Diphenyl Diselenide1

[1666-13-3]  · C12H10Se2  · Diphenyl Diselenide  · (MW 312.14)

(source of phenylseleno functionality, reactive with wide variety of organic nucleophiles,2-13 electrophiles,14-24 and radicals;25-27 source of phenylseleno radicals28-31)

Physical Data: mp 63-64 °C.

Solubility: sol MeOH, EtOH, ether, THF, toluene, and most common organic solvents; insol water.

Form Supplied in: yellow powder; widely available.

Preparative Methods: synthesized by reaction of Phenylmagnesium Bromide with Selenium, followed by treatment with Bromine.32 This method is superior to older methods33 in that it does not generate the toxic byproducts H2Se and PhSeH.

Handling, Storage, and Precautions: is air stable, has a faint odor, and is not appreciably hygroscopic. Organoselenides are reputed to be highly toxic, although not as toxic as inorganic selenium compounds such as H2Se or SeO2.1b Use in a fume hood.

Introduction.

Diphenyl diselenide is most frequently used as a reagent for incorporation of the phenylseleno functionality into molecules. The phenylseleno group provides useful functionality arising from the variety of reactions in which it can be subsequently involved. The most noted reaction of organoselenides is their oxidative elimination, which generates alkenes from phenyl selenides under mild, neutral conditions.34 Phenyl selenides can also undergo radical reduction35 and certain radical alkylation reactions.36 Other potentially valuable synthetic uses of phenyl selenides include reductive lithiation37 and a-deprotonation.38

Incorporation of Nucleophilic Phenylseleno Reagents.

Diphenyl diselenide and Benzeneselenol are the most popular reagents for the generation of nucleophilic phenyl selenide. Diphenyl diselenide is usually the preferred precursor due to its greater ease in handling. Selenolate anions are potent, soft nucleophiles.2

There are many popular and generally applicable procedures for the generation of benzeneselenolate anions from PhSeSePh. Treatment of PhSeSePh with Sodium Borohydride provides a very convenient method for the generation of the benzeneselenolate anion.3 The nucleophilicity of the anion thus formed is apparently decreased due to complexation with borane.4 Uncomplexed sodium benzeneselenolate can be generated upon reduction of PhSeSePh with Sodium Hydride5 or Sodium metal.4 Generation of sodium benzeneselenolate upon treatment of PhSeSePh with Rongalite (Sodium Hydroxymethanesulfinate) has been mentioned as being particularly amenable to large scale preparations, due to the absence of H2 evolution.6

The benzeneselenolate anion is reactive with a variety of carbon electrophiles. It is reactive with benzyl (eq 1) and alkyl halides,8 leading to the formation of simple alkyl phenyl selenides. The benzeneselenolate anion is also useful in the nucleophilic ring opening of oxiranes (eq 2).3 This method can be of limited value with unsymmetrical oxiranes, as regioselectivity is often poor. While the borane-complexed benzeneselenolate anion generated from treatment of PhSeSePh with NaBH4 is not a reactive enough nucleophile to cleave esters,4,9 a variety of more reactive benzeneselenolate anions are quite effective in this regard (eq 3).4,9,10 A particularly reactive form can be formed by reaction of PhSeSePh with Lithium Aluminum Hydride. This species is capable of reaction with oxetanes and oxolanes, cleaving the ethereal carbon-oxygen bond (eq 4).11

The benzeneselenolate anion also adds in a conjugate fashion to unsaturated carbonyl compounds. Addition to a-methylene lactones proceeds quite readily (eq 5). Given the facility with which subsequent oxidative elimination of the phenylseleno group can be carried out, thus regenerating unsaturation, an effective means of protecting a labile a-methylene lactone is available.12 The benzeneselenolate anion can also be generated electrochemically and added to unsaturated ketones and esters in a conjugate fashion (eq 6).13

Incorporation of Electrophilic Phenylseleno Reagents.

A variety of carbanion nucleophiles react with PhSeSePh to generate the corresponding phenylseleno-substituted product. While PhSeSePh is not as electrophilic as other organoselenium reagents, such as Benzeneselenenyl Chloride, Benzeneselenenyl Bromide, or N-Phenylselenophthalimide, there are numerous situations where it can be used to supply electrophilic phenyl selenide.

Diphenyl diselenide reacts readily with many organometallic species (eq 7).14 Similar reactivity has also been observed with ester and lactone enolates (eq 8)15 and nitrile-stabilized carbanions.16 The reaction of ketone enolates with PhSeSePh usually fails due to an unfavorable equilibrium constant (eq 9).17 However, this unfavorable equilibrium can be driven to completion upon addition of O2,18 which converts the PhSe- formed in the reaction to PhSeSePh.

