Radical cascades in synthesis
Nature utilises several modes of construction to synthesise a plethora of
important polycyclic natural products. This is illustrated in a brief summary in
the Introduction which describes the electrophilic processes involved in
terpene biosynthesis. The attempts made by synthetic organic chemists to
mimic these electrophilic reactions are then described, and the concept of
exploiting tandem, free radical reactions in such processes is then introduced.
Chapter Two examines the uses of tandem, free radical processes with the
ultimate goal of an efficient and flexible synthesis of the CD-ring portion
found in vitamin D3. A review of investigations into the use of tandem radical
macrocyclisation-transannulations and also sequential radical cyclisations is
presented as the background to our work in this area. Application of these
strategies towards the synthesis of the CD-portion of vitamin D3 has
culminated in the synthesis of a range of interesting substituted 5,6- and 6,6-
ring fused carbobicycles.
A related study of radical-mediated transannulation reactions in medium and
large ring, naturally occurring terpenes is described in Chapter Three.
Successful transannulation of the II-membered ring sesquiterpene humulene,
via a radical addition-transannulation process, is presented along with a
discussion of product manipulation to provide a crystal suitable for X-ray
analysis. Finally, our attempts to cyclise the diterpenes (+)-cembrene, (+)-isocembrene
and (+)-cembrenene under a variety of similar radical conditions are