Direct azidation of unprotected carbohydrates under Mitsunobu conditions using hydrazoic acid

Article abstract of DOI:10.1016/j.tetlet.2009.09.173

A single step procedure for the direct and regioselective synthesis of carbohydrate azides from unprotected sugars using hydrazoic acid under Mitsunobu conditions is reported. A series of mono-, di-, or triazido polyhydroxylated systems are described.

Full text of DOI:10.1016/j.tetlet.2009.09.173

Tetrahedron Letters 50 (2009) 7043–7047
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Tetrahedron Letters
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Direct azidation of unprotected carbohydrates under Mitsunobu conditions
using hydrazoic acid
c
a,b
Céline Besset a,b, Stéphane Chambert a,b, , Bernard Fenet , Yves Queneau
*
a INSA-Lyon, Institut de Chimie et de Biochimie Moléculaires et Supramoléculaires, Laboratoire de Chimie Organique, Bât. Jules Verne, 20 Avenue Albert Einstein,
F-69621 Villeurbanne, France
b ICBMS, UMR 5246 CNRS, Université de Lyon, Université Lyon 1, INSA-Lyon, CPE-Lyon, Bât. Curien, 43 bd du 11 novembre 1918, F-69622 Villeurbanne, France
c CCRMN, Université de Lyon, Université Lyon 1, CPE-Lyon, Bât. Curien, 43 bd du 11 novembre 1918, F-69622 Villeurbanne, France
a r t i c l e i n f o
a b s t r a c t
Article history:
A single step procedure for the direct and regioselective synthesis of carbohydrate azides from unpro-
tected sugars using hydrazoic acid under Mitsunobu conditions is reported. A series of mono-, di-, or
triazido polyhydroxylated systems are described.
Received 21 August 2009
Revised 25 September 2009
Accepted 29 September 2009
Available online 2 October 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Azidation
Unprotected carbohydrates
Hydrazoic acid
Mitsunobu
Azides are valuable intermediates in organic chemistry. Usually
obtained by the replacement of hydroxyl groups, their chemical
stability and their easy reduction make them attractive compounds
for obtaining the corresponding amines. Azides have gained even
more interest with the discovery of the mild and effective Cu(I)-
catalysed 1,3-dipolar Huisgen cycloaddition of azides with al-
kynes1 (belonging to ‘click’ chemistry2). This method has been used
for the synthesis of a wide range of 1,2,3-triazoles and has also
found some promising applications in polymer and material sci-
ence.3 In this context, carbohydrates bearing azido functions have
emerged as attractive intermediates,4 bringing to the obtained
‘click’ adducts their intrinsic properties (biological role, polarity,
solubility, biocompatibility, biodegradability, etc.) or for serving
as scaffolds in drug discovery studies.5 Reduction of azido carbohy-
drates could also give access to new aminoglycosides, an important
class of biologically active compounds. In the context of our studies
concerning the direct and selective modification of unprotected
carbohydrates,6 we wished to exploit the multifunctionality of car-
bohydrates as well as their structural diversity for the rapid and
efficient production of polyhydroxylated azides of defined
structure.
as illustrated by the work of Hanessian et al. who first described
the selective azidation of the 6-position of methyl pyranosides
using a PPh3/N-bromosuccinimide/NaN3 system.7 Later on, the azi-
dation of the anomeric position of carbohydrates in a one-pot pro-
cedure was described using similar systems8 and the direct
azidation of mono- or oligosaccharides, using PPh3/CBr4 with so-
dium or lithium azide was also reported.9,10 Reactions proceeded
with good selectivity, but in some cases led to the formation of
undesired brominated or anhydro side products arising from an
incomplete substitution of intermediates or intramolecular cycli-
zation, respectively.
These limitations led us to envisage an alternative route, explor-
ing the direct azidations of unprotected carbohydrates using
hydrazoic acid under Mitsunobu conditions. Hydrazoic acid has
been shown to be very reactive under these conditions11 and the
Mitsunobu reactions have indeed been reported as very clean
and effective even for the difficult substitution of allylic or homo-
allylic hydroxyl groups.12 This approach was extended to the azi-
dation of partially protected carbohydrates13 and was also
employed in nucleoside modification.14 Moreover, hydrazoic acid
(pKa 4.7) is an ideal candidate for carbohydrate modification since
the mild reaction conditions used are compatible with most glyco-
sidic linkages.
