One pot conversion of carbohydrates alcohol into chloride via benzotriazole sulfonate

Article abstract of DOI:10.1016/j.tet.2013.01.044

A one pot method for chloro-dehydroxylation of carbohydrates alcohol including sterically and electrically hindered ones in excellent yield was developed. The benzotriazole-1-sulfonate proposed to play a crucial role in the reaction medium, which undergoes substitution by chloride ion in the reaction medium to give only desired chloride derivative without the formation of side product. The optimized methodology can be used in the synthesis of number of biologically active compounds or chiral synthones.

Full text of DOI:10.1016/j.tet.2013.01.044

Tetrahedron 69 (2013) 2608e2612
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
One pot conversion of carbohydrates alcohol into chloride via
benzotriazole sulfonate
*
Chandra S. Azad, Anil K. Saxena
Division of Medicinal and Process Chemistry Division, Central Drug Research Institute (CDRI), CSIR, Chattar Manzil Palace, MG Road, Lucknow 226001,
Uttar Pradesh, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A one pot method for chloro-dehydroxylation of carbohydrates alcohol including sterically and electri-
cally hindered ones in excellent yield was developed. The benzotriazole-1-sulfonate proposed to play
a crucial role in the reaction medium, which undergoes substitution by chloride ion in the reaction
medium to give only desired chloride derivative without the formation of side product. The optimized
methodology can be used in the synthesis of number of biologically active compounds or chiral
synthones.
Received 8 November 2012
Received in revised form 8 January 2013
Accepted 15 January 2013
Available online 24 January 2013
Dedicated to Professor Richard R. Schmidt
on the occasion of his 78th birthday.
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Deoxyhalogeno-carbohydrate
Bezotriazole-1-sulfonate
Alcohols to chloride
Appel reaction
1. Introduction
life, high cost and cumbersome application in large scale synthesis.
Appel reaction, a milestone in this direction where triphenyl-
Deoxyhalogeno-carbohydrates are of key importance to carbo-
hydrate and medicinal chemists as they are used as potent artificial
sweeteners,1 male antifertility agents,2 hepatocyte cellular glycos-
aminoglycan inhibitors3 and major scaffolds in antibiotics.4 Re-
cently halogenated carbohydrates have been shown to be a part of
phosphine (PPh3) and carbon tetrachloride or bromide are used in
the conversion of alcohols into halides (I, Scheme 1).11 The major
disadvantage associated with the Appel reaction is the formation of
triphenylphosphine oxide and its removal from the reaction mix-
ture. Further attempts have been made by different research
groups, which include (II) conversion of alcohol into chloride with
the retention of configuration treating its xanthates with thionyl
chloride,12 (III) conversion of alcohols into halide with the aid of the
Vilsmeier-type reagent (PPh3, N-bromosucciniminde and DMF)13
and (IV) conversion of hydroxyl into halides by treating its O-al-
kyl isoureas derivatives with N-halosuccinimide (Scheme 1).14
pharmacophores.5 The 2-deoxy-
D-glucose known for its medicinal
utility,6 can be easily synthesized from the corresponding 2-halo
derivatives of glucose via free radical elimination.7 In general, the
conversion of alcohol functionality of carbohydrate into halide in-
volves first the conversion of alcohol into nucleofugal group e.g.,
mesylate, tosylate, triflate and imidazylate etc., followed by its
substitution with an appropriate nucleophile.8 In general mesylates
and tosylates are considered as good leaving groups but not in the
field of the carbohydrate chemistry because their substitution in-
volves drastic reaction conditions, such as heating at 130 ꢀC for 80 h
in DMF and that too provide nominal amount of the desired
product.9 Though the replacement of mesylates and tosylates by
triflates, substantially extended the scope of reactivity10 of these
sulfonic esters towards nucleophilic substitution reaction, but the
major limitations of some triflate esters are their inadequate self
Condition I: CBr4 or CCl4, PPh3
X
OH
R'
Conditions I-IV
II:a) CS2, MeI; b) SOCl2.
