Light-induced modular ligation of conventional RAFT polymers

Article abstract of DOI:10.1002/anie.201206905

Making light work of RAFT conjugation: A non-activated RAFT agent at the end of RAFT polymers can readily be coupled with ortho-quinodimethanes (photoenols) in a photo-triggered Diels-Alder reaction under mild conditions without catalyst (see scheme). The

Full text of DOI:10.1002/anie.201206905

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DOI: 10.1002/anie.201206905
Click Polymer Ligation
Light-Induced Modular Ligation of Conventional RAFT Polymers**
Kim K. Oehlenschlaeger, Jan O. Mueller, Niklas B. Heine, Mathias Glassner,
Nathalie K. Guimard, Guillaume Delaittre, Friedrich G. Schmidt, and Christopher Barner-
Kowollik*
Materials engineering has become one of the most studied
areas in contemporary chemistry. Very significant contribu-
tions to this ever-expanding field have been made by
creatively combining controlled/living polymerization (LP)
techniques with a special subset of conjugation techniques,
known as click reactions.[1] Some well-known examples of
reactions in macromolecular science, which may fulfill the
click criteria, are copper-catalyzed azide–alkyne cycloaddi-
tions (CuAAC),[2] (hetero) Diels–Alder cycloadditions
((H)DA),[3] oxime ligations,[4] and nitrile imine tetrazole-ene
cycloadditions (NITEC).[5]
The advantages of click chemistry include mild reaction
conditions, practically quantitative conversion and selectivity
(i.e., allowing orthogonal reactions to be performed), and the
applicability to a wide range of materials. Consequently, click
chemistry has proven to be very beneficial for functionalizing
polymers as well as generating sophisticated polymeric
architectures. Given the utility of click chemistry, it comes
as no surprise that there is a continued effort to develop new
click-type reactions to expand the toolbox of techniques that
can be employed in macromolecular design.
Many of the aforementioned click reactions require
functional groups for the controlled polymerization step
that are different from those needed for the subsequent
polymer–polymer coupling. However, one click reaction that
has been employed for a wide range of macromolecular
applications[3b,6] is the RAFT–HDA (reversible addition-
fragmentation chain transfer–HDA) process, which utilizes
a RAFT agent that serves two purposes: The chain-transfer
agent mediates polymerization and acts as a reactive end-
group for post-polymerization HDA conjugation.[3b] RAFT
polymerization, one of the most powerful LP techniques,[7]
allows for the generation of a great variety of polymeric
materials in terms of chemical structure, microstructure,
architecture, and properties.[8] Unfortunately, not every
RAFT agent is a suitable reagent for thermally driven HDA
chemistry owing to the high activation energy associated with
this reaction. The unfavorable reaction energetics stem from
=
the presence of the electron-rich C S bond of the dithioester,
which results in a relatively large highest occupied molecular
orbital (HOMO) lowest unoccupied molecular orbital
(LUMO) gap for the diene–dithioester pair. Furthermore,
only a few dithioesters have been found to allow for both LP
and polymer–polymer coupling within an acceptable time
frame. Benzyl(diethoxyphosphoryl) dithioformate, benzyl-
pyridin-2-yldithioformate, and benzylphenyl sulfonyldithio-
formate all bear a highly electron-withdrawing Z group,
which lowers the energy of the molecular orbitals and,
therefore, reduces the HOMO–LUMO gap between the
diene and dienophile (i.e., the RAFT agent). The addition of
a Lewis or Brønsted acid can further reduce the frontier
molecular orbital gap such that the HDA reaction can
proceed in a few minutes at ambient temperature.[9] Never-
theless, the electron-deficient nature of the aforementioned
RAFT agents tends to decrease their ability to mediate and
control polymerization and, consequently, limits the selection
of monomers that can be polymerized. One possible strategy
for overcoming this limitation and, thus, expanding the
applications of RAFT polymers in modular macromolecular
design is to identify a highly reactive diene that can undergo
a HDA reaction with non-activated (i.e., electron-rich)
RAFT agents. In this context, photoenols, which represent
highly reactive dienes, have recently been employed by us in
other DA-based reactions to generate complex macromolec-
ular architectures[10] and to perform spatially controlled
surface grafting.[11] Photoenols can be generated by irradiat-
ing ortho-alkyl-substituted aromatic ketones or aldehydes
with UV light.[12]
[*] K. K. Oehlenschlaeger,[+] J. O. Mueller,[+] N. B. Heine, M. Glassner,
Dr. N. K. Guimard, Dr. G. Delaittre, Prof. Dr. C. Barner-Kowollik
Preparative Macromolecular Chemistry, Institut fꢀr Technische
Chemie und Polymerchemie, Karlsruhe Institute of Technology
(KIT)
Engesserstrasse 18, 76128 Karlsruhe (Deutschland)
E-mail: christopher.barner-kowollik@kit.edu
Homepage: http://www.macroarc.de
Herein, the successful catalyst-free HDA conjugation of
a non-activated dithioester, 2-cyanopropyl dithiobenzoate
(CPDB), with a reactive photoenol diene at ambient temper-
ature is demonstrated for the first time. CPDB was selected as
the dithioester of choice since it can be considered as one of
the most universal RAFT agents. Indeed, it is able to control
the radical polymerization of most common vinylic mono-
mers (i.e., (meth)acrylates, (meth)acrylamides, styrenics).[13]
In an exploratory study, the HDA reaction between the
photoenol precursor 2-methoxy-6-methylbenzaldehyde (2)
and CPDB-functionalized poly(methyl methacrylate)
(PMMA; 1) was confirmed (Scheme 1). The efficiency of
Dr. F. G. Schmidt
Evonik Industries AG
Paul-Baumann-Strasse 1, 45764 Marl (Deutschland)
[+] These authors contributed equally to this work.
