A modular approach toward functionalized three-dimensional macromolecules: From synthetic concepts to practical applications

Article abstract of DOI:10.1021/ja028392s

A new strategy for the preparation of functional, multiarm star polymers via nitroxide-mediated "living" radical polymerization has been explored. The generality of this approach to the synthesis of three-dimensional macromolecular architectures allows for the construction of nanoscopically defined materials from a wide range of different homo, block, and random copolymers combining both apolar and polar vinylic repeat units. Functional groups can also be included along the backbone or as peripheral/chain end groups, thereby modulating the reactivity and polarity of defined portions of the stars. This modular approach to the synthesis of three-dimensional macromolecules permits the application of these tailored materials as multifunctional hosts for hydrogen bonding, nanoparticle formation, and as scaffolds for catalytic groups. Examples of applications of the functional stars in catalysis include their use in a Heck-type coupling as well as an enantioselective addition reaction.

Full text of DOI:10.1021/ja028392s

Published on Web 12/18/2002
A Modular Approach toward Functionalized
Three-Dimensional Macromolecules: From Synthetic
Concepts to Practical Applications
Anton W. Bosman,†,‡ Robert Vestberg,† Andi Heumann,† Jean M. J. Fre´chet,*,‡ and
Craig J. Hawker*,†
Contribution from the IBM Almaden Research Center, 650 Harry Road, San Jose, California
95120, Department of Chemistry, UniVersity of California, Berkeley, California 94720-1460, and
Lawrence Berkeley National Laboratory, Berkeley, California 94720
Received September 3, 2002; E-mail: frechet@cchem.berkeley.edu; hawker@almaden.ibm.com
Abstract: A new strategy for the preparation of functional, multiarm star polymers via nitroxide-mediated
“living” radical polymerization has been explored. The generality of this approach to the synthesis of three-
dimensional macromolecular architectures allows for the construction of nanoscopically defined materials
from a wide range of different homo, block, and random copolymers combining both apolar and polar vinylic
repeat units. Functional groups can also be included along the backbone or as peripheral/chain end groups,
thereby modulating the reactivity and polarity of defined portions of the stars. This modular approach to
the synthesis of three-dimensional macromolecules permits the application of these tailored materials as
multifunctional hosts for hydrogen bonding, nanoparticle formation, and as scaffolds for catalytic groups.
Examples of applications of the functional stars in catalysis include their use in a Heck-type coupling as
well as an enantioselective addition reaction.
Introduction
recently experienced a renewed interest due to their potential
for greater accessibility by living free radical procedures.8
Previously, multiarm star polymers have been prepared by
living ionic procedures;9 however, the synthetically demanding
nature of this approach and its lack of compatibility with a
variety of functional groups have limited the applicability of
The growing demand for well-defined and functional soft
materials in nanoscale applications has led to a dramatic increase
in the development of procedures that combine architectural
control with flexibility in the incorporation of functional
groups.1-4 The unusual solution and interfacial properties of
these tailor-made macromolecules make them suitable as active
materials in nanotechnology with recent examples including
shell cross-linked nanoparticles,5 hyperbranched macromol-
ecules,6 dendrimers,7 etc. While not as highly branched as these
three-dimensional polymeric architectures, star polymers have
(5) (a) Ma, Q. G.; Remsen, E. E.; Clark, C. G.; Kowalewski, T.; Wooley, K.
L. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 5058-5063. (b) Huang, H.;
Remsen, E. E.; Kowalewski, T.; Wooley, K. L. J. Am. Chem. Soc. 1999,
121, 3805. (c) Becker, M. L.; Remsen, E. E.; Wooley, K. L. J. Polym.
Sci., Polym. Chem. 2001, 39, 4152. (d) Bu¨tu¨n, V.; Wang, X. S.; de Paz
Ba´n˜ez, M. V.; Robinson, K. L.; Billingham, N. C.; Armes, S. P.; Tuzar, Z.
Macromolecules 2000, 33, 1. (e) Liu, S.; Armes, S. P. J. Am. Chem. Soc.
2001, 123, 9910.
(6) (a) Guan, Z. B. J. Am. Chem. Soc. 2002, 124, 5616. (b) Bolton, D. H.;
Wooley, K. L. J. Polym. Sci., Polym. Chem. 2002, 40, 823. (c) Sunder, A.;
Quincy, M. F.; Mulhaupt, R.; Frey, H. Angew. Chem., Int. Ed. 1999, 38,
2928. (d) Jikei, M.; Fujii, K.; Kakimoto, M. J. Polym. Sci., Polym. Chem.
2001, 39, 3304. (e) Bernal, D. P.; Bankey, N.; Cockayne, R. C.; Fossum,
E. J. Polym. Sci., Polym. Chem. 2002, 40, 1456. (f) Thompson, D. S.;
Markoski, L. J.; Moore, J. S.; Sendijarevic, I.; Lee, A.; McHugh, A. J.
Macromolecules 2000, 33, 6412. (g) Simon, P. F. W.; Mu¨ller, A. H. E.
Macromolecules 2001, 34, 6206. (h) Hawker, C. J.; Lee, R.; Fre´chet, J. M.
J. J. Am. Chem. Soc. 1991, 113, 4583.
† IBM Almaden Research Center.
‡ University of California and Lawrence Berkeley National Laboratory.
(1) (a) Kato, T. Science 2002, 295, 2414. (b) Yu, S. M.; Soto, C. M.; Tirrell,
D. A. J. Am. Chem. Soc. 2000, 122, 6552. (c) Farrer, R. A.; Copeland, G.
T.; Previte, M. J. R.; Okamoto, M. M.; Miller, S. J.; Fourkas, J. T. J. Am.
Chem. Soc. 2002, 124, 1994. (d) Peerlings, H. W. I.; Van Benthem, R. A.
T. M.; Meijer, E. W. J. Polym. Sci., Polym. Chem. 2001, 39, 3112. (e)
Wooley, K. L.; Clark, C. J. Polym. Sci., Polym. Chem. 2000, 38, 1397. (f)
Nishinaga, T.; Tanatani, A.; Oh, K.; Moore, J. S. J. Am. Chem. Soc. 2002,
124, 5934.
(2) (a) Percec, V.; Cho, W. D.; Ungar, G.; Yeardley, D. J. P. Angew. Chem.,
Int. Ed. 2000, 39, 1597. (b) Ma, H.; Jen, A. K. Y. AdV. Mater. 2001, 13,
1201. (c) Ma, Q.; Remsen, E. E.; Kowalewski, T.; Wooley, K. L. J. Am.
Chem. Soc. 2001, 123, 4627. (d) Nam, J. M.; Park, S. J.; Mirkin, C. A. J.
Am. Chem. Soc. 2002, 124, 3820.
(3) (a) Zubarev, E.; Stupp, S. I. J. Am. Chem. Soc. 2002, 124, 5762. (b) Weil,
T.; Wiesler, U. M.; Herrmann, A.; Bauer, R.; Hofkens, J.; De Schryver,
F.; Mu¨llen, K. J. Am. Chem. Soc. 2001, 123, 8101. (c) Tew, G. N.; Pralle,
M. U.; Stupp, S. I. J. Am. Chem. Soc. 1999, 121, 9852. (d) Hill, D. J.;
Mio, M. J.; Prince, R. B.; Hughes, T. S.; Moore, J. S. Chem. ReV. 2001,
101, 3893-4012.
(4) (a) Liu, S.; O’Brien, D. F. J. Am. Chem. Soc. 2002, 124, 6037. (b)
Brunsveld, L.; Meijer, E. W.; Prince, R. B.; Moore, J. S. J. Am. Chem.
Soc. 2001, 123, 7978. (c) Gossl, I.; Shu, L.; Schluter, A. D.; Rabe, J. P. J.
Am. Chem. Soc. 2002, 124, 6860. (d) El-Ghayoury, A.; Schenning, A. P.
H. J.; Meijer, E. W. J. Polym. Sci., Polym. Chem. 2002, 40, 4020. (e) Zheng,
H.; Lee, I.; Rubner, M. F.; Hammond, P. T. AdV. Mater. 2002, 14, 569.
(7) (a) Stiriba, S. E.; Frey, H.; Haag, R. Angew. Chem., Int. Ed. 2002, 41,
1329. (b) Gibson, H. W.; Yamaguchi, N.; Hamilton, L.; Jones, J. W. J.
Am. Chem. Soc. 2002, 124, 4653. (c) Bosman, A. W.; Jansen, H. M.; Meijer,
E. W. Chem. ReV. 1999, 99, 1665. (d) Devadoss, C.; Bharathi, P.; Moore,
J. S. Angew. Chem., Int. Ed. Engl. 1997, 36, 1633. (e) Vetter, S.; Koch, S.;
Schluter, A. D. J. Polym. Sci., Polym. Chem. 2001, 39, 1940. (f) Percec,
V.; Obata, M.; Rudick, J. G.; De, B. B.; Glodde, M.; Bera, T. K.; Magonov,
S. N.; Balagurusamy, V. S. K.; Heiney, P. A. J. Polym. Sci., Polym. Chem.
2002, 40, 3509. (g) Marsitzky, D.; Vestberg, R.; Blainey, P.; Tang, B. T.;
Hawker, C. J.; Carter, K. R. J. Am. Chem. Soc. 2001, 123, 6965. (h) Piotti,
M. E.; Rivera, F.; Bond, R.; Hawker, C. J.; Fre´chet, J. M. J. J. Am. Chem.
Soc. 1999, 121, 9471-9472. (i) Tomalia, D. A.; Fre´chet, J. M. J. J. Polym.
Sci., Polym. Chem. 2002, 40, 2719.
(8) (a) Hawker, C. J.; Bosman, A. W.; Harth, E. Chem. ReV. 2001, 101, 3661-
3688. (b) Kamigaito, M.; Ando, T.; Sawamoto, M. Chem. ReV. 2001, 101,
3689-3746. (c) Matyjaszewski, K.; Xia, J. Chem. ReV. 2001, 101, 2921-
2990.
9
10.1021/ja028392s CCC: $25.00 © 2003 American Chemical Society
J. AM. CHEM. SOC. 2003, 125, 715-728
715

