1374
S. K. Madhusudan et al. / Carbohydrate Research 340 (2005) 1373–1377
O
O
BnBr, solid NaOH
TBAI, THF
BnO
AcO
OR
OR
Scheme 1. Direct conversion of acyl-protected sugars into alkyl-protected sugar derivatives.
reaction protocol for this purpose has not been de-
scribed, despite its advantages such as ease of applica-
tion, simple workup, and use of inexpensive and
relatively safe reagents.
warming ceric sulfate (2% Ce(SO4)2 in 2 N H2SO4)
sprayed plates on a hot plate or in an oven at
ꢀ100 °C. Silica gel 230–400 mesh was used for column
chromatography. FAB mass spectra were recorded on
JEOL SX 102/DA-6000 mass using Argon/Xenon
In a first set of experiments, a well-stirred solution of
tri-O-acetyl-D-glucal (1.0 mmol) in THF (5.0 mL) was
treated with benzyl bromide (4.0 equiv) and powdered
NaOH (10 equiv) at room temperature in the presence
of a catalytic amount of tetrabutylammonium iodide
(TBAI), a phase transfer catalyst. The reaction was moni-
tored by TLC and after stirring for 3.0 h at room tem-
perature, the clean formation of a product with higher
Rf value was observed. After some experimentation, it
was found that the use of 1.5 equiv of benzyl bromide
and 2.0 equiv of solid NaOH per acetyl group of the acet-
ylated sugars in the presence of TBAI (0.1 equiv with
respect to the sugar derivative) in THF were the best con-
ditions. A number of solvents have been recommended in
the literature for use in alkylation reactions and these
were evaluated. It was found that THF and 1,4-dioxane
offered almost equal efficacy and were the best solvents
for this reaction. The use of a phase transfer catalyst is
essential because the reaction does not go to the comple-
tion in the absence of the catalyst, even at prolonged
reaction times. Other commonly used phase transfer cata-
lysts such as tetrabutylammonium hydrogen sulfate and
tetrabutylammonium bromide were also tested and both
were found to be as effective as TBAI. Under the same
reaction conditions, a number of acylated monosaccha-
ride derivatives have been alkylated in excellent yield
by using various alkyl halides (Table 1).
In conclusion, high yielding, one-pot heterogeneous
reaction conditions have been devised for the direct con-
version of acyl-protected sugars into the corresponding
alkylated sugar derivatives, thus avoiding the conven-
tional two-step procedure of deacylation and alkylation.
A large number of protecting groups on the sugar resi-
due were unaffected under these conditions. This proto-
col should be attractive to synthetic carbohydrate
chemists as it is operationally simple, economically con-
venient, less toxic to the environment, and reduces the
number of reaction steps.
1
(6 kV, 10 MA) as the FAB gas. H and 13C NMR spec-
tra were recorded on Bruker Advance DPX 200 MHz
¨
using TMS as the internal reference. Chemical shift val-
ues are expressed in ppm. Elemental analysis was carried
out on a Carlo ERBA-1108 analyzer. Commercially
available grades of organic solvents of adequate purity
are used; THF was distilled from sodium-benzophenone
prior to use. Products of all known compounds gave
1
acceptable H NMR and 13C NMR data that matched
that reported in the references cited in Table 1.
1.2. Typical experimental protocol
Preparation of 3,4,6-tri-O-benzyl-D-glucal: To a solution
of 3,4,6-tri-O-acetyl-D-glucal (2.8 g, 10.3 mmol) in THF
(10 mL) were added powdered NaOH (2.5 g,
62.5 mmol), TBAI (100 mg, 0.27 mmol), and benzyl bro-
mide (5.5 mL, 46.24 mmol) successively and the reaction
mixture was allowed to stir briskly for 3 h at room tem-
perature. After completion as monitored by TLC, the
reaction mixture was poured into water and extracted
with CH2Cl2. The organic layer was washed with water,
dried (Na2SO4), and concentrated to dryness. The crude
reaction product was purified over SiO2 using hexane–
EtOAc as the eluant to furnish pure 2,4,6-tri-O-benzyl-
D-glucal (4.1 g, 95%). IR (liquid film): 3031, 2896,
1
1647, 1591, 1452, 1097, 1047, 734, 694 cmꢁ1; H NMR
(CDCl3): d 7.34–7.22 (m, 15H, aromatic), 6.42 (dd,
1H, J = 6.1, 1.0 Hz, H-1), 4.87 (dd, 1H, J = 6.3,
2.7 Hz, H-2), 4.18–4.21 (m, 1H, H-3), 4.07–4.01 (m,
1H, H-4), 3.89–3.81 (m, 1H, H-5), 3.79–3.74 (m, 2H,
H-6a,b); 13C NMR (CDCl3): d 145.1, 128.8–128.0 (aro-
matic), 100.4, 77.2, 76.2, 74.9, 74.2, 73.9, 70.9, 69.0.
1.3. Isopropyl 4,6-di-O-benzyl-2,3-dideoxy-a-D-erythro-
hex-2-enopyranoside (2h)
Yellow oil; IR (liquid film): 3032, 2866, 2374, 1455,
25
1372, 1308, 1095, 1026, 737, 697 cmꢁ1; ½aꢂ +92.3 (c
D
1. Experimental
1.0, CHCl3); 1H NMR (CDCl3): 7.40–7.00 (m, 10H, aro-
matic), 6.09–6.02 (m, 1H, H-2), 5.83–5.73 (dt, 1H,
J = 2.5, 2.5 Hz, H-3), 5.11 (br s, 1H, H-1), 4.83–4.77
(d, 1H, J = 11.7 Hz, PhCH2), 4.67–4.40 (m, 3H,
PhCH2), 4.20–4.14 (dd, 1H, J = 9.4, 1.3 Hz, H-4),
1.1. General methods
All reactions were monitored by thin layer chromatogra-
phy on silica gel coated plates; spots were visualized by
4.02–3.93 (m, 1H, H-5), 3.80–3.64 (m, 3H, H-6a,b
,