The research described in this thesis covers two fields of investigation:
1) Biaryl and styrene Synthesis by Cross-Coupling of Fluorous-tagged Photo-activated
Arylgermanes and Towards the Preparation of Boscalid and Analogues
Biaryls are generally prepared by cross-coupling between aryl metals. However, even the
most robust of these aryl metal species cannot be carried through complex synthetic
sequences due to their reactivity particularly towards electrophiles. In this thesis, the
development of trialkylgermanes as ‘safety-catch’ coupling precursors for biaryl and styrene
synthesis was achieved. The safety-catch germanes are fluorous-tagged to facilitate parallel
synthesis using fluorous SPE techniques and are activated towards Pd(0)-catalysed
cross-coupling with aryl bromides by oxidative photolysis using a UV lamp. The stability
profile of the fluorous-tagged arylgermanes was examined. They are stable under strong
basic, nucleophilic and reductive conditions but labile in acidic and oxidative environments.
This stability profile provides unique opportunities for synthetic route design in target
orientated syntheses by allowing the germane group to be installed early in the sequence but
only activated for cross-coupling when required. This method has been applied to the
synthesis of the plant anti-fungal agent boscalid® and its alkynyl derivatives.
2) Novel Protocol for Solid Phase Synthesis of Radio-iodinated Ligands for Imaging
of Cannabinoid Receptors in the Brain
Rimonabant® is a CB1 receptor antagonist indicated for the treatment of obesity, metabolic
syndrome, addiction and smoking cessation. Radio-labelled analogues are potential PET
(Positron Emission Tomography) and SPECT (Single Photon Emission Computed
Tomography) imaging agents for visualising the distribution of cannabinoid receptors in
the brain for medical research. Conventional methods for the preparation of radio-iodinated
cannabinoid receptor ligands employ organostannane precursors which undergo
electrophilic ipso-iododestannylation with concomitant formation of toxic organostannane
by-products. Rigorous removed of organostannane residues is necessary prior to injection
the ligand for in vivo experiments. In this thesis, a novel, non-toxic, solid-supported and
facile approach for the parallel synthesis of iodinated cannabinoid receptor ligands based
on the skeleton of rimonabant has been demonstrated.