A R T I C L E S
Bosman et al.
Figure 1. Schematic representation of the modular approach to star polymers.
this strategy. In contrast, recent reports from a number of
groups10 have detailed the application of nitroxide11 or ATRP12
living radical polymerizations to the synthesis of star polymers,
which overcomes many of these limitations. While a number
of approaches are possible, the most promising involves the
coupling of preformed linear chains, containing a dormant chain
end, with a cross-linkable monomer such as divinylbenzene.
Traditionally, such an approach has been complicated by the
large number of reaction and structure variables that limits the
ability to optimize and control the structure of the resulting star
polymers. This deficiency has recently been overcome by
employing high-throughput “combinatorial” techniques for the
rapid screening and optimization of these multivariable systems
and has permitted the synthesis of well-defined three-dimen-
sional star polymers by living free radical techniques.13
functionalized materials. As shown in Figure 1, the applicability
of living free radical procedures to the preparation of function-
alized block and random copolymers from hydrophilic, hydro-
phobic, or fluorinated segments, potentially containing acidic,
basic, or H-bonding groups, enables the production of libraries
of linear polymers incorporating combinations of these features.
While this structural diversity is important, a critical feature of
our approach is the incorporation of a dormant initiating group
at one of the chain ends of these linear polymers.14 Activation
of these chain ends, followed by their coupling under conditions
optimized for star polymer formation, then leads to a myriad
of functionalized three-dimensional star polymers with accurate
control over molecular weight, arm length, and both the nature
and the placement of functional groups. These unique structures
are useful in a range of applications as supramolecular hosts,
catalytic scaffolds, or substrates for nanoparticle formation.
In this report, we describe the development of a modular
approach for the preparation of functionalized star polymers,
which permits the custom synthesis of a wide variety of
Experimental Section
General Methods. DMF, technical grade DVB (55% m- and
p-divinylbenzene, with the remainder consisting mostly m- and p-
ethylstyrene), all monomers, and reagents were used as obtained
(Aldrich), except for 2- and 4-vinylpyridine, which were purified over
alumina. Toluene and THF were distilled from sodium under a nitrogen
atmosphere. The CDCl3 employed in the hydrogen-bonding experiments
was dried by passing over alumina before use. Nitroxide 1 and
alkoxyamines 2 and 3 were prepared as described by Hawker et al.15,16
The L-Tyr-based ligand 4,17 dendritic initiator 5,18 and 2,6-bis-
(acetylamino)pyridine 619 were synthesized according to literature
(9) (a) Tsoukatos, T.; Hadjichristidis, N. J. Polym. Sci., Part A: Polym. Chem.
2002, 40, 2575. (b) Al-Muallem, H. A.; Knauss, D. M. J. Polym. Sci.,
Polym. Chem. 2001, 39, 3547. (c) Hull, D. L.; Kennedy, J. P. J. Polym.
Sci., Polym. Chem. 2001, 39, 1525. (d) Moschogianni, P.; Pispas, S.;
Hadjichristidis, N. J. Polym. Sci., Polym. Chem. 2001, 39, 650.
(10) (a) Narrainen, A. P.; Pascual, S.; Haddleton, D. M. J. Polym. Sci., Polym.
Chem. 2002, 40, 439. (b) Stenzel-Rosenbaum, M.; Davis, T. P.; Chen, V.;
Fane, A. G. J. Polym. Sci., Polym. Chem. 2001, 39, 2777. (c) Quinn, J. F.;
Chaplin, R. P.; Davis, T. P. J. Polym. Sci., Polym. Chem. 2002, 40, 2956.
(11) (a) Tsoukatos, T.; Pispas, S.; Hadjichristidis, N. J. Polym. Sci., Polym. Chem.
2001, 39, 320. (b) Pasquale, A. J.; Long, T. E. J. Polym. Sci., Polym. Chem.
2001, 39, 216. (c) Hawker, C. J. Angew Chem., Int. Ed. Engl. 1995, 34,
1456.
(12) (a) Baek, K. Y.; Kamigaito, M.; Sawamoto, M. J. Polym. Sci., Polym. Chem.
2002, 40, 1972. (b) Baek, K. Y.; Kamigaito, M.; Sawamoto, M. J. Polym.
Sci., Polym. Chem. 2002, 40, 2245. (c) Baek, K. Y.; Kamigaito, M.;
Sawamoto, M. J. Polym. Sci., Polym. Chem. 2002, 40, 633. (d) Zhang, X.;
Xia, J. H.; Matyjaszewski, K. Macromolecules 2000, 33, 2340.
(13) Bosman, A. W.; Heumann, A.; Klaerner, G.; Fre´chet, J. M. J.; Hawker, C.
J. J. Am. Chem. Soc. 2001, 123, 6461.
(14) (a) Burguiere, C.; Dourges, M. A.; Charleux, B.; Varion, J. P. Macromol-
ecules 1999, 32, 3883-3890. (b) Hawker, C. J.; Hedrick, J. L. Macro-
molecules 1995, 28, 2993. (c) Hawker, C. J. J. Am. Chem. Soc. 1994, 116,
11185.
(15) Dao, J.; Benoit, D.; Hawker, C. J. J. Polym. Sci., Part A: Polym. Chem.
1998, 36, 2161-67.
9
716 J. AM. CHEM. SOC. VOL. 125, NO. 3, 2003

Functionalized Three-Dimensional Macromolecules
A R T I C L E S
procedures. Column chromatography was carried out with Merck silica
gel, 230-400 mesh. NMR spectra were recorded on a Bruker AM 250
(250 MHz) spectrometer with the residual protonated solvent peak as
internal standard. GPC was carried out on a Waters chromatograph
connected to a Waters 410 differential refractometer with THF as the
carrier solvent. Absorption spectra were recorded in degassed THF
solution (containing no stabilizers) on a Cary 50 UV-visible spectro-
photometer. Optical rotation was measured on a Jasco DIP-370 digital
polarimeter. MALDI-TOF mass spectrometry was performed on a
PerSeptive Biosystems Voyager DE mass spectrometer operating in
linear mode, using dithranol in combination with silver trifluoroacetate
as matrix. Transmission electron micrographs of unstained samples were
recorded on a JEOL JEM 2000 FX at 80 kV. Transmission electron
microscopy grids were prepared by placing one drop of a toluene
solution (0.5 mg/mL) on a carbon-covered copper grid followed by
immediate drainage.
131.12 (d), 128.43 (d), 127.33 (d), 127.16 (d), 127.03 (d), 126.42 (d),
126.21 (d), 83.19 (d), 82.34 (d), 72.10 (d), 63.05 (t), 60.68 (s), 60.52
(s), 32.17 (d), 31.70 (d), 28.50 (q), 28.24 (q), 24.73 (q), 23.09 (q),
22.10 (q), 21.19 (q). Anal. Calcd for C23H33NO2: C, 77.7; H, 9.35; N,
3.94. Found: C, 77.6; H, 9.13; N, 3.68.
2,2,5-Trimethyl-3-(1′-p-azidomethylphenylethoxy)-4-phenyl-3-
azahexane, 9. A mixture of the alkoxyamine, 3 (8.74 g, 23.0 mmol),
sodium azide (4.40 g, 68.0 mmol), and 18-crown-6 (100 mg) was stirred
in dimethyl sulfoxide (60 mL) at 60 °C for 16 h. The reaction mixture
was then poured into water (600 mL) and extracted with dichloro-
methane (3 × 150 mL). The combined organic fractions were dried on
MgSO4, evaporated to dryness, and purified by flash chromatography
eluting with dichloromethane. The azido derivative, 9, was obtained
1
as a colorless gum (7.38 g, 83.4%). IR (film): 2098 cm-1 (azide). H
NMR both diastereomers (250 MHz, CDCl3): δ 7.10-7.40 ppm (m,
18H), 4.73 ppm (q, 2H), 4.16 ppm (d, 4H), 3.44 ppm (d, 1H, J ) 10.8
Hz), 3.30 ppm (d, 1H, J ) 10.8 Hz), 2.39 ppm (m, 1H), 1.60 ppm (d,
3H, J ) 6.3 Hz), 1.49 ppm (d, 3H, J ) 6.3 Hz), 1.40 ppm (m, 1H),
1.28 ppm (d, 3H, J ) 6.3 Hz), 1.03 ppm (s, 9H), 0.90 ppm (d, 3H, J
) 6.3 Hz), 0.82 ppm (s, 9H), 0.63 ppm (d, 3H, J ) 6.6 Hz), 0.24 ppm
(d, 3H, J ) 6.6 Hz). 13C NMR (APT) (63 MHz, CDCl3, both
diastereomers): δ 146.28 (s), 145.25 (s), 142.63 (s), 135.56 (d), 131.10
(d), 128.43 (d), 128.30 (d), 127.28 (d), 127.11 (d), 127.00 (d), 126.53
(d), 126.25 (d), 83.25 (d), 82.21 (d), 72.09 (d), 63.13 (t), 60.70 (s),
60.58 (s), 50.35 (t), 32.23 (d), 31.76 (d), 28.46 (q), 28.19 (q), 24.82
(q), 23.13 (q), 22.09 (q), 21.27 (q). Anal. Calcd for C23H33N4O: C,
72.6; H, 8.46; N, 14.72. Found: C, 72.6; H, 8.58; N, 14.93.
2,2,5-Trimethyl-3-(4′-p-acetoxymethylphenylethoxy)-4-phenyl-3-
azahexane, 7. The chloromethyl substituted alkoxyamine,15 3 (14.0 g,
37.5 mmol), and potassium acetate (9.20 g, 93.8 mmol) were stirred at
room temperature in hexamethylphosphorus triamide (HMPT, 100 mL)
for 48 h. After being diluted with dichloromethane (400 mL) and
washed with water (4 × 250 mL), the organic fraction was concentrated
and passed through a short silica column eluting with dichloromethane/
hexane, 9:1, gradually increasing to dichloromethane/hexane, 1:1. This
gave the acetoxymethyl derivative, 7, as a colorless gum (13.7 g,
1
91.8%). H NMR both diastereomers (250 MHz, CDCl3): δ 7.10-
7.40 ppm (m, 18H), 5.12 ppm (d, 2H, J ) 9.3 Hz), 4.91 ppm (ds, 4H,
J ) 3.2 Hz), 3.45 ppm (d, 1H, J ) 10.8 Hz), 3.31 ppm (d, 1H, J )
10.8 Hz), 2.44 ppm (m, 1H), 1.60 ppm (d, 3H, J ) 6.3 Hz), 1.52 ppm
(d, 3H, J ) 6.3 Hz), 1.41 ppm (m, 1H), 1.28 ppm (d, 3H, J ) 6.3 Hz),
1.07 ppm (s, 9H), 0.88 ppm (d, 3H, J ) 6.3 Hz), 0.81 ppm (s, 9H),
0.60 ppm (d, 3H, J ) 6.6 Hz), 0.21 ppm (d, 3H, J ) 6.6 Hz). 13C
NMR (APT) (63 MHz, CDCl3, both diastereomers): δ 172.54 (s),
146.03 (s), 145.27 (s), 142.80 (s), 142.35 (s), 135.78 (d), 131.04 (d),
128.51 (d), 127.36 (d), 127.31 (d), 127.19 (d), 127.05 (d), 126.50 (d),
126.37 (d), 126.23 (d), 83.23 (d), 82.30 (d), 72.12 (d), 72.10 (d), 63.20
(t), 60.55 (s), 60.48 (s), 46.20 (d), 32.07 (d), 31.77 (d), 28.45 (q), 28.23
(q), 25.48 (q), 24.70 (q), 23.08 (q), 23.01 (q), 22.12 (q), 21.30 (q),
21.19 (q). Anal. Calcd for C25H35NO3: C, 75.5; H, 8.87; N, 3.52.
Found: C, 75.3; H, 8.82; N, 3.70.
2,2,5-Trimethyl-3-(4′-p-hydroxymethylphenylethoxy)-4-phenyl-
3-azahexane, 8. 2,2,5-Trimethyl-3-(1′-p-acetoxymethylphenylethoxy)-
4-phenyl-3-azahexane, 7 (19.9 g, 50.0 mmol), was mixed with water
(100 mL), ethanol (30 mL), 18-crown-6 (0.20 g, 0.76 mmol), and
sodium hydroxide (5.00 g, 125 mmol). The two-phase system was
vigorously stirred and heated at reflux for 18 h. The reaction mixture
was then cooled, extracted with dichloromethane, dried over magnesium
sulfate, and concentrated. The crude product was purified by column
chromatography eluting with dichloromethane/petroleum ether 3:2,
gradually increasing to dichloromethane to give the hydroxyl-func-
tionalized alkoxyamine, 8, as a colorless oil (15.8 g, 89.1% yield). 1H
NMR both diastereomers (250 MHz, CDCl3): δ 7.10-7.40 ppm (m,
18H), 4.96 ppm (m, 2H), 4.74 ppm (m, 4H), 3.40 ppm (d, 1H, J )
10.8 Hz), 3.31 ppm (d, 1H, J ) 10.8 Hz), 2.42 ppm (m, 1H), 1.59
ppm (d, 3H, J ) 6.3 Hz), 1.50 ppm (d, 3H, J ) 6.3 Hz), 1.41 ppm (m,
1H), 1.32 ppm (d, 3H, J ) 6.3 Hz), 1.05 ppm (s, 9H), 0.93 ppm (d,
3H, J ) 6.3 Hz), 0.78 ppm (s, 9H), 0.61 ppm (d, 3H, J ) 6.6 Hz),
0.19 ppm (d, 3H, J ) 6.6 Hz). 13C NMR (APT) (63 MHz, CDCl3,
both diastereomers): δ 146.11 (s), 145.24 (s), 142.55 (s), 135.67 (d),
2,2,5-Trimethyl-3-(1′-p-aminomethylphenylethoxy)-4-phenyl-3-
azahexane, 10. Lithium aluminum hydride (920 mg, 25.0 mmol) was
slowly added to 2,2,5-trimethyl-3-(1′-p-azidomethylphenylethoxy)-4-
phenyl-3-azahexane, 9 (7.90 g, 25.0 mmol), dissolved in dry THF (150
mL), and cooled to 0 °C. After being stirred under argon for 16 h,
water (1 mL) was slowly added to the reaction mixture, followed by
filtration and concentration by rotary evaporation. The crude product
was purified by column chromatography eluting with dichloromethane,
gradually increasing to 10% methanol/dichloromethane to give the
1
amino derivative, 10, as a colorless gum (6.70 g, 91.0%). H NMR
both diastereomers (250 MHz, CDCl3): δ 7.10-7.40 ppm (m, 18H),
4.93 ppm (q, 2H, J ) 6 Hz), 3.89 ppm (d, 4H, J ) 9.6 Hz), 3.41 ppm
(d, 1H, J ) 10.8 Hz), 3.28 ppm (d, 1H, J ) 10.8 Hz), 2.40 ppm (m,
1H), 1.61 ppm (d, 3H, J ) 6.3 Hz), 1.48 ppm (d, 3H, J ) 6.3 Hz),
1.40 ppm (m, 1H), 1.27 ppm (d, 3H, J ) 6.3 Hz), 1.02 ppm (s, 9H),
0.90 ppm (d, 3H, J ) 6.3 Hz), 0.81 ppm (s, 9H), 0.57 ppm (d, 3H, J
) 6.6 Hz), 0.22 ppm (d, 3H, J ) 6.6 Hz). 13C NMR (APT) (63 MHz,
CDCl3, both diastereomers): δ 146.31 (s), 145.37 (s), 142.80 (s), 135.67
(d), 131.22 (d), 128.56 (d), 128.45 (d), 128.31 (d), 127.32 (d), 127.08
(d), 127.04 (d), 126.62 (d), 126.29 (d), 83.32 (d), 82.28 (d), 72.16 (d),
63.21 (t), 60.71 (s), 60.46 (s), 56.32 (t), 32.15 (d), 31.69 (d), 28.51
(q), 28.30 (q), 24.80 (q), 23.17 (q), 22.13 (q), 21.32 (q). Anal. Calcd
for C23H34N2O: C, 77.92; H, 9.67; N, 7.90. Found: C, 77.80; H, 9.43;
N, 8.03.
2,2,5-Trimethyl-3-(1′-p-(t-butyloxycarbonylamidomethylphen-
ylethoxy)-4-phenyl-3-azahexane, 11. Di-tert-butyl dicarbonate (0.89
g, 4.10 mmol) was slowly added to 2,2,5-trimethyl-3-(1′-p-aminom-
ethylphenylethoxy)-4-phenyl-3-azahexane, 10 (1.20 g, 3.40 mmol), and
triethylamine (500 mg, 4.95 mmol) dissolved in dry dichloromethane
(10 mL). After being stirred at room temperature under argon for 12
h, the reaction mixture was washed with saturated NaHCO3 (25 mL),
followed by water (25 mL). The organic fraction was evaporated to
dryness and purified by flash chromatography using dichloromethane
as eluent to give the protected amino derivative, 11, as a colorless gum
(1.50 g, 94.9%). IR (film): 3352 cm-1 (N-H), 1704 cm-1 (amide).
1H NMR both diastereomers (250 MHz, CDCl3): δ 7.10-7.40 ppm
(m, 18H), 4.88 ppm (m, 2H), 4.74 ppm (br, 2H), 4.22 ppm (m, 4H),
3.41 ppm (d, 1H, J ) 10.8 Hz), 3.30 ppm (d, 1H, J ) 10.8 Hz), 2.43
ppm (m, 1H), 1.60 ppm (d, 3H, J ) 6.3 Hz), 1.49 ppm (d, 3H, J ) 6.3
(16) (a) Harth, E.; Hawker, C. J.; Fan, W.; Waymouth, R. M. Macromolecules
2001, 34, 3856. (b) Hawker, C. J.; Barclay, G. G.; Orellana, A.; Dao, J.;
Devonport, W. Macromolecules 1996, 29, 5245.
(17) Itsuno, S.; Nakano, M.; Ito, K.; Hirao, A.; Owa, M.; Kanda, N.; Nakahama,
S. J. Chem. Soc., Perkin Trans. 1 1985, 2615.
(18) Leduc, M. R.; Hawker, C. J.; Dao, J.; Fre´chet, J. M. J. J. Am. Chem. Soc.
1996, 118, 11111.
(19) Feibush, B.; Figueroa, A.; Charles, R.; Onan, K. D.; Feibush, P.; Karger,
B. L. J. Am. Chem. Soc. 1986, 108, 3310.
9
J. AM. CHEM. SOC. VOL. 125, NO. 3, 2003 717

