Click chemistry as an efficient tool to access β-cyclodextrin dimers

Article abstract of DOI:10.1016/j.tet.2008.05.095

The Cu(I)-catalyzed azide-alkyne cycloaddition has enabled practical and efficient preparation of hydroxylated, permethylated and peracylated β-cyclodextrin dimers in good yields starting from mono-6-azido-β-cyclodextrin and ortho-, meta- or para-bis-(pro

Full text of DOI:10.1016/j.tet.2008.05.095

Tetrahedron 64 (2008) 7159–7163
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Click chemistry as an efficient tool to access
b-cyclodextrin dimers
Maxime Mourer, Fr e´ d e´ ric Hapiot, Eric Monflier, St e´ phane Menuel *
ꢀ
Universit e´ d’Artois, Unit e´ de Catalyse et de Chimie du Solide, UMR CNRS n 8181, Facult e´ Jean Perrin, rue Jean Souvraz, S.P.18, 62307 Lens C e´ dex, France
a r t i c l e i n f o
a b s t r a c t
Article history:
The Cu(I)-catalyzed azide–alkyne cycloaddition has enabled practical and efficient preparation of hy-
Received 20 May 2008
Accepted 21 May 2008
Available online 24 May 2008
droxylated, permethylated and peracylated
azido- -cyclodextrin and ortho-, meta- or para-bis-(prop-2-ynyloxy)benzenes as spacers.
Ó 2008 Elsevier Ltd. All rights reserved.
b-cyclodextrin dimers in good yields starting from mono-6-
b
Keywords:
Click chemistry
Cycloaddition
Cyclodextrin
Dimers
Supramolecular chemistry
1
. Introduction
of numerous 1,2,3-triazole derivatives and constitutes one of the
5
current main topic of interest in organic chemistry. Although click
6
During the past 14 years, our intensive efforts to promote the
use of native and modified -, - or -cyclodextrin (CD) in catalysis
chemistry has already been used in the synthesis of CD derivatives,
a
b
g
the preparation of CD dimers has never been described by this
led us to understand the multifunctional properties of these glu-
copyranosic torus-like macro-rings. We especially focused on their
method. Herein, we report on the synthesis of bis-(
pounds by Cu(I)-mediated cycloaddition of mono-6-azido-
b
-CD) com-
1
b
-CD
role as mass transfer promoter, substrate-discriminating tool, dis-
persing agent or nanoparticle stabilizers in water or un-
conventional media. To carry our investigations a step further, the
elaboration of more complex CD structures is now required. Among
the possible CD-based derivatives, dimeric species were of partic-
ular interest because they could supramolecularly interact with
several catalytic partners in a confined chemical environment and
revealed enhanced molecular binding ability by multiple recogni-
tion. Thus, the closeness of these entities could have beneficial
consequences on the catalytic system performances.
derivatives with ortho-, meta- or para-diethynylbenzenes. In order
to access dimers soluble in various solvents, the nature of the CD-
substitutents has been varied. These new CDs were fully charac-
terized by NMR, mass spectrometry (MALDI-TOF–TOF).
2
2. Results and discussion
In order to test the viability of our approach, we first set out to
assess the ability of native
tion with alkynes. To this end, mono-6-azido-
native -CD in two steps as previously described, was treated with
b-CD to undergo 1,3-dipolar cycloaddi-
b
-CD, prepared from
7
Since the first synthesis of a CD dimer by Breslow et al., re-
searchers exercised creativity to prepare original dimeric CD-based
b
ortho-, meta- and para-bis-(prop-2-ynyloxy)benzenes in the pres-
ence of stoichiometric quantities of hydrated copper sulfate with
regard to the alkyne function to effect cyclization (Scheme 1). The
reaction was performed at room temperature overnight.
