[73462-83-6]  · C12H17N3O2  · (235.29)

(reagent used in cycloaddition reactions1 as a dienophile of high reactivity for the trapping of unstable intermediates,2,3 and 1,3-dienes,4 the preparation of optically active axially symmetric molecules,5 and the resolution of hydrocarbons and chiral dienes6,7)

Alternate Name: 4-(1,7,7-trimethylbicyclo[2.2.1]hept-2-yl)-[1,2,4]triazole-3,5-dione.

Physical Data: mp 152-154 °C; sublimation point 75-85 °C at 0.1 Torr; [a]20D -77 (c 5.7, CH2Cl2)

Form Supplied in: red solid prepared from optically pure d-camphor oxime8 in a five-step sequence (1): reduction with sodium in n-amyl alcohol followed by fractional recrystallization of the resulting hydrochloride salts of bornylamines9,10 gives the endo-isomer in enantiomerically pure form; treatment with phosgene and direct condensation of the isocyanate with (ethoxycarbonyl)hydrazine gives a compound which cyclizes upon treatment with base; subsequent nitrogen dioxide oxidation furnishes (-)-endo-bornyltriazolinedione as a red crystalline solid.11-13

Form Supplied in: 

Handling, Storage, and Precautions: stable for prolonged periods when stored cold in the absence of light; easy to handle; solid.

The main interest in (-)-endo-bornyltriazolinedione resides with its high dienophilic character in cycloaddition processes to yield separable mixtures of diastereoisomeric urazoles. The non-destructive resolution of cyclooctatetraenes, which allows direct access to optically pure derivatives, is a typical illustration and has been amply demonstrated.14-19 Typically, (-)-endo-bornyltriazolinedione is heated with racemic 1,2,3-trimethylcyclooctatetraene in ethyl acetate to afford a mixture of diastereoisomeric adducts, which can be separated by fractional recrystallization from ethyl acetate and hexane. HPLC is an alternative separation technique leading to both enantiomerically pure antipodes. The chiral auxiliary is subsequently removed by basic hydrolysis-manganese dioxide oxidation to afford the optically pure cyclooctatetraenes (2).

This method of resolution of polyolefins has been extensively studied for cyclooctatetraene systems where excellent enantiomeric excesses are normally observed. Lanthanide-induced shifting can be used to determine the diastereoisomeric composition of the urazoles.14 Alternate means for the resolution of polyenes based on kinetic resolution using (+)-tetra-2-pinanylborane have been described,20,21 but this reagent consumes valuable substrate. Chiral platinum complexes22 can also be used but at prohibitive cost on a large scale and with poor regioselectivity when several coordination sites are present.

The utilization of an optically active triazolinedione for asymmetric transfer has also led to the preparation of enantiomerically pure polycyclic hydrocarbons. The method provides a straightforward means for introducing optical activity into chiral propellanes that possess a conjugated diene unit. Racemic propellane5 reacts with (-)-endo-bornyltriazolinedione in ethyl acetate at -78 °C to give, after HPLC separation, the two optically pure urazoles. Subsequent reduction with lithium aluminum hydride affords the two propellanes in enantiomerically pure form (3).

From a purely synthetic viewpoint, triazolinedione adducts have served as substrates for gaining access to numerous target molecules such as prismane,23 semibullvalene,24 bridged semibullvalenes,25 elassovalene,26 caged compounds,27 and azoalkanes. Indeed, the title reagent can be used not only as a chiral source, but also as an azo donor. In the synthesis of 4,5-diazatwis-4-ene,28 for example, (-)-endo-bornyltriazolinedione was a pivotal reactant that allowed incorporation of the azo unit in addition to providing a means for resolution. The first step involved cycloaddition to cyclooctatetraene dibromide with formation of a separable mixture of diastereoisomers. Eventual removal of the chiral moiety in a modified hydrolysis-oxidation sequence yielded the desired azo compound (4).

The high crystallinity of the urazole obtained by cycloaddition has also made (-)-endo-bornyltriazolinedione a useful reagent for obtaining crystalline derivatives. Diels-Alder cycloaddition of (-)-endo-bornyltriazolinedione to a diene of unknown configuration resulted in the formation of a single cycloadduct4 whose structure was confirmed by X-ray diffraction analysis of the urazole (5).

