Thermally reversible dendronized step-polymers based on sequential Huisgen 1,3-dipolar cycloaddition and diels-alder "click" reactions

Article abstract of DOI:10.1021/ma902180r

Thermally labile dendronized AA-BB step polymers are described. First through third generation dendritic bisfuran monomers 6a-6c were prepared in part by the Cu(I)-catalyzed azide-alkyne Huisgen 1,3-dipolar cycloaddition reaction and in turn polymerized b

Full text of DOI:10.1021/ma902180r

1270 Macromolecules 2010, 43, 1270–1276
DOI: 10.1021/ma902180r
Thermally Reversible Dendronized Step-Polymers Based on Sequential
Huisgen 1,3-Dipolar Cycloaddition and Diels-Alder “Click” Reactions
Nathan W. Polaske,† Dominic V. McGrath,*,† and James R. McElhanon*,‡
‡
†Department of Chemistry, University of Arizona, Tucson, Arizona 85721 and Organic Materials Department,
Sandia National Laboratories, Albuquerque, New Mexico 87185
Received October 2, 2009; Revised Manuscript Received December 8, 2009
ABSTRACT: Thermally labile dendronized AA-BB step polymers are described. First through third
generation dendritic bisfuran monomers 6a-6c were prepared in part by the Cu(I)-catalyzed azide-alkyne
Huisgen 1,3-dipolar cycloaddition reaction and in turn polymerized by the reversible furan-maleimide
Diels-Alder reaction. The Diels-Alder reaction conditions were optimized through end-capping studies
with N-phenylmaleimide (7). Dendronized step polymers 10a-10c were then formed from reaction with
bismaleimide 9 and their assembly, disassembly, and reassembly behavior studied by GPC.
Introduction
drons began with the synthesis of the general scaffold. By
preparing a symmetric molecule containing two furan
Dendritic polymers are an interesting class of macromolecular
architectures that have generated much attention in recent years.1
The ability to readily derivatize these compounds while fine-
tuning their properties is highly desirable as it allows for rapid
production and screening of novel materials. The efficient and
selective nature of cycloaddition (CA) reactions2 lend themselves
well to the synthesis and modification of dendritic and other
hyperbranched polymers.3 Among the CA reactions, the azide-
alkyne Huisgen 1,3-dipolar CA4 has become a useful method for
peripheral modification of dendrimers and dendritic polymers,5
while the [4 þ 2] Diels-Alder (DA) CA6 has been widely used
in dendritic polymerizations.7 Because of their high reliability,
selectivity, robust character, and the availability of starting
materials, these two CAs have been included in the select group
of “click chemistry” reactions.8
groups and two terminal alkynes, nonreversible functionali-
zation by way of the azide-alkyne Huisgen 1,3-dipolar CA
could first be performed, followed by thermally reversible
polymerization using the Diels-Alder reaction between the
bisfurans and a bismaleimide.
Furfuryl 4-chlorobutanoate (1) was coupled to 2,5-dibromo-
hydroquinone (2) in the presence of KI and K2CO3 in DMF at
elevated temperature to give dibromo bisfuran 3 (Scheme 1).
Next, 3 was subjected to Sonogashira29 conditions to couple
TMS-acetylene, followed by TMS deprotection with TBAF in
THF. The resulting dialkynyl bisfuran 4was then functionalized
with Frechet dendritic benzyl azides 5a-5c30 in the presence of
ꢀ
Cu(PPh3)3Br and Hunig’s base. The Huisgen 1,3-dipolar CA
reactions proceeded smoothly to give the dendritic bisfurans
6a-6c in high yield. All new compounds were fully character-
ized by 1H and 13C NMR along with ESI or MALDI MS and
combustion analysis. Elution volumes of dialkynyl bisfuran
4 and dendritic bisfurans 6a-6c, determined using GPC
(Figure 1), confirmed the increasing hydrodynamic size with
increasing dendrimer generation.
Stimuli-responsive dendronized polymers9 hold great potential
for the production of “smart” polymeric materials.10 The reversi-
bility of the furan-maleimide DA reaction11 has been shown to
have utility in the production of thermally responsive systems,12
including segment block dendrimers,13 simple linear polymers,14,15
cross-linking linear polymers,16 and alternating copolymers.17 In
addition, it has been used to prepare hydrogel,18 nonlinear opti-
cal,19 self-healing,20 and interpenetrating network (IPN)21 materi-
als as well as for nanoscale lithography.22 Previous work from our
group has reported the use of furan-maleimide DA adducts in
thermally cleavable foams,23 encapsulants,24 surfactants,25,26 and
other dendritic macromolecular assemblies.27 Herein we report the
preparation and characterization of first through third generation
linear dendronized step polymers28 from monomers that were
derivatized by the azide-alkyne Huisgen 1,3-dipolar CA and
polymerized by the furan-maleimide DA reaction. These materi-
als represent the first examples of linear covalent dendronized
polymers with thermal reversibility.
1H NMR Analysis of End-Capping Study with N-Phenyl-
maleimide. In an effort to optimize the DA reaction condi-
tions, dendritic bisfuran 6a was first allowed to react with a
monomaleimide to yield a bis-DA adduct, the formation of
1
which could be monitored by H NMR. The DA reaction
of furan and maleimide occurs at temperatures <60 °C,11
with recent examples utilizing temperatures between 50 and
55 °C.13,26,27 Hence, 1.0 equiv of [G-1] bisfuran 6a was
combined with 2.0 equiv of N-phenylmaleimide (7) in a
minimal quantity of CDCl3 (Scheme 2). Previous examples
of the furan-maleimide DA reaction report repeated solvent
concentration as a method for encouraging the progress of
the reaction26,27 along with promoting the formation of the
thermodynamically stable exo isomer.31 Therefore, the reac-
tion vessel was left open, the mixture heated to 50 °C, and a
fresh minimal quantity of CDCl3 added every 24 h. Aliquots
were removed at regular time intervals and analyzed by 1H
NMR.
