Shape persistent hybrid dendrimers from benzene and triazole via 'click chemistry'

Article abstract of DOI:10.1016/j.tet.2014.03.037

Fully aromatic rigid dendrimers have been synthesized at room temperature based on two different 'click'-reactions: The dendronization was carried out via the copper catalyzed azide-alkyne Huisgen cycloaddition or Diels-Alder cycloaddition, respectively.

Full text of DOI:10.1016/j.tet.2014.03.037

Tetrahedron xxx (2014) 1e7
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Shape persistent hybrid dendrimers from benzene and triazole via
‘click chemistry’q
*
ꢀ
€
€
Rene Stangenberg, David Turp, Klaus Mullen
Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Fully aromatic rigid dendrimers have been synthesized at room temperature based on two different
‘click’-reactions: The dendronization was carried out via the copper catalyzed azideealkyne Huisgen
cycloaddition or DielseAlder cycloaddition, respectively. The feasible combination of both reactions leads
to dendrimer hybrids. Stiff aromatic dendrimers, whose highly nitrogen containing scaffolds are solely
based on interconnected benzene and triazole rings, were created.
Received 6 January 2014
Received in revised form 11 March 2014
Accepted 12 March 2014
Available online xxx
Ó 2014 Published by Elsevier Ltd.
Keywords:
Dendrimer
Polyphenylene
Triazole
Click chemistry
Synthesis
1. Introduction
reacting alkynes with a tetracylones to form new benzene rings.
PPDs constitute a special class of dendrimers due to their shape
Dendrimers represent macromolecules with a monodisperse
structure and a defined number of functional groups, which can be
build-up by a huge variety of different synthetic methods.1 Within
all these methods easily manageable and exothermic reactions
with high yields and selectivity are necessary to achieve full con-
version of all reactive groups. So called ‘click reactions’2 enable
‘clicking’ together different suitably functionalized components. In
dendrimer chemistry, click reactions have been used for the func-
tionalization of dendrimer peripheries,3 for linking together several
ready-made dendrons to a single core (convergent synthesis)4 or
for divergent dendrimer growth.5,6 Triazole-rich flexible den-
drimers have been synthesized by a convergent approach using the
Huisgen reaction.7 With regard to dendrimer synthesis, the copper
catalyzed Huisgen cycloaddition between azides and alkynes is not
the only type of ‘click reaction’ that has been utilized. More and
more procedures are now being developed, which do not require
metal catalysis.8 The DielseAlder [4þ2]-cycloaddition can be used
for the modular synthesis of polyphenylene dendrimers (PPD), by
persistent character, which does not allow for either collapsing or
swelling of the scaffold.9
Within this work, experiments have been made regarding the
applicability of click chemistry for the synthesis of stiff dendrimers
at room temperature. The final nitrogen rich macromolecules were
built up from benzene and triazole rings forming a polyphenylene-
triazole dendrimer.y The requirement of ethynyl functions for both
PPD chemistry10 and azideealkyne click chemistry11 invites for
a combination of both concepts for dendrimer hybrids (see Fig. 1).
Fig. 1. Schematic illustration of azideealkyne Huisgen cycloaddition and DielseAlder
cycloaddition.
y
We use the term ‘polyphenylene-triazole dendrimer’ somewhat undefined. The
presented dendrimers are built from different substituted benzene rings, which are
tilted packed and twisted. The name polyphenylene dendrimers in principle does
not adequately reflect the different substituent types ranging from phenyl to tet-
raphenyl substituted benzene. The triazole unit occurs as a twofold substituted
entity.
q
Parts of this work were taken from the Dissertation Dendronized Ions by Dr.
€
David Turp, Mainz 2012.
* Corresponding author. Tel.: þ49 (0) 6131 379 151; fax: þ49 (0) 6131 379 350;
€
e-mail address: muellen@mpip-mainz.mpg.de (K. Mullen).
0040-4020/$ e see front matter Ó 2014 Published by Elsevier Ltd.
http://dx.doi.org/10.1016/j.tet.2014.03.037
Please cite this article in press as: Stangenberg, R.; et al., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.03.037

2
R. Stangenberg et al. / Tetrahedron xxx (2014) 1e7
2. Results/discussion
to disperse the ethynyl functionalized species 11 in ortho-xylene
and react with tetracyclone
at 160 ꢀC to achieve the
7
2.1. Synthesis
polyphenylene-triazole dendrimer 13. We proved that
polyphenylene-triazole scaffolds are stable enough to endure the
harsh conditions that are required for the growth of PPDs via
DielseAlder-reaction.17
A dendritic shell is always built around a single core to obtain
a dendrimer. We used 1,3,5-triethynylbenzene (8) and tetrakis(4-
ethynylphenyl)methane (14)12 to grow dendrimers in a trigonal
planar or a tetrahedral geometry, respectively. To enable the syn-
thesis of dendritically branched polyphenylene-triazole scaffolds,
an ethynyl functionalized phenyl azide is required that can serve as
a branching unit. Phenyl azides can easily be obtained via conver-
sion of the according phenyl amines.13 ((5-Azido-2-methyl-1,3-
phenylene)bis(ethyne-2,1-diyl))bis(triisopro pylsilane) (3) was se-
lected as a suitable building block for dendritic growth, which can
be synthesized in two steps starting from 3,5-dibromo-4-
methylaniline (1) as described for comparable compounds
(Fig. 2).6 After functionalization with Triisopropylsilyl (TIPS)-acet-
ylene via Sonogashira coupling, azide 3 was obtained using tert-
butyl nitrite (t-BuONO) and trimethylsilyl azide (TMSN3) as azide
source.13 Although azide 3 could be stored at 3 ꢀC, it was usually
prepared freshly for every growth step. Aniline 4 is a very large and
bulky aryl amine that somewhat resembles the structure of poly-
phenylenes (compare Figs. 2 and 3).14 It was converted to the
according azide 5 using the above mentioned method. For the end
capping of phenylene-triazole dendrimers, the bulky phenyl azide
5 and the commercially available azidobenzene 6 or tetracyclone 7
have been tested.