III:PPh3, NBS, DMF;
IV:a) DIC, Cu(OTf)2
b) NBS or NCS
R'
X= Br,Cl
R
R
Scheme 1. Various protocol for simple conversion of alcohol to halide (Br or Cl).
All these methods involve harsh reaction conditions and ex-
pensive reagents. Furthermore, the formation of halides from
nucleofugal groups leads in the formation of unsaturated products
due to competitive elimination reaction. Therefore, investigations
* Corresponding author. Tel.: þ91 522 2612411 8x4268, þ91 522 2624273; fax:
þ91 522 2623405/2623938; e-mail addresses: anilsak@gmail.com, ak_saxena@
cdri.nic.in (A.K. Saxena).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.01.044

C.S. Azad, A.K. Saxena / Tetrahedron 69 (2013) 2608e2612
2609
were made to find a new, simple, cost effective and one pot method
for the synthesis of deoxy-halogenated carbohydrate.
We describe herein one pot conversion of sterically and elec-
tronically hindered alcohol of carbohydrates to their respective
chlorides via benzotriazole sulfonate (Btz), which was designed on
the basis of imidazole-1-sulfonate (Imz, Fig. 1). The Imz is known
for its cost effectiveness and good nucleofugal properties.15 Unlike
Imz, which is used after isolation and purification from the reaction
mixture, the Btz synthesized from sulfuryl chloride and 1,2,3-
benzotriazole (BtH) was used as such without isolation (in situ)
for converting the alcohol of carbohydrates to their respective
chloride derivative (1be7b, Fig. 2). The in situ generated Btz pos-
sibly fragments into BtH and SO3, may be due to the remote acti-
vation of carbon bearing eOH group by the benzotriazolium salt
(BtHþClꢁ) during the reaction, which leads to the displacement of
nucleofuge (sulfonic ester). This has been exemplified in the con-
version of carbohydrates alcohol (carb-OH) to their corresponding
chloride in excellent yield. These chlorides may be useful synthons
for the synthesis of bioactive molecules.
Scheme 2. (i) First approach: SO2Cl2, BtH, DMF, ꢁ40 ꢀC. (ii) Second approach: NaH,
DMF, BtSO2Bt, ꢁ40 ꢀC. (iii) Third approach: (a) NH(SiMe3)2, Py; (b) Bu4NF, DCM,
BtSO2Bt.
In the first approach the isolated product was the chloride de-
rivative of the corresponding carb-OH instead of the expected Btz,
while in the second and third approach a complex nonseperable
mixture was obtained. Thus the unusual formation of chloride
derivative in 88e96% yield with complete inversion of configura-
tion in the first approach is only possible through Btz. Although, Btz
was not isolated from the reaction mixture, but its formation can be
explained on the basis of the product obtained. In order to identify
the role of BtH, the reaction was performed between carb-OH (1a)
and sulfuryl chloride without BtH under the similar reaction con-
ditions viz. temperature ꢁ40 ꢀC, time 24 h to yield the chloride
derivative (2b) in less than 10% yield with retention of configura-
tion. This reaction may involve the chlorosulfonate ester, which
might have been substituted by the chloride ion through SNi
Mechanism (Scheme 3). However the formation of the product in
presence of BtH suggests that Btz is formed in the reaction and gets
substituted by the chloride ion due to its high nucleofugal property
to give an excellent yield of the chloride derivatives 1be7b. These
derivatives were characterized by the state of art techniques like
Fig. 1. Schematic representation of Imz and Btz.
