Synthesis of Fréchet type dendritic benzyl propargyl ether and Fréchet type triazole dendrimer

Article abstract of DOI:10.1016/j.tet.2005.10.039

Fréchet type dendritic benzyl propargyl ethers were synthesized by the reaction of propargyl bromide with the corresponding Fréchet type dendritic benzyl alcohol. A propargyl focal point functionalized dendrons were applied for the construction of symmetr

Full text of DOI:10.1016/j.tet.2005.10.039

Tetrahedron 62 (2006) 894–900
´
Synthesis of Frechet type dendritic benzyl propargyl
´
ether and Frechet type triazole dendrimer
a
a
b
b
Jae Wook Lee,a, Jung Hwan Kim, Byung-Ku Kim, Won Suk Shin and Sung-Ho Jin
*
aDepartment of Chemistry, Dong-A University, Hadan-2-dong, Busan 604-714, South Korea
bDepartment of Chemistry Education and Center for Plastic Information System, Pusan National University, Busan 609-735, South Korea
Received 12 September 2005; revised 13 October 2005; accepted 14 October 2005
Available online 8 November 2005
´
Abstract—Frechet type dendritic benzyl propargyl ethers were synthesized by the reaction of propargyl bromide with the corresponding
Frechet type dendritic benzyl alcohol. A propargyl focal point functionalized dendrons were applied for the construction of symmetric and
´
unsymmetric dendrimers containing 1,2,3-triazole rings as connectors via click chemistry with a tripodal azide core or a azide focal point
´
functionalized Frechet type dendrons.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
Huisgen’s 1,3-dipolar cycloaddition reaction between
alkynes and azides is one of the prototype reactions in
click chemistry.4 This click chemistry is a modular
approach that uses the most practical and reliable chemical
transformations and has found in many applications in
organic chemistry,5 drug discovery,6 bioconjugations,7
material science,8 and synthesis of polymer9 and
dendrimer.10
Terminal alkynes are versatile intermediates in synthetic
organic and material chemistry due to their characteristic
reactions such as metathesis reaction, metal-catalyzed
coupling reactions including sonogashira coupling reaction
and oxidative homocoupling, and so on. Another important
viewpoint in synthetic chemistry is 1,3-dipolar cyclo-
addition reaction with organoazides to provide heterocyclic
five membered rings. Since the 1,3-dipolar cycloaddition of
alkynes with azides was investigated by Huisgen et al.1 it
has been attracted much attention because of the synthetic
importance of the aromatic and nonaromatic five-membered
[1,2,3]-triazole heterocycles.2 The traditional method for
producing the triazole by cycloaddition requires elevated
temperature, typically in refluxing conditions and also
provides a mixture of 1,4-disubstituted and 1,5-disubstituted
triazoles.
Because dendrimers contain three distinct structural parts
that are the core, end-groups, and branched units
connecting core and periphery, there are three strategies
for triazole dendrimers. Therefore, three types of triazole
dendrimer having triazole unit(s) at core(s), every
branching points, and peripheries, have been synthesized
convergently and/or divergently. The convergent method
for dendrimer containing triazole unit(s) at core can be
facilitated by fewer coupling reaction(s) between a
dendron-azide and a dendron-alkyne, between a dendron-
azide and multi-alkynes, or between a dendron-alkyne
and multi-azides and by convenient purifications.
A relatively few applications using the alkynyl-dendron
in dendrimer synthesis have been reported. Because of
the high yields and lack of byproducts provided by the
click chemistry for stitching together dendrons and core
unit, the various dendrimers having functional building
block at core could be obtained easily and shown the
characteristic behaviors. Due to our interest in developing
new functional dendrimers, we became involved in
exploring efficient cycloaddition reaction that provides
an easy access to dendrimers. Here we present the
Recently, Tornøe and Sharpless independently reported a
copper(I)-catalyzed Huisgen [2C3] dipolar cycloaddition
reaction between an terminal alkyne and an organic azide in
which the 1,4-regioisomer is exclusively formed and which
also allows the rapid synthesis of compound libraries.3 The
reaction is highly chemoselective affording only the desired
1,2,3-triazole even in the presence of a large variety of other
functional groups. In addition, the reaction is high yielding
and can be carried out in water. The Cu(I)-catalyzed
Keywords: Alkyne; Azide; Cycloaddition; Dendrimer; 1,2,3-Triazoles.
*
Corresponding author. Tel.: C82 51 200 7251; fax: C82 51 200 7259;
e-mail: jlee@donga.ac.kr
´
synthesis of propargyl-functionalized Frechet-type
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.10.039

J. W. Lee et al. / Tetrahedron 62 (2006) 894–900
895
Figure 1. Structures of acetylenic-dendrons 1-Dm (mZ1–4: generation of dendron).
Figure 2. Synthetic strategies of triazole dendrimers via the Cu(I)-catalyzed 1,3-dipolar cycloaddition reactions. Conditions: 5 mol% CuSO4$5H2O/10 mol%
sodium ascorbate with respect to alkyne, DMF/H2O (4:1), 50–60 8C.
dendrons 1-Dm (Fig. 1) and their application to the
convergent synthesis of dendrimers using click chemistry
with a tripodal azide core or an azide focal point
exhibit the chemical stability associated with ether linkages
and good solubility in organic solvents.11 Due to these
´
reasons we selected the Frechet-type dendrons in the design
and synthesis of the propargyl focal point functionalized
´
functionalized Frechet type dendrons (Fig. 2). The
fundamental study reported herein details the growth of
dendrimers convergently with triazole linkages between
the core and dendrons.
