M. W. Carland et al. / Tetrahedron Letters 42 (2001) 4737–4739
4739
SeCH2Ph
Cl
SeCH2Ph
Cl
O
Cl
O
NH2
KH / THF
SeCH2Ph
N
O
Cl
Cl
Cl
N
H
21
23 (59%)
22 (68%)
NaI / acetone
Se
I
Se
N
SeCH2Ph
O
NaI
N
N
22
O
O
Ph
O
25
24 (44%)
Scheme 4.
References
under reflux, the selenocycle (20) was isolated in 18%
yield (Scheme 3).
1. (a) Schiesser, C. H.; Wild, L. M. Tetrahedron 1996, 52,
13265–13314; (b) Walton, J. Acc. Chem. Res. 1998, 31,
99.
Our alternative approach to these classes of compound
began with the previously reported 3,3-dichloro-2,2-
dimethylpropionyl chloride15 (21) which was converted
firstly into the corresponding benzylseleno amide (22)
by reaction with 2-benzylselenoaniline and then into the
chloroazetidinone (23) following the general procedure
reported by Beckwith and Boate.15 To our surprise,
treatment of chloride (23) with one equivalent of
sodium iodide in acetone did not provide the expected
iodide, rather, the ring-closed selenopenem nucleus (24)
was obtained in 44% isolated yield (Scheme 4).16 Pre-
sumably the corresponding iodide is formed in situ, but
undergoes rapid intramolecular attack by the nucleo-
philic benzylseleno moiety to provide 24. Indeed, this
transformation represents a further example of the syn-
thetic utility of the intramolecular nucleophilic chem-
istry associated with benzyl selenides.8,9
2. Lyons, J. E.; Schiesser, C. H.; Sutej, K. J. Org. Chem.
1993, 58, 5632.
3. Fong, M. C.; Schiesser, C. H. J. Org. Chem. 1997, 62,
3103.
4. Laws, M. J.; Schiesser, C. H.; White, J. M.; Zheng, S.-L.
Aust. J. Chem. 2000, 53, 277.
5. Fong, M. C.; Schiesser, C. H. Tetrahedron Lett. 1993, 34,
4347.
6. Lucas, M. A.; Nguyen, O. T. K.; Schiesser, C. H.; Zheng,
S.-L. Tetrahedron 2000, 56, 3995.
7. (a) Engman, L.; Laws, M. J.; Malmstro¨m, J.; Schiesser,
C. H.; Zugaro, L. M. J. Org. Chem. 1999, 64, 6764; (b)
Al-Maharik, N.; Engman, L.; Malmstro¨m, J.; Schiesser,
C. H. J. Org. Chem., submitted.
8. Fong, M. C.; Laws, M. J.; Schiesser, C. H. Aust. J.
Chem. 1995, 48, 1221.
9. Lucas, M. A.; Schiesser, C. H. J. Org. Chem. 1998, 63,
3032.
10. Henry, C. M. Chem. Eng. News 2000, March, 41.
11. Williams, D. H.; Bardsley, B. Angew. Chem., Int. Ed.
1999, 38, 1172.
In order to demonstrate the generality of this method-
ology, the acyl-substituted selenopenem (25) was pre-
pared in an analogous manner starting with 21 and the
readily available 2-benzylseleno-4-benzoylaniline in
39% yield.
12. Alpegiani, M.; Bedeschi, A.; Franceschi, G.; Perrone, E.
Tetrahedron Lett. 1986, 27, 3041.
In summary, we report that the selenocephem and
selenopenam nuclei are conveniently prepared by either
intramolecular homolytic or nucleophilic substitution
chemistry involving the benzylseleno moiety. These
compounds and further derivatives which are currently
under investigation are expected to exhibit interesting
biological properties.
13. These transformations were always accompanied by the
formation of quantities of dibenzyl diselenide, pre-
sumably formed through elimination processes competi-
tive with alkylation. When poorer electrophiles were
employed (e.g. MeI), dibenzyl diselenide became the only
identifiable product.
14. Duddeck, H. Prog. Nucl. Magn. Reson. Spectrosc. 1995,
27, 1.
15. Beckwith, A. L. J.; Boate, D. R. J. Org. Chem. 1988, 53,
4339.
Acknowledgements
16. This transformation is catalytic in sodium iodide. While
5–10% mol NaI will effect cyclisation, the reaction pro-
ceeds at a more convenient rate with the addition of one
equivalent of NaI. In our hands, addition of more than
one equivalent proved detrimental with lower yields of
product.
Generous support from the Australian Research Coun-
cil is gratefully acknowledged. The award of a Mel-
bourne University Research Scholarship to M.W.C. is
also acknowledged.
.