Applications of (-)-endo-bornyltriazolinedione to asymmetric synthesis in cycloaddition reactions have shown low levels of induction. In the examples studied, (-)-endo-bornyltriazolinedione reacted almost instantaneously with various dienes even at low temperature (<96 °C) resulting in low asymmetric induction (<10%).29 The high reactivity of triazolinedione in [4+2] p-cycloadditions due to its high dienophilicity minimized differentiation between the transition states and has to date impeded its use in asymmetric synthesis.

Related Reagents.

4-phenyl-1,2,4-triazoline-3,5-dione; (-)-(a)-(methylbenzyl) triazolinedione; (dehydroabiethyl)triazolinedione; (+)-tetra-2-pinanylborane; chiral platinum complexes.

1. Diels, O., Chem. Ber. 1914, 47, 2183.
2. Paquette, L. A.; Wang, T. Z., J. Am. Chem. Soc. 1988, 110, 3663.
3. Horn, K. A.; Browne, A. R.; Paquette, L. A., J. Org. Chem. 1980, 45, 5381.
4. Paquette, L. A.; Bzowej, E. I.; Kreuzholz, R., Organometallics 1996, 15, 4857.
5. Klobucar, W. D.; Paquette, L. A.; Blount, J. F., J. Org. Chem. 1981, 46, 4021.
6. Gardlik, J. M.; Paquette, L. A., Tetrahedron Lett. 1979, 20, 3597.
7. Paquette, L. A.; Doehner, R. F.; Jenkins, J. A.; Blount, J. F., J. Am. Chem. Soc. 1980, 102, 1188.
8. von Auwers, K., Chem. Ber. 1889, 22, 605.
9. Forster, M. O., J. Chem. Soc. 1898, 386.
10. Hückel, W.; Rieckmann, P., Justus Liebigs Ann. Chem. 1959, 625, 1.
11. Cookson, R. C.; Gilani, S. S. H.; Stevens, I. D. R., Tetrahedron Lett. 1962, 3, 615.
12. Cookson, R. C.; Gilani, S. S. H.; Stevens, I. D. R., J. Chem. Soc. (C) 1967, 1905.
13. Goering, H. L.; Eikenberry, J. N.; Koermer, G. S., J. Am. Chem. Soc. 1971, 93, 5913.
14. Paquette, L. A.; Trova, M. P.; Luo, J.; Clough, A. E.; Anderson, L. B., J. Am. Chem. Soc. 1990, 112, 228.
15. Paquette, L. A.; Trova, M. P., Tetrahedron Lett. 1986, 27, 1895.
16. Paquette, L. A.; Hanzawa, Y.; Hefferon, G. J.; Blount, J. F., J. Org. Chem. 1982, 47, 265.
17. Klobucar, W. D.; Burson, R. L.; Paquette, L. A., J. Org. Chem. 1981, 46, 2680.
18. Paquette, L. A.; Hanzawa, Y.; McCullough; K. J.; Tagle, B.; Swenson, W.; Clardy, J., J. Am. Chem. Soc. 1981, 103, 2262.
19. Paquette, L. A.; Gardlik, J. M.; Johnson, L. K.; McCullough, K. J., J. Am. Chem. Soc. 1980, 102, 5026.
20. Brown, H. C.; Ayyangar, N. R.; Zweifel, G., J. Am. Chem. Soc. 1964, 86, 397.
21. Brown, H. C.; Ayyangar, N. R.; Zweifel, G., J. Am. Chem. Soc. 1964, 86, 1071.
22. Cope, A. C.; Moore, W. R.; Bach, R. D.; Winkler, J. S., J. Am. Chem. Soc. 1970, 92, 1243.
23. Katz, T. J.; Acton, N., J. Am. Chem. Soc. 1973, 95, 2738 and references therein.
24. Paquette, L. A., J. Am. Chem. Soc. 1970, 92, 5765 and references therein.
25. Burson, R. L.; Paquette, L. A., Tetrahedron 1978, 34, 1307 and references therein.
26. Paquette, L. A.; Wallis, T. G.; Kempe, T.; Christoph, G. G.; Springer, J.; Clardy, J., J. Am. Chem. Soc. 1977, 99, 6946 and references therein.
27. Paquette, L. A.; James, D. R.; Birnberg, G. H., J. Am. Chem. Soc. 1974, 96, 7454 and references therein.
28. Jenkins, J. A.; Doehner, R. F.; Paquette, L. A., J. Am. Chem. Soc. 1980, 102, 2131.
29. Paquette, L. A.; Doehner, R. F., J. Org. Chem. 1980, 45, 5105.

Fabrice Gallou

The Ohio State University, Columbus, OH, USA

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