[6160-65-2]  · C7H6N4S  · 1,1-Thiocarbonyldiimidazole  · (MW 178.24)

(conversion of vicinal diols to alkenes;1 deoxygenation of alcohols;13 thiocarbonyl transfer agent29)

Alternate Name: TCDI.

Physical Data: mp 101-103 °C.

Solubility: sol many organic solvents including THF, CH2Cl2, toluene.

Form Supplied in: yellow solid; 90% pure or >97% pure.

Preparative Methods: prepared by the reaction of Thiophosgene with 2 equiv of Imidazole.

Purification: can be recrystallized from THF to give yellow crystals; can also be sublimed.

Handling, Storage, and Precautions: very hygroscopic; should be reacted and stored in a dry atmosphere.

Alkene Synthesis.

The Corey-Winter alkene synthesis is an effective method for the deoxygenation of vicinal diols.1,2 The method involves formation of a 1,3-dioxolane-2-thione [cyclic thionocarbonate (or thiocarbonate)] by treatment of a vicinal diol with TCDI. Decomposition of the thionocarbonate, usually with a phosphorus compound, affords the alkene (eq 1).3 The breakdown of the thionocarbonate occurs in a stereospecific sense; details of investigations into the mechanism have been summarized.1

The conditions required for the introduction of the thiocarbonyl group vary greatly, depending on the structure of the diol.1,4 The thionocarbonate may also be prepared without TCDI. The reaction of vicinal diols with thiophosgene/DMAP/CH2Cl2/0 °C,5 with base/CS2/MeI/heat,1 or with 1,1-thiocarbonyl-2,2-pyridone/toluene/110 °C6 also provides thionocarbonates. Along with phosphines and phosphites, other reagents can decompose the thionocarbonates, but not always in a stereospecific manner. The Corey-Hopkins reagent 1,3-dimethyl-2-phenyl-1,3,2-diazaphospholidine,5 along with Raney Nickel7 and Bis(1,5-cyclooctadiene)nickel(0),8 affords products of stereospecific cis-elimination, while the alkyl iodide/Zinc combination9 and Pentacarbonyliron10 yield products of nonstereospecific elimination or unknown stereochemistry.

The Corey-Winter synthesis has proved useful for the generation of a large number of structurally interesting alkenes,1 including some unstable alkenes that must be captured in situ (eq 2).4

The method has found its niche in the chemistry of sugars. Their polyhydroxylated nature make them excellent substrates provided the by-standing hydroxyls are protected (eq 3).11 The 2- and 3-oxygens of nucleosides are readily are removed under the Corey-Winter conditions.12

Radical Chemistry.

Treatment of secondary alcohols with 1 equiv of TCDI affords an imidazole-1-thiocarbonyl derivative (imidazolide), which can be reduced to a CH2 unit under Tri-n-butylstannane (TBTH) radical chain reaction conditions.13,14 The deoxygenation of secondary alcohols by way of an imidazolide or other thiocarbonyl derivative is called the Barton-McCombie reaction (eq 4).6,14 Since imidazolide formation (TCDI, reflux, 65 °C) and the subsequent radical chemistry are done under neutral or near-neutral conditions, the overall reduction is tolerant of the presence of many sorts of functional groups. Furthermore, the low solvation requirements of radical species permits deoxygenation in sterically congested environments (eq 5).15

The mechanism of the radical attack at the thiocarbonyl group and the ensuing breakdown has been outlined elsewhere.13,14 Some groups have studied the comparative chemistries of the possible thiocarbonyl derivatives, with no particularly obvious trends arising.13,16,17 There are numerous reports of the deoxygenation of carbohydrates13,16,18 and related polyhydroxylated species.14,17,19,20 In one instance of amino glycoside deoxygenation, the C(3)-OH group can be selectively functionalized with TCDI, while the C(5)-OH group is unaffected and the radical reduction proceeds without protection of the C(5)-OH group (eq 6).20

Reduction of tertiary alcohols is not recommended due to the instability of the tertiary imidazolide, although, as an alternative, a thioformaldehyde version has been developed.21 Imidazolides from primary alcohols do not respond well to the same conditions as the secondary systems, but performing the radical chemistry at 130-150 °C can lead to deoxygenation.22 As an alternative to the high-temperature radical chemistry, the imidazolide can be converted by methanolysis to a thiocarbonate which can be reduced at room temperature (Et3B, TBTH, benzene).23 Tin hydride treatment of thionocarbonates derived from primary/secondary diols affords, after base exposure, the product of selective reduction of the secondary site, leaving the primary hydroxyl (eq 7).14,24 The approach has also been successfully applied to 1,3-diols.24,25

Since the reduction method proceeds via radical chemistry, the intermediate radicals are prone to bimolecular chemistry and unimolecular reactions such as rearrangements or b-scission, if suitable functionality is proximal.14 Indeed, the imidazolides have been employed as radical precursors when rearrangement is the desired result.14

Thiocarbonyl Transfer.