[**] C.B.-K. is grateful for continued support from Evonik Industries and
the Karlsruhe Institute of Technology (KIT) in the context of the
Excellence Initiative for leading German universities as well as the
Ministry of Science and Arts of the state of Baden-Wꢀrttemberg.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201206905.
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Scheme 1. Photo-conjugation of the dithiobenzoate end-capped poly(-
methyl methacrylate) 1 with 2-methoxy-6-methylbenzaldehyde (2),
yielding the isothiochroman 3.
the new conjugation reaction was further evaluated for block
copolymer synthesis. Finally, the application of the conjuga-
tion technique to photoenol-functionalized poly(e-caprolac-
tone)s (PCLs) 4 and 5 of different molar masses, as well as to
RAFT polymers of different molar masses and monomer
composition, shows that the new methodology can be applied
to a wide range of polymers.
Figure 1. UV/Vis spectra of the RAFT polymer 1 (solid line) and the
irradiated mixture of 1 and 2 (dashed line) after precipitation from the
reaction mixture.
CPDB was synthesized according to a literature method[14]
and subsequently utilized as a chain-transfer agent in the
RAFT polymerization of methyl methacrylate. Poly(methyl
methacrylate) 1 was obtained with a number-average molar
mass (Mn) of 3300 gmolÀ1 and a polydispersity (PDI) of 1.27.
End-group functionalization of 1 with the photoenol precur-
sor 2 was achieved by irradiating a deoxygenated solution of
1 (10 mgmLÀ1) and 2 (1.1 equiv) in acetonitrile for 3 h at
ambient temperature. The photoenol precursor 2 was selected
for this reaction because it is the most reactive photoenol
tested to date.[10b] Its high reactivity is believed to originate
corresponding to the p–p* transition is drastically reduced
after the reaction compared to that of the starting material.
The presence of aromatic substituents in the product can
explain the remaining low absorbance in this region. In
addition, the absence of a n–p* transition further indicates
that there is no longer any detectable thiocarbonyl functional
group present in the product.
from the significant overlap of its absorption spectrum (lmax
=
SEC/ESI-MS analysis confirmed that the conjugation
reaction occured since a comparison of the MS spectra of the
starting material and the product clearly reveals that the
mass-to-charge (m/z) signal associated with the RAFT
polymer 1 is shifted by 149.9 amu, which corresponds very
well to the exact mass of 2 (M = 150.07 gmolÀ1; Figure 2). The
SEC/ESI-MS spectrum of the product also reveals the
presence of a minor impurity, as well as a trace amount of
starting material. Although the presence of starting material
would seem to contradict the UV/Vis results, it should be
noted that the detection limit of ESI-MS is lower than that of
UV/Vis spectroscopy and it is possible that the presence of
a small amount of starting material could easily be masked by
the absorption spectrum of the product.
315 nm) with the emission spectrum of the employed UV
lamp (Comedico Arimed B6; lmax = 320 nm) (Figure S2 in the
Supporting Information).
