Regioselective azidotrimethylsilylation of carbohydrates and applications thereof

Article abstract of DOI:10.1039/c2ob26324f

Azidotrimethylsilylation of carbohydrates (monosaccharides and disaccharides) has been achieved in high yields under Mitsunobu conditions. The azidation of carbohydrates is effected at 0 °C essentially only at the primary alcoholic position in mono, di- and triols in protected/unprotected glycosides, whereas the remaining secondary hydroxyl groups got silylated. Surprisingly, no azidation of the secondary hydroxyls was observed in all the carbohydrate substrates. Applications of the methodology for the synthesis of amino sugars, triazoles and azasugars are reported.

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ARTICLE TYPE
Regioselective azidotrimethylsilylation of carbohydrates and
applications thereof
Mallikharjuna Rao L,a Syed Khalid Yousuf,a Debaraj Mukherjee,a Subhash Chandra Tanejaa*
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
5
DOI: 10.1039/b000000x
Azidotrimethylsilylation of carbohydrates (monosaccharides and disaccharides) has been achieved in high
o
yields under Mitsunobu conditions. The azidation of carbohydrates is affected at 0 C essentially only at
the primary alcoholic position in mono, diꢀ and triols in protected/unprotected glycosides, whereas the
remaining secondary hydroxyl groups got silylated. Surprisingly, no azidation was observed in the
10 secondary hydroxyls in all the carbohydrate substrates. Applications of the methodology for the synthesis
of aminosugars, triazoles and azasugars are reported.
Organic azides are among the most versatile functional groups in
precursors for regioselective oneꢀpot glycosylation.10
organic synthesis. They have fascinated the chemists ever since 50 In carbohydrate chemistry, several methods of the synthesis of
their discovery.1 Besides their use in dipolar cycloadditions,2
15 which clearly contributed to the renaissance of azide chemistry,
they are the excellent reaction partners for a wide variety of
transformations.3 They act as precursors of highly reactive
glycosyl azides have been explored, i.e. reactions of glycosyl
halides with metal azides or tetramethylguanidinium azide under
homogeneous conditions or by using phase transfer catalysts11 of
glycosyl esters with trimethylsilyl azide in the presence of a
intermediates such as nitrenes and nitrenium ions, as well as more 55 Lewis acid catalyst;12 reacting cyclic 1,2ꢀsulfite sugar
common and ubiquitous functional groups such as amines,
20 aziridines, triazoles etc.1 Although, among the most reactive
functional groups, azides are often completely inert, at least from
a kinetic point of view. In this context, carbohydrates bearing
derivatives13 and thiocarbonate ring opening with NaN3.14 The
selective azidation of the terminal hydroxyl group in
monosaccharides for the synthesis of 6ꢀdeoxyꢀ6ꢀazidoꢀ2,3,4ꢀtriꢀ
Oꢀtrimethylsilyl ethers involves multiple reaction steps i.e.
azido functions have emerged as attractive intermediates, 60 tosylation of primary ꢀOH group, base mediated silylation of
bringing forth the ‘click’ adducts with their intrinsic properties
25 (polarity, solubility, biocompatibility, biodegradability including
biological role etc.) or for serving as scaffolds in drug discovery
studies.4 The reduction of azido carbohydrates could also give an
secondary ꢀOH groups by TMSCl followed by steroselective
nucleophilic substitution of Oꢀtosyl group by NaN3.15 Thus, the
synthesis of azido derivatives of carbohydrates is not a trivial task
and problems are frequently encountered because of the harsh
access to new aminoglycosides,5 an important class of 65 experimental conditions such as the requirement of higher
biologically active compounds. Recently, Seeberger et al.6
30 demonstrated the compatibility of the azido group during alkene
metathesis of saccharides, thus exploited their use as protecting
groups in carbohydrate chemistry. In addition to their chemical
temperatures.
During the recent past one pot tandem reactions,16 wherein more
than one useful transformation can be carried out under the same
reaction conditions without adding additional reagents and
importance, biological utilisation of carbohydrate azides is 70 catalysts, have emerged as a powerful tool to achieve synthetic
remarkable. This can be supported by the use of AZT against
35 AIDS and the use of azides in receptor compounds during photo
affinity labelling.7
targets. Hence, in continuance of our recent efforts towards the
development of one pot reaction strategies in carbohydrate
chemistry,17 we herein disclose one pot regioselective tandem
azidotrimethylsilylation of sugars using TMSN3 as a source of
Furthermore, Oꢀsilylation could be the method of choice for
protecting sugar hydroxyl groups in
a
complex synthetic 75 counter ions under Mitsunobu conditions.
Although,
sequence, because deꢀsilylation can be effected selectively in the
40 presence of other ether protecting groups. Silyl ethers of sugar
derivatives can be easily converted into their formates using
either PPh3/CBr4 in HCOOEt/H2O8 or Vilsmeier reagents.9 Wang
et al. utilized silylethers of monosaccharide building blocks as
regioselective and stereospecific azidotrimethylsilylation of 1,2ꢀ
and 1,3ꢀdiols by TMSN3 is reported under Mitsunobu conditions
18 there is no systematic study of this reaction on unprotected and
protected carbohydrates except a few example of protected
80 monosaccharides.18b Therefore, recognizing the huge importance
of azide and silyl protecting groups in carbohydrate chemistry,
we envisaged the exploitation of TMSN3 under Mitsunobu
conditions for tandem azidotrimethylsilylation of carbohydrate
monosaccharides.
45 *Corresponding Author. Tel.:+91-191-2569000; fax: +91-191-2569111;
e-mail: sctaneja@iiim.ac.in,,
aNPC(Microbes), CSIRꢀ Indian Institute of Integrative Medicine, Canal
Road Jammu Tawi, Indiaꢀ180001.
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Table 2. Reaction of different carbohydrates with TMSN3 under
Mitsunobu conditions
Initially, acetonide protected glucofuranoside 1 was selected as a
model substrate to evaluate the efficacy of azidosilylation using
TMSN3 under different experimental conditions (Scheme 1). The
reaction of 1 with TMSN3 (1.3 equiv.), DIAD (1.2 equiv.) and
TPP (1.2 equiv.) at room temperature was completed in 1.5 h
affording a mixture of two products 1a (80%) and 1b (20%)
(Scheme 1).
Entry
Substrate
Reagents in
equiv.
PPh3/DIAD
/TMSN3
Producta
Yieldb %
5
N3
1
HO
HO
HO
O
O
HO
TMSO
1.2/1.2/1.3
ꢀdoꢀ
95
87
PPh3 (1.2 equiv.)
DIAD (1.2 equiv.)
TMSN3 (1.3 equiv.)
O
O
N3
TMSO
O
TMSO
TMSO
BnO
O
BnO
O
HO
O
O
HO
2
2a
+
O
O
O
O
O
Toluene, rt., 1.5 h
BnO
O
BnO
BnO
N3
1
O
O
HO
1a, 80%
1b, 20%
TMSO
2
O
Scheme 1. Reaction of glucofuranoside 1 with TMSN3
O
O
EtO
O
EtO
3
3a
10 The major product 1a was identified as 6ꢀazidoꢀ6ꢀdeoxyꢀ3ꢀOꢀ
benzylꢀ5ꢀOꢀtrimethylsilylꢀ1,2ꢀacetonideglucofuranoside, while
N3
O
O
HO
TMSO
3
4
ꢀdoꢀ
ꢀdoꢀ
88
92
1b was identified as persilylated product on the basis of NMR
and IR spectral data. The upfield shift of CH2 (δ, 55.1 ppm) in the
13C NMR of 1a indicated the azidation at primary hydroxyl
15 group. The formation of 1a can be easily explained by
conventional reaction pathway through the formation of
silyloxyphosphonium ion intermediate followed by nucleophilic
attack by azide ion at less hindered terminal carbon (Fig. 1).18a
O
O
O
O
O
O
4
4a
HO
N3
TMSO
HO
O
O
OAc
OAc
O
O
O
O
5a
5
O
O
Ph
Ph
No steric hinderance
O
5
6
O
ꢀdoꢀ
ꢀdoꢀ
72
89
O
HO
TMSO
N3
OH
OTMS
OMe
Ph
Ph
N3
OMe
6
6a
P
O
O
OH
Ph
O
O
SiMe3
TMSO
BnO
HO
BnO
O
O
HO
O
HO
O
O
PPh3
OBn
BnO
O
Ph
OBn
OMe
OMe
P
7a
TMSN3
7
O
N3
O
Ph
O
Sterically
hinderance
O
Ph
BnO
O
BnO
1
Me3Si
Ph
Ph
HO
HO
N3
O
O
O
O
S-tolyl
S-tolyl
7
1.8/1.8/2.0
ꢀdoꢀ
82*
81
P
X
O
TMSO
Ph
OH
O
OH
OTMS
9a
O
BnO
9
N3
20
Fig.1. Explanation for regioselectivity
O
8
9
OMe
OMe
OTMS
In order to obtain 1a as the sole product, the substitution of DIAD
with DEAD or DBAD under varied reaction conditions (Table 1)
did not make any difference in the pattern of product formation.
However, using DIAD as oxidiser and toluene as a solvent (Table
25 1, entries 7) at lower temperature (0 °C), there was a marked
change in the product distribution and 1a was obtained almost as
an exclusive product.
OH
OH
TMSO
10
10a
N3
OH
OTMS
O
OH
O
TMSO
TMSO
HO
2.4/2.4/2.6
ꢀdoꢀ
89
90
HO
OBn
12a
OBn
12
OH
N3
OH
OTMS
O
O
TMSO
TMSO
10
11
HO
HO
OMe
13a
OMe
SPh
13
Table 1: Optimization of reaction conditions
OTMS
OH
OH
Yieldc%
N3
Entry
Phosphine
activatora
Solventb
Temp.
