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Synlett 2011(3): 361-364  
DOI: 10.1055/s-0030-1259328
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Boric Acid Mediated N-Acylation of Sulfoximines

Aswinkumar Garimallaprabhakaran, Michael Harmata*
Department of Chemistry, University of Missouri-Columbia, Columbia, MO 65211, USA
Fax: +1(573)8822754; e-Mail: harmatam@missouri.edu;
Further Information

Publication History

Received 4 November 2010
Publication Date:
19 January 2011 (online)

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Abstract

The N-acylation of a sulfoximine with carboxylic acids was accomplished with boric acid and several boronic acids. Aliphatic acids give fair yields of products while acids related to phenylacetic and phenoxyacetic acids perform much better. Aromatic acids are ineffective in this process.

Key words

sulfoximine - boric acid - boronic acid - amidation - acylation

    References and Notes

  • 1a Worch C. Mayer AC. Bolm C. Synthesis and Use of Chiral Sulfoximines, In Organosulfur Chemistry in Asymmetric Synthesis   Toru T. Bolm C. Wiley-VCH; Weinheim: 2008.  p.209-229  
    Google Scholar
  • 1b Okamura H. Bolm C. Chem. Lett.  2004,  33:  482 
    Google Scholar
  • 1c Harmata M. Chemtracts  2003,  16:  660 
    Google Scholar
  • 1d Reggelin M. Zur C. Synthesis  2000,  1 
    Google Scholar
  • 2a Harmata M. Rayanil K.-O. Espejo VR. Barnes CL. J. Org. Chem.  2009,  74:  3214 
    Google Scholar
  • 2b Harmata M. Cai Z. Chen Y. J. Org. Chem.  2009,  74:  5559 
    Google Scholar
  • 2c Harmata M. Huang C. Chen Y. Zheng P. Gao X. Ying W. Synlett  2008,  2051 
    Google Scholar
  • 2d Harmata M. Rayanil K.-O. Gomes MG. Zheng P. Calkins NL. Kim S.-Y. Fan Y. Bumbu V. Lee DR. Wacharasindhu S. Hong X. Org. Lett.  2005,  7:  143 
    Google Scholar
  • 2e Harmata M. Hong X. Org. Lett.  2005,  7:  3581 
    Google Scholar
  • 2f Harmata M. Hong X. J. Am. Chem. Soc.  2003,  125:  5754 
    Google Scholar
  • 2g Harmata M. Pavri N. Angew. Chem. Int. Ed.  1999,  38:  2419 
    Google Scholar
  • 2h Harmata M. Claassen RJ. Tetrahedron Lett.  1991,  32:  6497 
    Google Scholar
  • 2i Harmata M. Tetrahedron Lett.  1989,  30:  437 
    Google Scholar
  • 3a Hwang KJ. Logusch EW. Tetrahedron Lett.  1987,  28:  4149 
    Google Scholar
  • 3b Bolm C. Hackenberger CPR. Simic O. Verrucci M. Müller D. Bienewald F. Synthesis  2002,  879 
    Google Scholar
  • 3c Bolm C. Müller D. Dalhoff C. Hackenberger CPR. Weinhold E. Bioorg. Med. Chem. Lett.  2003,  13:  3207 
    Google Scholar
  • 3d Hackenberger CPR. Raabe G. Bolm C. Chem. Eur. J.  2004,  10:  2942 
    Google Scholar
  • 3e Cho GY. Okamura H. Bolm C. J. Org. Chem.  2005,  70:  2346 
    Google Scholar
  • 4a Barajas JGH. Mendez LYV. Kouznetsov VV. Stashenko EE. Synthesis  2008,  377 
    Google Scholar
  • 4b Maki T. Ishihara K. Yamamoto H. Tetrahedron  2007,  63:  8645 
    Google Scholar
  • 4c Arnold K. Davies B. Giles RL. Grosjean C. Smith GE. Whiting A. Adv. Synth. Catal.  2006,  348:  813 
    Google Scholar
  • 4d Tang P. Org. Synth.  2005,  81:  262 
    Google Scholar
  • 4e Latta R. Springsteen G. Wang B. Synthesis  2001,  1611 
    Google Scholar
  • 5a Zoubi RM. Marion O. Hall DG. Angew. Chem. Int. Ed.  2008,  47:  2876 
    Google Scholar
  • 5b Ishihara K. Ohara S. Yamamoto H. Org. Synth.  2003,  79:  176 
    Google Scholar
  • 6 Brandt J. Gais H.-J. Tetrahedron: Asymmetry  1997,  8:  909 
    CrossrefGoogle Scholar
  • 7 Marcelli T. Angew. Chem. Int. Ed.  2010,  49:  6840 
    CrossrefGoogle Scholar
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Typical Procedure: A flame-dried, 50-mL single-neck round-bottomed flask was equipped with a Dean-Stark trap topped with a reflux condenser fitted with nitrogen inlet, and a Teflon-coated magnetic stirring bar. The reaction vessel was charged with racemic 1 (1 g, 6.45 mmol), carboxylic acid (7.09 mmol, 1.1 equiv), boric acid (310 mg, 0.8 equiv, 5.12 mmol) and toluene (20 mL, 0.32 M). The apparatus (save the condenser) was wrapped in aluminum foil to prevent heat loss. The reaction mixture was heated at reflux for 24 h, and H2O (ca. 0.1 mL) was collected in the Dean-Stark trap. The remaining volume of toluene in the flask
was ca. 10 mL, corresponding to approximately 0.645 M concentration of the reactants. The mixture was allowed to cool at ambient temperature and worked up in one of two ways.
The reaction mass was dissolved in EtOAc (50 mL) and washed with sat. NaHCO3 (3 × 50 mL) solution to remove any unreacted carboxylic acid and boric acid present. The collected organic layer was washed once with 3 N HCl (50 mL), followed by brine (50 mL). The organic layers were collected, dried with MgSO4 and filtered and the solvent was removed under vacuum. The crude product was pure in many cases and did not need further purification.
In an alternative workup, the reaction mass was dissolved in EtOAc (50 mL) and washed with brine (50 mL) and the organic layer was dried with MgSO4 and filtered and the solvent was removed under vacuum. The crude product was purified by flash column chromatography using 20-40% EtOAc-hexanes mixtures to afford pure product.