Following irradiation, the product was isolated by precip-
itation in cold n-hexane. The success of the reaction can be
qualitatively assessed by comparing the color of the reaction
mixture prior to and after irradiation. The initially pink
solution became colorless during irradiation, indicating the
consumption of the chromophoric dithioester end group. In
addition, a control experiment in which a pure solution of
1 was exposed to UV light for an extended period of time
revealed the persistence of the pink coloration and suggested
that the dithioester is stable under these conditions. Thus, it is
reasonable to assume that 1 undergoes a reaction
with 2 in the presence of UV light. The nature and
success of this reaction were determined by size-
exclusion chromatography/electrospray ioniza-
tion-mass spectrometry (SEC/ESI-MS), electro-
spray ionization-collision-induced dissociation-
mass spectrometry (ESI-CID-MS), 1H NMR spec-
troscopy, and UV/Vis spectroscopy (Figure 1).
UV/Vis spectroscopy was employed to assess
the difference in absorbance of the RAFT poly-
mer 1 and the product 3 because the typical strong
p–p* and weak n–p* (n = lone-pair electrons)
transitions of the thiocarbonyl moiety, which are
characteristic for RAFT agents, should be absent
in the absorption spectrum of the product if
Figure 2. SEC/ESI-MS spectra of the PMMA 1 before (top) and after (bottom) the
conjugation reaction with 2. The spectra correspond to the polymer eluted at later
1 partakes in the desired HDA cycloaddition.
Indeed, the absorption maximum at 300 nm retention times (lower molar masses).
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6.5 to 8 ppm region emerge, which correlates
well with the aromatic protons k’, l’, and m’ of
the cycloadduct 3. In addition, the total inte-
gration value for the signals arising from the
aromatic protons corresponds to eight protons,
which is in perfect agreement with the number
of aromatic protons expected for the product.
Moreover, the presence of two new resonance
signals at d = 5 ppm and 5.5 ppm further sug-
gests the formation of the desired product since
these signals can be attributed to the new
protons i’ and p’ of the isothiochroman.
To assess the scope of the photo-induced
HDA reaction, modular formation of block
copolymers consisting of a RAFT polymer,
(i.e., PMMA 1, polystyrene (PS), or poly(meth-
yl acrylate (PMA)) and a photoenol-function-
alized PCL (4 or 5, see Scheme 2) were inves-
tigated. Therefore, a ring-opening polymeri-
zation (ROP) initiator carrying the photoenol
moiety was first synthesized following the
synthetic route depicted in Scheme 2.
Figure 3. a) ESI-CID-MS spectra of the RAFT-HDA product (bottom) and of the
resulting daughter ion (top). The right-hand-side depicts the proposed fragmentation
process of the mother ion. b) Structures predicted to result from the fragmentation of
the daughter ion. All structures depicted in (a) and (b) are detected as sodium
adducts.
The ROP of e-caprolactone was subse-
quently performed in the presence of the
photoenol-functionalized initiator and triazabi-
Although the results from SEC/ESI-MS and UV/Vis
spectroscopy both confirm the successful coupling of 1 with 2,
these results do not reveal any information about the nature
of the chemical bond formed. Therefore, ESI-CID-MS was
carried out to determine the chemical structure of the product
(Figure 3). The most abundant daughter ion resulting from
ESI-CID-MS fragmentation of CPDB end-capped poly-
(methyl methacrylate)s contains a terminal double bond
resulting from the elimination of benzodithioic acid.[15] In
contrast to the fragmentation pattern of the dithioester-based
polymer, the RAFT–HDA product was found to generate no
unsaturated fragment. Instead, the primary daughter ion
obtained from the fragmentation of the HDA product is
a thiol end-capped polymer (m/z 824.38 amu) that results
cyclodecene in toluene under inert gas at ambient temper-
ature for 5 h or 7 h (Scheme 2). Precipitation of the products
in cold n-hexane resulted in the short PCL 4 (Mn =
2000 gmolÀ1, PDI = 1.25) and the longer PCL 5 (Mn =
8400 gmolÀ1, PDI = 1.08), respectively. Quantitative end-
1
group functionalization was demonstrated by H NMR spec-
troscopy, through the comparison of the resonance signals
corresponding to the aromatic end group protons (d =
7.35 ppm and 6.8 ppm in CDCl3) with the characteristic
terminal hydroxymethylene proton resonances (d = 3.64 ppm
in CDCl3).