(°C)
Time
(h)
O
O
(1a:1b)d
ꢀdoꢀ
87
TMSO
HO
SPh
OTMS
14a
OH
14
1
2
3
4
5
6
7
8
9
DIAD
DEAD
DBAD
DIAD
DIAD
DIAD
DIAD
DIAD
DIAD
Toluene
Toluene
Toluene
DMF
rt.
rt.
rt.
rt.
rt.
rt.
0
1.5
3.0
2.0
4.0
2.5
2.5
1.5
1.0
5.0
60 (4:1)
75(3:2)
70(3:2)
50(4:1)
62(7:3)
60(7:3)
95(19:1)
0:0*
aIdentified by spectroscopic analysis. bIsolated yield after column
35 chromatography.* β :α = >99:1.
At higher temperature 60 oC, only primary azidation was
observed probably by deprotection of silyl group mediated by the
basic nature of side products. Following optimization of the
reaction conditions, the scope of the reaction was explored on a
40 panel of vicinal 1,2ꢀsugar diols (Table 2, compounds 2ꢀ6) and
1,3ꢀdiol (Table 2, compound 7). In all the substrates, the
transformations proceeded smoothly leading to the formation of
the azidotrimethylsilylated products in good to excellent yields
except with 6 where only the persilylated product was obtained.
45 From these examples, it may be construed that for the
THF
DCM
Toluene
Toluene
Toluene
60
ꢀ10
94(19:1)
a In all the cases 1.2 equiv. were used. b 5 mL/100 mg of substrate. c
30 Isolated yield of 1a. d Characterized through spectroscopic analysis.
*Only primary azidation was observed.
2
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HO
PPh3 (1.8 equiv.)
DIAD (1.8 equiv.)
TMSN3 (2.0 equiv.)
Table 3. Reaction of 1,4, 1,5ꢀ diols, primary and secondary hydroxyls
with TMSN3 under Mitsunobu conditions
N3
O
O
HO
TMSO
O
O
Producta
Yieldb %
O
HO
Entry
Substrate
Reagents in
equiv.
PPh3/DIAD/
TMSN3
O
TMSO
Toluene, 0 0C, 1.5 h
8
8a, 95%
Dꢀglucofuranose with
Scheme 2. Reaction of 1,2ꢀisopropylideneꢀαꢀ
TMSN3
OH
O
N3
azidotrimethylsilylation of sugars, the presence of a free primary
hydroxyl group is an essential requirement. Next, we extended
this study to triꢀhydroxy sugar derivatives. Thus, 1,2ꢀprotected
glucofuranoside (8) was allowed to react with TMSN3 under the
standardized reaction conditions to afford 8a (95%) as the sole
product (Scheme 2). It was observed that 2 equiv. of TMSN3
10 under standardized reaction conditions was sufficient to afford
the desired product. The regioselectivity of the reaction was high
as analyzed from the spectroscopic data. Reaction of other triꢀ
hydroxy compounds (Table 2, entries 7, 8) under optimized
conditions also proceeded smoothly, affording the primary
15 azidotrimethylsilylated products in good to excellent yields.
The importance and versatility of the reagent system in
unprotected carbohydrates became evident, when the reaction of
O
1
1.8/1.8/2.0
ꢀdoꢀ
65
68
BnO
HO
BnO
RO
5
OH
15
OR
OMe
OMe
15a, R = TMS
OBn
OBn
N3
OH
O
O
2
3
SPh
OTMS
SPh
TMSO
HO
OH
16
16a
N3
HO
O
O
ꢀ1.2/1.2/1.3ꢀ
ꢀdoꢀ
90
OMe
OMe
OH
17
OBn OTMS
OBn
17a
HO
MeO
O
N3
MeO
O
4
5
75
70
O
O
O
TMSO
OH
O
18a
18
methylꢀαꢀDꢀglucopyranoside (11) under the optimized reaction
conditions was studied. As expected the reaction proceeded with
20 high regioselectivity, leading to the formation of product 11a in
90% yield along with the formation of small amounts of 11b (
5%) as a side product (Scheme 3).
N3
BnO
O
HO
BnO
O
ꢀdoꢀ
ꢀdoꢀ
OMe
OTMS
OMe
BnO
OH
OH
BnO
19a
19
N3
6
OR
OH
PPh3 (2.4 equiv.)
DIAD (2.4 equiv.)
TMSN3 (2.6 equiv.)
N3
BnO
O
O
O
HO
BnO
O
68*
RO
RO
O
RO
RO
+
HO
HO
OMe
OTMS
20a
OR
OR
OH
OMe
OBn
R = TMS
OMe
OMe
OMe
Toluene, 0 oC, 2 h
OBn
11
11a, 90%
11b, 5%
20
O
Scheme 3. Reaction of methylꢀαꢀ
D
ꢀglucopyranoside with TMSN3
O
HO
RO
BnO
BnO
7
8
ꢀdoꢀ
80
OH
25 Similar results were obtained with
benzylꢀ or methylꢀαꢀ
OR
22
OMe
R = TMS
OMe
mannosides and thioꢀβꢀgalactoside (Table 2, entries 9ꢀ11). The
stereochemistry at the anomeric centre hardly affects the
regioselectivity or rate of the reaction.
22a
O
O
N3
OH
O
O
1.0/1.0/1.0
67*
O
O
Bittman et al18 have explained the regioselective and
30 stereosepecific azidation of 1,2ꢀ and 1,3ꢀ diols by TMSN3 via
Mitsunobu reaction. While working with 1,4ꢀdiol, the authors
ended up with a cyclic ether (furan). In the case of carbohydrates,
there are no other reports related to the reactions of 1,4ꢀ and 1,5ꢀ
diols with Mitsunobu reagent system. Therefore, to study the
O
O
O
O
23
23a
O
O
O
O
O
O
9
1.0/1.0/1.0
85
O
O
O
O
HO
TMSO
24
24a
35 behaviour of 1,4ꢀsugar diols, methyl 4ꢀOꢀbenzyl−αꢀDꢀ
aIdentified by spectroscopic analysis. bIsolated yield after column
55 chromatography. *20% of silylated product was also formed.
glucopyranoside (15) was subjected to react with TMSN3 under
the standardised reaction conditions. Predictably, 15 was
converted exclusively to the 6ꢀazidoꢀ2,3ꢀdiꢀOꢀsilyl derivative 15a
(Table 3, entry 1). Similar results were obtained from thioꢀ4ꢀOꢀ
hydroxyl
group
leading
to
the
formation
of
azidotrimethylsilylated product 19a (70%) and 20a (68%) (Table
3, entries 5, 6) respectively. The reagent system was successfully
applied to disaccharide sucrose (21) with three free primary
60 hydroxyl groups. It was found that the reaction proceeded
smoothly leading to the formation of diazido derivative 21b as
the major product (58%) along with the formation of of
persilylated compound 21a (20%) (Scheme 4). The
regioselectivity of the azidation was determined through 2D
65 NMR analysis.
40 benzylꢀαꢀ
azidosilyl derivative 16a (Table 3, entry 2). Furthermore, the
reaction of furanoꢀsugar derivatives methylꢀ3ꢀOꢀbenzylꢀαꢀ
ribofuanoside (17) and methylꢀ5ꢀOꢀmethylꢀ1,2ꢀOꢀ(1ꢀ
methylethylidene)ꢀαꢀ ꢀglucofuranose (18) afforded the
Dꢀgalactopyranoside (16) leading to the formation of
D
ꢀ
D
45 azidotrimethylsilylated product 17a and 18a in almost
quantitative yield (Table 3, entries 3, 4). Encouraged by the
results, next we studied the reaction of 1,5ꢀsugar diols i.e. methyl
Contrary to the literature reports18a of azidosilylation of 1,2ꢀ and
1,3ꢀdiols, the formation of five and six membered cyclic
phosphonium ions and the concomitant nucleophilic attack from
the less hindered side may easily explain the regioselectivity of
5,3ꢀdiꢀOꢀbenzylꢀαꢀ
Dꢀglucofuranose (19) and methylꢀ5,3ꢀdiꢀOꢀ
benzylꢀαꢀ ꢀallofuranose (20) under the optimized reaction
D
50 conditions. In 1,5ꢀsugar diols too, under stipulated reaction
conditions regioslective azidation occurred at the primary
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OR
diacetonide glucofuranoside 24 (Table 3, entry 9) also afforded
the corresponding azido compound 23a (67%) and silylated
compound 24a (85%) respectively. After establishing one pot
30 tandem azidotrimethylsilylation methodology in sugar diols,
triols, unprotected glycosides and disaccharides, we exploited the
OR
O
OR
RO
RO
O
OR
OH
O
OH
O
OR
OH
PPh3 (4.8 equiv.)
DIAD (4.8 equiv.)
TMSN3 (5.2 equiv.)
OR
HO
HO
O
21a, 20%
OH
R = TMS
O
+
N3
OH
OH
OR
O
methodology in
chemically/medicinally useful compounds.
Due to the huge biological importance of amino sugars, we
35 initially tried oneꢀpot aminoꢀsilylation of methylꢀαꢀ
ribofuranoside (10) and methylꢀαꢀ ꢀ mannopyranoside (13) under
Staudinger’s conditions19 and successfully achieved the synthesis
of 5ꢀdeoxyꢀ5ꢀaminoꢀ2,3ꢀtrimethylsilyloxy methylꢀαꢀ
ribofuranoside (25) and 6ꢀdeoxyꢀ6ꢀaminoꢀ2,3,4ꢀtrimethylsilyloxy
the
synthesis
of some
of the
OR
O
21
THF, 0 oC, 3h
RO
RO
OR
O
N3
OR
21b, 58%
D
ꢀ
R = TMS
D
Scheme 4. Reaction of sucrose (21) with TMSN3
azidosilylation. In case of normal 1,2ꢀ and 1,3ꢀdiols,18a the attack
of the nucleophile at the secondary position is due to inductive
effects which largely overcome steric hindrance. However, in 1,4ꢀ
and 1,5ꢀ diols, the formation of the cyclic phosphonium ion
intermediate seems to be less favoured due to many factors
including steric hindrance. Thus, the regioselectivity of 1,4ꢀ and
1,5ꢀ diols may possibly be rationalised by the stereoelectronic
10 factors or on the basis of reactivities of the primary and the
secondary hydroxyl groups. In general primary hydroxyls groups
are more reactive than the secondary ones, whereas TMSN3 is a
weak nucleophile, therefore, the azidation of the primary
hydroxyls groups is favoured. In other words, failure of azidation
15 at secondary hydroxyl groups may be assigned to their inability to
generate oxophosphonium ion in carbohydrates. This observation
D
ꢀ
5
40 methylꢀαꢀDꢀmannopyranoside (26) respectively (Schemeꢀ5).
