Logo Beilstein Institut

Electrophilic trifluoromethylselenolation of terminal alkynes with Se-(trifluoromethyl) 4-methylbenzenesulfonoselenoate

  1. 1 ORCID Logo ,
  2. 1 ORCID Logo and
  3. 1,2 ORCID Logo
1Institute of Chemistry and Biochemistry, Univ Lyon, Université Lyon 1, CNRS, 43 Bd du 11 novembre 1918, F-69622 Villeurbanne, France
2CERMEP-In vivo Imaging, Groupement Hospitalier Est, 59 Bd Pinel, F-69003 Lyon, France
  1. Corresponding author email
This article is part of the Thematic Series "Organo-fluorine chemistry IV".
Guest Editor: D. O'Hagan
Beilstein J. Org. Chem. 2017, 13, 2626–2630. https://doi.org/10.3762/bjoc.13.260
Received 22 Sep 2017, Accepted 21 Nov 2017, Published 07 Dec 2017
Full Research Paper
cc by logo
PDF
Album
Supp Info
Cite

Abstract

Herein the nucleophilic addition of Se-(trifluoromethyl) 4-methylbenzenesulfonoselenoate, a stable and easy-to-handle reagent, to alkynes is described. This reaction provides trifluoromethylselenylated vinyl sulfones with good results and the method was extended also to higher fluorinated homologs. The obtained compounds are valuable building blocks for further syntheses of fluoroalkylselenolated molecules.

Keywords: alkynes; nucleophilic addition; perfluoroalkylselenolation; Se-(trifluoromethyl) 4-methylbenzenesulfonoselenoate; trifluoromethylselenolation

Introduction

Over the last decades, fluorinated compounds have been the subject of growing interest [1,2]. The specific properties introduced by fluorinated groups have contributed to the “success story” of fluorinated molecules. Nowadays, fluorinated compounds find applications in various fields, from life sciences to materials [3-15]. In the objective to design new molecules with specific properties, novel fluorinated substituents have been developed, such as diverse trifluoromethylchalcogeno groups, due to their particular electronic properties [16] and, more especially, to their high lipophilicity [17]. Whereas the CF3O and CF3S substituents have been largely studied [18-23], the CF3Se group, albeit known, has gained only little attention until recently. However, selenylated derivatives present pertinent properties and have found some interest in materials [24], life sciences [25-33] and drug design [34-37]. Furthermore, very recently, the Hansch lipophilicity parameter of CF3Se has been determined (πR = 1.29) – a high value lying between that of CF3O and CF3S [38]. Consequently, trifluoromethylselenolated molecules could represent interesting alternatives in the modulation of properties for various applications.

Despite such potential interest for CF3Se compounds, methods to their syntheses remain still limited [39]. Direct trifluoromethylselenolation reactions have recently gained renewed interest and mainly follow two strategies. The nucleophilic approach is based on the use of the CF3Se− anion which must be prepared from stoichiometric amounts of metallic selenium [40-53]. Concerning the electrophilic approach, two reagents, that are easy to obtain, have been described: CF3SeCl [38,54-67] and CF3SeTs [68].

Results and Discussion

Recently, we have described the electrophilic addition of CF3SeCl to alkenes to access α-chloro-β-trifluoromethylselenolated molecules [65]. These products are particularly interesting because the presence of the chlorine substituent opens the way to post-functionalization and thereby to syntheses of more elaborated compounds. However, the similar reaction with alkynes has failed and only a complex mixture was observed which is basically due to the high reactivity of CF3SeCl.

To overcome this issue, we have developed another easier-to-use reagent with a more controlled reactivity to perform electrophilic trifluoromethylselenolations, namely Se-(trifluoromethyl) 4-methylbenzenesulfonoselenoate (1a). This reagent is easily obtained by reacting sodium toluenesulfinate with in situ formed CF3SeCl [68]. With this reagent at hand we envisaged the trifluoromethylselenolation of alkynes.