Several methods for the azidation of unprotected carbohydrates
have been reported. All are based on the synthesis of halogenated
deoxysugars followed by their in situ substitution by azide anions
Importantly, due to its well-documented toxicity and explosive
properties,15 precise and careful procedures have to be followed to
avoid the risks linked to the use of this reagent.16 Two different proce-
dures were used for producing HN3. The first was the production
* Corresponding author. Fax: +33 (0) 4 72 43 88 96.
E-mail address: stephane.chambert@insa-lyon.fr (S. Chambert).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.09.173

7044
C. Besset et al. / Tetrahedron Letters 50 (2009) 7043–7047
of a dry HN3 solution in toluene according to a literature pro-
tocol,17 this solution was then directly used in the Mitsunobu reac-
tions (method A). The second was the direct treatment of an excess
of NaN3 by concentrated H2SO4 in DMF, the obtained mixture was
dried using sodium sulfate before being added to the carbohydrate
solution in DMF and Mitsunobu reactions were directly performed
in this medium (method B). According to the literature,17 a 5%
solution is obtained in the case of method A while in method B
the concentration of HN3 is directly related to the amounts of
sulfuric acid introduced in the solution. For safety concerns, using
both methods, HN3 concentrations were not evaluated and an
excess of HN3 was used while the stoichiometry of the reactions
was controlled by the amounts of PPh3 and DIAD employed.
The azidation reactions were first performed on four different
unprotected nonreducing di- and trisaccharides, namely sucrose
(1), trehalose (2), melezitose (3), and raffinose (4) (Chart 1). When
sucrose (up to 10 g) was treated in DMF overnight with PPh3 and
DIAD in the presence of an excess of hydrazoic acid using method
A or method B, the known 6-azido-6-deoxysucrose (5) and 6,60-diaz-
ido-6,60-dideoxysucrose (6) were obtained in various ratios (Chart
1).18 The influence of the amount of the PPh3/DIAD system was stud-
ied (see Table 1, entries 1–5), showing that when 2 equiv of PPh3/
DIAD (compared to sucrose) were used, a 61% isolated yield of azide
5 was reached by taking advantage of theregioselectivity of the reac-
tion for primary hydroxyl groups. Comparatively, the use of diphen-
ylphosphoryl azide (DPPA), a substitute for HN3, did not give
R1
R1
6
O
OH
O
O
HO
HO
1'
HO
HO
R1
OH
6'
1
OH
O
HO
HO
R2 6''
O
HO
HO
OH
O
O
OH
O
R3
OH
OH
HO
HO
1''
O
HO
O
R2
OH
HO
R2
O
1
2
3
: R1=OH, R2=OH
: R1=OH, R2=OH
: R1=OH, R2=OH, R3=OH
9: R1=N3, R2=OH, R3=OH
10: R1=OH, R2=N3, R3=OH
5: R1=N3, R2=OH
6: R1=N3, R2=N3
7: R1=N3, R2=OH
8: R1=N3, R2=N3
11
: R1=N3, R2=N3, R3=OH
12: R1=N3, R2=N3, R3=N3
OH
O
HO
6"
O
1"
O
HO
HO
HO
6'
O
O
OH
HO
HO
OH
OH
O
O
1
OH
O
O
HO
OH
6
1'
HO
HO
HO
O
O
OH
OH
R
OH
4: R=OH
13: R=N3
14
Chart 1. Structures of the nonreducing starting carbohydrates and of the corresponding obtained azides. Reagent and conditions: see Table 1.
Table 1
Azidation of unprotected nonreducing carbohydrates
Entry
Starting carbohydrate
Methoda
PPh3/DIAD (equiv)
Products and yieldsb (%)
1
5
6
1
2
3
4
5
A
B
A
B
A
2
2
4
4
61
59
50
55
—
9
12
49
30
65
10
2
3
7
8
16
—
6
7
8
A
B
A
4
4
10
49
30
—
89
9, 10 (9:10)
21 (1:4)
34 (1:4)
46 (1:4)
—
11
—
33
11
—
12
—
8
—
61
9
A
A
B
A
2
4
4
10
10
11
12
4
13
7
19
14
11
44
35
13
14
15
A
A
A
5.4
10c
10d
Reagents and conditions: HN3, DIAD, PPh3, DMF, 0 °C to rt, 24 h (unless other indications).19
a
A: HN3 solution in toluene, B: in situ generated HN3 in DMF, see in the text.
