Ethynyl p-Tolyl Sulfone1

[13894-21-8]  · C9H8O2S  · Ethynyl p-Tolyl Sulfone  · (MW 180.22)

(dienophile used in electrocyclic reactions such as dipolar cycloaddition,2-4 Diels-Alder reaction,5-7 and ene cyclization;8 electron-poor Michael acceptor in conjugate additions;9-17 undergoes direct displacement with organometallic complexes to give aryl- or alkylacetylenes18)

Alternate Name: p-toluenesulfonylacetylene.

Physical Data: colorless crystals, mp 74-75 °C, mp 75 °C (hexane-ethyl acetate, 95:5).19

Solubility: sol most organic solvents.

Analysis of Reagent Purity: based on combustion and spectral examination.19

Preparative Methods: has been prepared by several groups over the years employing a variety of synthetic strategies including ethynyl Grignard addition to p-toluenesulfonyl fluoride,20 dehydroiodination of (E)-2-iodo-1-tosyl-1-ethene,21 oxidative elimination of b-[(4-methylphenyl)seleno]vinyl sulfone,22 dehydrobromination of cis- and trans-2-bromovinyl 4-methylphenyl sulfone,23 diazotization of 4-[(4-methylphenyl)sulfonyl]-5-aminoisoxazole,24 and oxidation of ethynyl thioether.25 The modified strategy commonly used today is an established Friedel-Crafts based procedure first performed by Bhattacharya et al.26 but recently exploited by Waykole and Paquette (eq 1).19 Its simplicity and mildness has shown it to be broadly useful since it bypasses the need for immoderate conditions encountered in the earlier strategies.19

Purification: recrystallization readily removes an impurity formed by flash chromatography.

Handling, Storage, and Precautions: decomposition of the intermediate complex p-toluenesulfonyl chloride-aluminum chloride-bis(trimethylsilyl)acetylene with hydrochloric acid and ice is exothermic and due caution is recommended. Also, a nitrogen atmosphere is suggested throughout its preparation due to the hygroscopic nature of the reagents and intermediate(s) involved.19

Dipolar Cycloadditions.

Padwa and Wannamaker2 have shown recently that ethynyl p-tolyl sulfone (1) undergoes a thermal 1,3-dipolar cycloaddition reaction with diazomethane (eq 2). Surprisingly, regioisomer (2) is formed in preference to N-methyl-4-(p-tolylsulfonyl)pyrazole, the expected isomer. Substitution of the acetylenic proton in (1) with the bulky trimethylsilyl group, however, furnishes only the expected regioisomer in quantitative yield following desilylation with fluoride. Further studies with 2-diazopropane led Padwa and Wannamaker to conclude that the difference in regioselectivity was primarily due to steric hindrance and not to an electronic effect.2

Heteroaromatic N-oxides and ylides are also suitable dipoles in this reaction.3,4 For example, 4-chloropyridine N-oxide undergoes a smooth and clean cyclization with (1) in boiling toluene to yield 3-tosylfuro[3,2-c]pyridine (3) in 65% yield (eq 3).

Diels-Alder Reactions.

The dienophilic properties of (1) in combination with the reductive elimination of the tosyl unit have made this compound a useful acetylene synthetic equivalent in various Diels-Alder reactions; it has a pivotal role in the synthesis of the elusive 7-azanorbornadiene (eq 4).5 Cycloaddition is easily accomplished on a preparative scale in 60% yield by heating (1) with N-methoxycarbonylpyrrole. Desulfonation of (4) with 6% Sodium Amalgam in buffered medium affords a 42% yield of protected 7-azanorbornadiene (5), which is converted to the parent compound in two steps (72% yield). Notably, the first C-unsubstituted derivative, 7-tosyl-7-azanorbornadiene was synthesized by a laborious route by Prinzbach and Babsch;27 however, cleavage of this protecting group was troublesome.5

Another use of (1) as an acetylene equivalent is in its central role in the construction of the polyhedron [4]peristylane, which can be prepared in only 11 steps (eq 5).6 Examples of Diels-Alder reactions between ethynyl p-tolyl sulfone and other dienes also exist.7

Ene Cyclizations.