The resulting dendrimers were purified first by column chro-
matography, precipitation in hexane and recycling gel permeation
chromatography (GPC). Surprisingly, the solubility of 11 in methy-
lene chloride was relatively low so that this solvent could be used to
purify 11 by the extraction of impurities from the non-dissolved
raw product. It is noteworthy that ethynyl functionalized species
10 and even more the deprotected species 11 both tend to form
aggregates. Aggregate formation was evidenced by the appearance
of white, solid precipitate in their solutions even at moderate
concentrations (approx. 10 mg/mL) in comparatively good solvents,
such as THF.
To reduce the tendency of aggregate formation the geometry
needs to be more sphere like to minimize interactions and increase
the solubility. Ethynyl functionalized tetraphenylmethane 14 has
frequently been utilized as a core for the build-up of polyphenylene
dendrimers.18 Due to its tetrahedral geometry, tetraphenylmethane
orients growing dendrons into all three spatial dimensions, and the
dendrimer adopts an overall globular shape already at compara-
tively low generations and low degrees of branching.10 Copper
catalyzed cycloaddition of bulky azide 5 gave the first generation
polyphenylene-triazole dendrimer 15 with a tetrahedral core (see
Fig. 3b). Dendrimer 15 can be regarded as a related structure to the
triazole-phenyl functionalized tetraphenylmethane 20 described in
literature (compare Fig. 3b and crystal structure in Fig. 4).19 In
analogy to the synthesis of 12, second generation dendrimers with
a tetrahedral core were obtained upon a tetraphenylmethane core
14 (Fig. 3b) and were purified in the same way as the trigonal planar
dendrimers. Despite the tetrahedral geometry of its core, den-
drimer 15 still showed a considerable tendency to aggregate. The
higher density second generation dendrimer 19 exhibited much
better solubility in THF and a reduced tendency to aggregate than
dendrimer 15 and 18, probably due to its more sphere like
character.
Fig. 2. Synthesis of branching unit 3 for the build-up of dendritic polyphenylene-
triazole scaffolds and suitable phenyl azide end capping unit 5, 6, and 7.
2.2. Characterization
1H and 13C NMR signals of all dendrimers could readily be
assigned and were used to confirm complete conversion as well as
purity. A detailed analysis of the proton NMR spectra is given
in Supplementary data. Measurements by means of MALDI-TOF
mass spectrometry show the formation of monodisperse macro-
molecules but also demonstrate that polyphenylene-triazole com-
pounds decompose easily upon laser irradiation. Three additional
signals at lower m/z ratios of 26 m/z appear due to a release of
nitrogen from triazole moieties (see Fig. 4 and Supplementary
data). It is however surprising that cleavage of nitrogen only oc-
curs up to three times, although four triazole rings are present in
the structure.
The build-up of dendritic scaffolds from benzene rich and hy-
drophobic building blocks makes the use of non-aqueous reaction
media necessary, in contrast to many other ‘click reactions’. Instead
of mixtures of water and tert-butanol, THF was used for dissolving
all starting materials, reagents and products. A catalytically active
Cuþ species is required, which is well soluble in the organic re-
action medium. To ensure a good solubilization of the Cuþ in THF,
the effective ligand Tris-benzyltriazolylmethyl amine (TBTA) was
employed. The ligand was previously synthesized by a click re-
action itself.15 Moreover, to ensure complete conversion of all al-
kyne moieties, an excess of the azide component (about 2e3 equiv
per alkyne function) was generally used. For the growth of the first
generation polyphenylene-triazole dendrimer 9 from a trigonal
planar core, 1,3,5-triethynylbenzene (8) was reacted with the bulky
azide 5 (Fig. 3a). To enable the synthesis of a second generation
polyphenylene-triazole dendrimer, azide building block 3 was
connected to the trigonal planar core 8, followed by an activation of
the resulting species 10 for another growth step via removal of its
TIPS-groups with TBAF in THF (see Fig. 3a) towards compound (11).
Compound 11 was converted to second generation polyphenylene-
triazole dendrimer 12 in THF at room temperature using bulky
azide 5 for end capping (Fig. 3a). Thermal degradation of 1,2,3-
triazole occurs between 218 ꢀC and 338 ꢀC.16 Thus we were able
2.3. Structure and shape persistence of polyphenylene-
triazole dendrimers
The crystal structure of a fourfold functionalized tetraphenyl-
methane comparable to 20 has been described and can be assigned
as a first generation triazole dendrimer,19 which indicates a strong
preference for a coplanar alignment of triazole and neighboring
benzene rings due to electronic conjugation and limited flexibility
based on the sp2-character of the aromatic subunits. Thus a rela-
tively flat overall orientation of dendrons could be expected, due to
the preference for coplanar alignment. Dendrimer
9 was
Please cite this article in press as: Stangenberg, R.; et al., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.03.037

R. Stangenberg et al. / Tetrahedron xxx (2014) 1e7
3
(A)
(B)
Fig. 3. a: Synthesis of first generation polyphenylene-triazole dendrimer 9 and first generation of ethynyl functionalized polyphenylene-triazole dendrimer 10 and 11, respectively,
with a trigonal planar core via copper catalyzed Huisgen cycloaddition at room temperature. Synthesis of second generation polyphenylene-triazole dendrimer 12 and second
generation polyphenylene-triazole hybrid dendrimer 13. (i) Cuþ, TEA, TBTA, THF, 23 ꢀC; (ii) TBAF, THF, 23 ꢀC. b: Synthesis of first generation polyphenylene-triazole dendrimer 15
and first generation of ethynyl functionalized polyphenylene-triazole dendrimer 16 and 17, respectively, with a tetrahedral core via copper catalyzed Huisgen cycloaddition at room
temperature. Structure of tetrakis(4-(1-phenyl-1H-1,2,3-triazol-4-yl)phenyl)methane 20. Synthesis of second generation polyphenylene-triazole dendrimer 18 and 19 acting on 17
by using of different end capping agents 5 or 6. (i) Cuþ, TEA, TBTA, THF, 23 ꢀC; (ii) TBAF, THF, 23 ꢀC.