Methods involving the reaction of less reactive nucleophiles with PhSeSePh usually involve in situ generation of the phenylselenium cation, or some other highly reactive phenyl selenide species. A variety of dialkyl ketones, aliphatic aldehydes, and even b-keto esters or b-diketones react with PhSeSePh in the presence of Selenium(IV) Oxide and a trace of H2SO4 (eq 10).19 Enol acetates react with PhSeSePh upon electrochemical anodic oxidation in the presence of Et4N+Br- (eq 11).20 It has been proposed that this method involves the in situ generation of PhSeBr. Phenyl selenoacetate is probably generated in situ upon reaction of PhSeSePh with Copper(II) Acetate or Lead(IV) Acetate.21 This reagent effects the trans-acetoxyselenation of alkenes. The phenylselenium cation has been generated from PhSeSePh upon photolysis in the presence of DCN, proceeding through a mechanism involving photoinduced electron transfer (eq 12),22 or upon treatment of PhSeSePh with (NH4)2S2O8.23 The phenylselenium cation thus generated induces selenolactonization and selenoetherification. Stereospecific selenoamination, proceeding through the possible intermediacy of a selenonium ion, has been reported upon reaction of cyclohexene with PhSeSePh in the presence of Chloramine-T (eq 13).24

Uses in Radical Reactions.

Diphenyl diselenide has been used as a source of phenylseleno radicals and as a radical trap, allowing for the introduction of phenylseleno functionality via radical reactions. Whereas photolysis of PhSeSePh has been shown to generate phenylseleno radicals reversibly, products arising from addition to simple alkenes have not been observed due to the reversible nature of this addition.28 This reversible addition has, however, been used to isomerize alkenes, as exemplified in the photochemical isomerization of vitamin D2 to 5,6-trans-vitamin D2 in the presence of PhSeSePh, which proceeds in 57% yield (eq 14).29 This isomerization only proceeds in 20-40% yield in the presence of Iodine.39

The addition of PhSeSePh to alkynes, however, has been observed under thermal (eq 15)30 or photochemical31 conditions, leading to predominantly (E) products.

Diphenyl diselenide can also be used as an effective radical trap. Generation of the 5-hexenyl radical from a suitable alkylmercury(II) chloride in the presence of PhSeSePh generates both a cyclized and uncyclized alkyl phenyl selenide (eq 16). By analysis of the product ratios under various reaction conditions, and the known rate of the hexenyl radical cyclization, a rate constant of 2.6 × 107 L mol-1 s-1 at 45 °C was obtained for the SH2 reaction of a primary alkyl radical with PhSeSePh.25 Diphenyl diselenide has also been used to trap radicals generated from a variety of other sources,26 including those generated photochemically from thiohydroxamate esters (eq 17).27

Other Uses.

Diphenyl diselenide can catalyze the allylic chlorination of alkenes with N-Chlorosuccinimide. The major product is usually a rearranged allylic chloride. This reaction is not believed to proceed through a radical mechanism, in contrast with most procedures for allylic chlorination (eq 18).40 Phenylselenoalkynes are formed in good yield upon reaction of terminal alkynes with (Diacetoxyiodo)benzene and PhSeSePh (eq 19).41

The carbene or carbenoid species generated from Diazomethane,42 a-diazo esters,43 or 6-diazopenicillinates44 will insert in the Se-Se bond of PhSeSePh to generate bis(phenylseleno) acetals (eq 20).

Terminal alkenes can be converted to a-phenylseleno ketones upon reaction with PhSeSePh, Bis(tri-n-butyltin) Oxide, and Br2 (eq 21).45 The initially formed reagent in this procedure is thought to be PhSeOSnBu3.

Related Reagents.

Diphenyl Disulfide; Diphenyl Ditelluride; 2,2-Dipyridyl Diselenide.


