p-Tolyl Vinyl Sulfoxide1

[36832-47-0]  · C9H10OS  · p-Tolyl Vinyl Sulfoxide  · (MW 166.26)

(a vinyl sulfoxide,2 typically used in enantiomerically pure form in conjugate additions,3 cycloadditions,4 and Pummerer-type reactions,5 and to prepare vinyl anions6)

Physical Data: bp 110 °C/1.0 mmHg; 79-80 °C/0.04 mmHg; (R)-(+)-enantiomer: [a]26D +421° (c 0.15, EtOH).

Solubility: sol most moderately polar to polar solvents.

Preparative Method: (R)-(+)-p-tolyl vinyl sulfoxide is usually prepared via Andersen sulfinylation,7 beginning with (1R,2S,5R,SS)-(-)-menthyl p-toluenesulfinate, which is prepared as follows.8 A two-neck round-bottom flask, equipped with N2 inlet and magnetic stirring bar, is purged with N2 and then charged with 2.75 equiv of Thionyl Chloride. Under a N2 atmosphere, anhydrous sodium p-toluenesulfinate (see Sodium Benzenesulfinate) is added in portions over 1 h, with the addition of dry benzene as needed to facilitate stirring. After stirring for an additional 1.75 h, additional benzene is added and the mixture transferred to a one-neck round-bottom flask. The volatiles are removed by rotary evaporation, with occasional addition of benzene to ensure that all excess SOCl2 has been removed. The flask, containing crude p-toluenesulfinyl chloride, is equipped with a magnetic stirring bar and constant pressure addition funnel. Ether is added and the resultant suspension is cooled to 0 °C. 1.0 Equiv of (1R,2S,5R)-(-)-menthol in excess pyridine is added over a few minutes, and the reaction is stirred overnight. The product is isolated by addition of ice, extraction, washing of the ether layer with 20% aq HCl, and drying (Na2SO4 + K2CO3). Filtration and concentration by rotary evaporation, followed by crystallization from acetone at -20 °C, affords the ester, mp 105-106 °C, [a]D25 -199.4° (c 1.5, acetone).

The ester is converted into (R)-(+)-p-tolyl vinyl sulfoxide in the following manner.9 A two-neck round-bottom flask equipped with constant pressure addition funnel, N2 inlet, and magnetic stirring bar is charged with a suspension of 1.3 equiv of (1R,2S,5R,SS)-(-)-menthyl p-toluenesulfinate in dry THF under N2. Cooling to -78 °C is followed by dropwise addition of 1.0 equiv of Vinylmagnesium Bromide in THF and slow warming to room temperature. Satd aq NH4Cl is added; separation is followed by drying (MgSO4) and concentration by rotary evaporation. Distillation under reduced pressure affords the sulfoxide. The corresponding (S)-(+)-p-tolyl vinyl sulfoxide may be prepared from (1S,2R,5S,RS)-(+)-menthyl p-toluenesulfinate. Alternative preparations via TBAF-mediated desilylation of (R)-(+)-p-tolyl a-trimethylsilylvinyl sulfone10 and hydrogenation of (R)-(+)-ethynyl p-tolyl sulfoxide2 are possible. Although rarely used, (RS)-p-tolyl vinyl sulfoxide should be available in a manner analogous to the preparation of (RS)-phenyl vinyl sulfoxide, by oxidation of the sulfide.11

Handling, Storage, and Precautions: sulfoxides are known to undergo thermal racemization.12

Conjugate Additions.

Compared to a,b-unsaturated ketones, vinylic sulfoxides are sluggish substrates for conjugate additions. Nonetheless, excellent chemical yields are obtained with heteroatom nucleophiles, including amines, thiols, and alcohols.9a,9c,13 Michael additions of active methylene compounds,13b,14 such as Diethyl Malonate or Ethyl Acetoacetate,15 are less satisfactory. Alkylmetal conjugate donor reagents, such as cuprate reagents, are rarely successful;16 a-metalation of the vinyl moiety usually competes or predominates.17 It is not uncommon to enhance reactivity by introducing an a-carbonyl substituent6 using an a-acylation strategy that exploits an intermediate conjugate addition (e.g. eq 1).18

Cycloadditions.

