ORGANIC
LETTERS
1999
Vol. 1, No. 8
1181-1182
Sugar-Derived Aziridines:
Functionalization via Lithiation of the
Aziridine Ring
,†
Philippe Bisseret,* Claire Bouix-Peter, Olivier Jacques, Ste´phanie Henriot, and
Jacques Eustache*
Laboratoire de Synthe`se Organique et de Chimie Microbienne - CNRS UPRESA 7015,
UniVersite´ de Haute-Alsace, Ecole Nationale Supe´rieure de Chimie de Mulhouse,
3, Rue Alfred Werner, F-68093 Mulhouse Cedex, France
j.eustache@uniV-mulhouse.fr
Received July 21, 1999
ABSTRACT
Stereoselective preparation of a new arabinose-derived aziridine and functionalization of the corresponding N-BH complex are described.
3
Regio- and stereoselective aspects are discussed.
In the course of a project aimed at identifying inhibitors of
mycobacterial arabinosyltransferases, we needed to prepare
a series of bicyclic sugar-derived aziridines (1; Figure 1).
reported.2 The key step in the synthesis of the latter
compounds was an intramolecular 1,3-dipolar cycloaddition
of δ-azidoalkenes. This reaction, however, is not general3
and may lead to imines or diazo compounds besides (or
instead of) the desired aziridines. In addition, the use of 1,3-
dipolar cycloadditions for the preparation of each member
of a series of functionalized aziridines, as required in a
medicinal chemistry program, would obviously be cumber-
some.
Vedejs and Kendall’s recent report on the functionalization
of simple aziridine-BH3 complexes by sequential deproto-
Figure 1. Sugar-derived bicyclic aziridines.
(2) Hudlicky, T.; Luna, H.; Price, J. D.; Rulin, F. J. Org. Chem. 1990,
55, 4683-4687.
(3) The thermal decomposition of olefinic azides is still not well
understood and may yield mixtures of products; see for instance: (a)
Logothetis, A. L. J. Am. Chem. Soc. 1965, 87, 749-753. (b) Bernet, B.;
Bulusu Murty, A. R. C.; Vasella, A. HelV. Chim. Acta 1990, 73, 940-958.
(c) Kru¨lle, T. M.; dela Fuente, C.; Pickering, L.; Aplin, R. T.; Tsitsanou,
K. E.; Zographos, S. E.; Oikonomakos, N. K.; Nash, R. J.; Griffiths, R. C.;
Fleet, G. W. J. Tetrahedron: Asymmetry 1997, 8, 3807-3820.
(4) Vedejs, E.; Kendall, J. T. J. Am. Chem. Soc. 1997, 119, 6941-6942.
(5) Bouix, C.; Bisseret, P.; Eustache, J. Tetrahedron Lett. 1998, 39, 825-
828.
(6) (a) Vasella, A.; Witzig, C.; Chiara, J.-L.; Martin-Lomas, M. HelV.
Chem. Acta 1991, 74, 2073-2077. (b) Alper, P. B.; Hung, S.-C.; Wong,
C.-H. Tetrahedron Lett. 1996, 34, 6029-6032. The thermal lability of azide
4 (previously prepared once by another route) has been noted: Pearson,
W. H.; Hines, V. A. Tetrahedron Lett. 1991, 32, 5513-5516.
Although simple 1-azabicyclo[3.1.0] octanes are known,3a
few nonsubstituted sugar-derived aziridines (2, R ) H) have
been found1 and, to the best of our knowledge, only two
examples of substituted analogues (2, R * H) have been
† E-mail: p.bisseret@univ-mulhouse.fr.
(1) (a) Martin, O. R.; Saavedra, O. M. Tetrahedron Lett. 1995, 36, 4027-
4030. (b) Martin, O. R.; Saavedra, O. M. Tetrahedron Lett. 1995, 36, 799-
802. (c) Paulsen, H.; Matzke, M.; Orthen, B.; Nuck, R.; Reutter, W. Liebigs
Ann. Chem. 1990, 953-963. (d) Tong, M. K.; Ganem, B. J. Am. Chem.
Soc. 1988, 110, 312-313.
10.1021/ol990841e CCC: $18.00 © 1999 American Chemical Society
Published on Web 09/16/1999