Regioselective conversion of primary alcohols into iodides in unprotected methyl furanosides and pyranosides

Article abstract of DOI:10.1055/s-2002-33641

Two methods are described for the regioselective displacement of the primary hydroxy group in methyl glycosides with iodide. The first method is a modification of a literature procedure employing triphenylphosphine and iodine, where purification has been

Full text of DOI:10.1055/s-2002-33641

PAPER
1721
Regioselective Conversion of Primary Alcohols into Iodides in Unprotected
Methyl Furanosides and Pyranosides
Regioselctive
h
i
f
Prim
l
a
ry
A
lc
i
ohols
i
p
n Methyl
G
lycoside
R
s
into Iodides . Skaanderup, Carina Storm Poulsen, Lene Hyldtoft, Malene R. Jørgensen, Robert Madsen*
Department of Chemistry, Building 201, Technical University of Denmark, 2800 Lyngby, Denmark
Fax +4545933968; E-mail: rm@kemi.dtu.dk
Received 4 April 2002
deoxy- -iodoglycosides. We also describe the develop-
ment of an alternative activating agent for this reaction us-
ing sterically hindered trihalobenzenesulfonates.
Abstract: Two methods are described for the regioselective dis-
placement of the primary hydroxy group in methyl glycosides with
iodide. The first method is a modification of a literature procedure
employing triphenylphosphine and iodine, where purification has
been carried out on a reverse phase column in order to efficiently
separate the desired iodoglycosides from triphenylphosphine oxide.
The second method employs a new procedure using sulfonylation in
pyridine with sterically hindered 2,4,6-trichloro- and 2,4,6-tribro-
mobenzenesulfonyl chloride. The sulfonates thus formed are effec-
tive leaving groups and substitution with iodide can be carried out
in a one-pot process. Protection of the iodoglycosides is also de-
scribed either by benzylation with benzyl trichloroacetimidate or
silylation with triethylsilyl chloride.
Iodination with Triphenylphosphine and Iodine
The combination of triphenylphosphine, iodine, and imi-
dazole has previously been employed as a cheap reagent
system for the regioselective iodination of methyl hex-
opyranosides.1c–e The role of imidazole is to accelerate the
reaction and to prevent triphenylphosphine and iodine
from forming a highly insoluble salt. Normally, the iodi-
nation is carried out in toluene at reflux. However, the
starting pyranosides and the products are not soluble un-
der these conditions. Instead, we found refluxing THF to
be a better solvent, which also allowed the reaction to be
carried out at a lower temperature. Hereby, methyl -D-
glucopyranoside was converted cleanly into the corre-
sponding 6-iodo compound 1 (Table 1). We were unable
to separate this from triphenylphosphine oxide by column
chromatography on silica gel. Various extraction proce-
dures were also unsuccessful. Instead, chromatography on
a reverse phase column with octadecyl capped silica gel
60 proved to be an efficient purification method. The im-
idazolium salts were first eluted from the column fol-
lowed by the product 1. This was subsequently
crystallized in 77% yield from ethanol. Triphenylphos-
phine oxide was not eluted from the column using water–
methanol (9:1). Washing with methanol regenerates the
column, and we have reused the same column more than
50 times. Due to the good separation, relatively large
amounts of material can be purified by this method, e.g.
reactions on a 10 g scale have been purified on a column
packed with 200 g of dry weight C18 silica gel.
Key words: carbohydrates, halogenation, regioselectivity, substi-
tution, sulfonates
Introduction
In carbohydrate chemistry regioselective substitution of a
primary hydroxy group with a halide (X = I, Br, or Cl) is
often carried out with triphenylphosphine in the presence
of a halide source (X2, CX4, or NXS).1–3 Although very
good regioselectivity is usually obtained, the method suf-
fers from one major drawback: the formation of triphe-
nylphosphine oxide. This can be very difficult and tedious
to remove. Several reports describe the regioselective io-
dination of unprotected methyl hexopyranosides with an
iodide source and triphenylphosphine.1a–f The 6-iodo-
glycosides thus formed have been separated from triphe-
nylphosphine oxide by acetylation1b–e or column
chromatography on silica gel 60.1a,f We recently needed a
number of unprotected methyl 6-deoxy-6-iodohexopyra-
nosides and 5-deoxy-5-iodopentofuranosides for zinc-
mediated fragmentations.4 However, we were often un-
able to separate the iodoglycosides from triphenylphos-
phine oxide by silica gel chromatography. Although good
separation was observed by TLC, the phosphine oxide and
the iodoglycosides co-eluted completely by normal col-
umn chromatography. This prompted us to look for other
methods, which either would employ a different activat-
ing agent or another chromatography technique. Herein,
we report our results on the use of reverse phase column
chromatography for purification of unprotected methyl -
In a similar way, methyl -D-mannopyranoside and -ga-
lactopyranoside were converted into their corresponding
6-iodoglycosides 2 and 3. It should be noted that methyl
-D-galactopyranoside is a monohydrate and as a result
2.5 equivalents of triphenylphosphine, iodine, and imida-
zole were used in this experiment. The method is also ap-
plicable for regioselective iodination of pentofuranosides.