Similarly, 2,3ꢀdipolar cycloadditions20 (Click reaction) to prepare
1,4ꢀtriazole derivatives 27 and 28 were equally successful using
1
1a and 13a as the starting material (Scheme 5). In the HNMR
spectra of 27 and 28, the downfield shift of azide protons
45 indicates the azide protons were at primary position.
In recent past the synthesis of aza sugars has gained much
attention due to their biological importance,21 we therefore
attempted the synthesis of tetrahydroxy azepane 29 using the
current methodology (Scheme 6). Thus benzylꢀαꢀDꢀ
50 mannopyranoside (12) was subjected to one pot azidosilylation
followed by reduction and reductive cyclisation using Pd/C. As
expected, azepane 29 was synthesized in 70% yield. The
literature method employed a longer route for its synthesis with
24% overall yield.22 The 1HNMR of compound 29 was in
55 complete agreement with literature data.22
was substantiated by reacting methylꢀ3ꢀO-benzylꢀαꢀDꢀ
xylopyranoside (22) with TMSN3 under standardised reaction
conditions. The formation of persilylated product 22a (Table 3,
20 entry 7) was in accordance to the proposed explanation on the
basis of the reactivity of hydroxyl groups. Further, as expected
the reaction of diacetonide galactopyranoside 23 (Table 3, entry
8) and
H
N
OH
HO
OH
O
(1) PPh3 /DIAD/TMSN3
HO
HO
HO
.HCl
OH
(2) Pd/C,H2, 1N HCl, MeOH, 36 h, 70%
PPh3 (1.8 equiv.)
DIAD (1.8 equiv.)
TMSN3 (2.0 equiv.)
HO
29
OBn
OTMS
O
12
PPh3 (1.0 equiv.)
N3
H2N
H2O (1 mL)
TMSO
TMSO
THF (10 mL)
O
OMe
OBn
TMSO
OTMS
10
8h
4h
25, 75%
OTs/OMs
PPh3 (2.4 equiv.)
DIAD (2.4 equiv.)
TMSN3 (2.6 equiv.)
THF (10 mL)
GPO
GPO
GPO
N3
GPO
GPO
GPO
O
O
PPh3 (1.0 equiv.)
H2O (1 mL)
OBn
OTMS
O
OBn
H2N
TMSO
TMSO
Literature method
overall yield
13
8h
4h
OMe
26, 78%
24% (ref.22)
EtO2C
Scheme 6. Synthesis of mannoazepane 29.
N
N
N
O
TMSO
In conclusion, we have demonstrated the efficacy of
methodology for the regioselective tandem
a
CO2Et (1.0 equiv.)
1a
O
O
BnO
CuI (5 mol%), MeCN, 6 h
60 azidotrimethylsilylation of carbohydrates under Mitsunobu
conditions. It was also established that the presence of a free
primary hydroxyl function in 1,2 and 1,3, 1,4, 1,5 diols and
protected/unprotected sugars is essential for azidation. Versatility
of the current process for the synthesis of aminoglycoside,
65 triazole and aza sugar such as tetrahydroxy azepane is also
disclosed. The methodology is facile and may find wider
applications in carbohydrate chemistry. Further applications of
this methodology for the synthesis of useful aza sugars and Nꢀ
glycosides are in progress and will be reported in due course of
27, >99%
MeO2C
N
CO2Me (1.0 equiv.)
13a
N
N
OTMS
O
TMSO
TMSO
CuI (5 mol%),
MeCN, 6h
OMe
28, >99%
25
Scheme 5. Synthesis of aminosugars and triazoles using the oneꢀpot
strategy
4
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general procedure 1 using 1.0 mmol (310 mg) of 1 to yield the
time.
60 desired product 1a (94%, 382 mg) as oily liquid. IR (CHCl3):
Experimental section
3032, 2957, 2110, 1290, 1253, 1026, 845 cmꢀ1. [α]20 = ꢀ35.0 (c,
D
1
General information
1.0, CHCl3). H NMR (200MHz, CDCl3), δ; 7.28−7.17 (m, 5H),
1H and 13C NMR spectra were recorded on Bruker 200, 400 and
500 MHz spectrometers (Model No. D 205/52ꢀ2382, Avance 500
5.75 (d, J = 3.68 Hz, 1H), 4.58 (d, J = 13.2 Hz, 1H), 4.47ꢀ4.39
(m, 2H), 4.06 (bs, 2H), 3.92 (s, 1H), 3.49 (dd, J = 2.1, 12.3 Hz,
65 1H, Hꢀ6a/b), 3.30 (ddd, J = 1.9, 12.4 Hz, 1H, Hꢀ6a/b), 1.39 (s,
3H), 1.33 (s, 3H), ꢀ4.818 (s, 9H). 13C NMR (50 MHz, CDCl3),
δ; 137.4, 128.5, 128.4, 128.3, 127.8, 127.3, 111.9, 105.0, 81.4,
81.2, 80.6, 71.6, 68.5, 55.1, 26.8, 26.3, 0.66. ESIꢀMS; 430
(M+Na)+; Anal. Cal. For C19H29N3O5Si; C, 56.00; H, 7.17; N,
70 10.31; Found C, 55.92; H, 7.02; N, 10.21.
5
)
with TMS as the internal standard. Chemical shifts are
expressed in parts per million (δ ppm). MS were recorded on
Waters LC Mass spectrometer (Model No. Symapt MS). Optical
rotations were measured on Perkin Elmer (Model No. 241).
10 Silica gel coated aluminium plates were used for TLC.Elemental
analyses were performed on Vario Elementar (Model No. EL).
Reagents and solvents used were mostly of LR grade.
General procedure (1) for the azidotrimethylsilylation of
diols. DIAD (1.3 mmol, 236 ꢁL) was injected at 0 °C to a
15 solution of a diol (1.0 mmol) and Ph3P (314 mg, 1.2 mmol) (both
thoroughly dried in inert atmosphere) in 18 mL of dry toluene.
The yellow reaction mixture was stirred at this temperature for 30
minutes under nitrogen followed by the addition of Me3SiN3 (1.3
mmol, 155 ꢁL). The reaction mixture was further stirred at the
20 same temperature for 3 h before allowed to warm to room
temperature. The completion of the reaction was monitored by
TLC. Evaporation of the solvent yielded a crude product, which
was dissolved in CH2Cl2 and passed through a pad of silica gel in
a sintered glass funnel to remove Ph3PO and salts. The pad was
6-Azido-3-O-benzyl-6-deoxy-l,2-O-(l-methyIethyIidene)-5-O-
trimethylsilyl-α-D-allofuranose (2a). Prepared by the general
procedure 1 using 1.0 mmol (310 mg) of 2 to yield the desired
product 2a (95%, 386 mg) as oily liquid. IR (CHCl3): 3033, 2967,
75 2101, 1292, 1253, 1026, 845, 740 cmꢀ1. [α]20 = ꢀ65.0 (c, 1.0,
D
CHCl3). 1H NMR (500MHz, CDCl3), δ; 7.25ꢀ7.14 (m, 5H), 5.75
(d, J = 3.5 Hz, 1H), 4.56 (d, J = 2.6 Hz, 1H), 4.45ꢀ4.43 (m, 2H),
4.05ꢀ4.03 (m, 2H), 3.93 (d, J = 8.6 Hz, 1H), 3.45 (d, J = 12.8 Hz,
1H, Hꢀ6a/b), 3.25 (dd, J = 11.1, 12.8 Hz, 1H, Hꢀ6a/b), 1.39 (s,
80 3H), 1.18 (s, 3H), 0.032 (s, 9H). 13C NMR (50 MHz, CDCl3),
δ; 137.4, 128.5, 128.4, 127.8, 127.3, 127.2, 111.9, 105.0, 81.7,
81.3, 80.6, 71.6, 68.5, 55.1, 26.8, 26.3, 0.4 (3C). ESIꢀMS; 430
+
(M+Na) ; Anal. Cal. for C19H29N3O5Si; C, 56.00; H, 7.17; N,
10.31; Found C, 55.92; H, 7.02; N, 10.21.
25 washed with
a mixture of hexanes-EtOAc (usually 6/1)
85 6-Azido-3-O-ethyl-6-deoxy-l,2-O-(l-methyIethyIidene)-5-O-
trimethylsilyl-α-D-glucofuranose (3a). Prepared by the general
procedure 1 using 1.0 mmol (248 mg) of 3 to yield the desired
product 3a (87%, 300 mg) as oily liquid. IR (CHCl3): 2976,
depending on the polarity of the products. The crude products
were purified by silica gel chromatography.
General procedure (2) for the azidotrimethylsilylation of
triols. DIAD (1.8 mmol, 354 ꢁL) was injected at 0 °C to a
30 solution of a triol (1.0 mmol) and Ph3P (472 mg, 1.8 mmol) (both
thoroughly dried in inert atmosphere) in 25 mL of dry toluene.
