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DOI: 10.1055/s-0039-1690991
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© Georg Thieme Verlag Stuttgart · New York

Cyanide-Mediated Synthesis of Sulfones and Sulfonamides from Vinyl Sulfones

Tamal Roy
,
The generous support from the Department of Chemistry, University of Copenhagen and the Novo Nordisk Fonden (Grant No. NNF17OC0027598) is gratefully acknowledged.
Further Information

Publication History

Received: 21 August 2019

Accepted after revision: 05 September 2019

Publication Date:
24 September 2019 (eFirst)

Published as part of the Special Section 11th EuCheMS Organic Division Young Investigator Workshop

Abstract

We report a facile synthesis of sulfones, β-keto sulfones, and sulfonamides from vinyl sulfones via an addition–elimination sequence where in situ generation of nucleophilic sulfinate ion is mediated by cyanide. The use vinyl sulfones renders high selectivity for S-alkylation to produce sulfones in high yields. In the presence of N-bromosuccinimide, primary and secondary amines underwent sulfonamide formation. A preliminary mechanistic study showed the formation of acrylonitrile as an innocent byproduct, without interfering with the desired reaction pathway while generating a sulfinate nucleophile.

Supporting Information

 
  • References and Notes

    • 1a Ahmad I, Shagufta Shagufta. Int. J. Pharm. Pharm. Sci. 2015; 7: 19
    • 1b Alba A.-NR, Companyó X, Rios R. Chem. Soc. Rev. 2010; 39: 2018
    • 1c Meadows DC, Gervay-Hague J. Med. Res. Rev. 2006; 26: 793
    • 1d Trost BM, Kalnmals CA. Chem. Eur. J. 2019; 25: 11193
    • 2a Kupwade RV. J. Chem. Rev. 2019; 1: 99
    • 2b Liu N.-W, Liang S, Manolikakes G. Synthesis 2016; 48: 1939
    • 3a Kaiser D, Klose I, Oost R, Neuhaus J, Maulide N. Chem. Rev. 2019; 119: 8701
    • 3b Aziz J, Messaoudi S, Alami M, Hamze A. Org. Biomol. Chem. 2014; 12: 9743
    • 3c Guyon H, Chachignon H, Cahard D. Beilstein J. Org. Chem. 2017; 13: 2764
  • 4 Shyam PK, Jang H.-Y. J. Org. Chem. 2017; 82: 1761
    • 5a Roy T, Kim MJ, Yang Y, Kim S, Kang G, Ren X, Kadziola A, Lee H.-Y, Baik M.-H, Lee J.-W. ACS Catal. 2019; 9: 6006
    • 5b Juhl M, Lee J.-W. Angew. Chem. Int. Ed. 2018; 57: 12318
  • 6 Kiyokawa K, Nagata T, Hayakawa J, Minakata S. Chem. Eur. J. 2015; 21: 1280
  • 7 Liu J, Zheng L. Adv. Synth. Catal. 2019; 361: 1710
  • 8 Zhu J, Yang W.-C, Wang X.-d, Wu L. Adv. Synth. Catal. 2018; 360: 386
    • 9a Baidya M, Kobayashi S, Mayr H. J. Am. Chem. Soc. 2010; 132: 4796
    • 9b Ji Y.-Z, Li H.-J, Zhang J.-Y, Wu Y.-C. Eur. J. Org. Chem. 2019; 1846
    • 10a Muneeswara M, Sundaravelu N, Sekar G. Tetrahedron 2019; 75: 3479
    • 10b Kumar N, Kumar A. ACS Sustainable Chem. Eng. 2019; 7: 9182
    • 10c Cai S, Chen D, Xu Y, Weng W, Li L, Zhang R, Huang M. Org. Biomol. Chem. 2016; 14: 4205
    • 11a Montgomery JI, Brown MF, Reilly U, Price LM, Abramite JA, Arcari J, Barham R, Che Y, Chen JM, Chung SW, Collantes EM, Desbonnet C, Doroski M, Doty J, Engtrakul JJ, Harris TM, Huband M, Knafels JD, Leach KL, Liu S, Marfat A, McAllister L, McElroy E, Menard CA, Mitton-Fry M, Mullins L, Noe MC, O’Donnell J, Oliver R, Penzien J, Plummer M, Shanmugasundaram V, Thoma C, Tomaras AP, Uccello DP, Vaz A, Wishka DG. J. Med. Chem. 2012; 55: 1662
    • 11b Aranapakam V, Grosu GT, Davis JM, Hu B, Ellingboe J, Baker JL, Skotnicki JS, Zask A, DiJoseph JF, Sung A, Sharr MA, Killar LM, Walter T, Jin G, Cowling R. J. Med. Chem. 2003; 46: 2361
  • 12 Markitanov YM, Timoshenko VM, Shermolovich YG. J. Sulfur Chem. 2014; 35: 188