Due to their better solubility in THF these pentofurano-
sides react within 30 minutes while the hexopyranosides
require about 2 hours for the iodination to go to comple-
tion.
Synthesis 2002, No. 12, Print: 06 09 2002.
Art Id.1437-210X,E;2002,0,12,1721,1727,ftx,en;P01402SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

1722
P. R. Skaanderup et al.
PAPER
Table 1 Iodination with Ph3P, I2, and Imidazole
Substrate
Product
Appearance
Yield (%)
I
HO
O
O
O
1
crystalline (EtOH)
77
HO
OMe
HO
OMe
OMe
HO
I
OH
HO
HO
OH
O
O
2
3
crystalline (Et2O)
86
51
HO
HO
OMe
OMe
HO
HO
OH
OH
HO
I
OH
OH
O
O
O
O
O
crystalline (MeOH)
HO
HO
OMe
OMe
HO
HO
O
O
O
O
OMe
4
5
6
syrup
syrup
syrup
80
79
78
HO
HO
I
OH
HO
OH
OMe
OMe
OMe
OMe
OMe
OMe
HO
HO
I
OH
HO
OH
HO
HO
I
HO
HO
HO
I
7
syrup ( : = 1:1)
74
OH
HO
OH
Table 2 Protection of Iodoglycosides
In the zinc-mediated fragmentations we also needed tri-
ethylsilyl and benzyl protected methyl -deoxy- -iodo-
glycosides.4 These ether protecting groups should be
installed directly on the iodoglycosides. Introduction of
triethylsilyl groups was straightforward using triethylsilyl
chloride and imidazole in dichloromethane (Table 2). The
basic conditions did not affect the primary iodide. Benzyl-
ation, on the other hand, gave rise to a complex mixture
under basic conditions with sodium hydride and benzyl
bromide. Instead, we found that benzylation could be car-
ried out under acidic conditions with benzyl trichloroace-
timidate and triflic acid in dioxane.5 The reaction is fast
and goes to completion within the time it takes to analyze
the mixture by TLC. The pyranosides are stable to the
strongly acidic medium while the furanosides are more la-
bile and should not be exposed to these conditions for
more than 10 min. This two step iodination-benzylation
procedure is shorter than the literature protocol for prepa-
ration of these benzylated iodoglycosides.6 Previous
methods have typically employed a temporary protection
of the primary hydroxy group followed by benzylation,
removal of the temporary protecting group, and iodination
of the primary position.
Sub- Methoda Product
strate
Yield
(%)
I
O
A
B
8 (R = TES)
9 (R = Bn)
94
80
1
RO
OMe
RO
RO
OR
I
O
O
A
B
10 (R = TES) 98
11 (R = Bn) 96
2
RO
OMe
OMe
OR
OR
I
A
B
12 (R = TES) 94
3
4
RO
13 (R = Bn)
73
RO
O
OMe
B
14
68
I
BnO
OBn
a Method A: TESCl, imidazole, CH2Cl2; Method B: BnOC(NH)CCl3,
TfOH, dioxane.
Synthesis 2002, No. 12, 1721–1727 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Regioselctive Conversion of Primary Alcohols in Methyl Glycosides into Iodides
1723
of substitution. For methyl -D-glucopyranoside a
byproduct sulfonylated in the 2-position was also isolated.