Please cite this article in press as: Stangenberg, R.; et al., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.03.037

4
R. Stangenberg et al. / Tetrahedron xxx (2014) 1e7
aggregates. Employment of bulky surface groups and an overall
spherical geometry helped to reduce their tendency to aggregate
and increased their solubility in THF and DCM. In addition to aryl-
triazole dendrimer synthesis, the potential for a combination with
polyphenylene dendrimer chemistry was tested. It was found that
the thermal stability of the triazole linkage is sufficient to allow for
a functionalization of dendritic aryl-triazole scaffolds with rigid
polyphenylenes. Due to the comparatively large size of the den-
drons and the energetic preference for a coplanar alignment of
neighboring triazole and benzene rings, the resulting dendritic
scaffolds are fairly stiff and hence retain voids. Moreover, the large
number of triazole moieties leads to nitrogen rich scaffolds in
which the nitrogen atoms may serve as coordination sites. The
combined properties of inherently porous aryl-triazole dendrimers
offers the possibility to use such dendrimers as host material for
sensing or storage application or might be suitable for ion
complexation.
In the future, polyphenylene-triazole dendrimers of higher
generations as well as dendrimers with different core geometries or
alternative building blocks will be synthesized. The applicability of
these nitrogen rich, stiff and porous materials as sensing layers for
the detection of specific guest molecules will be tested. More fun-
damentally, the concept of reacting ethynyl groups at room tem-
perature might be exploited to functionalize polyphenylene
dendrimers with temperature sensitive surface moieties.
4. Experimental section
4.1. General information
Fig. 4. MALDI-TOF of polyphenylene-triazole compounds 13 (up left) and 16 (up right).
Single crystal structure of first generation polyphenylene-triazole dendrimer 9 with
a
trigonal planar core (mid). For crystallographic data of compound
9 see
Supplementary data and the Cambridge Crystallographic Data Centre (CCDC).
Proton (1H NMR) and carbon (13C NMR) nuclear magnetic res-
onance spectra were recorded at 300, 500 or 700 MHz and 100, 125
or 175 MHz, respectively. The chemical shifts are given in parts per
million. The solvent proton signals were used as a reference value.
Data are reported as singlet (s), doublet (d), triplet (t), and multiplet
crystallized as colorless triclinic prisms (Fig. 4). In contrast to 20 the
steric demand of the ortho-phenyl rings of each 2,4,6-
triphenylbenzene moiety enforces a twisting of benzene rings out
of their common plane with neighboring triazole rings, while all
triazole rings retain their almost coplanar alignment with the
central benzene ring of the core. The alignment is only slightly
disturbed due to packing effects in the crystal lattice.
A comparison of the modeled structures of the second genera-
tion dendrimers 18 and 19 (see Supplementary data) indicates that
the energetically favored coplanar alignment of phenyl and triazole
rings is not only disturbed by the large spatial demand of bulky
2,4,6-triphenylbenzene moieties in 19, but also by the methyl group
of each branching phenyl ring in both dendrimers 18 an 19. Due to
the largely increased solubility and reduced aggregation of den-
drimers endcapped with bulky azide 5 as compared to small azi-
dobenzene 6, the larger azide 5 is the preferable end capping unit.
The dendritic scaffold resulting from building block 3 is not as rigid
as typical PPD scaffolds, but should nevertheless be much stiffer
than the dendritic scaffolds based on triazoles via click reactions
that have been reported so far due to the conjugation between
connected rings.5a
ꢁ
(m). Column chromatography was done using 32e63, 60 A silica
gel. All solvents were dried before using. The starting materials was
purchased from Sigma Aldrich and used without further
purification.
4.2. 4-Methyl-3,5-bis((triisopropylsilyl)ethynyl)aniline (2)
15.00 g (56.61 mmol) 3,5-dibromo-4-methylaniline 1, 2.97 g
(11.32 mmol) PPh3, 2.16 g (11.32 mmol) CuI, and 3.97 g (5.66 mmol)
Pd(PPh3)2Cl2 were dissolved in a mixture of 140 mL triethylamine
and 150 mL toluene. The mixture was heated to 80 ꢀC under argon.
21.68 g (26.67 mL, 118.89 mmol) TiPS-acetylene was added drop-
wise (orange suspension turns black) and the mixture was stirred at
80 ꢀC over night. Water was added to the mixture and the organic
phase was washed with satd NH4Cl (aq), 1 N HCl(aq), 10% Na2CO3
(aq), and dried over MgSO4. After evaporation of the solvent, the
crude product was purified by column chromatography using firstly
hexane and then a 10:1 mixture of petrol ether and ethyl acetate as
eluent to yield 22.71 g (86%) of the pure compound as viscous
yellow oil. Rf (PE/EtOAc¼10/1)¼0.65. 1H NMR (300 MHz, THF-d8,
3. Conclusion
A new class of dendrimer hybrids has been presented. Utiliza-
tion of the copper catalyzed azide-alkyne Huisgen- and Diel-
seAlder cycloaddition has enabled the synthesis of a number of
different dendrimers at room temperature, which are entirely
constituted from benzene and triazole rings. Thus the introduction
of temperature sensitive groups becomes possible. Two distinct
cores with different geometries (trigonal planar and tetrahedral)
have been used to generate polyphenylene-triazole dendrimers
with either preferentially flat or globular overall shapes. Many of
the intermediate aryl-triazole species as well as some of the final
aryl-triazole dendrimers showed a pronounced tendency to form
298 K) d 6.72 (s, 2H, Hc), 4.46 (s, 2H, Ha), 2.47 (s, 3H, Hf), 1.16 (m,
42H, HiþHj). 13C NMR (75 MHz, THF-d8, 298 K)
d 146.95 (C, Cb),
131.34 (C, Ce), 124.76 (C, Cd), 119.66 (CeH, Cc), 107.88 (C, Cg), 93.38
(C, Ch), 19.30 (CH3, Cj), 18.84 (CH3, Cf), 12.45 (CeH, Ci) FDMS (m/z):
calcd for C29H49NSi2: 467.3, found: 467.4.