Polymer conjugations of the different RAFT polymers
with the photoenol-functionalized PCLs were performed. A
short block copolymer was synthesized from equimolar ratios
of PCL 4 and PMMA 1, determined from the Mn values
À
from the cleavage of the S C bond that was part of the
1
dithioester group. Such a process is only conceivable if the
thiocarbonyl group is converted into a thioketal, permitting
the generation of two stable fragments (i.e., the polymeric
thiol and a cyclic thioether). Additional ESI-CID-MS experi-
ments performed on the daughter ion resulted in a fragmen-
tation pattern that would be expected for methyl methacry-
late polymers,[15a] although an isobaric thiolactone series
would also give rise to the same fragmentation pattern. These
results support the hypothesis that a polymeric thiol fragment
was obtained as the daughter ion of the product.
calculated by H NMR spectroscopy. Larger block copoly-
Finally, the most conclusive evidence for the successful
HDA cycloaddition between the non-activated dithioester-
terminated polymer 1 and the highly reactive diene precursor
2 was obtained by NMR spectroscopy (Figure 4). The
1H NMR spectrum of the irradiated solution of 1 and 2
revealed a significant change in the signals between d = 6.5
and 8 ppm that are associated with the aromatic protons.
Specifically, the NMR signals associated with the phenyl
protons a–c shift upfield and new resonance signals in the d =
Figure 4. 1H NMR spectra of the reactants 2-methoxy-6-methylbenzal-
dehyde (2) and dithiobenzoate end-capped PMMA 1, as well as the
isothiochroman 3 formed after irradiation for 3 h at ambient temper-
ature.
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Scheme 2. Synthesis of the photoenol-functionalized PCLs 4 and 5.
Reagents and conditions: a) K2S2O8, CuSO4, acetonitrile, 908C, 45 min;
b) AlCl3, CH2Cl2, room temperature, 16 h; c) 11-bromo-1-undecanol,
K2CO3, DMF, room temperature, 72 h; d) e-caprolactone, triazabicyclo-
decene, toluene, room temperature, 5 h or 7 h depending on the Mn
targeted.
mers were obtained by combining CPDB-functionalized PS
or PMA with PCL 5. SEC and SEC/ESI-MS analyses
(Figure S7) of the short block copolymer formed from PCL
4 and PMMA 1 confirmed the success of the conjugation
reaction. Owing to the large size of the other block copoly-
mers generated, only SEC analysis could be employed to
evaluate the efficacy of these reactions. Representative SEC
traces of the individual building blocks and the copolymer
products for the PMMA–PCL and PMA–PCL systems are
illustrated in Figure 5. The results of the PS–PCL block-
copolymer formation are available in the Supporting Infor-
mation (Figure S8).
Figure 5. Normalized SEC traces of a) PMMA 1 (Mn =3300 gmolÀ1),
PCL 4 (Mn =2000 gmolÀ1) and the block copolymer
(Mn =5900 gmolÀ1). An ESI-MS analysis of the PMMA-b-PCL is shown
in Figure S7a and Table S1. b) PMA (Mn =5400 gmolÀ1), PCL 5
(Mn =8400 gmolÀ1) and the block copolymer (Mn =13000 gmolÀ1).
In comparison with the SEC curves of each starting
material, the chromatograms of the block copolymers are
significantly shifted towards higher molar masses. These
results clearly indicate the successful coupling of the single
blocks. The SEC traces for all the block copolymers indicate
that very high conversion is achieved for all of the conjugation
reactions because the measured Mn values are found to be in
good agreement with the theoretically predicted Mn values
for the copolymer (Table 1). Note that the slight differences
between the experimental and theoretical values originate
from the complex elution behavior of the block copolymers
which arises because of the differing properties of each
block.[16]
Although the block copolymer formation was very
efficient for all polymer blocks, a very small amount of
starting material can be detected in the chromatogram for
both the PMA–PCL and PS–PCL systems. The presence of
the starting material can be explained by considering that
RAFT polymerization usually yields a small fraction of non-
thiocarbonylthio functional chains from termination reac-
tions.[13a,17] Such ꢀdeadꢁ polymer chains are DA unreactive
and, thus, an equimolar amount of the PCL polymer block
will also remain. Additionally, it is not surprising that more
residual starting material is detected for the block copolymer
formed from higher molecular-weight RAFT polymers
because significantly more dead polymer chains are generated
when the RAFT polymerization is conducted for an extended
period of time and to higher conversions.
Table 1: The Mn values of the homopolymer building blocks and the
copolymers prepared.[a]
Monomer
(RAFT)
Mn RAFT
Mn ROP
Mn Block
polymer
polymer
copolymer
[gmolÀ1
]
[gmolÀ1
]
[gmolÀ1
]
Methyl methacrylate
Methyl acrylate
Styrene
3300
5400
5900
2000
8400
8400
5900
13000
13400
[a] The Mn values are generated based on a PMMA calibration curve and
the Mark–Houwink constants for PMMA to better compare the Mn
values of the single blocks with those of the corresponding block
copolymers.
