MODERN SYNTHETIC STRATEGIES FOR SUBSTITUTED VINYL SULFONES
DOI:
https://doi.org/10.58407/bht.1.26.18Keywords:
sulfones, vinyl sulfones, synthesis, substituted vinyl sulfones, enaminosulfones, aminovinyl sulfonesAbstract
Purpose of the work. The study aims to systematize and generalize current scientific data regarding synthetic approaches to the formation of substituted vinyl sulfones. This allows to specify the most effective strategies and predicting future directions for utilizing these compounds in modern organic and medicinal synthesis.
Methodology. A comprehensive analysis of publications in peer-reviewed scientific journals over the past two decades was conducted. Methods of comparative analysis, generalization, and critical evaluation of research results in the field of modern organic synthesis were employed. Particular attention was paid to studies that experimentally proves the advantages of novel synthetic methods compared to classics.
Scientific novelty. The work systematizes and critically analyzes the mass of data of recent years on the evolution of synthetic strategies for the creation of functionalized vinyl sulfones for the first time, which allowed us to present a conceptual map of modern approaches to the design of a vinyl sulfone fragment with a high level of regio- and stereocontrol in a single overview format.
Conclusions. The current state of development of methods for the synthesis of vinyl sulfones indicates a steady trend towards the introduction of metallocatalytic, electro- and photochemical methods, as well as the use of mild oxidation systems that provide high regio- and stereoselectivity of the process. Analysis of literary sources shows that the starting materials for introducing a vinyl fragment into the system are usually alkenes, alkynes and cinnamic acids, while the sources of the sulfonyl group most often are sulfinates, sulfonyl chlorides and sulfonyl hydrazides.
Modern approaches to the synthesis of β-aminovinyl sulfones focus on high chemoselectivity and the use of mild conditions, where control over the activation of C–H and C–N bonds plays a key role. It has been established that the direction of the reaction critically depends on the nature of the environment: the use of dimethyl sulfoxide and photocatalysis leads to formation of enamine sulfones, while aqueous conditions usually initiates the formation of sulfamides.
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References
Acton, Q. A. (Ed.). (2013). Sulfones – Advances in research and application. ScholarlyEditions.
Alba, A. N., Companyó, X., & Rios, R. (2010). Sulfones: new reagents in organocatalysis. Chemical Society reviews, 39(6), 2018–2033. https://doi.org/10.1039/b911852g
Al-Sader, B. H., & Kadri, M. (1985). Kinetics and mechanism of the 1,3-dipolar cycloaddition of phenyl azides to methyl 3-pyrrolidinoacrylate. Tetrahedron letters, 26(38), 4661-4664. https://doi.org/10.1016/S0040-4039(00)98779-3
Breitschaft, F. A., Saak, A. L., Krumbiegel, C., Bartolomeu, A. de A., Weyhermüller, T., & Waldvogel, S. R. (2025). Multicomponent electrosynthesis of enaminyl sulfonates starting from alkylamines, SO2, and alcohols. Organic Letters, 27(5), 1210–1215. https://doi.org/10.1021/acs.orglett.4c04746
Cacchi, S., Fabrizi, G., Goggiamani, A., Parisi, L. M., & Bernini, R. (2004). Unsymmetrical diaryl sulfones and aryl vinyl sulfones through palladium-catalyzed coupling of aryl and vinyl halides or triflates with sulfinic acid salts. The Journal of Organic Chemistry, 69(17), 5608–5614. https://doi.org/10.1021/jo0493469
Cai, S., Xu, Y., Chen, D., Li, L., Chen, Q., Huang, M., & Weng, W. (2016). Visible-light-enabled decarboxylative sulfonylation of cinnamic acids with sulfonylhydrazides under transition-metal-free conditions. Organic Letters, 18(12), 2990–2993. https://doi.org/10.1021/acs.orglett.6b01353
Cai, Y., Zhang, R., Sun, D., Xu, S., & Zhou, Q. (2017). Eosin Y-sensitized photocatalytic reaction of tertiary aliphatic amines with arenesulfonyl chlorides under visible-light irradiation. Synlett, 28(13), 1630–1635. https://doi.org/10.1055/s-0036-1588828
Cheng, Z., Sun, P., Tang, A., Jin, W., & Liu, C. (2019). Switchable synthesis of aryl sulfones and sulfoxides through solvent-promoted oxidation of sulfides with O2/air. Organic Letters, 21(22), 8925–8929. https://doi.org/10.1021/acs.orglett.9b03192
