As part of our continuing work in radical chemistry, we
have devised a flexible and efficient approach to the synthesis
of [1,2,4]triazole, imidazole, and benzimidazole derivatives.
Our synthetic design, depicted in Scheme 1, relies on the
case of xanthate 1d and olefin 2d, the presence of the acid
proved to be more crucial since the 79% yield of adduct 3f
dramatically falls to 0% yield when addition of CSA was
omitted.10 This modified protocol turned out to be quite
efficient, as demonstrated by the examples shown in Table
1. Many functional groups may be tolerated in the xanthate
Scheme 1. Synthetic Route to Functionalized Nitrogen
Heterocycles
Table 1. Radical Additions of Xanthates to Olefins 2a-d in
the Presence of Camphorsulfonic Acid
rich chemistry of xanthates.9 Thus, radical addition of
xanthate 1 to olefin 2 would lead directly to a variety of
functionalized nitrogen heterocycles 3. However, since the
xanthate functionality is sensitive to nucleophilic attack, this
radical addition fails with substrates containing basic nitrogen
functionality. We therefore modified our normal experimental
procedure by adding 1 equiv of camphorsulfonic acid (CSA)
for each basic site on the olefin. Under these conditions, the
reaction proceeded more cleanly in the case of olefins 2a,b
and the presence of acid was indispensable to obtaining
xanthate adducts with olefins 2c-e.
Indeed, when a solution of xanthate 1a, olefin 2a (2 equiv),
and CSA (2 equiv) in 1,2-dichloroethane (1 M) was heated
to reflux in the presence of a catalytic amount of lauroyl
peroxide (DLP), the 60% yield of adduct 3a obtained without
the presence of the acid was improved to 75% yield. In the
(5) (a) Allin, S. A.; Barton, W. R. S.; Bowman, W. R.; McInally, T.
Tetrahedron Lett. 2002, in press. (b) Allin, S. A.; Barton, W. R. S.; Bowman,
W. R.; McInally, T. Tetrahedron Lett. 2001, 42, 7887. (c) Aldabbagh, F.;
Bowman, W. R.; Mann, E.; Slawin, A. M. Z. Tetrahedron 1999, 55, 8111.
(d) Aldabbagh, F.; Bowman, W. R. Tetrahedron 1999, 55, 4109. (e)
Aldabbagh, F.; Bowman, W. R.; Mann, E. Tetrahedron Lett. 1997, 38, 7937.
(f) Aldabbagh, F.; Bowman, W. R. Tetrahedron Lett. 1997, 38, 3793.
(6) Marco-Contelles, J.; Rodr´ıguez-Ferna´ndez, M. J. Org. Chem. 2001,
66, 3717.
(7) (a) Bennasar, M.-L.; Roca, T.; Griera, R.; Bosch, J. J. Org. Chem.
2001, 66, 7547. (b) Byers, J. H.; Kosterlitz, J. A.; Steinberg, P. L. C. R.
Acad. Sci. Paris, Chem. 2001, 4, 471. (c) Ziegler, F. E.; Belema, M. J.
Org. Chem. 1997, 62, 1083. (d) Moody, C. J.; Norton, C. L. J. Chem. Soc.,
Perkin Trans. 1 1997, 2639. (e) Moody, C. J.; Norton, C. L. Tetrahedron
Lett. 1995, 36, 9051.
a The adduct was obtained in 60% yield without addition of CSA.
b Tetralone 4 was also isolated in 10% yield. c Rapid degradation was
observed and no adduct was obtained when CSA was not added.
(8) Antonio, Y.; De La Cruz, E.; Galeazzi; E.; Guzman, A.; Bray, B. L.;
Greenhouse, R.; Kurtz, L. J.; Lustig, D. A.; Maddox, M. L.; Muchowski,
J. M. Can. J. Chem. 1994, 72, 15.
(9) (a) Quiclet-Sire, B.; Zard, S. Z. Phosphorus, Sulfur Silicon 1999,
137. (b) Quiclet-Sire, B.; Zard S. Z. Angew. Chem., Int. Ed. Engl. 1997,
36, 672.
(10) Rapid degradation of the starting material was observed.
(11) For the synthesis of tetralones by radical cyclisation, see: Liard,
A.; Quiclet-Sire, B.; Saicic, R. N.; Zard, S. Z. Tetrahedron Lett. 1997, 38,
1759.
(12) For the synthesis of benzazepinones by radical cyclization, see:
Kaoudi, T.; Quiclet-Sire, B.; Seguin, S.; Zard S. Z. Angew. Chem., Int. Ed.
2000, 39, 731.
as well as in the olefinic partner, allowing the synthesis of
a variety of functionalized nitrogen heterocycles.
More complex molecules may be constructed by further
transformation of the xanthate adduct. In the case of adducts
3b and 3c, refluxing in 1,2-dichloroethane with 1 equiv of
CSA and the gradual addition of a stoichiometric amount of
peroxide induced ring closure onto the aromatic ring to give
the corresponding tetralone 4 in 75% yield and benz-
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Org. Lett., Vol. 4, No. 24, 2002