Incorporation of functional guest molecules into an internally functionalizable dendrimer through olefin metathesis

Article abstract of DOI:10.1021/ma050818a

A poly(aryl ether) dendrimer bearing 22 allyl groups throughout the interior of the molecule has been prepared using a convergent synthetic approach. The internal functionalities of this dendrimer can be used to attach small molecule guests to the interio

Full text of DOI:10.1021/ma050818a

6276
Macromolecules 2005, 38, 6276-6284
Incorporation of Functional Guest Molecules into an Internally
Functionalizable Dendrimer through Olefin Metathesis
Catherine O. Liang and Jean M. J. Fre´chet*
Department of Chemistry, University of California, Berkeley, California 94720-1460, and
Material Sciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road,
Berkeley, California 94720
Received April 18, 2005; Revised Manuscript Received May 18, 2005
ABSTRACT: A poly(aryl ether) dendrimer bearing 22 allyl groups throughout the interior of the molecule
has been prepared using a convergent synthetic approach. The internal functionalities of this dendrimer
can be used to attach small molecule guests to the interior of the dendrimer using olefin metathesis. A
ruthenium-based Grubbs catalyst was used to covalently attach an allylated pyrene and imidazolidinone
via cross-metathesis. The extent of coupling was estimated by UV, NMR, and elemental analysis data.
The high tolerance of cross-metathesis to a range of functional groups enables the incorporation of a
wide range of molecules and provides access to different inner environments in one step from a single
source of dendrimer.
Introduction
incorporated at the beginning of dendrimer synthesis
may be sensitive to the reaction sequence required for
dendrimer growth and may complicate preparation. In
the postmodification approach, a monomer repeat unit
bearing a functional “handle” that is capable of further
derivatization may be used in the construction of the
dendrimer. Once construction of the dendrimer has been
completed, the “handle” is modified to provide a func-
tionalized macromolecule in a single step and avoids
exposure of the newly incorporated functionality to the
dendrimer growth steps.22
This report describes the incorporation of an inter-
nally functionalizable handle that is compatible with
both dendrimer growth and subsequent transformation
steps into other functionalities. In line with the post-
modification approach, a poly(benzyl ether) dendritic
platform containing internal allyl ether groups at each
branched monomer was selected. The allyl group was
chosen as an internal moiety that is inert to dendrimer
growth steps and serves as a precursor to other func-
tionalities. The robust polyether backbone24 is rugged
enough to endure many different reaction conditions
and provides an electron-rich environment. A key
advantage of this approach is the ease of introduction
of the functionality of interest by modification of the
reactive handle, thus transforming the “generic” den-
drimer into an internally functionalized macromolecule
in a single step.
Derivatization of the macromolecule can be accom-
plished by olefin metathesis, which has become an
important carbon-carbon bond forming reaction in
organic synthesis.32-34 A particularly useful form of
olefin metathesis is cross-metathesis (CM) in which an
olefinic product is formed after joining two substituted
alkenes (Scheme 1), a reaction driven to completion by
evolution of volatile ethylene byproduct when terminal
olefins are selected as reactive partners. The ruthenium-
based catalysts used in olefin metathesis have excep-
tional functional group tolerance and are selective
toward olefins over alcohols, esters, aldehydes, acids,
and ketones.32 The utility of this metal-catalyzed reac-
tion for the preparation of polymers and natural prod-
ucts has been reviewed,32-34 and its application to the
In the 20 years that have followed their discovery,
dendrimers have been the object of numerous studies
seeking to exploit the unique molecular architecture and
physical properties of these macromolecules.1 The highly
branched, monodisperse dendrimers are characterized
by a globular morphology at higher generations and can
be segmented into periphery, interior, and core sections.
The well-developed anatomy of dendrimers has encour-
aged their use in a variety of applications including site
isolation,1-7 drug delivery,8-12 biomimetics,2,13-15 and
catalysis.2,4,16-21
Dendrimer repeat units and branches have tradition-
ally functioned as a skeleton and a connection between
the periphery and core; however, they also largely
control the characteristics of the nanoenvironment
generated within the dendrimer.18,19,22-24 Such local
environment is greatly influenced by the chemical
makeup and polarity of the repeat unit as well as its
chemical differentiation from the surrounding medium
in order to provide a unique interior context. For
instance, the influence of poly(aryl ether) branches on
the local nanoenvironment surrounding a solvato-
chromic probe located at the focal point or core of a
family of dendrimers was noted3 more than a decade
ago as the absorbance of the probe shifts with increasing
dendrimer generation. Aside affecting local polarity,
dendrimer repeat units may also provide a platform for
cooperativity between branches.25-30 The recognition of
their utility has prompted investigations into internal
manipulation and functionalization of the dendrim-
er.19,22,23
Functionalization of the dendrimer interior can be
achieved via either pre-19 or postmodification31 methods.
