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Synlett 2002(11): 1910-1912
DOI: 10.1055/s-2002-34900
LETTER
© Georg Thieme Verlag Stuttgart · New York

Synthesis of 3-Sila Derivatives of l-Ascorbic Acid via Mitsunobu Reaction

Cyril Rubio, Jacques Susperregui, Laurent Latxague, Gérard Déléris*
Unité INSERM 443, Groupe de Chimie Bio-organique, Université V. Segalen Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France
Fax: +33(5)57571002; e-Mail: gerard.deleris@u-bordeaux2.fr;
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Publication History

Received 12 September 2002
Publication Date:
21 October 2002 (online)

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Abstract

Various 3-sila derivatives of l-ascorbic acid were synthesized in satisfactory yields. The ether link was formed by an unusual aspect of the Mitsunobu reaction, without the need of protecting the remaining hydroxy groups.

Key words

Mitsunobu reaction - ethers - silicon compounds - ascorbic acid - bioorganic chemistry

11

All NMR experiments were conducted in CDCl3. For convenience, proton and carbon chemical shifts for the l-ascorbic acid moiety are detailed for compound 6 only. For all other molecules (7-13) a single list is provided and attributions for l-ascorbic acid (Asc. Ac.) can be derived from the reference compound 6.
General Procedure for Mitsunobu Reaction:
In a typical experiment, a mixture of ascorbic acid (12 mmol) and triphenylphosphine (12 mmol) was suspended in anhyd THF (15 mL) and kept at -10 °C under nitrogen in a Schlenck tube. Then, chloroalkylhydroxysilane (9.6 mmol) and DEAD (12 mmol) in THF (5 mL) were added dropwise over 1 h. The reaction mixture was kept at -10 °C for 24 h before being filtered, concentrated and purified by chromatography.
Compound 6: 1H NMR: δ = 0.10 [s, 6 H, (CH3)2Si], 0.62-0.70 [m, 4 H, (CH2Si)2], 1.26-1.38 (m, 2 H, SiCH2CH 2), 1.52-1.58 (m, 2 H, CH 2CH2O), 1.70 (q, 2 H, J = 7.0 Hz, CH 2CH2Cl), 3.51 (t, 2 H, J = 6.3 Hz, CH2Cl), 3.75-3.80 (m, 2 H, OCH2), 3.90-3.95 (m, 1 H, H5), 4.40-4.45 (m, 2 H, H6), 4.64 (d, 1 H, H4). 13C NMR: δ = -4.70 [(CH3)2Si], 9.11 (SiCH2), 14.2 (SiCH2), 23.85 (SiCH2 CH2), 25.5 (SiCH2 CH2), 37.5 (CH2CH2Cl), 44.6 (CH2Cl), 63.48 (CH2O), 70.04 (C5), 74.24 (C6), 76.36 (C4), 118.20 (C2), 151.20 (C3), 172.02 (C1).
Compound 7: 1H NMR: δ = 0.10 [s, 6 H, (CH3)2Si], 0.62-0.70 [m, 4 H, (CH2Si)2], 1.26-1.38 [m, 4 H, (SiCH2CH 2)2], 1.53-1.58 (m, 2 H, CH 2CH2O), 1.70 (q, 2 H, J = 7.0 Hz, CH 2CH2Cl), 3.5 (t, 2 H, J = 6.3 Hz, CH2Cl), 3.75-3.80 (m, 2 H, OCH2), [4.0, 4.45, 4.64 for Asc. Ac.]. 13C NMR: δ = -4.70 [(CH3)2Si], 9.11 (SiCH2), 14.2 (SiCH2), 23.85 (SiCH2 CH2), 25.5 (SiCH2 CH2), 35.3 [Si(CH2)2 CH2], 37.5 (CH2CH2Cl), 44.6 (CH2Cl), 63.48 (CH2O), [70.1, 74.2, 76.45, 118.3, 151.12, 172.14 for Asc. Ac.].