Results and Discussion
Synthesis of Dendritic Bisfuran Monomers. The convergent
approach to developing the desired multifunctionalized den-
The formation of DA adduct 8 was monitored by both the
disappearance of the free maleimide protons of 7 and the
appearance of the bridgehead protons of 8 (Figures S1-S8 of
*Corresponding authors: e-mail jrmcelh@sandia.gov, phone 505-
844-9165 (J.R.M.); e-mail mcgrath@u.arizona.edu, phone 520-626-
4690, fax 520-621-8407 (D.V.M.).
pubs.acs.org/Macromolecules
Published on Web 12/31/2009
r 2009 American Chemical Society

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Macromolecules, Vol. 43, No. 3, 2010 1271
Scheme 1
Scheme 2
Figure 1. GPC chromatograms of dialkynyl bisfuran 4 and dendritic
bisfurans 6a-6c.
the Supporting Information). While the free maleimide
protons appeared as a singlet at 6.86 ppm, the bridgehead
protons arose from multiple species and therefore consti-
tuted multiple signals. The exo protons were seen as an AB
system with doublets centered at 3.06 and 2.97 ppm. A
doublet centered at 3.42 ppm and a complex multiplet at
∼3.7 ppm signified the endo isomer.14 Although several
different sources of the bridgehead protons were present
throughout the reaction (endo-endo, endo-exo, exo-exo,
and exo and endo mono-DA adducts), the chemical shifts for
the exo and endo protons were nearly identical throughout,
allowing for definitive measurements.
During the assembly of 8, the bridgehead proton signals
were monitored and plotted as a percentage of the sum of the

1272 Macromolecules, Vol. 43, No. 3, 2010
Polaske et al.
Figure 3. Disassembly of DA adduct 8 followed by the appearance of
free maleimide protons in the 1H NMR (TCE-d2, 1 mM) at 110 °C.
Figure 2. Reaction progress and endo composition of the assembly and
reassembly of DA adduct 8 heated to 50 °C in CDCl3 for indicated time
as monitored by 1H NMR.
Scheme 3
bridgehead and free maleimide proton signal (Figure 2). At
time zero, no bridgehead proton signals were observed. Over
time, the formation of 8 was evidenced by the appearance of
the endo and exo bridgehead protons along with a decrease
in the free maleimide proton signal at 6.86 ppm. After 8 h,
75% of maleimide 7 had reacted, and after 120 h, 88% had
reacted. An apparent equilibrium appeared to be established
by this point, as after 240 h the consumed maleimide 7
increased only slightly to 90%. In addition, the quantity of
endo isomer was measured by plotting the endo bridgehead
proton signal as a percentage of the sum of the endo and exo
bridgehead protons. As expected, the kinetically favored
endo isomer initially dominated the mixture (71% after
1 h), while over time the thermodynamically favored exo
isomer took precedence (29% endo after 120 h and 11%
endo after 240 h).31
The disassembly of 8 was investigated by 1H NMR using a
purified sample from the assembly experiment described
above. The retro-DA reaction of furan-maleimide has been
shown to take place at temperatures >60 °C,11 with tem-
peratures between 90 and 120 °C typically employed.13,26,27
To achieve these high temperatures, 1,1,2,2-tetrachloro-
ethane-d2 (TCE-d2) was used as the solvent. In this solvent,
the free maleimide proton signal of 7 appeared at 6.20 ppm,
while the bridgehead proton signals of 8 appeared as an AB
system with two doublets centered at 2.41 and 2.33 ppm (exo
isomer) and as a doublet centered at 2.78 ppm and a complex
multiplet at ∼3.0 ppm (endo isomer).14
isomer also progressed similarly, with a composition of 70%
after 4 h and 14% after 120 h.
GPC Analysis of Polymer Assembly, Disassembly, and
Reassembly. With acceptable conditions for the DA reac-
tions in hand, the step polymerizations of dendritic bisfurans
6a-6c and the commercially available 1,10-(methylenedi-4,1-
phenylene)bismaleimide (9) were performed. The reactions
were carried out similarly to the end-capping study with N-
phenylmaleimide (7). Accordingly, dendritic bisfurans 6a-
6c (1.0 equiv) were combined with bismaleimide 9 (1.0 equiv),
and the mixtures were dissolved in a minimal quantity of
CHCl3 and heated to 50 °C (Scheme 3). The reaction vessels
were left open, and a fresh minimal quantity of CHCl3 was
added every 24 h.
GPC proved to be an excellent method for qualitatively
monitoring the progress of the polymerizations along with
estimating their molecular weights using polystyrene stan-
dards. During the assembly, aliquots were removed at reg-
ular time intervals and monitored by GPC (Figure 4). In each
case, a gradual growth of polymer was observed as evidenced
by the appearance of peaks at smaller retention volumes. Not
surprisingly, the formation of first generation DA polymer
10a appeared to progress faster than second generation
polymer 10b, which was faster still than third generation
polymer 10c. In the case of 10a, most of the monomer 6a and
other low molecular weight oligomers were consumed within
240 h, while in the case of third generation polymer 10c, the
A solution of DA adduct 8 in TCE-d2 (1 mM) was heated
to 110 °C and monitored by 1H NMR at regular time
intervals. After only 5 min, 40% of the retro-DA reaction
had completed (Figure 3). After 30 min, the reaction was
93% complete, and after 60 min, the reaction was complete
as evidenced by the absence of the bridgehead protons of 8. A
first-order rate constant14 of 88 ms-1 was determined for the
disassembly reaction at this temperature.32
Finally, the thermal reassembly of 8 was performed using
the disassembled sample from above under similar condi-
tions as the initial assembly. The fragmented reaction mix-
ture was concentrated in vacuo and heated to 50 °C in a
minimal quantity of CDCl3. The reaction vessel was left open
and a new minimal quantity of CDCl3 was added every 24 h.
