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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

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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).

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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)-].