Alternating copolymerization by nitroxide-mediated polymerization and subsequent orthogonal functionalization

Article abstract of DOI:10.1002/anie.201412206

A novel method for the preparation of functionalized alternating copolymers is presented. Nitroxide-mediated polymerization of hexafluoroisopropyl acrylate with 7-octenyl vinyl ether provides the corresponding alternating polymer, which can be chemically modified using two orthogonal polymer-analogous reactions. A thiol-ene click reaction followed by amidation provides dual-functionalized alternating copolymers. The potential of this method is illustrated by the preparation of a small library (15 examples) of functionalized alternating copolymers. Alternating through double click: The title reaction of A with hexafluoroisopropyl acrylate (HFIPA) provides alternating polymer B, which can be chemically modified using two orthogonal polymer-analogous reactions. With this method, a small library of fifteen functionalized alternating copolymers was prepared.

Full text of DOI:10.1002/anie.201412206

Angewandte
Chemie
DOI: 10.1002/anie.201412206
Sequence-Controlled Polymerization
Alternating Copolymerization by Nitroxide-Mediated Polymerization
and Subsequent Orthogonal Functionalization**
Matthias Tesch, Johannes A. M. Hepperle, Henning Klaasen, Matthias Letzel, and
Armido Studer*
Abstract: A novel method for the preparation of functional-
ized alternating copolymers is presented. Nitroxide-mediated
polymerization of hexafluoroisopropyl acrylate with 7-octenyl
vinyl ether provides the corresponding alternating polymer,
which can be chemically modified using two orthogonal
polymer-analogous reactions. A thiol–ene click reaction fol-
lowed by amidation provides dual-functionalized alternating
copolymers. The potential of this method is illustrated by the
preparation of a small library (15 examples) of functionalized
alternating copolymers.
bear functional groups in their side chains that are chemically
orthogonal.[7] Hence, a single type of alternating copolymer 3
with defined molecular weight and a narrow polydispersity
index (PDI) can selectively react by sequential orthogonal
polymer-analogous reactions, such as amidation[8] and thiol–
ene click reactions,[9] to give various alternating polymers
4 (x,y) bearing different functionalities, which should show
distinct properties (Scheme 1).
Natural polymers such as proteins show broad and defined
structural and biological properties owing to the sequence-
controlled incorporation of various functional monomers.
Compared to their natural counterparts, the properties of
synthetic polymers are far less diverse and less specific
because they are generally composed of fewer monomer
building blocks, and sequence-defined incorporation cannot
be achieved. Sequence control is therefore one of the greatest
challenges in modern polymer science. Recently, great
advances have been achieved in the field of radical polymer-
ization along these lines.[1,2] Over the past decade, controlled
living radical polymerization (CLRP) has been intensively
studied, and several new methods have been developed.[3]
Proper tuning of the electronic properties of two different
monomer units allows the formation of an alternating
copolymer. However, controlled alternating copolymeriza-
tion using CLRP is still not well established, and only a few
examples have been reported. Successfully used monomer
pairs are styrene/maleic anhydride,[4] styrene/methacrylates,[5]
and vinyl ethers/methacrylates.[6] It is obvious that these
approaches currently lack generality in terms of the prepa-
ration of larger series of alternating polymeric materials.
We herein present a conceptually novel approach that
comprises alternating nitroxide-mediated radical polymeri-
zation (NMP) of two electronically distinct monomers 1 and 2
followed by two polymer-analogous reactions. The monomers
Scheme 1. Synthesis of various alternating polymers by sequence-
controlled NMP and subsequent orthogonal polymer functionalization.
As the active ester component we chose hexafluoroiso-
propyl ester, which is known to be readily amidated.[10]
Importantly, the corresponding monomer, 1,1,1,3,3,3-hexa-
fluoroisopropyl acrylate (HFIPA, 1), is commercially avail-
able, but to our surprise, HFIPA has not been used in CLRP
thus far. Therefore, we started our investigations by studying
the NMP of 1 using the sterically hindered alkoxyamine 5 as
the initiator/regulator (Scheme 2).[11] Controlled polymeri-
zations performed in sealed tubes at 1008C delivered poly-
(HFIPA) with a narrow PDI. For example, a conversion of
[*] M. Tesch, J. A. M. Hepperle, H. Klaasen, M. Letzel,
Prof. Dr. A. Studer
Organisch-Chemisches Institut
Westfꢀlische Wilhelms-Universitꢀt
Corrensstrasse 40, 48149 Mꢁnster (Germany)
E-mail: studer@uni-muenster.de
[**] We thank the DFG (SFB 858) for supporting our work. The reviewers
are acknowledged for helpful comments, and we also thank Prof. Dr.
Christopher Barner-Kowollik for fruitful discussions. Dr. Heinrich
Luftmann is acknowledged for conducting some MS studies.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201412206.