  • 13 General Procedure for the Synthesis of Sulfones 2a–m Vinyl sulfone (0.4 mmol) and tetraethylammonium cyanide (1.05 equiv, 0.42 mmol) were dissolved in DCM (1 mL). The reaction mixture was stirred for 5 min, and a solution of an appropriate electrophile (1.05 equiv, 0.42 mmol) in DCM (0.5 mL) was added dropwise. The resultant reaction mixture was stirred at room temperature. After completion of the reaction (checked by crude 1H NMR or GC–MS), water (10 mL) was added to the reaction mixture, and the product was extracted with ethyl acetate (3 × 10 mL). The combined organic layers were washed with brine (10 mL), dried over anhydrous Na2SO4, and concentrated under vacuum. The crude product thus obtained was purified by column chromatography using 10–20% ethyl acetate in petroleum ether. (Benzylsulfonyl)benzene (2a) Compound 2a (87 mg, 94%) was synthesized using the general procedure for the synthesis of sulfones and isolated as a white solid. 1H NMR (500 MHz, CDCl3): δ = 7.66–7.56 (m, 3 H), 7.47–7.42 (m, 2 H), 7.35–7.29 (m, 1 H), 7.28–7.23 (m, 2 H), 7.13–7.04 (m, 2 H), 4.31 (s, 2 H). 13C NMR (126 MHz, CDCl3): δ = 138.0, 133.8, 131.0, 129.0, 128.9, 128.8, 128.7, 128.3, 63.0. HRMS (EI): m/z calcd for C13H13O2S [M + H]+: 233.0636; found: 233.0636. 1-Phenyl-2-(phenylsulfonyl)ethan-1-one (2k) Compound 2k (96 mg, 92%) was synthesized using the general procedure for the synthesis of sulfones and isolated as a white solid. 1H NMR (500 MHz, CDCl3): δ = 7.95–7.93 (m, 2 H), 7.91–7.89 (m, 2 H), 7.68–7.60 (m, 2 H), 7.60–7.54 (m, 2 H), 7.50–7.47 (m, 2 H), 4.74 (s, 2 H). 13C NMR (126 MHz, CDCl3): δ = 188.1, 138.9, 135.9, 134.5, 134.4, 129.4, 129.4, 129.0, 128.7, 63.6. HRMS (EI): m/z calcd for C14H13O3S [M + H]+: 261.0585; found: 261.0586.
  • 14 General Procedure for the Synthesis of Sulfonamides 4a–f N-Bromosuccinimide (1.5 equiv, 0.6 mmol) was added portionwise to a vial containing a solution of an appropriate amine (1.5 equiv, 0.6 mmol) in DCM (1 mL). In another vial, vinyl sulfone (0.4 mmol) and tetraethylammonium cyanide (1.05 equiv, 0.42 mmol) were taken together with DCM (1 mL) and stirred for 5 min. The later solution was then added dropwise to the former mixture. The combined reaction mixture was allowed to stir at room temperature. After completion of the reaction (checked by crude 1H NMR and TLC), water (10 mL) was added to the reaction mixture, and the product was extracted with ethyl acetate (3 × 10 mL). The combined organic layers were washed with brine (10 mL), dried over anhydrous Na2SO4, and concentrated under vacuum. The crude product thus obtained was purified by column chromatography using 10–20% ethyl acetate in petroleum ether. 4-(Phenylsulfonyl)morpholine (4a) Compound 4a (86 mg, 95%) was synthesized using the general procedure for the synthesis of sulfonamides and isolated as a white solid. 1H NMR (500 MHz, CDCl3): δ = 7.78–7.74 (m, 2 H), 7.66–7.61 (m, 1 H), 7.59–7.54 (m, 2 H), 3.77–3.72 (m, 4 H), 3.03–2.98 (m, 4 H). 13C NMR (126 MHz, CDCl3): δ = 135.3, 133.2, 129.3, 128.0, 66.2, 46.1. HRMS (EI): m/z calcd for C10H14NO3S [M + H]+: 228.0694; found: 228.0693.
    • 15a Yan H, Suk OhJ, Lee J.-W, Song CE. Nat. Commun. 2012; 3: 1212
    • 15b Park SY, Liu Y, Oh JS, Kweon YK, Jeong YB, Duan M, Tan Y, Lee J.-W, Yan H, Song CE. Chem. Eur. J. 2018; 24: 1020
    • 15c Liu Y, Ao J, Paladhi S, Song CE, Yan H. J. Am. Chem. Soc. 2016; 138: 16486

    • For a review, see:
    • 15d Oliveira MT, Lee J.-W. ChemCatChem 2017; 9: 377
  • 16 Sun S, Yu J.-T, Jiang Y, Cheng J. Adv. Synth. Catal. 2015; 357: 2022