In the premodification strategy, monomer units that
contain the desired functional group are used in the
construction of the dendrimer framework. Including
functional groups at the start of the synthesis allows
for layering of different functionalities through the
stepwise growth sequence. However, functional groups
* Corresponding author. E-mail frechet@berkeley.edu.
10.1021/ma050818a CCC: $30.25 © 2005 American Chemical Society
Published on Web 06/23/2005

Macromolecules, Vol. 38, No. 15, 2005
Incorporation of Guest Molecules into Dendrimers 6277
Scheme 1. Cross-Metathesis of Terminal Olefins
Results in an Unsaturated Product and Ethylene
Gasa
The ester focal point of compound 9 was then reduced
to furnish the benzylic alcohol 10 and activated through
a bromination step to give 11. The electrophilic site of
11 was then allowed to react with diol 2 in a single
growth step, yielding a generation 2 dendron 12.
Repetition of the reduction, bromination, and ether
coupling steps through three more cycles afforded the
generation 5 dendrimer 21.
As a result of its versatility, the convergent synthesis
enabled the preparation of precisely layered dendrimers
with allyl functional handles at all, or some, of the
layers. The increase in molecular weight between den-
drimer generations was reflected in the size-exclusion
chromatography (SEC) peaks, which indicated de-
creased elution volumes as the size of the dendrimer
increased (Figure 1). The narrow SEC peaks were
characterized by a low polydispersity index (PDI) for
each generation of dendrimer and was measured as 1.02
for generation 5 dendrimer 21 obtained after four
consecutive growth cycles. Matrix-assisted laser desorp-
tion/ionization (MALDI) mass spectrometry data of
compound 21 revealed a mass of 11 002 Da, which is
within 0.04% of the expected mass (Figure 2). Overall,
both the SEC and MALDI data support the identity of
generation 5 dendrimer 21 having a low polydispersity.
a The second-generation Grubbs catalyst 1 is shown above.
preparation of unusual dendrimers has been pioneered
by Zimmerman and co-workers.35-40
Therefore, the internal allyl-functionalized dendrim-
ers prepared in this work have been tested in intermo-
lecular cross-couplings experiments between the allyl
handle and complementary small molecule guests. A
pyrene derivative was selected for incorporation into the
dendrimer since its UV absorbance could be used to
monitor and quantify its loading into the dendrimer.
Similarly, the covalent attachment of a catalytic mol-
ecule, an allyl imidazolidinone derivative useful in the
catalysis of Diels-Alder reactions, was studied with
generations 3 and 5 dendrimers.
In addition, atomic force microscopy (AFM) images
of dendrimer 21 in the dry state were obtained (Figure
3) showing large and small aggregates and perhaps even
isolated molecules on the mica surface. Images of two
different sized aggregates that are relatively uniform
in shape and size are observed and remain unchanged
after 24 h. Aggregation of the dendrimers may be
attributed to the attractive hydrophobic interactions
between the molecules and chain entanglement of the
tetradecyl periphery. A cross-sectional analysis of the
smaller structures (circled) reveals a height of ≈3.5 nm.
This is in accordance with the estimated size of a
generation 5 Fre´chet-type dendrimer.45
Intramolecular Metathesis of the (G-5) Den-
drimer. Recent advances in the development of cata-
lysts for metathesis reactions include a ruthenium-
based molecule containing a substituted N-heterocyclic
carbene ligand referred to as “Grubbs second-generation
catalyst” 1.46 This catalyst is particularly attractive as
its attributes include high activity, broad functional
group compatibility, mild reaction conditions, and ease
of use.