OH
Ph
O
Ph
O
Ph
O
O
O
O
O
O
O
OH
O
O
O
O
O
OH
O
OH
O
OBn
O
O
O
O
OH
O
OBn
O
OH
O
O
O
O
O
MeO
OBn
6a
MeO
OH
MeO
NHCbz
5a
1a
4a
3a
2a
7a
SO2Cl2 (1.5 eq), BtH (6.0 eq)
DCM, -5oC, 6.5 h
Cl
Ph
Ph
O
Ph
O
Cl
O
O
O
O
O
O
O
O
O
O
OBn
Cl
O
Cl
O
O
O
O
O
Cl
O
O
OBn
O
Cl
OBn
O
O
O
O
O
O
MeO
NHCbz
MeO
Cl
MeO
7b
(92%)
1b
(95%)
6b
(88%)
2b
(96%)
3b
(93%)
4b
(92%)
5b
(90%)
Fig. 2. One pot conversion of alcohols into chlorides.
In view of several successful attempts in increasing the stability
and reactivity of benzotriazole derived reagents over the corre-
sponding imidazole derivatives,16 possibly due to the increase in
their electron withdrawing nature as compared to corresponding
imidazole derivatives, the Btz analogue of Imz was synthesized.
Three approaches were adopted for the synthesis of Btz. In the first
approach the carb-OH was reacted with sulfuryl chloride at ꢁ40 ꢀC
in DMF in the presence of BtH. In the second approach, the carb-OH
was converted to its sodium salt with NaH at 0 ꢀC, which was
reacted with BtSO2Bt at ꢁ40 ꢀC. The BtSO2Bt was prepared by the
action of sulfuryl chloride with 1-(trimethylsilyl)-benzotriazole
according to the reported procedure.17 In the third approach, carb-
OH was converted into its silyl ether with the HMDS in pyridine.
The silyl ether was then reacted with BtSO2Bt in presence of Bu4NF
under reflux (Scheme 2).
Scheme 3. Plausible reaction mechanism.

2610
C.S. Azad, A.K. Saxena / Tetrahedron 69 (2013) 2608e2612
NMR, IR, Mass and elemental analysis. The isolation of Btz by the
second and third approach was not successful and complex non
separable mixture was formed in both cases. The results obtained in
the present methodology are better than the earlier reported
methods, which are summarized in Table 1.
instead of the desired product (7b) by the involvement of N-car-
bamate.23 However in our presented methodology the synthesis of
7b is better both in terms of yield and without the formation of
side product oxazolidine. The 6b and 7b can easily be utilized in
the synthesis of 3-deoxy derivative by its reduction with Bu3SnH
in refluxing toluene in the presence of 2-20-azoisobutyronitrile
(AIBN).7
Table 1
Preparation of chlorides from alcohols of carbohydrates moiety (1a)
2. Conclusion
In conclusion, we have developed one pot conversion for the
sterically and electronically hindered alcohol of carbohydrates into
their corresponding chloride derivatives in excellent yield by the
cost effective hitherto unknown in situ generated reagent (Btz),
which plays an important role in the formation of desired product
via SN2 type reaction. The present methodology may be considered
complementary to the Appel reaction, which involves the forma-
tion of side product (triphenylphosphine oxide). Application of this
reagent system allows for conversion of carb-OH into chlorides
under mild reaction conditions, including short reaction time and
devoid of side products.
Entry
1.
Reaction conditions
(i) Tf2O, Py, DCM
Yield
22%
Ref.
19
(ii) But4NCl, C6H6,
(i) Tf2O, Py, DCM
D, 12 h
2.
62%
19
(ii).Bu4NCl, NaHCO3, C6H6, D, 18 h
(i) Imidazole, NCS, PPh3, C6H5Cl,
(i) PPh3,DEAD,4-MeC6H4SO2Cl
(ii) Toluene, D,5 h
SO2Cl2, BtH, DMF, ꢁ40 ꢀC
3.
4.
D
, 3 h
54%
5%
13
24
a
5.
95%
a
The present methodology.