1. Several recently published books describe organoselenium chemistry in general, with many examples of diphenyl diselenide reactions: (a) Paulmier, C. Selenium Reagents and Intermediates in Organic Synthesis; Pergamon: Oxford, 1986. (b) Krief, A.; Hevesi, L. Organoselenium Chemistry I; Springer: Berlin, 1988. (c) Organoselenium Chemistry; Liotta, D., Ed.; Wiley: New York, 1987. (d) The Chemistry of Organoselenium and Tellurium Compounds; Patai, S.; Rappaport, Z., Eds.; Wiley: New York, 1986.
2. (a) Pearson, R. G.; Sobel, H.; Songsted, J. JACS 1968, 90, 319. (b) Baker, A. D.; Armen, G. H.; Guang-di, Y.; Liotta, D.; Flannagan, N.; Barnum, C.; Saindane, M.; Zima, G.; Grossman, J. JOC 1981, 46, 4127.
3. Sharpless, K. B.; Lauer, R. F. JACS 1973, 95, 2697.
4. Liotta, D.; Markiewicz, W.; Santiesteban, H. TL 1977, 4365.
5. Dowd, P.; Kennedy, P. SC 1981, 11, 935.
6. Reich, H. J.; Chow, F.; Shah, S. K. JACS 1979, 101, 6638.
7. Mitchell, R. H. CC 1974, 990.
8. Sharpless, K. B.; Young, M. W. JOC 1975, 40, 947.
9. Liotta, D.; Santiesteban, H. TL 1977, 4369.
10. (a) Liotta, D.; Sunay, U.; Santiesteban, H.: Markiewicz, W. JOC 1981, 46, 2605. (b) Scarborough, R.; Smith, A. B. TL 1977, 4361. (c) Liotta, D. ACR 1984, 17, 28.
11. Haraguchi, K.; Tanaka, H.; Miyasaka, T. S 1989, 434.
12. Grieco, P. A.; Miyashita, M. TL 1974, 1869.
13. Torii, S.; Inokuchi, T.; Hasegawa, N. CL 1980, 639.
14. Reich, H. J.; Willis, W. W., Jr.; Clark, P. D. JOC 1981, 46, 2775.
15. Grieco. P. A.; Miyashita, M. JOC 1974, 39, 120.
16. Brattesani, D. N.; Heathcock, C. H. TL 1974, 2279.
17. Reich, H. J.; Renga, J. M.; Reich, I. L. JACS 1975, 97, 5434.
18. Smith, A. B., III; Richmond, R. E. JACS 1983, 105, 575.
19. Miyoshi, N.; Yamamoto, T.; Kambe, N.; Murai, S.; Sonoda, N. TL 1982, 23, 4813.
20. Torii, S.; Uneyama, K.; Ono, M. TL 1980, 21, 2741.
21. Miyoshi, N.; Ohno, K.; Kondo, K.; Murai, S.; Sonoda, N. CL 1979, 1309.
22. Pandey, G.; Soma Sekhar, B. B. V. JOC 1992, 57, 4019.
23. Tiecco, M.; Testaferri, L.; Tingoli, M.; Bartoli, D.; Balducci, R. JOC 1990, 55, 429.
24. (a) Barton, D. H. R.; Britten-Kelley, M. R.; Ferreira, D. JCS(P1) 1978, 1090. (b) Barton, D. H. R.; Britten-Kelley, M. R.; Ferreira, D. JCS(P1) 1978, 1682.
25. (a) Russell, G. A.; Tashtoush, H. JACS 1983, 105, 1398. (b) Newcomb, M. T 1993, 49, 1151.
26. (a) Deniau, J.; Duong, K. N. V.; Gaudemer, A.; Bougeard, P.; Johnson, M. D. JCS(P2) 1981, 393. (b) Perkins, M. J.; Turner, E. S. CC 1981, 139.
27. Barton, D. H. R.; Bridon, D.; Zard, S. Z. TL 1984, 25, 5777.
28. Ito, O. JACS 1983, 105, 850.
29. Barrett, A. G. M.; Barton, D. H. R.; Johnson, G. S 1978, 741.
30. Ogawa, A.; Takami, N.; Sekiguchi, M.; Yokoyama, H. CL 1991, 2241.
31. Ogawa, A.; Yokoyama, H.; Yokoyama, K.; Masawaki, T.; Kambe, N.; Sonoda, N. JOC 1991, 56, 5721.
32. Reich, H. J.; Cohen, M. L.; Clark, P. S. OS 1979, 59, 141.
33. Taster, D. G. OSC 1955, 3, 771.
34. (a) Jones, D. N.; Mundy, D.; Whitehouse, R. D. CC 1970, 86. (b) Reich, H. J.; Wollowitz, S.; Trend, J. E.; Chow, F.; Wendelborn, D. F. JOC 1978, 43, 1697.
35. Clive, D. L. J.; Chittattu, G. J.; Farina, V.; Kiel, W. A.; Menchen, S. M.; Russell, C. G.; Singh, A.; Wong, C. K.; Curtis, N. J. JACS 1980, 102, 4438.
36. (a) Keck, G. E.; Enholm, E. J.; Yates, J. B.; Wiley, M. R. T 1985, 41, 4079. (b) Keck, G. E.; Byers, J. H. JOC 1985, 50, 5442.
37. (a) Dumont, W.; Bayet, P.; Krief, A. AG(E) 1974, 13, 804. (b) Seebach, D.; Beck, A. K. AG(E) 1978, 17, 806.
38. Sevrin, M.; Denis, J. N.; Krief, A. AG(E) 1978, 17, 526.
39. Fieser, L. F.; Fieser, M. Steroids; Reinhold: New York, 1959; pp 146-150.
40. Hori, T.; Sharpless, K. B. JOC 1979, 44, 4204.
41. Tingoli, M.; Tiecco, M.; Testaferri, M.; Balducci, R. SL 1993, 211.
42. Petragnani, N.; Schill, G. CB 1970, 103, 2271.
43. Pellicciari, R.; Curini, M.; Ceccherelli, P; Fringuelli, R. CC 1979, 440.
44. (a) Giddings, P. J.; John, D. I.; Thomas, E. J. TL 1980, 21, 399. (b) Giddings, P. J.; John, D. I.; Thomas, E. J.; Williams, D. J. JCS(P2) 1982, 2757.
45. Kuwajima, I.; Shimizu, M. TL 1978, 1277.

Jeffrey H. Byers

Middlebury College, VT, USA



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