Ethynyl p-tolyl sulfone has been shown by Snider et al.8 to undergo a Ethylaluminum Dichloride-catalyzed ene cyclization with alkenes to furnish a functionalized two-carbon fragment, a vinyl sulfone, which is a versatile synthon.28 For example, 2,3-dimethyl-2-butene reacts with (1) in the presence of catalytic ethylaluminum dichloride to give dienyl sulfone (6) in 89% yield (eq 6). In general, these reactions proceed at 25 °C in aromatic solvents and are best for highly substituted, i.e. electron-rich, alkenes. Good yields of ene adducts are obtained from all alkenes with at least one disubstituted carbon.8 Monosubstituted alkenes give low yields of adducts while 1,2-disubstituted alkenes give low yields of a mixture of ene product and cyclobutene byproduct.8 The choice of ethylaluminum dichloride as catalyst appears to be optimal.

Conjugate Additions.

As a class of compounds, arylsulfonylalkynes behave as good Michael acceptors toward nucleophiles such as amines,9 alkoxides,10 thiolates,11 hydroxylamines,12 cuprates,13 malonate anions,14 and other enolates15 (eq 7). Some examples are provided in Table 1.

Oxygen- and sulfur-containing anionic nucleophiles such as alkoxides and thiolates add kinetically in a cis fashion to yield the (Z)-isomer; however, over extended periods of time, isomerization to the more stable (E)-isomer can be accomplished via an addition/elimination pathway.11a,29 Nevertheless, several different mechanistic pathways have been postulated and may be operative, depending on the nature of the substrate.11a,29 Cuprates, in general, react to give almost exclusively (100-95%) the (E)-isomer at 0 °C, but at lower temperatures, such as -78 °C, the (Z)-isomer begins to make a minor (5-20%) contribution, perhaps through reactive intermediate (E) to (Z) isomerization.13 In contrast, soft enolates like malonate anions give predominately the (Z)-isomer.14 Owing to transition-state stabilization of the cis configuration, neutral nucleophiles like amines add stereospecifically in a trans manner to give (E)-isomer unless the adducts are capable of immonium-type resonance, in which case the addition is followed by an extremely rapid isomerization to the (Z) configuration.9 Moreover, hydroxylamines also undergo conjugate addition to (1), but ensuing tautomerization provides nitrones usually as the main product.12

Dialkylaminoalkynes have been shown by Himbert and Kosack16 also to react with (1) through its extended conjugation at room temperature to give 2-amino-5-(p-tolylsulfinyl)furans, which, if desired, can be thermally isomerized to maleic acid derivatives. N-Methyl-N-ethynylamine (8), for example, was stirred at rt with ethynyl p-tolyl sulfone to give (9) in 64% yield.17 Isomerization of (9) in refluxing acetonitrile for 3 h gave almost exclusively the (Z)-maleate (10) (eq 8). The (E)-isomer was barely detectable by NMR spectroscopy.

Direct Displacement.

Replacement of the arylsulfonyl group in substrates like (1) by various alkyl and aryl Grignard or lithium complexes has been reported.17 The reaction is believed to involve initial attachment of the organometallic to the sulfonyl-bearing (a) carbon followed by expulsion of the arylsulfinate leaving group.17 Such a transformation offers another synthetic route to aryl- or alkylacetylenes. As such, mesitylmagnesium bromide reacts with ethynyl p-tolyl sulfone to give mesitylacetylene (11) in 85% yield (eq 9).