For methyl -D-mannopyranoside some anhydride forma-
Iodination with Trihalobenzenesulfonates and Sodi-
um Iodide
Simultaneous with our use of reverse phase chromatogra- tion occurred during the substitution reaction. In general,
phy in the regioselective iodination reaction we also con- tribromo reagent B showed a slightly better regioselectiv-
sidered other activation techniques that would not involve ity than trichloro reagent A. However, B is also the most
triphenylphosphine. In this regard, we were particularly expensive reagent12 and is not commercially available.
interested in sulfonate esters. Methane- and p-toluene- Substitution of these sulfonate esters in pyridine is sensi-
sulfonates have been used in carbohydrate chemistry for a tive to water and vigorously anhydrous conditions must be
long time.7 However, the substitution of these groups with maintained to prevent hydrolysis. Sodium iodide is pre-
nucleophiles often require rather high temperatures. The ferred for the substitution because it is cheap and easy to
p-bromobenzenesulfonate is about 4 times better as a dry while lithium iodide was found to be more difficult to
leaving group, but has only been used on a few occas- handle in these reactions.
sions.8 Instead, the trifluoromethanesulfonate has found
HO
HO
I
widespread applications due to its superior leaving group
properties.9 However, a major drawback of all these sul-
fonates is the lack of regioselectivity in the sulfonylation
of polyhydroxy compounds. A good regioselectivity can
be obtained with 2,4,6-trimethylbenzenesulfonyl chlor-
ide, but the corresponding sulfonate ester is here a rather
poor leaving group in displacement reactions.10 Interest-
ingly, the corresponding 2,4,6-trichloro- and 2,4,6-tribro-
mobenzenesulfonyl chlorides A and B (Figure) are both
known, but have found very little use in organic chemis-
try.11 The corresponding sulfonate esters are about 30
times better leaving groups than the p-toluenesulfonate
ester.11 Furthermore, the steric bulk imposed by the hal-
ides in the ortho positions should also make A and B very
regioselective reagents.
A or B
O
O
pyridine
OMe
HO
OMe
then NaI
R2
R2
R1
R1
HO
HO
R1 R2 Reagent Product Yield(%)
OH
OH
H
H
H
A
B
A
B
1
1
2
2
66
80
68
70
OH
OH
H
Scheme 1
The tandem sulfonylation-iodide substitution reaction can
also be applied to methyl pentofuranosides. Reacting me-
thyl -D-arabinofuranoside with reagent A followed by
addition of sodium iodide gave rise to the 5-iodofurano-
side 5 in 57% yield (Scheme 2). Interestingly, the tandem
reaction could be further extended by including the trieth-
ylsilylation reaction in the same pot. After treatment with
the sulfonylating agent and sodium iodide, the pyridine
mixture was cooled to 0 °C and triethylsilyl chloride was
added. By stirring overnight, the triethylsilylated 5-io-
doarabinofuranoside 15 was obtained in 53% yield. This
yield could be increased to 67% by using the more regio-
selective reagent B. Similar results were obtained when
the methyl furanoside of 2-deoxyribose was subjected to
this cascade reaction.
Cl
Br
Cl
SO2Cl
Br
SO2Cl
Cl
Br
B
A
Figure The structures of 2,4,6-trichloro- and 2,4,6-tribromobenze-
nesulfonyl chlorides A and B
Sulfonyl chlorides A and B can both be prepared from the
corresponding 1,3,5-trihalobenzene by treatment with
chlorosulfonic acid.11 Sulfonyl chloride A is also com-
mercially available. When methyl -D-glucopyranoside
and -D-mannopyranoside were treated with A or B in py-
ridine at –15 °C sulfonylation occurred primarily in the 6-
position (Scheme 1). Although, the generated sulfonate
esters were stable enough to be isolated and purified by
flash chromatography, it was soon realized that the subse-
quent substitution reaction with iodide could in fact be
carried out in the same pot. After completion of the sulfo-
nylation reaction a small amount of DMF was added and
the mixture stirred for 15 minutes. This was followed by
addition of sodium iodide and stirring at 40 °C for 1.5
hours. Hereby, the corresponding 6-iodoglycosides were
obtained in yields ranging from 66% to 80%. Molecular
iodine was formed during the substitution if DMF was not
added. The liberated iodine proved detrimental to the re-
action and caused cleavage of the sulfonate ester instead
O
O
OMe
OMe
A or B, pyridine
HO
I
then NaI,
HO
R
TESO
R
then TESCl
A, pyridine
then NaI
57%
R
Reagent Product Yield(%)
OTES
OTES
H
A
B
A
B
15
15
16
16
53
67
48
52
(R = OH)
O
OMe
I
H
HO
OH
5
Scheme 2
Synthesis 2002, No. 12, 1721–1727 ISSN 0039-7881 © Thieme Stuttgart · New York

1724
P. R. Skaanderup et al.
PAPER
The physical and spectral data of all the -iodoglycosides with trihalobenzenesulfonyl chlorides A or B in pyridine.
prepared are listed in Tables 3– 5.