3. Experimental
3.1. General method
In order to widen the scope of the novel methodology, the
studies were extended to optimize the reaction conditions and its
applicability to different sterically and electronically hindered carb-
OH. Hence the reactions were performed using different solvents at
different temperatures and time. The best results were obtained
with the DCM as solvent at temperature range ꢁ5 ꢀC to ꢁ0 ꢀC for
6.5 h. Thus the conditions for the first approach were optimized in
terms of temperature, time and solvent to give the desired chloride
derivative in excellent yield. Based on these results, we hypothe-
sized the mechanism of our reaction as shown in Scheme 3. When
the reaction was performed without BtH there was the retention of
configuration in 1a, while in the presence of BtH the reaction
yielded the completely inverted product, the plausible pathways
adopted in the reaction might be SNi and SN2, respectively
(Scheme 3).
Reagent grade solvents were used for the extraction and flash
chromatography. All the reagents and chemicals were purchased
from SigmaeAldrich Chemical Co., Lancaster and were used di-
rectly without further purification. The progress of reactions was
checked by analytical thin-layer chromatography (TLC, Merck silica
gel 60F-254 plates). The plates were visualized first with UV illu-
mination followed by charring with 10% H2SO4 in CH3OH. Flash
column chromatography was performed using silica gel (230e400
mesh). The solvent compositions reported for all chromatographic
separations are on a volume/volume (v/v) basis. 1H NMR spectra
were recorded at either 200 or 300 MHz and are reported in parts
per million (ppm) on the
internal standard.13C NMR spectra were recorded at either 50 or
75 MHz and are reported in parts per million (ppm) on the scale
relative to CDCl3 77.00). Mass spectra were obtained using JEOL
d scale relative to tetramethylsilane as an
d
(d
The formation of 1b in excellent yield through Btz as compared
to triflate (Table 1) may be explained in two ways, first may be due
to the poor approach of nucleophile because of dipolar interaction
(electronically hindrance)18 and second because of the formation
of unsaturated side products.19 Further the more facile formation
of 2b than 1b may be due the lesser steric and electronic hin-
drance at C-3 of 2a than 1a. The conversion of primary alcoholic
group of 3b directly into its chloride has been reported by the
Samuelsson et al. in excellent yield but the method involved the
use of triphenylphosphine dichloride, which gives triphenylphos-
phine oxide as a side product, which is difficult to be removed
from the reaction at the time of workup and involves the separate
reagent preparation.20 The present one pot methodology provides
3b in excellent yield with easy workup, and without any separate
preparation of reagent. The same is true in case of xylose de-
rivative 4b. The substitution by chloride at C2 position of 5a to
give 5b has been reported in poor yield because of torsional,
electrostatic and steric strain in the transition state.21,22 Whereas
in our case the formation of 5b from 5a in 90% yield is the first
report and may be utilized in the synthesis of potent bioactive 2-
SX-102 (ESI) instrument. Melting points were determined on a Mel
Temp II melting point apparatus and are uncorrected.
3.2. General procedure
First approach: Freshly distilled sulfuryl chloride (1.5 mmol) was
added to the stirred solution of carbohydrate (1 mmol) in DCM
(10 ml) in an RB flask under nitrogen atmosphere at ꢁ5ꢀe0 ꢀC using
NaCl ice bath. The stirring was continued for 40 min at 0 ꢀC and
benzotriazole (6.0 mmol) in DCM (10 ml) was added. The reaction
mixture was stirred at room temperature for 6.5 h and precipitated
salt was filtered. The filtrate was washed with water (3ꢂ50 ml) and
the organic layer was then washed with saturated solution of
Na2CO3 to remove excess of benzotriazole. The combined organic
extract was dried over Na2SO4, and filtered. The filtrate was dried
under vacuum to give chloro derivative.