Intramolecular metathesis reactions were initially
explored with the (G-5) dendrimer 21. In the absence
of small molecule guests the dendrimer containing 22
allyl groups was treated with the Grubbs catalyst
(Scheme 3). A maximum of 11 “cross-links” between the
repeat units bearing allyl groups within the dendrimer
was possible. The resulting MALDI mass spectrum
(Figure 4) of the intramolecularly metathesized den-
drimer 22 showed a molecular weight of 10 787 Da (M
+ H), which represent a mass loss of 211 Da from the
starting material (10 998, M + H). This reduction in
weight corresponds to between 7 and 8 molecules of
ethylene (196-224), which in turn indicates the possible
formation of an equivalent amount of bonds within the
dendrimer. 7-8 internal “cross-links” per dendrimer out
of a possible 11 translates into 64-73% of allyl groups
participating in the metathesis reaction. In addition, the
SEC trace of compound 22 showed a monomodal peak
with a Mw/PDI of 8644 Da/1.02, which represents a mass
loss of 812 Da from the precursor 21 (Figure 4, inset).
Results and Discussion
Preparation of an Internally Functionalizable
Dendrimer. The dendrimer was prepared using a
convergent synthesis41 and a monomer bearing allyl
groups. Commercially available 3,5-dihydroxymethyl-
benzoate (2) was reacted with a substoichiometric
amount of allyl bromide to afford the mono- and bis-
allylated compounds 3 and 4, respectively, which were
separated through flash chromatography (Scheme 2).
Heating the monoallyl ether intermediate 3 furnished
the allyl-substituted Claisen rearranged products 5 and
6 isolated in a 1:2.7 ratio, respectively, after separation
by flash chromatography.42-44
The bis-allylated intermediate 4 was also subjected
to Claisen rearrangement conditions and the crude
purified to yield isomeric products 7 and 8 in an
approximately 1:2 ratio. At first glance, the doubly
allylated compound 8 appears very attractive for its
symmetry and its ability to introduce two allyl groups
simultaneously in the dendrimer layers. However, when
8 was used in the convergent synthesis of the den-
drimer, routine reactions on the ester focal point became
difficult to carry out. For example, reduction of the focal
ester groups to the corresponding primary alcohol with
lithium aluminum hydride required very long reaction
times at elevated temperatures, and activation of the
benzylic alcohol through a bromination step did not
proceed at all under routine conditions.41 These prob-
lems were attributed to the steric hindrance resulting
from the allyl substituents flanking both sides of the
reactive focal group in 8. To avoid the reactivity issues
encountered with the doubly substituted monomers
such as 8, dendrimer syntheses were exclusively carried
out with the monoallylated building blocks 5 and 6.
The convergent growth sequence of a generation 5
dendrimer began with the preparation of the peripheral
groups. Tetradecyl chain ends were chosen to ensure
compatibility with nonpolar solvents and to assist with
subsequent encapsulation of the interior functionalities.
To that end, monomer 6 was coupled to tetradecyl
bromide to yield compound 9 (Scheme 3).

6278 Liang and Fre´chet
Macromolecules, Vol. 38, No. 15, 2005
Scheme 2. Preparation of Allyl-Containing Monomer Repeat Unitsa
a Reagents and conditions: (a) allyl bromide; K2CO3, 18-crown-6, acetone 60 °C, 2 days; (b) o-dichlorobenzene, 180 °C, 2 days.
The lack of dendrimer “dimers” suggested that cross-
coupling between dendrimer molecules was avoided at
the reaction concentration of 2.0 mM even without
having to carry the reaction at ultrahigh dilutions.47,48
The 1H NMR spectrum of the metathesized compound
22 after metathesis was characterized by broadening
of the peaks (Figure 5i) when compared to the spectrum
of the (G-5) dendrimer precursor (Figure 5ii). Compari-
son of the integration values from the 1H NMR spectrum
of 22 provides quantitative information on the degree
of cross-linking within the dendrimer. Signals in regions
A, B, and C (Figure 5ii) correspond to the allyl group
(CH, 22 H), aromatic protons (ArH, 70 H), and ester/
tetradecyl protons (CO2CH3, (-OCH2(CH2)12CH3)32,
67 H), respectively. After metathesis, the remaining
unreacted allyl units in the dendrimer (Figure 5i, A)
were calculated from the integration value. This value
was normalized to the integration values from regions
B or C, which remain theoretically unchanged because
they do not participate in the reaction. This leads to an
estimated formation of 6.5-7.2 internal bonds, suggest-
ing that ca. 59-74% of the allyl groups participated in
olefin metathesis. These values correlate well with the
MALDI mass spectral data discussed previously.
