S. M. Allin et al. / Tetrahedron Letters 43 (2002) 4191–4193
4193
The mechanism of the oxidative step (14 to 15) is not
clear but the stability of the stable p-radical intermedi-
ate (e.g. 14) is crucial.2–4,7,9 Reduction by H-abstraction
from Bu3SnH or (TMS)3SiH is unfavourable which
allows time for interception by the radical initiator
ACCN (in Bu3SnH reactions) or a radical breakdown
product from ACCN or Et3B in respective reactions.
Evidence indicates H-abstraction from the p-radical
intermediates.4,9 For the Et3B reactions the abstracting
radical is probably ethyl radical generated in the oxy-
gen-induced breakdown of Et3B. The reactions using
ACCN needed greater than one equivalent of the radi-
cal initiator indicating involvement of ACCN or break-
down products (e.g. 1-cyanocyclohex-1-yl radicals) as
has been observed in most of these Bu3SnH-mediated
‘oxidative’ cyclisations.2–11 An alternative mechanism
involving addition of 2-cyanoprop-2-yl radicals (result-
ing from AIBN) to the p-radical followed by non
radical elimination has also been proposed.5
man, W. R.; Bridge, C. F.; Brookes, P. J. Chem. Soc.,
Perkin Trans. 1 2000, 1–14.
2. Studer, A.; Bossart, M. In Radicals in Organic Synthesis;
Renaud, P.; Sibi, M. P., Eds.; Wiley–VCH: Weinheim,
2001; Vol. 2, Chapter 1.4, pp. 62–80.
3. (a) Aldabbagh, F.; Bowman, W. R.; Mann, E. Tetra-
hedron Lett. 1997, 38, 7937–7940; (b) Aldabbagh, F.;
Bowman, W. R.; Mann, E.; Slawin, A. M. Z. Tetrahedron
1999, 55, 8111–8128.
4. Allin, S. M.; Barton, W. R. S.; Bowman, W. R.; Mc-
Inally, T. Tetrahedron Lett. 2001, 42, 7887–7890.
5. Bennasar, M.-L.; Roca, T.; Griera, R.; Bosch, J. J. Org.
Chem. 2001, 66, 7547–7551.
6. (a) Harrowven, D. C.; Sutton, B. J.; Coulton, S. Tetra-
hedron Lett. 2001, 42, 9061–9064; (b) Hoarau, C.; Cou-
ture, A.; Cornet, H.; Deniau, E.; Grandclaudon, P. J.
Org. Chem. 2001, 66, 8064–8069.
7. Marco-Contelles, J.; Rodr´ıquez-Ferna´ndez, M. J. Org.
Chem. 2001, 66, 3717–3725.
8. Nadin, A.; Harrison, T. Tetrahedron Lett. 1999, 40,
4073–4076.
In contrast, the attempted cyclisation reactions with
radical precursors 10a–c which have a 3-dimethoxy-
methyl substituent, only yielded reduced uncyclised
products. Even the most favoured six-membered ring
cyclisation from precursor 10b failed. This cyclisation
was attempted with both Bu3SnH and the slower
(TMS)3SiH/Et3B protocol at room temperature. We
suggest that unlike the 4-Ph and 4-CO2Et substi-
tuents, the 3-dimethoxymethyl substituent does not
stabilise the potential cyclised radical and hence cyclisa-
tion is unfavourable.
9. Bowman, W. R.; Mann, E.; Parr, J. J. Chem. Soc., Perkin
Trans. 1 2000, 2991–2999.
10. Storey, J. M. D. Tetrahedron Lett. 2000, 40, 8173–8176.
11. Ellis, M. J.; Stevens, M. F. G. J. Chem. Soc., Perkin
Trans. 1 2001, 3180–3185.
12. Schro¨ter, H.-B.; Neumann, D.; Katritzky, A. R.; Swin-
bourne, F. J. Tetrahedron 1966, 22, 2895–2897.
13. (a) Kulinkovich, O.; Masalov, N.; Tyvorskii, V.;
Dekimpe, N.; Keppens, M. Tetrahedron Lett. 1996, 37,
1095–1096; (b) Shen, J. K.; Katayama, H.; Takatsu, N.;
Shiro, I. J. Chem. Soc., Perkin Trans. 1 1993, 2087–2097;
(c) Guzma´n-Pe´rez, A.; Maldonado, L. A. Synth. Com-
mun. 1991, 21, 1667–1674; (d) Ranganathan, D.;
Bamezai, S.; Saini, S. Indian J. Chem. Sect. B 1991, 30,
169–175; (e) Ranganathan, D.; Bamezai, S. Synth. Com-
mun. 1985, 15, 259–265; (f) Takano, S.; Imamura, Y.;
Ogasawara, K. Heterocycles 1982, 19, 1223–1225.
14. (a) Ravikanth, V.; Ramesh, P.; Diwan, P. V.;
Venkateswarlu, Y. Biochem. Syst. Ecol. 2001, 29, 753–
754; (b) Aladesanmi, S. A.; Nia, R.; Fontaine, C.; Pais,
M. Phytochemistry 1995, 35, 1053–1055; (c) Aladesanmi,
A. J.; Nia, R.; Nahrstedt, A. Planta Med. 1998, 64,
90–91.
Acknowledgements
We thank AstraZeneca (R&D Charnwood) and the
EPSRC for an EPSRC CASE Postgraduate Research
Studentship (WRSB), AstraZeneca (R&D Charnwood)
for generous funding and the EPSRC Mass Spectrome-
try Unit, Swansea University, Wales for mass spectra.
References
15. Bowman, W. R.; Bridge, C. F.; Brookes, P.; Cloonan, M.
O.; Leach, D. C. J. Chem. Soc., Perkin Trans. 1 2002,
58–68.
1. (a) Bowman, W. R.; Cloonan, M. O.; Krintel, S. L. J.
Chem. Soc., Perkin Trans. 1 2001, 2885–2991; (b) Bow-