Download PDF
Synlett 2008(14): 2191-2195  
DOI: 10.1055/s-2008-1078252
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Sulfur Ylide Mediated Three-Component Aziridination and Epoxidation Reactions Using Vinyl Sulfonium Salts

Christoforos G. Kokotos, Eoghan M. McGarrigle, Varinder K. Aggarwal*
School of Chemistry, University of Bristol, Cantock’s Close, Bristol BS8 1TS, UK
Fax: +44(117)9298611; e-Mail: v.aggarwal@bristol.ac.uk;
Further Information

Publication History

Received 18 July 2008
Publication Date:
05 August 2008 (online)

    Permissions and Reprints All articles of this category

Abstract

Coupling of diphenylvinyl sulfonium triflate with nucleophiles and either aldehydes or imines gives epoxides and aziridines, respectively, in a three-component reaction. cis-Aziridines could be formed in good diastereomeric ratio, and the selectivity was correlated to the reactivity of the imine. This represents the first study of cis/trans selectivity in the reactions of imines with non­stabilized sulfur ylides.

Key words

sulfur ylides - epoxidations - aziridinations - multicomponent reactions - vinyl sulfonium salts

    References and Notes

  • Reviews:
  • 1a Syamala M. Org. Prep. Proced. Int.  2005,  37:  103 
    Google Scholar
  • 1b Noyori R. Suzuki M. Chemtracts  1990,  3:  173 
    Google Scholar
  • 2a Yar M. McGarrigle EM. Aggarwal VK. Angew. Chem. Int. Ed.  2008,  47:  3784 ; Angew. Chem. 2008, 120, 3844
    Google Scholar
  • 2b Unthank MG. Tavassoli B. Aggarwal VK. Org. Lett.  2008,  10:  1501 
    Google Scholar
  • 2c Unthank MG. Hussain N. Aggarwal VK. Angew. Chem. Int. Ed.  2006,  45:  7066 ; Angew. Chem. 2006, 118, 7224
    Google Scholar
  • 3a Kim K. Jimenez LS. Tetrahedron: Asymmetry  2001,  12:  999 
    Google Scholar
  • 3b Wang Y. Zhang W. Colandrea VJ. Jimenez LS. Tetrahedron  1999,  55:  10659 
    Google Scholar
  • There is one isolated report of an epoxidation reaction of a butadienylsulfonium salt with a β-keto ester and aldehyde. See:
  • 4a Rowbottom MW. Mathews N. Gallagher T. J. Chem. Soc., Perkin Trans. 1  1998,  3927 
    Google Scholar
  • For a related example using vinyl selenonium salts, see:
  • 4b Watanabe Y. Ueno Y. Toru T. Bull. Chem. Soc. Jpn.  1993,  66:  2042 
    Google Scholar
  • 5 Corey EJ. Oppolzer W. J. Am. Chem. Soc.  1964,  86:  1899 
    CrossrefGoogle Scholar
  • Nucleophiles with two acidic protons on the same atom have been shown to react with vinyl sulfonium salts to give three-membered rings:
  • 6a Gosselck J. Béress L. Schenk H. Angew. Chem., Int. Ed. Engl.  1966,  5:  596 ; Angew. Chem. 1966, 78, 606
    Google Scholar
  • 6b Johnson CR. Lockard JP. Tetrahedron Lett.  1971,  12:  4589 
    Google Scholar
  • 6c Takaki K. Agawa T. J. Org. Chem.  1977,  42:  3303 
    Google Scholar
  • 6d Matsuo J. Yamanaka H. Kawana A. Mukaiyama T. Chem. Lett.  2003,  32:  392 
    Google Scholar
  • In cases where the nucleophile can be resonance-stabilized forming enolates, five-membered rings have also been obtained:
  • 6e Braun H. Huber G. Tetrahedron Lett.  1976,  17:  2121 
    Google Scholar
  • 6f Batty JW. Howes PD. Stirling CJM. J. Chem. Soc., Perkin Trans. 1  1973,  65 ; ref. 6b
    Google Scholar
  • For leading references on aziridination reactions of sulfonium methylides with imines, see:
  • 7a Aggarwal VK. Coogan MP. Stenson RA. Jones RVH. Fieldhouse R. Blacker J. Eur. J. Org. Chem.  2002,  319 
    Google Scholar
  • 7b Aggarwal VK. Stenson RA. Jones RVH. Fieldhouse R. Blacker J. Tetrahedron Lett.  2001,  42:  1587 
    Google Scholar
  • For leading references on aziridinations with other types of sulfur ylides, see:
  • 8a McGarrigle EM. Myers EL. Illa O. Shaw MA. Riches SL. Aggarwal VK. Chem. Rev.  2007,  107:  5841 
    Google Scholar
  • 8b Hou XL. Wu J. Fan RH. Ding CH. Luo ZB. Dai LX. Synlett  2006,  181 
    Google Scholar
  • 8c Tang Y. Ye S. Sun X.-L. Synlett  2005,  2720 
    Google Scholar
  • 8d Aggarwal VK. Badine DM. Moorthie VA. In Aziridines and Epoxides in Asymmetric Synthesis   Yudin AK. Wiley-VCH; Weinheim: 2006.  Chap. 1.
    Google Scholar
  • Only cis-aziridine was obtained in the reaction of(dimethylamino)-p-tolyloxosulfonium ethylide with PhCH=NPh, see:
  • 8e Johnson CR. Janiga ER. J. Am. Chem. Soc.  1973,  95:  7692 
    Google Scholar
  • 9 Aggarwal VK. Charmant JPH. Ciampi C. Hornby JM. O’Brien CJ. Hynd G. Parsons R. J. Chem. Soc., Perkin Trans. 1  2001,  3159 
    CrossrefGoogle Scholar
  • 10a Robiette R. J. Org. Chem.  2006,  71:  2726 
    Google Scholar
  • 10b Janardanan D. Sunoj RB. Chem. Eur. J.  2007,  13:  4805 
    Google Scholar
  • 11 Seebach D. Golinsky J. Helv. Chim. Acta  1981,  64:  1413 
    CrossrefGoogle Scholar
12