Cross-Metathesis with an Allylated Pyrene De-
rivative. To investigate the ability of the dendrimer to
covalently incorporate guest molecules, a small molecule
guest that can be quantified by ultraviolet (UV) spec-
troscopy in an absorbance region distinct from the
absorbance signals of the dendrimer was chosen. The
absorbance maximum of allylated pyrene 24, easily
prepared from pyrene butanol 23, is at 344 nm, which
is within the transparent region of the UV spectrum of
the dendrimer. In addition to its UV characteristics and
ease of preparation, allylated pyrene 24 is aromatic,
which, we speculate, may promote its accumulation
within the polyaryl dendrimer through π-stacking.
Preparation of the guest molecule was accomplished
through treatment of the alcohol 23 with base and allyl
bromide to furnish 24 (Scheme 4).
molecular pathway and the limitations on selectivity of
the reactive partners, a mixture of products with
varying degrees of incorporation of both intramolecular
“cross-links” and pyrene moieties was expected. Follow-
ing purification of the dendrimer-pyrene conjugate,
SEC analysis of the purified product afforded a mono-
modal peak of molecular weight 9.0 kDa (based on
polystyrene standards) with a narrow polydispersity of
1.02.
Quantification of incorporated pyrene per gram of
conjugate material 25 was determined using UV mea-
surements. First, the molar absorptivity of the small
molecule pyrene derivative 24 was determined by
measuring the absorption of a series of dilutions. The
absorption intensity (344 nm) was plotted as a function
of sample concentration in THF. Applying Beer’s law,
the coefficient (ꢀ ) 46 234 M-1 cm-1) was determined
from the slope of the line (Figure 6).
With the extinction coefficient of the allylated pyrene
determined, the amount of the pyrene incorporated
inside the dendrimer-pyrene conjugate 25 was quanti-
fied. The absorption intensity of a series of dendrimer-
pyrene conjugate 25 dilutions was measured at the
pyrene absorption maximum of 344 nm (Figure 7).
Applying the previously determined molar absorp-
tivity coefficient suggests a loading of 460 ( 20 µmol of
pyrene per gram of conjugate. This value translates to
an average of ca. 5.7 molecules of pyrene per dendrimer
molecule; therefore, nearly 60% of the guest molecules
were incorporated into the dendrimer, which is signifi-
cant given that the dendrimer undergoes a competing
metathesis reaction through intramolecular cyclization.
Cross-Metathesis with a Catalytically Active
Imidazolidinone Derivative. The second functional
molecule chosen for inclusion within the dendrimer was
an imidazolidinone derivative. This organocatalytic
molecule has been shown to catalyze enantioselective
Diels-Alder additions, 1,3-dipolar cycloadditions, and
Friedel-Crafts alkylations.49-51 In addition to the cata-
lytic properties of the imidazolidinone derivative, this
molecule was chosen as a guest because it can be easily
synthesized with a pendant allyl group, and the nitrogen
content of the conjugate can be used to help quantify
the loading. Therefore, the imidazolidinone guest mol-
ecule was prepared via a convenient two-step procedure
from commercially available L-phenylalanine methyl
ester hydrochloride 26 (Scheme 5). Formation of the
amide 27 was followed by acid-catalyzed ring closure
Generation 5 dendrimer (G-5) 21 was mixed with 10
equiv of allylated pyrene 24 in the presence of Grubb’s
catalyst 1 to afford dendrimer conjugate 25 containing
bound dye molecules (Scheme 3). This metathesis
process was expected to lead to both intermolecular
coupling reactions involving the small molecule and the
dendrimer as well as intramolecular coupling reactions
within the dendrimer. Because of the competitive intra-

Macromolecules, Vol. 38, No. 15, 2005
Incorporation of Guest Molecules into Dendrimers 6279
Scheme 3. Convergent Growth of Generation 5 Dendrimer Containing 22 Inner Allyl Groupsa
a Reagents and conditions: (a) tetradecyl bromide, K2CO3, acetone, 40 °C, 2.5 days; (b) LiAlH4, THF, 0 °C-RT; (c) CBr4, PPh3,
iPr2NEt, THF; (d) 2, K2CO3, acetone, 60 °C, 2 days; (e) 6, K2CO3, acetone, 60 °C, 2 days; (f) 5, K2CO3, acetone, 60 °C, 2 days.
and treatment with HCl to give the product 28. An
excess of the guest molecule 28 was combined with the
(G-3) dendrimer 15 or the (G-5) dendrimer 21 in the
presence of the second-generation Grubbs catalyst 1.