A R T I C L E S
Bosman et al.
Hz), 1.41 ppm (m, 1H), 1.32 ppm (d, 3H, J ) 6.3 Hz), 1.20 ppm (s,
18H), 1.02 ppm (s, 9H), 0.88 ppm (d, 3H, J ) 6.3 Hz), 0.81 ppm (s,
freeze/thaw cycles, sealed under argon, and heated at 125 °C for 16 h.
The reaction mixture was then diluted with dichloromethane (20 mL)
and precipitated in methanol (500 mL). The colorless gum was collected
and dried in vacuo to give the poly(n-butyl acrylate) derivative (6.01
g, 78.0%).
9H), 0.60 ppm (d, 3H, J ) 6.6 Hz), 0.21 ppm (d, 3H, J ) 6.6 Hz). 13
C
NMR (APT) (63 MHz, CDCl3, both diastereomers): δ 173.54 (s),
146.65 (s), 145.44 (s), 142.72 (s), 135.51 (d), 132.13 (d), 128.62 (d),
128.50 (d), 128.45 (d), 128.28 (d), 127.40 (d), 127.11 (d), 127.01 (d),
126.24 (d), 83.25 (d), 82.34 (d), 74.17 (s), 72.20 (d), 63.34 (t), 60.82
(s), 60.45 (s), 54.45 (t), 33.10 (q), 32.10 (d), 31.78 (d), 28.45 (q), 28.23
(q), 24.81 (q), 23.33 (q), 22.16 (q), 21.36 (q). Anal. Calcd for
C29H42N2O3: C, 74.64; H, 9.07; N, 6.00. Found: C, 74.31; H, 8.89; N,
5.78.
General Procedure for N-Isopropylacrylamide Polymerization,
26. A mixture of N-isopropylacrylamide (8.40 g, 74.0 mmol),
alkoxyamine 2 (476 mg, 1.50 mmol), nitroxide 1 (17 mg, 78 µmol),
and DMF (9 mL) was degassed by three freeze/thaw cycles, sealed
under argon, and heated at 125 °C for 48 h. The reaction mixture was
then diluted with dichloromethane (25 mL) and precipitated in diethyl
ether (500 mL). The white powder was filtered, and then dried in vacuo
to give the desired poly(N-isopropylacrylamide) linear polymer, 26 (5.71
g, 64.3%).
2,2,5-Trimethyl-3-(1′-p-((S)-(-)-2′′-amino-3′′-p-oxyphenyl)-1′′,1′′-
diphenylpropan-1′′-ol)-benzylethoxy)-4-phenyl-3-azahexane, 12. NaH
(0.23 g, 6.30 mmol) was slowly added to a mixture of 417 (0.50 g,
1.57 mmol) and 18-crown-6 (10 mg) dissolved in THF (10 mL) under
a constant argon flow. After 15 min, alkoxyamine, 3 (0.58 g, 1.57
mmol), was added to the reaction mixture, which was subsequently
heated at reflux under argon for 16 h. After the addition of a few drops
of water to neutralize the excess NaH, the reaction mixture was
concentrated, dissolved in dichloromethane (50 mL), and washed with
water (2 × 50 mL). The crude product was obtained after drying with
Na2SO4 and evaporation to dryness. The pure compound, 12, was
obtained as a yellowish solid after flash chromatography eluting with
dichloromethane gradually increasing to 10% methanol/dichloromethane
(903 mg, 86.2%). IR (KBr): 3439 cm-1 (NH). 1H NMR both
diastereomers (250 MHz, CDCl3): δ 6.80-7.70 ppm (m, 46H), 4.93
ppm (m, 2H), 4.84 ppm (m, 2H), 4.05 ppm (m, 2H), 3.41 ppm (d, 1H,
J ) 10.8 Hz), 3.30 ppm (d, 1H, J ) 10.8 Hz), 2.42 ppm (m, 1H), 1.63
ppm (d, 3H, J ) 6.3 Hz), 1.52 ppm (d, 3H, J ) 6.3 Hz), 1.39 ppm (m,
1H), 1.30 ppm (d, 3H, J ) 6.3 Hz), 1.04 ppm (s, 9H), 0.92 ppm (d,
3H, J ) 6.3 Hz), 0.80 ppm (s, 9H), 0.61 ppm (d, 3H, J ) 6.6 Hz),
0.20 ppm (d, 3H, J ) 6.6 Hz). Anal. Calcd for C44H52N2O3: C, 80.45;
H, 7.98; N, 4.26. Found: C, 80.56; H, 7.74; N, 3.97.
General Procedure for N,N-Dimethylacrylamide Polymerization,
27-29. A mixture of N,N-dimethylacrylamide (3.38 g, 34.0 mmol),
alkoxyamine 2 (264 mg, 0.81 mmol), and nitroxide 1 (9.0 mg, 41 µmol)
was degassed by three freeze/thaw cycles, sealed under argon, and
heated at 125 °C for 16 h. The reaction mixture was then diluted with
dichloromethane (20 mL) and precipitated in hexanes (500 mL). The
white powder was filtered, and then dried in vacuo to give the
alkoxyamine-terminated poly(N,N-dimethylacrylamide) derivative (2.62
g, 72.0%).
General Procedure for 2-Vinylpyridine Polymerization, 30. A
mixture of 2-vinylpyridine (10.0 g, 95.0 mmol) and the alkoxyamine
2 (746 mg, 2.3 mmol) was degassed by three freeze/thaw cycles, sealed
under argon, and heated at 125 °C for 5 h. The reaction mixture was
then diluted with dichloromethane (30 mL) and precipitated in hexanes
(500 mL). The yellowish powder was filtered, and then dried in vacuo
to give the desired alkoxyamine-terminated poly(2-vinylpyridine), 30
(8.87 g, 82.5%).
General Procedure for Formation of Star Polymers, 31-47. A
mixture of the polymeric macroinitiator, 16 (2.07 g, 0.36 mmol, Mn )
5700, PDI ) 1.08), styrene (315 mg, 3.03 mmol), and divinylbenzene
(156 mg, 1.20 mmol) was dissolved in DMF (8.0 mL), degassed by
three freeze/thaw cycles, and sealed under argon. The polymerization
mixture was then stirred at 125 °C for 16 h, allowed to cool, and the
star polymer, 33, was obtained after precipitation using propan-2-ol
(2.08 g, 82%, Mn ) 74 000, PDI ) 1.19). Poly(N-isopropylacrylamide)-
containing stars were precipitated with diethyl ether as nonsolvent at 0
°C, whereas hexanes were used as nonsolvent for the poly(N,N-
dimethylacrylamide)-containing stars.
2,2,5-Trimethyl-3-(1′-p-((S)-(-)-2′′-(t-butyl-oxy-carbonylamide)-
3′′-p-oxyphenyl)-1′′,1′′-diphenylpropan-1′′-ol)-benzylethoxy)-4-phen-
yl-3-azahexane, 13. Di-tert-butyl dicarbonate (6.04 g, 27.0 mmol) was
slowly added to a mixture of 2,2,5-trimethyl-3-(1′-p-((S)-(-)-2′′-amino-
3′′-p-oxyphenyl)-1′′,1′′-diphenylpropan-1′′-ol)-benzylethoxy)-4-phenyl-
3-azahexane, 12 (7.89 g, 11.7 mmol), and triethylamine (3.75 g, 37
mmol) dissolved in dry THF (75 mL). After being stirred for 2 h at
room temperature, the solvent was evaporated, and the crude product
was dissolved in ethyl acetate (200 mL), followed by washing with
saturated NaHCO3 (2 × 100 mL). Drying and evaporation to dryness
gave the crude product, which was purified by flash chromatography
eluting with dichloromethane gradually increasing to 10% diethyl ether/
dichloromethane to give the carbamate, 13, as a yellow gum (4.98 g,
56.2%). IR (KBr): 3439 cm-1 (NH), 1645 cm-1 (carbamate). 1H NMR
both diastereomers (250 MHz, CDCl3): δ 7.7-6.8 ppm (m, 46H), 4.94
ppm (m, 2H), 4.81 ppm (m, 2H), 4.63 (br, 2H), 3.70 ppm (m, 2H),
3.27 ppm (d, 1H, J ) 10.8 Hz), 3.10 ppm (d, 1H, J ) 10.8 Hz), 2.69
ppm (m, 4H), 2.42 ppm (m, 1H), 1.61 ppm (d, 3H, J ) 6.3 Hz), 1.48
ppm (d, 3H, J ) 6.3 Hz), 1.40 ppm (m, 1H), 1.32 ppm (d, 3H, J ) 6.3
Hz), 1.24 ppm (s, 18H), 1.05 ppm (s, 9H), 0.91 ppm (d, 3H, J ) 6.3
Hz), 0.80 ppm (s, 9H), 0.59 ppm (d, 3H, J ) 6.6 Hz), 0.23 ppm (d,
3H, J ) 6.6 Hz). Anal. Calcd for C49H60N2O5: C, 77.75; H, 7.99; N,
3.70. Found: C, 77.62; H, 7.89; N, 3.46.
General Procedure for Block Copolymer Formation: Prepara-
tion of Poly(n-butyl Acrylate)-b-polystyrene, 48-59. A mixture of
the alkoxyamine-terminated poly(n-butyl acrylate) starting block, 24
(2.00 g, 0.40 mmol, Mn ) 5000, PDI ) 1.09), was dissolved in styrene
(2.50 g, 24.0 mmol), degassed by three freeze/thaw cycles, sealed under
argon, and the polymerization reaction was heated at 125 °C for 8 h.
The solidified reaction mixture was then dissolved in dichloromethane
(20 mL) and precipitated (2×) into methanol (500 mL). The precipitate
was then collected by vacuum filtration and dried to give the desired
block copolymer, 53, as a white solid (4.06 g, 90.2%, Mn ) 9700, PDI
) 1.12).
X-ray Analysis. Crystals were obtained after separation of both
diastereoisomers of 3 with flash chromatography on silica using
petroleum ether/dichloromethane 10:1 as eluent, followed by crystal-
lization from a mixture of dichloromethane/hexane. The X-ray structure
analyses data were collected with a Bruker SMART CCD area-detector
diffractometer using graphite monochromated Mo KR radiation (T )
-119 ( 1 °C). Data were corrected for Lorentz and polarization effects.
The structure was solved by direct methods20 and expanded using
Fourier techniques.21 The non-hydrogen atoms were refined anisotro-
pically. Hydrogen atoms were included but not refined. Crystal data:
Macroinitiators. General Procedure for Styrene Polymerization,
14-23. A mixture of styrene (11.5 g, 111 mmol) and the alkoxyamine,
2 (601 mg, 1.80 mmol), was degassed by three freeze/thaw cycles,
sealed under argon, and heated at 125 °C for 8 h. The viscous reaction
mixture was then dissolved in dichloromethane (25 mL) and precipitated
in methanol (1 L). The white powder was filtered, and then dried in
vacuo to give the alkoxyamine-terminated polystyrene (10.0 g, 82.5%).
General Procedure for Acrylate Polymerization, 24, 25. A mixture
of n-butyl acrylate (7.36 g, 58.0 mmol), the alkoxyamine 2 (348 mg,
1.10 mmol), and nitroxide 1 (13 mg, 58 µmol) was degassed by three
(20) Altomare, A.; Cascarano, M.; Giacovazzo, C.; Guagliardi, A. J. Appl.
Crystallogr. 1993, 26, 343.
9
718 J. AM. CHEM. SOC. VOL. 125, NO. 3, 2003