Das, B., Lingaiah, M., Damodar, K., & Bhunia, N. (2011). An efficient synthesis of vinyl sulfones from alkenes and aryl sulfinates. Synthesis, 2011(18), 2941–2944. https://doi.org/10.1055/s-0030-1260142
Eberlin, M. N., & Kascheres, C. (1988). Catalyzed reaction of diazodiphenylethanone and related diazo ketones with enaminones as a source of pyrroles. The Journal of Organic Chemistry, 53(9), 2084-2086. https://doi.org/10.1021/jo00244a042
Fang, P., Wang, Q., Shen, X., Zhao, J., Wang, F., & Liu, Z.-Q. (2024). Electrochemical synthesis of vinyl, alkyl, and allyl sulfones from sodium sulfinates and olefins. The Journal of Organic Chemistry, 89(17), 12619–12627. https://doi.org/10.1021/acs.joc.4c01548
Ge, Q.-Q., Qian, J.-S., & Xuan, J. (2019). Electron donor-acceptor complex enabled decarboxylative sulfonylation of cinnamic acids under visible-light irradiation. The Journal of Organic Chemistry, 84(13), 8691–8701. https://doi.org/10.1021/acs.joc.9b00552
Goh, J., Maraswami, M., & Loh, T.-P. (2021). Synthesis of vinylic sulfones in aqueous media. Organic Letters, 23(3), 1060–1065. https://doi.org/10.1021/acs.orglett.0c04257
Guan, Z.-H., Zuo, W., Zhao, L.-B., Ren, Z.-H., & Liang, Y.-M. (2007). An economical and convenient synthesis of vinyl sulfones. Synthesis, 2007(10), 1465–1470. https://doi.org/10.1055/s-2007-966039
He, F.-S., Gong, X., Rojsitthisak, P., & Wu, J. (2019). Direct C-H methylsulfonylation of alkenes with the insertion of sulfur dioxide. The Journal of Organic Chemistry, 84(20), 13159–13163. https://doi.org/10.1021/acs.joc.9b01729
Jiang, Q., Xu, B., Jia, J., Zhao, A., Zhao, Y.-R., Li, Y.-Y., He, N.-N., & Guo, C.-C. (2014). Copper-catalyzed aerobic decarboxylative sulfonylation of cinnamic acids with sodium sulfinates: Stereospecific synthesis of (E)-alkenyl sulfones. The Journal of Organic Chemistry, 79(16), 7372–7379. https://doi.org/10.1021/jo5010845
Jiang, Z., You, K., Wu, H., Xu, M., Wang, T., & Luo, J. (2024). Photochemical halogen-bonding promoted synthesis of vinyl sulfones via vinyl and sulfonyl radicals. Organic Letters, 26(4), 631–635. https://doi.org/10.1021/acs.orglett.3c03958
Kadari, L., Palakodety, R. K., & Yallapragada, L. P. (2017). Iodine-catalyzed facile approach to sulfones employing TosMIC as a sulfonylating agent. Organic Letters, 19(10), 2580–2583. https://doi.org/10.1021/acs.orglett.7b00896
Kim, H.-S., & Lee, S. (2019). Electrochemical coupling of arylsulfonyl hydrazides and tertiary amines for the synthesis of β-amidovinyl sulfones. European Journal of Organic Chemistry, 2019(44), 7338–7341. https://doi.org/10.1002/ejoc.201901277
Lai, J., Chang, L., & Yuan, G. (2016). I2/TBHP mediated C–N and C–H bond cleavage of tertiary amines toward selective synthesis of sulfonamides and β-arylsulfonyl enamines: The solvent effect on reaction. Organic Letters, 18(13), 3190–3193. https://doi.org/10.1021/acs.orglett.6b01428
Li, X., Shi, X., Fang, M., & Xu, X. (2013). Iron halide-mediated regio- and stereoselective halosulfonylation of terminal alkynes with sulfonylhydrazides: Synthesis of (E)-β-chloro and bromo vinylsulfones. The Journal of Organic Chemistry, 78(18), 9499–9504. https://doi.org/10.1021/jo401581n
Lu, N., Zhang, Z., Ma, N., Wu, C., Zhang, G., Liu, Q., & Liu, T. (2018). Copper-catalyzed difunctionalization of allenes with sulfonyl iodides leading to (E)-α-iodomethyl vinylsulfones. Organic Letters, 20(14), 4318–4322. https://doi.org/10.1021/acs.orglett.8b01765
Mao, S., Gao, Y.-R., Zhu, X.-Q., Guo, D.-D., & Wang, Y.-Q. (2015). Copper-catalyzed radical reaction of N-tosylhydrazones: Stereoselective synthesis of (E)-vinyl sulfones. Organic Letters, 17(7), 1692–1695. https://doi.org/10.1021/acs.orglett.5b00461
Morales-Sanfrutos, J., Lopez-Jaramillo, J., Ortega-Muñoz, M., Megia-Fernandez, A., Perez-Balderas, F., Hernandez-Mateo, F., & Santoyo-Gonzalez, F. (2010). Vinyl sulfone: a versatile function for simple bioconjugation and immobilization. Organic & biomolecular chemistry, 8(3), 667–675. https://doi.org/10.1039/b920576d
Nair, V., Augustine, A., & Suja, T. D. (2002). CAN mediated reaction of aryl sulfinates with alkenes and alkynes: Synthesis of vinyl sulfones, β-iodovinyl sulfones and acetylenic sulfones. Synthesis, 2002(15), 2259–2265. https://doi.org/10.1055/s-2002-34838