The obtained dimers were classically purified on silica gel with
an acetonitrile/water gradient furnishing the desired 1,2,3-triazole
rings in good yields (50–65%). As an example, the mass spectrum of
3
structures. Nevertheless, the synthesis of many dimers described
in the literature was often fastidious and time-consuming. Conse-
quently, we tried to develop new efficient synthetic pathways to
access a library of bridged bis-(b-CD) hosts for supramolecular ca-
talysis. For that purpose, we used one of the most reliable reactions
in click chemistry, namely the copper-catalyzed azide–alkyne cy-
4
cloaddition. This reaction appeared to be a great alternative to the
1a is displayed on Figure 1.
traditional thermal Huisgen 1,3-dipolar cycloaddition. Its de-
velopment by Sharpless et al. a few years ago enabled the synthesis
Given that the ortho isomer is more sterically hindered than its
meta- and para-derivatives, it was thought that this may have
a detrimental effect on the double cycloaddition. In fact, despite the
bulky environment of the ortho structure, no loss in yield was noted
indicating that the cycloaddition can be efficiently realized what-
ever be the isomer. The use of stoichiometric amounts of
*
Corresponding author. Tel.: þ33 3 21791773; fax: þ33 2 21791755.
E-mail address: stephane.menuel@univ-artois.fr (S. Menuel).
0
040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.05.095

7160
M. Mourer et al. / Tetrahedron 64 (2008) 7159–7163
N3
N
N
N
RO
7
O
H6'a
H6'b
β
O
OH
+
O
HO 7
HB
6
OH 7
OH 7
RO 7
OR 6
H5
HA
HA
1
2
3
: R=H
a: ortho
H5
: R=Me
: R=Ac
b: meta
c: para
HB
HO 7
O
H6'a
HO 6
N
N
H6'b
CuSO4.xH2O sodium ascorbate
DMF, RT
N
H-5
H-6
OR
OR
RO
7
6
β
H-6'
CH O
2
N
N
7
O
N
N
O
ppm
.6
N
RO
N
7
6
β
OR 6
HB
RO 7
1
a-c, 2a-c, 3a-c
HA
6.8
7.0
Scheme 1. Synthesis of hydroxylated, permethylated and peracylated b-CD dimers.
CuSO
4 2
$xH O was justified by the complexing properties of the CD
secondary hydroxyl face whose interaction with copper has been
8
Htriazole
widely exploited in the synthesis of mono-tosylated
b-CD. An
excess hydrated copper sulfate was therefore needed for the cy-
cloaddition to take place on the CD primary face. Note that stoi-
chiometric amounts of CuSO $xH O were also required in click
4 2
7
.2
3 ppm
2
O and deduced structure
7
6
5
4
dendrimer synthesis because of Cu trapping in a nitrogen-based
dendritic structure.9
ꢀ
Figure 2. Partial 2D T-ROESY spectrum of 1c at 25 C in D
of 1c.
Looking carefully at the 1H NMR spectra, our attention was
drawn by the presence of two distorted doublets at 6.86 and
6
.77 ppm with a coupling constant of 7.45 Hz in the aromatic region
the molecule in water. The situation was very different in DMSO-d6
since a well-defined singlet integrating for 4H was obtained at
6.98 ppm indicating that the phenyl protons are magnetically
equivalent. DMSO being a dissociating solvent, the structure of 1c
was deployed in those conditions. Note that T-ROESY spectra of 1a
of the 1c para-isomer spectrum when a singlet was expected for
a symmetric structure. This AB system was interpreted as two
groups of magnetically nonequivalent phenyl protons. To get more
information on this astonishing observation, 2D T-ROESY NMR
experiments have been carried out and led to very interesting re-
sults (Fig. 2).
and 1b in D O did not reveale any contact between the phenyl and
2
the CD protons. This observation suggested that the bent arrange-
Indeed, cross-peaks were detected between the two H
matic protons (6.86 ppm) and the H-5 (3.65 ppm) and H-6
3.84 ppm) CD protons confirming the partial inclusion of the
phenyl group in the CD cavities (Fig. 1). Cross-peaks between the
two H aromatic protons (6.77 ppm) and protons in the environ-
A
aro-
ment of the ortho- and meta-dialkynyl precursors a and b did not
allow interaction between the phenyl group and the CD cavity. In
that case, dimers with the phenyl group outside the CD cavity were
obtained.
