A new solid-supported iterative divergent/convergent strategy for the synthesis of dendrimers

Article abstract of DOI:10.1016/S0040-4039(01)00058-2

A rapid and convenient solid-supported iterative divergent/convergent approach was developed to prepare rigid phenylacetylene dendrimers. The generation number grows very rapidly and the purification at each step is very simple.

Full text of DOI:10.1016/S0040-4039(01)00058-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 2181–2184
A new solid-supported iterative divergent/convergent strategy for
the synthesis of dendrimers
Chunyan Chi, Jishan Wu, Xianhong Wang,* Xiaojiang Zhao, Ji Li and Fosong Wang
State Key Laboratory of Polymer Physics and Chemistry, Open Laboratory of Polymer Chemistry,
Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China
Received 9 November 2000; revised 3 January 2001; accepted 10 January 2001
Abstract—A rapid and convenient solid-supported iterative divergent/convergent approach was developed to prepare rigid
phenylacetylene dendrimers. The generation number grows very rapidly and the purification at each step is very simple. © 2001
Elsevier Science Ltd. All rights reserved.
Dendrimers are highly-branched, perfectly symmetrical,
tree-like macromolecules emanating from a central
core. The advent of dendrimers represents a major
breakthrough in synthetic chemistry. Recently they
have evolved from a laboratory curiosity into an impor-
tant trend in current chemistry, attracting increasing
attention from a broad community of scientists.
method takes the reverse course. The skeleton is con-
structed stepwise starting from the end groups towards
the inside and is finally treated with a multifunctional
core molecule to yield the dendrimers. Scheme 1 (right)
shows the scheme for the convergent approach.
Problems usually occur in the divergent approach from
the incomplete reaction of the end groups, since these
structural defects accumulate with the build-up of the
next generation. Because the by-products have very
similar physical properties, chromatographic separation
is not always successful. Hence, higher generations of
divergently built-up dendrimers always contain certain
structural defects. In the convergent method, a segment
growing with each reaction step is coupled with only
one branching unit. It is usually difficult to construct
Dendrimers can usually be synthesized by either a
convergent1 or a divergent approach.2 In the divergent
approach, the growth of dendrimers starts from a
multi-functional core, and one branching unit after
another is attached to the core molecule step by step.
Through a series of reaction and purification, the den-
drimers grow outwards until steric effects prevent fur-
ther reactions of the end groups. Scheme 1 (left) shows
a scheme for the divergent approach. The convergent
Scheme 1. The divergent (left) and convergent (right) strategy for synthesis of dendrimers.
* Corresponding author.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00058-2

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C. Chi et al. / Tetrahedron Letters 42 (2001) 2181–2184
higher generations due to the steric problems arising
from the reaction of segments and the core molecule.
phenol was converted into its potassium salts with
K2CO3 in acetone, and 3,5-diiodo-4-ethoxy-nitrobenzen
1 was obtained in 95% yield by addition of ethyl iodide.
The nitro group in compound 1 was reduced into an
amino group by reacting with SnCl2·2H2O in alcohol at
elevated temperature, 3,5-diiodo-4-ethoxy-aniline 2 was
obtained in 98% yield. Reaction of compound 2 with
BF3·Et2O and tert-butyl nitrite at −20°C gave (3,5-
diiodo-4-ethoxy) diazonium tetrafluoroborate 3 in 90%
yield. The resulting diazonium tetrafluoroborate salt
reacted with n-propylaminomethyl polystyrene5 under
basic conditions like (K2CO3) in DMF to give polymer-
supported aryliodides 4. Finally, the Heck–Cassar–
Sonogashira–Hagihara reaction6 of compound 4 and
excess trimethylsilylacetylene in the presence of
Pd(dba)2–CuI–PPh3 gave the polymer-supported
monomer 5.
The reactions of the end group in the solid-phase
synthesis of dendrimers were completed by using large
excesses of reagents and the product was purified easily
by extensive washing.3,4 Therefore, the difficulty derived
from incomplete reactions or steric problems for diver-
gent or convergent routes may be overcome. In this
communication, a rapid and convenient solid-supported
iterative divergent/convergent approach was developed
to prepare dendrimers. The advantages of this
approach are that the generation number grows very
rapidly and the purification at each step is very simple.
Scheme 2 outlines the synthetic approach. A solid-sup-
ported monomer with two inactive end groups X was
divided into two portions. In one portion, the end
group X was activated by converting to X%. The other
portion was activated by breaking the covalent link
between the monomer and solid resin to give an active
monomer bearing a Y% group at the core. Cross-cou-
pling reaction of the two activated portions eliminated
X%Y%, forming the solid-supported second generation
monodendron, a type of asymmetric dendrimer, pos-
sessing the same end groups as the monomer. This
procedure can be repeated with a doubling of genera-
tion number after each iteration, while the generation
number grows step by step in either the divergent or
convergent strategy. Moreover, large excess of reagents
used in this procedure causes the purification process to
be as simple as a matter of extensive washing, whereas
purification is a repeated and time-consuming in either
the divergent or the convergent strategy. Therefore, in
this approach, the generation number grows exponen-
tially and the purification at each step is very simple. At
The starting monomer 5 was then divided into two
portions. The trimethylsilyl groups in one portion were
removed and replaced with hydrogen atoms by reaction
with tetrabutylammonium fluoride (TBAF) in THF to
give polymer-supported diacetylene P-G1-(H)2. The
other portion was heated to 115°C in methyl iodide in
a sealed tube to give aryl iodide I-G1-(TMS)2.4 Similar
Heck–Cassar–Sonogashira–Hagihara reaction of P-G1-
(H)2 and I-G1-(TMS)2 gave the second generation poly-
mer-supported monodendron P-G2-(TMS)4. This
procedure was repeated with a doubling of generation
number after an iteration to give the fourth generation
polymer-supported
monodendron
P-G4-(TMS)16,
which was followed by deprotection of the triazene
linkage from the solid support with MeI to give the
highly soluble fourth generation monodendron I-G4-
(TMS)16.
the same time, both the core (P-Gn-(X%) ) and the
n
branching unit (Y%-Gn-(X) ) grow during th2e formation
Transmittance FT-IR spectroscopy followed the whole
solid-phase approach. The peaks at 2157 ( 1) cm−1 in
P-G1-(TMS)2, P-G2-(TMS)4 and P-G4-(TMS)16 were
characteristic of the stretching vibration for a car-
bonꢀcarbon triple bond in trimethylsilyl-protected
acetylenes. However, after desilylation, the peak at
3311 cm−1 was observed in P-G1-(H)2 and P-G2-(H)4,
which was characteristic of the stretching vibration for
carbon–hydrogen in the terminal acetylene. I-G1-
(TMS)2 and I-G2-(TMS)4 were confirmed by NMR and
EI-MS. As for I-G4-(TMS)16, its molecular weight was
n
2
of the molecular skeleton, indicating that both diver-
gent and convergent concepts were involved. Therefore,
such a synthetic strategy overcomes the shortcomings
existent in both divergent and convergent routes. This
approach was employed to prepare phenylacetylene
dendrimers, which are promising electroluminescent
and NLO materials.
The Merrifield’s peptide resin-supported monomer was
prepared according to Scheme 3. 2,6-Diiodo-4-nitro-
Scheme 2. Solid-supported iterative divergent/convergent strategy for synthesis of dendrimers.