The products were characterized by NMR, IR, MS, and mp (where appropriate). Satisfactory elemental analyses and/or HRMS were obtained for all compounds. Full details and spectra are available from the authors.

13

N ,4-Dimethyl- N -{[1-(toluene-4-sulfonyl)-3-phenyl-2-aziridinyl]methyl}benzenesulfonamide (Table 2, Entry 2) cis-Isomer as a colourless oil; R f = 0.40 (EtOAc-PE, 3:7). IR (film): 1598 (Ar), 1330 (SO2), 1160 (SO2) cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 7.86 (2 H, d, J = 8.3 Hz, ArH), 7.50 (2 H, d, J = 8.3 Hz, ArH), 7.35 (2 H, d, J = 8.3 Hz, ArH), 7.27-7.16 (7 H, m, ArH), 3.93 (1 H, d, J = 7.0 Hz, NCHPh), 3.25-3.14 (2 H, m, NCHH and NCHCH2), 2.53 (1 H, dd, J = 14.3, 7.0 Hz, NCHH), 2.44 (6 H, s, 2 × CH3), 2.38 (3 H, s, CH3). ¹³C NMR (100.5 MHz, CDCl3): δ = 145.0 (C), 143.5 (C), 136.2 (C), 135.9 (C), 132.0 (C), 130.0 (CH), 129.9 (CH), 129.7 (CH), 128.6 (CH), 128.3 (CH), 127.4 (CH), 127.3 (CH), 47.6 (CH2), 44.4 (CH), 44.1 (CH), 35.4 (CH3), 21.7 (CH3), 21.5 (CH3). MS (CI): m/z (%) = 471 (14) [MH+], 198 (100) [Ts(Me)NCH2 +]; trans-isomer (obtained as a mixture with cis-isomer) as a colorless oil; R f = 0.40 (EtOAc-PE, 3:7). IR (film): νmax = 1599 (Ar), 1332 (SO2), 1161 (SO2) cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 7.77 (2 H, d, J = 8.3 Hz, ArH), 7.69 (2 H, d, J = 8.3 Hz, ArH), 7.31 (2 H, d, J = 8.3 Hz, ArH), 7.26-7.19 (7 H, m, ArH), 3.85 (1 H, d, J = 3.8 Hz, NCHPh), 3.55 (1 H, dd, J = 14.6, 8.6 Hz, NCHH), 3.03 (1 H, ddd, J = 8.6, 8.6, 3.8 Hz, NCHCH2N), 2.43 (6 H, s, 2 × CH3), 2.42-2.38 (4 H, m, NCHH and CH3). ¹³C NMR (100.5 MHz, CDCl3): δ = 144.9 (C), 143.6 (C), 136.2 (C), 134.0 (C), 132.0 (C), 129.9 (CH), 129.8 (CH), 128.6 (CH), 128.5 (CH), 127.4 (CH), 127.3 (CH), 126.9 (CH), 49.6 (CH), 49.0 (CH2), 48.8 (CH), 36.5 (CH3), 21.7 (CH3), 21.5 (CH3). MS (CI): m/z (%) = 471 (14) [MH+], 198 (100) [Ts(Me)NCH2 +].