The yellow reaction mixture was stirred at this temperature for 30
minutes under nitrogen followed by the addition of Me3SiN3 (2.0
mmol, 239 ꢁL). The reaction mixture was further stirred at the
35 same temperature for 3 h before allowed to warm to room
temperature. The completion of the reaction was monitored by
TLC. The crude product after evaporation of the solvent was
dissolved in CH2Cl2 and passed through a pad of silica gel in a
sintered glass funnel to remove Ph3PO and salts. The pad was
2102, 1290, 1081, 843 cmꢀ1. [α]20 = ꢀ53.0 (c, 1.0, CHCl3). 1H
D
90 NMR (500MHz, CDCl3), δ; 5.67 (d, J = 3.7 Hz, 1H), 4.40 (d, J =
3.7 Hz, 1H), 3.94 (dd, J = 2.7, 6.1 Hz, 1H), 3.96ꢀ3.94 (m, 1H),
3.67 (d, J = 2.7 Hz, 1H), 3.52 (dd, J = 1.9, 5.1 Hz, 1H), 3.39 (dd,
J = 2.3, 10.4 Hz, 1H), 3.29 (dd, J = 1.9, 5.1 Hz, 1H, Hꢀ6a/b), 3.17
(dd, J = 5.1, 7.6 Hz, 1H, Hꢀ6a/b), 1.32 (s, 3H), 1.14 (s, 3H), 1.05
95 (t, J =6.9 Hz, 3H), 0.006 (s, 9H). 13C NMR (50 MHz, CDCl3),
δ ; 111.6, 104.6, 81.0, 80.9, 80.0, 66.8, 64.8, 53.0, 26.4, 26.1,
14.6, 0.21 (3C). ESIꢀMS; 368 (M+Na)+; Anal. Cal. for
C14H27N3O5Si; C, 48.67; H, 7.88; N, 12.16; Found C, 48.53; H,
7.76; N, 12.03.
40 washed with
a mixture of hexanes-EtOAc (usually 6/1)
100 6-Azido-3-O-propargyl-6-deoxy-l,2-O-(l-methyIethyIidene)-5-
O-trimethylsilyl-α-D-glucofuranose (4a). Prepared by the
general procedure 1 using 1.0 mmol (258 mg) of 4 to yield the
desired product 4a (88%, 312 mg) as oily liquid. IR (CHCl3):
depending on the polarity of the products. The crude products
were purified by silica gel chromatography.
General procedure (3) for the azidosilylation of unprotected
glycosides. DIAD (2.4 mmol, 472 µL) was injected at 0 °C to a
45 solution of an unprotected glycoside (1.0 mmol) and Ph3P (628
mg, 2.4 mmol) in 30 mL of toluene as described above. The
reaction mixture was stirred for 30 minutes under nitrogen
followed by the addition of Me3SiN3 (2.6 mmol, 311 ꢁL). The
reaction mixture was further stirred at the same temperature for 3
50 h before allowed to warm to room temperature. The completion
of the reaction was monitored by TLC. The crude product after
evaporation of the solvent was dissolved in CH2Cl2 and passed
through a pad of silica gel in a sintered glass funnel to remove
Ph3PO and salts. The pad was washed with a mixture of hexanes-
55 EtOAc (usually 6/1) depending on the polarity of the products.
The crude products were purified by silica gel chromatography.
6-Azido-3-O-benzyl-6-deoxy-l,2-O-(l-methyIethyIidene)-5-O-
trimethylsilyl-α-D-glucofuranose (1a). It was prepared by the
3300, 2957, 2104, 1252, 844, 669 cmꢀ1. [α]20 = ꢀ51.0 (c, 1.0,
D
105 CHCl3). 1H NMR (400 MHz, CDCl3), δ; 5.84 (d, J = 4.0 Hz, 1H),
4.68 (d, J = 3.6 Hz, 1H), 4.23 (dd, J = 2.4, 5.6 Hz, 1H), 4.17 (dd,
J = 2.8, 8.8 Hz, 1H), 4.10 (dd, J = 2.8, 4.8 Hz, 1H), 4.08 (d, J =
3.2 Hz, 2H), 3.55 (dd, J = 2.8, 12.8 Hz, 1H, Hꢀ6a/b), 3.34 (dd, J =
4.8, 12.8 Hz, 1H, Hꢀ6a/b), 2.48 (s, 1H), 1.49 (s, 3H), 1.30 (s, 3H),
110 0.178 (s, 9H). 13C NMR (50MHz, CDCl3), δ; 111.5, 104.4, 80.4,
80.2, 80.0, 78.2, 75.4, 67.8, 56.6, 54.4, 26.2, 25.8, ꢀ0.47 (3C).
ESIꢀMS; 378 (M+Na)+; Anal. Cal. for C15H25N3O5Si; C, 50.68;
H, 7.09; N, 11.82; Found C, 50.51; H, 6.93; N, 11.70.
6-azido-6-deoxy-5-O-trimethylsilyl-2,3-O-(l-
115 methyIethyIidene)-1-acetyl-α-
D
-mannofuranose
(5a).
Prepared by the general procedure 1 using 1.0 mmol (262 mg) of
5 to yield the desired product 5a (92%, 330 mg) as oily liquid. IR
(CHCl3): 2959, 2102, 1231, 1053, 845 cmꢀ1. [α]20 = +25.0 (c,
D
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130.2, 130.1, 130.0, 90.3, 73.1, 72.5, 70.5, 70.1, 21.2, 0.23 (3C),
0.16 (3C). ESIꢀMS; 448 (M+Na)+;
Anal. Cal. for
1
1.0, CHCl3). H NMR (500 MHz, CDCl3), δ; 5.98 (bs, 1H), 4.60
(dd, J = 3.3, 6.8 Hz, 1H), 4.49 (d, J = 6.8 Hz, 1H), 3.95ꢀ3.93 (m,
1H), 3.88 (dd, J = 3.2, 8.9 Hz, 1H), 3.27 (dd, J = 2.5, 12.7 Hz,
1H, Hꢀ6a/b), 3.11 (dd, J = 5.0, 12.7 Hz, 1H, Hꢀ6a/b), 1.87 (s, 3H),
C17H29N3O3SSi2; C, 50.79; H, 7.34; N, 9.87; Found C, 50.34; H,
7.24; N, 9.70.
5
1.28 (s, 3H), 1.09 (s, 3H), ꢀ0.006 (s, 9H). 13C NMR (50 MHz, 65 Methyl
5-azido-5-deoxy-2,3-di-O-trimethylsily-α-D-
CDCl3), δ; 169.2, 112.7, 101.2, 84.7, 81.5, 78.9, 68.9, 54.8, 25.9,
24.6, 21.6, 0.23 (3C). ESIꢀMS; 382 (M+Na)+; Anal. Cal. for
C14H25N3O6Si; C, 46.78; H, 7.01; N, 11.69; Found C, 46.57; H,
6.92; N, 11.53.
ribofuranoside (10a). Prepared by the general procedure 2 using
1.0 mmol (192 mg) of 10 to yield the desired product 10a (81%,
292 mg) as oily liquid. IR (CHCl3): 2954, 2106, 1255, 1056, 844
cmꢀ1. [α]20 = +37.0 (c, 1.0, CHCl3). 1H NMR (500 MHz,
D
10 Methyl
4,6-O-benzylidene-2,3-di-O-trimethylsilyl-α-
D
-
70 CDCl3), δ; 3.90 (t, J = 3.3, 1H), 3.62 (dd, J = 5.3, 11.6, 1H), 3.65ꢀ
3.63 (m, 1H), 3.35 (s, 3H), 3.07 (d, J = 4.0 Hz, 1H), 3.06 (dd, J =
11.5, 13.6 Hz, 1H, Hꢀ6a/b), 3.03 (dd, J = 4.0, 11.5 Hz, 1H, Hꢀ
6a/b), ꢀ0.015 (s, 9H), ꢀ0.044 (s, 9H). 13CNMR (50 MHz, CDCl3),
δ; 104.7, 73.4, 70.6, 69.3, 66.6, 56.8, 0.29 (3C), 0.14 (3C). ESIꢀ
glucopyranoside (6a). Prepared by the general procedure 1 using
1.0 mmol (282 mg) of 6 to yield the desired product 6a (72%,
306 mg) as oily liquid. IR (CHCl3): 3034, 2997, 1290, 1058cmꢀ1.
1H NMR (500 MHz, CDCl3), δ; 7.32ꢀ7.30 (m, 2H), 7.20ꢀ7.16 (m,
15 3H), 5.33 (s, 1H), 4.45 (d, J = 3.7 Hz, 1H), 4.09 (dd, J = 4.7, 10.4 75 MS; 384 (M+Na)+. Anal. Cal. For C12H27N3O4Si2; C, 43.21; H,
Hz, 1H), 3.78 (t, J = 8.9 Hz, 1H), 3.63ꢀ3.61 (m, 1H), 3.53 (t, J =
10.2 Hz, 1H), 3.44 (dd, J = 3.7, 8.7 Hz, 1 H), 3.25 (s, 3H), 3.23ꢀ
3.21 (m, 1H), ꢀ0.01 (s, 9H), ꢀ0.07 (s, 9H). 13C NMR (50 MHz,
CDCl3), δ; 137.0, 128.5, 128.4, 127.8, 127.7, 125.8, 101.3,
8.16; N, 12.60; Found C, 43.02; H, 8.03; N, 12.49.
Methyl 6-azido-6-deoxy-2,3,4-tri-O-trimethylsilyl-α-
glucopyranoside (11a). Prepared by the general procedure 3
using 1.0 mmol, (194 mg) of 11 to yield the desired product 11a
D-
20 100.6, 81.7, 73.8, 71.4, 68.7, 62.0, 55.0, 0.5 (3C), 0.3 (3C). ESIꢀ 80 (90%, 391 mg) as oily liquid. IR (CHCl3): 2958, 2099, 1253,
MS; 449 (M+Na)+; Anal. Cal. For C21H36O5Si2; C, 56.30; H,
8.03; Found C, 56.21; H, 7.91.