Functionalized Three-Dimensional Macromolecules
A R T I C L E S
C23H32NOCl, Mr ) 373.96, colorless prismatic crystal (0.22 × 0.21 ×
0.19 mm), primitive monoclinic cell, P21/n (no. 14) with a )
8.7967(4) Å, b ) 8.8891(2) Å, c ) 27.195(2) Å, â ) 96.139(2)°, V )
2114.3(2) Å3, Z ) 4, Dc ) 1.17 g/cm3, µ(Mo KR) ) 15.89 cm-1, 9091
reflections measured (3.50 < 2θ < 45.00°), 3772 unique (Rint ) 0.032),
R1 ) 0.031 (for 1842 I > 3.00 σ(I)). No residual density outside -0.16
roacetic acid under standard conditions, in dry toluene (1.5 mL) was
added benzaldehyde (120 µL, 20 mol equiv with respect to each Tyr-
end group). After being stirred for 16 h under an argon atmosphere,
the reaction mixture was cooled to 0 °C, and a 1 M solution of Et2Zn
in hexane (2.7 mL, 3 mol equiv to benzaldehyde) was added. After 8
h, the reaction was quenched with 1 M HCl and extracted with
dichloromethane. GC-MS and 1H NMR analysis of the extract showed
quantitative conversion to 1-phenylpropanol. GC analysis with a chiral
stationary phase (â-Dex capillary column, Supelco Co.) gave an ee of
71%, whereas the negative sign of the optical rotation showed
predominant formation of the S-configuration.
Pd-Nanoparticle Formation and Catalysis. The palladium nano-
particle was prepared by dissolving the PSt-P2VP star, 71 (200 mg,
0.27 mmol equiv of 2VP), in toluene (10 mL) and subsequent addition
of palladium acetate (15 mg, 0.25 mol Pd(OAc)2 per mol 2VP). After
the mixture was stirred at room temperature for 4 h under an argon
atmosphere, complete dissolution of the palladium salts was observed,
and a clear light orange solution was obtained. The solution was diluted
with ethanol (5 mL) followed by heating to 80 °C for 16 h. The resulting
dark brown solution was concentrated followed by precipitation in
methanol. After being dried in vacuo, the Pd(0)-containing star, 78,
was obtained as a dark brown precipitate.
and 0.25 e Å-3
.
Dye Complexation Studies. To a solution of the PSt-P(4VP-r-St)
star, 72 (50 mg, 0.06 mmol 4VP), in a mixture of toluene (5 mL) and
chloroform (1 mL) was added coumarin-3-carboxylic acid, 60 (6.0 mg,
0.032 mmol), or Zn(II) protoporphyrin IX, 61 (9.0 mg, 0.014 mmol).
After being stirred overnight, a deeply colored solution was obtained
that was subsequently filtered over Celite, concentrated, and evaporated
to dryness. The complexation behavior of the dye was studied by a
range of spectroscopic techniques.
H-Bonded Complexes with Maleimide-Functionalized Stars. FT-
IR spectra were obtained in deuterated chloroform (5-10 mM) using
1
NaCl cells with a 1 mm path length. H NMR titration experiments
were performed by portionwise addition of the maleimide-functionalized
star, 73, to a solution of 2,6-bis(acetylamino)pyridine, 6 (17 mM), in
deuterated chloroform. The association constant was determined using
a nonlinear least-squares fitting procedure.55
Enantioselective Addition of Et2Zn to Benzaldehyde. To a solution
of tyrosine-functionalized star, 39 (220 mg), deprotected with trifluo-
Hydrogenation experiments were performed by dissolving the Pd-
containing star, 78 (10 mg, 0.007 mmol of Pd), in THF (15 mL) in an
argon atmosphere. The reaction mixture was purged with hydrogen,
and subsequently 0.5 mL (4.9 mmol) of cyclohexene was added while
a hydrogen atmosphere was maintained at a pressure of 1 atm. After 1
h at 30 °C, a sample was taken from the reaction mixture, precipitated
in methanol, filtered through a microfilter, and analyzed with GC-MS.
The Heck coupling was performed by dissolving the Pd-containing
star, 78 (28 mg, 0.019 mmol of Pd), in xylenes (10 mL) followed by
the addition of 1-bromo-4-nitrobenzene (788 mg, 3.9 mmol), n-butyl
acrylate (2.5 g, 20 mmol), tri-n-butylamine (1.1 g, 5.9 mmol), and
tetradecane (200 mg) as internal standard. After the mixture was heated
to 125 °C, aliquots were taken from the reaction mixture, precipitated
in methanol, filtered through a microfilter, and analyzed with GC. After
2 h, the reaction was washed with water (3 × 20 mL), evaporated to
(21) Beurskens, P. T.; Admiraal, G.; Beurskens, G.; Bosman, W. P.; de Gelder,
R.; Israel, R.; Smits, J. M. M. The DIRDIF-94 Program System; Technical
Report of the Crystallography Laboratory, University of Nijmegen, The
Netherlands, 1994.
(22) (a) Sawamoto, M.; Kamigaito, M. CHEMTECH 1999, 29, 30-38. (b)
Malmstrom, E. E.; Hawker, C. J. Macromol. Chem. Phys. 1998, 199, 923.
(c) Matyjaszewski, K. Controlled Radical Polymerization ACS Symposium
Series 685; Matyjaszewski, K., Ed.; American Chemical Society: Wash-
ington, DC, 1998; pp 1-25. (d) Hawker, C. J. Acc. Chem. Res. 1997, 30,
373.
(23) (a) Baek, K. Y.; Kamigaito, M.; Sawamoto, M. Macromolecules 2001, 34,
7629. (b) Matyjaszewski, K.; Miller, P. J.; Pyun, J.; Kickelbick, G.;
Diamanti, S. Macromolecules 1999, 32, 6526.
(24) (a) Benoit, D.; Grimaldi, S.; Robin, S.; Finet, J. P.; Tordo, P.; Gnanou, Y.
J. Am. Chem. Soc. 2000, 122, 5929. (b) Benoit, D.; Chaplinski, V.; Braslau,
R.; Hawker, C. J. J. Am. Chem. Soc. 1999, 121, 3904.
(25) Benoit, D.; Harth, E.; Fox, P.; Waymouth, R. M.; Hawker, C. J.
Macromolecules 2000, 33, 363.
(26) Husemann, M.; Malmstrom, E.; McNamara, M.; Mate, M.; Mecerreyes,
D.; Benoit, D.; Hedrick, J.; Mansky, P.; Huang, E.; Russell, T.; Hawker,
C. J. Macromolecules 1999, 32, 1424.
(27) Bignozzi, M. C.; Ober, C. K.; Laus, M. Macromol. Rapid Commun. 1999,
20, 622.
(28) (a) Ananchenko, G. S.; Souaille, M.; Fischer, H.; LeMercier, C.; Tordo, P.
J. Polym. Sci., Part A: Polym. Chem. 2002, 40, 3264. (b) Ananchenko, G.
S.; Fischer, H. J. Polym. Sci., Part A: Polym. Chem. 2001, 39, 3604. (c)
Fischer, H. J. Polym. Sci., Part A: Polym. Chem. 1999, 37, 1885.
(29) Go¨tz, H.; Harth, E.; Schiller, S. M.; Frank, C. W.; Knoll, W.; Hawker, C.
J. J. Polym. Sci., Part A: Polym. Chem. 2002, 40, 3379.
(30) Skene, W. G.; Scaiano, J. C.; Yap, G. P. A. Macromolecules 2000, 33,
3536.
(31) Bowman, D. F.; Gillan, T.; Ingold, K. U. J. Am. Chem. Soc. 1971, 93,
6555.
(32) Spek, A. L. PLUTON. A Program for Plotting Molecules and Crystal
Structures; University of Utrecht, Utrecht, Netherlands, 1995.
(33) Li, D.; Brittain, W. J. Macromolecules 1998, 31, 3852.
(34) Rodlert, M.; Harth, E.; Rees, I.; Hawker, C. J. J. Polym. Sci., Polym. Chem.
2000, 38, 4749.
(35) The number of arms was estimated by determining the absolute molecular
weight of the star polymer by either MALLS or viscosity experiments,
and, after assuming that 90% of the mass of the star polymer is due to
the arms (10% is due to the core), it was estimated by dividing this
final molecular weight by the molecular weight of the starting linear
polymer.
1
dryness, and analyzed by H NMR.
(42) Kragl, U.; Dreisbach, C. Angew. Chem., Int. Ed. Engl. 1996, 35, 642.
Hovestad, N. J.; Eggeling, E. B.; Heidbu¨chel, H. J.; Jastrzebski, J. T. B.
H.; Kragl, U.; Keim, W.; Vogt, D.; van Koten, G. Angew. Chem., Int. Ed.
1999, 38, 1655.
(43) Jung, M. E.; Lyster, M. A. J. Am. Chem. Soc. 1977, 99, 968. Zhang, Q.;
Remsen, E. E.; Wooley, K. L. J. Am. Chem. Soc. 2000, 122, 3642.
(44) Kline, S. R. Langmuir 1999, 15, 2726-2732.
(45) Benoit, D.; Hawker, C. J.; Huang, E. E.; Lin, Z.; Russell, T. P.
Macromolecules 2000, 33, 1505.
(46) (a) Hawker, C. J.; Fre´chet, J. M. J. J. Am. Chem. Soc. 1990, 112, 7638. (b)
Hawker, C. J.; Fre´chet, J. M. J. J. Chem. Soc., Chem. Commun. 1990, 1010.
(c) Wooley, K. L.; Hawker, C. J.; Frechet, J. M. J. J. Chem. Soc., Perkin
Trans. 1 1991, 1059.
(47) Jeong, M.; Mackay, M. E.; Vestberg, R.; Hawker, C. J. Macromolecules
2001, 34, 4927.
(48) Leduc, M. R.; Hayes, W.; Fre´chet, J. M. J. J. Polym. Sci., Polym. Chem.
1998, 36, 1.
(49) (a) Kumar, U.; Kato, T.; Fre´chet, J. M. J. J. Am. Chem. Soc. 1996, 118,
11111. (b) Kato, T.; Kihara, H.; Ujiie, S.; Uryu, S.; Fre´chet, J. M. J.
Macromolecules 1996, 29, 8734. (c) Kihara, H.; Kato, T.; Uryu, S.; Fre´chet,
J. M. J. Chem. Mater. 1996, 8, 961. (d) Kato, T.; Fre´chet, J. M. J.
Macromolecules 1989, 22, 3818.
(50) Hecht, S.; Vladimorov, N.; Fre´chet, J. M. J. J. Am. Chem. Soc. 2001, 123,
18.
(36) (a) Grubbs, R. B.; Dean, J. M.; Broz, M. E.; Bates, F. S. Macromolecules
2000, 33, 9522. (b) Hawker, C. J.; Hedrick, J. L.; Malmstrom, E. E.;
Trollsas, M.; Mecerreys, D.; Dubois, P.; Jerome, R. Macromolecules 1998,
31, 213.
(37) (a) Hedrick, J. L.; Miller, R. D.; Hawker, C. J.; Carter, K. R.; Volksen,
W.; Yoon, D. Y.; Trollsas, M. AdV. Mater. 1998, 10, 1049. (b) Hawker, C.
J.; Hedrick, J. L.; Miller, R. D.; Volksen, W. MRS Bull. 2000, 25, 54. (c)
Yang, S.; Mirau, P. A.; Pai, C. S.; Nalamasu, O.; Reichmanis, E.; Lin, E.
K.; Lee, H. J.; Gidley, D. W.; Sun, J. N. Chem. Mater. 2001, 13, 2762.
(38) Itsuno, S.; Fre´chet, J. M. J. J. Org. Chem. 1987, 52, 4140.
(39) Chung, Y. M.; Rhee, H. K. Chem. Commun. 2002, 238.
(40) Peerlings, H. W. I.; Meijer, E. W. Chem.-Eur. J. 1997, 3, 1563.
(41) Itsuno, S.; Sakurai, Y.; Ito, K.; Maruyama, T.; Nakahama, S.; Fre´chet, J.
M. J. J. Org. Chem. 1990, 55, 304.
(51) (a) Abraham, R. J.; Fell, S. C. M.; Pearson, H. Tetrahedron 1979, 35, 1759.
(b) Dolphin, D., Ed. The Porphyrins; Academic Press: New York,
1978.
(52) (a) Sijbesma, R. P.; Beijer, F. H.; Brunsveld, L.; Folmer, B. J. B.;
Hirschberg, J. J. K. K.; Lange, R. F. M.; Lowe, J. K. L.; Meijer, E. W.
Science 1997, 278, 1601. (b) Sherrington, D. C.; Taskinen, K. A. Chem.
Soc. ReV. 2001, 30, 83. (c) Sherrington, D. C. J. Polym. Sci., Polym. Chem.
2001, 39, 2364.
(53) Lange, R. F. M.; Meijer, E. W. Macromolecules 1995, 28, 782.
(54) Lange, R. F. M.; Beijer, F. H.; Sijbesma, R. P.; Hooft, R. W. W.; Kooijman,
H.; Spek, A. L.; Kroon, J.; Meijer, E. W. Angew. Chem., Int. Ed. Engl.
1997, 36, 969.
(55) Beijer, F. H.; Sijbesma, R. P.; Vekemans, J. A. J. M.; Meijer, E. W.;
Kooijman, H.; Spek, A. L. J. Org. Chem. 1996, 61, 6371.
9
J. AM. CHEM. SOC. VOL. 125, NO. 3, 2003 719

