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

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.

carbohydrates - fructose - protecting groups - regioselectivity - silyl migration

References

1a Bredereck H. Henning I. Zinner H. Chem. Ber.  1953,  86:  476 

1b Bredereck H. Protzer W. Chem. Ber.  1954,  87:  1873 

2

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) ų, Z = 6 (2 independent molecules), D _c = 1.034 g cm^-3, µ(Cu-K_α) = 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|), 2θ_max = 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.

3

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).

4

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).

5

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).

6

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]⁺.

7

Oral communication by Henry Rzepa.

8

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.

9a Yoon S. J. Korean Chem. Soc.  2002,  46:  590 

9b Arias-Pérez MS. López MS. Santos MJ. J. Chem. Soc., Perkin Trans. 2  2002,  1549 

9c Li Y. Horton D. Barberousse V. Samreth S. Bellamy F. Carbohydr. Res.  1999,  316:  104 

9d Akai S. Nishino N. Iwata Y. Hiyama J. Kawashima E. Sato K. Ishido Y. Tetrahedron Lett.  1998,  39:  5583 

10a Brook AG. J. Am. Chem. Soc.  1958,  80:  1886 

10b Brook AG. Acc. Chem. Res.  1974,  7:  77