1057, 845cmꢀ1. [α]20 = +68.0 (c, 1.0, CHCl3). 1H NMR (500
D
MHz, CDCl3), δ; 4.46 (d, J = 3.6 Hz, 1H), 3.56ꢀ3.55 (m, 1H),
3.52 (dd, J = 2.4, 6.4 Hz, 1H), 3.32 (dd, J = 3.6, 13.2 Hz, 1H),
3.28 (dd, J = 2.4, 13.2 Hz, 1H), 3.24 (dd, J = 6.0, 9.6 Hz, 1H, Hꢀ
85 6a/b), 3.21 (s, 3H, ꢀOCH3), 3.17 (dd, J = 6.0, 13.2 Hz, 1H, Hꢀ
6a/b), 0.029 (s, 9H), ꢀ0.014 (s, 9H), ꢀ0.027 (s, 9H). 13C NMR (50
MHz, CDCl3), δ; 99.8, 74.8, 73.7, 73.0, 70.8, 54.5, 51.6, 0.98
(3C), 0.94 (3C), 0.68 (3C). ESIꢀMS; 458 (M+Na)+ ; Anal. Cal.
for C16H37N3O5Si3 ; C, 44.10; H, 8.56; N, 9.64. Found C, 39.92;
90 H, 8.43; N, 9.53.
Methyl 6-Azido-2,3-di-O-benzyl-6-deoxy-4-O-trimethylsilyl-α-
D-glucopyranoside (7a). Prepared by the general procedure 2
25 using 1.0mmol (374 mg) of 7 to yield the desired product 7a
(89%, 419 mg) as oily liquid. IR (CHCl3): 3032, 2098, 1252,
1053, 842cmꢀ1. [α]20 = +55.0 (c, 1.0, CHCl3). 1H NMR (400
D
MHz, CDCl3), δ; 7.26ꢀ7.34 (m, 10H), 4.99 (d, J = 11.2 Hz, 1H),
4.73 (d, J = 11.2 Hz, 1H), 4.68 (bs, 1H), 4.59 (d, J = 2.0 Hz, 1H),
30 4.58 (d, J = 10.4 Hz, 1H), 3.75ꢀ3.70 (m, 2H), 3.54 (d, J = 9.2 Hz,
1H), 3.49 (dd, J = 3.6, 9.6 Hz, 1H), 3.45 (dd, J = 2.4, 12.8 Hz,
1H, Hꢀ6a/b), 3.39 (s, 3H, ꢀOCH3), 3.33 (dd, J = 5.6 12.8 Hz, 1H,
Hꢀ6a/b), 0.094 (s, 9H). 13C NMR (50 MHz, CDCl3), δ; 138.3,
137.4, 127.8, 127.7, 127.6, 127.5, 127.4, 127.3, 126.9, 126.7,
35 126.6, 126.5, 97.3, 80.8, 79.6, 74.7, 72.7, 71.1, 70.4, 54.7, 50.7, ꢀ
0.23 (3C). ESIꢀMS; 494 (M+Na)+; Anal. Cal. for C24H33N3O5Si;
C, 61.12; H, 7.05; N, 8.91; Found C, 61.02; H, 6.93; N, 8.70.
6-Azido-6-deoxy-l,2-O-(l-methyIethyIidene)-3,5-di-O-
Benzyl
6-azido-6-deoxy-2,3,4-tri-O-trimethylsilyl-α-D-
mannopyranoside (12a). Prepared by the general procedure 3
using 1.0 mmol (270 mg) of 12 to yield the desired product 12a
(89%, 454 mg) as oily liquid. IR (CHCl3): 3035, 2956, 2100,
1
95 1250, 1099, 842cmꢀ1. [α]20 = +46.0 (c, 1.0, CHCl3). H NMR
D
(400 MHz, CDCl3); δ; 7.22ꢀ7.15 (m, 5H), 4.61 (d, J = 12.0 Hz,
1H), 4.54 (d, J = 1.6 Hz, 1H), 4.38 (d, J = 12 Hz, 1H), 3.7 (d, J =
9.2 Hz, 1H), 3.67 (dd, J = 2.4, 4.0 Hz, 1H), 3.63 (dd, J = 2.4, 10
Hz, 1H), 3.59ꢀ3.57 (m, 1H), 3.26 (dd, J = 2.4, 12.8 Hz, 1H, Hꢀ
100 6a/b), 3.19 (dd, J = 6.8, 12.8 Hz, 1H, Hꢀ6a/b), ꢀ0.009 (s, 9H), ꢀ
0.024 (s, 9H), ꢀ0.04 (s, 9H). 13C NMR (100 MHz, CDCl3),
δ; 137.2, 127.6, 127.5, 127.4, 126.2, 126.1, 99.5, 73.2, 73.1, 72.1,
68.8, 68.5, 51.1, 0.46 (3C), 0.37 (3C), 0.34 (3C). ESIꢀMS; 534
(M+Na)+; Anal. Cal. for C22H41N3O5Si3; C, 51.63; H, 8.07; N,
105 8.21; Found C, 51.34; H, 7.89; N, 8.01.
trimethylsilyl-α-D-glucofuranose (8a). Prepared by the general
40 procedure 2 using 1.0 mmol (220 mg) of 8 to yield the desired
product 8a (95%, 369 mg) as oily liquid. IR (CHCl3): 2962, 2100,
1
1253, 1058, 843 cmꢀ1. [α]20 = ꢀ15.0 (c, 1.0, CHCl3). H NMR
D
(400MHz, CDCl3), δ; 5.84 (d, J = 3.6 Hz, 1H), 4.40 (d, J = 3.6
Hz, 1H), 4.20 (d, J = 2.0 Hz, 1H), 4.10ꢀ4.04 (m, 2H), 3.55 (dd, J
45 = 5.2, 12.4 Hz, 1H, Hꢀ6a/b), 3.42 (dd, J = 5.2, 8.0 Hz, 1H, Hꢀ
6a/b), 1.47 (s, 3H), 1.30 (s, 3H), 0.185 (s, 9H), 0.176 (s, 9H). 13
C
NMR (50 MHz, CDCl3), δ; 111.9, 104.9, 84.4, 81.6, 75.2, 68.8,
54.9, 26.7, 26.3, 0.61 (3C), 0.46 (3C). ESIꢀMS; 412 (M+Na)+;
Anal. Cal. for C15H31N3O5Si2; C, 46.24; H, 8.02; N, 10.79; Found
50 C, 46.11; H, 7.93; N, 10.70.
Methyl
6-azido-6-deoxy-2,3,4-tri-O-trimethylsilyl-α-D-
mannopyranoside (13a). Prepared by the general procedure 3
using 1.0 (194 mg) of 13 to yield the desired product 13a (90%,
391 mg) as oily liquid. IR (CHCl3): 2958, 2914, 2099, 1252,
110 1154, 1020, 840, 752 cmꢀ1. [α]20 = +73.0 (c, 1.0, CHCl3). H
1
Thio-p-toluoyl
5-azido-5-deoxy-2,3-di-O-trimethylsily-β-D-
D
ribofuranoside (9a). Prepared by the general procedure 2 using
1.0 mmol (256 mg) of 9 to yield the desired product 9a (82%,
NMR (500 MHz, CDCl3), δ; 4.34 (bs, 1H), 3.68 (t, J = 9.0 Hz,
1H), 3.63 (d, J = 1.5 Hz, 1H), 3.57 (dd, J = 2.5, 8.8 Hz, 1H),
3.51ꢀ3.50 (m, 1H), 3.28 (dd, J = 2.1, 12.8 Hz, 1H, Hꢀ6a/b), 3.23
(s, 3H, ꢀOCH3), 3.19 (dd, J = 7.1, 12.8 Hz, 1H, Hꢀ6a/b), ꢀ0.021 (s,
115 9H), ꢀ0.034 (s, 9H), ꢀ0.096 (s, 9H). 13C NMR (50 MHz, CDCl3),
δ; 101.4, 73.04, 73.02, 72.03, 68.7, 54.4, 51.0, 0.38 (3C), 0.24
(3C), 0.15 (3C). ESIꢀMS; 458 (M+Na)+; Anal. Cal. for
C16H37N3O5Si3; C, 44.10; H, 8.56; N, 9.64; Found C, 44.01; H,
348 mg) as oily liquid. IR (CHCl3): 3034, 2957, 2108, 1253,
1
55 1088, 843cmꢀ1. [α]20 = = +43.0 (c, 1.0, CHCl3). H NMR (500
D
MHz, CDCl3), δ; 7.22ꢀ7.19 (m, 2H), 6.97ꢀ6.92 (m, 2H), 4.28 (d, J
= 9.1 Hz, 1H), 3.71 (dd, J = 5.2, 11.4 Hz, 1H), 3.45ꢀ3.43 (m, 1H),
3.35ꢀ3.33 (m, 1H), 3.09 (dd, J = 10.4, 16.1Hz, 1H, Hꢀ5a/b), 3.01
(dd, J = 10.4, 11.4 Hz, 1H, Hꢀ5a/b), 2.16 (s, 3H), 0.04 (s, 9H),
60 0.006 (s, 9H). 13C NMR (50MHz, CDCl3), δ; 137.8, 132.7, 132.6,
6
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8.43; N, 9.50.
Thiophenyl
78.7, 73.6, 72.3, 55.3, 53.3, 0.00(3C). ESIꢀMS; 374 (M+Na)+;
60 Anal. Cal. For C16H25N3O4Si; C, 54.68; H, 7.17; N, 11.96; Found
C, 54.57; H, 7.07; N, 11.85.