The dendrimer-imidazolidinone conjugate products
(G-3)-imid. 29 and (G-5)-imidazolidinone 30 were pre-
cipitated from methanol as a low-melting solid while
excess small molecule impurities were soluble in metha-
nol and eliminated in the filtrate.
drimer if one assumes that no intramolecular metath-
esis occurs within the dendrimer itself. However, since
intramolecular “cross-linking” of the dendrimer is a
competing reaction, a mixture of intra- and intermo-
lecular coupled products was again expected. Analysis
of the product by MALDI mass spectrometry revealed
discrete peaks corresponding to the attachment of 1-4
small molecules to the macromolecule (Figure 8). The
peak labeled 29a with a mass of 2831 matches that
expected for a dendrimer with two internal “cross-links”
and one imidazolidinone derivative. Peak 29e with a
mass of 3536 Da, also visible in the spectrum, matches
Reaction of the small molecule guest 28 with the
(G-3) macromolecule 15 can only lead to a maximum
theoretical loading of five imidazolidinones per den-

6280 Liang and Fre´chet
Macromolecules, Vol. 38, No. 15, 2005
of the broad peak, 10.6 kDa, approximates a completely
internally “cross-linked” particle with no imidazolidi-
nones (10 682 Da). The detectable upper limit of the
observed distribution, 13.7 kDa, corresponds to the
incorporation of ≈13 molecules of 28 per dendrimer
with formation of up to four internal “cross-links”
(13 686 Da).
Although MALDI mass spectrometry is not a quan-
titative measurement, it does provide relative abun-
dances as in this example where the ionization efficiency
of the various products was likely to be similar to one
another. The most abundant peak at 12.2 kDa cor-
responded to approximately 7 molecules of 28 per
dendrimer and 7 internal “cross-links” (12 307 Da). As
in the case of the reaction with the lower generation
dendrimer, separation of the individual products by SEC
or silica gel chromatography was not feasible.
Figure 1. Overlapping SEC traces comparing generation 1-5
compounds with methyl ester focal points (9, 12, 15, 18, 21).
The nitrogen content of compound 30 (1.38%), corre-
sponding to 493 µmol of imidazolidinone residue per
gram of conjugate material, suggests an average of six
cross-couplings per macromolecule, in agreement with
the MALDI data. This suggests that 27% of all possible
olefinic sites within dendrimer 21 were cross-coupled
with the imidazolidinone derivative 30.
Complete loading of the dendrimer 21 with small
molecule guests 24 or 28 is unlikely considering the fact
that the competing metathesis coupling is an intra-
molecular reaction. The compact, globular nature of the
larger dendrimer results in close packing of the allyl-
containing branches, which aids in the reaction between
allyl units on proximal branches. In addition, contrac-
tion of the dendrimer morphology may be further
encouraged by the tendency of the dendrimer to mini-
mize the interaction between the electron-rich poly(aryl
ether) interior and the nonpolar hexane solvent, en-
hancing proximity between branches. The effective
increase in local concentration of allyl groups belonging
to the branches of the macromolecule favors intra-
molecular coupling within the dendrimer over intermo-
lecular dendrimer-guest coupling. Another factor lim-
iting the amount of the imidazolidinone salt 28 incorp-
orated into the dendrimer cavities is the charge-charge
repulsion that is experienced by the small molecule. The
tendency of charged molecules to repel one another
would make it unlikely for the imidazolidinone HCl salt
to accumulate into the interior of the dendrimer, reduc-
ing both the local concentration of allylated 28 and the
likelihood of 28 cross-coupling with a dendritic allyl
group. Given these considerations, the ability to incor-
porate an average of 4 and 6 guest molecules 28 into
(G-3) and (G-5) dendrimers, respectively, is significant
since the competitive intramolecular “cross-linking”
path of the dendrimer is likely to be favored.
