STEREOSELECTIVE TRANSFORMATIONS OF INTRAMOLECULAR CYCLOADDITION PRODUCTS

In this work, the intramolecular cycloaddition of furan dienes was investigated. At equilibrium, amide-tethered substrates form acyclic precursor : cycloadduct mixtures. Higher portion of cycloadduct proved to be favoured by bulky nitrogen-groups, polar solvents, higher temperature and the presence of some Lewis acids. It was demonstrated that the equilibrium can be displaced by coupling a reversible Diels-Alder cycloaddition to an irreversible and chemoselective reaction, such as Pd-catalysed hydrogenation or mCPBA epoxidation, resulting in the complete transformation of the mixture starting material to the functionalised cycloadduct. A range of asymmetric transformations were also investigated to resolve the racemic mixture derived from the Diels-Alder reaction. The Sharpless dihydroxylation showed a high level of chemoselectivity but it was not able to discriminate between the cycloadduct enantiomers. The Jacobsen epoxidation was not chemoselective but, in absence of Diels-Alder starting material, produced cycloadduct epoxides in modest enantioselectivity via kinetic resolution and dynamic kinetic resolution. Non-symmetrical transformation of the olefin, by asymmetric hydroboration-oxidation, provided regioisomeric alcohols in good enantiomeric excess by regiodivergent resolution.