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Synlett 2002(2): 0358-0360
DOI: 10.1055/s-2002-19772
LETTER
© Georg Thieme Verlag Stuttgart · New York

Dehydration of Quinate Derivatives: Synthesis of a Difluoromethylene Homologue of Shikimic Acid

Julian M. Boxa, Laurence M. Harwooda, Jane L. Humphreysb, Gareth A. Morrisb, Perrine M. Redonb, Roger C. Whitehead*b
a Department of Chemistry, The University of Reading, Whiteknights, Reading, Berkshire, RG6 6AD, UK
b Department of Chemistry, The University of Manchester, Oxford Road, Manchester, M13 9PL, UK
Fax: +44(161)2754939; e-Mail: roger.whitehead@man.ac.uk ;
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Publication History

Received 14 November 2001
Publication Date:
02 February 2007 (online)

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Abstract

An optimised procedure for the conversion of a quinate to shikimate structure has been developed using Martin"s Sulfurane {Ph2S[OC(CF3)2Ph]2}. This protocol has been exploited in the synthesis of a novel difluoromethylene homologue of shikimic acid.

Key words

acetals - antibiotics - fluorine - Reformatsky reaction

    References

  • 1 Haslam E. In Shikimic Acid, Metabolites and Metabolism   Wiley; New York: 1993. 
  • 2 Rich RH. Bartlett PA. J. Org. Chem.  1996,  61:  3916 
    Search in Google Scholar
  • 3 Brettle R. Cross R. Frederickson M. Haslam E. MacBeath FS. Davies GM. Bioorg. Med. Chem. Lett.  1996,  6:  1275 
    CrossrefSearch in Google Scholar
  • 4 Brettle R. Cross R. Frederickson M. Haslam E. MacBeath FS. Tetrahedron  1996,  52:  10547 
    CrossrefSearch in Google Scholar
  • 5 Jiang S. Singh G. Boam DJ. Coggins JR. Tetrahedron: Asymmetry  1999,  10:  4087 
    CrossrefSearch in Google Scholar
  • 6 Weigert FJ. Shenvi A. J. Fluorine Chem.  1994,  66:  19 
    Search in Google Scholar
  • 7 Sutherland JK. Watkins WJ. Bailey JP. Chapman AK. Davies GM. J. Chem. Soc., Chem. Commun.  1989,  1386 
    Crossref
  • 8 Bowles S. Campbell MM. Sainsbury M. Davies GM. Tetrahedron Lett.  1989,  30:  3711 
    CrossrefSearch in Google Scholar
  • 9 For a review see: Ley SV. Baeschlin DK. Dixon DJ. Foster AC. Owen DR. Ince SJ. Priepke HWM. Reynolds DJ. Chem. Rev.  2001,  101:  53 
    CrossrefSearch in Google Scholar
  • 10 Montchamp JL. Tian F. Hart ME. Frost JW. J. Org. Chem.  1996,  61:  3897 
    Search in Google Scholar
  • 11 Shinada T. Yoshida Y. Ohfune Y. Tetrahedron Lett.  1998,  39:  6027 
    CrossrefSearch in Google Scholar
  • 12 See: Jiang S. Singh G. Tetrahedron  1998,  54:  4697 ; and references cited therein
    CrossrefSearch in Google Scholar
  • 13 Arhart RJ. Martin JC. J. Am. Chem. Soc.  1972,  94:  5003 
    CrossrefSearch in Google Scholar
  • 14 Martin JC. Arhart RJ. Franz JA. Perozzi EF. Kaplan LJ. Org. Synth.  1988,  163 
  • 15 Burgess EM. Penton HR. Taylor EA. J. Org. Chem.  1973,  38:  26 
    CrossrefSearch in Google Scholar
  • 17 Dehydration of a substrate similar to 9 using POCl3 has recently been reported: Shih T.-L. Wu S.-H. Tetrahedron Lett.  2000,  41:  2957 
    CrossrefSearch in Google Scholar
  • 18 Chahoua L. Baltas M. Gorrichon L. Tisnès P. Zedde C. J. Org. Chem.  1992,  57:  5798 
    Search in Google Scholar
  • 19 Hallinan EA. Fried J. Tetrahedron Lett.  1984,  25:  2301 
    CrossrefSearch in Google Scholar
  • 20 Heteronuclear 1H-19F NOE"s were measured by cross-peak integration of pulsed field gradient heteronuclear NOESY (HOESY) spectra measured using a Varian INOVA 400 spectrometer. No special equipment was used; fluorine pulses were applied directly to a single-tuned proton coil. Clear heteronuclear NOE"s were observed between fluorine and protons 2β, 6β, 2α and 6α in descending order of strength.
16