The reaction progress was monitored by 1H using the chemi-
cal shifts as outlined in the initial assembly. The reassembly
progressed similarly to the initial assembly, with the reaction
77% complete after 8 h, 91% complete after 48 h, and 95%
complete after 120 h (Figure 2). The concentration of endo

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Macromolecules, Vol. 43, No. 3, 2010 1273
Figure 6. Polymer disassembly of dendritic DA polymers 10a (black,
left), 10b (blue, middle), and 10c (red, right) at 110 °C in TCE (1 mM
based on polystyrene-equivalent Mn values). (A) t = 0; (B) t = 5 min;
(C) t = 10 min; (D) t = 20 min; (E) t = 30 min; (F) t = 60 min.
Figure 4. Polymer assembly of dendritic DA polymers 10a (black, left),
10b (blue, middle), and 10c (red, right) at 50 °C in CHCl3. (A) t = 0; (B)
t = 8 h; (C) t = 24 h; (D) t = 48 h; (E) t = 120 h; (F) t = 240 h.
Figure 5. Polystyrene-equivalent Mn values for the assembly and
reassembly of dendritic DA polymers 10a-10c at 50 °C in CHCl3 for
indicated time.
Figure 7. Polymer reassembly of dendritic DA polymers 10a (black,
left), 10b (blue, middle), and 10c (red, right) at 50 °C in CHCl3. (A) t =
0; (B) t = 8 h; (C) t = 24 h; (D) t = 48 h; (E) t = 120 h; (F) t = 240 h.
monomer 6c was still a major contributor to the GPC trace.
From the appearance of the GPC traces, there was no
evidence for selectivity in product formation.
Polystyrene-equivalent number-average molecular weights
(Mn) were also derived from the GPC chromatograms for the
assembly of 10a-10c (Figure 5). This plot showed a gradual
increase in polymer size over time, with the largest increase
occurring during the first 48 h. After 240 h of reaction time at
50 °C, the reaction mixtures were divided in half. The first
half of the reaction mixtures were precipitated twice from
CH2Cl2 and hexanes to give polystyrene-equivalent Mn
values of 9100, 8900, and 9500 g/mol and degrees of poly-
merization of 5.9, 3.7, and 2.3 for 10a-10c, respectively. The
other half of the reaction mixtures were removed from the
heat and allowed to stand at room temperature for an
additional 35 days. After this time, polystyrene-equivalent
Mn values of 8400, 10 000, and 10 800 g/mol and degrees of
polymerization of 5.5, 4.2, and 2.6 were found for 10a-10c,
respectively.
(1 mM based on polystyrene-equivalent Mn values) were
prepared and heated to 110 °C. After only 5 min, most of the
higher molecular weight polymers had degraded to mono-
mer and smaller oligomers (Figure 6). At 30 min, mostly
monomers were present, and after 60 min, the polymers had
completely disassembled to monomers 6a-6c. The time
course of the reaction was nearly identical to the disassembly
of N-phenylmaleimide DA adduct 8. In addition, polymers
10a-10c all proceeded similarly, requiring 60 min to com-
plete. This was most likely due to the first-order nature of the
retro-DA reaction as opposed to the second-order nature of
the polymerization.14
To demonstrate the repeatable nature of this thermally
reversible system, reassembly of the disassembled polymers
from above was performed using the same conditions as for the
initial assembly. As expected, the reassembly reactions pro-
ceeded in a similar fashion to the initial assembly reactions, with
first generation dendritic polymer 10a growing at a faster initial
rate than second generation polymer 10b (Figure 7). Both 10a
The precipitated polymers 10a-10c from the assembly
experiment described above were then subjected to the
disassembly conditions. Hence, TCE solutions of 10a-10c

1274 Macromolecules, Vol. 43, No. 3, 2010
Polaske et al.
and 10b formed considerably faster than third generation poly-
mer 10c, which still showed considerable amounts of monomer
6c after 240 h. The crude polystyrene-equivalent Mn values for
each polymerization at regular time intervals were also deter-
mined (Figure 5). All three polymers increased in size quickly
over the first 48 h. At this time, the growth of the polystyrene-
equivalent Mn value for first generation polymer 10a slowed
considerably, ending at 4500 g/mol after 240 h. The polystyrene-
equivalent Mn values for second and third generation polymer
10b and 10c both continued to grow, albeit at a slower rate,
reaching values of 6700 and 7800 g/mol, respectively, after 240
h. These polystyrene-equivalent Mn values corresponded to
degrees of polymerization of 2.9, 2.8, and 1.9 for 10a-10c,
respectively.