To our delight, the addition of 1a to phenylacetylene (2a) at room temperature, without any other practical precautions, lead to the expected addition product 3a with good yield (Scheme 1).

[1860-5397-13-260-i1]

Scheme 1: Electrophilic addition of 1a to alkynes. Yields shown are those of isolated products; yields determined by 19F NMR spectroscopy with PhOCF3 as an internal standard are shown in parentheses.

Subsequently, the reaction was extended to various arylalkynes and afforded, in general, good yields. Satisfactory to excellent results were observed whatever the electronic character (donor or acceptor) of the substituents on the phenyl moiety were. Even highly electron-withdrawing groups led to satisfactory yields of the products 3h–j. The reaction is also not too sensitive to steric hindrance because good results were obtained also with ortho-substituted substrates 3c,e,i. Nevertheless, the reaction with aliphatic alkyne 2k, resulted in a low yield (28%).

The reaction is stereoselective with the exclusive formation of the trans-isomers. Further, a high regioselectivity is observed but, surprisingly, the anti-Markovnikov regioisomers were obtained. The stereochemistry and regiochemistry were confirmed thanks to the X-ray structure of compound 3a (Figure 1).

[1860-5397-13-260-1]

Figure 1: Single-crystal X-ray structure of 3a.

From a mechanistic point of view, the reaction starts certainly with the intermediate formation of the trifluoromethylselenonium ion I. This is in accordance with the observed trans-selectivity due to the anti opening of I by the toluenesulfinate anion. The regioselectivity could be rationalized by the steric hindrance between the aromatic moiety and the large nucleophile (toluenesulfinate anion) which favors the attack on the less hindered side (Scheme 2, pathway a). Such sensitivity to steric hindrance of I was confirmed by the lack of reactions observed with internal alkynes.

[1860-5397-13-260-i2]

Scheme 2: Mechanism proposal.

Higher homologs of reagent 1a are also available, the reaction was briefly performed with 1b and 1c (Scheme 3). The expected products were obtained with good yields. The tridecafluorohexylselenyl group in product 5a makes this compound interesting because it opens the way to applications in the design of fluorinated polymers or surfactants.

[1860-5397-13-260-i3]

Scheme 3: Perfluoroalkylselenolation of alkynes. Yields shown are those of isolated products; yields determined by 19F NMR spectroscopy with PhOCF3 as an internal standard are shown in parentheses.

Conclusion

To conclude, Se-(trifluoromethyl) 4-methylbenzenesulfonoselenoate and Se-(perfluoroalkyl) 4-methylbenzenesulfonoselenoate have been confirmed as valuable bench-stable reagents to perform perfluoroalkylselenolations. Nucleophilic additions with alkynes to provide perfluoroalkylselenolated vinyl sulfones can easily be carried out. Se-(Trifluoromethyl) 4-methylbenzenesulfonoselenoate and Se-(perfluoroalkyl) 4-methylbenzenesulfonoselenoate constitute interesting building blocks for various applications.

Experimental

Typical procedure: To a flask equipped with a magnetic stir bar were added 1 (0.25 mmol, 1.1 equiv), alkyne 2 (0.23 mmol, 1.0 equiv), and anhydrous THF (1 mL). The reaction was stirred at 25 °C for 15–18 hours (conversion was checked by 19F NMR with PhOCF3 as internal standard). The crude residue was purified by chromatography to afford the desired products 3–5.

Supporting Information

Supporting Information File 1: Additional experimental and analytical data and NMR spectra.
Format: PDF Size: 5.1 MB Download

Acknowledgements

Clément Ghiazza holds a doctoral fellowship from la Région Rhône Alpes. The authors are grateful to the CNRS and the French Ministry of Research for financial support. The French Fluorine Network is also acknowledged for its support. We thank Dr. Erwann Jeanneau (Centre de Diffractométrie Henri Longchambon) for collecting the crystallographic data and solving the structure of 3a.