Due to the good leaving group properties of trihalobenze-
nesulfonates these can undergo an SN2 reaction with io-
dide directly in the pyridine solution. A subsequent
triethylsilyl protection of the remaining secondary hy-
droxy groups can also be performed in the same pot. The
regioselectivity with these trihalobenzenesulfonates is
slightly lower than with triphenylphosphine and iodine
particularly when trichloro reagent A is used. However,
the sulfonylation method is sometimes more convenient
especially when a subsequent protection step can be car-
ried out in the same mixture.
Table 3 Physical Data for -Iodoglycosides
a
Prod- Rf
uct
Mp (°C)
[ ]D
1
2
0.37 (CHCl3–MeOH, 8:1)
147–148b
119–120c
173–174d
70–71e
syrup
+ 99.7b
+ 59.3c
+139.0
– 76.1e
+ 78.6
+101.4
0.32 (CHCl3–MeOH, 8:1)
0.31 (CHCl3–MeOH, 8:1)
0.57 (CHCl3–MeOH, 9:1)
0.46 (CHCl3–MeOH, 9:1)
0.54 (hexane–EtOAc, 1:1)
0.40 (CHCl3–MeOH, 9:1)
0.58 (hexane–EtOAc, 20:1)
0.60 (hexane–EtOAc, 4:1)
0.57 (hexane–EtOAc, 20:1)
0.59 (hexane–EtOAc, 4:1)
0.59 (hexane–EtOAc, 20:1)
0.55 (hexane–EtOAc, 4:1)
0.58 (hexane–EtOAc, 4:1)
0.72 (hexane–EtOAc, 9:1)
0.52 (hexane–EtOAc, 9:1)
3
4
5
TLC was performed on aluminum plates precoated with silica gel
60 F254 (Merck). Compounds were visualized by heating after dip-
ping in a solution of Ce(SO4)2 (2.5 g) and (NH4)6Mo7O24 (6.25 g) in
10% aq H2SO4 (250 mL). Flash chromatography was performed us-
ing silica gel 60 (0.040–0.063 mm, Merck). Reverse phase flash
chromatography was carried out with silica gel 60 C18 (0.040–0.063
mm, Macherey-Nagel). NMR spectra were recorded on a Varian
Unity Inova 500 or a Varian Mercury 300 spectrometer. Optical ro-
tations were measured on a Perkin-Elmer 241 polarimeter. THF and
dioxane were distilled from sodium and benzophenone while pyri-
dine was distilled from CaH2. Methyl furanosides of ribose, arabin-
ose, and 2-deoxyribose were prepared anomerically pure by
literature methods.14 Microanalyses were conducted by the Depart-
ment of Chemistry at the University of Copenhagen. All new com-
pounds gave satisfactory analyses: C 0.35; H 0.30.
6
syrup
f
7
syrup
–
8
syrup
+ 65.2
+ 32.1g
+ 35.9
+ 28.4h
+ 68.5
+ 23.1i
+ 16.4
+ 1.4
9
61–62g
syrup
10
11
12
13
14
15
16
syrup
syrup
syrup
syrup
Iodination of Methyl Glycosides with Ph3P, I2, and Imidazole;
General Procedure
syrup
A soln of the methyl glycoside (500 mg), Ph3P (1.5 equiv), and im-
idazole (2.0 equiv) in anhyd THF (20 mL) was refluxed followed by
the addition of a sol of I2 (1.5 equiv) in THF (5 mL). The resulting
yellow/orange solution was refluxed until TLC revealed full con-
sumption of the starting material (0.5–2 h). A white precipitate of
imidazole hydroiodide was formed. The mixture was cooled to r.t.,
filtered, and concentrated to give a yellow/orange syrup. This was
purified by reverse phase column chromatography using H2O–
MeOH (9:1). Iodofuranosides 4–7 were obtained as syrups while io-
dopyranosides 1–3 were isolated as crystals and recrystallized. io-
dopyranoside 4 crystallized on standing (Table 1, Table 3, Table 4).