Aryl vinyl sulfoxides are useful, moderately reactive, dienophiles in [4 + 2] cycloadditions;11a they function, for example, as synthons for Acetylene,19 Ethylene,20 vinylsilanes,21 and ketene.22 Enantiomerically pure aryl vinyl sulfoxides can be used to induce asymmetry in Diels-Alder reactions.4,13a,18,23 In an application to 1,3-dipolar cycloaddition, (R)-(+)-p-tolyl vinyl sulfoxide reacts with the N-phenyl nitrone of benzaldehyde to produce a 95:5 mixture of (3R,4R,RSS)-3-phenyl-4-(p-tolylsulfinyl)isoxazolidines in 57% yield (eq 2); the asymmetric induction at C-3 exceeds 90%.23a

Pummerer-Type Reactions.

An alternative to activating aryl vinyl sulfoxides to nucleophilic addition by a-acylation is to employ an additive Pummerer-type reaction,24 which is initiated by attack of an electrophile on the sulfoxide oxygen and results in a,b-disubstituted alkyl aryl sulfides. p-Tolyl vinyl sulfoxide undergoes vicinal Pummerer diallylation with excess Allylmagnesium Bromide (eq 3);23b similarly, enantiomerically pure aryl vinyl sulfoxides have been used in highly efficient asymmetric syntheses of quaternary carbon centers25 and g-butyrolactones.26 Although aryl vinyl sulfoxides are unreactive under classical Pummerer reaction conditions, an anomalous Pummerer reaction between Isopropenyl Acetate and phenyl vinyl sulfoxides provides a route to b-keto sulfides.27

Other Reactions.

Electrophilic addition of Bromine to (R)-(+)-p-tolyl vinyl sulfoxide is chemically efficient, but proceeds with low asymmetric induction.9c,28 Triphenylstannane, on the other hand, fails to undergo addition.29 Homopolymerization of (R)-(+)-p-tolyl vinyl sulfoxide fails when any of a number of radical initiators are used, but copolymerization with styrene in bulk using Azobisisobutyronitrile as initiator produces an optically active polymer.9a Finally, aryl vinyl sulfoxides can be converted to their corresponding sulfoximides using N-aminophthalimide and Lead(IV) Acetate; the configuration of the sulfur center apparently is retained.13c,30


