Novel Approaches to Industrially
Important Polyhalides Using Free Radicals
| Jenny M. Barks,a Bruce C. Gilbert,b
Andrew F. Parsonsb and Bala Upeandranb
aSyngenta Technology and Projects, Leeds Road, Huddersfield,
HD2 1FF, UK
bDepartment of Chemistry, University of York, Heslington,
York, YO10 5DD, UK |
 |
There are a considerable number of polyhalogenated molecules of industrial
(particularly agrochemical) importance, which contain the -CCl3
and related groups. This functional group is found in more than 35000 organic
compounds and many of these compounds exhibit a wide range of biological
activity. For example, compounds 1 and 2 have strong insecticidal
activities.
This project explores new free radical based reactions which can be used
to produce carbon-centred polyhalogenated radicals from polyhalogenated
alkane precursors (e.g. CHCl3, CCl4, BrCCl3,
CF3CCl3, etc.) using radical initiators. The resultant
halogenated radicals (e.g. Cl3C.)
can be trapped with a variety of alkenes in inter- or intra-molecular carbon-carbon
bond forming reactions to give a range of halogenated products (Scheme
1).
Scheme 1
A THF-mediated radical addition-cyclisation reaction of a variety of
alkenes or dienes to form acyclic or cyclic derivatives under mild, neutral
reaction conditions has been investigated. Low yields were observed for
intermolecular addition reactions but moderate to good yields of cyclic
products were obtained from dienes. The major by-product when using
BrCCl3 was bromoacetal 3, which was formed from THF and
BrCCl3 in a competing ionic reaction.
This work then led to the development of a new method for alcohol protection.
The method works extremely well when using THF and good to excellent yields
of THF ethers were obtained from primary or secondary alcohols.2
Scheme 2
In addition, organophosphorus mediated radical addition-cyclisation
reactions using diphenylphosphine oxide or diethyl phosphite (as the hydrogen
atom donor) have been developed. Good to excellent yields of cyclic products
were obtained when using diethyl phosphite, CCl4 and a series
of dienes in a variety of solvents.3
Scheme 3
This methodology will be applied to the synthesis of biologically important
natural products (e.g. pyrethrins, kainic acid analogues., etc.).
1. M. S. Kharasch, E. V. Jensen and W. H. Ury, Science, 1945,
102,
128.
2. J. M. Barks, B. C. Gilbert, A. F. Parsons and B. Upeandran, Tetrahedron
Lett., 2000, 41, 6249.
3. J. M. Barks, B. C. Gilbert, A. F. Parsons and B. Upeandran, Tetrahedron
Lett., 2001, 42, 3137.
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