Synthesis of difunctionalized dendrimers: An approach to main-chain poly(dendrimers)

Article abstract of DOI:10.1016/S0040-4039(02)01656-8

Synthesis of benzyl ether dendrimers that are difunctionalized at their peripheries are described. These dendrimers should form the basis for a new class of main-chain dendritic polymers. The steric protection afforded at higher generation during the synt

Full text of DOI:10.1016/S0040-4039(02)01656-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 7217–7220
Synthesis of difunctionalized dendrimers: an approach to
main-chain poly(dendrimers)
Renuka N. Ganesh, Joshua Shraberg, Patrick G. Sheridan and S. Thayumanavan*
Department of Chemistry, Tulane University, New Orleans, LA 70118, USA
Received 15 July 2002; accepted 7 August 2002
Abstract—Synthesis of benzyl ether dendrimers that are difunctionalized at their peripheries are described. These dendrimers
should form the basis for a new class of main-chain dendritic polymers. The steric protection afforded at higher generation during
the synthesis allows for facile access to these selectively functionalized dendrimers. © 2002 Elsevier Science Ltd. All rights
reserved.
Dendrimers have attracted a lot of attention among
chemists over the past decade due to the potential
applications in several areas of chemistry.1 For exam-
ple, dendritic architectures have found use in areas such
as catalysis,2 biomimetics,3 supramolecular chemistry,4
surface chemistry,5 light harvesting materials,6 and
medicine.7 The need for synthesizing new dendrimers
has increased dramatically with such application-ori-
ented interests in this class of macromolecules. We have
been interested in synthesizing dendrimers that have
only two reactive functional groups in their periphery.
Such dendrimers are useful as monomer units in new
polymeric architectures, as schematically illustrated in
Fig. 1.
mers such as the types shown in Fig. 1. To achieve
these main-chain polymeric dendrimers, it is necessary
that we specifically functionalize the dendrimers, such
that only two of the peripheral monomers have poly-
merizable functional groups. For this purpose, between
the two limiting synthetic approaches, convergent syn-
thesis is preferred due to the control it provides.11
Fre´chet and co-workers have developed protocols
where they synthesized dendrimers with limited number
of cyano groups in the dendritic periphery.12,13 More
recently, Schlu¨ter and co-workers have developed a
similar strategy in which bromo functionalities were
incorporated in specific locations of a benzyl ether
dendrimer.14 Also notable is a particularly elegant
approach developed by Simanek and co-workers, where
the synthetic viability of incorporating functionalities in
specific locations of a dendrimer is high.15 However, we
embarked on developing the synthetic protocols out-
lined here, because of the following: (a) We are inter-
ested in developing synthetic methodology for benzyl
ether dendrimers, a backbone that we have used for our
new amphiphilic dendrimer design.16 Our long-term
goal is to synthesize polymers of the type shown in Fig.
The supramolecular architecture arising from such
polymers should be interesting. For example, Schlu¨ter
and co-workers have incorporated dendrons as side
chains of polymers such as polystyrene and poly(p-
phenylene) and have observed the formation of
nanocylinders.8–10 This observation sparked our interest
in probing dendritic architectures in which the den-
drimer is part of the main chain. In particular, we are
interested in synthesizing amphiphilic block co-poly-
Figure 1. Polymer architectures achievable with difunctionalized dendrimers: (a) alternating main-chain copolymer of a dendrimer
and a linear chain; (b) polymer with dendrimer repeat units; (c) polymers containing two different dendrimers as alternating
comonomers; (d) polymerized dendrons.
* Corresponding author. Tel.: +1-504-862-3586; fax: +1-504-865-5596; e-mail: thai@tulane.edu
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01656-8

