Reductive elimination of a 1,2- acetoxy-bromide to a double bond
SyntheticPage 78
DOI:
Submitted: August 16, 2001, published: August 17, 2001
Authors
Melanie Reich (m.t.reich@sussex.ac.uk)
A contribution from
Chemicals
carbohydrate (2,3,4-tri-O-acetyl-6-deoxy-a-D-galactopyranosyl-1-bromide) (prepared, 1 equiv.),
zinc dust (Avocado, 6 equiv.),
50 % aqueous acetic acid (2.5 mL/mmol),
ethyl acetate (GPR, 0.01 mL/mmol),
water (0.01 mL/mmol),
dichloromethane (GPR, 2.5 mL/mmol),
water (2 x 0.2 mL/mmol),
saturated sodium hydrogen carbonate (2 x 0.2 mL/mmol),
brine (0.2 mL/mmol)
zinc dust (Avocado, 6 equiv.),
50 % aqueous acetic acid (2.5 mL/mmol),
ethyl acetate (GPR, 0.01 mL/mmol),
water (0.01 mL/mmol),
dichloromethane (GPR, 2.5 mL/mmol),
water (2 x 0.2 mL/mmol),
saturated sodium hydrogen carbonate (2 x 0.2 mL/mmol),
brine (0.2 mL/mmol)
Procedure
To a suspension of zinc dust (18.9 g, 0.29 mol, 6 equiv.) in 50 % aqueous acetic acid (125 mL) was added the carbohydrate (17.0 g, 48.16 mmol, 1 equiv.) in ethyl acetate (25 mL) over 1 hour at -20 °C with strong magnetic stirring. As soon as all starting material had been added the reaction was complete by thin layer chromatography. The suspension was filtered while still cold and the residue washed with a little ethyl acetate (20 mL) and water (20 mL). The filtrate was diluted with dichloromethane (250 mL) and washed with cold water, saturated aqueous sodium hydrogen carbonate solution (2 x 50 mL) and brine (1 x 50 mL). This followed drying of the organic fraction over sodium sulfate and solvent removal in vacuo to give the crude product. After purification by flash column chromatography (petroleum ether/ethyl acetate, 5 : 1) the desired glycal was obtained as a white solid (5.8 g, 56 %).
Author Comments
This procedure has been carried out numerous times on a maximum of 17 g of starting material. The moderate yield can be attributed to the specific saccharide derivative. Hence, changes in reaction temperature and other variations in the procedure were investigated, however only moderate yields could be achieved. A new method, recently desribed by Forbes utilises Vitamin B12 (see other references) and has been shown to improve yields for more sensitive glycals. This may also improve conversion to the fucal, but has not been investigated as yet. The corresponding galactose derivative is obtained in 87 % (0 °C for 1 h, scale: 5 to 50 g). This glycal can also be synthesised in a one-pot procedure, however in slightly lower overall yield (see other references).
NMR data: H-1 refers to the anomeric proton.
Data
dH(300 MHz; CDCl3) 6.43 (1 H, dd, J 6.5 and 2.0, H-1), 5.55-5.43 (1 H, m, H-4), 5.25 (1 H, dt, J 5.0 and 2.0, H-3), 4.60 (1 H, dt, J 6.5 and 2.0, H-2), 4.18 (1 H, q, J 6.5, H-5), 2.12 (3 H, s, CH3CO), 1.98 (3 H, s, CH3CO), 1.24 (3 H, d, J 6.4, CH3)
Lead Reference
A. P. Kozikowski, J. Lee, J. Org. Chem., 1990, 55, 863
Other References
(a) E. Fischer, Chem. Ber., 1914, 47, 196; (b) R. L. Whistler, M. L. Wolfrom, (A. Rosenthal, D. Read), Methods in Carbohydrate Chemistry II, Academic Press, New York, 1963, 457; (c) B. K. Shull, B. K., Z. Wu, M. Koreeda, J. Carbohydr. Chem., 1996, 15, 8, 955 (one-pot procedure); (d) C. L. Forbes, R. W. Franck, J. Org. Chem., 1999, 64, 1424 (Vitamin B12)