(
B
With the synthesis of the hydroxylated
attention next turned to the synthesis of permethylated
mers. Methylation of mono-tosylated -CD with excess methyl io-
dide furnished the mono-tosylated permethylated -CD that
underwent a nucleophilic substitution with NaN . Subsequent
Cu(I)-catalyzed cycloaddition in the presence of the dieth-
ynylbenzene isomers gave the permethylated -CD dimers in very
b
-CD dimers in hand,
ment of the triazole ring also confirmed the precise arrangement of
b
-CD di-
b
b
3
b
good yields (70–90%) after purification on silica gel with
a dichloromethane–methanol mixture. Contrary to what was ob-
served for 1c, the aromatic protons of 2c gave a singlet at 6.90 ppm
integrating for 4H indicative of the absence of inclusion phenom-
enon. The steric hindrance generated by the methyls is probably the
explanation of such behaviour. The presence of hydrophobic
methyls also has influence on the solubility of the dimers since
permethylated
b
-CD dimers were slightly soluble in water and very
-CD,
soluble in organic solvents. When compared to hydoxylated
b
the reaction time was shorter (15 min vs 18 h, respectively) and the
yields higher. We suggested that both results were a consequence
of the absence of interaction between the methylated CDs and the
copper salt.
Figure 1. Mass spectrum of 1a.

M. Mourer et al. / Tetrahedron 64 (2008) 7159–7163
7161
Finally, the study has been extended to peracylated
Acetylation of mono-6-azido- -CD was carried out in an acetic
anhydride–pyridine (1:2) mixture at 80 C for 4 h giving the
expected mono-azido-peracylated -CD in quantitative yield. The
b
-CD.
was refluxed for 16 h. After evaporation of the solvent, the crude
product was purified by column chromatography using silica gel
and chloroform as eluant.
b
ꢀ
b
Huisgen [2þ3] cycloaddition was then performed in the same ex-
4.2.1. 1,2-Bis(prop-2-ynyloxy)benzene (a)
1
perimental conditions than those described above for hydroxylated
White powder. Yield 98%. H NMR (300 MHz, CDCl
3
)
d
7.08 (m,
), 2.51 (t, 2H, J 2.19 Hz);
147.6, 122.2, 115.1, 78.7, 73.9, 56.9.
: C 77.40, H 5.41, O 17.18. Found: C 76.43, H
b
-CD and led, after purification on silica gel, to the peracetylated
b-
2H), 6.98 (m, 2H), 4.76 (d, 4H, J 2.19 Hz, CH
2
C{ H} NMR (75 MHz, CDCl ) d
3
13
1
CD dimers in good yields (40–50%). The steric hindrance generated
by the acyl groups might certainly explain the loss in reactivity
since the accessibility to the azide function was strongly reduced.
The peracylated dimers were not soluble in water but very soluble
in organic solvents. Note that deacetylation of 3c by a Zemplen
reaction led to the hydroxylated dimer 1c indicating that the whole
dimeric structure was stable in basic conditions.
Anal. Calcd for C12
5.32, O 18.25.
H
10
O
2
4.2.2. 1,3-Bis(prop-2-ynyloxy)benzene (b)
1
White powder. Yield 96%. H NMR (300 MHz, CDCl
3
)
d
7.20 (m,
1H), 6.62 (m, 3H), 4.67 (d, 4H, J 2.19 Hz), 2.53 (t, 2H, J 2.19 Hz);
1
3
1
C{ H} NMR (75 MHz, CDCl
56.0. Anal. Calcd for C12
6.36, H 5.61, O 18.03.