4.3. ((5-Azido-2-methyl-1,3-phenylene)bis(ethyne-2,1-diyl))
bis(triisopropylsilane) (3)
1.320 g (2.824 mmol) 2 were dissolved in a mixture of aceto-
nitrile and THF (9:1) in an open flask. The mixture was cooled to
Please cite this article in press as: Stangenberg, R.; et al., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.03.037

R. Stangenberg et al. / Tetrahedron xxx (2014) 1e7
5
0
ꢀC. 0.874 g (8.473 mmol, 1.01 mL) tert-butyl nitrite and 0.814 g
solvent) as eluent to yield 490 mg (90%) of the product as a colorless
(7.061 mmol, 0.93 mL) trimethylsilyl azide (release of N2!) were
added dropwise and the solution was allowed to warm to room
temperature. Two liquid phases were obtained, which were ho-
mogenized by addition of THF. The orange solution was adsorbed
on silica and purified by column chromatography using hexane as
eluent to yield 1289 g (92%) of the pure product as viscous yellow
solid. 1H NMR (300 MHz, THF-d8, 298 K)
d 9.27 (s, 3H, Hd), 8.63 (s,
3H, Ha), 8.10 (s, 6H, Hf), 2.74 (s, 9H, Hi), 1.21 (s, 126H, HlþHm). 13
C
NMR (75 MHz, THF-d8, 298 K) d 148.70 (C, Cc), 143.78 (C), 136.33 (C),
133.38 (C), 126.13 (C, Cg), 124.25 (CeH, Cf), 123.15 (CeH, Ca), 120.10
(CeH, Cd), 105.51 (C, Cj), 97.60 (C, Ck), 19.91 (CH3, Ci), 19.27 (CH3,
Cm), 12.43 (CeH, Cl) MALDI-TOF (m/z): calcd for C99H147N9Si6:
1631.0, found: 1633.5.
oil. Rf (hexane)¼0.50. 1H NMR (300 MHz, THF-d8, 298 K)
2H, Hb), 2.61 (s, 3H, He), 1.17 (m, 42H, HhþHi).
d 7.12 (s,
4.7. 1,3,5-Tris(1-(3,5-diethynyl-4-methylphenyl)-1H-1,2,3-
triazol-4-yl)benzene (11)
4.4. 20-Azido-50-phenyl-1,10:30,100-terphenyl (5)
2.000 g (6.223 mmol) 50-phenyl-[1,10:30,100-terphenyl]-20-amine
4 were dissolved in a mixture of acetonitrile and THF (5:1) in an
open flask. The mixture was cooled to 0 ꢀC. 1.925 g (18.668 mmol,
2.22 mL) tert-butyl nitrite and 1.792 g (15.556 mmol, 2.05 mL)
trimethylsilyl azide (release of N2!) were added dropwise and the
solution was allowed to warm to room temperature. The solution
was adsorbed on silica and purified by column chromatography
using a 4:1 mixture of hexane and ethyl acetate as eluent to yield
2.108 g (98%) of the pure product as viscous yellow oil. Rf (hexane/
To a solution of 200 mg (0.123 mmol) 10 in THF (50 mL) was
added dropwise
a solution of tetrabutylammonium fluoride
(240 mg, 0.858 mmol) in THF (10 mL). The mixture was stirred for
2 h at room temperature and then filtered over silica. After removal
of the solvent under vacuum, the solid remainder was dispersed in
methylene chloride, filtered, washed with methylene chloride and
dried to afford 66 mg (0.095 mmol, 78%) of the compound as
a colorless powder. 1H NMR (300 MHz, THF-d8, 298 K)
d
9.22 (s, 3H,
Hd), 8.63 (s, 3H, Ha), 8.16 (s, 6H, Hf), 4.06 (s, 6H, Hk), 2.66 (s, 9H, Hi).
13C NMR (176 MHz, THF-d8, 298 K)
148.82 (C), 143.72 (C), 136.38
EtOAc¼4/1)¼0.80. 1H NMR (300 MHz, THF-d8, 298 K)
d
7.69 (d,
d
3JHH¼7.2 Hz, 2H, Hb), 7.61 (s, 2H, Ha), 7.58 (d, 3JHH¼7.0 Hz, 4H, He),
(C), 133.38 (C), 125.50 (C, Cg), 124.70 (CeH, Cf), 123.28 (CeH, Ca),
119.79 (CeH, Cd), 84.83 (Cj), 81.87 (Ck), 19.08 (CH3, Ci) MALDI-TOF
(m/z): calcd for C45H27N9: 693.2, found: no signal due to UV laser
induced decomposition.
