Phenylsulfonylethylene1

[5535-48-8]  · C8H8O2S  · Phenylsulfonylethylene  · (MW 168.23)

(Michael acceptor;2 equivalent to ethylene,3 terminal alkenes,3 and ketene4 in cycloaddition reactions; adds radicals;5 precursor to a-substituted vinyl sulfones6)

Alternate Name: phenyl vinyl sulfone.

Physical Data: mp 67-69 °C.

Solubility: sol common organic solvents.

Form Supplied in: colorless solid; commercially available.

Preparative Methods: usually prepared by Hydrogen Peroxide oxidation of Phenyl Vinyl Sulfide. The latter can be prepared by nucleophilic substitution of one mole of phenylthiolate with one mole of dibromoethylene and elimination,7 or by other methods.8

Handling, Storage, and Precautions: good alkylating agent; should be handled with care. Use in a fume hood.

Nucleophilic Additions.

Phenylsulfonylethylene is a powerful Michael acceptor. It readily adds heteroatomic nucleophiles such as amines,9 alkoxides,10 and thiolates.11 Amines and especially thiolates can be reverted back to the sulfonylethylene and nucleophile under mildly basic conditions, thus providing a method for protection of these functional groups.11,12 The reaction with hydroperoxides and hydrogen peroxide in basic media may be controlled to give either the epoxide or the Michael addition product.13

Stabilized carbon nucleophiles add readily to phenyl vinyl sulfone and examples abound. As one example, a step in the synthesis of the biologically active natural product (+)-brefeldin A can be cited (eq 1).14 The base is usually a nonnucleophilic amine but the reaction can also be carried out under solid-liquid phase-transfer catalysis.15 In general, the Michael addition of phenylsulfonylethylene provides a method for two-carbon chain elongation.

Nucleophilic nonstabilized carbanions, as Grignard or lithium reagents, can add to vinyl sulfones.16 The direct addition can be complicated by polymerization arising from deprotonation of the a-vinyl proton and self-condensation.6 Addition of the more nucleophilic organocuprates is more efficient (eq 2),17a but is not always devoid of problems.17b

The enolate of cyclohexenone reacts with phenylsulfonylethylene in the presence of HMPA to give tricyclic derivatives in a single synthetic step (eq 3).18 A method for a-alkylation of a,b-enones involves the addition of a,b-enones to phenylsulfonylethylene under 1,8-Diazabicyclo[5.4.0]undec-7-ene catalysis at high temperature (eq 4).19 In this case, phenylsulfonylethylene functions as the electrophile in a Baylis-Hillman-type reaction.20

Neutral carbon nucleophiles such as enamines give [2 + 2] cycloadducts that can be isolated21 or hydrolyzed to the keto sulfones.22 Chiral imines react with phenylsulfonylethylene to lead, after hydrolysis, to substituted ketones in high yield with high regio- and enantioselectivity (eq 5).23a Enamino esters are far less reactive than imines and activation by high pressure is necessary.23b

The Stetter reaction is an unusual type of Michael addition. It involves a mechanism that resembles the benzoin condensation where the aldehydic carbon functions as the nucleophile. It makes available g-keto sulfones, and hence 1,4-diketones, by a thiazolium salt-catalyzed addition (eq 6).24

Diels-Alder Cycloadditions.1c

Phenylsulfonylethylene enters into [4 + 2] p cycloadditions as a relatively reactive dienophile, usually with modest to high regioselectivity. The reactivity is such to allow addition to most dienes,3,25 either symmetrical as cyclopentadiene, 1,3-cyclohexadiene, 2,3-dimethylbutadiene, and anthracene, or nonsymmetrical as isoprene, myrcene, 1-methoxy-3-trimethylsilyloxy-1,3-butadiene (Danishefsky's diene), 1,5,5-trimethylcyclopentadiene,25b 1-methoxy-1,3-cyclohexadiene, steroids,25e and many others.25 Studies on the stereoselectivity of addition to norbornyl- and norbornenyl-fused cyclopentadienes (eq 7)26a as well as anti,anti-2,3-diethylenenorbornane and -norbornene,27a or other similar systems,27b in comparison with those observed using other dienophiles have been reported.

The sulfonyl group can be replaced with hydrogen by reductive desulfonylation with Sodium Amalgam or Samarium(II) Iodide in HMPA.28 In these cases the cycloaddition-reduction sequence equals the cycloaddition of ethylene, as in the example of eq 7. Since the adducts can be alkylated prior to desulfonylation, phenylsulfonylethylene can be viewed also as an equivalent of terminal alkenes in cycloaddition reactions3 (eq 8).29 Thermal or base-induced elimination of benzenesulfinic acid from the adducts makes phenylsulfonylethylene equivalent to acetylene in cycloaddition reactions. This thermal reaction, however, seldom occurs in acceptable yields30 and the base-induced b-elimination occurs only when a relatively acidic proton at the b-carbon is available.