6-azido-6-deoxy-2,3,4-tri-O-trimethylsilyl-β-D-
galactopyranoside 14a. Prepared by the general procedure 3
using 1.0 mmol (272 mg) of 14 to yield the desired product 14a
(87%, 446 mg) as oily liquid. IR (CHCl3): 3061, 2956, 2109,
6-Azido-5-O-methyl-6-deoxy-l,2-O-(l-methyIethyIidene)-3-O-
5
trimethylsilyl-α-
D-glucofuranose (18a). It was prepared by the
1251, 1146, 844, 746 cmꢀ1. [α]20 = +46.3 (c, 1.0, CHCl3). 1H
general procedure 1 using 0.51 mmol (120 mg) of 18 to yield the
D
NMR (400 MHz, CDCl3), δ; 7.48ꢀ7.45 (m, 2H), 7.27ꢀ7.22 (m, 65 desired product 18a (75%, 127 mg) as a syrapy liquid. IR
3H), 4.49 (d, J = 9.2 Hz, 1H), 3.54 (t, J = 0.8 Hz, 1H), 3.49 (dd, J
= 8.0, 9.6 Hz, 1H), 3.43 (dd, J = 6.0, 11.2 Hz, 1H), 3.38 (d, J =
10 8.0 Hz, 1H), 3.28 (dd, J = 0.8, 1.6 Hz, 1H, Hꢀ6a/b), 3.26 (dd, J =
(CHCl3): 2998, 2106, 1290, 1054, 843cmꢀ1. [α]20D = ꢀ37.8 (c, 1.0,
CHCl3). 1H NMR (400 MHz, CDCl3) δ; 5.86 (d, J = 3.6 Hz, 1H),
4.36 (d, J =3.6 Hz, 1H), 4.28 (d, J =2.4 Hz, 1H), 4.16 (dd, J =2.8,
8.8 Hz, 1H), 3.75 (dd, J =2.8, 13.6 Hz, 1H), 3.59 (dd, J = 4.0,
1.6, 5.6 Hz, 1H, Hꢀ6a/b), 0.196 (s, 9H), 0.146 (s, 9H), 0.11 (s,
9H). 13C NMR (50 MHz, CDCl3), δ; 133.5, 130.8, 130.7, 128.7, 70 13.6, 1H, Hꢀ6a/b), 3.43 (s, 3H, ꢀOCH3), 3.39 (dd, J = 4.0, 11.6
128.6, 127.3, 89.3, 78.0, 74.5, 64.1, 51.8, 0.88 (3C), 0.63 (3C),
0.45 (3C). ESIꢀMS; 536. (M+Na)+; Anal. Cal. For
15 C21H39N3O4SSi3; 49.08; H, 7.65; N, 8.18; .Found C, 39.91; H,
7.51; N, 8.01.
1H, Hꢀ6a/b), 1.56 (s, 3H), 1.33 (s, 3H), 0.19(s, 9H).13C NMR
(100 MHz, CDCl3) δ; 111.9, 104.8, 85.1, 79.3, 75.6, 74.0, 57.2,
50.4, 26.7, 26.4, 0.3 (3C). ESIꢀMS; 354 (M+Na)+; Anal. Cal. For
C13H25N3O5Si; C, 47.11; H, 7.60; N, 12.68; Found C, 46.98; H,
Metyl 6-azido-6-deoxy-4-O-benzyl-2,3-di-O-trimethylsilyl-α- 75 7.49; N, 12.52.
-glucopyranoside (15a). It was prepared by the general Methyl
D
6-azido-3,5-di-O-benzyl-2-O-trimethylsilyl-α-D-
procedure 2 using 0.52 mmol (150 mg) of 15 to yield the desired
20 product 15a (65%, 160 mg) as oily liquid. IR (CHCl3): 3035,
glucofuranoside (19a). It was prepared by the general procedure
1 using 0.53 mmol (200 mg) of 19 to yield the desired product
19a (70%, 176 mg) as syrapy liquid. IR (CHCl3): 3034, 2927.96,
2985, 2109, 1290, 1057, 846, 754 cmꢀ1. [α]20 = +130.0 (c, 1.0,
D
CHCl3). H NMR (400 MHz, CDCl3) δ; 7.18ꢀ7.11 (m, 5H), 4.74 80 2101.02, 1254.20, 1154.56, 1032.62, 844, 734cmꢀ1. [α]20D = ꢀ28.9
1
1
(d, J =11.6 Hz, 1H), 4.45 (d, J = 3.6 Hz, 1H), 4.35 (d, J = 1.6Hz,
1H), 3.75 (dd, J = 3.6, 8.8 Hz, 1H), 3.56 (ddd, J =2.4, 6.0, 10.0,
25 Hz, 1H), 3.36 (dd, J = 3.6, 9.2Hz, 1H), 3.20 (s, 3H, ꢀOCH3), 3.16
(dd, J = 7.2, 11.6 Hz, 1H, Hꢀ6a/b), 3.11 (dd, J = 5.6, 7.2 Hz, 1H,
(c, 1.0, CHCl3). H NMR (500 MHz, CDCl3), δ; 7.32ꢀ7.25 (m,
10H), 4.72 (s, 1H), 4.66 (d, J =11.2 Hz, 1H), 4.61(d, J =11.9 Hz,
1H), 4.53 (s, 1H), 4.49 (d, J =11.4 Hz, 1H), 4.35 (dd, J =4.4, 8.6
Hz, 1H), 4.16 (s, 1H), 4.04 (m, 1H), 3.87 (d, J = 4.6 Hz, 1H),
H6a/b), ꢀ0.02 (s, 9H), ꢀ0.09 (s, 9H). 13C NMR (125MHz, CDCl3) 85 3.71 (dd, J = 2.4, 13.1 Hz, 1H, Hꢀ6a/b), 3.43 (dd, J = 4.6, 13.1Hz,
δ; 137.5, 128.1, 128.0, 127.8, 127.3, 127.0, 99.5, 79.2, 74.8, 74.3,
73.4, 69.3, 54.7, 52.9, 0.51 (3C), 0.46 (3C). ESIꢀMS; 476
30 (M+Na)+; Anal. Cal. For; C20H35N3O5Si2; C, 52.95; H, 7.78; N,
9.26; Found C, 52.83; H, 7.65; N, 9.17.
1H, Hꢀ6a/b), 3.38 (s, 3H, ꢀOCH3), 0.09 (s, 9H).13C NMR (125
MHz, CDCl3) δ; 138.1, 137.8, 128.5, 128.4, 128.3, 128.2, 128.1,
128.0, 127.9, 127.86, 127.84, 127.7, 110.8, 83.0, 80.4, 78.5, 76.4,
72.4, 72.1, 56.2, 52.1, 0.00 (3C). ESIꢀMS; 494 (M+Na)+; Anal.
Thiophenyl
trimethylsilyl-β-
the general procedure 2 using 0.27 mmol (100 mg) of 16 to yield
6-azido-6-deoxy-4-O-benzyl-2,3-di-O- 90 Cal. For C24H33N3O5Si; C, 61.12; H, 7.05; N, 8.91; Found C,
-galactopyranoside (16a). It was prepared by 61.02; H, 6.97; N, 8.82.
Methyl 6-azido-3,5-di-O-benzyl-2-O-trimethylsilyl-α-D-
D
35 the desired product 16a (68%, 99.7 mg) as a syrapy liquid. IR
allofuranoside (20a). It was prepared by the general procedure 1
using 0.53 mmol (200 mg) of 20 to yield the desired product 20a
(CHCl3): 2987, 2105, 1290, 1049 cmꢀ1. [α]20 = +43.5 (c, 1.0,
D
1
CHCl3). HNMR (400 MHz, CDCl3) δ; 7.31ꢀ7.28 (m, 2H), 7.16ꢀ 95 (68%, 171 mg) as a syrapy liquid. IR (CHCl3): 3038, 2956, 2105,
7.10 (m, 5H), 7.09ꢀ7.02 (m, 3H), 4.80 (d, J = 11.2 Hz, 1H), 4.40
(s, 1H), 4.36 (d, J = 9.6 Hz, 1H), 3.82 (t, J = 8.8 Hz, 1H), 3.44ꢀ
40 3.42 (m, 1H), 3.41ꢀ3.40 (m, 1H), 3.36 (d, J = 6.8 Hz, 1H), 3.33
(dd, J = 0.8, 4.8 Hz, 1H, Hꢀ6a/b), 2.99 (dd, J = 4.8, 11.6 Hz, 1H,
1255, 1157, 1038, 845, 738cmꢀ1. [α]20 = ꢀ68.9 (c, 1.0, CHCl3).
D
1H NMR (500 MHz, CDCl3), δ; 7.32ꢀ7.24 (m, 10H), 4.71 (s, 1H),
4.64 (d, J =11.2 Hz, 1H), 4.62(d, J =11.9 Hz, 1H), 4.55 (s, 1H),
4.52 (d, J =11.4 Hz, 1H), 4.37 (dd, J = 4.4, 8.6 Hz, 1H), 4.17 (s,
H6a/b), 0.01(s, 9H), ꢀ0.04 (s, 9H). 13C NMR (125 MHz, CDCl3) 100 1H), 4.04 (m, 1H), 3.98 (d, J = 4.0 Hz, 1H), 3.71 (dd, J =2.4,
δ; 138.4, 134.6, 131.4, 131.1, 129.1, 128.7, 128.5, 128.2, 128.0,
127.9, 127.3, 126.9, 89.8, 77.7, 77.3, 77.0, 74.9, 71.1, 51.3, 1.1
45 (3C), 0.40 (3C). ESIꢀMS; 554 (M+Na)+; Anal. Cal. For
C25H37N3O4SSi2; C, 56.46; H, 7.01; N, 7.90; Found C, 56.34; H,
6.90; N, 7.79.
13.6 Hz, 1H, Hꢀ6a/b), 3.43 (dd, J = 4.6, 13.6 Hz, 1H, Hꢀ6a/b),
3.38 (s, 3H, ꢀOCH3), 0.09 (s, 9H).13C NMR (125 MHz, CDCl3) δ,
138.1, 137.8, 128.5, 128.4, 128.3, 128.2, 128.1, 128.0, 127.9,
127.86, 127.84, 127.7, 110.8, 83.0, 81.5, 79.0, 76.4, 72.4, 72.1,
105 56.2, 52.1, 0.00 (3C). ESIꢀMS; 494 (M+Na)+; Anal. Cal. For
C24H33N3O5Si; C, 61.12; H, 7.05; N, 8.91; Found C, 61.02; H,
6.97; N, 8.82.