References

  1. Dolbier, W. R., Jr. J. Fluorine Chem. 2005, 126, 157–163. doi:10.1016/j.jfluchem.2004.09.033
    Return to citation in text: [1]
  2. Kirsch, P. Introduction. Modern Fluoroorganic Chemistry, 2nd ed.; Wiley-VCH: Weinheim, Germany, 2013; pp 1–24.
    Return to citation in text: [1]
  3. Becker, A. Inventory of Industrial Fluoro-biochemicals; Eyrolles: Paris, 1996.
    Return to citation in text: [1]
  4. Smart, B. E. J. Fluorine Chem. 2001, 109, 3–11. doi:10.1016/S0022-1139(01)00375-X
    Return to citation in text: [1]
  5. Hagmann, W. K. J. Med. Chem. 2008, 51, 4359–4369. doi:10.1021/jm800219f
    Return to citation in text: [1]
  6. Wang, J.; Sánchez-Roselló, M.; Aceña, J. L.; del Pozo, C.; Sorochinsky, A. E.; Fustero, S.; Soloshonok, V. A.; Liu, H. Chem. Rev. 2014, 114, 2432–2506. doi:10.1021/cr4002879
    Return to citation in text: [1]
  7. Gillis, E. P.; Eastman, K. J.; Hill, M. D.; Donnelly, D. J.; Meanwell, N. A. J. Med. Chem. 2015, 58, 8315–8359. doi:10.1021/acs.jmedchem.5b00258
    Return to citation in text: [1]
  8. Zhou, Y.; Wang, J.; Gu, Z.; Wang, S.; Zhu, W.; Aceña, J. L.; Soloshonok, V. A.; Izawa, K.; Liu, H. Chem. Rev. 2016, 116, 422–518. doi:10.1021/acs.chemrev.5b00392
    Return to citation in text: [1]
  9. Theodoridis, G. Chapter 4 Fluorine-Containing Agrochemicals: An Overview of Recent Developments. In Advances in Fluorine Science; Tressaud, A., Ed.; Elsevier: Amsterdam, 2006; Vol. 2, pp 121–175. doi:10.1016/S1872-0358(06)02004-5
    Return to citation in text: [1]
  10. Jeschke, P. Pest Manage. Sci. 2010, 66, 10–27. doi:10.1002/ps.1829
    Return to citation in text: [1]
  11. Fujiwara, T.; O’Hagan, D. J. Fluorine Chem. 2014, 167, 16–29. doi:10.1016/j.jfluchem.2014.06.014
    Return to citation in text: [1]
  12. Pagliaro, M.; Ciriminna, R. J. Mater. Chem. 2005, 15, 4981–4991. doi:10.1039/b507583c
    Return to citation in text: [1]
  13. Hird, M. Chem. Soc. Rev. 2007, 36, 2070–2095. doi:10.1039/b610738a
    Return to citation in text: [1]
  14. Chopra, D.; Row, T. N. G. CrystEngComm 2011, 13, 2175–2186. doi:10.1039/c0ce00538j
    Return to citation in text: [1]
  15. Berger, R.; Resnati, G.; Metrangolo, P.; Weber, E.; Hulliger, J. Chem. Soc. Rev. 2011, 40, 3496–3508. doi:10.1039/c0cs00221f
    Return to citation in text: [1]
  16. Hansch, C.; Leo, A.; Taft, R. W. Chem. Rev. 1991, 91, 165–195. doi:10.1021/cr00002a004
    Return to citation in text: [1]
  17. Leo, A.; Hansch, C.; Elkins, D. Chem. Rev. 1971, 71, 525–616. doi:10.1021/cr60274a001
    Return to citation in text: [1]
  18. Toulgoat, F.; Alazet, S.; Billard, T. Eur. J. Org. Chem. 2014, 2415–2428. doi:10.1002/ejoc.201301857
    Return to citation in text: [1]