Second approach: NaH 60% (1.5 mmol) was taken in 50 ml RB
flask and freshly distilled DMF (5 ml) was added under nitrogen
atmosphere followed by the addition of alcohol (1 mmol). The
mixture was stirred continuously for about 45 min and cooled to
ꢁ40 ꢀC. N,N0-sulfuryldibezotriazole (BtSO2Bt) (1.5 mmol) in 5 ml of
DMF was added and stirred for 45 min at ꢁ40 ꢀC, red coloration was
observed in the reaction mixture. 25 ml cold water was added in
the reaction mixture and then extracted with the DCM. The
deoxy-D-glucose by its reduction with tributyltin hydride
(Bu3SnH). Similarly nucleophilic substitution at C3 of 6a and 7a to
give 6b and 7b, respectively has also been reported difficult due to
the steric hindrance of axial anomeric substitutent.18 In the case of
7a it has also led to formation of oxazolidine as side product

C.S. Azad, A.K. Saxena / Tetrahedron 69 (2013) 2608e2612
2611
combined organic layer repeatedly washed with water to remove
DMF, then dried over Na2SO4 and dried under vacuum to dryness.
Third approach: Alcohol (1.5 mmol) was taken in 50 ml RB flask
and 5 ml pyridine, 1 ml hexamethyldisilazane and 0.5 ml of tri-
methylsilyl chloride (TMSCl) is added consecutively, and stirred for
45 min at room temperature followed by the evaporation to the
dryness. The residue so left was dissolved in 10 ml of dichloro-
methane and 2.5 ml of tetrabutyl ammonium fluoride (TBAF) in THF
(1 M) and BtSO2Bt (1.5 mmol) added consecutively. The reaction
mixture was refluxed under nitrogen atmosphere for about 5 h and
then diluted with DCM, washed with water, dried over Na2SO4 and
evaporated under vacuum to dryness.
using first approach is purified using column chromatography
(5e10% EtOAc/hexane) to give the title compound (0.470 g, 90%) as
ꢀ
20
an oil; [
a
]
C þ4.2 (c 0.3, CHCl3); IR (nmax, Neat, cmꢁ1): 1590, 1465,
D
1360, 1250, 785; 1H NMR (300 MHz, CDCl3) : dH 7.58e6.97 (m, 10H),
5.69 (s, 1H), 5.02 (d, J¼11.9 Hz, 1H), 4.90 (d, J¼12.1 Hz, 1H), 4.79 (s,
1H), 4.45 (d, J¼10.3 Hz, 1H), 4.34 (d, J¼8.0 Hz, 2H), 4.08e3.74 (m,
3H), 3.39 (s, 3H). 13C NMR (75 MHz, CDCl3): dC 138.91, 138.03,
129.24, 128.48, 128.30, 128.18, 127.51, 126.02, 102.08, 95.90, 79.14,
75.77, 73.72, 67.01, 60.80, 59.57, 55.32; Anal. Calcd for C21H23ClO5
(390.12): 64.53; H, 5.93%, Found: C, 64.47; H, 5.2.79. ES-MS (MþHþ)
391.1 m/z.
