J. J. Chen et al. / Tetrahedron Letters 43 (2002) 4083–4085
4085
Preparation of tetrazole (Table 2, 7c): Benzaldehyde
(0.10 ml, 0.9 mmol) and piperidine (0.11 ml, 1.26
mmol) were mixed in THF/MeOH (1/1) for 5 h. TMS-
N3 (0.12 ml, 0.9 mmol) was added. The solution was
then added to the resin 1 (0.2 g, 0.18 mmol) and the
suspension was agitated for 16 h. The resin was washed
with MeOH, DMF, MeOH and dichloromethane
(DCM), followed by cleavage with 15% TFA/DCM
(2×15 min). The cleavage filtrate was collected and
evaporated to dryness. The crude product was purified
on preparative HPLC to yield 39 mg of the product
(89%).11
5. For preparations of diketopiperazine and benzodi-
azepines via Ugi MCR, see: (a) Keating, T. A.; Arm-
strong, R. W. J. Org. Chem. 1996, 61, 8935; (b) Hulme,
C.; Cherrier, M. P. Tetrahedron Lett. 1999, 40, 5296–
5299; (c) Hulme, C.; Ma, L.; Kumar, V. N.; Krolikowski,
P. H.; Allen, A. C.; Labaudiniere, R. Tetrahedron Lett.
2000, 41, 1509–1514.
6. The structure of 4c and 4d:
Acknowledgements
7. (a) Ugi, I. Angew. Chem., Int. Ed. Engl. 1962, 1, 8; (b)
Nixey, T.; Kelly, M.; Hulme, C. Tetrahedron Lett. 2000,
41, 8729–8733.
8. For recent progress on tetrazole chemistry, see: Butler, R.
N. In Comprehensive Heterocyclic Chemistry; Katritzky,
A. R.; Rees, C. W.; Scriven, E. F. V., Eds; Pergamon:
Oxford, UK, 1996; Vol. 4.
The author thanks Mr. Thomas Burt and Ms. Anne
Russell for their analytical support.
References
9. There are only few practical routes to 5-substituted 1H-
tetrazoles, see: Demko, Z. P.; Sharpless, K. B. J. Org.
Chem. 2001, 66, 7945–7950, and references cited therein.
10. Spectral data for 4a: 1H NMR (300 MHz, CD3OD, l)
7.68 (m, 2H), 8.10 (m, 1H), 7.52 (m, 3H), 7.93 (m, 1H),
6.03 (s, 1H), 3.89 (s, 3H), 3.80 (m, 4H) 3.12 (m, 4H).
13C{1H} (150 MHz, CD3OD, l) 28.1, 39.8, 46.3, 51.6,
55.5, 69.1, 113.4, 113.8, 120.0, 130.3, 137.5, 160.3, 166.1,
168.5. MS (DCI): m/z 291 [M+H]+.
1. Chen, J. J.; Golebiowski, A.; McClenaghan, J.; Klopfen-
stein, S. R.; West, L. Tetrahedron Lett. 2001, 42, 2269–
2271.
2. For a recent reviews on Ugi and Passerini reactions, see:
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3168–3210.
3. Keating, T. A.; Armstrong, R. W. J. Am. Chem. Soc.
1996, 118, 2574–2583.
11. Spectral data for 7c: 1H NMR (300 MHz, CD3OD, l)
7.69 (m, 2H), 7.52 (m, 3H), 6.04 (s, 1H), 3.25 (m, 4H),
1.87 (m, 4H) 1.66 (m, 2H). 13C{1H} (150 MHz, CD3OD,
l) 21.5, 22.8, 52.6, 65.6, 129.6, 130.1, 130.6, 130.7. MS
(DCI): m/z 244 [M+H]+.
4. For other examples of universal isonitriles, see: (a)
Hulme, C.; Peng, J.; Morton, G.; Salvino, J. M.; Herpin,
T.; Labaudiniere, R. Tetrahedron Lett. 1998, 39, 7227–
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