Jury

  • Prof. Johan WOUTERS (UNamur), Chair
  • Prof. Steve LANNERS (UNamur), secretary
  • Prof. Stéphane VINCENT (UNamur)
  • Prof. Johan WINNE (UGent)
  • Prof. Andrew MITCHELL (Illinois State University)

Abstract

Taxpropellane is a taxane complex with a particularly elaborate structure. Although its biological properties are still unknown, its structural complexity makes it a synthetic target of choice. The approach developed in this thesis is based on a retrosynthetic simplification toward a bicyclo[5.4.0]undecane, the preparation of which requires new methodologies, in particular the development of an (5+2) oxydopyrylium cycloaddition using a temporary bridge to construct the required bicyclic compounds.

Oxydopyrylium species are highly reactive aromatic intermediates, commonly used to synthesize 7-membered rings via cycloaddition reactions. Their use for intermolecular cycloadditions is severely limited due to their rapid dimerization when the dipolarophile is not sufficiently reactive. The strategy developed in this work relies on the use of a temporary ether-type linker to overcome this limitation. Numerous bicyclic compounds have thus been efficiently synthesized using this methodology. We have shown that this diastereoselectivity depends solely on how the two reactive fragments are linked. Thus, the proposed methodology allows for complete control of stereoselectivity. The cleavage of the linker has also been investigated. This can be achieved in two different ways. This work extends the use of oxidopyrylium ions in synthesis, and this methodology will be applied to the total synthesis of taxpropellane, following the synthesis of a suitable dipolarophile also described here.