Isolated yields.
Reaction time 76 h.
Reaction time 1 h.
b
c
d

C. Besset et al. / Tetrahedron Letters 50 (2009) 7043–7047
7045
R
R
HO
OH
OH OH
O
O
O
O
HO
HO
HO
HO
HO
HO
N3
OH
OH
O
OH
HO
HO
HO
OH
O
N3
OH
15
: R=OH
17
: R=N3
16
19
20
: R=OH
: R=N3
OH
18
N3
HO
N3
AcO
N3
OH
O
OH
OH
OH
OAcN3
OH N3
O
O
O
OAc
O
OAc
N3
N3
OAc
OH
21
OAc
OH
OH
OAc
24
OH
23
AcO
22
25
OAc
N3
R
R
O
O
HO
HO
HO
HO
O
OH
OH
OH
N3
O
O
OAc
HO
HO
O
O
OAc
AcO
N3
OH
26
27
29
28
30
: R=OH
: R=N3
: R=OH
: R=N3
OH
OH
Chart 2. Structures of reducing sugars and of the obtained azides.
satisfactoryresults, leadingtocompounds 5 and 6 in only20% and 5%
yields, respectively. The products were also found to be more diffi-
cult to purify from side products arising from the use of DPPA. Diaz-
ide 6 was obtained as the major compound in 65% yield when
10 equiv of PPh3/DIAD were used. When compared to previous re-
ports on sucrose azidation,9 the present method was found to give
slightly better yields using a simpler purification protocol.
Table 2
Azidation of glucose
Entry Starting
Methoda PPh3/
DIAD
Products and yieldsb (%)
carbohydrate
(equiv)
Glucose
15, 16
(15:16)
88 (5:2)
—
17, 18
(17:18)
—
91 (3:1)
71 (3:1)
81 (3:1)
The same procedure was applied to trehalose (2) to furnish effi-
ciently the known monoazide 720 and diazide 821 in maximum iso-
lated yields of 49% and 89%, respectively (Table 1, entries 6–8). The
direct azidations of melezitose (3) and raffinose (4), two commer-
cially available nonreducing trisaccharides containing a sucrose
scaffold, were then studied. When melezitose was treated with
2 equiv of PPh3/DIAD, an inseparable mixture of the two monoaz-
ides 9 and 10 was obtained (Table 1, entry 9), in which the primary
hydroxyl groups of the glucosyl moieties are transformed with fas-
ter reaction rates and the 600 position reacted faster than the 6 po-
sition. Increasing the amounts of PPh3/DIAD resulted in the
formation of diazide 11 and triazide 12, in up to 61% yield of the
latter when 10 equiv was employed (Table 1; entries 10–12). The
hydroxyl reactivity order, 600 > 6 > 60, is consistent with what was
observed for esterification under Mitsunobu conditions.6 The sub-
stitution position were assessed by an upfielded shift of the carbon
atoms linked to the azide functions compared to the corresponding
carbon shift on the starting carbohydrate.
In the case of raffinose (4), 3,6-anhydroraffinose (14) was ob-
served as the main product,6 but the known 6-azido-6-deoxyraffi-
nose22 (13) could be obtained in 35% yield when a tenfold excess of
PPh3/DIAD was used and the reaction was stopped after one hour
in order to favor the azidation reaction versus the intramolecular
cyclization (Table 1, entry 15).
Once achieved on nonreducing carbohydrates, we wished to ex-
tend the study to aldoses and ketoses. As an example of aldose, glu-
cose was studied first. Subjected to the same direct azidation
conditions, it gave access to four different known glucosyl mono-
and diazides 15–18 (Chart 2).23 The reaction showed a higher reac-
tivity of the anomeric position as well as a stereoselectivity for the
formation of b anomers. When performed using 2 equiv of PPh3/
DIAD (Table 2, entry 1) the reaction gave monoazides 15 and 16
in 88% yield. When 4 equiv of PPh3/DIAD were used, diazides 17
and 18 could be obtained in 91% yield (Table 2, entry 2) and higher
amounts of reagents did not promote further increase of the yield.