´
dendrons. The terminal acetylenic Frechet-type dendrons
1-Dm (mZ1–4: generation of dendron) were synthesized by
the propargylation of the corresponding dendritic benzyl
´
alcohols with propargyl bromide (Scheme 1). The Frechet-
type benzyl alcohols 6-Dm (mZ1–4: generation of
dendron) were prepared according to the reported pro-
cedure.12 For the synthesis of the propargyl focal point
2. Results and discussion
´
functionalized Frechet-type dendrons 1-Dm, we have
reacted the corresponding dendritic benzyl alcohols 6-Dm
with propargyl bromide in the presence of NaH in THF.
The poly(benzyl ether) dendrons, now frequently referred to
´
as Frechet-type dendrons, have been utilized by a number of
groups because they are relatively readily accessed and

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J. W. Lee et al. / Tetrahedron 62 (2006) 894–900
Scheme 1. Synthesis of acetylenic-dendrons 1-Dm. Conditions: NaH, THF, propargyl bromide, rt, w10 h.
The reaction of propargyl bromide with first generation
dendritic benzyl alcohol 6-D1 in THF in the presence of
NaH provided the first generation dendritic benzyl
propargyl ether 1-D1 in 97% yield. Next, we conducted
the reaction for the preparation of higher generation
dendrons. The reactions of propargyl bromide with 6-D2,
6-D3, and 6-D4 in the same condition gave the dendritic
benzyl propargyl ether 1-D2, 1-D3, and 1-D4 in yields of 92,
93, and 88%, respectively. All dendrons were confirmed by
1H and 13C NMR spectroscopy, IR spectroscopy, and their
FAB mass spectra.
for 3-G1, 7.11 and 7.49 ppm for 3-G2, 7.04 and 7.39 ppm
for 3-G3, and 6.96 and 7.34 ppm for 3-G4, respectively. The
peaks of the benzylic protons adjacent to the nitrogen of
triazole in dendrimers 3-Gn were found at 5.43 ppm for
3-G1, 5.42 ppm for 3-G2, 5.32 ppm for 3-G3, and 5.22 ppm
for 3-G4, respectively. As the dendrimer generation
increased, the peaks of the benzene protons of core, the
triazole protons, and the benzylic protons adjacent to the
nitrogen of triazole showed up-field shift. In third and fourth
generation dendrimers it is observed that the benzene
protons of core, the triazole protons, and the benzylic
protons adjacent to the nitrogen of triazole are influenced by
the larger dendritic effect changing their microenviron-
ment.13 Analysis of the dendrimers by FAB or MALDI-TOF
mass spectrometry as well as by gel-permeation chromato-
graphy (GPC) provides no signs of products with defects
that would arise from incomplete coupling (Fig. 3).
As expected, the obtained dendrimer possessed a very
well-defined molecular structure with very low polydisper-
sity values (PDIZ1.01–1.04). IR data also confirmed that
For the construction of the triazole dendrimer 3-Gn via the
1,3-dipolar cycloaddition reactions between acetylene-
dendrons 1-Dm and the tripodal azide 2, we simply utilized
the click chemistry condition, which is well-documented.
The active Cu(I) species, generated in situ by reacting
CuSO4$5H2O with sodium ascorbate as the reducing agent,
provide the 1,4-disubstituted 1,2,3-triazole in excellent
yield.3a We carried out the reactions in a 4:1 solvent ratio
of DMF to H2O using 5 mol% CuSO4$5H2O with 10 mol%
sodium ascorbate with respect to alkyne at 50–60 8C. The
reaction progress could be checked by TLC. The generation
and disappearance of the intermediates, which are mono-
and/or di-triazole derivatives, were monitored by TLC runs
of the reaction mixture. The reaction of 1,3,5-tris(azido-
methyl)benzene 2 with 1-D1 in 0.1 M solution provided the
triazole dendrimer 3-G1 having just 1,4-disubstituted 1,2,3-
triazole units in yield of 89% after 18 h. Given the success in
using cycloaddition reaction in the synthesis of first
generation dendrimer, we expanded this reaction to get
higher generation dendrimers. Reaction of 1,3,5-tris(azido-
methyl)benzene 2 with 1-D2 and 1-D3 afforded the triazole
dendrimers 3-G2 and 3-G3 in yields of 88 and 80%,
respectively, after 26 h. In case of 1-D4, the triazole
dendrimer 3-G4 was obtained in 80% yield after 28 h. For
completion of the reaction between the dendritic acetylene
and the tripodal core, the higher generation dendron takes
longer time than the lower generation dendron. This
observation led us to imagine that the reaction between
the dendritic acetylene and the tripodal azide core was
kinetically controlled by the accessibility of acetylide due to
the steric hindrance (bulkiness) of dendron and spatial
congestion of tripodal core region. Therefore, the results
showed that the formation of triazole between tripodal azide
and propargyl-dendrons can be regarded as a new connector
to construct various dendrimers and functional materials.
neither alkyne (w3285 cmK1) nor azide (2098 cmK1
)
residues remain in the final dendrimer.
Figure 3. GPC diagrams of dendrimers 3-Gn obtained from THF eluent.