  19. Xu, X.-H.; Matsuzaki, K.; Shibata, N. Chem. Rev. 2015, 115, 731–764. doi:10.1021/cr500193b
    Return to citation in text: [1]
  20. Toulgoat, F.; Billard, T. Towards CF3S Group: From Trifluoromethylation of Sulfides to Direct Trifluoromethylthiolation. In Modern Synthesis Processes and Reactivity of Fluorinated Compounds: Progress in Fluorine Science; Groult, H.; Leroux, F.; Tressaud, A., Eds.; Elsevier Science: London, United Kingdom, 2017; pp 141–179. doi:10.1016/B978-0-12-803740-9.00006-8
    Return to citation in text: [1]
  21. Leroux, F. R.; Manteau, B.; Vors, J.-P.; Pazenok, S. Beilstein J. Org. Chem. 2008, 4, No. 13. doi:10.3762/bjoc.4.13
    Return to citation in text: [1]
  22. Besset, T.; Jubault, P.; Pannecoucke, X.; Poisson, T. Org. Chem. Front. 2016, 3, 1004–1010. doi:10.1039/C6QO00164E
    Return to citation in text: [1]
  23. Tlili, A.; Toulgoat, F.; Billard, T. Angew. Chem. 2016, 128, 11900–11909. doi:10.1002/ange.201603697
    Return to citation in text: [1]
  24. Romashov, L. V.; Ananikov, V. P. Chem. – Eur. J. 2013, 19, 17640–17660. doi:10.1002/chem.201302115
    Return to citation in text: [1]
  25. Wessjohann, L. A.; Schneider, A.; Abbas, M.; Brandt, W. Biol. Chem. 2007, 388, 997–1006. doi:10.1515/BC.2007.138
    Return to citation in text: [1]
  26. Bodnar, M.; Konieczka, P.; Namiesnik, J. J. Environ. Sci. Health, Part C: Environ. Carcinog. Ecotoxicol. Rev. 2012, 30, 225–252. doi:10.1080/10590501.2012.705164
    Return to citation in text: [1]
  27. Holben, D. H.; Smith, A. M. J. Am. Diet. Assoc. 1999, 99, 836–843. doi:10.1016/S0002-8223(99)00198-4
    Return to citation in text: [1]
  28. Brown, K. M.; Arhur, J. R. Public Health Nutr. 2001, 4, 593–599. doi:10.1079/PHN2001143
    Return to citation in text: [1]
  29. Kyriakopoulos, A.; Behne, D. Rev. Physiol., Biochem. Pharmacol. 2002, 145, 1–46. doi:10.1007/BFb0116430
    Return to citation in text: [1]
  30. Lu, J.; Holmgren, A. J. Biol. Chem. 2009, 284, 723–727. doi:10.1074/jbc.R800045200
    Return to citation in text: [1]
  31. Pacuła, A. J.; Kaczor, K. B.; Wojtowicz, A.; Antosiewicz, J.; Janecka, A.; Długosz, A.; Janecki, T.; Ścianowski, J. Bioorg. Med. Chem. 2017, 25, 126–131. doi:10.1016/j.bmc.2016.10.018
    Return to citation in text: [1]
  32. Combs, G. F., Jr.; Gray, W. P. Pharmacol. Ther. 1998, 79, 179–192. doi:10.1016/S0163-7258(98)00014-X
    Return to citation in text: [1]
  33. Rayman, M. P. Lancet 2000, 356, 233–241. doi:10.1016/S0140-6736(00)02490-9
    Return to citation in text: [1]
  34. Abdulah, R.; Miyazaki, K.; Nakazawa, M.; Koyama, H. J. Trace Elem. Med. Biol. 2005, 19, 141–150. doi:10.1016/j.jtemb.2005.09.003
    Return to citation in text: [1]