Given the success of the polymer-conjugation technique,
the reaction kinetics for the formation of PMA–PCL and PS–
PCL block copolymers were investigated (Figure 6 and
Figure S9 and S10). Both reactions were found to proceed
to completion within 10 min.[18] Interestingly, the reaction
between the photoenol-capped PCL and PS proceeds some-
what slower than the reaction between the same PCL block
and PMA, which may be explained by the greater stiffness of
the PS backbone compared to that of the PMA backbone.
Steric hindrance could also play a role. Nevertheless, the
kinetic exploration reveals that rapid photoenol-based poly-
mer–polymer conjugation can be achieved for RAFT poly-
mers of different chemical compositions.
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Kowollik, A. J. Inglis, Macromol. Chem. Phys. 2009, 210, 987 –
992.
[2] W. H. Binder, R. Sachsenhofer, Macromol. Rapid Commun.
2008, 29, 952 – 981.
[3] a) M. A. Tasdelen, Polym. Chem. 2011, 2, 2133 – 2145; b) A. J.
Inglis, M. H. Stenzel, C. Barner-Kowollik, Macromol. Rapid
Commun. 2009, 30, 1792 – 1798.
[4] a) K. L. Heredia, Z. P. Tolstyka, H. D. Maynard, Macromole-
cules 2007, 40, 4772 – 4779; b) T. Pauloehrl, G. Delaittre, M.
Bruns, M. Meißler, H. G. Bçrner, M. Bastmeyer, C. Barner-
Kowollik, Angew. Chem. 2012, 124, 9316 – 9319; Angew. Chem.
Int. Ed. 2012, 51, 9181 – 9184.
[5] M. Dietrich, G. Delaittre, J. P. Blinco, A. J. Inglis, M. Bruns, C.
Barner-Kowollik, Adv. Funct. Mater. 2012, 22, 304 – 312.
[6] a) L. Nebhani, S. Sinnwell, A. J. Inglis, M. H. Stenzel, C. Barner-
Kowollik, L. Barner, Macromol. Rapid Commun. 2008, 29,
1431 – 1437; b) S. Sinnwell, A. J. Inglis, T. P. Davis, M. H. Stenzel,
C. Barner-Kowollik, Chem. Commun. 2008, 2052 – 2054; c) S.
Sinnwell, A. J. Inglis, M. H. Stenzel, C. Barner-Kowollik, Macro-
mol. Rapid Commun. 2008, 29, 1090 – 1096; d) S. Sinnwell, M.
Lammens, M. H. Stenzel, F. E. Du Prez, C. Barner-Kowollik, J.
Polym. Sci. Part A 2009, 47, 2207 – 2213; e) M. Glassner, G.
Delaittre, M. Kaupp, J. P. Blinco, C. Barner-Kowollik, J. Am.
Chem. Soc. 2012, 134, 7274 – 7277.
Figure 6. Kinetic study of the block copolymer formation of the PMA–
PCL (c) and PS–PCL (a) systems. The dependence of the appar-
ent block copolymer Mn on reaction time is plotted. The fits are
a guide to the eye only.
[7] a) K. Matyjaszewski, Macromolecules 2012, 45, 4015 – 4039; b) J.
Nicolas, Y. Guillaneuf, C. Lefay, D. Bertin, D. Gigmes, B.
Charleux, Prog. Polym. Sci. 2012, DOI: 10.1016/j.progpolymsci.
[8] a) C. Boyer, M. H. Stenzel, T. P. Davis, J. Polym. Sci. Part A 2011,
49, 551 – 595; b) C. Barner-Kowollik, Handbook of RAFT
Polymerization, Wiley-VCH, Weinheim, 2008.
[9] a) A. J. Inglis, S. Sinnwell, M. H. Stenzel, C. Barner-Kowollik,
Angew. Chem. 2009, 121, 2447 – 2450; Angew. Chem. Int. Ed.
2009, 48, 2411 – 2414; b) L. Nebhani, S. Sinnwell, C. Y. Lin, M. L.
Coote, M. H. Stenzel, C. Barner-Kowollik, J. Polym. Sci. Part A
2009, 47, 6053 – 6071.
[10] a) M. Glassner, K. K. Oehlenschlaeger, T. Gruendling, C.