Procedure for the Preparation of Compound 11: A solution of Martin"s Sulfurane (4.83 g, 7.18 mmol) in CH2Cl2 (25 mL) was added dropwise to a solution of silylated quinate 9 (2.08 g, 4.79 mmol) in CH2Cl2 (35 mL) under an atmosphere of N2 at r.t. The resulting pale yellow solution was stirred for 24 h when the residual solvent was removed in vacuo to yield the crude product as an orange solid. Purification by flash column chromatography (5% EtOAc in cyclohexane) followed by recrystallisation from MeOH-H2O furnished the target compound 11 as a colourless solid (1.66 g, 83%); mp 74-75 °C; [α]D 22 -16.4 (c 1.0 in CH2Cl2); (Found: C, 57.7; H, 8.7. C20H36O7Si requires C, 57.7; H 8.7%); IR (film, cm-1): 1724 (C=O), 1649 (C=C). δH (400 MHz; CDCl3) 0.10 and 0.12 [2 × 3 H, s, (CH3)2Si], 0.89 [9 H, s, (CH3)3C], 1.28 and 1.29 (2 × 3 H, s, 2 × butyl CH3), 2.21 [1 H, ddd, J = 17.6, 10.4, 2.6 Hz, C(6)Hβ], 2.80 [1 H, dd, J = 17.6, 6.0 Hz, C(6)Hα], 3.23 and 3.24 (2 × 3 H, s, 2 × acetal OCH3), 3.48
[1 H, dd, J = 10.9, 3.9 Hz, C(4)H], 3.75 (3 H, s, CO2CH3), 4.11 [1 H, ddd, J = 10.9, 10.4 Hz, 6.0 Hz, C(5)H], 4.31 [1 H, dd, J = 5.5, 3.9 Hz, C(3)H], 6.77 [1 H, dd, J = 5.5, 2.6 Hz, C(2)H]; δC (75.4 MHz; CDCl3) -4.89 and -4.76 [(CH3)2Si], 17.60 and 17.76 (2 × butyl CH3), 18.27 [(CH3)3CSi], 25.68 [(CH3)3CSi], 30.34 [C(6)H2], 47.53 and 47.68 (2 × acetal OCH3), 51.87 (CO2CH3), 62.29 [C(5)H], 65.89 [C(3)H], 70.75 [C(4)H], 98.64 and 99.41 (2 × acetal C), 129.67 [C(1)], 136.64 [C(2)H], 166.97 (CO2CH3); m/z (CI/NH3) 434 (MNH4 +, 25%), 402(95), 385(80), 285(45), 270(85), 85(100); (Found: 434.2584. C20H40NO7Si requires 434.2574).

21

Data for compound 2: Viscous oil; δH (300 MHz; D2O) 1.96 [1 H, dd, J = 17.7, 7.0 Hz, one of C(6)H2], 2.46 [1 H, dd, J = 17.7, 5.4 Hz, one of C(6)H2], 3.56 [1 H, dd, J = 8.9, 4.5 Hz, C(4)H], 3.85 [1 H, ddd, J = 8.9, 7.0, 5.4 Hz, C(5)H], 4.19-4.25 [1 H, m, C(3)H], 6.01 [1 H, br, s, C(2)H]. δC (75.4 MHz; D2O) 28.99 [C(6)H2], 65.26, 65.97 and 71.16 [C(3)H, C(4)H and C(5)H], 113.90 (t, J = 251 Hz, CF2CO2H), 127.38 [t, J = 8 Hz, C(2)H], 131.25 [t, J = 24.1 Hz, C(1)], 167.73 (br, C=O); δF (282.4 MHz; D2O) -105.26 (1 F, d, J = 245 Hz), -105.59 (1 F, d, J = 245 Hz). m/z (negative ion electrospray) 223 [(M-H)-].