To probe the viability of our approach, we next investigated
the synthesis of triazole dendrimer 5-Gmn from the
coupling reactions between acetylenic-dendron 1-Dm and
azido-dendron 4-Dn (entries 1–4 in Table 1). The same
reaction condition as the previous trimerization was utilized
in the hetero-dimerization reaction between an azide and an
alkyne. The reaction of 1-D1 with 4-D1 in a 4:1 solvent ratio
of DMF to H2O using 5 mol% CuSO4$5H2O with 10 mol%
sodium ascorbate at 50–60 8C provided the just 1,4-
disubstituted 1,2,3-triazole product 5-G11 in 90% yield.
Given the success in using cycloaddition reaction in the
synthesis of first generation dendrimer, we expanded this
1
All dendrimers 3-Gn were confirmed by H and 13C NMR
spectroscopy. From their H NMR spectra (CDCl3), the
1
peaks of the benzene protons of core and the triazole protons
in dendrimers 3-Gn were found at 7.11 and 7.49 ppm

J. W. Lee et al. / Tetrahedron 62 (2006) 894–900
897
reaction to get higher generation dendrimers (entries 2–4 in
Table 1). Reactions of 1-D2 with 4-D2, 1-D3 with 4-D3,
and 1-D4 with 4-D4 in a same conditions provided
1,4-disubstituted 1,2,3-triazole symmetrical dendrimers
5-G22, 5-G33, and 5-G44 in yields of 89, 94, and 95%,
respectively. For completion of the reaction between two
dendrons, the higher generation dendrons take slightly
longer time than the lower generation dendrons which can
be imagined by the simple steric hindrance of dendrons.
Whereas the trimerization reaction between dendrons and
core to provide 3-Gn is more sluggish than the coupling
reaction between two dendrons because there are some
limitation in the accessibility of acetylide due to the
additional spatial congestion of core region. All symmetric
dendrimers were also confirmed by 1H and 13C NMR
spectroscopy and FAB and MALDI mass spectra. From
investigated two synthetic strategies. The first one is based
on the reactions of lower generations acetylenic-dendrons
1-D1 or 1-D2 with 4-Dn (entries 5–9 in Table 1). The second
strategy involves the reactions using higher generations
acetylenic dendrons 1-D3 and 1-D4 (entries 10–11 in
Table 1). The reactions of 1-D1 with 4-D2, 4-D3, and 4-D4
provided 1,4-disubstituted 1,2,3-triazole unsymmetrical
dendrimers 5-G12, 5-G13, and 5-G14 in yields of 84, 90,
and 85%, respectively. The reactions of 1-D2 with 4-D1 and
4-D4 provided 1,4-disubstituted 1,2,3-triazole unsymme-
trical dendrimers 5-G21 and 5-G24 in yields of 85 and 92%,
respectively. The reactions of 1-D3 with 4-D1 and of 1-D4
with 4-D2 provided 1,4-disubstituted 1,2,3-triazole
unsymmetrical dendrimers 5-G31 and 5-G42 in yields of
92 and 88%, respectively. Therefore, the results showed that
the formation of triazole between azide-dendrons and
propargyl-dendrons are found to be an efficient connector
to construct various unsymmetric dendrimers and may be
applied for the synthesis of functional materials. We are
currently investigated the synthesis of various unsymmetric
functional dendrimers using the different kinds of dendrons.
1
their H NMR spectra (CDCl3), the peaks of the benzylic
protons adjacent to the nitrogen of triazole and the triazole
proton in dendrimers 5-Gmn were found at 5.42 and
7.48 ppm for 5-G11, 5.42 and 7.44 ppm for 5-G22, 5.39 and
7.44 ppm for 5-G33, and 5.34 and 7.42 ppm for 5-G44,
respectively. As the dendrimer generation increased, the
peaks of the benzylic protons adjacent to the nitrogen of
triazole and the triazole proton showed slightly up-field
shift. Analysis of the higher dendrimers by gel-permeation
chromatography (GPC) shows very low polydispersity
values, PDIZ1.02 and 1.04 for 5-G33 and 5-G44,
respectively (Fig. 4).
All unsymmetric dendrimers were confirmed by 1H and 13
NMR spectroscopy and FAB mass spectra.
C
3. Conclusion
We have demonstrated that the propargyl-functionalized
´
Frechet-type dendrons are synthesized by the propargyl-
ation of the corresponding Frechet type dendritic benzyl
´
Table 1. Synthesis of triazole dendrimers 5-Gmn from azido-dendrons
1-Dm and acetylenic-dendrons 4-Dn
alcohol and that the trimerization reactions between tripodal
azide and acetylene-dendrons and the coupling reactions
between azido dendrons and acetylenic dendrons lead to the
formation of symmetric triazole dendrimers in high yields.
Furthermore, such reactions between dendrons of different
size afford unsymmetrical triazole dendrimers. This reaction
may then provide an insight into designing various
(un)symmetrical dendrimers such as amphiphilic dendri-
mers. We are currently working towards various functional
dendrimers using this strategy for various applications.
Entry
1-Dm
4-Dn
Rxn time (h) Product Yield (%)a
1
2
3
4
5
6
7
8
1-D1
1-D2
1-D3
1-D4
1-D1
1-D1
1-D1
1-D2
1-D2
1-D3
1-D4
4-D1
4-D2
4-D3
4-D4
4-D2
4-D3
4-D4
4-D1
4-D4
4-D1
4-D2
5
6
7
8
6
6
7
6
7
7
7
5-G11
5-G22
5-G33
5-G44
5-G12
5-G13
5-G14
5-G21
5-G24
5-G31
5-G42
90
89
94
95
84
90
85
85
92
92
88
9
10
11
a Isolated yields.