C. Chi et al. / Tetrahedron Letters 42 (2001) 2181–2184
2183
Scheme 3. Synthesis of phenylacetylene dendrimers by a solid-supported iterative divergent/convergent approach. (a) TBAF,
THF; (b) MeI, 115°C; (c) Pd(dba)2–CuI–PPh3, 2:1 (v/v) NEt3/THF, 70°C.
References
confirmed by matrix-assisted laser desorption/ioniza-
tion mass spectroscopy (MALI-MS 3804.4), and four
distinguished peaks from 7.808 to 7.558 ppm with
integration of 1:2:4:8 were observed in its 1H NMR
spectrum.7
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7. Selected characterization data of the first, second and
fourth generation monodendrons.
In conclusion, an efficient solid-supported iterative
divergent/convergent synthetic strategy was developed
to prepare soluble phenylacetylene dendrimers. The
advantages of this approach are that the generation
number grows very rapidly and the purification at each
step is very simple.
I-G1-(TMS)2: IR 2959, 2899, 2156, 1559, 1477, 1442,
1385, 1249, 1002, 843, 759, 700, 651 cm−1; H NMR (400
MHz, CDCl3) l 7.67 (s, 2H), 4.24 (q, J=14 Hz, 2H), 1.41
(t, J=7.2 Hz, 3H), 0.24 (s, 18H); EI-MS. Calcd for [M]+:
m/e 440. Found: m/e 440.
1
Acknowledgements
This work was supported by the key basic research
grants in the Ninth Five-year Plan of the Chinese
Academy of Sciences, and National Natural Science
Foundation under 20074036.
I-G2-(TMS)4: IR 2959, 2899, 2217, 2156, 1561, 1478,
1
1447, 1384, 1249, 1033, 1006, 843, 759, 698, 649 cm−1; H
NMR (400 MHz, CDCl3) l 7.71 (s, 2H), 7.52 (s, 4H), 4.33
(overlapping q, J=14 Hz, 6H), 1.46 (overlapping t, J=7.2

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C. Chi et al. / Tetrahedron Letters 42 (2001) 2181–2184
Hz, 9H), 0.26 (s, 36H); 13C NMR (100 MHz, CDCl3) l
649, 615 cm−1; 1H NMR (400 MHz, CDCl3) l 7.81 (s, 2H),
7.64 (s, 4H), 7.60 (s, 8H), 7.56 (s, 16H), 4.37 (overlapping
q, J=14 Hz, 30H), 1.50 (overlapping t, J=7.2 Hz, 45H),
0.265 (s, 144H); 13C NMR (100 MHz, CDCl3) l 162.06,
161.06, 146.60, 136.67, 136.30, 118.23, 99.86, 92.41, 84.78,
70.38, 69.97, 29.66, 16.00, 15.77, −0.213; MALDI-TOF
MS: calcd for [M]+: m/e 3805.7. Found: m/e 3804.4.
162.08, 160.78, 141.59, 136.62, 119.81, 118.22, 117.99,
99.87, 99.79, 92.93, 85.31, 84.08, 70.31, 69.95, 15.94,
15.76, −0.221; EI-MS. Calcd for [M]+: m/e 920. Found:
m/e 919.
I-G4-(TMS)16: IR 2960, 2898, 2216, 2156, 1588, 1558,
1478, 1446, 1384, 1249, 1104, 1034, 1008, 842, 758, 698,
.