1. De Lucchi, O.; Modena, G. T 1984, 40, 2585.
2. Padwa, A.; Wannamaker, M. W. T 1990, 46, 1145.
3. Abramovitch, R. A.; Deeb, A.; Kishore, D.; Mpango, G. B. W.; Shinkai, I. G 1988, 118, 167.
4. Acheson, R. M.; Ansell, P. J. JCS(P1) 1987, 1275.
5. Altenbach, H.-J.; Blech, B.; Marco, J. A.; Vogel, E. AG(E) 1982, 21, 778.
6. Paquette, L. A.; Fisher, J. W.; Browne, A. R.; Doecke, C. W. JACS 1985, 107, 686.
7. (a) Davis, A. P.; Whitman, G. H. CC 1980, 639. (b) Tobe, Y.; Takahashi, T.; Ishikawa, T.; Yoshimura, M.; Suwa, M.; Kobiro, K; Kakiuchi, K; Gleiter, R. JACS 1990, 112, 8889. (c) Chow, T. J.; Lin, T.-H. Bull. Inst. Chem. Acad. Sin. 1986, 33, 47. (d) Chow, T. J.; Chao, Y.-S. SC 1988, 18, 1875.
8. Snider, B. B.; Kirk, T. C.; Roush, D. M.; Gonzalez, D. JOC 1980, 45, 5015.
9. (a) Truce, W. E.; Brady, D. G. JOC 1966, 31, 3543. (b) Maioli, L.; Modena, G. Ric. Sci. 1959, 29, 1931.
10. Van der Sluijs, M. J.; Stirling, C. J. M. JCS(P2) 1974, 1268.
11. (a) Truce, W. E.; Tichenor, G. J. W. JOC 1972, 37, 2391. (b) Stirling, C. J. M. JCS 1964, 5856. (c) De Lucchi, O.; Marchioro, C.; Valle, G.; Modena, G. CC 1985, 878. (d) De Lucchi, O.; Lucchini, V.; Marchioro, C.; Valle, G.; Modena, G. JOC 1986, 51, 1457.
12. (a) Sanders, J. A.; Hovius, K.; Engberts, J. B. F. N. JOC 1974, 39, 2641. (b) Aurich, H. G.; Hahn, K. CB 1979, 112, 2769.
13. Fiandanese, V.; Marchese, G.; Naso, F. TL 1978, 5131.
14. Eisch, J. J.; Behrooz, M.; Dua, S. K. JOM 1985, 285, 121.
15. Steglich, W.; Wegman, H. S 1980, 481.
16. Himbert, G.; Kosack, S. CB 1988, 121, 2163.
17. Himbert, G.; Kosack, S.; Maas, G. AG 1984, 96, 308.
18. (a) Eisch, J. J.; Shafi, B.; Odom, J. D.; Rheingold, A. L. JACS 1990, 112, 1847. (b) Smorada, R. L.; Truce, W. E. JOC 1979, 44, 3444.
19. Waykole, L.; Paquette, L. A. OS 1989, 67, 149.
20. Frye, L. L.; Sullivan, E. L.; Cusack, K. P.; Funaro, J. M. JOC 1992, 57, 697.
21. Iwata, N.; Morioka, T.; Kobayashi, T.; Asada, T.; Kinoshita, H.; Inomata, K. BCJ 1992, 65, 1379.
22. Back, T. G.; Collins, S.; Kerr, R. G. JOC 1983, 48, 3077.
23. Naso, F.; Ronzini, L. JCS(P1) 1974, 340.
24. Beccalli, E. M.; Manfredi, A.; Marchesini, A. JOC 1985, 50, 2372.
25. (a) Snider, B. B.; Kirk, T. C.; Roush, D. M.; Gonzalez, D. JOC 1980, 45, 5015. (b) Maioli, L.; Modena, G. Ric. Sci. 1959, 29, 1931.
26. Bhattacharya, S. N.; Josiah, B. M.; Walton, D. R. M. Organomet. Chem. Synth. 1971, 1, 145.
27. Prinzbach, H.; Babsch, H. H 1978, 11, 113.
28. Magnus, P. T 1977, 33, 2019.
29. Di Nunno, L.; Modena, G.; Scorrano, G. JCS(B) 1966, 1186.

Denis R. St. Laurent & Neelakautan Balasubramanian

Bristol-Myers Squibb Co., Wallingford, CT, USA



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