Barner-Kowollik, Macromolecules 2011, 44, 4681 – 4689; b) T.
Gruendling, K. K. Oehlenschlaeger, E. Frick, M. Glassner, C.
Schmid, C. Barner-Kowollik, Macromol. Rapid Commun. 2011,
32, 807 – 812.
[11] T. Pauloehrl, G. Delaittre, V. Winkler, A. Welle, M. Bruns, H. G.
Bçrner, A. M. Greiner, M. Bastmeyer, C. Barner-Kowollik,
Angew. Chem. 2012, 124, 1096 – 1099; Angew. Chem. Int. Ed.
2012, 51, 1071 – 1074.
To conclude, a novel polymer conjugation reaction for
a non-activated dithioester was established, which is based on
a light-triggered HDA reaction with a highly reactive photo-
enol diene. Near quantitative coupling is achieved within
short reaction times at ambient temperature without a cata-
lyst. Coupling of a RAFT polymer with a small photoenol
molecule was first verified by ESI-MS. 1H NMR spectroscopy
and ESI-CID-MS techniques were utilized to confirm the
isothiochroman linkage formation in the HDA–RAFT prod-
uct. Furthermore, the applicability of the conjugation tech-
nique to the formation of block copolymers from different
types and sizes of polymer blocks was demonstrated. The
novel polymer-conjugation reaction increases the number of
well-defined photo-clickable polymers that can be generated
as it can be applied to a conventional RAFT agent, which is
suitable for the living polymerization of a wide range of
monomers. Therefore, the novel reaction provides a key
advantage for synthetic chemists in a variety of applications,
such as surface patterning, macromolecular architecture
design, three-dimensional network formation, bio-conjuga-
tion, and step-growth polymer synthesis. The ability to
perform modular ligation on conventional RAFT polymers
greatly expands the synthetic toolbox available to macro-
molecular chemists.
[12] a) P. G. Sammes, Tetrahedron 1976, 32, 405 – 422; b) J. L. Charl-
ton, M. M. Alauddin, Tetrahedron 1987, 43, 2873 – 2889; c) J. L.
Segura, N. Martꢂn, Chem. Rev. 1999, 99, 3199 – 3246.
[13] a) G. Moad, E. Rizzardo, S. H. Thang, Aust. J. Chem. 2005, 58,
379 – 410; b) G. Moad, E. Rizzardo, S. H. Thang, Aust. J. Chem.
2006, 59, 669 – 692; c) G. Moad, E. Rizzardo, S. H. Thang, Aust. J.
Chem. 2009, 62, 1402 – 1472.
[14] S. Perrier, C. Barner-Kowollik, J. F. Quinn, P. Vana, T. P. Davis,
Macromolecules 2002, 35, 8300 – 8306.
Received: August 26, 2012
Published online: October 22, 2012
[15] a) L. Charles, M. Lejars, A. Margaillan, C. Bressy, Int. J. Mass
Spectrom. 2012, 311, 31 – 39; b) A. T. Jackson, S. E. Slade, J. H.
Scrivens, Int. J. Mass Spectrom. 2004, 238, 265 – 277.
[16] C. Barner-Kowollik, Macromol. Rapid Commun. 2009, 30,
1625 – 1631.
[17] G. Moad, J. Chiefari, Y. K. Chong, J. Krstina, R. T. A. Maya-
dunne, A. Postma, E. Rizzardo, S. H. Thang, Polym. Int. 2000, 49,
993 – 1001.
Keywords: click chemistry · Diels–Alder reaction · photoenols ·
.
polymer ligation · RAFT agents
[18] The solutions were deoxygenated by three consecutive freeze–
pump–thaw cycles. It is noteworthy that the deoxygenation
method has an influence on the overall kinetics. Indeed, the
execution of three freeze–pump–thaw cycles yields faster
reactions than those after deoxygenation by nitrogen bubbling.
[1] a) C. Barner-Kowollik, F. E. Du Prez, P. Espeel, C. J. Hawker, T.
Junkers, H. Schlaad, W. Van Camp, Angew. Chem. 2011, 123, 61 –
64; Angew. Chem. Int. Ed. 2011, 50, 60 – 62; b) H. C. Kolb, M. G.
Finn, K. B. Sharpless, Angew. Chem. 2001, 113, 2056 – 2075;
Angew. Chem. Int. Ed. 2001, 40, 2004 – 2021; c) C. J. Hawker,
K. L. Wooley, Science 2005, 309, 1200 – 1205; d) C. Barner-
766
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