7.49e7.29 (m, 9H, HcþHdþHfþHg). 13C NMR (75 MHz, THF-d8,
298 K)
d 140.94 (C), 139.84 (C), 139.71 (C), 138.28 (C), 134.91 (C),
130.46 (CeH, Cf), 129.91 (CeH), 129.78 (CeH), 129.31 (CeH, Ce),
128.65 (CeH), 128.49 (CH, Cd), 127.89 (CeH) FDMS (m/z): calcd for
C
24H17N3: 347.1, found: 346.7.
4.8. Compound (12)
4.5. 1-(1-(50-Phenyl-[1,10:30,100-terphenyl]-20-yl)-1H-1,2,3-
triazol-4-yl)-3,5-bis(1-(50-phenyl-[1,10:30,100-terphenyl]-40-yl)-
1H-1,2,3-triazol-4-yl)benzene (9)
40 mg (0.058 mmol) of ethynyl functionalized compound 11 and
240 mg (0.692 mmol) of azide 5 were dissolved in THF. To the so-
lution were added 17 mg (0.088 mmol) sodium ascorbate, 23 mg
(0.044 mmol) TBTA, 1 mL triethylamine and 11 mg (0.044 mmol)
CuSO4$5H2O. The solution was stirred at room temperature for 16 h
and then purified by column chromatography using firstly a mixture
of hexane and ethyl acetate (4:1) and then THF as eluent. After re-
moval of the solvent in vacuum, the crude product was dissolved in
THF, precipitated in hexane, filtered, dried, dissolved in chloroform
and purified by recycling GPC to afford 68 mg (0.024 mmol, 42%) of
the compound as a colorless powder. 1H NMR (700 MHz, THF-d8,
10 mg (0.067 mmol) of 1,3,5-triethynylbenzene 8 and 139 mg
(0.400 mmol) of azide 5 were dissolved in THF. To the solution
were added 10 mg (0.051 mmol) sodium ascorbate, 13 mg
(0.025 mmol) TBTA, 0.5 mL triethylamine, and 6 mg (0.025 mmol)
CuSO4$5H2O. The solution was stirred at room temperature for
16 h and then purified by column chromatography using firstly
a mixture of hexane and ethyl acetate (4:1) and then THF as elu-
ent. After removal of the solvent in vacuum, the crude product was
dissolved in methylene chloride, precipitated in hexane, filtered,
dried, dissolved in chloroform, and purified by recycling GPC to
afford 50 mg (0.042 mmol, 63%) of the compound as a colorless
298 K) d 9.11 (s, 3H, Hb), 8.67 (s, 3H, Ha), 8.05 (s, 6H, Hc), 7.88 (s, 12H,
Hf), 7.86 (s, 6H, He), 7.83 (d, 3JHH¼8.1 Hz, 12H, Hg), 7.49 (t,
3JHH¼7.7 Hz, 12H, Hh), 7.40 (t, 3JHH¼7.3 Hz, 3H, Hi), 7.33e7.28 (n.r.,
60H, HjþHkþHl), 1.87 (s, 9H, Hd). 13C NMR (126 MHz, THF-d8, 298 K)
powder. 1H NMR (300 MHz, THF-d8, 298 K)
d
8.02 (s, 3H, Ha), 7.95
d 146.33 (C), 144.16 (C), 142.12 (C), 140.68 (C), 139.28 (C), 137.06 (C),
(s, 3H, Hd), 7.83 (s, 6H, Hg), 7.82 (d, 3JHH¼7.4 Hz, 6H, Hj), 7.48 (t,
133.58 (C), 129.97 (CeH), 129.71 (CeH), 129.66 (CeH), 129.55 (CeH),
129.25 (CeH), 129.10 (CeH), 128.95 (CeH), 128.79 (CeH), 128.33
(CeH),18.11(CH3) MALDI-TOF (m/z): calcd for C189H129N27Si6: 2778.1,
found: no signal due to UV laser induced decomposition.
3JHH¼7.4 Hz, 6H, Hk), 7.39 (t, 3JHH¼7.3 Hz, 3H, Hl), 7.28e7.14 (n.r.,
30H, HnþHoþHp). 13C NMR (75 MHz, THF-d8, 298 K)
d 147.25 (C,
Cc), 144.01 (C), 142.10 (C, Cm), 140.69 (C), 139.22 (C, Ce), 133.61 (C),
132.85 (C), 129.93 (CeH, Ck), 129.57 (CeH, CgþCo), 129.10 (CeH,
ClþCn), 128.59 (CeH, Cp), 128.31 (CeH, Cj), 125.01 (CeH, Ca), 122.35
(CeH, Cd) FDMS (m/z): calcd for C84H57N9: 1191.5, found: no signal
due to UV laser induced decomposition. XRD: colorless prisms,
triclinic, P-1.