Bisfurfuryl 4,40-[(2,5-Dibromo-1,4-phenylene)bisoxy]dibuta-
noate (3). To a 500 mL round-bottom flask equipped with
a stirbar was added 2,5-dibromohydroquinone (2) (5.00 g,
18.7 mmol), furfuryl 4-chlorobutanoate (1) (9.20 g, 46.8 mmol),
K2CO3 (12.9 g, 93.3 mmol), KI (1.55 g, 9.35 mmol), and DMF
(150 mL). The flask was fitted with a reflux condenser, and the
mixture was heated to 140 °C for 2.5 h. After cooling, the solvent
was removed under reduced pressure, and the solid residue was
resuspended in EtOAc, filtered, and the solid washed several
times with EtOAc. The filtrate was collected, and the solvent was
removed under reduced pressure, followed by purification by
flash chromatography (silica gel, CH2Cl2) and recrystallization
from hexanes:EtOAc to give 3 (5.21 g, 46% yield) as off-white
needles: mp 96-98 °C. 1H NMR (600 MHz, CDCl3): δ 7.42 (d,
J = 1 Hz, 2H), 7.06 (s, 2H), 6.40 (d, J = 3 Hz, 2H), 6.36-6.35
(m, 2H), 5.09 (s, 4H), 3.98 (t, J = 6 Hz, 4H), 2.60 (t, J = 7 Hz,
4H), 2.17-2.08 (m, 4H). 13C NMR (125 MHz, CDCl3): δ 172.6,
149.9, 149.4, 143.2, 118.6, 111.2, 110.6, 110.5, 68.9, 58.1, 30.5,
24.5. MS (ESI) m/z 622.9 [M þ Na]þ. Anal. Calcd for
C24H24Br2O8: C, 48.02; H, 4.03. Found: C, 47.95; H, 4.10.
Bisfurfuryl 4,40-[(2,5-Diethynyl-1,4-phenylene)bisoxy]dibuta-
noate (4). To a heavy walled Schlenk flask equipped with
a stirbar was added 3 (1.00 g, 1.66 mmol), TMS-acetylene
(560 mg, 6.64 mmol), Pd(PPh3)2Cl2 (116 mg, 0.166 mmol), CuI
(30.0 mg, 0.166 mmol), triethylamine (10 mL), PPh3 (44.0 mg,
0.166 mmol), and DMF (20 mL). Four cycles of freeze-
pump-thaw were performed, followed by heating to 55 °C for
16 h. After cooling, the mixture was transferred to a 250 mL
round-bottom flask. The solvent was removed under reduced
pressure, and the solid residue was resuspended in EtOAc,
filtered, and the solid washed several times with EtOAc. The
filtrate was collected, and the solvent was removed under
reduced pressure, followed by resuspension in THF (50 mL).
TBAF (1.0 M in THF, 3.32 mL, 3.32 mmol) was then added
dropwise with stirring, and the mixture was allowed to stir for
15 min. The mixture was quenched with a saturated NH4Cl
solution (25 mL), and the organic layer was separated, dried
over MgSO4, and filtered. After concentration under reduced
pressure, the residue was purified by flash chromatography
(silica gel, CH2Cl2) to give 4 (410 mg, 51% yield) as a yellow-
orange solid: mp 82-84 °C. 1H NMR (600 MHz, CDCl3): δ 7.40
(s, 2H), 6.91 (s, 2H), 6.38 (d, J = 3 Hz, 2H), 6.34 (s, 2H), 5.07 (s,
4H), 3.98 (t, J = 6 Hz, 4H), 3.32 (s, 2H), 2.57 (t, J = 7 Hz, 4H),
2.13-2.08 (m, 4H). 13C NMR (150 MHz, CDCl3): δ 172.6,
153.7, 149.4, 143.2, 117.8, 113.3, 110.53, 110.47, 82.8, 79.4, 68.2,
58.0, 30.3, 24.4. MS (ESI) m/z 513.3 [M þ Na]þ. Anal. Calcd for
C28H26O8: C, 68.56; H, 5.34. Found: C, 68.11; H, 5.85.
Summary
The synthesis and study of a thermally reversible dendritic step
polymer utilizing sequential “click” reactions has been described.
First through third generation benzyl aryl ether azide dendrons
5a-5c were added to a central dialkynyl bisfuran scaffold 4 with
the Huisgen 1,3-dipolar CA, followed by a 1H NMR study of the
assembly, disassembly, and reassembly of DA adduct 8. After
acceptable DA reaction conditions were determined, dendritic
bisfuran monomers 6a-6c were polymerized with bismaleimide
9, and the thermal assembly, disassembly, and reassembly reac-
tions were studied by GPC. Both NMR and GPC studies
demonstrated that dendritic bisfuran monomers 6a-6c undergo
assembly and disassembly cleanly and predictably using relatively
mild temperature conditions.
Experimental Section
Materials and Methods. NMR data were collected on Bruker
500 and 600 MHz spectrometers running Xwinnmr (Bruker).
Chemical shifts were referenced to the deuterated solvent reso-
1
nance for H (7.26 ppm for CDCl3 and 5.32 ppm for TCE-d2)
and 13C NMR (77.0 ppm for CDCl3). GPC studies were
performed using a Waters Alliance 2695 separations module
˚
with Jordi DVB columns (500, 1000, and 10 000 A columns in
series) with THF as the mobile phase at a flow rate of 1 mL/min.
Data were collected with a Waters 2996 photodiode array
detector at 323 nm using Empower software (Waters). All
chemicals were purchased from commercial suppliers and used
as received unless otherwise noted. Commercially available
1,10-(methylenedi-4,1-phenylene)bismaleimide (9) was pur-
chased from Aldrich (95%) and recrystallized from CH2Cl2/
hexanes before use.
[G-1] Azide (5a)30. To a 200 mL round-bottom flask under an
N2 atmosphere was added [G-1]-OH33 (3.00 g, 9.39 mmol),
DBU (1.70 g, 11.3 mmol), and CH2Cl2 (50 mL). The mixture
was cooled to 0 °C in an ice bath, followed by dropwise addition
of diphenylphosphoryl azide (3.10 g, 11.3 mmol). The reaction
was allowed to warm to rt and was stirred for 16 h. The solvent
was removed under reduced pressure, followed by purification
by flash chromatography (silica gel, 1:1 CH2Cl2-hexanes) to
give 5a (2.46 g, 76% yield) as a colorless, viscous oil that
solidified to a white solid upon standing: mp 67-69 °C, lit.30
Furfuryl 4-Chlorobutanoate (1).