syrup
+ 95.8
a c = 2.0, CHCl3.
b Lit.1b mp 146–147 °C, [ ]D +101.5 (c = 1.0, H2O).
c Lit.15 mp 120–122 °C, [ ]D25 +55.5 (c = 0.4, H2O).
d Decomposition. Lit.16 mp 162 °C (dec.).
e Lit.17 mp 68–70 °C, [ ]D22 –78.3 (c = 1.05, CHCl3).
f 1:1 Mixture of anomers.
g Lit.13 mp 68–69 °C, [ ]D20 +36.0 (c = 1.05, CHCl3).
h Lit.6 [ ]D20 +26 (c = 1.39, CHCl3).
i Lit.6 [ ]D20 +23 (c = 1.10, CHCl3).
Triethylsilylation of Iodoglycosides 1–3; General Procedure
To a soln of the iodopyranoside 1–3 (500 mg, 1.6 mmol) and imida-
zole (570 mg, 8.4 mmol) in CH2Cl2 (15 mL) was added triethylsilyl
chloride (1.2 mL, 7.1 mmol) over 2 min at r.t. Imidazole hydrochlo-
ride was observed as a white precipitate. The reaction had gone to
completion after stirring for 24 h and H2O (10 mL) was then added.
The layers were separated and the organic layer dried (K2CO3), con-
centrated, and the syrupy residue purified by flash chromatography
with hexane–Et3N (20:1) (Table 2, Table 3, Table 5).
Conclusion
We have shown that chromatography on a reverse phase
column is an effective method for purifying unprotected
methyl -deoxy- -iodo-glycosides, which have been pre-
pared by treating methyl glycosides with triphenylphos-
phine, iodine, and imidazole in THF. Although, reverse
phase columns are expensive they can be reused many
times and due to the good separation relatively large
amounts of material can be purified in each experiment.
Subsequently, the iodoglycosides can be triethylsilyl or
benzyl protected. This provides a short synthesis of pro-
tected iodoglycosides useful for fragmentation reactions
with zinc.4,6,13
Benzylation of Iodoglycosides 1–4 with Benzyl Trichloroacet-
imidate; General Procedure
To an ice-cooled solution of the iodoglycoside 1–4 (500 mg) and
benzyl trichloroacetimidate (1.3 equiv for each hydroxy group) in
anhyd dioxane (10 mL) was added triflic acid (5–10 drops). Enough
acid should be added to ensure that the mixture is strongly acidic.
The reaction had gone to completion within 10 min at r.t. The mix-
ture was diluted with Et2O (20 mL) and washed with sat. aq
NaHCO3 (20 mL). The organic phase was dried (K2CO3), concen-
trated, and the residue purified by flash chromatography using hex-
ane–EtOAc (5:1) (Table 2, Table 3, Table 5).
