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Synlett 2005(15): 2385-2387  
DOI: 10.1055/s-2005-872660
LETTER
© Georg Thieme Verlag Stuttgart · New York

Observation of a 1,5-Silyl-Migration on Fructose

Stefan Furegati, Andrew J. P. White, Andrew D. Miller*
Imperial College Genetic Therapies Centre, Department of Chemistry, Flowers Building, Armstrong Road, Imperial College London, London SW7 2AZ, UK
Fax: +44(20)75945803; e-Mail: a.miller@imperial.ac.uk;
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Publication History

Received 15 June 2005
Publication Date:
08 August 2005 (online)

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Abstract

During synthetic studies involving fructose, an unexpected silyl migration was observed - resulting in a sterically more crowded product. 1,4-Silyl migrations have been observed previously taking place in several different carbohydrate derivatives. However, here we report for the first time an apparent base-assisted 1,5-silyl migration in fructose, identified by evidence from X-ray crystallography and 2D-NMR spectroscopy. This novel migration is related to the Brook rearrangement, and appears to be mediated via an anionic, cyclic transition state involving pentavalent silicon.

Key words

carbohydrates - fructose - protecting groups - regioselectivity - silyl migration

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d-Fructose: [α]D 22 -90.9 (c 10.34, H2O).
Analytical data of 2a: [α]D 22 +5.4 (c 5.00, MeOH); mp = 91.5-93.5 °C; R f = 0.62 (SiO2, EtOAc). 1H NMR (400 MHz, CDCl3): δ = -0.03-0.01 (12 H, m, CH3-Si), 0.78-0.82 (18 H, m, CH3-C-Si), 3.72-4.34 (10 H, m, 2 CH2, 3 CH, 3 OH). 13C NMR (100.4 MHz, CDCl3, two conformations): δ = -5.63, -5.62, -5.59, -5.53, -5.46, -5.39, -5.37, -5.30 (4 C, CH3-Si), 18.4, 18.5 (2 C, C-Si), 25.81, 25.90, 25.94 (6 C, CH3-C-Si), 63.6, 64.0 (CH2), 64.6, 66.8 (CH2), 77.5, 78.8 (CH), 78.9, 79.0 (CH), 85.7, 87.8 (CH), 104.2, 106.3 (C-2). MS (ESI): m/z (%) = 431 (100) [M + Na]+. Crystal data: crystal derived from toluene, C18H40O6Si2, M = 408.68, trigonal, P31 (no. 144), a = 17.0933 (13) Å, c = 15.5690 (16) Å, V = 3939.5 (6) Å3, Z = 6 (2 independent molecules), D c = 1.034 g cm-3, µ(Cu-Kα) = 1.433 mm-1, T = 293 K, colorless needles, Oxford Diffraction Xcalibur PX Ultra diffractometer; 8947 independent measured reflections, F 2 refinement, R 1 = 0.094, wR 2 = 0.252, 4167 independent observed reflections [|F o| > 4σ(|F o|), 2θmax = 143°], 592 parameters. The absolute structure of 2a was determined by a combination of R-factor tests [R 1 + = 0.0935, R 1 - = 0.0960] and by use of the Flack parameter [x + = +0.00(8)]. CCDC 270727.

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Analytical data of 3b: [α]D 22 -12.9 (c 0.500, MeOH); R f = 0.21 (SiO2, hexane-Et2O 19:1). 1H NMR (400 MHz, CDCl3): δ = -0.10-0.00 (12 H, m, CH3-Si), 0.77-0.85 (18 H, m, CH3-C-Si), 3.46-4.80 (13 H, m, 5 CH2, 3 CH), 7.12-7.31 (15 arom. H). 13C NMR (100.4 MHz, CDCl3, two conformations): δ = -5.31, -5.27, -5.24, -5.18, -4.92, -4.21 (4 C, CH3-Si), 17.9, 18.3, 18.4 (2 C, C-Si), 25.7, 25.8, 25.83, 25.9, 26.0 (6 C, CH3-C-Si), 63.0, 64.7, 64.8, 66.9, 67.6, 69.4, 72.2, 72.6, 72.9, 73.4 (5 C, CH2), 76.5, 80.1, 80.2, 82.8, 84.5, 85.5 (3 C, CH), 104.7, 104.8 (C-2), 127.1, 127.2, 127.5, 127.52, 127.6, 127.67, 127.7, 127.8, 127.85, 127.9, 128.0, 128.1, 128.2, 128.23, 128.3, 128.4, 128.5 (15 arom. CH), 138.3, 138.4, 138.43, 138.5, 138.6 (3 arom. C). MS (ESI): m/z (%) = 701 (100) [M + Na]+, 517 (35).

