June 1998
SYNLETT
589
(6) Warrener, R. N.; Schultz, A. C.; Butler, D. N.; Wang, S.;
Mahadevan, I. B.; Russell, R. A. Chem. Commun. 1997, 1023.
(7) For an earlier report on the preparation of polarofacial molecules
based on 7-oxanorbornanes, see Warrener, R. N.; Butler, D. N.;
Liao, W. Y.; Pitt, I. G.; Russell, R. A. Tetrahedron Lett. 1991, 32,
1889.
(8) Meinwald, J.; Wiley, G. A. J. Am. Chem. Soc. 1958, 80, 3667.
(9) Mitsudo, T.; Naruse, H.; Kondo, T.; Ozaki, Y.; Watanabe, Y. Angew.
1994, , 580. Mitsudo, T.; Kokuryo, K.; Shinsugi,
33
T.; Nakagawa, Y.; Watanabe, Y.; Takegami, Y. J. Org. Chem. 1979,
44, 4492.
Chem., Int. Ed.
Scheme 4
We next turned our attention to introducing multiple nitrogen bridges
into the polynorbornane via the dual aza-ACE reaction. The required
(10) New compounds gave satisfactory 13C NMR, MS and micro
analytical data or high resolution mass spectra. Representative
physical and 1H NMR spectral data:
10
bis-aziridine 21 was prepared as outlined in Scheme 5. In this case, the
7: m.p. 149-150 °C (ethanol); 1H NMR (CDCl ) δ 1.74 (1H, d,
=
9
J
3
cyclobutene-1,2-diester groups in 19 are reluctant to add benzyl azide 6
10.9 Hz); 2.03 (1H, d, J = 10.9 Hz); 2.31 (3H, s); 2.32 (3H, s); 2.35
(1H, d, J = 6.8 Hz); 2.47 (1H, d, J = 6.8 Hz); 3.53 (3H, s); 3.66 (1H,
s); 3.84 (3H. s); 4.85 (2H, s); 6.80 (2H, s); 7.30-7.36 (5H, nm).
8: m.p. 135-136 °C (ethanol); 1H NMR (CDCl3) δ 1.92 (1H, d, J =
10.4 Hz); 2.16 (2H, d, J = 10.4 Hz); 2.33 (6H, s); 2.44 (2H, s); 3.77
(6H, s); 3.85 (2H, s); 3.98 (2H, s); 6.82 (2H, s); 7.25 (1H, t, J = 7.6
Hz); 7.31 (2H, t, J = 7.3 Hz); 7.39 (2H, d, J = 7.3 Hz).
under thermal conditions, but do so satisfactorily when compressed
15
together at 14 kbar. The resultant mixture of C -isomer 20a and σ-
2
isomer 20b is not separated but deazetised photochemically to the
10
common bis-aziridine 21.
Reaction of 21 with N-Boc-7-aza-
10
benzonorbornadiene 15 produced the [5]polynorbornane 22
containing four aza-bridges. The structure of 22 was again determined
by NMR spectral symmetry at elevated temperature.
10: m.p. 192-4 °C (methylene chloride/methanol). 1H NMR
(CDCl3) δ 1.93 (1Η, d, J = 8.9 Hz); 2.28 (6H, s); 2.48 (2H, s); 3.49
(6H, s); 3.55 (2H, s), 3.70 (1H, d, J = 8.9 Hz); 3.76 (2H, s); 3.79
(6H, s); 6.75(2H, s); 7.18-7.28 (5H, m).
12: m.p. 213−214 °C (methylene chloride/petroleum ether 40-
60oC).1H NMR (CDCl3) δ 1.35 (1Η, d, J = 9.4 Hz); 2.26 (2H, s);
2.28 (6H, s); 3.16 (2H, nm); 3.61 (1H, d, J = 9.4 Hz); 3.64 (2H, s);
3.90 (6H, s); 3.92 (2H, s); 6.77 (2H, s); 7.20 (1H, t, J = 7.9 Hz); 7.28
(2H, t, J = 7.2 Hz); 7.44 (2H, d, J = 7.2 Hz).