Figure 2. MALDI mass spectrum of the generation 5 com-
pound 21.
the mass of a dendrimer containing four imidazolidinone
units and no “cross-links”. While MALDI was a helpful
technique in detecting single ion mass peaks (Table 1),
actual isolation of discrete products by SEC or silica gel
chromatography could not be achieved.
Nitrogen analysis also proved convenient to estimate
the amount of catalytic residues per gram of conjugate.
Therefore, elemental analysis of the (G-3)-imidazolidi-
none product 29 indicated a nitrogen content of 2.32%.
This value corresponds to 829 µmol of imidazolidinone
groups per gram of product. On the basis of this
calculation, an average incorporation of close to three
catalytic residues per dendrimer molecule or 60% func-
tionalization of the allyl bearing sites can be calculated.
This average is in line with MALDI mass spectra data,
which confirmed the presence of products containing
between 1 and 4 guest molecules.
To further favor intermolecular cross-coupling reac-
tions and maximize guest loading, the (G-5)-dendrimer
21 was reacted with 9 equiv of the imidazolidinone
derivative 28 per allyl site within the macromolecule.
This metathesis reaction could theoretically lead to the
incorporation of 22 guest molecules or, in the absence
of intermolecular couplings, the formation of 11 “cross-
links”. Once again, a mixture of intra- and intermolecu-
lar metathesis products was expected. The large number
of possible cross-metathesis products from (G-5)-imida-
zolidinone couplings result in a broad, undefined dis-
tribution as observed by MALDI MS (Figure 9). In
theory, the lowest and highest MW products that can
possibly be generated from the reaction are the com-
pletely internally “cross-linked” molecule at 10.7 kDa
and the fully cross-coupled 22 imidazolidinone contain-
ing product at 15.7 kDa, respectively. The lower limit
SEC chromatograms of the (G-5) product 30 have an
observed polystyrene equivalent molecular weight (Mw)
of 9087 Da and Mw/Mn 1.02. The data acquired from
SEC greatly underestimate molecular weight when
compared to the MALDI mass data, which clearly show
the presence of products with MW ranging from 10.5 to
13.7 kDa. The underestimation of SEC data is expected
given that linear polystyrene standards were used for
calibration and that the higher generation globular
dendrons exhibit a decreased hydrodynamic volume due
to their globular shape.
For the lower generation dendrimers, the observed
SEC data is closer to the theoretical value. In the case
of the (G-3)-imidazolidinone conjugate 28, the observed

Macromolecules, Vol. 38, No. 15, 2005
Incorporation of Guest Molecules into Dendrimers 6281
Figure 3. AFM image of large and small aggregates of generation 5 dendrimer 21 (left). Cross-sectional analysis of small aggregate
(right).
Scheme 4. Preparation of Allyl Pyrene Butyl Ether
Compound 24a
a Reagents and conditions: KH, dichloromethane, allyl
bromide, 6 h, 0 °C-RT.
“dimer” formation between the macromolecules may be
attributed to the presence of the long chain ends, which
may help encapsulate the core, and to the position of
the allyl groups buried deep throughout the interior of
the dendrimer.
Figure 4. MALDI mass spectrum and SEC trace (inset) of
metathesized (G-5)-dendrimer 22.
Evaluation of the Imidazolidinone-Loaded Den-
drimer. To test whether intramolecular “cross-linking”
impaired access to the dendrimer, the dendrimer-
imidazolidinone conjugate 30 was evaluated for its
ability to catalyze the [4 + 2] cycloaddition between
cinnamaldehyde and cyclopentadiene in decane (Scheme
6). Reaction progress was monitored through consump-
tion of the aldehyde and followed by gas chromatogra-
phy. Although the kinetic investigation was complicated
due to the complexity of the dendrimer system, which
contains a number of different catalytic species, a
comparison of reaction progress with time provided
some qualitative insight into the performance of the
different catalysts.
At a 1.0 M reaction concentration in decane and in
the presence of 5 mol % of catalyst, the conversion of
cinnamaldehyde after 3 days was 73% for the small
molecule catalyst 28 and 69% for the (G-5)-imidazoli-
dinone conjugate 30 containing reactions (Table 2).