A round-bottom flask
equipped with a stirbar was charged with furfuryl alcohol
(5.60 g, 56.7 mmol), triethylamine (8.60 g, 85.1 mmol), and
CH2Cl2 (50 mL). The mixture was cooled to 0 °C in an ice bath,
followed by dropwise addition of 4-chlorobutyryl chloride (8.00
g, 56.7 mmol). The mixture was stirred for 1 h at 0 °C and was
then allowed to warm to room temperature (rt) over the course
of 1 h. The solvent was removed under reduced pressure, and the
solid residue was resuspended in hexanes (50 mL). The suspen-
sion was filtered and washed several times with hexanes. The
filtrate was collected and extracted with 0.5 M HCl (3 ꢀ 100
mL), 0.5 M NaOH (3 ꢀ 100 mL), and brine (100 mL). The
organics were collected, dried over MgSO4, filtered, and the
solvent removed under reduced pressure to yield 1 (10.8 g, 94%
yield) as a light brown oil. The product was shown to be >95%
pure by 1H NMR and was carried forward without further
purification. 1H NMR (600 MHz, CDCl3): δ 7.43-7.42 (m, 1H),
6.42-6.40 (m, 1H), 6.37-6.36 (m, 1H), 5.08 (s, 2H), 3.59 (t, J =
6 Hz, 2H), 2.53 (t, J = 7 Hz, 2H), 2.15-2.05 (m, 2H). 13C NMR
(125 MHz, CDCl3): δ 172.2, 149.3, 143.2, 110.6, 110.5, 58.1,
44.0, 31.1, 27.6.
1
69 °C. H NMR (500 MHz, CDCl3): δ 7.45-7.35 (m, 10H),
6.61-6.58 (m, 3H), 5.06 (s, 4H), 4.28 (s, 2H). 13C NMR (125
MHz, CDCl3): δ 160.2, 137.6, 136.6, 128.5, 128.0, 127.5, 107.2,
101.8, 70.1, 54.8.
[G-2] Azide (5b)30. To a 200 mL round-bottom flask under an
N2 atmosphere was added [G-2]-OH33 (4.00 g, 5.37 mmol),
DBU (2.22 g, 8.06 mmol), and CH2Cl2 (50 mL). The mixture
was cooled to 0 °C in an ice bath, followed by dropwise addition
of diphenylphosphoryl azide (1.23 g, 8.06 mmol). The reaction
was allowed to warm to rt and was stirred for 16 h. The solvent
was removed under reduced pressure, followed by purification
by flash chromatography (silica gel, CH2Cl2) to give 5b (2.90 g,
1
71% yield) as a white foam: mp 108-109 °C, lit.30 110 °C. H

Article
Macromolecules, Vol. 43, No. 3, 2010 1275
NMR (600 MHz, CDCl3): δ 7.43-7.31 (m, 20H), 6.68 (d, J = 2
Hz, 4H), 6.59-6.55 (m, 5H), 5.04 (s, 8H), 4.98 (s, 4H), 4.26 (s,
2H). 13C NMR (125 MHz, CDCl3): δ 160.11, 160.07, 139.0,
137.6, 136.7, 128.5, 128.0, 127.5, 107.2, 106.3, 101.8, 101.6, 70.1,
70.0, 54.8.
70.03, 69.98, 69.91, 67.7, 58.0, 54.0, 30.8, 24.8. MS (MALDI in
-
N6O36: C, 76.67; H, 5.62; N, 2.25. Found: C, 76.90; H, 6.00;
N, 2.20.
dithranol) m/z 3728.3 [M þ H]þ. Anal. Calcd for C238H208
[G-1] DA Adduct (8). [G-1] bisfuran 6a (100 mg, 84.6 μmol)
and N-phenylmaleimide 7 (14.7 mg, 84.6 μmol) were dissolved in
CDCl3 (500 μL), and the mixture was heated to 50 °C in an open
vial. Every 24 h, fresh CDCl3 (500 μL) was added. After 10 days,
the residue was purified by flash chromatography (silica gel, 9:1
CH2Cl2-acetone) to give 8 (75 mg, 65% yield,34 93% exo
[G-3] Azide (5c)30. To a 250 mL round-bottom flask under an
N2 atmosphere was added [G-3]-OH33 (2.50 g, 1.57 mmol),
DBU (353 mg, 2.35 mmol), and CH2Cl2 (50 mL). The mixture
was cooled to 0 °C in an ice bath, followed by dropwise addition
of diphenylphosphoryl azide (645 mg, 2.35 mmol). The reaction
was allowed to warm to rt and was stirred for 16 h. The solvent
was removed under reduced pressure, followed by purification
by flash chromatography (silica gel, CH2Cl2) to give 5c (2.46 g,
76% yield) as a white, waxy solid. 1H NMR (600 MHz, CDCl3):
δ 7.41-7.30 (m, 40H), 6.68-6.66 (m, 12H), 6.58-6.54 (m, 9H),
5.02 (s, 16H), 4.97 (s, 12H), 4.23 (s, 2H). 13C NMR (125 MHz,
CDCl3): δ 160.1, 160.0, 139.1, 139.0, 137.6, 136.7, 128.5, 127.9,
127.5, 107.2, 106.4, 101.8, 101.63, 101.59, 70.1, 70.04, 70.00,
54.8.