Methyl 5-azido-5-deoxy-3-O-benzyl-2-O-trimethylsilyl-α-D-
ribofuranoside (17a). It was prepared by the general procedure 1
50 using 0.787 mmol (200 mg) of 17 to yield the desired product
17a (90%, 248 mg) as oily liquid. IR (CHCl3): 3037, 2927, 2101,
6,6’-di-azido-6,6’-di-deoxy-2,3,4,1’,3’,4’-hexa-O-
trimethylsilyl sucrose (21b). Prepared by the general procedure
1252, 1158, 1036,847, 765cmꢀ1. [α]20 = +31.6 (c, 1.0, CHCl3). 110 3 using 0.28 mmol (100 mg) of 21 to yield the desired product
D
1H NMR, (400 MHz, CDCl3) δ; 7.19ꢀ7.12 (m, 5H ), 4.55 (s, 1H),
4.45 (d, J =11.6 Hz, 1H), 4.24 (d, J = 11.6 Hz, 1H), 4.06 (m,
55 1H), 3.95 (d, J = 4.0 Hz, 1H), 3.74 (dd, J =4.0, 7.6 Hz, 1H), 3.25
(dd, J = 3.2, 13.2 Hz, 1H, Hꢀ5a/b), 3.20 (s, 3H, ꢀOCH3), 3.03 (dd,
21b (58%, 142 mg) as oily liquid. IR (CHCl3): 2954, 2901, 2110,
1257, 1148, 846, 748cmꢀ1 [α]20D = ꢀ58.6 (c, 1.0, CHCl3). 1H NMR
(400 MHz, CDCl3), δ; 5.07 (d, J = 4.2 Hz, 1H), 4.16 ( d, J = 8.0
Hz, 1H), 3.85 (t, J = 8.0 Hz, 1H), 3.79ꢀ3.73 (m, 1H), 3.71ꢀ3.64
J = 6.0, 13.2 Hz, 1H, Hꢀ5a/b), 0.008 (s, 9H).13C NMR (100 MHz, 115 (m, 2H), 3.61 (dd, J = 8.9 Hz, 17.9 Hz, 1H), 3.52 (dd, J = 8.6,
CDCl3) δ; 137.4, 128.4, 128.3, 127.8, 127.7, 127.6, 109.0, 79.4,
13.0 Hz, 1H), 3.38 (d, J =11.1 Hz, 2H), 3.26 (d, J = 12.0 Hz, 1H),
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(s, 3H), 2.89ꢀ2.87 (m, 1H), 2.65ꢀ2.63 (m, 1H), 0.037 (s, 9H),
ꢀ0.01 (s, 9H), ꢀ0.02 (s, 9H), ꢀ0.028 (s, 9H), ꢀ0.03 (s, 9H), ꢀ0.033 60 0.026 (s, 9H), 0.020 (s, 9H). 13C NMR (50 MHz, CDCl3),
3.22ꢀ3.19 (m, 2H), 3.05 (dd, J = 3.5, 12.6 Hz 1H), ꢀ0.005 (s, 9H),
(s, 9H). 13C NMR (50 MHz, CDCl3), δ; 103.9, 91.8, 80.4, 76.2,
73.4, 72.9, 72.8, 72.2, 62.8, 53.1, 52.0, 1.1(3C), 1.0 (3C), 0.6
(3C), 0.5 (3C), 0.04 (3C), 0.02 (3C). ESIꢀMS; 862. (M+Na)+;
Anal. Cal. For C31H70N6O9Si6 ; C, 44.36; H, 8.41; N, 10.01;
Found C, 44.43; H, 8.36; N, 10.08.
δ 101.5, 74.7, 73.2, 72.2, 69.8, 54.3, 43.0, 0.75 (3C), 0.59 (3C),
0.46 (3C). ESIꢀMS; 432 (M+Na) +; Anal. Cal. For C16H39NO5Si3;
C, 46.90; H, 9.59; N, 3.42; Found C, 46.98; H, 9.50; N, 4.51.
Preparation and spectral data for 27. It was prepared by the
65 reported procedure.20 1H NMR (400 MHz, CDCl3), δ; 8.20 (s,
1H), 7.42ꢀ7.31 (m, 5H), 5.97 (d, J = 3.2 Hz, 1H), 4.87 (dd, J =
2.0, 13.2 Hz, 1H), 4.75 (d, J = 12.0 Hz, 1H), 4.69 (d, J = 3.2 Hz,
1H), 4.59 (d, J = 12.0 Hz, 1H), 4.58ꢀ4.51 (m, 2H), 4.47 (dd, J =
2.4, 4.4 Hz, 1H), 4.45 (dd, J = 2.8, 4.0 Hz, 1H), 4.04 (dd, J = 3.2,
5
Methyl
3-O-benzyl-2,4-di-O-trimethylsilyl-α-D-
xylopyranoside (22a). It was prepared by the general procedure
10 1 using 0.59 mmol (150 mg) of 22 to yield the desired product
22a (80%, 188 mg) as 0ily liquid. IR (CHCl3): 3032, 2969, 1259,
1
1163, 1056, 849, 742cmꢀ1. [α]20 = ꢀ 39.5 (c, 1.0, CHCl3). H 70 5.6 Hz, 1H), 4.01 (d, J = 3.2 Hz, 1H), 1.53 (s, 3H), 1.44 (t, J = 7.2
D
NMR (500 MHz, CDCl3), δ; 7.37ꢀ7.25 (m, 5H), 4.82 (d, J = 11.3
Hz, 1H), 4.78 (d, J = 11.3 Hz, 1H), 4.06 (d, J = 7.5 Hz, 1H), 3.78
15 (dd, J =5.4, 11.4 Hz, 1H), 3.72ꢀ3.68 (m, 1H), 3.49 (s, 3H, ꢀ
OCH3), 3.41 (dd, J = 7.6, 8.8 Hz, 1H), 3.29 (dd, J = 8.8, 10.4 Hz,
Hz, 3H), 1.37 (s, 3H), 0.007 (s, 9H).13C NMR (100 MHz, CDCl3)
δ, 160.8, 139.8, 137.0, 129.0, 128.8, 128.4, 128.0, 127.9, 127.5,
112.0, 104.9, 82.1, 81.1, 80.0, 72.1, 67.9, 61.1, 54.1, 26.8, 26.7,
14.2, ꢀ0.05 (3C). ESIꢀMS; 528 (M+Na)+; Anal. Cal. For
1H), 3.18 (dd, J = 10.4, 11.2 Hz, 1H), 0.11 (s, 9H), 0.09 (s, 9H). 75 C24H35N3O7Si; C, 57.01; H, 6.98; N, 8.31; Found C, 56.93; H,
13C NMR (125 MHz, CDCl3) δ; 138.9, 128.1, 128.0, 127.6,
127.5, 127.2, 105.2, 85.5, 75.4, 70.9, 66.3, 57.0, 0.5 (3C), 0.1
20 (3C). ESIꢀMS; 421 (M+Na)+; Anal. Cal. For C19H34O5Si2; C,
57.25; H, 8.60; Found C, 57.13; H, 8.49.
6.85; N, 8.23.
Preparation and spectral data for 28. It was prepared by the
reported procedure.20 1H NMR (500 MHz, CDCl3), δ 8.35 (s,
1H), 4.81 (d, J = 2.4 Hz, 1H), 4.43 (d, J = 9.6 Hz, 1H), 4.41 (d, J
80 = 2.4 Hz, 1H), 3.97 (s, 3H), 3.82ꢀ3.80 (m, 1H), 3.74ꢀ3.71 (m,
3H), 3.01 (s, 3H), 0.10 (s, 9H), 0.09 (s, 9H), ꢀ0.015 (s, 9H). 13C
NMR (50 MHz, CDCl3), δ 161.2, 139.5, 129.2, 101.8, 73.2, 71.3,
71.2, 68.4, 54.7, 51.7, 51.2, 1.2, 1.0, 0.7. ESIꢀMS; 449 (M+Na)
+; Anal. Cal. For C21H43N3O7Si3; C, 46.21; H, 7.95; N, 8.08;
6-azido-6-deoxy-l,2,
3,4-di--O-(l-methyIethyIidene)-α-D-
galactopyranoside (23a). It was prepared by the general
procedure 1 using 1.0 mmol (260 mg) of 23 to yield the desired
25 product 23a (67%, 190 mg) as oily liquid. IR (CHCl3): 2987,
1
2110, 1290, 1054cmꢀ1. [α]20 = ꢀ27.6 (c, 1.0, CHCl3), H NMR,
D
(400 MHz, CDCl3) δ; 5.64 (d, J = 4.8 Hz, 1H), 4.73 (dd, J = 2.4, 85 Found C, 46.11; H, 7.81; N, 7.96.
(3R,4R,5R,6R )-Tetrahydroxyazepane (1,6-
dideoxy-1,6-imino- -mannitol) 29). Crude azidosilylated (12a)
8.0 Hz, 1H), 4.43 (dd, J = 2.8, 6.4 Hz, 1H), 4.29 (dd, J =2.0, 8.0
Hz, 1H), 4.01 (m, 1H), 3.61 (dd, J =8.0, 12.8 Hz, 1H, Hꢀ6a/b),
30 3.46 (dd, J =5.2, 12.8 Hz, 1H, Hꢀ6a/b), 1.67 (s, 3H), 1.56 (s, 3H),
1.41 (s, 6H). 13C NMR (100 MHz, CDCl3) δ; 110.0, 109.1, 96.7,
71.6, 71.0, 70.8, 61.7, 51.1, 26.4, 26.3, 25.2, 24.8. ESIꢀMS; 308
(M+Na)+; Anal. Cal. For C12H19N3O5; C, 50.52; H, 6.71; N,
14.73; Found C, 50.41; H, 6.62; N, 14.61.