3.2.6. Methyl 3-O-benzyl-4,6-O-benzylidene-3-chloro-3-deoxy-a-D-
3.2.1. 3-Chloro(R)-3-deoxy-1,2:5,6-di-O-isoproplylidene-
anose (1b). The crude product obtained from 1 g 1a using first
approach was purified using column chromatography (5% EtOAc/
a
-
D
-allofur-
altroside (6b). The crude product obtained from 1.0 g 6a using first
approach was purified using column chromatography (15% EtOAc/
hexane) to give the title compound (0.92 g, 88%) as off white solid;
20 ꢀC
hexane) to give the title compound (1.01 g, 95%) as off white solid;
mp 83e84 ꢀC (from hexane); [
a
]
þ188 (c 0.5, CHCl3); IR (nmax
,
D
20 ꢀC
mp 53e54 ꢀC (from hexane); [
a
]
þ42 (c 0.5, CHCl3); IR (nmax
,
Neat, cmꢁ1): 1465, 1397, 1210, 715; 1H NMR (300 MHz, CDCl3)
:7.8e7.1 (m, 10H), 5.77 (s, 1H), 4.95e4.84 (m, 2H), 4.65 (m, 1H), 4.43
(m, 1H), 4.22 (m, 1H), 3.8e4.18 (m, 4H), 3.40 (s, 3H); 13C NMR
D
Neat, cmꢁ1): 1435, 1373, 1150, 740; 1H NMR (300 MHz, CDCl3):
6.01 (d, J¼3.6 Hz, 1H), 5.42e5.21 (m, 1H), 4.92 (d, J¼3.7 Hz, 1H),
4.40e4.20 (m, 2H), 4.16 (m, 1H), 4.10e3.93 (m, 1H), 1.47e1.24 (m,
12H); 13C NMR (75 MHz, CDCl3):
113.03, 107.52, 101.05, 81.27,
d
(75 MHz, CDCl3):
d 137.17, 136.83, 129.04, 128.57, 128.18, 127.79,
d
126.37, 101.86, 98.86, 77.87, 76.32, 73.58, 67.85, 66.33, 63.22, 55.08;
Elemental Anal. for C21H23ClO5 (390.12) Calcd C, 64.53; H, 5.93%,
Found: C, 64.21; H, 5.84. ES-MS (MþHþ) 391.1 m/z.
79.93, 72.90, 69.23 63.93, 27.43, 26.61, 25.43, 24.94; Anal. Calcd for
C12H19ClO5 (278.09): C, 51.71; H, 6.87%, Found: C, 51.63; H, 5.79. ES-
MS (MþHþ) 279.1 m/z.
3.2.7. Methyl 4,6-O-benzylidene-2-benzyloxycarbonylamino-2,3-
3.2.2. 3-Chloro(S)-3-deoxy-1,2:5,6-di-O-isoproplylidene-
a-
D
-allofur-
dideoxy-3-ioso-a-D-allopyranoside (7b). The crude product ob-
anose (2b). The crude product obtained from 1 g 2a using first ap-
proach was purified using column chromatography (5% EtOAc/
tained from 0.5 g of 7a using first approach was purified using col-
umn chromatography (30% EtOAc/hexane) to give the title
hexane) to give the title compound (1.01 g, 96%) as off white solid;
compound (0.480 g, 92%) as an off white solid; mp 99e102 ꢀC (from
20 ꢀC
20 ꢀC
mp 63e64 ꢀC (from hexane); [
a
]
D
ꢁ39 (c 0.5, CHCl3); IR (nmax
,
ethanol); [
a
]
D
e19.5 (c 0.7, CHCl3); IR (nmax, Neat, cmꢁ1):1585,
Neat, cmꢁ1): 1432,1369,1148, 739; 1H NMR (300 MHz, CDCl3):
d
5.99
1456, 1345, 950, 815, 785; 1H NMR (300 MHz, CDCl3):
d 7.58e7.42
(d, J¼3.7 Hz, 1H), 4.95e5.01 (m, 1H), 4.46e4.40 (m, 3H), 4.40e4.38
(m, 2H), 7.26 (d, J¼23.4 Hz, 8H), 5.77 (s, 1H), 5.06 (d, J¼14.3 Hz, 3H),
(m, 1H), 4.24e4.20 (m, 1H), 1.79e1.57 (m, 12H); 13C NMR (75 MHz,
4.81 (s, 1H), 4.52e4.17 (m, 1H), 4.17e3.85 (m, 1H), 3.36 (s, 3H); 13C
CDCl3):
d
113.01, 107.53, 105.57, 81.26, 79.93, 72.88, 69.23, 63.93,
NMR (75 MHz, CDCl3): d 155.96, 136.74, 129.06, 128.68, 128.20,
27.42, 26.59, 25.14, 24.94; Anal. Calcd for C12H19ClO5 (278.09): C,
128.04,126.37,103.87,101.99, 76.62, 68.92, 67.42, 66.95, 60.60, 57.78,
55.29; Anal. Calcd for C22H24ClNO6 (433.88): C, 60.90; H, 5.58; N,
3.23%. Found: C, 60.53; H, 5.18; N, 3.14. ES-MS (MþHþ) 434.9 m/z.