4. Experimental
1H NMR spectra were recorded on a 300 or 500 MHz NMR
spectrometer using the residual proton resonance of the
solvent as the internal standard. Chemical shifts are reported
in parts per million (ppm). When peak multiplicities are
given, the following abbreviations are used: s, singlet; d,
doublet; t, triplet; q, quartet; quin, quintet; d of d, doublet of
a doublet; m, multiplet; br, broad. 13C NMR spectra were
proton decoupled and recorded on a 75 or 125 MHz NMR
spectrometer using the carbon signal of the deuterated
solvent as the internal standard. EI, FAB, and MALDI mass
spectra were obtained from Korea Basic Science Institute in
Daegu or Daejeon and POSTECH. Flash chromatography
was performed with 37–75 mm silica gel. Analytical thin
layer chromatography was performed on silica plates with
F-254 indicator and the visualization was accomplished by
UV lamp or using an iodine chamber. Polydispersity (PDI)
of dendrimers was determined by gel permeation chroma-
tography (GPC) analysis relative to polystyrene calibration
(Agilent 1100 series GPC, Plgel 5 mm MIXED-C, refractive
Figure 4. GPC diagrams of dendrimers 5-Gmn obtained from THF eluent.
Next, we turned our attention toward the formation of
unsymmetrical 1,2,3-triazole dendrimers. We have

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J. W. Lee et al. / Tetrahedron 62 (2006) 894–900
index detector) in THF solution. All chemicals were
obtained from commercial sources and used as received,
unless otherwise mentioned. THF was distilled over
Na/Ph2CO ketyl. Dendritic benzyl alcohols 6-Dm and
azides 4-Dn12 and 1,3,5-tris(azidomethyl)benzene14 used
here were prepared according to previously reported
procedure.
m/z 2110.9 [MC], 1960.9, 1687.9; HRMS (FAB): Calcd for
C124H126O31: 2110.8283. Found: 2111.8361 [MCCH].
4.2. Synthesis of 1,2,3-triazole dendrimers 3-Gn by
reaction between 1,3,5-tris(azidomethyl)benzene 2
and acetylene-dendrons 1-Dm
General procedure: A solution of 1,3,5-tris(azidomethyl)-
benzene 2 (0.01 mmol) and acetylene-dendrons 1-Dm
(0.03 mmol) in DMF–H2O (4:1, 1 mL) in the presence of
15 mol% CuSO4$5H2O with 30 mol% sodium ascorbate
was stirred at 50–60 8C for 18–28 h. The reaction was
monitored by TLC regarding on the disappearance of 1-Dm
and the generation and disappearance of mono- and/or
di-triazole derivatives. The reaction mixture was poured
into brine (20 mL) and the resulting solution was extracted
with EtOAc (20 mL!3). The combined organic phase was
dried with sodium sulfate, concentrated, and purified by
column chromatography (EtOAc/Hex system) to afford the
desired product.
4.1. Synthesis of dendritic benzyl propargyl ether
(1-Dm)
General procedure. Dendritic benzyl alcohol 6-Dm
(1 mmol) was added to a THF (10 mL) solution of sodium
hydride (1.2 mmol). After stirred under nitrogen for 30 min,
propargyl bromide (1.2 mmol) was added and the mixture
was stirred for w10 h. The reaction mixture was poured
slowly into cold brine (20 mL) and the resulting solution
was extracted with EtOAc (20 mL!3). The combined
organic phase was dried with sodium sulfate, concentrated,
and purified by column chromatography (EtOAc/Hex
system) to afford the desired product 1-Dn.
4.2.1. Compound 3-G1. A yellowish gum; 89% yield; IR
2923, 2854, 1597, 1465, 1203, 1154, 1067, 1051 cmK1; 1H
NMR (500 MHz, CDCl3) d 3.75 (s, 18H), 4.51 (s, 6H), 4.62
(s, 6H), 5.43 (s, 6H), 6.36 (m, 3H), 6.48 (m, 6H), 7.11
(s, 3H), 7.49 (s, 3H); 13C NMR (75 MHz, CDCl3) d 161.3,
146.2, 140.5, 137.3, 128.0, 123.2, 106.1, 100.1, 73.0, 64.0,
55.7, 53.7; MS (FAB): m/z 862.3 [MC], 694.2, 647.4, 544.2;
HRMS (FAB) Calcd for C45H51N9O9: 861.3810. Found:
862.3888 [MCCH]. PDI: 1.01.
4.1.1. Compound 1-D1. A colorless oil; 97% yield;
IR 3286, 2942, 2840, 2115, 1599, 1463, 1205, 1155,
1
1067 cmK1; H NMR (500 MHz, CDCl3) d 2.47 (t, JZ
2.4 Hz, 1H), 3.79 (s, 6H), 4.18 (d, JZ2.4 Hz, 2H), 4.56 (s,
2H), 6.40 (d, JZ2.1 Hz, 1H), 6.52 (d, JZ2.1 Hz, 2H); 13C
NMR (75 MHz, CDCl3) d 160.9, 139.6, 105.7, 100.0, 79.6,
74.6, 71.5, 57.0, 55.3; MS (EI): m/z 206 [MC], 166, 152,
137; HRMS (EI) Calcd for C12H14O3: 206.0943. Found:
206.0943.