Prek, B., Bezenšek, J., Kasunič, M., Grošelj, U., Svete, J., & Stanovnik, B. (2014). Reactions of enaminones and related compounds with N, N-dimethylacetamide dimethyl acetal. A simple one-pot metal-free synthesis of polysubstituted benzene derivatives. Tetrahedron, 70(14), 2359-2369. https://doi.org/10.1016/j.tet.2014.02.039
Qian, P., Bi, M., Su, J., Zha, Z., & Wang, Z. (2016). Electrosynthesis of (E)-vinyl sulfones directly from cinnamic acids and sodium sulfinates via decarboxylative sulfono functionalization. The Journal of Organic Chemistry, 81(11), 4876–4882. https://doi.org/10.1021/acs.joc.6b00661
Rao, W.-H., Li, Y.-G., Jiang, L.-L., Gao, C., Wang, Y.-Z., Liu, J.-F., Zhou, F.-Y., Zou, G.-D., & Cao, X. (2024). Nickel-catalyzed direct sulfonylation of styrenes and unactivated aliphatic alkenes with sulfonyl chlorides. The Journal of Organic Chemistry, 89(14), 9755–9768. https://doi.org/10.1021/acs.joc.4c00094
Rawat, A., Roy, M., Jyoti, A., Kaushik, S., Verma, K., & Srivastava, V. K. (2021). Cysteine proteases: Battling pathogenic parasitic protozoans with omnipresent enzymes. Microbiological research, 249, 126784. https://doi.org/10.1016/j.micres.2021.126784
Reddy, G. J., Latha, D., Thirupathaiah, C., & Rao, K. S. (2005). A facile synthesis of 2, 3-disubstituted-6-arylpyridines from enaminones using montmorillonite K10 as solid acid support. Tetrahedron letters, 46(2), 301-302. https://doi.org/10.1016/j.tetlet.2004.11.071
Rong, G., Mao, J., Yan, H., Zheng, Y., & Zhang, G. (2015). Phosphoric acid-mediated synthesis of vinyl sulfones through decarboxylative coupling reactions of sodium sulfinates with phenylpropiolic acids. The Journal of Organic Chemistry, 80(15), 7652–7657. https://doi.org/10.1021/acs.joc.5b01212
Scott, K. A., & Njardarson, J. T. (2018). Analysis of US FDA-Approved Drugs Containing Sulfur Atoms. Topics in current chemistry (Cham), 376(1), 5. https://doi.org/10.1007/s41061-018-0184-5
Shelke, G. M., Rao, V. K., Pericherla, K., & Kumar, A. (2014). An efficient and facile synthesis of vinyl sulfones via microwave-assisted copper triflate catalyzed hydrosulfonylation of alkynes. Synlett, 25(16), 2345–2349. https://doi.org/10.1055/s-0034-1378546
Shiri, M., Salehi, P., Mohammadpour, Z., Salehi, P., & Notash, B. (2021). Cs2CO3-mediated regio- and stereoselective sulfonylation of 1,1-dibromo-1-alkenes with sodium sulfinates. Synthesis, 53, 1149–1156. https://doi.org/10.1055/s-0040-1706295
Singh, R., Allam, B. K., Singh, N., Kumari, K., Singh, S. K., & Singh, K. N. (2015). A direct metal-free decarboxylative sulfono functionalization (DSF) of cinnamic acids to α, β-unsaturated phenyl sulfones. Organic Letters, 17(11), 2656–2659. https://doi.org/10.1021/acs.orglett.5b01037
Spivey, A. C., Srikaran, R., Diaper, C. M., & Turner, D. J. (2003). Traceless solid phase synthesis of 2-substituted pyrimidines using an ‘off-the-shelf’chlorogermane-functionalised resin. Organic & biomolecular chemistry, 1(10), 1638-1640. https://doi.org/10.1039/B303064D
Stanovnik, B., & Svete, J. (2004). Synthesis of heterocycles from alkyl 3-(dimethylamino)propenoates and related enaminones. Chemical reviews, 104(5), 2433–2480. https://doi.org/10.1021/cr020093y
Strasser, S., Wappl, C., & Slugovc, C. (2017). Solvent-free macrocyclisation by nucleophile-mediated oxa-Michael addition polymerisation of divinyl sulfone and alcohols. Polymer Chemistry, 8(11), 1797-1804. https://doi.org/10.1039/C7PY00152E
Taneda, H., Inamoto, K., & Kondo, Y. (2014). Direct condensation of functionalized sp 3 carbons with formanilides for enamine synthesis using an in situ generated HMDS amide catalyst. Chemical Communications, 50(49), 6523-6525. https://doi.org/10.1039/C4CC02228A
Tang, Y., Jiang, L., Li, S., Chen, X., Li, C., & Zhang, X. (2025). Iodine-promoted for synthesis of (Z)-β-dithiocarbamate enamine derivatives in water and their antibacterial evaluation. Journal of Molecular Structure, 1322, 140356. https://doi.org/10.1016/j.molstruc.2024.140356
Taniguchi, N. (2011). Stereoselective synthesis of (E)-alkenyl sulfones from alkenes or alkynes via copper-catalyzed oxidation of sodium sulfinates. Synlett, 2011(09), 1308–1312. https://doi.org/10.1055/s-0030-1260544
Venkataraman, K. (Ed.). (2012). The Chemistry of Synthetic Dyes V4 (Vol. 4). Elsevier.