Because of the intrinsic reactivity of the two molecules
used in this Diels-Alder reaction, the uncatalyzed
control reaction proceeded to an extent of 42%. The
macromolecular catalyst 30 could be recovered from the
reaction mixture by precipitation in methanol and
reused under the same reaction conditions. Progress of
the reaction after 1 day reached 32% for the recycled
catalyst, which was comparable to the 35% conversion
observed for the freshly prepared material.
Figure 5. 1H NMR spectra of (i) intramolecularly metathe-
sized product 22 and (ii) (G-5)-dendrimer 21 in CDCl3.
polystyrene equivalent Mw of 3770 Da and Mw/Mn 1.01
is comparable to MALDI mass data (2.8-3.5 kDa).
Further analysis of the SEC chromatograms indicated
a monomodal peak for both products 29 and 30. The
chromatography data showed a narrow polydispersity
(1.01-1.02) and the absence of molecular weight species
corresponding to dimerized macromolecules. Although
olefin metathesis of allyl-containing dendrimers can
result in unwanted dimerization between macromol-
ecules especially at high reaction concentrations,35,38,48
intermolecular metathesis between (G-5) dendrimers
bearing 22 allyl groups was avoided with reaction
concentrations up to 3 mM. The ability to prevent
To verify that the structural integrity of the imida-
zolidinone was not affected by the conditions used

6282 Liang and Fre´chet
Macromolecules, Vol. 38, No. 15, 2005
Figure 6. Absorbance spectra of allylated pyrene 24 at various concentrations (left). Beer’s law plot of absorbance intensity at
344 nm with respect to concentration (right).
Figure 8. MALDI mass spectrum of (G-5)-imidazolidinone
conjugate 29.
Figure 7. UV absorption spectra of the allylated pyrene
monomer 24, dendrimer-pyrene conjugate 25, and dendrimer
21.
Scheme 5. Preparation of Compound 28 and
Subsequent Coupling with Dendrimersa
Figure 9. MALDI mass spectrum of (G-5)-imidazolidinone
conjugate compound 30.
Table 1. Products Identified in the MALDI Mass
Spectrum for Compound 29
imidazolidinone
obsd calcd value
residues per dendrimer cross-links value
(M + H)+
29a
29b
29c
29d
29e
1
2
3
3
4
2
1
1
0
0
2831
3076
3292
3319
3536
2831
3075
3292
3320
3536
a Reagents and conditions: (a) allylamine, RT, N2, 1 day;
(b) acetone, methyl alcohol, p-TSA, 60 °C, 1.5 days;
(c) dendrimer 21 or 15, Grubbs catalyst 1, dichloromethane,
45 °C.
the uncatalyzed control reaction reached a conversion
of 20% (Figure 10). As can be seen in Figure 10, the
conversion achieved with the monomeric catalyst 28
essentially matched that obtained with the dimer,
indicating that exposure of the imidazolidinone to
metathesis conditions does not impair its catalyst activ-
ity.
during its coupling by metathesis, thus affecting its
potential as a catalyst, the monomeric catalyst 28 was
homocoupled to give the dimer 31 (Scheme 7) and then
tested in the same Diels-Alder reaction.
Because 31 had limited solubility in decane, the
reaction had to be carried out in methanol, a medium
in which the reaction proceeds at a significantly faster
rate. Therefore, conversion of the cinnamaldehyde in the
presence of catalyst 31 reached 96% within 22 h while
The data obtained in these experiments also confirms
that the formation of intramolecular “cross-links” by
metathesis within the dendrimer does not noticeably
impair transport of small molecule reagents into the
interior of the dendrimer.

Macromolecules, Vol. 38, No. 15, 2005
Incorporation of Guest Molecules into Dendrimers 6283
Acknowledgment. Funding for this research was
provided by the National Science Foundation (DMR-
0317514) and, in part, the Biomolecular Program of the
Department of Energy at LBNL (DE-AC03-76SF00098).
C.L. also thanks the Eastman-Kodak Company for
fellowship support.
Supporting Information Available: Details on the syn-
thesis and characterization of dendrimers, guest molecules,
dendrimer-guest conjugates, and catalysis experiments. This
material is available free of charge via the Internet at
http://pubs.acs.org.
References and Notes
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The convergent preparation of a monodisperse poly-
(aryl ether) dendrimer containing allyl groups located
throughout the interior of the molecule enables the
attachment of guest molecules through olefin metath-
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