  35. Angeli, A.; Tanini, D.; Viglianisi, C.; Panzella, L.; Capperucci, A.; Menichetti, S.; Supuran, C. T. Bioorg. Med. Chem. 2017, 25, 2518–2523. doi:10.1016/j.bmc.2017.03.013
    Return to citation in text: [1]
  36. Thangamani, S.; Younis, W.; Seleem, M. N. Sci. Rep. 2015, 5, No. 11596. doi:10.1038/srep11596
    Return to citation in text: [1]
  37. Singh, N.; Sharpley, A. L.; Emir, U. E.; Masaki, C.; Herzallah, M. M.; Gluck, M. A.; Sharp, T.; Harmer, C. J.; Vasudevan, S. R.; Cowen, P. J.; Churchill, G. C. Neuropsychopharmacology 2016, 41, 1768–1778. doi:10.1038/npp.2015.343
    Return to citation in text: [1]
  38. Glenadel, Q.; Ismalaj, E.; Billard, T. Eur. J. Org. Chem. 2017, 530–533. doi:10.1002/ejoc.201601526
    Return to citation in text: [1] [2]
  39. Zhang, C. J. Chin. Chem. Soc. 2017, 64, 457–463. doi:10.1002/jccs.201600861
    Return to citation in text: [1]
  40. Chen, C.; Ouyang, L.; Lin, Q.; Liu, Y.; Hou, C.; Yuan, Y.; Weng, Z. Chem. – Eur. J. 2014, 20, 657–661. doi:10.1002/chem.201303934
    Return to citation in text: [1]
  41. Rong, M.; Huang, R.; You, Y.; Weng, Z. Tetrahedron 2014, 70, 8872–8878. doi:10.1016/j.tet.2014.09.091
    Return to citation in text: [1]
  42. Zhu, P.; He, X.; Chen, X.; You, Y.; Yuan, Y.; Weng, Z. Tetrahedron 2014, 70, 672–677. doi:10.1016/j.tet.2013.11.093
    Return to citation in text: [1]
  43. Aufiero, M.; Sperger, T.; Tsang, A. S.-K.; Schoenebeck, F. Angew. Chem. 2015, 127, 10462–10466. doi:10.1002/ange.201503388
    Return to citation in text: [1]
  44. Hou, C.; Lin, X.; Huang, Y.; Chen, Z.; Weng, Z. Synthesis 2015, 47, 969–975. doi:10.1055/s-0034-1379972
    Return to citation in text: [1]
  45. Lefebvre, Q.; Pluta, R.; Rueping, M. Chem. Commun. 2015, 51, 4394–4397. doi:10.1039/C4CC10212F
    Return to citation in text: [1]
  46. Wang, Y.; You, Y.; Weng, Z. Org. Chem. Front. 2015, 2, 574–577. doi:10.1039/C5QO00045A
    Return to citation in text: [1]
  47. Wu, C.; Huang, Y.; Chen, Z.; Weng, Z. Tetrahedron Lett. 2015, 56, 3838–3841. doi:10.1016/j.tetlet.2015.04.088
    Return to citation in text: [1]
  48. Fang, W.-Y.; Dong, T.; Han, J.-B.; Zha, G.-F.; Zhang, C.-P. Org. Biomol. Chem. 2016, 14, 11502–11509. doi:10.1039/C6OB02107G
    Return to citation in text: [1]
  49. Matheis, C.; Krause, T.; Bragoni, V.; Goossen, L. J. Chem. – Eur. J. 2016, 22, 12270–12273. doi:10.1002/chem.201602730
    Return to citation in text: [1]
  50. Matheis, C.; Wagner, V.; Goossen, L. J. Chem. – Eur. J. 2016, 22, 79–82. doi:10.1002/chem.201503524
    Return to citation in text: [1]
  51. Tian, Q.; Weng, Z. Chin. J. Chem. 2016, 34, 505–510. doi:10.1002/cjoc.201600052
    Return to citation in text: [1]
