Development and application of the vinylepoxide – dihydrofuran rearrangement

Abstract

The vinylepoxide - diliydrofuran rearrangement offers a route to substituted 2,3- dihydrofurans with a high degree of diastereoselectivity. The rearrangement proceeds via an ylide-type intermediate arising from the thermolysis of a carbon-carbon epoxide bond. This thesis discusses work aimed at developing the rearrangement, introducing asymmetric control, and application of the dihydrofuran products in target molecule synthesis. Synthesis of the vinylepoxide rearrangement precursors is described, and development of the rearrangement to achieve a moderate scale rearrangement process is discussed. Alternative rearrangement technologies are also explored. Asymmetric induction into the rearrangement was approached by the use of chiral auxiliaries and in particular C2 symmetric amines. A novel synthesis of (S,S)-2,5-diphenylpyrrolidine and (S,S)-2,6-diphenylpiperidine is reported. High degrees of enantiomeric purity were achieved through the application of an effective oxazaborolidine catalyst in the reduction of dibenzoylethane and dibenzoylpropane. Use of this chiral reduction catalyst on further diketones is described. Application of the dihydrofuran products in the synthesis of several 2,6-disubstituted- 3,7-dioxabicyclo[3.3.0]octanes. These compounds, commonly termed furofuran lignans exhibit a wide range of biological properties. The dihydrofuran products were combined with a range of dimethylacetals, in a one pot synthesis, with high degrees of stereocontrol, by a Noyori type transacetalisation. Further derivatisation of these bicyclic compounds was accomplished and is discussed.Finally, with the vinylepoxide - dihydrofuran rearrangement established a preliminary exploration of the related vinylaziridine - 2-pyrroline rearrangement is reported.