3
)
d
158.9, 130.1, 108.0, 108.0, 78.6, 75.7,
3
. Conclusion
10 2
H O : C 77.40, H 5.41, O 17.18. Found: C
7
To sum up, we showed that click chemistry is a powerful tool to
synthesize a library of dimeric
b
-CDs starting from mono-6-azido-
4.2.3. 1,4-Bis(prop-2-ynyloxy)benzene (c)
1
b
-CD and dialkynylbenzene derivatives. Further studies aimed at
White powder. Yield 67%. H NMR (300 MHz, CDCl
3
13
)
d
1
6.93 (s,
exploring and exploiting their complexing properties are currently
in progress in our laboratory. Their catalytic behaviour is also under
investigation in various solvents. Indeed, hydroxylated dimers are
appropriate for aqueous catalysis when permethylated ones are of
particular interest for catalysis in organic solvents. Peracylated di-
4H), 4.64 (d, 4H, J 2.19 Hz), 2.51 (t, 2H, J 2.19 Hz); C{ H} NMR
(75 MHz, CDCl 152.5, 116.1, 78.9, 75.5, 56.6. Anal. Calcd for
: C 77.40, H 5.41, O 17.18. Found: C 76.45, H 5.55, O 18.00.
3
) d
12 10 2
C H O
4.3. General procedure for the Huisgen [2D3] cycloadditions
on mono-6-azido- -CD
mers, for their part, are preferentially devoted to supercritical CO
2
b
catalysis.10 Whatever the structure, their use should lead to en-
hanced complexing properties of substrates or phosphines. Surely,
their field of application may be greatly broadened and an ex-
panded appreciation of their potential in biology, for example,
could also be envisaged.
To a solution of dialkynyl derivative (67 mg, 0.36 mmol) in DMF
(30 mL) was added mono-6-azido- -CD (1 g, 0.87 mmol) and hy-
b
drated copper sulfate (180 mg, 0.36 mmol). After subsequent
dropwise addition of a freshly prepared solution of sodium ascor-
bate (288 mg, 1.44 mmol) dissolved in a water/DMF mixture (50/
50), the solution was stirred for 18 h at room temperature. After
evaporation of the solvent, the crude product was purified by col-
4
4
. Experimental
.1. General
umn chromatography using silica gel with a CH
mixture as eluant.
3 2
CN–H O (7:3)
All chemicals were purchased from Acros and Aldrich Chemicals
A
in their highest purity. All solvents were used as-supplied without
further purification. Distilled water was used in all experiments.
Analytical thin-layer chromatography (TLC) was performed on E.
Merck aluminium-backed silica gel (Silica Gel F254). Compounds
were identifiedusingUVfluorescence and/orstainingwithasolution
of phosphomolybdic acid in aqueous sulfuric acid and ethanol. NMR
spectra were recorded on a Bruker DRX300 spectrometer operating
4.3.1. Bis-1,2-[1-(6 -deoxy-
b
-
D
-cyclodextrin)-1,2,3-triazol-4-
ylmethoxy]benzene (1a)
White powder. Yield 53%. H NMR (300 MHz, D
7.31 (m, 2H), 6.90 (m, 2H), 5.30–5.20 (m, 32H), 4.09–3.42 (m, 70H);
C{ H} NMR (75 MHz, D
81.4, 73.9, 73.5, 72.6, 59.3, 51.6; MS calcd for C96
2527.82, found 2527.83. Anal. Calcd for
58H O$3CH CN: C 33.34, H 7.49, N 3.43, O 55.74. Found: C 34.22,
1
2
O)
d
7.82 (s, 2H),
13
1
2
O) d 159.7, 158.3, 146.4, 143.9, 102.3, 91.0,
H
148
96 148 6 70
N O $
6
N O70Na
C
H
1
13
at 300 MHz for H nuclei and 75 MHz for C nuclei. CDCl
3
(99.50%
2
3
isotopic purity), DMSO-d (99.80% isotopic purity) and D O (99.92%
6
2
H 6.27, N 3.55, O 56.96.
1
isotopic purity) were purchased from Euriso-Top. H NMR data are
reported as chemical shift, multiplicity (s, singlet; d, doublet; m,
multiplet), relative integral, coupling constant (J in hertz). The 2D T-
ROESYexperiments were run using the software supplied by Bruker.