While virtually all uses of TCDI involve a thiocarbonyl transfer reaction, this section covers those uses of the thiocarbonyl transfer that do not lead to radical chemistry or alkene syntheses. TCDI has been used for the simple placement of a thiocarbonyl group between two nucleophilic atoms of one26 or two molecules.27 An alcohol which has been converted to an imidazolide is a reactive functionality for coupling reactions,28 for sigmatropic rearrangements,29 and for elimination (eq 8).30 The TCDI alternative 1,1-thiocarbonyl-2,2-pyridone6 seems to be an excellent thiocarbonyl transfer agent.

1. Block, E. OR 1984, 30, 457.
2. Corey, E. J.; and Winter, R. A. E. JACS 1963, 85, 2677.
3. Koreeda, M.; Koizumi, N.; Teicher, B. A. CC 1976, 1035.
4. Greenhouse, R.; Borden, W. T.; Ravindranathan, T.; Hirotsu, K.; Clardy, J. JACS 1977, 99, 6955.
5. Corey, E. J.; Hopkins, P. B. TL 1982, 23, 1979.
6. Kim, S.; Yi, K. Y. JOC 1986, 51, 2613.
7. Ireland, R. E.; Anderson, R. C.; Badoud, R.; Fitzsimmons, B. J.; McGarvey, G. J.; Thaisrivongs, S.; Wilcox, C. S. JACS 1983, 105, 1988.
8. Semmelhack, M. F.; Stauffer, R. D. TL 1973, 2667.
9. Vedejs, E.; Wu, E. S. C. JOC 1974, 39, 3641.
10. Daub, J.; Trautz, V.; Erhardt, U. TL 1972, 4435.
11. (a) Akiyama, T.; Shima, H.; Ozaki, S. TL 1991, 32, 5593. (b) Horton, D.; Turner, W. N. TL 1964, 2531.
12. Manchand, P. S.; Belica, P. S.; Holman, M. J.; Huang, T.-N.; Maehr, H.; Tam, S. Y.-K.; Yang, R. T. JOC 1992, 57, 3473.
13. Barton, D. H. R.; McCombie, S. W. JCS(P1) 1975, 1574.
14. (a) McCombie, S. W. COS 1991, 8, 811. (b) Hartwig, W. T 1983, 39, 2609. (c) Crich, D.; Quintero, L. CRV 1989, 89, 1413.
15. Corey, E. J.; Ghosh, A. K. TL 1988, 29, 3205.
16. Rasmussen, J. R.; Slinger, C. J.; Kordish, R. J.; Newman-Evans, D. D. JOC 1981, 46, 4843.
17. Robins, M. J.; Wilson, J. S.; Hansske, F. JACS 1983, 105, 4059.
18. Lin, T.-H.; Ková&cbreve;, P.; Glaudemans, C. P. J. Carbohydr. Res. 1989, 188, 228.
19. Piccirilli, J. A.; Krauch, T.; MacPherson, L. J.; Benner, S. A. HCA 1991, 74, 397.
20. Carney, R. E.; McAlpine, J. B.; Jackson, M.; Stanaszek, R. S.; Washburn, W. H.; Cirovic, M.; Mueller, S. L. J. Antibiot. 1978, 31, 441.
21. Barton, D. H. R.; Hartwig, W.; Hay Motherwell, R. S.; Motherwell, W. B.; Stange, A. TL 1982, 23, 2019.
22. Barton, D. H. R.; Motherwell, W. B.; Stange, A. S 1981, 743.
23. Chu, C. K.; Ullas, G. V.; Jeong, L. S.; Ahn, S. K.; Doboszewski, B.; Lin, Z. X.; Beach, J. W.; Schinazi, R. F. JMC 1990, 33, 1553.
24. Barton, D. H. R.; Subramanian, R. JCS(P1) 1977, 1718.
25. (a) Mubarak, A. M.; Brown, D. M. TL 1981, 22, 683. (b) Suzuki, M.; Yanagisawa, A.; Noyori, R. TL 1984, 25, 1383.
26. Chiang, L.-Y., Shu, P.; Holt, D.; Cowan, D. JOC 1983, 48, 4713.
27. Sugimoto, H.; Makino, I.; Hirai, K. JOC 1988, 53, 2263.
28. Ley, S. V.; Armstrong, A.; Diez-Martin, D.; Ford, M. J.; Grice, P.; Knight, J. G.; Kolb, H. C.; Madin, A.; Marby, C. A.; Mukherjee, S.; Shaw, A. N.; Slawin, A. M. Z.; Vile, S.; White, A. D.; Williams, D. J.; Woods, M. JCS(P1) 1991, 667.
29. Nicolaou, K. C.; Groneberg, R. D.; Miyazaki, T.; Stylianides, N. A.; Schulze, T. J.; Stahl, W. JACS 1990, 112, 8193.
30. Ge, Y.; Isoe, S. CL 1992, 139.

Adrian L. Schwan

University of Guelph, Ontario, Canada

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