Cycloaddition to 1-methoxy-3-trimethylsilyloxy-1,3-butadiene followed by direct acetalization provides an adduct that undergoes regiospecific g-alkylation. This process has been applied in a synthesis of zingiberenol as described in eq 9.31 Phenylsulfonylethylene efficiently traps 1,3-diradicals generated by extrusion of nitrogen (eq 10). During this research an efficient oxidative desulfonylation of the resulting adducts with the molybdenum complex Oxodiperoxymolybdenum(pyridine)(hexamethylphosphoric triamide) (MoOPH) was developed so that phenylsulfonylethylene can be also used as a ketene equivalent in cycloadditions (eq 10).4

Dipolar Cycloadditions.

Pyrazoles are synthesized in excellent yield by reaction of diazomethanes with phenylsulfonylethylene or other a,b-unsaturated sulfones.32 Nitrile oxides react with phenyl vinyl sulfone with high selectivity to give the 5-phenylsulfonylisoxazoline as the sole or predominant product (eq 11).32 1-Methyl-3-oxidopyridinium affords regio- and stereoselectively an adduct that can be transformed into 2a- and 2b-tropanols (eq 12).33

Oximes undergo tandem Michael addition dipolar cycloaddition to give isoxazolidine derivatives. In this reaction the nitrones generated by the Michael addition are trapped by an external dipolarophile such as N-methylmaleimide (eq 13),34a or intramolecularly if an alkene is available (eq 14).34b A somewhat similar reactivity is displayed by pyridinium or isoquinolinium methylides.34c

Radical Additions.5

Alkyl radicals derived from decarboxylation of carboxylic acids by the Barton method add to phenylsulfonylethylene.35 The adducts undergo a wide variety of transformations including conversion to a two-carbon homologous carboxylic acid or to substituted vinyl sulfones. The conversion of the adducts into hydrocarbons, ketones, and other functional groups is also possible. An example of an application to the synthesis of substituted 2-azetidinones from tartaric acid is shown in eq 15.36 Multiple radical additions occur when the carboxylic acid possesses accessible double bonds, as in eq 16.37 The adduct incorporates stereoselectively (three out of four stereogenic centers) two molecules of phenylsulfonylethylene.

Radicals generated by other means also add to phenylsulfonylethylene.38

a-Substituted Vinyl Sulfones via Direct Lithiation or Baylis-Hillman and Related Reactions.

The direct alkylation of the vinyl anion of phenylsulfonylethylene is made difficult by a rapid polymerization due to self-condensation of the vinyl anion with the reagent itself.6 Indirect methods to overcome this problem are available. These engage in protection of the double bond by means of secondary amines (eq 17)6b or trimethylsilyl compounds.39 With aldehydes as electrophiles, the Baylis-Hillman reaction20 is possible (eq 18).40 The allylic alcohols produced can be subjected to numerous transformations; for example, (E)-selective dehydration to give 1,3-alkadienes (eq 18)41a or modified Jones oxidation to a-methylene-b-keto sulfones.41b

Other Reactions.

Phenylsulfonylethylenes are dimerized by low cathodic currents to give trans-1,2-substituted cyclobutanes.42 Carbonyl-stabilized sulfur ylides give cyclopropanes (eq 19).43 Finally, the hydroformylation catalyzed by a rhodium complex gives mostly the branched-chain aldehyde PhSO2CH(CHO)Me.44