T-ROESYexperiments were preferred to classical ROESYexperiments
asthis sequenceprovidesreliable dipolarcross-peakswithaminimal
contribution of scalar transfer. Mixing times for T-ROESY experi-
ments were set at 300 ms. The datamatrix for theT-ROESY was made
of 512 free induction decays, 1 K points each, resulting from the co-
addition of 32 scans. The real resolution was 1.5–6.0 Hz/point in F2
and F1 dimensions. They were transformed in the nonphase-sensi-
tive mode after QSINE window processing. Mass spectra were
recorded on a MALDI-TOF–TOF Bruker Daltonics Ultraflex II in posi-
tive reflectron mode with 2,5-DHB as matrix.
A
4.3.2. Bis-1,3-[1-(6 -deoxy-
b
-
D
-cyclodextrin)-1,2,3-triazol-4-
ylmethoxy]benzene (1b)
White powder. Yield 65%. H NMR (300 MHz, D
7.71 (s, 1H), 7.05 (m, 3H), 5.41–5.21 (m, 32H), 4.21–3.21 (m, 70H);
C{ H} NMR (75 MHz, D
88.3, 85.1, 73.9, 72.9, 72.3, 59.6, 51.5; MS calcd for C96
2527.82, found 2528.10. Anal. Calcd for C96 N O70$53H
148 6 2
33.32, H 7.40, N 2.43, O 56.86. Found: C 32.49, H 6.08, N 2.63, O
58.80.
1
2
O) d 7.99 (s, 2H),
1
3
1
2
O) d 149.1, 147.8, 143.8, 126.2, 123.3, 101.9,
148
H N
6
O
O: C
70Na
H
A
4.3.3. Bis-1,4-[1-(6 -deoxy-
b-
D-cyclodextrin)-1,2,3-triazol-4-
ylmethoxy]benzene (1c)
1
White powder. Yield 64%. H NMR (300 MHz, D
2
O) d 7.62 (br s,
2
H), 6.86 (d, 2H, J 7.45 Hz), 6.77 (d, 2H, J 7.45 Hz), 5.34–5.26 (m,
1
4
.2. General procedure for the synthesis of the dialkynyl
32H), 4.21–2.99 (m, 70H); H NMR (300 MHz, DMSO-d
6
) d 8.15 (s,
precursors
2H), 6.98 (s, 4H), 5.88–5.66 (m, 28H), 5.03 (s, 4H), 4.78 (m, 14H),
4
.48 (m, 14H), 4.31 (m, 2H), 3.99 (m, 2H), 3.65–3.47 (m, 26H),
13
1
To a solution of hydroxyphenol in acetone (250 mL) was added
propargyl bromide (2.3 equiv) and CsCO (3 equiv). The solution
2 6
3.40–3.28 (m, overlapped with residual H O in DMSO-d ); C{ H}
3
2
NMR (75 MHz, D O) d 154.6, 150.7, 121.4, 115.4, 102.2, 83.3, 81.7,

7162
M. Mourer et al. / Tetrahedron 64 (2008) 7159–7163
A
7
4.1, 73.5, 72.7, 60.6, 51.5; MS calcd for C96
H
148
N
6
O
70Na 2527.82,
O$3CH CN: C
5.06, H 7.30, N 3.61, O 54.03. Found: C 36.57, H 6.59, N 3.39, O
4.5.2. Bis-1,3-[1-(6 -deoxy-permethylated-
b-
D
-cyclodextrin)-1,2,3-
found 2528.10. Anal. Calcd for C96
H
148
N
6
O
70$48H
2
3
triazol-4-ylmethoxy]benzene (3b)
White powder. Yield 51%. H NMR (300 MHz, CDCl
2H), 7.20 (m, 1H), 6.65 (m, 2H), 6.58 (m, 1H), 5.32–5.06 (m, 32H),
1
3
5
3
)
d
7.70 (br s,
5.45.
