Organic Syntheses, Coll. Vol. 7, p.139 (1990); Vol. 64, p.57 (1986).
DEOXYGENATION OF SECONDARY ALCOHOLS: 3-DEOXY-1,2:5,6-DI-O-ISOPROPYLIDENE-α-d-ribo-HEXOFURANOSE
. A 1-L, three-necked, round-bottomed flask
equipped with a magnetic stirring bar
, nitrogen-inlet adapter
, pressure-equalizing addition funnel
, and stopper is charged with 26.0 g (0.10 mol) of 1,2:5,6-di-O-isopropylidene-α-D-glucofuranose
, 25 mg of imidazole (Note 1)
, and 400 mL of anhydrous tetrahydrofuran (Note 2)
. The reaction vessel is flushed with nitrogen
and a nitrogen atmosphere is maintained during the ensuing steps. Over a 5-min period, 7.2 g (0.150 mol) of a 50% sodium hydride
dispersion (Note 3)
is added. Vigorous gas evolution is observed. After the reaction mixture is stirred for 20 min, 22.8 g (0.30 mol) of carbon disulfide
is added all at once. Stirring is continued for 30 min, after which time 25.3 g (0.177 mol) of iodomethane
is added in a single portion. The reaction mixture is stirred for another 15 min, and 5.0 mL of glacial acetic acid
is added dropwise to destroy excess sodium hydride
. The solution is filtered (Note 4)
and the filtrate is concentrated on a rotary evaporator
. The semisolid residue is extracted with three 100-mL portions of ether
, and the combined ether
extracts are washed with two 100-mL portions of saturated sodium bicarbonate
solution and two 100-mL portions of water. The ethereal solution is dried over anhydrous magnesium sulfate
, the drying agent is removed by filtration, and the solvent is removed by rotary evaporation. The product is dried further at 0.05 mm overnight. The resulting orange syrup is distilled (Kugelrohr) to give 32.2–33.0 g
) of product, bp 153–160°C (0.5–1.0 mm) (Note 5)
. A dry, 1-L, round-bottomed flask is equipped with a magnetic stirring bar and a reflux condenser
to which a nitrogen inlet is attached. The apparatus is charged with 500 mL of anhydrous toluene (Note 6)
, 24.7 g (0.085 mol) of tributyltin hydride (Note 7)
and 19.25 g (0.055 mol) of 1,2:5,6-di-O-isopropylidene-3-O-(S-methyldithiocarbonate)-α-D-glucofuranose
. The reaction mixture is heated at reflux under a nitrogen atmosphere until TLC analysis indicates the disappearance of starting materials (4–7 hr) (Note 8)
. During this time the reaction solution changes from deep yellow to nearly colorless. The toluene
is removed on a rotary evaporator to yield a thick, oily residue that is partitioned between 250-mL portions of petroleum ether
. The acetonitrile
layer is separated and washed with three 100-mL portions of petroleum ether
and is then concentrated on a rotary evaporator. The residual yellow oil is taken up in hexane-ethyl acetate (10 : 1) and filtered through a pad of silica gel (Note 9)
. The filtrate is concentrated and the residual oil is distilled to give 10.0 g
) of product as a colorless syrup, bp 72–73°C (0.2 mm)
1.4474 (Note 10)
Sodium hydride, a 50% dispersion in mineral oil, was purchased from Alfa Products, Morton Thiokol, Inc.
It is not necessary to remove the mineral oil before conducting the reaction.
The submitters report pure product with bp 135–136°C (0.07 mm)
. The material obtained by the checkers is pure by NMR analysis. It shows 1
H NMR (CDCl3
) δ: 1.35 (s, 6 H), 1.42 (s, 3 H), 1.55 (s, 3 H), 2.60 (s, 3 H), 3.90–4.40 (m, 4 H), 4.68 (d, 1 H), 5.85–6.0 (m, 2 H).
was dried by distilling the toluene–water azeotrope and then cooling the remaining liquid under an atmosphere of nitrogen.
An E. Merck Silica Gel 60 F-254 0.25-mm plate
was used for the TLC analysis.
Silica Woelm TSC, obtained from Woelm Pharma, was used.
The product is pure by NMR and TLC analyses and shows 1
H NMR (CDCl3
) δ: 1.27 (s, 3 H), 1.31 (s, 3 H), 1.38 (s, 3 H), 1.46 (s, 3 H), 1.60–1.90 (m, 1 H), 2.05–2.30 (dd, 1 H), 3.65–4.25 (m, 4 H), 4.71 (t, 1 H), 5.77 (d, 1 H).
This procedure illustrates a simple, general method for the deoxygenation of secondary hydroxyl groups. It is particularly useful for reducing hindered alcohols. The method was first described by Barton and McCombie,3
who have reviewed a number of other examples.4
The tributyltin hydride
reduction usually proceeds without complications. The most common byproduct is starting alcohol, which is postulated to be derived from a mixed thioacetal
Use of the phenyl thionocarbonate
ester has been reported to minimize this side reaction in cases where it is a problem.6
has been prepared by a variety of other methods, the most widely used of which is the Raney nickel
reduction of the 3-S-[(methylthio)carbonyl]-3-thioglucofuranose derivative
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