1. (a) Posner, G. H. In The Chemistry of Sulfones and Sulfoxides; Patai, S.; Rappoport, Z., Eds.; Wiley: New York, 1988; pp 823-849. (b) Durst, T. In Comprehensive Organic Chemistry; Barton, D. H. R.; Ollis, W. D., Eds.; Pergamon: New York, 1979, Vol. 3, p 121.
2. Kosugi, H.; Kitaoka, M.; Tagami, K.; Takahashi, A.; Uda, H. JOC 1987, 52, 1078.
3. Perlmutter, P. Conjugate Addition Reactions in Organic Synthesis; Pergamon: New York, 1992; p 310.
4. Krohn, K. In Organic Synthesis Highlights; Mulzer, J.; Altenbach, H.-J.; Braun, M.; Krohn, K.; Reissig, H.-U., Eds.; VCH: New York, 1991; p 54.
5. De Lucchi, O.; Miotti, U.; Modena, G. OR 1991, 40, 157.
6. Posner, G. H. ACR 1987, 20, 72.
7. (a) Andersen, K. K.; Gaffield, W.; Papanikolaou, N. E.; Foley, J. W.; Perkins, R. I. JACS 1964, 86, 5637. (b) Andersen, K. K. TL 1962, 93.
8. (a) Hulce, M.; Mallamo, J. P.; Frye, L. L.; Kogan, T. P.; Posner, G. H. OSC 1990, 7, 495. (b) Solladié, G. S 1981, 185.
9. (a) Mulvaney, J. E.; Ottaviani, R. A. J Polym. Sci. A-1 1970, 8, 2293. (b) Koizumi, T.; Hirai, H.; Yoshii, E. JOC 1982, 47, 4004. (c) Abbott, D. J.; Colonna, S.; Stirling, C. J. M. JCS(P1) 1976, 492.
10. Cheng, H.-C.; Yan, T.-H. TL 1990, 31, 673.
11. (a) Paquette, L. A.; Carr, R. V. C. OSC 1990, 7, 453. (b) Smith, M. B. SC 1986, 16, 85.
12. (a) Krohn, K. In Organic Synthesis Highlights; Mulzer, J.; Altenbach, H.-J.; Braun, M.; Krohn, K.; Reissig, H.-U., Eds.; VCH: New York, 1991; p 14. (b) Morrison, J. D.; Mosher, H. S. Asymmetric Organic Reactions; American Chemical Society: Washington, 1976; p 19.
13. (a) Maignan, C.; Guessous, A.; Rouessac, F. TL 1986, 27, 2603. (b) Tanikaga, R.; Sugihara, H.; Tanaka, K.; Kaji, A. S 1977, 299. (c) Annunziata, R.; Cinquini, M.; Colonna, S. JCS(P1) 1980, 2422.
14. Ono, N.; Miyake, H.; Tanikaga, R.; Kaji, A. JOC 1982, 47, 5017.
15. Tsuchihashi, G.; Mitamura, S.; Inoue, S.; Ogura, K. TL 1972, 323.
16. Sugihara, H.; Tanikaga, R.; Tanaka, K.; Kaji, A. BCJ 1978, 51, 655.
17. (a) Posner, G. H.; Tang, P.-W. JOC 1978, 43, 4131. (b) Posner, G. H.; Tang, P.-W., Mallamo, J. P. TL 1978, 3995. (c) Okamura, H.; Mitsuhira, Y.; Miura, M.; Takei, H. CL 1978, 517.
18. Alexandre, C.; Belkadi, O.; Maignan, C. S 1992, 547.
19. Paquette, L. A.; Moerck, R. E.; Harirchian, B.; Magnus, P. D. JACS 1978, 100, 1597.
20. Carr, R. V. C.; Paquette, L. A. JACS 1980, 102, 853.
21. Daniels, R. G.; Paquette, L. A. JOC 1981, 46, 2901.
22. Little, R. D.; Myong, S. O. TL 1980, 21, 3339.
23. (a) Koizumi, T.; Hirai, H.; Yoshii, E. JOC 1982, 47, 4004. (b) Iwata, C.; Maezaki, N.; Kurumada, T.; Fukuyama, H.; Sugiyama, K.; Imanishi, T. CC 1991, 1408.
24. (a) Posner, G. H.; Asirvatham, E.; Ali, S. F. CC 1985, 542. (b) King, R. R. JOC 1980, 45, 5347. (c) Yamagiwa, S.; Sato, H.; Hoshi, N.; Kosugi, H.; Uda, H. JCS(P1) 1979, 570. (d) Réamonn, L. S. S.; O'Sullivan, W. I. CC 1976, 642.
25. Imanishi, T.; Kurumada, T.; Maezaki, N.; Sugiyama, K.; Iwata, C. CC 1991, 1409.
26. Marino, J. P.; Perez, A. D. JACS 1984, 106, 7643.
27. De Lucchi, O.; Marchioro, G.; Modena, G. CC 1984, 513.
28. Abbott, D. J.; Stirling, C. J. M. CC 1971, 472.
29. Wardell, J. L.; Wigzell, J. M. JOM 1983, 244, 225.
30. Colonna, S.; Stirling, C. J. M. JCS(P1) 1974, 2120.

Martin Hulce

Creighton University, Omaha, NE, USA



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