D
(
product was obtained following the general procedure (3) using
12 (7.7 mmol, 1.5 gm) followed by the consequent addition of
90 Pd/C (10 mol%) in methnol and 1N HCl (35 mL, 5;1) and
hydrogenated (1 atm) for 36h. The mixture was filtered through a
layer of celite and washed several times with methanol (20 mL),
the filtrate was evaporated under high vacuo. The resulting
material was extracted with diethylether and water. The aqueous
95 layer was collected and evaporated under high vaccum. The crude
material was recrystallised from methanolꢀether (4 mL, 5:1) to
obtain the desired product 29 as a white solid in 70% overall
yield. The spectral data of 29 was in accordance to the reported
one.22
35 3-O-trimethylsilyl-l,2,
5,6-di--O-(l-methyIethyIidene)- α-D-
glucofuranoside (24a). It was prepared by the general procedure
1 using 0.57 mmol (150 mg) of 24 to yield the desired product
24a (85%, 162 mg) as oily liquid. IR (CHCl3): 2959, 1256, 1154,
1053, 845, 745cmꢀ1. [α]20D = ꢀ 41.5 (c, 1.0, CHCl3). 1H NMR (400
40 MHz, CDCl3), δ; 5.88 (d, J =3.6 Hz, 1H), 4.21 (dd, J =2.4, 8.0
Hz, 1H), 4.18ꢀ4.17 (m, 1H), 4.16 (d, J =3.2 Hz, 1H), 4.09ꢀ 4.08
(m, 1H), 4.04 (dd, J = 2.8, 8.4 Hz, 1H), 3.96 (dd, J =6.0, 8.4 Hz,
1H), 1.56 (s, 3H), 1.32 (s, 3H), 1.27 (s, 3H), 1.24 (s, 3H), 0.16 (s,
9H). ESIꢀMS; 355 (M+Na)+; Anal. Cal. For C15H28O6Si; C,
45 54.19; H, 8.49; Found C, 54.04; H, 8.36.
100 Acknowledgments: Authors are highly thankful to the
Director IIIM Jammu for the support. MA and SKY
acknowledge the UGC (JRF) and DST for fellowship
(INSPIRE faculty, IFCHꢀ18) and DST for funding under
the project GAPꢀ1145.
Methyl
5-amino-5-deoxy-2,3-di-O-trimethylsilyl-α-D-
ribofuranoside (25). It was prepared by the reported procedure.19
1H NMR (200 MHz, CDCl3) δ; 3.91(d, J = 7.4 Hz, 1H), 3.65 (dd,
J = 4.9, 10.9 Hz, 1H), 3.09 (d, J = 10.0 Hz, 1H), 3.33 (s, 3H, ꢀ
50 OCH3), 3.09 (d, J = 10.3 Hz, 1H), 3.02 (d, J = 5.6 Hz, 1H), 2.64ꢀ
2.55 (m, 1H), 0.0008 (s, 18H). 13C NMR (100 MHz, CDCl3) δ;
104.8, 75.0, 71.0, 67.0, 59.6, 56.6, 0.30 (3C), ꢀ0.00(3C). ESIꢀMS;
356 (M+Na)+; Anal. Cal. For C12H27N3O4Si2; C, 43.21; H, 8.16;
N, 12.60;; Found C, 43.10; H, 8.03; N, 12.43.
105
Notes and references
† Electronic Supplementary Information (ESI) available: [Full
1
experimental procedures and copies of H and 13C NMR are available].
See DOI: 10.1039/b000000x/
1 S. Bräse, C. Gil, K. Knepper, V. Zimmermann, Angew. Chem. Int.
Ed. 2005, 44, 5188ꢀ5240.
2 H. C. Kolb, M. G. Finn, K. B. Sharpless, Angew. Chem., 2001, 113,
2056ꢀ2075.
3 (a) P. A. S. Smith, Org. React. 1946, 3, 337ꢀ349. (b) J. H. Boyer, F.
110
55 Methyl
6-amino-6-deoxy-2,3,4-tri-O-trimethylsilyl-α-D-
mannopyranoside (26). It was prepared by the reported
procedure.19 1H NMR (500MHz, CDCl3), δ; 4.36 (bs, 1Η), 3.63
(d, J = 1.5 Hz, 1H), 3.60ꢀ3.53 (m, 2H), 3.21ꢀ3.19 (m, 1H), 3.18
115 C. Canter, Chem. Rev. 1954, 54, 1ꢀ57.
4 (a) R. N. de Oliveira, D. Sinou, R. M. Srivastava, J. Carbohydr.
Chem. 2006, 25, 407–425 and references cited therein. (b) B. L.
Wilkinson, L. F. Bornaghi, S. A. Poulsen, T. A. Houston, Tetrahedron.
8
| Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]

Page 9 of 10
Organic & Biomolecular Chemistry
View Online
2006, 62, 8115–8125. (c) W.ꢀQ. Fan, A. R. Katritzky, In Comprehensive
Heterocyclic Chemistry II; A. R. Katritzky, C. W. Rees, E. F. V. Scriven,
Eds.; Elsevier Science: Oxford, 1996; Vol. 4, pp1–126.
5 J. Zhang, A. Litke, K. Keller, R. Rai, C. W. Chang, Bioorg. Med.
Chem. 2010, 18, 1396ꢀ405.
5
6 T. Kanemitsu, P. H. Seeberger, Org. Lett. 2003, 5, 4541ꢀ4544.
7 T. Pathak, Chem. Rev. 2002, 102, 1623ꢀ1667.
8 H. Hagiwara, K. Morohashi, H. Sakai, T. Suzuki, M. Ando,
Tetrahedron 1998, 54, 5845ꢀ5852.
9 A. Vilsmeier, A. Haack, Chem. Ber. 1927, 60, 119.
10
10 C. ꢀC. Wang, J. ꢀC. Lee, S. ꢀY. Luo, S. S. Kulkarni, Y. ꢀW. Huang,
C. ꢀC. Lee, K. ꢀL. Chang, S. ꢀC. Hung. Nature 2007, 446, 896ꢀ899.
11 (a) C. Li, A. Arasappan, P. L. Fuchs, Tetrahedron Lett. 1993, 34,
3535ꢀ3538. (b) C. Peto, G. Batta, Z. Gyo¨rgydea´k, F. Sztaricskai, Liebigs
15 Ann. Chem. 1991, 505ꢀ507. (c) J. Thiem, D. ꢀC. T. Wiemann, Angew.
Chem., Int. Ed. Engl. 1990, 29, 80ꢀ82.
12 M. C. Viaud, P. Rollin, Synthesis. 1990, 130ꢀ132.
13 A. Guiller, C. H. Gagnieu, H. Pacheco, J. Carbohydr. Chem. 1986,
5, 161ꢀ168.
14 Á. de Cienfuegos, C. Rodrīguez, A. J. Mota, R. Robles, Org. Lett.
2003, 5, 2743ꢀ2745.
20
15 R. P. McGeary, S. R. Amini, V. W. S. Tang, I. Toth, J. Org. Chem.
2004, 69, 2727ꢀ2730.
16 (a) S. N. Greszler, J. S. Johnson, Angew. Chem., Int. Ed. 2009, 48,
25 3689ꢀ3691. (b) S. N. Greszler, J. T. Malinowski, J. S. Johnson, J. Am.
Chem. Soc. 2010, 132, 17393ꢀ17395.
17 (a) D. Mukherjee, B. A. Shah, P. Gupta, S. C. Taneja, J. Org.
Chem. 2007, 72, 8965–8968. (b) D. Mukherjee, S. K. Yousuf, S. C.
Taneja, Org. Lett. 2008, 10, 4831–4834. (c) N. Thota, D. Mukherjee, M.
30 V. Reddy, S. K.Yousuf, S. Koul, S. C. Taneja, Org. Biomol. Chem. 2009,
7, 1280–1283. (d) S. K. Yousuf, D. Mukherjee, S. C. Taneja, J. Org.
Chem. 2010, 75, 3097–3100.
18 (a) L. He, M. Wanunu, HꢀS. Byun, R. Bittman, J. Org. Chem. 1999,
64, 6049ꢀ6055 and references cited therein. (b) D. Lafont, P. Boullanger,
35 J. Carbohydr. Chem., 1999, 18, 675ꢀ688.
19 J. Li, F. –I. Chiang, H. –N. Chen, C. –W. T. Chang, J. Org. Chem.
2007, 72, 4055ꢀ4066.
20 K. P. Kaliappan, P. Palanichamy, M. Subham, Synlett 2009, 2162ꢀ
2166.
21 H. Li, T. Liu, Y. Zhang, S. Favre, C. Bello, P. Vogel. T. D.
Butters. N. G. Oikonomakos, J. Marrot, Y. Bl riot, Chem. Bio. Chem.,
2008, 9, 253ꢀ260.
22 C. C. Joseph, H. Regeling, B. Zwanenburg, G. J. F. Chittenden,
Tetrahedron. 2002, 58, 6907–6911.
40
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This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 9

Organic & Biomolecular Chemistry
Page 10 of 10
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Graphical abstract:
Azidotrimethylsilylation of carbohydrates (monosaccharides and disaccharides) has been
achieved in high yields under Mitsunobu conditions. The azidation of carbohydrates is
o
affected at 0 C essentially only at the primary alcoholic position in mono, di- and triols in
protected/unprotected glycosides, whereas the remaining secondary hydroxyl groups got
silylated. Surprisingly, no azidation was observed in the secondary hydroxyls in all the
carbohydrate substrates. Applications of the methodology for the synthesis of aminosugars,
triazoles and azasugars are reported.
N3
TMSO
HO
HO
O
O
PPh3, DIAD
O
O
TMSN3, Toluene, 0 0C
O
O
RO
OH
O
RO
80-95%
N3
Aminosugars
Triazoles
Azasugars
O
PPh3, DIAD
TMSO
TMSN3, Toluene, 0 0C
OR
HO
87-90%
OR