Voutyritsa, E., Triandafillidi, I., & Kokotos, C. G. (2017). Green organocatalytic oxidation of sulfides to sulfoxides and sulfones. Synthesis, 49(04), 917–924. https://doi.org/10.1055/s-0036-1588315
Wang, L., Yue, H., Yang, D., Cui, H., Zhu, M., Wang, J., Wei, W., & Wang, H. (2017). Metal-free oxidative coupling of aromatic alkenes with thiols leading to (E)-vinyl sulfones. The Journal of Organic Chemistry, 82(13), 6857–6864. https://doi.org/10.1021/acs.joc.7b00994
Wang, P.-L., Gao, H., Jiang, Z.-S., Li, C., Tian, Z.-A., & Li, P.-H. (2020). Electrochemical synthesis of vinyl sulfones by sulfonylation of styrenes with a catalytic amount of potassium iodide. Synlett, 31(17), 1720–1724. https://doi.org/10.1055/s-0040-1707212
Wang, Y., Xiong, G., Zhang, C., & Chen, Y. (2021). Controllable activation of β-alkyl nitroalkenes: Regioselective synthesis of allyl and vinyl sulfones. The Journal of Organic Chemistry, 86(5), 4018–4026. https://doi.org/10.1021/acs.joc.0c02869
Xu, Q.-L., Dai, L.-X., & You, S.-L. (2010). Tandem Ir-catalyzed allylic substitution reaction of allyl sulfinates and isomerization. Organic Letters, 12(4), 800–803. https://doi.org/10.1021/ol902873q
Xue, N., Guo, R., Tu, X., Luo, W., Deng, W., & Xiang, J. (2016). Efficient synthesis of vinyl sulfones by manganese-catalyzed decarboxylative coupling of cinnamic acids with aromatic sulfinic acid sodium salts. Synlett, 27(19), 2695–2698. https://doi.org/10.1055/s-0035-1562476
Yao, W., Lv, K., Xie, Z., Qiu, H., & Ma, M. (2023). Catalyst-free electrochemical sulfonylation of organoboronic acids. The Journal of Organic Chemistry, 88(4), 2296–2305. https://doi.org/10.1021/acs.joc.2c02690
Zhai, H. (2006). Synthesis of Nitrogen Heterocycles Using Unsaturated Sulfones (Doctoral dissertation, University оf Calgary).
Zhang, M., & Zeng, X. (2021). Metal-free radical thiocyanatosulfonation of terminal alkynes in aqueous medium. Organic Letters, 23(9), 3326–3330. https://doi.org/10.1021/acs.orglett.1c00820
Zhang, M., Zhao, W., Ma, J., Li, J., Meng, Q., Shen, C., & Zeng, X. (2023). Syn-selective chlorosulfonylation of alkynes via a copper-powder-initiated atom transfer radical addition reaction and mechanistic studies. Organic Letters, 25(1), 231–235. https://doi.org/10.1021/acs.orglett.2c04074
Zhao, Y., Lai, Y.-L., Du, K.-S., Lin, D.-Z., & Huang, J.-M. (2017). Electrochemical decarboxylative sulfonylation of cinnamic acids with aromatic sulfonylhydrazides to vinyl sulfones. The Journal of Organic Chemistry, 82(18), 9655–9661. https://doi.org/10.1021/acs.joc.7b01741
Zhou, C., & Zeng, X. (2021). Iodosulfonylation of alkynes under ultrasound irradiation. Synthesis, 53(24), 4614–4620. https://doi.org/10.1055/a-1559-3346
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