We have also developed an alternative iodination proce-
dure. Methyl glycosides are regioselectively sulfonylated
Synthesis 2002, No. 12, 1721–1727 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Regioselctive Conversion of Primary Alcohols in Methyl Glycosides into Iodides
1725
Table 4 1H and 13C NMRa Data of Unprotected Methyl -Deoxy- -iodoglycosides, , J (Hz)
OCH3
3.53
3.53
3.55
J1,2
H-1
4.83
4.82
4.89
J2,3
H-2
3.67
4.02
3.88
J3,4
H-3
3.77
3.85
3.88
J4,5
H-4
3.39
3.66
4.17
J5,6
H-5
3.52
3.54
4.12
J5,6
H-6,6
3.70, 3.47
3.72, 3.46
3.45, 3.40
J6,6
H
1
2
3
J
1
2
3
3.8
9.8
9.4
9.4
2.1
6.4
10.7
1.7
3.4
9.4
9.4
2.6
6.8
11.1
b
2.0
-
1.5
0
4.5
9.0
10.5
OCH3
3.36
3.38
3.36
3.47
3.36
J1,2
H-1
H-2
4.08
4.15
2.21
4.15
4.26
J3,4
H-3
4.19
3.91
4.07
4.27
4.12
J4,5
H-4
4.03
4.08
4.11
4.38
4.58
J4,5
H-5
3.32
3.39
3.23
3.31
3.31
J5,5
H-5
H
4
5
4.83
4.94
5.11
5.03
4.91
J2,3
3.26
3.33
6c
7
3.15
3.22
7
3.29
J
4
0
5.1
5.6
6.0
7.7
9.8
5
0
2.1
3.4
6.8
6.0
10.2
10.7
9.8
6c
7
4.7
6.4
2.1
4.7
6.4
4.3
3.0
4.7
8.1
6.4
7
0
0
3.8
8.1
6.8
9.4
OCH3
56.0
55.7
56.1
55.2
55.1
54.9
56.0
55.1
C-1
C-2
71.9
70.5
68.4d
75.6
80.7
40.8
78.2
79.4
C-3
73.2
70.8
70.0d
75.5
81.0
75.6
76.5
75.9
C-4
74.1
71.3
70.8
82.7
84.5
86.0
79.2
83.5
C-5
70.8
72.2
72.0
7.7
C-6
7.3
6.9
3.1
C
1
2
3
4
5
6
7
7
100.0
101.8
100.1
108.1
109.0
105.6
102.2
109.1
6.7
6.4
1.7
2.0
a 1H NMR (500 MHz) and 13C NMR (75 MHz) of compounds 1–3 were recorded in D2O while compounds 4–7 were recorded in CDCl3.
b Not determined due to overlapping signals.
c
= 1.98 (H-2 , J1,2 0 Hz, J2,2 = 14.1 Hz, J2 ,3 0 Hz).
d Assignments may be reversed.
Sulfonylation and Displacement of the Sulfonyl Group in Meth-
yl Glycosides with Iodide; General Procedure (Schemes 1 and 2)
The methyl glycoside (500 mg, syrups were dried azeotropically
with pyridine) was dissolved in anhyd pyridine (9 mL) and the mix-
ture was cooled to –15 °C under argon. A solution of the sulfonyl
chloride A or B (1.3 equiv) in pyridine (3 mL) was added by syringe
and the mixture was stirred at –15 °C for 90 min. It was then al-
lowed to warm to r.t. over 1 h. Anhyd DMF (0.5 mL) was added fol-
lowed by stirring for an additional 15 min. Finely powdered NaI (3
equiv, dried in vacuo at 225 °C) was then added and the mixture
was stirred at 40 °C for 90 min. For isolation of unprotected
iodoglycosides, the pyridine mixture was diluted with EtOAc (100
Synthesis 2002, No. 12, 1721–1727 ISSN 0039-7881 © Thieme Stuttgart · New York

1726
P. R. Skaanderup et al.
PAPER
Table 5 NMRa Data of Protected Methyl -Deoxy- -iodoglycosides
OCH3
3.43
H-1
4.67
4.63
H-2
3.50
3.55
H-3
3.81
4.02
H-4
3.25
3.35
H-5
3.46
3.47
H-5
–
H-6
3.57
3.47
H-6
3.16
3.29
Others
H
8
1.01–0.93, 0.75–0.51
9
3.43
–
7.35–7.26, 5.00, 4.95, 4.81,
4.80, 4.69, 4.67
b
b
b
10
11
3.48
3.38
4.58
4.76
–
–
–
3.54
3.52
–
–
3.63
3.57
3.34
3.33
1.07–1.01, 0.76–0.66
3.80
3.90
3.78
7.40-7.26, 4.99, 4.76, 4.72,
4.68, 4.62 (2 H)
12
13
3.44
3.42
4.66
4.65
3.96
4.02
3.86
3.93
4.03
4.03
3.87
3.85
–
–
3.31