1
2
3
4
A
A
B
A
2
4
4
10
—
—
Reagents and conditions: HN3, DIAD, PPh3, DMF, 0 °C to rt, 24 h.19
a
A: HN3 solution in toluene, B: in situ generated HN3 in DMF, see in the text.
Isolated yields.
b
During the course of this study, some elegant works focusing on
anomeric modifications of unprotected aldoses for the synthesis of
b-glycosyl azides were reported;24,25 we thus concentrated our ef-
forts toward the modification of ketoses. Two sugars were selected
for this purpose: fructose (19) and isomaltulose (20), a readily avail-
able disaccharide. Azidation of fructose using method A or B led to
complex mixtures of azido carbohydrates and four fractions were
isolated after the regular workup and column chromatography.
Three fractions contained the new monoazide 21 and diazides 22
and 23, the structures of which were assessed by NOESY NMR exper-
iments. C-2 13C NMR chemical shifts possessing
a configurations of
compounds 21 and 22 were found at 100.2 and 100.5 ppm, respec-
tively. On the other hand, the chemicalshift of thequaternarycarbon
was found at 98.0 ppm for diazide 23 bearing a b configuration. The
fourth fraction was an inseparable mixture of different monoazido-
saccharides26 and was thus subjectedto acetylationconditionsin or-
der to identify the structures: three acetylated monoazides 24–26
were characterized. An inseparable mixture of fructopyranosides
25 and 26 was isolated, their structures were confirmed by compar-
ison with the NMR spectra of structurally related thio-analogs.27 Dif-
ferent reaction conditions were employed for reacting fructose (19).
For example, when fructose was treated with 2 equiv of PPh3/DIAD
(Table 3, entry 1) only monoazides were obtained, diazides 22 and
23were observedwhen4 equiv ofthesamereagentswereemployed
(Table 3, entry 2). These results showed a higher reactivity of the
hemiacetalic hydroxyl group compared to the primary alcohol func-
tions of fructose.

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C. Besset et al. / Tetrahedron Letters 50 (2009) 7043–7047
Table 3
Azidation of ketoses
Entry
Starting carbohydrate
Methoda
PPh3/DIAD (equiv)
Products and yieldsb (%)
19
21
24
4
22
—
19
18
23
—
19
15
Other monoazidesc
70
50
45
1
2
3
A
A
B
2
4
4
5
20
27
20
33
8
35
—
28
33
48
11
47
—
29
—
7
34
5
30
—
7
35
6
15
4
5
6
7
8
A
A
A
B
A
2
2.7
4
4
10
3
Reagents and conditions: HN3, DIAD, PPh3, DMF, 0 °C to rt, 24 h.19
a
A: HN3 solution in toluene, B: in situ generated HN3 in DMF, see in the text.
Isolated yields.
Precursors of acetylated compounds 24–26.
b
c
Figure 1. 2D NMR HSQC-NOESY spectra of compounds 28 (top) and 27 (bottom). 2D spectra where acquired at 500 MHz on a Bruker DRX500 spectrometer. Direct HSQC
peaks are in red, relayed NOESY peaks in blue. Only the b configuration of compound 28 led NOESY cross peak between protons H-1 and H-5.
The direct azidation of isomaltulose (20) gave monoazides 27
and 28 when 2 equiv of PPh3/DIAD (Table 2, entry 4) were used,
hence showing the regioselectivity of the reaction for the hemiac-
etalic hydroxyl group. The use of greater amounts such as 4 equiv
of the same reagents resulted in the observation of a total of four
compounds on the TLC (Table 3, entry 6). These four compounds

C. Besset et al. / Tetrahedron Letters 50 (2009) 7043–7047
7047
3. (a) Lutz, J.-F. Angew. Chem., Int. Ed. 2007, 46, 1018–1025; (b) Qiu, X. P.; Tanaka,
F.; Winnik, F. M. Macromolecules 2007, 40, 7069–7071; (c) Bernard, J.; Save, M.;
Arathoon, B.; Charleux, B. J. Polym. Sci., Part A 2008, 46, 2845–2857; (d) Binauld,
S.; Damiron, D.; Hamaide, T.; Drockenmüller, E.; Pascault, J.-P.; Fleury, E. Chem.
Commun. 2008, 4138–4141; (e) Nagao, Y.; Takasu, A. Macromol. Rapid. Commun.