14

Diethyl 2-Methyl-2-({1-[(4-methylphenyl)sulfonyl]-3-phenyl-2-aziridinyl}methyl)malonate (Table 3, Entry 3)
cis/trans-Isomers (3:1) as a colorless oil (89%); R f = 0.30 (EtOAc-PE, 2:8). IR (film): 1761 (OCO), 1162 (SO2) cm-¹. ¹H NMR (400 MHz, CDCl3): δ(cis) = 7.85 (2 H, d, J = 8.3 Hz, ArH), 7.32-7.17 (7 H, m, ArH), 4.19-4.02 (4 H, m, 2 × OCH2), 3.87 (1 H, d, J = 7.2 Hz, NCHPh), 2.99-2.91 (1 H, m, NCHCH2), 2.43 (3 H, s, CH3), 1.87 (1 H, dd, J = 14.9, 5.8 Hz, CHH), 1.70 (1 H, dd, J = 14.9, 6.4 Hz, CHH), 1.31 (3 H, s, CH3), 1.27-1.11 (6 H, m, 2 × CH3). ¹³C NMR (100.5 MHz, CDCl3): δ = 171.5 (C), 171.4 (C), 144.7 (C), 144.6 (C), 132.4 (C), 129.8 (CH), 129.6 (CH), 128.5 (CH), 128.2 (CH), 127.6 (CH), 61.8 (CH2), 61.6 (CH2), 52.4 (C), 45.1 (CH), 42.7 (CH), 31.1 (CH2), 21.6 (CH3), 19.5 (CH3), 13.9 (CH3), 13.8 (CH3). ¹H NMR (400 MHz, CDCl3): δ(trans) = 7.78 (2 H, d, J = 8.3 Hz, ArH), 7.32-7.17 (7 H, m, ArH), 4.19-4.02 (4 H, m, 2 × OCH2), 3.78 (1 H, d, J = 4.2 Hz, NCHPh), 2.99-2.91 (1 H, m, NCHCH2), 2.49-2.36 (5 H, m, CH2 and CH3), 1.31 (3 H, s, CH3), 1.27-1.11 (6 H, m, 2 × CH3). ¹³C NMR (100.5 MHz, CDCl3): δ = 171.5 (C), 171.4 (C), 144.4 (C), 143.6 (C), 134.8 (C), 129.8 (CH), 128.8 (CH), 128.5 (CH), 127.4 (CH), 126.7 (CH), 61.8 (CH2), 61.7 (CH2), 52.9 (C), 46.2 (CH), 43.7 (CH), 31.9 (CH2), 21.6 (CH3), 20.7 (CH3), 13.9 (CH3), 13.8 (CH3). MS (CI): m/z (%) = 460 (28) [MH+] , 414 (17) [M+ - EtO], 286 (100) [M+ - C(CO2Et)2Me].