4.9. Compound (13)
22 mg (0.019 mmol) of ethynyl functionalized compound 11 and
89 mg (0.231 mmol) tetraphenylcyclopentadienone 7 were dis-
persed in o-xylene (5 mL) in a microwave tube. The argon bubbled
mixture was stirred at 160 ꢀC for 14 h. After cooling to room tem-
perature, the mixture was purified by column chromatography using
firstly a 10:1 mixture of hexane and ethyl acetate and then methy-
lene chloride as eluent. After removal of the solvent in vacuo, the
product was dissolved in methylene chloride, precipitated in hexane,
filtered and dried to afford 44 mg (0.055 mmol, 81%) of the pure
compound as a colorless powder. In NMR measurements, two local
conformations A and B could be discerned (see paragraph 3.3.3 for
4.6. 1,3,5-Tris(1-(4-methyl-3,5-bis((triisopropylsilyl)ethynyl)
phenyl)-1H-1,2,3-triazol-4-yl)benzene (10)
50 mg (0.333 mmol) 1,3,5-triethynylbenzene 8 and 0.987 g
(1.998 mmol) of AB2 azide 3 were dissolved in THF. To the solution
were added 50 mg (0.253 mmol) sodium ascorbate, 67 mg
(0.127 mmol) TBTA, 2 mL triethylamine and 32 mg (0.127 mmol)
CuSO4$5H2O. The solution was stirred at room temperature for
15 h. After adsorption to silica, the solution was purified by column
chromatography using firstly hexane and then mixtures of hexane
and ethyl acetate (10:1 to 4:1; consumption of large amounts of
details): 1H NMR (700 MHz, THF-d8, 298 K)
d
8.84e8.81 (ꢁ3s, 3H),
8.56e8.53 (3s, 3H), 8.52e8.41 (ꢁ8s, 3Hþ3H), 7.72 (ꢁ3s, 6H), 7.57
(ꢁ3s, 6H), 7.46 (ꢁ3s, 6H), 7.16e7.05 (n.r., 30Hþ30H), 7.11 (ꢁ3s, 6H),
Please cite this article in press as: Stangenberg, R.; et al., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.03.037

6
R. Stangenberg et al. / Tetrahedron xxx (2014) 1e7
6.98 (s), 6.95e6.77 (n.r.), 6.61 (s), 2.23 (s, 9H), 1.92 (s, 9H). 13C NMR
(176 MHz, THF-d8, 298 K) 148.31 (C), 148.18 (C), 144.39 (C), 144.37
(273 mg, 0.978 mmol) in THF (10 mL). The mixture was stirred for
2 h at room temperature. After washing three times with a con-
centrated aqueous solution of sodium chloride, the solution was
filtered over silica and the solvent removed under vacuum to afford
44 mg (0.039 mmol, 38%) of the product as a beige-white powder.
Rf (hexane/EtOAc¼10/1)¼0.00. 1H NMR (300 MHz, THF-d8, 298 K)
d
(C), 143.23 (C), 142.94 (C), 142.87 (C), 142.75 (C), 141.88 (C), 141.79 (C),
141.48 (C), 141.41 (C), 141.17 (C), 141.13 (C), 141.07 (C), 140.98 (C),
140.93 (C), 140.82 (C), 140.74 (C), 135.15 (C), 135.01 (C), 134.60 (C),
134.52 (C), 133.40 (C), 133.32 (C), 132.68 (CeH), 132.64 (CeH), 132.54
(CeH), 132.49 (CeH), 132.39 (CeH), 131.92 (CeH), 130.98 (CeH),
130.92 (CeH), 128.52 (CeH), 128.49 (CeH), 127.97 (CeH), 127.88
(CeH), 127.77 (CeH), 127.69 (CeH), 127.62 (CeH), 127.58 (CeH),
127.55 (CeH), 127.22 (CeH), 127.18 (CeH), 126.84 (CeH), 126.79
(CeH), 126.57 (CeH), 126.34 (CeH), 126.27 (CeH), 121.69 (CeH),
121.53 (CeH), 19.77 (CH3), 19.30 (CH3), MALDI-TOF (m/z): calcd for
d
8.90 (s, 4H, Hg), 8.05 (s, 8H, Hi), 7.93 (d, 3JHH¼8.5 Hz, 8H, Hc), 7.47
(d, 3JHH¼8.5 Hz, 8H, Hd), 4.03 (s, 8H, Hn), 2.63 (s, 12H, Hl). 13C NMR
(75 MHz, THF-d8, 298 K)
d 148.83 (C), 147.66 (C), 143.59 (C), 136.32
(C),132.54 (CeH, Cd), 129.99 (C), 125.99 (C), 125.37 (CeH, Cc), 124.55
(CeH, Ci), 118.98 (CeH, Cg), 85.08 (Cn), 81.80 (Cm), 19.10 (Cl) MALDI-
TOF (m/z): calcd for C77H48N12: 1140.4, found: no signal due to UV
laser induced decomposition.
C
213H147N9: 2832.5, found: 2833.5 (þdecomposition due to UV laser
irradiation: eN2, e2N2, e3N2).
4.10. Tetrakis(4-(1-(50-phenyl-[1,10:30,10’-terphenyl]-20-yl)-1H-
1,2,3-triazol-4-yl)phenyl)methane (15)
4.13. Tetrakis(4-(1-(4-methyl-3,5-bis(1-phenyl-1H-1,2,3-
triazol-4-yl)phenyl)-1H-1,2,3-triazol-4-yl)phenyl)methane
(18)
10 mg (0.024 mmol) ethynyl functionalized tetraphenylmethane
core 14 and 67 mg (0.192 mmol) bulky azide 5 were dissolved in
THF. To the solution were added 5 mg (0.024 mmol) sodium
ascorbate, 6 mg (0.012 mmol) TBTA, 0.5 mL triethylamine and 3 mg
(0.012 mmol) CuSO4$5H2O. The solution was stirred at room tem-
perature for 16 h, whereupon a yellow-white suspension was ob-
tained. The suspension was purified by column chromatography