2009, 30, 199–203.
4. Dedola, S.; Nepogodiev, S. A.; Field, R. A. Org. Biomol. Chem. 2007, 5, 1006–1017.
5. For recent reviews, see: (a) Meutermans, W.; Le, G. T.; Becker, B. ChemMedChem
2006, 1, 1164–1194; (b) Murphy, P. V. Eur. J. Org. Chem. 2007, 4177–4187.
6. (a) Molinier, V.; Fitremann, J.; Bouchu, A.; Queneau, Y. Tetrahedron: Asymmetry
2004, 15, 1753–1762; (b) Queneau, Y.; Jarosz, S.; Lewandowski, B.; Fitremann, J.
Adv. Carbohydr. Chem. Biochem. 2007, 61, 217–292; (c) Besset, C.; Chambert, S.;
Queneau, Y.; Kerverdo, S.; Rolland, H.; Guilbot, J. Crabohydr. Res. 2008, 343,
929–935.
7. Hanessian, S.; Ducharme, D.; Massé, R.; Capmau, M. L. Carbohydr. Res. 1978, 63,
265–269.
8. Moulay-Larbi, L.; Fréchou, C.; Demailly, G. Tetrahedron Lett. 1994, 35, 2175–
2178.
9. Jiménez Blanco, J. L.; García Fernández, J. M.; Defaye, J. Carbohydr. Res. 1997,
303, 367–372.
10. Gouin, S. G.; Kovensky, J. Tetrahedron Lett. 2007, 48, 2875–2879.
11. Mitsunobu, O. Synthesis 1981, 1–28.
could be separated by column chromatography and besides mono-
azides 27 and 28, diazides 29 and 30 were isolated and character-
ized. However, the attribution of the configuration at the anomeric
center of the fructosyl moiety was complicated due to the very
small chemical shift range of the protons involved. To overcome
this problem, 2D NMR HSQC-NOESY experiments were employed
for spreading proton signals onto the carbon dimension. In spite
of the low sensitivity of the method, the configurations of the
fructofuranosyl moieties were identified easily by visualizing the
nOe correlation between H-1 and H-5. As shown in Figure 1, this
correlation was detected in the case of compound 28 while the
same correlation is absent on the spectrum of azide 27. When lar-
ger amounts of PPh3/DIAD were used (10 equiv, see Table 3, entry
8) no monoazide could be detected by TLC and only diazides 29
and 30 were isolated, but in poor yields (the TLC indicated the for-
mation of a great number of less polar compounds).
In summary, the straightforward regioselective azidation of
unprotected carbohydrates using hydrazoic acid under Mitsunobu
conditions offers a new access to complex polyhydroxylated azido
structures readily available for further modifications by taking
advantage of the different reactivity of the hydroxyl groups present
on the sugar backbones. The reactions, easy to set up, proceeded in
moderate to good yields and could be performed on a multi-gram
scale without the production of undesired halogenated derivatives
usually observed in the protocols involving halogen displacements
for achieving the same transformations. The use of a HN3 solution
in toluene (method A) gave better yields than the in situ generation
of HN3 in DMF (method B). We are currently using this azidation
strategy for the production of gram quantities of pure azido
carbohydrates.
12. For example, see: (a) Kan, C.-C.; Bittman, Y. J. Biochemistry 1992, 31, 1866–
1874; (b) Keppler, F.; Jahn, E. M.; Hickman, V.; Carell, T. Angew. Chem., Int. Ed.
2007, 46, 2325–2327.
13. For a review, see: Kumara Swamy, K. C.; Bhuvan Kumar, N. N.; Balaraman, E.;
Pavan Kumar, K. V. P. Chem. Rev. 2009, 109, 1651–2551.
14. For a review, see: Pathak, T. Chem. Rev. 2002, 102, 1623–1668.
15. See: Bertterton, E. A. Crit. Rev. Environ. Sci. Technol. 2003, 33, 423–458. and
references therein.
16. One can notably mention: (i) only diluted HN3 solution was used, (ii) for
avoiding any leak problems, the reactions were performed in septa-plugged
flasks and the HN3 solution was transferred through the use of cannulas using a
nitrogen flux, (iii) neutralizations were performed to stop the reactions and the
extractions were thus run in basic media, (iv) all glassware were kept in a
sodium hydroxide solution before cleaning.