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Analytical data of 4b: [α]D 22 -17.6 (c 1.07, MeOH); R f = 0.21 (SiO2, EtOAc-hexane 3:2). 1H NMR (400 MHz, CDCl3): δ = 2.38-4.84 (15 H, m, 5 CH2, 3 CH, 2 OH), 7.18-7.39 (15 arom. H). 13C NMR (100.4 MHz, CDCl3, two conformations): δ = 63.5, 64.4, 64.7, 64.9, 65.2, 70.9, 72.8, 72.9, 73.0, 73.6 (5 C, CH2), 76.5, 79.6, 80.5, 82.7, 84.8, 84.9 (3 C, CH), 104.8, 105.1 (C-2), 127.4, 127.45, 127.5, 127.6, 127.7, 127.8, 127.82, 127.86, 127.9, 128.0, 128.1, 128.16, 128.2, 128.3, 128.49, 128.50, 128.53, 128.7 (15 arom. CH), 137.8, 137.9, 138.0, 138.3, 138.7. 138.9 (3 arom. C). MS (ESI): m/z (%) = 473 (20) [M + Na]+, 186 (100).

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Analytical data of 1b: [α]D 22 -3.9 (c 1.07, MeOH); R f = 0.17 (SiO2, Et2O-hexane 1:1). 1H NMR (400 MHz, DMSO-d 6, 60 °C): δ = 3.03, 3.26 (2 H, 2 d, J = 9.5 Hz, CH2-1), 3.62 (1 H, dd, J = 11.1, 6.0 Hz, CH2-6), 3.77 (1 H, dd, J = 11.1, 2.4 Hz, CH2-6), 3.92-3.95 (1 H, m, CH-5), 4.12-4.23 (1 H, m, CH-4), 4.28 (1 H, d, J = 7.8 Hz, CH-3), 4.56 (6 H, s, 3 × CH2-Ph), 5.50 (1 H, d, J = 5.6 Hz, OH-CH-4), 7.12-7.50 (30 H, m, arom. H). 13C NMR (100.4 MHz, DMSO-d 6, 60 °C, the only fructose derivative found here displaying only one conformation): δ = 63.7 (CH2-Ph), 66.2 (CH2-1), 70.3 (CH2-6), 71.7 (CH2-Ph), 72.4 (CH2-Ph), 74.7 (CH-4), 80.0 (CH-5), 85.0 (CH-3), 103.8 (C-2), 126.5, 126.9, 126.95, 127.0, 127.1, 127.2, 127.25, 127.3, 127.4, 127.5, 127.7, 127.8, 127.9, 128.0, 128.05, 128.1, 128.3, 128.4 (30 arom. CH), 138.5, 138.9, 143.5, 147.8 (6 arom. C). The assignment of the 1H- and 13C NMR spectra was based on COSY, HSQC and HMBC spectra (unsuccessful for CPh3 though). NOESY cross peaks between CH-3 and both CH 2-1 proved that the β-anomer was present. MS (ESI): m/z (%) = 715 (19) [M + Na]+, 243 (26) [Ph3C]+, 186 (100).

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Analytical data of 2b. Acid quenching or warming to r.t. lead to an exothermic reaction resulting in complex mixtures. Isolation of 2b - the main product whereas no 2a was found - was only successful when the cold mixture was subjected to column chromatography very quickly: [α]D 22 ca. 0 (c 1.05, MeOH); R f = 0.13 (SiO2, EtOAc-hexane 1:2). 1H NMR (400 MHz, CDCl3): δ = 0.03-0.19 (12 H, m, CH3-Si), 0.86-0.95 (18 H, m, CH3-C-Si), 3.49-4.25 (10 H, m, 2 CH2, 3 CH, 3 OH). 13C NMR (100.4 MHz, CDCl3, two conformations): δ = -4.9, -4.8, -4.6, -4.5, -3.6 (4 C, CH3-Si), 17.8, 17.9, 18.3, 18.4 (2 C, C-Si), 25.6, 25.6, 25.7, 25.8 (6 C,
CH3-C-Si), 63.2, 63.4 (CH2), 64.5, 65.7 (CH2), 77.2, 77.6 (CH), 79.1, 79.2 (CH), 84.4, 86.9 (CH), 103.3, 107.2 (2-C). MS (ESI): m/z (%) = 431 (100) [M + Na]+.

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Oral communication by Henry Rzepa.

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Molecular mechanics (MM2) of Chem3D Ultra 9.0: for 2a the X-ray data of the conformation yielding the lower energy were used whereas for 2b several conformations were tried and again the one resulting in the lowest energy was chosen.