A R T I C L E S
Bosman et al.
Results and Discussion
One of the attractive features of living free radical polymer-
izations, which makes these procedures applicable for the
formation of star polymers, is the presence of a dormant
initiating group at one of the polymer chain ends.22 This dormant
chain end, an alkoxyamine functionality in the case of nitroxide-
mediated living free radical polymerization, is obtained as a
direct result of the mechanism of the polymerization in which
the mediating nitroxide radical is continually cleaved and
reinserted at the growing chain end. Under the appropriate
conditions, reactivation of this dormant chain end in the presence
of a cross-linking monomer, such as divinylbenzene, leads to
the coupling of a multiplicity of these starting linear chains to
give a highly branched star polymer in a single step.23
Obviously, the ultimate structure of this star polymer is dictated
to a large extent by the structure of the starting linear polymer.
However, the versatility of the living free radical approach
enabling not only the preparation of chains functionalized either
at the chain end or along the backbone, but also that of random
copolymers or block copolymers, can lead to a wealth of
different functionalized star polymers.
End Group Functionality. These synthetic possibilities were
initially examined by introducing the functional groups specif-
ically at the multiple chain ends of the star polymers in a
controlled fashion. To succeed in the preparation of chain-end-
functionalized star polymers, it is critical to have access to the
corresponding functionalized initiators while also ensuring that
the telechelic polymers derived from these initiators have a high
degree of chain end retention (ca. 95-100%). One family of
alkoxyamine initiators that fulfills both of these criteria is the
recently introduced R-hydrido alkoxyamines24 that contain a
hydrogen atom attached to a carbon located R to the nitroxide
nitrogen. Experimental results have proven the applicability of
this family of initiators to the controlled polymerization of a
wide variety of monomers,25-27 while combined kinetic and
theoretical studies have highlighted their usefulness in proce-
dures where the persistent radical effect (PRE) is operative.28
This ability to control polymerizations is a surprising result given
the general lack of stability of nitroxides with hydrogen atoms
in the R-position and their propensity toward decomposition,
for example, by disproportionation.31 To better understand this
important new family of alkoxyamine-based initiators, the crystal
structure of the p-chloromethyl derivative, 3,15,29 has been
resolved by X-ray spectroscopy.
Figure 2. X-ray structure32 of 3.
Table 1. Molecular Weight Data for Alkoxyamine-Terminated
Homopolymersa
alkoxyamine-terminated homopolymers
b
M
n,NMR
M
n,GPC
b
entry
initiator
monomer
DP
(kDa)
(kDa)
M /M
w
n
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
2
2
3
3
8
8
8
11
13
13
2
2
8
2
8
8
2
St
St
St
St
St
St
St
St
48
84
57
96
45
55
65
47
44
55
45
40
31
44
55
90
34
5.3
9.0
5.7
10.3
4.8
5.5
7.1
5.2
5.2
6.3
5.4
5.5
3.9
5.2
7.1
10.2
3.6
5.5
9.1
5.8
9.9
4.4
5.1
7.2
4.3
4.7
6.0
5.0
4.6
2.6
8.9
10.3
14.4
5.5
1.09
1.07
1.08
1.10
1.06
1.08
1.10
1.08
1.12
1.14
1.09
1.12
1.12
1.09
1.06
1.12
1.14
St
St
nBA
tBA
NIPAM
DMA
DMA
DMA
2VP
a Molecular weight data after purification; GPC data relative to PS-
standards. b Obtained by integration of H NMR signals.
1
The conversion of the p-chloromethyl functionality into a
variety of other functional groups is facilitated by the inertness
of the alkoxyamine group to basic and reducing reaction
conditions (see Scheme 1).29 For example, substitution of the
chloromethyl functionality with sodium azide followed by
reduction with lithium aluminum hydride gives 10 containing
a benzylic amine. Alternatively, substitution with potassium
acetate followed by basic hydrolysis resulted in a molecule, 8,
with a benzylic alcohol functionality. More complex functional
groups such as the L-Tyr-based ligand,17 4, could also be
introduced using nucleophilic displacement.
The compatibility of these functional groups with living free
radical procedures was then demonstrated by the polymerization
of a variety of vinyl monomers from these functionalized
initiators. As shown in Tables 1-4, in each case, the polym-
erization proved to be successful, although it was necessary to
protect the amine function with a Boc-group, 11, to prevent
formation of a small (approximately 2-5%) amount of higher
molecular weight coupled product. Of particular note is the
ability to control the polymerization of functionalized monomers
such as N,N-dimethylacrylamide (DMA) and N-isopropylacryl-
amide (NIPAM), both of which are difficult to polymerize in a
controlled fashion under typical ATRP conditions.33
Depicted in Figure 2 is the SS-diastereoisomer, present
together with its enantiomer in the crystal. The N-O-C bond
lengths and angles are comparable to those found in the crystal
structures of other alkoxyamines.30 However, the most intriguing
aspect of the structure is the O(1)-N(1)-C(10)-H(11) torsion
angle of 167.54°. This results in an almost transoid orientation
of the proton with respect to the oxygen and is most likely a
direct result of steric hindrance between the tert-butyl group
on the nitrogen and the isopropyl and phenyl moieties on the
adjacent carbon C(10). Because disproportionation is thought
to occur via a five-membered transition state with the O and
the H-atoms cisoid,31 the tendency of nitroxides, such as 1, to
undergo disproportionation is significantly reduced and may
explain their significantly improved performance in living free
radical polymerizations as compared to traditional TEMPO
(2,2,6,6-tetramethylpiperidinyloxy) systems.
9
720 J. AM. CHEM. SOC. VOL. 125, NO. 3, 2003