using firstly a 4:1 mixture of hexane and ethyl acetate and then
methylene chloride as eluent to yield 0.017 g (40%) of the com-
20 mg (0.018 mmol) of ethynyl functionalized compound 17 and
33 mg (0.280 mmol) of phenyl azide 6 were dissolved in THF. To the
solution were added 7 mg (0.035 mmol) sodium ascorbate, 9 mg
(0.018 mmol) TBTA, 0.5 mL triethylamine and 9 mg (0.018 mmol)
CuSO4$5H2O. The solution was stirred at room temperature for
15 h. The obtained suspension was exposed to ultrasonic sound and
filtered. The remaining solid was washed firstly with a mixture of
hexane and ethyl acetate (4:1) and then acetonitrile, whereupon
the solid was transferred into THF for dissolution. After 2 h, the
obtained solution was filtered over cotton fibers and the solvent
removed in vacuum to yield 8 mg (0.004 mmol, 23%) of the com-
pound as a white solid. 1H NMR (700 MHz, CD2Cl2, 298 K)
d 7.79 (s,
8H, Hj), 7.75 (d, 3JHH¼7.7 Hz, 8H, Hm), 7.51 (t, 3JHH¼7.5 Hz, 8H, Hn),
7.49 (s, 4H, Hg), 7.49 (d, 3JHH¼8.4 Hz, 8H, Hc), 7.44 (t, 3JHH¼7.4 Hz,
4H, Ho), 7.28 (m, 24H, HqþHs), 7.24 (d, 3JHH¼8.4 Hz, 8H, Hd), 7.23
pound as a white solid. 1H NMR (500 MHz, THF-d8, 298 K)
d 9.00 (s,
(m, 16H, Hr). 13C NMR (75 MHz, CD2Cl2, 298 K)
d
146.98 (C), 146.87
4H, Hc), 8.83 (s, 8H, Hf), 8.37 (s, 8H, Hd), 7.98 (d, 3JHH¼7.7 Hz, 16H,
Hg), 7.97 (d, 3JHH¼8.1 Hz, 8H, Ha), 7.58 (t, 3JHH¼7.7 Hz, 16H, Hh),
7.50 (d, 3JHH¼8.1 Hz, 8H, Hb), 7.45 (t, 3JHH¼7.4 Hz, 8H, Hi), 2.79 (s,
(C), 143.63 (C), 141.10 (C), 140.00 (C), 138.41 (C), 132.53 (C), 131.52
(CeH, Cd), 129.61 (CeH, Cn), 129.37 (CeH, Cj), 128.98 (CeH, Cr),
128.87 (CeH, CoþCq), 128.64 (C), 128.37 (CeH, Cs), 127.86 (CeH,
Cm), 125.59 (CeH, Cc), 123.74 (CeH, Cg) FDMS (m/z): calcd for
12H, He). 13C NMR (126 MHz, THF-d8, 298 K)
d 149.19 (C), 148.07 (C),
147.72 (C),142.92 (C),137.75 (C),134.44 (C),132.49 (CeH, Cb),130.72
(CeH, Ch), 129.41 (CeH, Ci), 126.07 (CeH, Ca), 122.36 (CeH, Cf),
121.20 (CeH, Cd), 121.15 (CeH, Cg), 119.16 (CeH, Cc), 19.03 (CeH, Ce)
MALDI-TOF (m/z): calcd for C125H88N36: 2093.8, found: no signal
due to UV laser induced decomposition.
C
129H88N12: 1805.7, found: no signal due to UV laser induced
decomposition.
4.11. Tetrakis(4-(1-(4-methyl-3,5-bis((triisopropylsilyl)ethy-
nyl)phenyl)-1H-1,2,3-triazol-4-yl)-phenyl)methane (16)
117 mg (0.281 mmol) ethynyl functionalized tetraphenyl-
methane core 14 and 1.110 g (2.247 mmol) of AB2 azide 3 were
dissolved in THF. To the solution were added 56 mg (0.281 mmol)
sodium ascorbate, 75 mg (0.140 mmol) TBTA, 3 mL triethylamine
and 35 mg (0.140 mmol) CuSO4$5H2O. The solution was stirred at
room temperature for 16 h. After adsorption to silica, the solution
was purified by column chromatography using firstly hexane and
then a mixture of hexane and ethyl acetate (10:1) as eluent to yield
578 mg (88%) of the product as a colorless solid. Rf (hexane/
4.14. Compound (19)
50 mg (0.044 mmol) of ethynyl functionalized compound 17 and
244 mg (0.701 mmol) of azide 5 were dissolved in THF. To the so-
lution were added 17 mg (0.088 mmol) sodium ascorbate, 23 mg
(0.044 mmol) TBTA, 1 mL triethylamine and 11 mg (0.044 mmol)
CuSO4$5H2O. The solution was stirred at room temperature for
16 h. The yellow solution was purified by column chromatography
using firstly a mixture of hexane and ethyl acetate (4:1) and then
THF as eluent. After removal of the solvent in vacuum, the crude
product was dissolved in methylene chloride, precipitated in hex-
ane, filtered, dried, dissolved in chloroform and purified by recy-
cling GPC to afford 88 mg (0.022 mmol, 51%) of the compound as
EtOAc¼10/1)¼0.72. 1H NMR (300 MHz, THF-d8, 298 K)
d 8.93 (s, 4H,
Hg), 8.00 (s, 8H, Hi), 7.93 (d, 3JHH¼8.5 Hz, 8H, Hc), 7.48 (d,
3JHH¼8.5 Hz, 8H, Hd), 2.71 (s, 12H, Hl), 1.19 (m, 168H, HoþHp). 13
C
NMR (75 MHz, THF-d8, 298 K)
d 148.67 (C), 147.53 (C), 143.52 (C),
136.19 (C), 132.35 (CeH, Cd), 129.89 (C), 125.93 (C), 125.90 (CeH, Cc),
124.16 (CeH, Ci), 119.13 (CeH, Cg), 105.36 (C, Cn), 97.47 (C, Cm), 19.75
(CH3, Cl), 19.12 (CH3, Cp), 12.28 (CeH, Co) MALDI-TOF (m/z): calcd
for C149H208N12Si8: 2390.5, found: 2393.4 (and fragments from UV
induced decomposition).