15

1-(4-Toluenesulfonyl)-2-phenyl-3-[(phenylsul-fanyl)methyl]aziridine (Table 3, Entry 6)
cis:trans-Isomers (1:5) as a colorless oil (33%); R f = 0.45 (EtOAc-PE, 3:7). IR (film): 1347 (SO2), 1164 (SO2) cm-¹. ¹H NMR (400 MHz, CDCl3): δ(cis) = 7.58 (2 H, d, J = 8.3 Hz, ArH), 7.35-7.08 (12 H, m, ArH), 4.03 (1 H, d, J = 7.0 Hz, NCHPh), 3.29-3.19 (2 H, m, NCHCHH), 2.62 (1 H, dd, J = 14.2, 7.0 Hz, CHH), 2.36 (3 H, s, CH3). ¹³C NMR (100.5 MHz, CDCl3): δ = 143.5 (C), 137.0 (C), 135.2 (C), 134.6 (C), 129.8 (CH), 129.7 (CH), 129.1 (CH), 128.8 (CH), 128.1 (CH), 127.7 (CH), 127.1 (CH), 126.6 (CH), 46.2 (CH), 45.1 (CH), 35.4 (CH2), 21.6 (CH3). ¹H NMR (400 MHz, CDCl3): δ(trans) = 7.81 (2 H, d, J = 8.3 Hz, ArH), 7.35-7.08 (12 H, m, ArH), 4.70 (1 H, d, J = 4.2 Hz, NCHPh), 3.73 (1 H, ddd, J = 7.0, 6.5, 4.2 Hz, NCHCH2), 3.12 (1 H, dd, J = 14.1, 6.5 Hz, CHH), 2.81 (1 H, dd, J = 14.1, 7.0 Hz, CHH), 2.42 (3 H, s, CH3). ¹³C NMR (100.5 MHz, CDCl3): δ = 144.7 (C), 137.2 (C), 135.0 (C), 134.4 (C), 129.9 (CH), 129.7 (CH), 129.6 (CH), 129.2 (CH), 129.0 (CH), 128.9 (CH), 128.2 (CH), 127.4 (CH), 48.9 (CH), 46.3 (CH), 35.6 (CH2), 21.7 (CH3). MS (CI): m/z (%) = 396 (3) [MH+], 224 (100) [MH+ - TsNH2], 155 (16) [Ts+].

16

Diethyl 2-(Acetylamino)-2-{[3-(4-methoxyphenyl)-1-(4-toluene-sulfonyl)-2-aziridinyl]methyl}malonate (Table 4, Entry 8) cis-Isomer as a colorless oil (62%); R f = 0.40 (EtOAc-PE, 4:6). IR (film): 1762 (OCO), 1160 (SO2) cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 7.79 (2 H, d, J = 8.3 Hz, ArH), 7.29 (2 H, d, J = 8.3 Hz, ArH), 7.21 (1 H, br s, NH), 6.95 (2 H, d, J = 8.7 Hz, ArH), 6.75 (2 H, d, J = 8.7 Hz, ArH), 4.41-4.09 (4 H, m, 2 × OCH2), 3.74 (1 H, d, J = 7.2 Hz, NCHAr), 3.73 (3 H, s, OCH3), 2.89 (1 H, ddd, J = 10.1, 7.2, 3.7 Hz, NCHCH2), 2.53 (1 H, dd, J = 15.1, 3.7 Hz, CHH), 2.41 (3 H, s, CH3), 2.10 (1 H, dd, J = 15.1, 10.1 Hz, CHH), 2.07 (3 H, s, CH3), 1.33-1.15 (6 H, m, 2 × CH3). ¹³C NMR (100.5 MHz, CDCl3): δ = 169.7 (C), 167.4 (C), 167.2 (C), 159.5 (C), 144.9 (C), 131.1 (C), 129.8 (CH), 128.5 (CH), 128.1 (CH), 123.8 (C), 114.0 (CH), 65.1 (C), 62.9 (CH2), 62.7 (CH2), 55.3 (CH3), 45.1 (CH), 41.1 (CH), 28.9 (CH2), 23.0 (CH3), 21.8 (CH3), 14.0 (CH3), 13.9 (CH3). MS (CI): m/z (%) = 533 (58) [MH+], 320 (100) [MH+ - TsNHAc].