1
isomer) as a white foam. Data for exo-exo isomer: H NMR
(600 MHz, CDCl3): δ 8.04 (s, 2H), 7.93 (s, 2H), 7.41-7.28 (m,
26H), 7.21-7.20 (m, 4H), 6.59-6.57 (m, 2H), 6.55 (d, J = 2 Hz,
4H), 6.50 (d, J = 5 Hz, 2H), 6.32 (d, J = 6 Hz, 2H), 5.49 (s, 4H),
5.31 (s, 2H), 4.99 (s, 8H), 4.85 and 4.50 (AB pattern, J = 13 Hz,
4H), 4.18 (t, J = 6 Hz, 4H), 3.06 and 2.97 (AB pattern, J = 6 Hz,
4H), 2.46 (t, J = 4 Hz, 4H), 2.19-2.10 (m, 4H). 13C NMR (150
MHz, CDCl3): δ 174.7, 173.3, 172.4, 160.3, 149.1, 143.1, 137.6,
137.2, 137.1, 136.4, 131.5, 129.0, 128.7, 128.5, 128.0, 127.5,
126.4, 123.6, 119.4, 110.9, 107.0, 101.9, 89.6, 81.4, 70.1, 67.8,
61.4, 53.9, 49.9, 48.3, 30.8, 29.4, 24.8. MS (ESI) m/z 1550.0 [M þ
Na]þ, 1375.9 [M - maleimide þ Na]þ, 1203.3 [6a þ Na]þ. Anal.
Calcd for C90H78N8O16: C, 70.76; H, 5.15; N, 7.34. Found: C,
70.28; H, 5.38; N, 7.46.
[G-1] Bisfuran (6a). In a small vial equipped with a stirbar, 4
(200 mg, 0.406 mmol), Cu(PPh3)3Br (76 mg, 0.0812 mmol), 5a
(308 mg, 0.893 mmol), DIEA (262 mg, 2.03 mmol), and CH2Cl2
(3.0 mL) were combined. The mixture was stirred at rt for 48 h,
at which point the solvent was removed under reduced pressure.
The residue was purified by flash chromatography (silica gel,
95:5 CH2Cl2-acetone) to give 6a (460 mg, 96% yield) as an off-
NMR Studies. To monitor assembly of DA adduct 8, [G-1]
bisfuran 6a (100 mg, 84.6 μmol) and N-phenylmaleimide (7)
(14.7 mg, 84.6 μmol) were dissolved in CDCl3 (500 μL), and the
mixture was heated to 50 °C in an open vial. Every 24 h, fresh
CDCl3 (500 μL) was added. At time intervals aliquots were
removed from the vial, and 1H NMR spectra were collected at
ambient temperature. To monitor disassembly, a solution
of purified bis-DA adduct 8 in TCE-d2 (1 mM) was heated to
110 °C in a sealed NMR tube. At time intervals the reaction was
removed from the heating bath, and 1H NMR spectra were
collected at ambient temperature. To monitor the reassembly,
the same disassembled sample of DA adduct 8 was concentrated
to dryness and redissolved in a minimal quantity of CDCl3. The
sample was heated to 50 °C in an open vial. At time intervals
aliquots were removed from the vial, and 1H NMR spectra were
collected at ambient temperature.
GPC Studies. To measure the assembly of dendritic DA
polymers 10a-10c, [G-n] bisfurans 6a-6c (1.0 equiv) and bisma-
leimide 9 (1.0 equiv) were dissolved in a minimal quantity of
CHCl3 and heated to 50 °C in open vials. Every 24 h, a fresh
minimal quantity of CHCl3 was added to each vial. At time
intervals aliquots were taken, dissolved in THF, and analyzed by
GPC. To monitor disassembly, each crude polymer mixture of
10a-10c was precipitated from CH2Cl2 and hexanes and heated to
110 °C in TCE (1 mM based on polystyrene-equivalent Mn values).
Aliquots were taken out at time intervals, diluted with THF, and
analyzed by GPC. To monitor reassembly, the same disassembled
polymer samples were concentrated to dryness and dissolved in a
minimal quantity of CHCl3. Every 24 h, a fresh minimal quantity
of CHCl3 was added to each vial. At time intervals aliquots were
taken, dissolved in THF, and analyzed by GPC.
1
white cotton-like solid: mp 162-164 °C. H NMR (500 MHz,
CDCl3): δ 8.08 (s, 2H), 7.97 (s, 2H), 7.39-7.28 (s, 22H), 6.59-
6.56 (m, 6H), 6.34-6.33 (m, 2H), 6.31-6.30 (m, 2H), 5.51 (s,
4H), 5.00 (s, 12H), 4.19 (t, J = 6 Hz, 4H), 2.45 (t, J = 7 Hz, 4H),
2.20-2.10 (m, 4H). 13C NMR (125 MHz, CDCl3): δ 172.4,
160.3, 149.2, 149.1, 143.1, 137.1, 136.4, 128.5, 128.0, 127.4,
123.5, 119.3, 110.8, 110.6, 110.5, 107.0, 102.0, 70.1, 67.8, 58.1,
54.0, 30.8, 24.8. MS (ESI) m/z 1203.4 [M þ Na]þ. Anal. Calcd
for C90H78N8O16: C, 71.17; H, 5.46; N, 7.11. Found: C, 70.91; H,
5.65; N, 7.39.
[G-2] Bisfuran (6b). In a small vial equipped with a stirbar, 4
(100 mg, 0.204 mmol), Cu(PPh3)3Br (38 mg, 0.0410 mmol), 5b
(346 mg, 0.449 mmol), DIEA (132 mg, 1.02 mmol), and CH2Cl2
(3.0 mL) were combined. The mixture was stirred at rt for 48 h,
at which point the solvent was removed under reduced pressure.