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R. N. Ganesh et al. / Tetrahedron Letters 43 (2002) 7217–7220
1 with these amphiphilic dendrimers. (b) We are inter-
ested in incorporating phenolic functional groups at
specific locations in the periphery, since these are ver-
satile polymerizable functionalities; for example, they
can react with diisocyanates. Some of the poly(den-
drimer) architectures that could be synthesized with our
current approach are represented in Fig. 1. The difunc-
tionalized dendrimers can be polymerized by reacting
with a diisocyanate comonomer. This comonomer
could be a hydrophilic oligomer, which can generate an
alternating copolymer containing a hydrophobic den-
drimer and a hydrophilic linear oligomer as the repeat
units (structure a, Fig. 1). Alternately, the comonomer
could be a short hydrophobic linker such as phenyldi-
isocyanate, which should afford essentially a homo-
polymer (structure b, Fig. 1). It is also possible to
incorporate complementary reactive functionalities in
two different difunctionalized dendrimers and copoly-
merize them to obtain alternating copolymers, as shown
by the structure c in Fig. 1. Since we are synthesizing
benzylether based dendrimers, it is also possible to
envision using a dendron that has a hydroxymethyl
group at the core and a single phenolic group at the
periphery to synthesize poly(dendrons) as illustrated by
the structure d in Fig. 1.
are unstable to the alkylation conditions of potassium
carbonate in acetone, THF or DMF. Therefore, we
used phenacyl group as the protecting group. The
phenacyl group has been previously demonstrated by
Hawker to be stable under benzyl ether dendrimer
assembly conditions.18 The synthesis of the first genera-
tion dendrimer is shown in Scheme 1. Treatment of
phenacyl bromide with 3-hydroxybenzyl alcohol (1)
afforded the phenacyl protected product 2 in 51% yield.
The hydroxymethyl group of 2 was converted to bro-
momethyl group to afford 3 in 86% yield. Treatment of
3,5-dihydroxybenzyl alcohol (4) with just 1 equiv. of
benzyl bromide afforded the monosubstituted product
6 in 29% yield. The rest of the product mixture con-
tained the disubstituted product 5. Compound 5 was
carried over to assemble the second-generation den-
drimer (see below). The reaction between 3 and 6 in the
presence of potassium carbonate in acetone afforded
the product 7 in 61% yield. The hydroxymethyl moiety
of 7 was converted to bromomethyl moiety using
triphenylphosphine and carbon tetrabromide to afford
8 in 95% yield. Treatment of the compound 8 with 0.5
equiv. of 4,4%-dihydroxybiphenyl (9) in THF afforded
the difunctionalized first generation dendrimer 1020 in
88% yield. When this reaction was carried out in ace-
tone, the yield of the product 10 was not optimal.
Improved yields were realized when the reaction was
carried out in THF. Deprotection of the phenacyl
group was facilitated by treating compound 10 with
zinc and acetic acid to afford the corresponding diphe-
nolic dendrimer.
We report here the synthesis of two difunctionalized
dendrimers. The functionalities that we have incorpo-
rated in these benzyl ether dendrimers are phenolic
functionalities. Since the assembly of the benzyl ether
dendrimers themselves heavily uses phenolic groups,17
we protected this functionality. First, we attempted the
use of tert-butyldimethylsilyl moiety as the protecting
group. However, we noted that these functional groups
The assembly of the second generation of the difunc-
tionalized dendrimer is shown in Scheme 2. The disub-
Scheme 1.

R. N. Ganesh et al. / Tetrahedron Letters 43 (2002) 7217–7220
7219
Scheme 2.
the mono- and disubstituted products, it is clear that
monosubstitution during the synthesis of higher genera-
tion dendrimers is easier due to steric protection. We
observed this phenomenon with even higher generation
dendrons in other systems.19 The unique topography of
the difunctionalized dendritic monomers reported
herein should permit the generation of novel main-
chain dendritic polymers. Progress towards achieving
such polymers is currently under way in our
laboratories.
stituted by-product 5 was treated with triphenylphos-
phine and carbon tetrabromide to afford the bro-
momethyl functionalized compound 11. Treatment of
11 with 1 equiv. of 4 afforded the monosubstituted
product 12 in 85% yield. Note that a similar reaction
with 1 equiv. of benzyl bromide in Scheme 1 afforded
only 29% yield. The higher yield obtained in the synthe-
sis of 12 is attributed to the increased steric protection
of the second phenolic group. After the first dendron is
substituted on to one of the phenolic groups of 4, the
second phenolic group becomes less reactive due to the
steric hindrance between the incoming dendron and the
one already substituted. Treatment of the compound 12
with 8 in the presence of potassium carbonate afforded
13 in 70% yield. Conversion of the hydroxymethyl
group to bromomethyl group was accomplished using
triphenylphosphine and carbon tetrabromide to afford
14 in 45% yield. Treatment of compound 14 with 0.5
equiv. of 9 afforded the second-generation difunctional-
ized dendrimer 15 in 70% yield.20
Acknowledgements
We are grateful to U.S. Army Institutes of Health
(NIGMS) for support. S.T. is a Cottrell Scholar
(Research Corporation) and an NSF-Career awardee.
Infrastructural support through Center for Microfabri-
cation (NSF-EPSCoR) and Tulane Institute for Macro-
molecular Engineering and Sciences (NASA) are
gratefully acknowledged.
In summary, we have outlined the synthesis of polymer-
izable, difunctionalized dendrimers. For this synthesis
to be facile, it is necessary to have one of the two
phenolic groups in dihydroxybenzyl alcohol more reac-
tive than the other. Although the synthesis of the first
generation dendrimers afforded statistical mixture of
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