51.71; H, 6.87%, Found: C, 51.64; H, 5.76. ES-MS (MþHþ) 279.1 m/z.
3.2.3. 6-Chloro-6-deoxy-1,2:3,4-di-O-isopropylidine-a-galactopyr-
anose (3b). The crude product obtained from 1.0 g 3a using first
approach was purified using column chromatography (5% EtOAc/
Acknowledgements
hexane) to give the title compound (1.0 g, 93%) as off white solid;
20 ꢀC
C.S.A. is thankful to CSIR, New Delhi for the award of SRF and
acknowledges, A.S. Kushwaha, Mr. Zahid Ali for their technical
support. The authors also acknowledge SAIF-CDRI for providing
spectral and analytical data. The CDRI communication number al-
lotted to this manuscript is 8391.
mp 43e44 ꢀC (from hexane); [
a
]
ꢁ58 (c 0.5, CHCl3); IR (nmax
,
D
Neat, cmꢁ1): 1440, 1370, 1120, 735; 1H NMR (300 MHz, CDCl3):
5.55 (d, J¼5.0 Hz, 1H), 4.72e4.52 (m, 3H), 4.37 (dd, J¼5.0, 2.6 Hz,
1H), 4.32e4.12 (m, 2H), 1.54 (s, 3H), 1.47 (s, 3H), 1.35 (s, 6H); 13C
NMR (75 MHz, CDCl3): 101.58, 108.29, 100.47, 75.48, 75.21, 73.28,
d
d
69.82, 68.48, 44.04, 27.49, 27.26, 26.08, 25.94; Elemental Anal. for
C12H19ClO5 (278.09) Calcd C, 51.71; H, 6.87%, Found: C, 51.65; H,
5.69. ES-MS (MþHþ) 279.1 m/z.
Supplementary data
Supplementary data related to this article can be found online at
http://dx.doi.org/10.1016/j.tet.2013.01.044.
3.2.4. 1,2-O-Isopropylidene-3-O-benzyl-5-deoxy-5-iodo-a-D-xylofur-
anose (4b). The crude product obtained from 1.0 g 4a using first
approach was purified using column chromatography (15% EtOAc/
References and notes
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20 ꢀC
mp 73e74 ꢀC (from hexane); [
a]
ꢁ39 (c 0.5, CHCl3); IR (nmax
,
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V. L. A.; Zhu, J.; Gopishetty, B.; Pei, D. Bioorg. Med. Chem. 2009, 17, 6699; (d)
D
Neat, cmꢁ1): 1430, 1363, 1114, 890, 732; 1H NMR (300 MHz, CDCl3) :
7.45e7.12 (m, 5H), 5.58 (1H), 4.75e4.55 (m, 3H), 4.28 (m, 1H),
3.78, (1H), 3.55e3.72 (m, 2H), 1.48 (3H), 1.31 (3H); 13C NMR
(75 MHz, CDCl3): 137.56, 128.30, 127.80, 127.74, 111.9, 81.75, 80.16,
d
d
79.32, 71.36, 39.60, 26.34, 25.81; Elemental. Anal. for C15H19ClO4
(298.10) Calcd C, 60.30; H, 6.41%, Found: C, 59.98; H, 6.31. ES-MS
(MþHþ) 299.1 m/z.
3.2.5. Methyl 3-O-benzyl-4,6-O-benzylidene-2-chloro-2-deoxy-
a-D-
mannopyranoside (5b). The crude product obtained from 0.5 g 5a

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