The residue was purified by flash chromatography (silica gel,
97:3 CH2Cl2-acetone) to give 6b (390 mg, 94% yield) as an off-
1
white foam: mp 145-148 °C. H NMR (500 MHz, CDCl3): δ
8.06 (s, 2H), 7.92 (s, 2H), 7.41-7.29 (m, 42H), 6.64 (d, J = 2 Hz,
8H), 6.56-6.54 (m, 10H), 6.31-6.30 (m, 2H), 6.27-6.26 (m,
2H), 5.49 (s, 4H), 5.01 (s, 16H), 4.97 (s, 4H), 4.94 (s, 8H), 4.09 (t,
J = 6 Hz, 4H), 2.41 (t, J = 7 Hz, 4H), 2.15-2.05 (m, 4H). 13C
NMR (125 MHz, CDCl3): δ 172.5, 160.3, 160.1, 149.3, 149.1,
143.1, 138.9, 137.2, 136.7, 128.5, 127.9, 127.5, 123.5, 110.9,
110.6, 110.5, 107.2, 106.4, 102.1, 101.7, 70.12, 70.05, 67.8,
58.1, 54.1, 30.9, 29.7, 24.9. MS (MALDI in dithranol) m/z
2030.0 [M þ H]þ. Anal. Calcd for C126H112N6O20: C, 74.54;
H, 5.56; N, 4.14. Found: C, 74.41; H, 5.34; N, 4.11.
[G-3] Bisfuran (6c). In a small vial equipped with a stirbar, 4
(50 mg, 0.102 mmol), Cu(PPh3)3Br (19 mg, 0.0203 mmol), 5c
(362 mg, 0.224 mmol), DIEA (66 mg, 0.510 mmol), and CH2Cl2
(3.0 mL) were combined. The mixture was stirred at rt for 48 h,
at which point the solvent was removed under reduced pressure.
The residue was purified by flash chromatography (silica gel,
98:2 CH2Cl2-acetone) to give 6c (340 mg, 90% yield) as an off-
white foam: mp 62-64 °C. 1H NMR (500 MHz, CDCl3): δ 8.07
(s, 2H), 7.93 (s, 2H), 7.43-7.29 (m, 82H), 6.69 (d, J = 2 Hz,
16H), 6.65-6.64 (m, 8H), 6.58-6.57 (m, 14H), 6.55-6.53 (m,
4H), 6.30-6.29 (m, 2H), 6.26-6.25 (m, 2H), 5.45 (s, 4H),
5.01-4.93 (m, 60H), 4.07 (t, J = 6 Hz, 4H), 2.39 (t, J = 7 Hz,
4H), 2.13-2.05 (m, 4H). 13C NMR (125 MHz, CDCl3): δ 172.5,
160.2, 160.0, 159.9, 149.2, 149.0, 143.1, 139.1, 138.8, 137.1,
136.7, 128.5, 128.31, 128.28, 127.9, 127.6, 127.5, 127.2, 123.5,
119.3, 110.7, 110.6, 110.5, 107.1, 106.3, 102.0, 101.54, 101.49,
Acknowledgment. This work was supported by the United
States Department of Energy (US DOE) under Contract DE-
AC04-94AL85000. Sandia is a multiprogram laboratory oper-
ated by Sandia Corporation, a Lockheed Martin Company, for
the US DOE. Certain trade names and company products are
identified in order to specify experimental procedures adequately.
In no case does such identification imply recommendation or
endorsement by the National Institute of Standards and Tech-
nology, nor does itimply that the productsare necessarily the best
available for the purpose.
Supporting Information Available: 1H NMR spectra of the
assembly of DA adduct 8. This material is available free of
charge via the Internet at http://pubs.acs.org.

1276 Macromolecules, Vol. 43, No. 3, 2010
Polaske et al.
References and Notes
(19) (a) Haller, M.; Luo, J.; Li, H.; Kim, T.-D.; Liao, Y.; Robinson,
B. H.; Dalton, L. R.; Jen, A. K. Y. Macromolecules 2004, 37, 688–
690. (b) Luo, J.; Haller, M.; Li, H.; Kim, T.-D.; Jen, A. K. Y. Adv.
Mater. 2003, 15, 1635–1638.
(20) (a) Bergman, S. D.; Wudl, F. J. Mater. Chem. 2008, 18, 41–62. (b)
Chen, X.; Dam, M. A.; Ono, K.; Mal, A.; Shen, H.; Nut, S. R.; Sheran,
K.; Wudl, F. Science 2002, 295, 1698–1702. (c) Chen, X.; Wudl, F.;
Mal, A. K.; Shen, H.; Nutt, S. R. Macromolecules 2003, 36, 1802–
1807. (d) Tian, Q.; Yuan, Y. C.; Rong, M. Z.; Zhang, M. Q. J. Mater.
Chem. 2009, 19, 1289–1296. (e) Zhang, Y.; Broekhuis, A. A.; Picchio-
ni, F. Macromolecules 2009, 42, 1906–1912.
(1) (a) Carlmark, A.; Hawker, C.; Hult, A.; Malkoch, M. Chem. Soc.
ꢀ
Rev. 2009, 38, 352–362. (b) Frechet, J. M. J.; Tomalia, D. Dendrimers
and Other Dendritic Polymers; Wiley: Chichester, England, 2001.
(c) Newkome, G. R.; Moorefield, C. N.; Vogtle, F. Dendrimers and
Dendrons: Concepts, Syntheses, Applications; Wiley-VCH:
Weinheim, 2001. (d) Grayson, S. M.; Frechet, J. M. J. Chem. Rev.
€
ꢀ
2001, 101, 3819–3867.
(2) Flemming, I. Pericyclic Reactions; Oxford University Press: Oxford,
1999.
(3) (a) Voit, B. New J. Chem. 2007, 31, 1139–1151. (b) Goodall, G. W.;
Hayes, W. Chem. Soc. Rev. 2006, 35, 280–312.
(4) (a) Huisgen, R.; Szeimies, G.; Moebius, L. Chem. Ber. 1967, 100,
2494–2507. (b) Padwa, A. 1,3-Dipolar Cycloaddition Chemistry;
Wiley: New York, 1984.