Functionalized Three-Dimensional Macromolecules
A R T I C L E S
Scheme 1. Synthesis of Functionalized Initiators, 8, 11, and 13, from the Chloromethyl Alkoxyamine, 3
Table 2. Molecular Weight Data for Homopolymer Starsa
Table 3. Molecular Weight Data for Block Copolymers
star polymers
M
n,GPC
entry
macroinitiator
block copolymer
PtBA-b-PSt
PnBA-b-PSt
PDMA-b-PSt
PNIPAAm-b-PSt
PSt-b-PtBA
PSt-b-PDMA
PSt-b-P4VBA
PSt-b-P2VP
PSt-b-P(4VP-r-St)
PSt-b-P(St-r-MI)-b-PSt
dendron-b-PSt
dendron-b-PSt
(kDa)a
M /M
w
n
M
n,GPC
conversion
(%)
macroinitiator
star no.
(kDa)
56
106
74 (195)c
117
72
76
67
58
73
M /M
48
49
50
51
52
53
54
55
56
57
58
59
25
24
27
26
14
14
14
14
14
14
77
77
12.1
9.7
9.3
6.5
7.6
7.3
7.4
8.2
8.0
11.1
6.8
9.2
1.24
1.12
1.14
1.33
1.18
1.17
1.20
1.11
1.06
1.16
1.07
1.09
w
n
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
1.35
1.22
1.19
1.20
1.22
1.16
1.26
1.21
1.28
1.19
85
87
82
79
83
85
90
92
83
78
70
102 (142)b
1.24 (1.95)b
1.27 (2.10)b
1.21
76 (81)b
85 (80)b
66
89 (160)b
a SEC data relative to PS-standards.
73
69
83
98
38
1.30
1.19
1.24
1.14
86
79
64
43
The high level of alkoxyamine chain end retention was further
confirmed by the efficiency achieved in forming well-defined
polystyrene stars from these chain-end-functionalized linear
polymers. Employing the optimized reaction conditions obtained
from previous combinatorial, high-throughput studies,13 we
heated a mixture of the functionalized linear polystyrenes, 14-
23, with molecular weights in the 3000-10 000 amu range,
divinylbenzene (DVB), and styrene in the ratio 1/4/10 at 125
°C in DMF (30 wt %) for 16 h. Highly branched polystyrene
stars, 31-40, with 40-50 arms35 and a narrow polydispersity
(PDI < 1.2), were obtained with no significant amount of
starting macromonomer remaining (Table 1). The globular,
three-dimensional nature of these star polymers is apparent from
the difference in polystyrene equivalent molecular weights as
determined by GPC and the absolute molecular weights as
determined by either viscosimetry or light scattering. For
1:1 27+28
30
a Molecular weight data for star polymers after purification; GPC data
relative to PS-standards. b GPC data in brackets are for optimized conditions
for polystyrene star formation. c Absolute molecular weight by light
scattering.
The resulting polymers were fully characterized by 1H NMR,
FT-IR, and MALDI-TOF measurements, which showed greater
than 95% incorporation of the desired R-functional end group
and greater than 95% retention of the ω-nitroxide end group
(Figure 3). These results confirm the high degree of end group
fidelity previously observed for polymers prepared using
derivatives of 2 and are in accord with previous work that
showed better than 95% retention of chain end groups for
polymers with molecular weights <25 000 amu.34
9
J. AM. CHEM. SOC. VOL. 125, NO. 3, 2003 721

A R T I C L E S
Bosman et al.
Table 4. Molecular Weight Data for Star Block Copolymersa
we obtained high molecular weight star polymers, 42-47, after
heating these homopolymers with divinylbenzene and styrene
in a 1/4/10 ratio at 125 °C. For the acrylamide and 2-vinyl
pyridine derivatives, excellent control over the coupling reaction
is observed leading to low polydispersity materials (Table 1).
In the case of the acrylate-based macroinitiators, these conditions
resulted in a poorly controlled coupling reaction, and multimo-
dal, high molecular weight star polymers were obtained with a
significantly increased polydispersity (PDI ) 1.95-2.10). High-
throughput optimization of the acrylate reaction system then
revealed that well-defined polyacrylate stars could be formed
by reducing the DVB and styrene concentrations from 1/4/10
to 1/3.4/8.2.
M
conversion
n,GPC
(kDa)b
entry
starting block copolymer
M /M
(%)
w
n
64
65
66
67
68
69
70
71
72
73
74
75
PtBA-b-PSt
PnBA-b-PSt
102
88
90
89
68
66
61
69
57
65
61
83
1.19
1.17
1.37
1.24
1.26
1.27
1.24
1.14
1.14
1.21
1.14
1.11
76
81
83
72
74
63
58
66
82
76
87
89
PDMA-b-PSt
PNIPAAm-b-PSt
PSt-b-PtBAc
PSt-b-PDMA
PSt-b-P4VBA
PSt-b-P2VP
PSt-b-P(4VP-r-St)
PSt-b-P(St-r-MI)-b-PSt
dendron-b-PSt
dendron-b-PSt
a Molecular weight data for star polymers after purification. b SEC data
relative to PS-standards. c Conditions for star polymer formation are the
same as those for the homopolyacrylate example.
From Table 1, it is apparent that the presence or absence of
functional groups attached to the initiating molecule had no
detectable effect on the structural control of the resulting star
copolymer. This is in agreement with earlier work36 for linear
polymers, which showed the compatibility of nitroxide-mediated
living free radical polymerization with a wide variety of
functional groups. As a consequence, formation of star polymers
by the coupling procedure described above should have a wide
tolerance of different functional groups resulting in the ability
to readily prepare functionalized, three-dimensional star poly-
mers. The modular nature of this approach also allows for
excellent control over the number, nature, and placement of these
functional groups.
A further benefit of this modular approach for the synthesis
of these star polymers is that it enables the preparation of star
polymers from mixtures of starting linear polymers. For
example, a 1:1 mixture of hydroxy-functionalized poly(N,N-
dimethylacrylamide), 28 (Mn ) 7100; PDI ) 1.06), initiated
with alkoxyamine, 8, and unfunctionalized poly(N,N-dimethyl-
acrylamide), 27 (Mn ) 5200; PDI ) 1.09), initiated with 2,
could be “knitted” together with divinylbenzene to give a
“mixed” star polymer, 46, with a degree of control similar to
that obtained with the homogeneous examples, 44 and 45
(Scheme 2).
Figure 3. 1H NMR spectrum of tyrosine chain-end-functionalized poly-
styrene, 22.
example, the polystyrene star, 33, was shown to have an absolute
molecular weight of 195 000, which contrasts with the GPC
molecular weight of 74 000, while the absolute molecular weight
of the poly(N,N-dimethylacrylamide) star (220 000), 44, was
significantly greater than the molecular weight measured by
GPC of 69 000. In both cases, a comparison of the absolute
molecular weight with the molecular weight determined by
NMR for the starting linear polymers (relative weight % in star
polymer was ca. 90%) allowed the number of arms per chain
to be calculated, ranging from 30 to 40 arms.
The generality of this approach for the formation of star
polymers was examined in detail by exploring functionalized
macroinitiators based on nonstyrenic monomers. As previously
shown,25-27 R-hydrido initiators, such as 2, are capable of
polymerizing a variety of non styrenic monomers such as tert-
butyl acrylate (tBA), N,N-dimethylacrylamide (DMA), N-
isopropylacrylamide (NIPAM), and 2-vinylpyridine (2VP) with
the acrylamide and acrylate derivatives requiring the presence
of 5 mol % of the corresponding nitroxide, 1, for controlled
polymerization.25 In each case, formation of the macroinitiators,
25-30, was a controlled process leading to low polydispersity
materials (PDI ) 1.09-1.18) with greater than 98% retention
of the dormant alkoxyamine group at the chain end (Table 1).
Using the optimized procedures developed for polystyrene stars,
The accessibility of these chain end functional groups was
demonstrated by the quantitative postfunctionalization of the
hydroxymethyl groups of 46 with the chromophore, 4-pyrene-
butyryl chloride. By comparing the extinction coefficients for
the chromophore-functionalized derivative of 46 with the
corresponding chromophore-functionalized derivatives of 45 and
44, we determined that approximately 50% of the chain ends
of 46 contain a hydroxyl group, in agreement with the synthetic
strategy. The synthesis of 46 is an excellent illustration of the
power of this modular approach when combined with the ability
to use dormant linear chains prepared by living free radical
procedures. By simply mixing two starting linear polymers, each
having dormant chain ends of essentially similar reactivity, we
obtained a complex macromolecular architecture in which the
number of chain end functional groups is controlled. It should
be noted that chains of different lengths or monomer composi-
tion can also be used, which leads to further possible structural
refinement. One potential application of these functionalized
star polymers is as pore generating materials for the preparation
of nanoporous thin films as low dielectric constant layers in
advanced microelectronic devices.37
The presence of the chain end functional groups at the
periphery of these star architectures, combined with their
9
722 J. AM. CHEM. SOC. VOL. 125, NO. 3, 2003

