DEVELOPMENT OF NEW METHODS FOR THE SYNTHESIS OF DIHYDROPYRANS AND TETRAHYDROPYRANS

This thesis detail attempts to develop a procedure, based on the Maitland-Japp reaction, for the formation of functionalised tetrahydropyran (THP) rings. Previous work in the Clarke group has focused on the development of the Maitland-Japp reaction, but it produced mixtures of diastereomeric THPs.
The work described in this thesis details the stereocontrolled synthesis of functionalised 2,6-cis- and 2,6-trans-THP rings from dihydropyran (DHP) rings, as well as the synthesis of 3,3,6-trisubstituted THP rings. The formation of 2,6-cis THP rings was achieved by the addition of hydride nucleophiles to C2-substituted DHPs, and trapping with carbon electrophiles. Treatment of 2H-DHPs with carbon nucleophiles led to the formation of 2, 6-trans THP rings. Reduction of 2H-DHPs with L-Selectride® produce the 3,6-disubstituted THP rings, while trapping of the intermediate enolate with carbon electrophiles give formation of 3,3,6-trisubstituted THP rings.
The development of a successful method for the synthesis of functionalised THP rings led to a synthesis of the A-ring of Lasonolide A and Diospongin B.