamycin has stimulated an intense research into the cyclization of the enediynes. In this research different functionalised enediynes were synthesised to investigate:- (i) the scope and limitations of the thermal cyclization reactions, (ii) the proposed biradical mechanism for the cyclization reactions, (iii) the intermolecular trappings of the proposed biradical, and (iv) the effect of sterically demanding groups on the rate of cyclization. In the process of testing these objectives, we have been able to synthesize highly functionalised heterocyclic rings by simple thermal cyclization reactions without using any metal catalyst. We have discovered that the cyclizations may have involved free radical mechanism or an ene reaction, followed by a Diels – Alder cycloaddition reactions. Interestingly the cyclised compound 2.1 shows two stereogenic centres at C2 and C4 with an absolute configuration of R and S respectively. An in-depth exploration of the stereochemistry of these reactions may increase their application in controlling the stereochemistry of ring systems through simple metal free thermal cyclization reactions. Confirmation of the specific mechanism constitutes an ongoing research within the Parsons group. Conclusively cyclization of highly functionalised enediynes had been proved to be a versatile route to the synthesis of diverse heterocyclic compounds. The ease of cyclizations of a majority of the enediynes in this study has shown that functionalisation and diversification of the core enediyne systems could be utilized in the synthesis of pharmaceutically important antitumour drugs