Compound 8: 1H NMR: δ = 0.10 [s, 6 H, (CH3)2Si], 0.63-0.70 [m, 4 H, (CH2Si)2], 1.28-1.40 {m, 6 H, [SiCH2(CH2)2CH2]}, 1.51-1.56 (m, 2 H, CH2CH2O), 1.72 (q, 2 H, J = 7.1 Hz, CH2CH2Cl), 3.5 (t, 2 H, J = 6.3 Hz CH2Cl), 3.78-3.83 (m, 2 H, OCH2), [3.92, 4.45, 4.64 for Asc. Ac.]. 13C NMR: δ = -4.70 [(CH3)2Si], 9.11 (SiCH2), 14.2 (SiCH2), 23.85 (SiCH2CH2), 25.5 (SiCH2CH2), 32.5 [Si(CH2)3CH2], 35.3 {[Si(CH2)2CH2]}, 37.5 (CH2CH2Cl), 44.6 (CH2Cl), 63.48 (CH2O), [70.12, 74.25, 76.25, 118.5, 151.4, 171.8 for Asc. Ac.].
Compound 9: 1H NMR: δ = 0.10 [s, 6 H, (CH3)2Si], 0.63-0.70 [m, 4 H, (CH2Si)2], 1.26-1.38 [m, 8 H, (SiCH2CH 2CH 2)2], 1.53-1.59 (m, 2 H, CH 2CH2O), 1.71 (q, 2 H, J = 7.0 Hz CH 2CH2Cl), 3.5 (t, 2 H, J = 6.3 Hz, CH2Cl), 3.79-3.84 (m, 2 H, OCH2), [4.01, 4.45, 4.6 for Asc. Ac.]. 13C NMR: δ = -4.70 [(CH3)2Si], 9.11 (SiCH2), 14.2 (SiCH2), 23.85 (SiCH2 CH2), 25.5 (SiCH2 CH2), 29.1 [Si(CH2)4 CH2], 32.5 [Si(CH2)3 CH2], 35.3 {[Si(CH2)2 CH2]}, 37.5 (CH2CH2Cl), 44.6 (CH2Cl), 63.5 (CH2O), [70.2, 74.0, 76.4, 118.2, 151.3, 172.1 for Asc. Ac.].
Compound 10: 1H NMR: δ = 0.22 [s, 6 H, (CH3)2Si], 0.53-0.58 [m, 2 H, (CH2Si], 1.31-1.35 (m, 2 H, SiCH2CH2), 1.70 (q, 2 H, J = 7.1 Hz, CH2CH2Cl), 2.83 (s, 2 H, CH2Cl), 3.83-3.89 (m, 2 H, -O-CH2CH=CH), [3.7, 3.9, 4.67 for Asc. Ac.], 5.85-5.95 (d, 1 H, J = 24.2 Hz, =CH-Si), 6.25-6.31 (td, 1 H, J = 24.2 Hz, =CH-CH2). 13C NMR: δ = -4.82 [(CH3)2Si], 9.11 (SiCH2), 21.0 (SiCH2CH2), 29.7 (CH2Cl), 37.1 (CH2CH2Cl), 63.2 (OCH2C=CH2), 124.4 (=CH-CH2), 147.7 (=CH-Si), [69.9, 74.9, 76.5, 119.5, 150.2, 172.0 for Asc. Ac.].
Compound 11: 1H NMR: δ = 0.22 [s, 6 H, (CH3)2Si], 0.52-0.60 [m, 2 H, (CH2Si], 1.30-1.35 (m, 2 H, SiCH2CH 2), 1.70 (q, 2 H, J = 7.1 Hz, CH 2CH2Cl), 2.83 (s, 2 H, CH2Cl), [3.72, 3.93, 4.67 for Asc. Ac.], 5.07-5.11 (m, 2 H, CH 2C=CH2), 5.72 (dd, 2 H, 2 J = 7.5 Hz, 4 J = 2.3 Hz, C=CH2). 13C NMR: δ = -4.82 [(CH3)2Si], 9.11 (SiCH2), 21.0 (SiCH2 CH2), 30.5 (CH2Cl), 37.1 (CH2CH2Cl), 63.20 (OCH2C=CH2), 128.50 (CH2 C=CH2), 143 (CH2C=CH2), [69.9, 74.9, 76.4, 119.5, 150.2, 172.5 for Asc. Ac.].
Compound 12: 1H NMR: δ = 0.22 [s, 6 H, (CH3)2Si], 2.83 (s, 2 H, CH2Cl), 3.69-3.75 (m, 2 H, H6), [3.93, 4.3, 4.7 for Asc. Ac.], 5.85-5.95 (d, 1 H, J = 24.1 Hz;, =CH-Si), 6.25-6.31 (td, 1 H, J = 24.1 Hz, =CH-CH2). 13C NMR. δ = -4.82 [(CH3)2Si], 29.70 (CH2Cl), 63.20 (OCH2C=CH2), 124.46 (=CH-CH2), 147.67 (=CH-Si), [69.90, 74.9, 76.45, 119.45, 150.2, 172.1 for Asc. Ac.].
Compound 13: 1H NMR: δ = 0.22 [s, 6 H, (CH3)2Si], 2.83 (s, 2 H, CH2Cl), 3.70-3.75 (m, 2 H, H6), [3.93, 4.3, 4.7 for Asc. Ac.], 5.08-5.14 (m, 2 H, CH 2C=CH2), 5.71 (dd, 2 H, 2 J = 7.5 Hz, 4 J = 2.3 Hz, C=CH 2). 13C NMR: δ = -4.82 [(CH3)2Si], 30.5 (CH2Cl), 63.20 (OCH2C=CH2), 128.50 (CH2 C=CH2), 143 (CH2C=CH2), [69.90, 74.90, 76.45, 119.45, 150.20, 172.05 for Asc. Ac.].