Functionalized Three-Dimensional Macromolecules
A R T I C L E S
Scheme 2. Graphical Representation of the Synthesis of a Poly(N,N-dimethylacrylamide) Star, 46, with 50% of the Chain Ends
Functionalized with Hydroxy Groups
multifunctional nature and nanoscale size, also suggests the use
of these structures as polymer supports for homogeneous
catalysis. On the basis of the synthetic strategy of Itsuno and
Fre´chet,38 the protected tyrosine initiator, 13, was prepared as
shown in Scheme 1 and used to initiate the polymerization of
styrene. The resulting telechelic polystyrene, 22 (Mn ) 5200,
PDI ) 1.12), contains both a chiral ligand and an R-hydrido
alkoxyamine as end groups and could therefore be used to
prepare the star polymer, 39, under standard conditions. This
gave a soluble, three-dimensional macromolecule, which, after
deprotection with trifluoroacetic acid, has ca. 40-50 L-tyrosine-
based ligands located at its periphery. These functionalized stars
could then be investigated as multifunctional chiral auxiliaries
for the catalytic alkylation of benzaldehyde with diethylzinc
(Scheme 3).39 Indeed, quantitative formation of the enantiomeric
alcohols, 62 and 63, was observed after stirring a mixture of
benzaldehyde and diethylzinc in the presence of deprotected
39 (0.05 mol equiv) for 8 h at 0 °C. Significantly, the use of
deprotected 39 led to stereoselective alkylation with an observed
enantiomeric excess, ee, of 71%, as compared to 18% for a
peripherally substituted dendrimer analogue40 and 77% for a
low molecular weight linear PS-analogue.41 The increased ee
as compared to the dendritic analogue which is due to functional
group accessibility and the ability to easily recycle these three-
dimensional structures when compared to short linear polymers
Scheme 3. Enantiomeric Alkylation of Benzaldehyde Catalyzed by
the L-Tyrosine-Functionalized Star Polystyrene, 39
demonstrate the viability of these chain-end-functionalized star
polymers as catalytic scaffolds. The high molecular weight and
branched nature of the scaffolds permit increased solubility and
functionality, leading to an efficient homogeneous system while
at the same time permitting the use of nanoseparation/filtration
techniques for catalyst recycling.42
Block Copolymer Stars. The great potential of the modular
approach to star polymers was further demonstrated by employ-
ing block copolymers as starting materials. In analogy with the
homopolymers studies described above, the presence of the
dormant alkoxyamine group at the chain end of a diblock
copolymer can be used as an initiating site for star formation
via chain coupling in the presence of divinylbenzene. The added
dimension afforded by block copolymers leads to a number of
potential advantages; for example, the use of an amphiphilic
9
J. AM. CHEM. SOC. VOL. 125, NO. 3, 2003 723

A R T I C L E S
Bosman et al.
Scheme 4. Synthesis of Poly(NIPAM)-b-polystyrene Star Block Copolymer, 67
diblock leads to a core-shell-type morphology with an apolar
interior and a polar corona or vice versa.
base demonstrated its amphiphilic nature. Alternatively, the acid
groups could be introduced directly into the star structure
by polymerizing the cetyltrimethylammonium salt of 4-vinyl-
benzoic acid (4VBA),44 with a PS-macroinitiator, 14, followed
by coupling of the resulting block copolymer, 54, with di-
vinyl benzene and neutralization of the carboxylate salt to give
a similar star, 70, with carboxylic groups in the core.
For the introduction of basic or chelating functionalities, either
2-vinyl pyridine or 4-vinyl pyridine was employed as monomers.
In the case of 2-vinyl pyridine, well-defined block copolymers
could be prepared from the polystyrene macroinitiator (Mn )
5300; PDI ) 1.09), 14, and the resulting diblock copolymer
(Mn ) 8200; PDI ) 1.11), 55, subsequently coupled with divinyl
benzene to give a PS-b-P2VP star, 71. Alternatively, the poly-
(2-vinylpyridine) block could be replaced with a random block
of styrene and 4-vinylpyridine (4VP) to give a polystyrene-b-
(styrene-r-4-vinylpyridine) copolymer, 56. Coupling of 56 then
leads to the star polymer, 72, in which the nanoenvironment of
the interior can be controlled by the percent incorporation of
4-vinylpyridine in the original block copolymer. By increasing
the amount of 4-vinyl pyridine in the core, both the number of
chelating or H-bond acceptor sites as well as the polarity of the
core increases.
The concept of a structured core can be further amplified by
introducing acceptor-donor-acceptor H-bonding arrays into
the star structure. These were introduced by copolymerizing a
mixture of maleimide and styrene from a PS-macroinitiator, 14,
using a high feed ratio of styrene to maleimide (9/1 St/MI).45
The resulting block copolymer, 57, consists of an initial PS-
block followed by a gradient styrene-maleimide copolymer and
a final PS-block. This copolymer was subsequently coupled with
DVB to give the functionalized star copolymer, 73, having a
polystyrene core surrounded by a shell of H-bonding units that,
in turn, is surrounded by a PS-corona.
A series of diblock copolymers were prepared by reaction of
the appropriate macroinitiators with styrene at 120 °C. This gave
the resulting block copolymers PBA-b-PS 48, 49, PDMA-b-PS
50, and PNIPAM-b-PS 51 as low polydispersity materials with
little or no detectable homopolymer contamination. As antici-
pated, coupling of these block copolymers with divinylbenzene
and styrene under the conditions defined above proceeded
smoothly in each case to give the corresponding star polymers,
64-67, in a controlled fashion (Scheme 4).
In contrast, the use of the reverse diblock copolymers as
starting materials would result in inverted materials in which
the polar core is surrounded by an apolar exterior. To achieve
these structures, the initial macroinitiator should be polystyrene
from which either tBA or DMA would subsequently be grown.
Although it has previously been reported24b that the polymer-
ization of acrylates from a polystyrene macroinitiator is
problematic, no difficulties were observed at these low molecular
weights, and well-defined block copolymers, such as 53, were
obtained. Subsequent coupling of 53 (Mn ) 7300, PDI ) 1.17)
gave the desired star block copolymer, 69 (Mn (abs) ) 175 000,
Mn (GPC) ) 66 000, PDI ) 1.17), in which a hydrophobic
polystyrene shell surrounds a hydrophilic DMA core. As was
the case with homopolymer examples, the polystyrene equivalent
molecular weights, as determined by GPC, were significantly
lower than their absolute molecular weights with the final star
polymers containing an average of 30-40 chains.
The reactivity of the internal functional groups was demon-
strated for the PS-PtBA star, 68, where hydrolysis of the tert-
butyl esters in the interior of the star with trimethylsilyliodide43
gives the amphiphilic polystyrene-b-poly(acrylic acid) star, 76,
in which a PSt-corona surrounds a polycarboxylic acid interior.
1H NMR and IR spectroscopy confirmed complete deprotection
of the tert-butyl groups, while the solubility of 76 in aqueous
The sophistication of the structural control during the
9
724 J. AM. CHEM. SOC. VOL. 125, NO. 3, 2003

Functionalized Three-Dimensional Macromolecules
A R T I C L E S
Scheme 5. Schematic Representation of the Synthesis of the Dendritic Star Block Copolymer, 75
synthesis of the above block copolymer stars demonstrates the
potential of this modular approach for the fabrication of
functionalized three-dimensional macromolecules. However, the
modular nature permits other, more complex, macromolecular
architectures to be employed as starting materials; the only
criteria is that an alkoxyamine group must be present at one of
the chain ends. Perhaps the best example of this structural
diversity is the synthesis and application of dendritic linear block
copolymers, 58 and 59, as starting materials for the preparation
of star polymers. A series of such hybrid structures were then
prepared by reaction of a fourth generation Fre´chet-type
dendron,46 77, containing an alkoxyamine group at the focal
point, with styrene under living free radical conditions to give
the hybrid linear-dendritic block copolymers, 59 (Scheme
5).18,47,48
Host-Guest Interaction Stars. The presence of the 4-vin-
ylpyridine units in the interior of the PSt-P(4VP-r-St) stars, 72,
makes it possible to use these entities as supramolecular
scaffolds for guests containing hydrogen bond donors, that is,
carboxylic acid functions. The driving force for formation of
these polymeric complexes49 is a combination of H-bonding and
the increased polarity of the nanoenvironment in the interior of
the polymer. Indeed, the chromophore, coumarin-3-carboxylic
acid, 60, which was practically insoluble in toluene, could be
solubilized in deuterated toluene upon addition of 72, as
The presence of an alkoxyamine chain end at one chain end
of the hybrid block copolymer, 59, then permits the coupling
of 59 with divinylbenzene, and, interestingly, this reaction was
not retarded by the presence of the sterically large dendritic
fragments. As a result, novel star structures, such as 75,
decorated with numerous dendron end groups on the periphery
were obtained. Monitoring the progress of this transformation
from dendritic initiator, 77, to block copolymer, 59, to star, 75,
could be conveniently accomplished by gel permeation chro-
matography, which shows the expected increase in molecular
weight and the associated low polydispersity of the products
(Figure 4).
Figure 4. GPC traces for the starting dendritic initiator, 77 (Mn ) 3400,
PDI ) 1.002), intermediate dendritic-polystyrene block copolymer, 59
(Mn ) 6800, PDI ) 1.07), and the final dendritic star block copolymer, 75
(Mn ) 72 000, PDI ) 1.19).
9
J. AM. CHEM. SOC. VOL. 125, NO. 3, 2003 725