4.2.2. Compound 3-G2. A yellowish gum; 88% yield; IR
2926, 2854, 1596, 1461, 1203, 1156, 1054 cmK1; 1H NMR
(300 MHz, CDCl3) d 3.77 (s, 36H), 4.50 (s, 6H), 4.61 (s,
6H), 4.94 (s, 12H), 5.42 (s, 6H), 6.39 (m, 6H), 6.52 (m, 3H),
6.55 (m, 12H), 6.57 (m, 6H), 7.11 (s, 3H), 7.44 (s, 3H); 13C
NMR (75 MHz, CDCl3) d 161.4, 160.4, 146.2, 140.6, 139.6,
137.3, 128.0, 123.1, 107.2, 105.7, 101.9, 100.3, 72.9, 70.4,
64.0, 55.8, 53.6; MS (FAB): m/z 1678.9 [MC], 663.5, 647.5;
HRMS (FAM) Calcd for C93H99N9O21: 1677.6956. Found:
1678.7034 [MCCH]. PDI: 1.01.
4.1.2. Compound 1-D2. A colorless oil; 92% yield;
IR 3285, 2939, 2838, 2116, 1598, 1459, 1204, 1154,
1
1054 cmK1; H NMR (500 MHz, CDCl3) d 2.46 (t, JZ
2.4 Hz, 1H), 3.80 (s, 12H), 4.16 (d, JZ2.4 Hz, 2H), 4.55 (s,
2H), 4.98 (s, 4H), 6.41 (d, JZ2.1 Hz, 2H), 6.55 (d, JZ
2.1 Hz, 1H), 6.57(m, 4H), 6.60 (m, 2H); 13C NMR (75 MHz,
CDCl3) d 161.0, 160.0, 139.7, 139.2, 106.9, 105.2, 101.7,
100.0, 79.6, 74.7, 71.4, 70.0, 57.1, 55.4; MS (EI): m/z 478
[MC], 438, 301, 151; HRMS (EI) Calcd for C28H30O7:
478.1992. Found: 478.1992.
4.2.3. Compound 3-G3. A yellowish gum; 80% yield; IR
2923, 2854, 1596, 1461, 1203, 1153, 1050 cmK1; 1H NMR
(300 MHz, CDCl3) d 3.75 (s, 72H), 4.48 (s, 6H), 4.59
(s, 6H), 4.92 (s, 36H), 5.32 (s, 6H), 6.38 (m, 12H), 6.49–6.64
(m, 39H), 6.64 (m, 12H), 7.04 (s, 3H), 7.39 (s, 3H); 13C
NMR (125 MHz, CDCl3) d 161.4, 160.47, 160.37, 146.1,
140.6, 139.7, 139.5, 137.3, 131.2, 128.0, 123.1, 107.1,
106.8, 105.7, 105.4, 102.0, 101.9, 100.4, 72.9, 70.5, 70.3,
64.0, 55.8, 53.6; MS (MALDI): Calcd for C189H195N9O45:
3310.3247. Found: 3333.2024 [MCC Na]. PDI: 1.03.
4.1.3. Compound 1-D3. A colorless gum; 93% yield;
IR 3284, 2938, 2838, 2117, 1598, 1458, 1203, 1153,
1
1050 cmK1; H NMR (500 MHz, CDCl3) d 2.46 (t, JZ
2.4 Hz, 1H), 3.79 (s, 24H), 4.16 (d, JZ2.4 Hz, 2H), 4.55 (s,
2H), 4.97 (s, 12H), 6.41 (m, 4H), 6.53–6.60 (m, 13H), 6.67
(m, 4H); 13C NMR (75 MHz, CDCl3) d 161.0, 160.1, 160.0,
139.7, 139.2, 139.1, 106.9, 106.4, 105.2, 101.6, 100.0, 79.6,
74.7, 71.4, 70.04, 70.0, 57.1, 55.3; MS (FAB): m/z 1021.5
[MC], 966.7, 572.9 410.2, 340.2; HRMS (FAB) Calcd for
C60H62O15: 1022.4089. Found: 1023.4167 [MCCH].
4.2.4. Compound 3-G4. A yellowish solid; mp 78–80 8C;
80% yield; IR 2933, 2839, 1599, 1462, 1203, 1157,
4.1.4. Compound 1-D4. A colorless gum; 88% yield; IR
3285, 2942, 2840, 2116, 1599, 1458, 1206, 1153, 1069,
1051 cmK1 1H NMR (300 MHz, CDCl3)
; d 3.72
(s, 144H), 4.44 (s, 6H), 4.54 (s, 6H), 4.89 (s, 84H), 5.22
(s, 6H), 6.36 (m, 24H), 6.52 (m, 73H), 6.62 (m, 38H), 6.96
(s, 3H), 7.34 (s, 3H); 13C NMR (125 MHz, CDCl3) d 161.4,
160.45, 160.37, 146.2, 146.0, 140.7, 139.7, 139.63, 139.56,
137.2, 132.6, 129.0, 128.9, 127.9, 123.2, 107.1, 106.8,
105.7, 105.4, 102.0, 101.9, 101.8, 100.3, 72.8, 70.4, 70.3,
69.9, 64.0, 55.7, 55.3, 55.1, 53.5; MS (MALDI): Calcd
1
1054 cmK1; H NMR (500 MHz, CDCl3) d 2.44 (t, JZ
2.4 Hz, 1H), 3.77 (s, 48H), 4.14 (d, JZ2.3 Hz, 2H), 4.53 (s,
2H), 4.95 (s, 28H), 6.39 (m, 8H), 6.55–6.60 (m, 26H), 6.66
(m, 11H); 13C NMR (125 MHz, CDCl3) d 161.0, 160.1,
160.0, 139.7, 139.2, 139.1, 107.0, 106.4, 105.2, 101.6,
100.0, 79.6, 74.7, 71.4, 70.03, 70.0, 75.1, 55.3; MS (FAB):

J. W. Lee et al. / Tetrahedron 62 (2006) 894–900
899
for C381H387N9O93: 6580.15. Found: 6603.42 [MCC Na].