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Data for selected compounds: Compound 3: crystalline white solid; R f 0.48 (40% EtOAc-hexanes); mp 94.5-98 ˚C; yield: 80%. IR (KBr): 3313, 3056, 2943, 2916, 1667, 1488, 1205, 981, 830, 744 cm-¹. ¹H NMR (500 MHz, CDCl3): δ = 7.86 (d, J = 7.5 Hz, 2 H), 7.66 (t, J = 7.5 Hz, 1 H), 7.54 (t, J = 7.5 Hz, 2 H), 7.30 (t, J = 7.5 Hz, 2 H), 6.98-6.93 (m, 3 H), 4.67 (s, 2 H), 3.38 (s, 3 H). ¹³C NMR (125 MHz, CDCl3): δ = 177.3, 158.2, 138.2, 133.9, 129.6, 129.3, 127.0, 121.1, 114.6, 68.9, 44.0. HRMS: m/z [M + Na+] calcd for C15H15NO3S: 312.0664; found: 312.0655. Compound 7: white solid; R f 0.48 (40% EtOAc-hexanes); mp 82.5-84 ˚C; yield: 75%. IR (KBr): 3059, 3017, 2924, 1634, 1445, 1209, 974, 837, 743 cm-¹. ¹H NMR (500 MHz, CDCl3): δ = 7.83 (d, J = 7.5 Hz, 2 H), 7.63 (t, J = 7.5 Hz, 1 H), 7.54 (t, J = 7.5 Hz, 2 H), 7.29-7.33 (m, 4 H), 7.23 (m, 1 H), 3.70 (s, 2 H), 3.28 (s, 3 H). ¹³C NMR (125 MHz, CDCl3): δ = 180.2, 138.6, 135.8, 133.6, 129.5, 129.4, 128.2, 128.2, 127.0, 126.5, 57.8, 57.6, 47.0, 46.6. HRMS: m/z [M + Na+] calcd for C15H15NO2S: 296.0716; found: 296.0713. Compound 11: fluffy white solid; R f 0.45 (40% EtOAc-hexanes); mp 131-133 ˚C; yield: 70%. IR (KBr): 3026, 3037, 2926, 1649, 1445, 1165, 973, 837, 744 cm-¹. ¹H NMR (500 MHz, CDCl3): δ = 7.76 (d, J = 7.5 Hz, 2 H), 7.63 (t, J = 7.5 Hz, 1 H), 7.54 (t, J = 7.5 Hz, 2 H), 7.29-7.33 (m, 10 H), 5.12 (s, 1 H), 3.27 (s, 3 H). ¹³C NMR (125 MHz, CDCl3): δ = 180.2, 140.0, 139.9, 138.5, 133.6, 129.4, 128.87, 128.86, 128.2, 127.0, 61.3, 43.9. HRMS: m/z [M + Na+] calcd for C21H19NO2S: 372.1029; found: 372.1019. Compound 15: white solid; R f 0.38 (40% EtOAc-hexanes); mp 59-60.5 ˚C; yield: 64%. IR (KBr): 3060, 3024, 2964, 2931, 1626, 1437, 1354, 1200, 979, 832, 743 cm-¹. ¹H NMR (500 MHz, CDCl3): δ = 7.97 (d, J = 7.5 Hz, 2 H), 7.68 (t, J = 7.5 Hz, 1 H), 7.58 (t, J = 7.5 Hz, 2 H), 3.34 (s, 3 H), 2.43 (q, J = 7.5 Hz, 2 H), 1.14 (t, J = 7.5 Hz, 3 H). ¹³C NMR (125 MHz, CDCl3): δ = 183.5, 138.9, 133.6, 129.5, 127.0, 44.1, 32.7, 9.6. HRMS: m/z [M + Na+] calcd for C10H13NO2S: 234.0559; found: 234.0560.

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Crystallographic data for 3 (CCDC 794098), 5 (CCDC 794100), 13 (CDDC 794099) and 19 (CCDC 794097) may be obtained from the Cambridge Crystallographic Data Centre (www.ccdc.cam.ac.uk/data_request/cif or by E-mail to data_request@ccdc.cam.ac.uk).