4
3
d
.85–4.62 (m, 14H), 4.58–4.49 (m, 14H), 4.35–4.01 (m, 28H), 3.75–
13
1
.64 (m, 14H), 2.08 (m, 120H); C{ H} NMR (75 MHz, CDCl
170.9, 169.6, 162.7, 159.6, 143.8, 131.1, 128.9, 107.6, 96.8, 71.4, 69.8,
9.7, 69.3, 63.6, 62.75, 20.9; MS calcd for C176 110Na 4208.24,
3
)
4
.4. General procedure for the Huisgen [2D3] cycloadditions
on mono-6-azido-permethylated b-CD
6
228 6
H N O
found 4209.19.
To a solution of dialkynyl derivative (12 mg, 0.065 mmol) in
DMF (30 mL) was added mono-azido permethylated -CD (244 mg,
.156 mmol) and hydrated copper sulfate (32 mg, 0.30 mmol). After
subsequent dropwise addition of a freshly prepared solution of
sodium ascorbate (51 mg, 0.259 mmol) dissolved in a water/DMF
mixture (50/50), the solution was stirred for 15 min at room tem-
perature. After evaporation of the solvent, the crude product was
b
A
4.5.3. Bis-1,4-[1-(6 -deoxy-permethylated-
b-D-cyclodextrin)-1,2,3-
0
triazol-4-ylmethoxy]benzene (3c)
1
White powder. Yield 36%. H NMR (300 MHz, CDCl
3
) d 7.80 (br s,
2H), 6.95 (s, 4H), 5.37–5.06 (m, 32H), 4.84–4.60 (m, 14H), 4.58–4.16
13
1
(
(
9
C
m, 42H), 3.75–3.58 (m, 14H), 2.11 (m, 120H); C{ H} NMR
75 MHz, CDCl 170.9, 169.6, 162.7, 159.6, 143.8, 131.1, 128.9, 107.6,
6.8, 71.4, 69.8, 69.7, 69.3, 63.6, 62.75, 20.9; MS calcd for
110Na 4208.24, found 4208.54.
3
) d
2 2
purified by column chromatography using silica gel with a CH Cl –
CH
3
OH (9:1) mixture as eluant.
176 228 6
H N O
A
4
.4.1. Bis-1,2-[1-(6 -deoxy-permethylated-
b
-D-cyclodextrin)-1,2,3-
4
.6. Synthesis of 1c by deacetylation of 3c (Zemplen reaction)
triazol-4-ylmethoxy]benzene (2a)
1
White powder. Yield 93%. H NMR (300 MHz, CDCl
3
) d 7.65 (s,
To a solution of 3c (12 mg, 0.006 mmol) in methanol (20 mL)
2
3
d
H), 6.95 (m, 2H), 6.82 (m, 2H), 5.17 (br s, 4H), 5.05 (br s, 28H), 4.02–
1
3
1
was slowly added MeONa (13 mg, 0.24 mmol). After 20 min stirring
at room temperature, the solution was neutralized with Amberlyst
.21 (m, 190H), 3.20–2.86 (m, 14H); C{ H} NMR (75 MHz, CDCl
148.2, 143.4, 130.9, 125.5, 121.9, 98.8, 81.9, 77.6, 71.2, 70.9, 70.7,
1.3, 58.9, 29.6; MS calcd for C136 70Na 3088.44, found
3
)
15 resin. The suspension was filtered and the filtrate evaporated.
6
3
228 6
H N O
The resulting product was purified by column chromatography
using silica gel with a CH CN–H O (7:3) mixture as eluant to give
3 2
088.83.
A
1c. Yield: 98%.
