[603-35-0]  · C18H15P  · Triphenylphosphine-2,4,5-Triiodoimidazole  · (MW 262.30) (2,4,5-triiodoimidazole)

[1746-25-4]  · C3HI3N2  · Triphenylphosphine-2,4,5-Triiodoimidazole  · (MW 445.76)

(deoxygenation of vicinal diols1 and epoxides to form alkenes; conversion of alcohols to iodides)

Physical Data: see Triphenylphosphine; 2,4,5-triiodoimidazole, mp 190-192 °C.

Preparative Methods: the reagent reported by Garegg and Samuelsson1,2 is prepared in situ by the combination of a 1:2 ratio of Triphenylphosphine and 2,4,5-triiodoimidazole in toluene or, preferably, toluene/acetonitrile.3 2,4,5-Triiodoimidazole is prepared via the treatment of Imidazole with Iodine and Sodium Hydroxide in a two-phase reaction in water/petroleum ether and recrystallized from methanol.3

General Discussion.

Triphenylphosphine-2,4,5-triiodoimidazole-imidazole was introduced as a alternative to the combination of triphenylphosphine-iodine-imidazole4-8 for the deoxygenation of vicinal diols. Subsequently, the mixture Triphenylphosphine-Iodoform-Imidazole9 and, more recently, Chlorodiphenylphosphine-iodine-imidazole10 were introduced as other alternative phosphine-derived reagents for diol reductive elimination. Methods for the conversion of vicinal diols to alkenes have found significant utility in organic synthesis and a number of nonphosphine-based methods have also been developed.11 Treatment of methyl 2,6-dibenzyl-a-D-glucopyranoside with triphenylphosphine-2,4,5-triiodoimidazole in a 2:1 excess over the substrate affords the unsaturated sugar in a reported 95% yield (eq 1).1 This conversion was recently used in the preparation of hexose nucleoside analogs.12

Samuelsson1 and others13 report that the reagent works best in the case of trans-diequatorial or trans-diaxial diols; however, Ozaki and co-workers14 used the reagent effectively on a mixture of cis- and trans-diols. Treatment of a 2:3 cis:trans mixture of diols affords the alkene (73% yield) (eq 2), which can subsequently be used in the synthesis of optically active inositol derivatives.

Kibayashi15 found the reagent useful in a synthesis of indolizidine 195B (gephyrotoxin 195B). Deoxygenation of the trans-diol affords the unsaturated nitrogen heterocycle in 79% yield (eq 3). Small amounts of the corresponding epoxide are isolated, suggesting that the deoxygenation proceeds via initial formation of the epoxide. Kibayashi modified the Samuelsson procedure with the addition of Zinc powder, a modification that had earlier been employed for the phosphine-iodine based deoxygenation of epoxides.4 Kibayashi suggests that the deoxygenation is stereospecific, although to date only the reactions of cyclic diols have been reported.

It is reported that the deoxygenation of a furanoside leads to formation of a furan,16 but Yoda employed Kibayashi's modified procedure to prepare optically active butenolides in 59-78% yield (eq 4).17

The triphenylphosphine-2,4,5-triiodoimidazole-imidazole mixture has also found use as an alternative to the more frequently used triphenylphosphine-iodine-imidazole2 mixture for the conversion of alcohols to iodides. For example, the iodide in eq 5 is prepared in 69% yield and used in the total synthesis of the antibiotic A23187.18 Furthermore, the conversion proceeds with clean inversion of configuration and the conditions are sufficiently mild to tolerate the presence of a benzyloxymethyl protecting group (eq 6).19,20

The reagent has found use in the conversion of hydroxy groups to iodides in carbohydrate substrates. For example, treatment of the protected furanose in eq 7 affords the corresponding iodide with clean inversion of configuration (78% yield).2,21 In some cases, secondary hydroxyl groups need not be protected. For example, treatment of benzyl 2-acetamido-2-deoxy-a-D-glucopyranoside with 4 equiv of triphenylphosphine and 2 equiv of 2,4,5-triiodoimidazole in toluene-acetonitrile (2:1) affords the corresponding 6-iodo derivative in 70% yield (eq 8).3 Toluene-acetonitrile solvent is reported to be superior to toluene alone, and other solvent systems may be applicable.22 Other selective substitutions in carbohydrates substrates are often possible.3,23

The corresponding triphenylphosphine-2,4,5-tribromoimidazole reagent behaves similarly.3,20,24

1. Garegg, P. J.; Samuelsson, B. S 1979, 10, 813.
2. Garegg, P. J.; Samuelsson, B. CC 1979, 22, 978.
3. Garegg, P. J.; Johansson, R.; Ortega, C.; Samuelsson, B. JCS(P1) 1982, 681.
4. Garegg, P. J.; Samuelsson, B. S 1979, 10, 469.
5. Garegg, P. J.; Johansson, R.; Samuelsson, B. J. Carbohydr. Chem. 1984, 3, 189.
6. Menicagli, R.; Malanga, C.; Pecunioso, A.; Lardicci, L. G 1985, 115, 23.
7. Pakulski, Z.; Zamojski, A. Carbohydr. Res. 1990, 205, 410.
8. Boldt, P.; Arensmann, E.; Blenke, M.; Kersten, H.; Tendler, H.; Trog, R.-S.; Jones, P. G.; Doering, D. CB 1992, 125, 1147.
9. Bessodes, M.; Abushanab, E.; Panzica, R. P. CC 1981, 26.
10. Liu, Z.; Classon, B.; Samuelsson, B. JOC 1990, 55, 4273.
11. Block, E. OR 1984, 30, 457.
12. Augustyns, K.; Vandendriessche, F.; Aerschot, A. V.; Busson, R.; Urbanke, C.; Herdewijn, P. Nucleic Acids Res. 1992, 20, 4711.
13. Kjolberg, O.; Neumann, K. ACS 1992, 46, 877.
14. Watanabe, Y.; Mitani, M.; Ozaki, S. CL 1987, 123.
15. Yamazaki, N.; Kibayashi, C. JACS 1989, 111, 1396.
16. Lacourt-Gadras, B.; Grignon-Dubois, M.; Rezzonico, B. Carbohydr. Res. 1992, 235, 281.
17. Yoda, H.; Shirakawa, K.; Takabe, K. CL 1991, 489.
18. Nakahara, Y.; Fujita, A.; Beppu, K.; Ogawa, T. T 1986, 42, 6465.
19. Kelly, T. R.; Chandrakumar, N. S.; Cutting, J. D.; Goehring, R. R.; Weibel, F. R. TL 1985, 26, 2173.
20. Classon, B.; Garegg, P. J.; Samuelsson, B. ACS 1984, 38B, 419.
21. Garegg, P. J.; Samuelsson, B. JCS(P1) 1980, 2866.
22. Lange, G.; Gottardo, C. SC 1990, 20, 1473.
23. Aspinall, G. O. ACR 1987, 20, 114.
24. Classon, B.; Garegg, P. J.; Samuelsson, B. CJC 1981, 59, 339.

James M. Takacs

University of Nebraska, Lincoln, NE, USA

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.