a colorless powder. 1H NMR (700 MHz, CD2Cl2, 298 K)
d 8.30 (s, 4H,
Hc), 7.91 (d, 3JHH¼8.5 Hz, 8H, Ha), 7.85 (s, 8H, Hd), 7.83 (s, 16H, Hg),
7.76 (d, 3JHH¼7.3 Hz, 16H, Hh), 7.53 (d, 3JHH¼8.5 Hz, 8H, Hb), 7.52
(t, 3JHH¼7.7 Hz, 16H, Hi), 7.46 (s, 8H, Hf), 7.45 (t, 3JHH¼7.4 Hz, 8H,
Hj), 7.35e7.31 (m, 48H, HkþHm), 7.28e7.25 (m, 32H, Hl), 1.71 (s, 12H,
He). 13C NMR (176 MHz, CD2Cl2, 298 K)
d 148.29 (C), 147.22 (C),
4.12. Tetrakis(4-(1-(3,5-diethynyl-4-methylphenyl)-1H-1,2,3-
triazol-4-yl)phenyl)methane (17)
145.76 (C), 143.77 (C), 141.08 (C), 139.94 (C), 138.44 (C), 135.34 (C),
135.29 (C), 133.22 (C), 132.45 (C), 132.13 (CeH, Cb), 129.62 (CeH, Ci),
129.33 (CeH, Cg), 129.01 (CeH, Ck), 128.97 (CeH, Cl), 128.90 (CeH,
Cj), 128.45 (CeH, Cm), 127.87 (CeH, Ch), 127.13 (CeH, Cf), 125.78
(CeH, Ca), 121.17 (CeH, Cd), 118.47 (CeH, Cc), 18.37 (CH3, Ce) MALDI-
To a solution of 238 mg (0.102 mmol) 16 in THF (50 mL) was
added dropwise
a solution of tetrabutylammonium fluoride
Please cite this article in press as: Stangenberg, R.; et al., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.03.037

R. Stangenberg et al. / Tetrahedron xxx (2014) 1e7
7
5. (a) Ornelas, C.; Aranzaes, J. R.; Salmon, L.; Astruc, D. Chem. dEur. J. 2008, 14,
50e64; (b) Binder, W. H.; Sachsenhofer, R. Macromol. Rapid Commun. 2007, 28,
15e54.
TOF (m/z): calcd for C269H184N36: 3919.6, found: no signal due to UV
laser induced decomposition.
6. Lewis, D. G.; Krasnova, L. B.; Skinner, P. J.; Fokin, V. V. Conductive Dendrimers
Obtained by Click Chemistry In Proceedings of the SPIE; 2010; p 10, 7755 Article
id. 775505.
Acknowledgements
7. Wu, P.; Feldman, A. K.; Nugent, A. K.; Hawker, C. J.; Scheel, A.; Voit, B.; Pyun, J.;
ꢀ
Frechet, J. M. J.; Sharpless, K. B.; Fokin, V. V. Angew. Chem., Int. Ed. 2004, 43,
We thank gratefully the Deutsche Forschungsgemeinschaft
(SFB625) for financial support.
3928e3932.
8. (a) Hoyle, C. E.; Bowman, C. N. Angew. Chem., Int. Ed. 2010, 49, 1540e1573; (b)
Becer, C. R.; Hoogenboom, R.; Schubert, U. S. Angew. Chem., Int. Ed. 2009, 48,
4900e4908.
Supplementary data
€
€
9. Wind, M.; Wiesler, U. M.; Saalwachter, K.; Mullen, K.; Spiess, H. W. Adv. Mater.
2001, 13, 752e756.
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2014.03.037.
10. Turp, D.; Nguyen, T.-T.-T.; Baumgarten, M.; Mullen, K. New J. Chem. 2012, 36,
282e298.
11. Binder, W. H.; Kluger, C. Curr. Org. Chem. 2006, 10, 1791e1815.
12. (a) Pandey, P.; Farha, O. K.; Spokoyny, A. M.; Mirkin, C. A.; Kanatzidis, M. G.;
Hupp, J. T.; Nguyen, S. T. J. Mater. Chem. 2011, 21, 1700e1703; (b) Su, D.; Menger,
F. M. Tetrahedron Lett. 1997, 38, 1485e1488.
References and notes
13. Barral, K.; Moorhouse, A. D.; Moses, J. E. Org. Lett. 2007, 9, 1809e1811.
14. Wu, J.; Grimsdale, A. C.; Mullen, K. J. Mater. Chem. 2005, 15, 41e52.
15. Chan, T. R.; Hilgraf, R.; Sharpless, K. B.; Fokin, V. V. Org. Lett. 2004, 6,
2853e2855.
16. Katritzky, A. R.; Wang, Z.; Tsikolia, M.; Hall, C. D.; Carman, M. Tetrahedron Lett.
2006, 47, 7653e7654.
17. Morgenroth, F. Chem. Commun. 1998, 1139e1140.
18. Wiesler, U.-M.; Mullen, K. Chem. Commun. 1999, 2293e2294.
19. Plietzsch, O.; Schilling, C. I.; Tolev, M.; Nieger, M.; Richert, C.; Muller, T.; Brase, S.
Org. Biomol. Chem. 2009, 7, 4734e4743.
1. (a) Moorefield, C. N.; Perera, S.; Newkome, G. R. Dendrimer Chemistry: Su-
pramolecular Perspectives and Applications In Dendrimer-Based Drug Delivery
Systems; John Wiley & Sons: 2012; pp 1e54; (b) Bosman, A. W.; Janssen, H. M.;
Meijer, E. W. Chem. Rev. 1999, 99, 1665e1688.
2. Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem., Int. Ed. 2001, 40,
2004e2021.
3. Camponovo, J.; Ruiz, J.; Cloutet, E.; Astruc, D. Chem. dEur. J. 2009, 15,
2990e3002.
4. (a) Lee, J. W.; Kim, J. H.; Kim, B.-K.; Kim, J. H.; Shin, W. S.; Jin, S.-H. Tetrahedron
2006, 62, 9193e9200; (b) Lee, J. W.; Kim, B.-K. Synthesis 2006, 4, 615e618.
Please cite this article in press as: Stangenberg, R.; et al., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.03.037