PDI: 1.04.
54.4; MS (MALDI): Calcd for C245H249N3O61: 4211.58.
Found: 4234.70 [MCCNa]. PDI: 1.04.
4.3.5. Compound 5-G12. A yellowish gum; 84% yield; 1H
NMR (300 MHz, CDCl3): d 3.76 (s, 6H), 3.79 (s, 12H), 4.53
(s, 2H), 4.65 (s, 2H), 4.93 (s, 4H), 5.42 (s, 2H), 6.37 (m, 1H),
6.41 (m, 2H), 6.49 (m, 4H), 6.54 (m, 4H), 6.57 (m, 1H), 7.45
(s, 1H); 13C NMR (75 MHz, CDCl3): d 161.4, 161.3, 160.8,
146.0, 140.6, 139.2, 137.1, 122.9, 107.7, 106.0, 105.6,
102.6, 100.4, 100.3, 73.0, 70.5, 64.1, 55.8, 55.7, 54.6; MS
(FAB): m/zZ672.3 [MCCH]; HRMS (FAB): m/z Calcd for
C37H41N3O9: 671.2843. Found: 672.2921 [MCCH].
4.3. Synthesis of 1,2,3-triazole dendrimers 5-Gmn
by reaction between propargyl-dendrons 1-Dm
and azido-dendrons 4-Dn
General procedure: A mixture of propargyl-dendrons 1-Dm
(0.10 mmol) and azido-dendrons 4-Dn (0.10 mmol) in
DMF–H2O (4:1, 1 mL) in the presence of 5 mol%
CuSO4$5H2O with 10 mol% sodium ascorbate was stirred
at 50 8C for w8 h. The reaction was monitored by TLC
regarding on the disappearance of 4-Dn. The reaction
mixture was poured into brine (20 mL) and the resulting
solution was extracted with EtOAc (20 mL!3). The
combined organic phase was dried with sodium sulfate,
concentrated, and purified by column chromatography
(EtOAc/Hex system) to afford the desired product.
4.3.6. Compound 5-G13. A yellowish gum; 90% yield; 1H
NMR (300 MHz, CDCl3): d 3.75 (s, 6H), 3.78 (s, 24H), 4.52
(s, 2H), 4.64 (s, 2H), 4.92 (s, 4H), 4.97 (s, 8H), 5.41 (s, 2H),
6.36 (m, 1H), 6.41 (m, 4H), 6.46–6.49 (m, 4H), 6.57 (m,
11H), 6.54 (m, 4H), 7.46 (s, 1H); 13C NMR (75 MHz,
CDCl3): d 161.7, 161.4, 161.3, 160.7, 160.5, 160.49, 160.4,
146.0, 140.7, 139.7, 139.6, 139.5, 139.3, 137.1, 122.9,
107.7, 107.2, 106.83, 106.8, 106.5, 106.0, 105.7, 102.1,
102.0, 101.9, 100.8, 100.38, 100.35, 100.27, 72.9, 72.8,
70.5, 70.4, 64.1, 55.8, 55.7, 54.6; MS (FAB): m/zZ1216.4
[MCCH], 663.5; HRMS (FAB): m/z Calcd for
C69H73N3O17: 1215.4940. Found: 1216.5018 [MCCH].
4.3.1. Compound 5-G11. A colorless oil; 90% yield; IR
2939, 2839, 1599, 1462, 1203, 1157, 1066, 1047 cmK1; 1H
NMR (300 MHz, CDCl3): d 3.75 (s, 6H), 3.78 (s, 6H), 4.52
(s, 2H), 4.65 (s, 2H), 5.42 (s, 2H), 6.37 (m, 1H), 6.40 (m,
3H), 6.49 (m, 2H), 7.48 (s, 1H); 13C NMR (75 MHz,
CDCl3): d 161.4, 161.0, 145.6, 140.2, 136.7, 122.5, 106.2,
105.6, 100.5, 99.9, 72.6, 63.8, 55.5, 55.4, 54.3; MS (EI):
m/zZ399 [MC], 233, 151; HRMS (EI): m/z Calcd for
C21H25N3O5: 399.1794. Found: 399.1796.