A R T I C L E S
Bosman et al.
Scheme 6. Structure of Coumarin-3-carboxylic Acid, 60, and
Zn(II)protoporphyrin IX, 61
Figure 5. UV-vis (left) and fluorescence (right) spectra of star 72 loaded
1
evidenced by H NMR spectroscopy. Significantly, the UV-
with Zn(II) protoporphyrin, 61, dissolved in toluene, excitation at λ ) 430
vis (λmax ) 290 and 340 nm) and fluorescence (λem ) 420 nm)
spectra for this host-guest complex in toluene demonstrated
that 60 was in a nonaggregated state, which suggests molecular
complexation of the coumarin carboxylic acid with the vinyl
pyridine moieties located within the star polymer.50 That
H-bonding is a driving force for this complex formation was
evident from FT-IR measurements which showed that the O-H
stretching band of the carboxylic acid for 60 shifts to lower
energies (broad absorption around 2507 cm-1), accompanied
nm.
by a shift in the carbonyl band from 1740 to 1757 cm-1 49
.
Alternatively, the ligating ability of the 4-vinylpyridine-
functionalized stars, 72, could be used to solubilize organo-
metallic systems such as zinc(II) protoporphyrin IX, 61 (ZnP-
PIX, Scheme 6). In this case, metal ligand interactions as well
as H-bonding are responsible for complex formation and
solubilization, with the signals belonging to the ZnPPIX nucleus
being clearly visible in the 1H NMR spectrum and the extreme
broadening of the resonances for the pyridine groups indicating
coordinative interaction of the pyridine nitrogens with the
Zn(II)-site in the protoporphyrins.51 UV-vis and fluorescence
studies of mixtures of ZnPPIX (61) and 72 (15 wt % of dye) in
toluene were in agreement with the pyridine coordination
observed in NMR experiments, as comparable UV-vis and
fluorescence spectra were obtained from a model system
consisting of native Zn-porphyrin, 61, dissolved in toluene
containing 1 M pyridine.
This supports the formation of a host-guest system (Figure
5).51 Moreover, the exact overlay of the SEC traces recorded
with dual RI and UV detection (420 nm, Soret band of the
porphyrin) confirmed the presence of the low molecular weight
dye in the star-shaped macromolecule and the strong degree of
encapsulation. Consequently, functionalized star polymers such
as 72 can be used to entrap a variety of interacting guest
molecules using a combination of H-bonding and metal-ligand
interactions.
Figure 6. (a) Infrared spectra of 2,6-bis(acetylamino)pyridine 6 (dot-
dashed), star 73 (dashed), and a 1:1 mixture of 6 and 73 in CDCl3 (8 mM)
(solid). (b) NMR titration curve obtained by addition of 73 to a 17 mM
solution of 6 in CDCl3.
unit) revealed a new broad absorption band in the amide-stretch
region of the infrared spectrum (Figure 6a). The appearance of
this band at lower energy (3311 cm-1) than those for the non-
H-bonded amides of the starting individual host and guest (3401
and 3424 cm-1, respectively) is indicative of the formation of
the targeted hydrogen bonded complex.
These findings were confirmed by 1H NMR titration of 2,6-
bis(acetylamino)pyridine, 6, with 73 in deuterated chloroform
via monitoring of the change in the chemical shift of the amide
protons of the guest being followed. Assuming that all male-
imide sites interact independently, we obtained an association
constant, Ka, of 14 ( 1 M-1 which is comparable to the reported
Ka for a small molecule model system with maleimide as the
ADA unit of 131 M-1 (Figure 6b).55,56 These results clearly
indicate that functionalized star polymers can be used as
scaffolds for the encapsulation and chelation of a variety of
guests.
This concept of using the interior of the star as a nanoscale
supramolecular environment was further investigated with a
more selective host-guest system based on the maleimide-
containing star 73. The acceptor-donor-acceptor (ADA) array
present in the maleimide repeat units makes it possible to use
multiple H-bonding as a directional and selective tool for
molecular recognition, and this behavior was investigated
with 2,6-bis(acetylamino)pyridine, 6, as the complementary
guest.19,52-54 Initial analysis of a mixture of 73 and 6 in
deuterated chloroform (1:1 molar ratio of guest:maleimide repeat
(56) Lange, R. F. M. Ph.D. Thesis, Eindhoven University of Technology,
November, 1997.
9
726 J. AM. CHEM. SOC. VOL. 125, NO. 3, 2003

Functionalized Three-Dimensional Macromolecules
A R T I C L E S
Figure 7. TEM micrograph of palladium-functionalized star, 78, dropcast
from toluene solution (0.5 mg/mL); white bar represents 20 nm.
Catalysis. As detailed above for chain-end-modified star
polymers, the use of the star architecture as a scaffold for the
placement of numerous catalytic sites is an exciting avenue of
research. However, the star architecture can also serve as a
stabilizing environment for the fabrication of catalytically active
metallic nanoparticles. Previously, poly(vinylpyridine)-contain-
ing block copolymer micelles have been utilized to stabilize
Pd-nanoclusters;57 however, the dynamic nature of polymeric
micelles makes them sensitive to environmental conditions. To
address this issue, covalent systems such as dendrimers,58
hyperbranched polymers,59 and star copolymers60 have recently
been employed as templates for nanoparticle formation, although
the challenges inherent to the use of large quantities of dendritic
macromolecules are a concern.7c To overcome this difficulty,
the 2-vinylpyridine-functionalized star polymer, PS-b-P2VP 71,
was investigated as a more readily available scaffold for the
preparation and stabilization of metallic nanoparticles. Addition
of Pd(OAc)2 to a toluene solution of 71 resulted in slow
solvation of the metal with formation of a clear light-orange
solution (broad absorptions at λmax ) 325 and 365 nm).
Subsequent reduction of the bound palladium cations was
performed using ethanol at elevated temperatures and could be
followed by a color change to dark brown. After being
precipitated in methanol, the star-stabilized palladium nanopar-
ticles, 78, were obtained as a dark brown solid, and TEM
analysis confirmed the formation of isolated Pd-nanoparticles
with diameters of 2-3 nm (Figure 7). Furthermore, SEC analysis
of these Pd-containing stars, 78, showed that they were almost
identical to the starting PS-b-P2VP star 71, demonstrating that
formation of the palladium nanoparticles did not induce ag-
glomeration of the star polymer. This lack of association
provides further support for the concept of using three-
dimensional star polymers to provide a sterically isolated internal
nanoenvironment in which a variety of reactions can take place.
To investigate the possibility of using these nanoparticles in
catalysis, initial studies were performed on the hydrogenation
reaction of cyclohexene. Indeed, cyclohexene conversion into
cyclohexane was catalyzed by the Pd-loaded star 78, with an
observed TOF (turnover frequency) of 138 h-1 atm (H2)-1. This
is comparable to the activity of other polymer stabilized Pd-
Figure 8. GC conversion of 1-bromo-4-nitro benzene, 79 (b), to the
corresponding cinnamate derivative, 81 (9), catalyzed by the Pd-containing
star 78.
Scheme 7. Heck Reaction of 1-Bromo-4-nitrobenzene, 79, with
n-Butyl Acrylate, 80, Catalyzed by the Pd-Containing Star
Polymer, 78
nanoparticles and demonstrates the potential for these materi-
als.57 This was further tested by examining the ability of these
palladium-containing stars, 78, to catalyze more demanding
transformations such as the Heck reaction (Scheme 7). Heating
a mixture of 1-bromo-4-nitrobenzene, 79, and n-butyl acrylate,
80, in xylene at 125 °C in the presence of 0.5 mol % of Pd
encapsulated in star 78, with tributylamine as base,57 led to
almost quantitative formation (96%) of the trans cinnamate, 81,
in 2 h after a short induction period, resulting in a TOF (turnover
frequency) of 95 h-1 (Figure 8).
Significantly, no formation of palladium black was observed
during the reaction, demonstrating the steric stabilization of the
nanoparticles. Of equal significance is the ability to perform
the reaction in nonpolar solvents such as xylene, instead of the
traditional polar amidic solvents. This illustrates the utility of
these functionalized three-dimensional macromolecules in creat-
ing a defined nanoenvironment, in this case, a nonpolar
polystyrene corona, soluble in xylene, surrounding the catalyti-
cally active interior. Precipitation of the reaction mixture in
methanol leads to recovery of the Pd-containing star catalyst,
82, which was reused five times without any observable
degradation in performance.
Conclusions
The ready availability of telechelic linear polymers from
nitroxide-mediated living free radical polymerizations has
permitted the development of a modular approach to function-
alized star macromolecules in which the nature, number, and
location of the functional groups can be varied to an unprec-
edented degree. As a consequence, libraries of linear polymeric
starting materials with different backbones and end groups can
be prepared and combined to give functionalized star architec-
tures with tailor-made physical and chemical properties. The
generality of this modular approach has been demonstrated by
the synthesis of three-dimensional nanomaterials from a wide
(57) (a) Antonietti, M.; Wenz, E.; Bronstein, L.; Seregina, M. AdV. Mater. 1995,
7, 1000. (b) Klingelho¨fer, S.; Heitz, W.; Greiner, A.; Oestreich, S.; Fo¨rster,
S.; Antonietti, M. J. Am. Chem. Soc. 1997, 119, 10116.
(58) Zhao, M.; Crooks, R. M. Angew. Chem., Int. Ed. 1999, 38, 364.
(59) Mecking, S.; Thomann, R.; Frey, H.; Sunder, A. Macromolecules 2000,
33, 3958.
(60) Youk, J. H.; Park, M. K.; Locklin, J.; Advincula, R.; Yang, J.; Mays, J.
Langmuir 2002, 18, 2455.
9
J. AM. CHEM. SOC. VOL. 125, NO. 3, 2003 727

A R T I C L E S
Bosman et al.
range of different block copolymers and random copolymers,
optionally with end group functionalities. These materials are
active as supramolecular hosts for the encapsulation of a variety
of guests, and as scaffolds for catalytic sites, which can be
located at either the periphery or the interior of the stars. The
diverse nature of these applications demonstrates the utility of
this modular, library-based approach to functionalized three-
dimensional macromolecules.
and resolving the X-ray structure of 3, respectively. The
assistance of G. Klaerner and D. Benoit, SYMYX Technologies,
in the high-throughput optimization and study of the formation
of the star polymers is recognized with thanks. A.W.B.
acknowledges The Netherlands Organization for Scientific
Research (NWO) for fellowship support. Financial support from
NSF (DMR-9808677, Center for Polymeric Interfaces and
Macromolecular Assemblies), IBM Corporation, AFOSR, and
the U.S. Department of Energy under grant DE-AC03-
76SF00098 is gratefully acknowledged.
Acknowledgment. J. Donners (Eindhoven University of
Technology, Netherlands) and Dr. A. G. Oliver (UCB) are
acknowledged for performing transmission electron spectroscopy
JA028392S
9
728 J. AM. CHEM. SOC. VOL. 125, NO. 3, 2003