1. (a) Magnus, P. D. T 1977, 33, 2019. (b) De Lucchi, O.; Pasquato, L. T 1988, 44, 6755. (c) Tanaka, K.; Kaji, A. In The Chemistry of Sulfones and Sulfoxides; Patai, S.; Rappoport, Z.; Stirling, C. J. M., Eds.; Wiley: Chichester, 1988; Chapter 15, pp 791-799. (d) Simpkins, N. S. T 1990, 46, 6951. (e) Padwa, A.; Murphree, S. S. Rev. Heteroatom Chem. 1992, 6, 241. (f) Simpkins, N. S. Sulfones in Organic Synthesis; Pergamon: Oxford, 1993.
2. Kader, A. T.; Stirling, C. J. M. JCS 1962, 3686.
3. (a) Carr, R. V. C.; Paquette, L. A. JACS 1980, 102, 853. (b) Carr, R. V. C.; William, R. V.; Paquette, L. A. JOC 1983, 48, 4976.
4. (a) Little, R. D.; Brown, L. TL 1980, 21, 2203. (b) Little, R. D.; Myong, S. O. TL 1980, 21, 3339.
5. (a) Barton, D. H. R.; Zard, S. Z. PAC 1986, 58, 675. (b) Giese, B. Radicals in Organic Synthesis: Formation of Carbon-Carbon Bonds; Pergamon: Oxford, 1986. (c) Wnuk, S. F. T 1993, 44, 9877.
6. (a) Eisch, J. J.; Galle, J. E. JOC 1979, 44, 3279. JOC 1980, 45, 4534. (b) Inomata, K.; Tanaka, Y.; Sasaoka, S.; Kinoshita, H.; Kotake, H. CL 1986, 341.
7. Paquette, L. A.; Carr, R. V. C. OS 1985, 64, 157.
8. (a) Brandsma, L.; Verkuijsse, H. D.; Schade, C.; Schleyer, P. v. R. CC 1986, 260. (b) Smith, M. B. SC 1986, 16, 85 and references cited therein.
9. McDowell, S. T.; Stirling, C. J. M. JCS(B) 1967, 343, 351.
10. Harmata, M.; Gamlath, C. B. JOC 1988, 53, 6154.
11. (a) Kuroki, Y.; Lett, R. TL 1984, 25, 197. (b) Horner, L.; Lindel, H. LA 1985, 22.
12. For a general discussion of the reaction, see: Marshall, D. R.; Thomas, P. J.; Stirling, C. J. M. CC 1975, 940.
13. (a) Zwanenburg, B.; ter Wiel, J. TL 1970, 935. (b) Curci, R.; Di Furia, F. TL 1974, 4085. (c) Clark, C.; Hermans, P.; Meth-Cohn, O.; Moore, C.; Taljaard, H. C.; van Vuuren, G. CC 1986, 1378. (d) Kropf, H.; Ball, M.; Hofmann, K. LA 1976, 2316.
14. Nakamura, K.; Kitayama, T.; Inoue, Y.; Ohno, A. BCJ 1990, 63, 91.
15. Skarzewski, J. S 1990, 1125.
16. Fabre, J.-L.; Julia, M.; Verpeaux, J.-N. BSF(2) 1985, 762.
17. (a) De Chirico, G.; Fiandanese, V.; Marchese, G.; Naso, F.; Sciacovelli, O. CC 1981, 523. (b) Posner, G. H.; Brunelle, D. J. JOC 1973, 38, 2747.
18. Cory, R. M.; Renneboog, R. M. JOC 1984, 49, 3898.
19. Hwu, J. R.; Hakimelahi, G. H.; Chou, C.-T. TL 1992, 33, 6469.
20. Drewes, S. E.; Roos, G. H. P. T 1988, 44, 4653.
21. (a) Risaliti, A.; Fatutta, S.; Forchiassin, M. T 1967, 23, 1451. (b) Fatutta, S.; Risaliti, A. JCS(P1) 1974, 2387.
22. (a) Elguero, J.; Jacquier, R.; Tarrago, G. BSF(2) 1968, 1149. (b) Rynbrandt, R. H.; Dutton, F. E. JOC 1975, 40, 2282.
23. (a) d'Angelo, J.; Revial, G. TA 1991, 2, 199. (b) Pinheiro, S.; Guingant, A.; Desmaele, D.; d'Angelo, J. TA 1992, 3, 1003.
24. (a) Stetter, H.; Bender, H.-J. CB 1981, 114, 1226. (b) Stetter, H. AG(E) 1976, 15, 639.
25. (a) Alder, K.; Rickert, H. F.; Windemuth, E. B 1938, 71, 2451. (b) Davies, D. I.; Rowley, P. J. JCS 1968, 1832. (c) Hayes, P. C.; Paquette, L. A. JOC 1983, 48, 1257. (d) Mandai, T.; Osaka, K.; Kawagishi, M.; Kawada, M.; Otera, J. JOC 1984, 49, 3595. (e) Bull, J. R.; Thomson, R. I. CC 1986, 451. (f) Chen, C.-W.; Beak, P. JOC 1986, 51, 3325. (f) Lautens, M.; Edwards, L. G. TL 1989, 30, 6813. (g) Haber, M.; Pindur, U. T 1991, 47, 1925.