17. Wolff, H.. In Organic Reactions; Adams, R., Bachmann, W. E., Fieser, L. F.,
Johnson, J. R., Snyder, H. R., Eds.; John Wiley & Sons: New York, 1959; Vol. III, p
327.
18. (a) Hough, L.; Mufti, K. S. Carbohydr. Res. 1972, 25, 497–503; (b) Khan, R.;
Bhardwaj, C. L.; Mufti, K. S.; Jenner, M. R. Carbohydr. Res. 1980, 78, 185–189.
19. Typical procedure (method A): A solution of sucrose (1, 2.04 g, 5.96 mmol) in
DMF (70 mL) was first dried by concentrating under vacuum to a 50 mL
volume. PPh3 (3.13 g, 2 equiv) was added and the obtained solution was then
cooled to 0 °C and placed under N2. A 5% HN3 solution in toluene (9.0 mL),
prepared under N2 according to a literature protocol (see Ref. 17), was added to
the solution through the use of a cannula. DIAD (2.35 mL, 2 equiv) was then
added and the reaction was let to warm up to room temperature over 1 h, then
it was further stirred for 24 h. Water (50 mL) was then added and the solution
was neutralized using a 28% ammonia solution. The obtained solution was
extracted with CH2Cl2 (3 ꢀ 50 mL), the aqueous layer was concentrated and
Acknowledgments
Financial support from MENSER and CNRS as well as a grant to
C.B. from CNRS and SEPPIC is gratefully acknowledged. The authors
also wish to thank Dr. Sébastien Kerverdo, Dr. Hervé Rolland and
Dr. Jérôme Guilbot for their interest in this work and for fruitful
discussions.
directly subjected to silica gel chromatography using
a CH2Cl2/acetone/
Supplementary data
methanol/water gradient (three different ratios were employed: 78/10/10/2,
67/15/15/3 and 56/20/20/4) and gave monoazide 5 (1.35 g, 61%) and diazide 6
(0.21 g, 9%) as well as unreacted sucrose (1, 0.61 g, 29%).
Supplementary data (characterization data for new compounds
9–12, 21–30, are available as well as their 1H NMR spectra) associ-
ated with this article can be found, in the online version, at
doi:10.1016/j.tetlet.2009.09.173.
20. Wang, M.; Tu, P. F.; Xu, Z. D.; Yang, M. Helv. Chim. Acta 2003, 86, 2637–2644.
21. Rose, J. D.; Maddry, J. A.; Comber, R. N.; Suling, W. J.; Wilson, L. N.; Reynolds, R.
C. Carbohydr. Res. 2002, 337, 105–120.
22. Hough, L.; Richardson, A. C.; Salam, M. A. Carbohydr. Res. 1980, 80, 117–122.
23. (a) Szarek, W. A.; Achmatowicz, O.; Plenkiewicz, J.; Radatus, B. K. Tetrahedron
1978, 34, 1427–1433; (b) Gyorgydeak, Z.; Szilagyi, L. Liebigs Ann. Chem. 1987, 3,
235–241; (c) Szilagyi, L.; Gyorgydeak, Z. Carbohydr. Res. 1985, 143, 21–41.
24. Gudmundsdottir, A. V.; Nitz, M. Org. Lett. 2008, 10, 3461–3463.
25. Tanaka, T.; Nagai, H.; Noguchi, M.; Kobayashi, A.; Shoda, S. Chem. Commun.
2009, 3378–3379.
References and notes
1. (a) Rostovtsev, V. V.; Green, L. G.; Folkin, V. V.; Sharpless, K. B. Angew. Chem., Int.
Ed. 2002, 41, 2596–2599; (b) Tornøe, C. W.; Christensen, C.; Meldal, M. J. Org.
Chem. 2002, 67, 3057–3064; for recent review, see: (c) Meldal, M.; Tornøe, C.
W. Chem. Rev. 2008, 108, 2952–3015.
26. Microanlaysis: Anal. Calcd for C6H11N3O5: C, 35.12; H, 5.40; N, 20.48. Found: C,
35.41; H, 5.47; N, 20.25.
2. Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem., Int. Ed. 2001, 40, 2004–
2021.
27. Goursaud, F.; Peyrane, F.; Veyrieres, A. Tetrahedron 2002, 58, 3629–3637.