  52. Wang, J.; Zhang, M.; Weng, Z. J. Fluorine Chem. 2017, 193, 24–32. doi:10.1016/j.jfluchem.2016.11.006
    Return to citation in text: [1]
  53. Dürr, A. B.; Fisher, H. C.; Kalvet, I.; Truong, K.-N.; Schoenebeck, F. Angew. Chem., Int. Ed. 2017, 56, 13431–13435. doi:10.1002/anie.201706423
    Return to citation in text: [1]
  54. Dale, J. W.; Emeléus, H. J.; Haszeldine, R. N. J. Chem. Soc. 1958, 2939–2945. doi:10.1039/JR9580002939
    Return to citation in text: [1]
  55. Yarovenko, N. N.; Shemanina, V. N.; Gazieva, G. B. Russ. J. Gen. Chem. 1959, 29, 924–927.
    Return to citation in text: [1]
  56. Yagupol'skii, L. M.; Voloshchuk, V. G. Russ. J. Gen. Chem. 1966, 36, 173–174.
    Return to citation in text: [1]
  57. Voloshchuk, V. G.; Yagupol'skii, L. M.; Syrova, G. P.; Bystrov, V. P. Russ. J. Gen. Chem. 1967, 37, 105–108.
    Return to citation in text: [1]
  58. Yagupol'skii, L. M.; Voloshchuk, V. G. Russ. J. Gen. Chem. 1967, 37, 1463–1465.
    Return to citation in text: [1]
  59. Yagupol'skii, L. M.; Voloshchuk, V. G. Russ. J. Gen. Chem. 1968, 38, 2426–2429.
    Return to citation in text: [1]
  60. Marsden, C. J. J. Fluorine Chem. 1975, 5, 401–422. doi:10.1016/S0022-1139(00)82499-9
    Return to citation in text: [1]
  61. Haas, A.; Praas, H.-W. Chem. Ber. 1992, 125, 571–579. doi:10.1002/cber.19921250308
    Return to citation in text: [1]
  62. Magnier, E.; Vit, E.; Wakselman, C. Synlett 2001, 1260–1262. doi:10.1055/s-2001-16050
    Return to citation in text: [1]
  63. Magnier, E.; Wakselman, C. Collect. Czech. Chem. Commun. 2002, 67, 1262–1266. doi:10.1135/cccc20021262
    Return to citation in text: [1]
  64. Glenadel, Q.; Ismalaj, E.; Billard, T. J. Org. Chem. 2016, 81, 8268–8275. doi:10.1021/acs.joc.6b01344
    Return to citation in text: [1]
  65. Ghiazza, C.; Glenadel, Q.; Tlili, A.; Billard, T. Eur. J. Org. Chem. 2017, 3812–3814. doi:10.1002/ejoc.201700643
    Return to citation in text: [1] [2]
  66. Ghiazza, C.; Tlili, A.; Billard, T. Molecules 2017, 22, 833–841. doi:10.3390/molecules22050833
    Return to citation in text: [1]
  67. Ghiazza, C.; Billard, T.; Tlili, A. Chem. – Eur. J. 2017, 23, 10013–10016. doi:10.1002/chem.201702028
    Return to citation in text: [1]
  68. Glenadel, Q.; Ghiazza, C.; Tlili, A.; Billard, T. Adv. Synth. Catal. 2017, 359, 3414–3420. doi:10.1002/adsc.201700904
    Return to citation in text: [1] [2]

© 2017 Ghiazza et al.; licensee Beilstein-Institut.
This is an Open Access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
The license is subject to the Beilstein Journal of Organic Chemistry terms and conditions: (http://www.beilstein-journals.org/bjoc)

Other Beilstein-Institut Open Science Activities
Journal Logo
Institut Logo
Preprint Logo
Symposia Logo