4
.4.2. Bis-1,3-[1-(6 -deoxy-permethylated-b-D-cyclodextrin)-1,2,3-
triazol-4-ylmethoxy]benzene (2b)
1
Acknowledgements
White powder. Yield 75%. H NMR (300 MHz, CDCl
3
) d 7.66 (s,
2
3
H), 7.10 (s, 1H), 6.51 (m, 2H), 6.41 (m, 1H), 5.05 (br s, 18H), 3.88–
.72 (m, 28H), 3.71–3.22 (m, 162H), 3.20–2.96 (m, 14H); 1 C{ H}
159.4, 143.2, 130.0, 125.0, 107.2, 101.8, 99.1,
1.9, 81.8, 71.1, 70.8, 70.7, 61.4, 59.0, 29.6; MS calcd for
3
1
This work was supported by the Centre National de la Recherche
Scientifique (CNRS). Dr. M.M. is grateful to the Agence Nationale de
la Recherche for financial support (ANR-07-CP2D-05-02). We thank
Dr. C. Machut for elemental analysis, Dr. C. Flahaut and J. Hachani
for mass spectrometry analyses and G. Crowyn for NMR
experiments.
3
NMR (75 MHz, CDCl ) d
8
C
H
136 228
N
6
O70Na 3088.44, found 3088.83.
A
4.4.3. Bis-1,4-[1-(6 -deoxy-permethylated-
b
-D-cyclodextrin)-1,2,3-
triazol-4-ylmethoxy]benzene (2c)
1
References and notes
White powder. Yield 78%. H NMR (300 MHz, CDCl
3
) d 7.78 (s,
2
H), 6.90 (s, 4H), 5.12 (br s, 18H), 3.92–3.68 (m, 28H), 3.65–3.21 (m,
1
. (a) Komiyama, M.; Monflier, E. Cyclodextrins and Their Complexes: Chemistry,
13
1
1
62H), 3.20–3.18 (m, 14H); C{ H} NMR (75 MHz, CDCl
43.6, 125.1, 116.2, 93.9, 77.6, 76.7, 71.3, 71.0, 69.8, 61.4, 59.2, 29.7;
MS calcd for C136 70Na 3088.44, found 3088.79.
3
)
d
152.9,
Analytical Methods, Applications; Dodziuk, H., Ed.; Wiley-VCH: Weinheim, 2006;
pp 93–105; Hapiot, F.; Tilloy, S.; Monflier, E. Chem. Rev. 2006, 106, 767–781.
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1
2
228 6
H N O
4
.5. General procedure for the Huisgen [2D3] cycloadditions
on mono-6-azido-peracylated -CD
b
To a solution of dialkynyl derivative (47 mg, 0.25 mmol) in DMF
30 mL) was added mono-azido peracylated -CD (1.1 g,
.55 mmol) and hydrated copper sulfate (125 mg, 0.50 mmol). After
3
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(
0
b
6
Monflier, E. Tetrahedron 2005, 61, 4811–4817; (i) Bricout, H.; Caron, L.; Monflier,
E. Catal. Today 2001, 66, 355–361.
subsequent dropwise addition of a freshly prepared solution of
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perature. After evaporation of the solvent, the crude product was
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2 2
CH
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OH (96:4) mixture as eluant.
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A
4.5.1. Bis-1,2-[1-(6 -deoxy-peracylated-
b-
D-cyclodextrin)-1,2,3-
triazol-4-ylmethoxy]benzene (3a)
1
White powder. Yield 48%. H NMR (300 MHz, CDCl
3
) d 7.70 (s,
4. (a) Huisgen, R.; Knorr, R.; Mobius, L.; Szeimies, G. Chem. Ber. 1965, 98, 4014–
2
H), 7.02 (m, 2H), 6.89 (m, 2H), 5.63–5.10 (m, 32H), 5.06–4.95 (m,
4021; (b) Tornoe, C. W.; Christensen, C.; Meldal, M. J. Org. Chem. 2002, 67, 3057–
1
2
4H), 4.86–4.74 (m, 14H), 4.64–4.10 (m, 28H), 3.78–3.42 (m, 14H),
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3
1
3
) d 171.0, 169.8, 148.7,
5
144.3, 131.3, 126.5, 116.2, 97.3, 77.0, 71.7, 70.5, 70.0, 63.9, 63.0, 21.2;
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H
228 6
N O
1979–1983; (c) Ning, X.; Guo, J.; Wolfert, M. A.; Boons, G.-J. Angew. Chem., Int.

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7