(21) Imai, Y.; Itoh, H.; Naka, K.; Chujo, Y. Macromolecules 2000, 33,
4343–4346.
(22) Gotsmann, B.; Duerig, U.; Frommer, J.; Hawker, C. J. Adv. Funct.
Mater. 2006, 16, 1499–1505.
(23) McElhanon, J. R.; Russick, E. M.; Wheeler, D. R.; Loy, D. A.;
Aubert, J. H. J. Appl. Polym. Sci. 2002, 85, 1496–1502.
(24) (a) Small, J. H.; Loy, D. A.; Wheeler, D. R.; McElhanon, J. R.;
Saunders, R. S. US Patent 6271335 B1, 2001; p 8. (b) Loy, D. A.;
Wheeler, D. R.; McElhanon, J. R.; Durbin-Voss, M. US Patent 6403753
B1, 2002; p 13. (c) Loy, D. A.; Wheeler, D. R.; Russick, E. M.;
McElhanon, J. R.; Sanders, R. S. US Patent 6337384 B1, 2002; p 7.
(25) (a) McElhanon, J. R.; Jamison, G. M.; Long, T. M.; Loy, D. A.;
Rahimian, K.; Simmons, B. A.; Staiger, C. L.; Wheeler, D. R.;
Zifer, T. US Patent 7351837 B1, 2008; p 12. (b) McElhanon, J. R.;
Simmons, B. A.; Zifer, T.; Jamison, G. M.; Loy, D. A.; Rahimian, K.;
Long, T. M.; Wheeler, D. R.; Staiger, C. L. US Patent 7022861 B1,
2006; p 19.
(26) McElhanon, J. R.; Zifer, T.; Kline, S. R.; Wheeler, D. R.; Loy, D.
A.; Jamison, G. M.; Long, T. M.; Rahimian, K.; Simmons, B. A.
Langmuir 2005, 21, 3259–3266.
(27) (a) McElhanon, J. R.; Wheeler, D. R. Org. Lett. 2001, 3, 2681–
2683. (b) Szalai, M. L.; McGrath, D. V.; Wheeler, D. R.; Zifer, T.;
McElhanon, J. R. Macromolecules 2007, 40, 818–823.
(28) (a) Frauenrath, H. Prog. Polym. Sci. 2005, 325–384. (b) Zhang, A.;
Shu, L.; Bo, Z.; Schl€uter, A. D. Macromol. Chem. Phys. 2003,
328–339.
(5) (a) Franc, G.; Kakkar, A. Chem. Commun. 2008, 5267–5276. (b) van
Wuytswinkel, G.; Verheyde, B.; Compernolle, F.; Toppet, S.; Dehaen,
W. J. Chem. Soc., Perkin Trans. 1 2000, 1337–1340. (c) 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, 3928–3932.
(6) Diels, O.; Alder, K. Justus Liebigs Ann. Chem. 1928, 460, 98–122.
(7) Franc, G.; Kakkar, A. K. Chem. Eur. J. 2009, 15, 5630–5639.
(8) (a) Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem., Int.
Ed. 2001, 40, 2004–2021. (b) Rostovtsev, V. V.; Green, L. G.; Fokin, V.
V.; Sharpless, K. B. Angew. Chem., Int. Ed. 2002, 41, 2596–2599.
(9) Gao, M.; Jia, X.; Kuang, G.; Li, Y.; Liang, D.; Wei, Y. Macro-
molecules 2009, 42, 4273–4281.
(10) Yerushalmi, R.; Scherz, A.; van der Boom, M.; Kraatz, H. B.
J. Mater. Chem 2005, 15, 4480–4487.
(11) Kwart, H.; King, K. Chem. Rev. 1968, 68, 414–447.
(12) Gandini, A.; Belgacem, M. N. Prog. Polym. Sci. 1997, 22, 1203–
1379.
(13) Kose, M. M.; Yesilbag, G.; Sanyal, A. Org. Lett. 2008, 10, 2353–
2356.
(14) Gandini, A.; Coelho, D.; Silvestre, A. J. D. Eur. Polym. J. 2008, 44,
4029–4036.
(29) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975,
4467–4470.
(30) Mahmud, I. M.; Zhou, N.; Wang, L.; Zhao, Y. Tetrahedron 2008,
64, 11420–11432.
(31) Cooley, J. H.; Williams, R. V. J. Chem. Educ. 1997, 74, 582–585.
(32) Rate constants for the assembly and disassembly of DA adduct 8
could not be determined due to the varying concentration during
the experiment.
(15) (a) Gousse, C.; Gandini, A. Polym. Bull. 1998, 40, 389–394. (b)
Gousse, C.; Gandini, A. Polym. Int. 1999, 48, 723–731. (c) Laita, H.;
Boufi, S.; Gandini, A. Eur. Polym. J. 1997, 33, 1203–1211. (d) White,
J. E. Ind. Eng. Chem. Prod. Res. Dev. 1986, 25, 395–400.
(16) (a) Canary, S. A.; Stevens, M. P. J. Polym. Sci., Part A: Polym.
Chem. 1992, 30, 1755–1760. (b) Gheneim, R.; Perez-Berumen, C.;
Gandini, A. Macromolecules 2002, 35, 7246–7253. (c) Gousse, C.;
Gandini, A.; Hodge, P. Macromolecules 1998, 31, 314–321.
(17) Kamahori, K.; Tada, S.; Ito, K.; Itsuno, S. Macromolecules 1999,
32, 541–547.
ꢀ
(33) Hawker, C. J.; Frechet, J. M. J. J. Am. Chem. Soc. 1990, 112, 7638–
7647.
(34) The yield of DA adduct 8 may be artificially low due to the removal
of aliquots during the reaction.
(18) Chujo, Y.; Sada, K.; Saegusa, T. Macromolecules 1990, 23,
2636–2641.