14: m.p. 199-200 °C (methylene chloride/methanol). 1H NMR
(CDCl3) δ 0.88 (1H, d, J = 8.9 Hz); 1.21 (1H, d, J = 9.9 Hz); 1.96
(2H, s); 2.23 (2H, s); 2.26 (6H, s); 2.44 (2H, d, J = 8.9 Hz); 2.65
(2H, s); 2.67 (1H, d, J = 9.9 Hz); 3.21 (2H, s); 3.85 (6H, s); 4.36
(2H, s); 6.05 (2H, t, J = 1.3 Hz); 6.72 (2H, s); 7.17 (1H, t, J = 7.8
Hz); 7.26 (2H, t, J = 7.3 Hz); 7.47 (2H, d, J = 7.3 Hz).
16: m.p. 129-130 °C 1H NMR (60 °C, CDCl3) δ 1.09 (1H, d, J = 9.6
Hz), 1.90 (2H, s), 2.14 (6H, s), 2.27 (2H, s), 3.04 (2H, s), 3.41 (1H,
d, J = 9.6 Hz), 3.74 (6H, s), 3.90 (2H, s), 4.91 (2H, bd s), 5.20 (2H,
s), 6.58 (2H, s), 6.99-7.30 (14H, m).
17: not isolated. 1H NMR (CDCl3) δ 2.38 (2H, s), 3.72 (6H, sbr),
3.92 (2H, s), 5.01 (2H, sbr), 5.79 (2H, s), 7.16-7.35 (14H, m).
18: 33%, m.p. 172-173 °C, 1H NMR (CDCl3, 67 °C) δ 2.06 (4Η, s),
3.68 (6H, s), 4.00 (2H, s), 4.94 (4H, s), 5.23 (4H, s), 7.02-7.30
(23H, m). Loss of symmetry occurs at ambient.
Scheme 5
In conclusion, we have shown that the aza-ACE reaction is a versatile
cycloaddition protocol and a worthy addition to our BLOCK coupling
program. The high stereoselectivity of the coupling process should
allow the production of polarofacial [n]polynorbornanes containing
multiple heterobridges and these and other novel systems will be
reported in due course.
Acknowledgments
J. R. M. acknowledges the award of a British Council Travel Grant and a
Senior CMA Visiting Fellowship. We thank Mr A. Peysan for
contributing to the early part of this project and to Dr M. Johnston for
help with advanced NMR techniques. Research Grant Programs at
Central Queensland University, Deakin University and an ARC Large
Grant helped fund this research.
21: not isolated. 1H NMR (CDCl3) δ 1.90 (2H, s), 2.15 (4H, s), 3.30
(2H, s), 3.72 (12H, s), 3.99 (4H, s), 7.22-7.40 (10H, m).
22:m.p. 181-183 °C (ether/petroleum ether); 1H NMR (CDCl3) δ
1.40 (4H, s), 1.94 (2H, s), 2.23 (4H, s), 2.71 (2H, s), 3.69 (12H, s),
3.78 (4H, s), 4.94 (4H, dbr), 5.17 (4H, s), 7.10-7.26 (28H, m).
(11) While there is a precedent for the ring-opening and trapping for the
ACE reaction (Gotthardt, H.; Huisgen, R.; Bayer, H. O. J. Am.
1970,
Chem. Soc.,
92, 4340), there is none for the aziridino
References and footnotes
cyclobutane ring-opening. Of course, the ring opening of simple
aziridines to 1,3-dipoles is well documented.12
(1) Building BLOCKs in Synthesis Part 4, for part 3, see Warrener, R.
N.; Margetic, D.; Russell, R. A. Synlett 1998, 585.
(12) R. Huisgen, "1,3-Dipolar Cycloaddition Chemistry", Ed A. Padwa,
Wiley-Interscience, 1984.
(2) on leave from Department of Chemistry, University of Leicester,
LE1 7RH, UK
(13) inter alia Davies, J. W.; Durrant, M. L.; Walker, M. P.; Belkacemi,
B.; Malpass, J. R. Tetrahedron 1992, 48, 861.
(3) Honorary visiting Professor CQU, from Department of Biological
and Chemical Sciences, Deakin University, Geelong, Victoria,
3217, Australia.
(14) Malpass, J. R.; Warrener, R. N.; Margetic, D.; Sun, G.; Butler,
D. N., 1997, unpublished results.
(4) inter alia Jones, C. D.; Simpkins, N. S. Tetrahedron Lett. 1998, 39,
1021, 1023 and references therein.
(15) Azides have been reported to react with alkenes under high
pressure. Anderson, G. T.; Henry, J. R.; Weinreb, S. M. J. Org.
Chem. 1991, 56, 6946.
(5) Sasaki, T.; Manabe, T.; Nishida, S. J. Org. Chem. 1980, 45, 476 and
479.