26. (a) Paquette, L. A.; Hayes, P. C.; Charumilind, P.; Böhm, M. C.; Gleiter, R.; Blount, J. F. JACS 1983, 105, 3148. (b) Paquette, L. A.; Charumilind, P.; Böhm, M. C.; Gleiter, R.; Bass, L. S.; Clardy, J. JACS 1983, 105, 3136. (c) Paquette, L. A.; Charumilind, P.; Kravetz, T. M.; Böhm, M. C.; Gleiter, R. JACS 1983, 105, 3126.
27. (a) Paquette, L. A.; Schaefer, G.; Blount, J. F. JACS 1983, 105, 3642. (b) Charumilind, P.; Paquette, L. A. JACS 1984, 106, 8225.
28. Künzer, H.; Stahnke, M.; Sauer, G.; Wiechert, R. TL 1991, 32, 1949.
29. (a) Herdeis, C.; Hartke, C. S 1988, 76. (b) Herdeis, C.; Hartke-Karger, C.; Lotter, H. AP 1990, 323, 937.
30. Nakayama, J.; Hirashima, A. JACS 1990, 112, 7648.
31. Kinney, W. A.; Crouse, G. D.; Paquette, L. A. JOC 1983, 48, 4986.
32. (a) Parham, W. E.; Blake, F. D.; Theissen, D. R. JOC 1962, 27, 2415. (b) Houk, K. N.; Chang, Y.-M.; Strozier, R. W.; Caramella, P. H 1977, 7, 793. (c) Barzaghi, M.; Beltrame, P. L.; Dalla Croce, P.; Del Buttero, P.; Licandro, E.; Maiorana, S.; Zecchi, G. JOC 1983, 48, 3807. (d) Hisano, T.; Harano, K.; Matsuoka, T.; Watanabe, S.; Matsuzaki, T. CPB 1989, 37, 907. (e) Asaki, T.; Aoyama, T.; Shioiri, T. H 1988, 27, 343.
33. Takahashi, T.; Hagi, T.; Kitano, K.; Takeuchi, Y.; Koizumi, T. CL 1989, 593.
34. (a) Grigg, R.; Heaney, F.; Surendrakumar, S.; Warnock, W. J. T 1991, 47, 4477. (b) Amstrong, P.; Grigg, R.; Heaney, F.; Surendrakumar, S.; Warnock, W. J. T 1991, 47, 4495. (c) Kanemasa, S.; Takenaka, S.; Watanabe, H.; Tsuge, O. JOC 1989, 54, 420.
35. (a) Barton, D. H. R.; Togo, H.; Zard, S. Z. TL 1985, 26, 6349. (b) Barton, D. H. R.; Géro, S. D.; Quiclet-Sire, B.; Samadi, M. CC 1988, 1372. (c) Barton, D. H. R.; Boivin, J.; Sarma, J.; da Silva, E.; Zard, S. Z. TL 1989, 30, 4237. (d) Boivin, J.; Crépon, E.; Zard, S. Z. TL 1991, 32, 199. (e) Barton, D. H. R.; Boivin, J.; Crépon, E.; Sarma, J.; Togo, H.; Zard, S. Z. T 1991, 47, 7091. (f) Barton, D. H. R.; Chern, C.-Y.; Jaszberenyi, J. C. TL 1991, 32, 3309. (g) Togo, H.; Ishigami, S.; Yokoyama, M. CL 1992, 1673. (h) Barton, D. H. R.; Samadi, M. T 1992, 48, 7083.
36. Barton, D. H. R.; Cléophax, J.; Gateau-Olesker, A.; Géro, S. D.; Tachdjian, C. T 1993, 49, 8381.
37. (a) Barton, D. H. R.; da Silva, E.; Zard, S. Z. CC 1988, 285. (b) Lee, E.; Lee, D. S. TL 1990, 31, 4341.
38. (a) Curran, D. P.; Chen, M.-H. JACS 1987, 109, 6558. (b) Rao, M. V.; Nagarajan, M. JOC 1988, 53, 1432. (c) Chatgilialoglu, C.; Giese, B.; Kopping, B. TL 1990, 31, 6013. (d) Togo, H.; Aoki, M.; Yokoyama, M. CL 1992, 2169.
39. Hsiao, C.-N.; Shechter, H. JOC 1988, 53, 2688.
40. (a) Auvray, P.; Knochel, P.; Normant, J. F. TL 1986, 27, 5095. (b) Auvray, P.; Knochel, P.; Normant, J. F. T 1988, 44, 6095.
41. (a) Hoffmann, H. M. R.; Weichert, A.; Slawin, A. M. Z.; Williams, D. J. T 1990, 46, 5591. (b) Weichert, A.; Hoffmann, H. M. R. JOC 1991, 56, 4098.
42. Delaunay, J.; Mabon, G.; Orliac, A.; Simonet, J. TL 1990, 31, 667.
43. Bhaskar Reddy, D. B.; Reddy, P. S.; Reddy, B. V.; Reddy, P. A. S 1987, 74.
44. Totland, K.; Alper, H. JOC 1993, 58, 3326.

Ottorino De Lucchi

Università di Venezia, Italy

Sergio Cossu

Università di Sassari, Italy



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