3.22
3.23
3.09
1.02–0.94, 0.73–0.52
7.41–7.26, 5.04, 4.89, 4.79,
4.76, 4.68, 4.63
14
15
16
3.37
3.40
3.38
4.93
4.69
4.99
J2,3
3.89
3.94
2.47
J3,4
3.95
4.04
3.96
J4,5
4.15
3.86
3.59
J4,5
–
3.38
3.47
3.47
J5,5
–
3.28
3.24
3.29
J5,6
2.1
2.6
3.4
2.6
8.1
7.7
–
–
–
7.39–7.26, 4.65, 4.60, 4.58, 4.51
–
–
0.98–0.96, 0.71–0.58
–
–
1.85 (H-2 ), 0.95, 0.60
JH,H J1,2
J5,6
8.5
6.4
J6,6
10.2
10.7
10.2
10.2
10.2
10.2
–
Others
–
8
9
3.4
3.8
3.0
1.7
3.4
3.8
0
9.0
8.5
8.5
9.5
9.0
9.4
–
–
J
Bn = 12.4, 11.1, 10.7
c
c
c
c
10
11
12
13
14
15
16
–
–
–
–
–
–
-
3.0
9.4
9.4
0
–
–
7.7
5.6
6.4
–
JBn = 12.4, 11.1
9.4
2.6
–
–
-
10.2
4.7
3.0
0
–
–
JBn = 12.0, 11.9, 11.1
JBn = 12.0, 11.5
6.8
5.1
3.9
3.4
C-3
74.9
81.8d
5.6
5.6
4.8
C-4
76.6
81.8d
10.7
10.8
10.8
C-5
71.2
69.6
0
4.0
6.8
–
–
–
-
6.0
OCH3
54.9
55.8
8.3
6.1
–
–
–
J1,2 = 2.8, J2,2 = 13.8, J2 ,3 = 5.6
Others
C-1
99.8
98.4
C-2
74.3
80.4
C-6
8.0
7.9
C
8
7.0, 7.0, 6.7, 6.4, 5.6, 5.4, 5.1
9
10
11
138.8, 138.3, 138.3, 128.8,
127.9, 76.0, 75.6, 73.7
55.1
55.0
100.3
99.0
71.6d
74.6
72.6d
79.9
72.6d
78.6
69.8d
71.4
7.8
7.0
7.0, 6.8, 6.7, 6.3, 5.1, 5.0, 4.7,
4.5
138.2, 138.2, 138.1, 128.3-
127.5, 75.3, 72.7, 72.0
12
13
55.5
55.5
100.4
98.7
69.5
72.3d
78.9
73.6
71.5d
71.2
4.4
3.3
7.0, 6.9, 6.7, 6.4, 5.2, 5.2, 4.9
75.8d
75.7d
138.5, 138.2, 138.1, 128.2–
127.3, 74.8, 73.4 (2 C)
14
55.1
106.0
79.9
81.5
80.1
8.4
–
137.4, 137.3, 128.2–127.4, 72.3,
72.2
15
16
55.4
55.2
108.1
104.1
77.0
42.1
75.7
75.3
80.5
80.8
9.3
7.9
–
–
6.8, 6.7, 4.9
6.6, 4.7
a 1H NMR (500 MHz, CDCl3), 13C NMR (75 MHz, CDCl3).
b
= 3.90–3.85 (m, 3 H).
c Not determined due to overlapping signals.
d Assignments may be reversed.
Synthesis 2002, No. 12, 1721–1727 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Regioselctive Conversion of Primary Alcohols in Methyl Glycosides into Iodides
1727
mL) and washed with 1 M aq HCl (30 mL). The aqueous layer was
extracted with EtOAc (2 100 mL) and the combined organic phas-
es were dried, concentrated, and the residue purified by flash chro-
matography with EtOAc. Alternatively, triethylsilylation could be
carried out in the same pot by the addition of triethylsilyl chloride
(5 equiv) at 0 °C to the pyridine mixture. After stirring overnight at
r.t. hexane (100 mL) was added and the solution washed with H2O
(3 25 mL). The organic phase was dried, concentrated, and the
residue purified by flash chromatography (eluent: hexane–Et3N,
99:1 hexane–EtOAc–Et3N, 97:2:1) (Table 3, Table 5).
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Acknowledgement
We thank the Danish Natural Science Research Council for the fi-
nancial support.
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(12) 1,3,5-Tribromobenzene is about 10 times more expensive
than 1,3,5-trichlorobenzene.
(13) Kleban, M.; Kautz, U.; Greul, J.; Hilgers, P.; Kugler, R.;
Dong, H.-Q.; Jäger, V. Synthesis 2000, 1027.
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Synthesis 2002, No. 12, 1721–1727 ISSN 0039-7881 © Thieme Stuttgart · New York