4.3.7. Compound 5-G14. A yellowish gum; 85% yield; 1H
NMR (300 MHz, CDCl3): d 3.72 (s, 6H), 3.77 (s, 48H), 4.50
(s, 2H), 4.63 (s, 2H), 4.91 (s, 4H), 4.96 (s, 24H), 5.38 (s, 2H),
6.35 (m, 1H), 6.40 (m, 8H), 6.48 (m, 3H), 6.56 (m, 22H),
6.63 (m, 4H), 6.67 (m, 10H), 7.45 (s, 1H); 13C NMR
(125 MHz, CDCl3): d 161.0, 160.9, 160.3, 160.1, 145.6,
140.2, 139.2, 139.1, 138.7, 136.8, 122.6, 107.3, 106.4,
105.6, 105.2, 102.0, 101.7, 101.6, 99.9, 99.8, 99.6, 72.5,
70.04, 70.0, 63.6, 55.33, 55.27, 54.1; MS (FAB): m/zZ
1216.4 [MCCH], 663.5; MS (FAB): Calcd for
C133H137N3O33: 2305.5. Found: 2305.9 [MC].
4.3.2. Compound 5-G22. A yellowish gum; 89% yield; IR
2939, 2839, 1596, 1458, 1206, 1153, 1050 cmK1; 1H NMR
(300 MHz, CDCl3): d 3.78 (s, 24H), 4.52 (s, 2H), 4.64
(s, 2H), 4.92 (s, 4H), 4.95 (s, 4H), 5.42 (s, 2H), 6.40 (m, 4H),
6.49–6.60 (m, 14H), 7.44 (s, 1H); 13C NMR (125 MHz,
CDCl3): d 161.0, 160.96, 160.3, 159.97, 145.5, 139.2, 138.8,
136.7, 122.5, 107.2, 106.8, 105.2, 102.1, 101.5, 100.0, 99.9,
72.6, 70.1, 70.0, 63.7, 55.4, 54.1; MS (FAB): m/zZ944.4
[MC]; HRMS (FAB): m/z Calcd for C53H57N3O13:
943.3891. Found: 944.3970 [MCCH].
4.3.8. Compound 5-G21. A yellowish gum; 85% yield; 1H
NMR (300 MHz, CDCl3): d 3.73 (s, 6H), 3.78 (s, 12H), 4.51
(s, 2H), 4.63 (s, 2H), 4.95 (s, 4H), 5.41 (s, 2H), 6.40 (m, 5H),
6.53–6.59 (m, 7H), 7.47 (s, 1H); 13C NMR (125 MHz,
CDCl3): d 161.3, 161.0, 160.7, 160.0, 145.5, 140.3, 139.2,
139.1, 136.7, 136.5, 122.5, 106.7, 106.1, 105.9,
105.2, 105.0, 101.5, 100.4, 99.9, 72.4, 70.0, 63.7, 55.4,
55.3, 54.2; MS (FAB): m/zZ672.3 [MCCH]; HRMS
(FAB): m/z Calcd for C37H41N3O9: 671.2843. Found:
672.2921 [MCCH].
4.3.3. Compound 5-G33. A yellowish gum; 94% yield; IR
2939, 2840, 1597, 1456, 1203, 1154, 1051 cmK1; 1H NMR
(500 MHz, CDCl3): d 3.77 (s, 48H), 4.51 (s, 2H), 4.63
(s, 2H), 4.89 (s, 4H), 4.94 (s, 20H), 5.39 (s, 2H), 6.40 (m,
6H), 6.45 (m, 2H), 6.55 (m, 24H), 6.62 (m, 4H), 6.65 (m,
6H), 7.44 (s, 1H); 13C NMR (75 MHz, CDCl3): d 161.1,
160.4, 160.2, 160.1, 160.0, 145.6, 140.4, 139.6, 139.4,
139.23, 139.2, 139.0, 136.9, 122.7, 107.2, 106.8, 106.5,
105.3, 102.2, 101.8, 101.7, 100.03, 100.0, 72.4, 70.1, 70.0,
63.7, 55.4, 54.1; MS (MALDI): Calcd for C117H121N3O29:
2031.8086. Found: 2054.7959 [MCC Na]. PDI: 1.02.
4.3.9. Compound 5-G24. A yellowish gum; 92% yield; 1H
NMR (300 MHz, CDCl3): d 3.75 (s, 12H), 3.78 (s, 48H),
4.49 (s, 2H), 4.62 (s, 2H), 4.91 (s, 8H), 4.95 (s, 24H), 5.39
(s, 2H), 6.40 (m, 10H), 6.47 (m, 2H), 6.56 (m, 30H), 6.62
(m, 4H), 6.66 (m, 8H), 7.44 (s, 1H); 13C NMR (75 MHz,
CDCl3): d 161.4, 161.36, 160.7, 160.5, 160.4, 146.0, 140.7,
139.7, 139.6, 139.55, 139.3, 137.3, 123.0, 107.6, 107.1,
106.8, 106.1, 105.7, 102.5, 102.0, 101.9, 100.3, 72.8, 70.5,
70.4, 64.0, 55.7, 54.5; MS (FAB): Calcd for C149H153N3O37:
2577.8. Found: 2577.4 [MC].
4.3.4. Compound 5-G44. A yellowish solid; mp 76–78 8C;
95% yield; IR 2936, 2836, 1596, 1456, 1206, 1153,
1
1051 cmK1; H NMR (500 MHz, CDCl3): d 3.75 (s, 96H),
4.49 (s, 2H), 4.61 (s, 2H), 4.86 (s, 6H), 4.92 (s, 50H), 5.34
(s, 2H), 6.38 (m, 16H), 6.42 (m, 2H), 6.55 (m, 54H), 6.60
(m, 4H), 6.65 (m, 14H), 7.42 (s, 1H); 13C NMR (125 MHz,
CDCl3): d 161.7, 161.4, 161.1, 160.7, 160.5, 160.4, 160.2,
145.9, 140.8, 139.8, 139.7, 139.63, 139.59, 139.3, 137.4,
123.1, 108.1, 107.5, 107.1, 106.8, 105.9, 105.7, 105.4,
102.4, 102.1, 101.9, 100.4, 72.7, 70.444, 70.37, 64.0, 55.7,
4.3.10. Compound 5-G31. A yellowish gum; 92% yield; 1H
NMR (500 MHz, CDCl3): d 3.73 (s, 6H), 3.78 (s, 24H), 4.52
(s, 2H), 4.64 (s, 2H), 4.96 (s, 4H), 4.98 (s, 8H), 5.40 (s, 2H),

900
J. W. Lee et al. / Tetrahedron 62 (2006) 894–900
3192. (b) Meng, J.-C.; Siuzdak, G.; Finn, M. G. Chem.
Commun. 2004, 2108. (c) Link, A. J.; Vink, M. K. S.;
Tirrell, D. A. J. Am. Chem. Soc. 2004, 126, 10598. (d)
Sivakumar, K.; Xie, F.; Cash, B. M.; Long, S.; Barnhill, H. N.;
Wang, Q. Org. Lett. 2004, 6, 4603 and references therein.
8. (a) Parent, M.; Mongin, O.; Kamada, K.; Katan, C.; Blanchard-
Desce, M. Chem. Commun. 2005, 2029. (b) Englert, B. C.;
Bakbak, S.; Bunz, U. H. F. Macromolecules 2005, 38, 5868.
6.39–6.41 (m, 7H), 6.52 (m, 1H), 6.57 (m, 13H), 6.67 (m,
3H), 7.46 (s, 1H); 13C NMR (125 MHz, CDCl3): d 161.7,
161.4, 160.5, 160.4, 145.9, 140.7, 139.7, 139.6, 137.1,
122.9, 107.2, 106.8, 106.6, 105.7, 102.0, 101.9, 100.9,
100.4, 72.9, 70.5, 70.4, 64.1, 55.8, 54.6; MS (FAB): m/zZ
1216.4 [MCCH], 753.5, 647.5; HRMS (FAB): m/z Calcd
for C69H73N3O17: 1215.4940. Found: 1216.5018 [MCCH].
4.3.11. Compound 5-G42. A yellowish gum; 88% yield; 1H
NMR (300 MHz, CDCl3): d 3.75 (s, 12H), 3.77 (s, 48H),
4.52 (s, 2H), 4.63 (s, 2H), 4.87 (s, 8H), 4.95 (s, 24H), 5.36
(s, 2H), 6.40 (m, 10H), 6.45 (m, 2H), 6.51 (m, 4H), 6.56 (m,
24H), 6.60 (m, 2H), 6.66 (m, 12H), 7.43 (s, 1H); 13C NMR
(75 MHz, CDCl3): d 161.1, 160.6, 160.4, 160.1, 160.0,
145.6, 140.4, 139.4, 139.3, 139.2, 138.9, 136.9, 122.6,
107.6, 107.2, 106.8, 106.5, 105.3, 102.2, 102.0, 101.7,
100.0, 72.5, 70.1, 69.8, 63.7, 55.4, 54.1; MS (FAB): Calcd
for C149H153N3O37: 2577.8. Found: 2577.4 [MC].
´
9. (a) Dıaz, D. D.; Punna, S.; Holzer, P.; McPherson, A. K.;
Sharpless, K. B.; Fokin, V. V.; Finn, M. G. J. Polym. Sci., Part
A 2004, 42, 4392. (b) Helms, B.; Mynar, J. L.; Hawker, C. J.;
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Frechet, J. M. J. J. Am. Chem. Soc. 2004, 126, 15020. (c)
Opsteen, J. A.; van Hest, J. C. M. Chem. Commun. 2005, 57.
(d) Mantovani, G.; Ladmiral, V.; Tao, L.; Haddleton, D. M.
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Chem. Commun. 2005, 2089. (e) Lutz, J.-F.; Borner, H. G.;
Weichenhan, K. Macromol. Rapid Commun. 2005, 26, 514. (f)
Binder, W. H.; Kluger, C. Macromolecules 2004, 37, 9321. (g)
Tsarevsky, N. V.; Sumerlin, B. S.; Matyjaszewski, K.
Macromolecules 2005, 38, 3558.
10. (a) Wu, P.; Feldman, A. K.; Nugent, A. K.; Hawker, C. J.;
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Scheel, A.; Voit, B.; Pyun, J.; Frechet, J. M. J.; Sharpless, K. B.;
Acknowledgements
Fokin, V. V. Angew. Chem., Int. Ed. 2004, 43, 3928. (b)
Malkoch, M.; Schleicher, K.; Drockenmuller, E.; Hawker, C. J.;
Russell, T. P.; Wu, P.; Fokin, V. V. Macromolecules 2005, 38,
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2005, 38, 5436. (d) Lee, J. W.; Kim, B. K. Bull. Korean Chem.
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This research was supported by the Ministry of Information
and communication, Korea, under the Information
Technology Research Center support program supervised
by the Institute of Information Technology Assessment.
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