Scheme 2. NMP of HFIPA (1) with the highly hindered alkoxyamine 5
as the initiator/regulator.
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75% was achieved within 20 hours at 1008C in neat HFIPA
with 1 mol% of 5 (16200 gmolÀ1, PDI 1.1; see the Supporting
Information).
We also tested whether the amine concentration can be
further reduced to obey the rules of a polymer-analogous click
reaction.[13] Decreasing the amine concentration to 1.2 equiv-
alents resulted in 80% conversion under otherwise identical
conditions (determined by 19F NMR spectroscopy). However,
upon increasing the temperature to 608C, amidation occurred
with complete conversion.
Moreover, poly(HFIPA) prepared by NMP (Mn =
20500 gmolÀ1, PDI 1.1) was successfully used as a macro-
initiator for the polymerization of styrene (neat styrene at
1008C, 24 h) to provide the corresponding block copolymer
poly(HFIPA-b-styrene) (85000 gmolÀ1, PDI 1.04), indicating
a high degree of livingness for the initial NMP of 1 (see the
Supporting Information). The living character was further
confirmed by ESI mass spectrometry of a low-molecular-
weight poly(HFIPA) sample (see the Supporting Informa-
tion).[12]
We then investigated the postfunctionalization of poly-
(HFIPA); the amidation of poly(HFIPA) (Mn =
10600 gmolÀ1, PDI 1.1, 1.0 equiv) with para-fluorobenzyl-
amine (4.0 equiv) in THF at room temperature for two hours
was chosen as the model reaction. After extraction of excess
amine with aqueous HCl, polyacrylamide 6a was isolated in
83% yield (Scheme 3). The degree of postfunctionalization
was readily determined by 19F NMR spectroscopy, which
showed that amidation occurred quantitatively (the CF3
signals of the hexafluoroisopropyl groups at ca. À74 ppm
completely vanished, and new signals for the para-fluorine
atom of the benzyl group appeared at ca. À117 ppm; for the
spectra, see the Supporting Information).
To study the substrate scope, we systematically varied the
amine component and used a low-molecular-weight poly-
(HFIPA) sample (Mn = 1650 gmolÀ1, PDI 1.1, 1.0 equiv) as
the substrate, which allows for determining the degree of
amidation by 1H NMR spectroscopy (see the Supporting
Information). Importantly, in the amidation with para-fluo-
robenzylamine, we did not see any difference in reactivity
upon switching from poly(HFIPA) with Mn = 10600 gmolÀ1
to the polymer with Mn = 1650 gmolÀ1. Therefore, we regard
the results that were obtained with the smaller poly(HFIPA)
as representative. Under the conditions specified in Scheme 3,
complete conversion was achieved for all tested amines, and
the yields given correspond to the isolated material after
aqueous workup. Amidation was quantitative with linear
aliphatic primary amines (see 6b, 6c), and a-branched as well
as b-branched aliphatic primary amines also turned out to be
good nucleophiles (6d–f). As expected, diethylamine is less
reactive for steric reasons, and a longer reaction time was
necessary for complete conversion (6g).
Gel permeation chromatography (GPC) showed that the
PDI (1.2) slightly increased while the molecular weight
(9000 gmolÀ1) decreased. The change in Mn is due to the
different GPC properties of poly(HFIPA) and 6a.
Having identified poly(HFIPA) as a valuable polymer for
polymer-analogous amidations, we addressed the alternating
polymerization of HFIPA using n-butyl vinyl ether (NBVE)
as the second monomer (Scheme 4).
Scheme 4. Copolymerization of HFIPA (1) and NBVE with initiator 5.
Polymerizations were performed in sealed tubes (90–
1008C, 5–240 min) with HFIPA (1.0 equiv) and various
amounts of NBVE (0.13–8.0 equiv) in the presence of
alkoxyamine 5 (0.5–20 mol%) under argon atmosphere
(Table 1). It is important to note that vinyl ethers do not
undergo homopolymerization under these conditions owing
to the electronic mismatch between the nucleophilic radical at
the chain end and the electron-rich character of the vinyl
ether double bond. Unreacted monomers were removed
under reduced pressure, and the resulting copolymers 7 were
analyzed by 1H NMR spectroscopy, GPC, and ESI mass
spectrometry (see the Supporting Information).
At a 1:1 monomer feed ratio, we obtained a copolymer
with an HFIPA/NBVE incorporation ratio of 55:45 and
Scheme 3. Amidation of poly(HFIPA) with primary and secondary
amines.
2
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Table 1: Copolymerization of HFIPA (1) with NBVE and OVE (2). Unless stated otherwise, reactions were carried out at 908C.
Entry
5
Vinyl ether HFIPA/vinyl ether Solvent
monomer ratio
t [min] Conv.
HFIPA/vinyl ether
Calc.
Mn PDI[b]
]
[mol%]
HFIPA [%] incorporation ratio[a] DPHFIPA [gmolÀ1 [b]
1
2
3
4
5
6
7
8
9
10
11[d]
12
13
14
15
2
2
2
2
0.5
1
5
10
20
NBVE
NBVE
NBVE
NBVE
NBVE
NBVE
NBVE
NBVE
NBVE
NBVE
NBVE
NBVE
NBVE
OVE
1:1
1:2
1:4
1:8
1:8
1:8
1:8
1:8
1:8
1:8
1:8
8:1
1:8
1:8
1:8
PhH
PhH
PhH
PhH
–
–
–
–
–
–
–
PhH
60
60
60
60
60
60
60
60
60
20
30
60
60
60
60
15
9
55:45
52:48
50:50
50:50
50:50
50:50
50:50
50:50
50:50
50:50
50:50
65:35
45:55
63:37
50:50
30
38
52
57
82
66
30
21
18
470
144
84
61
38
9200 1.4
12000 1.2
16700 1.2
18200 1.2
26500 1.4
21300 1.3
9500 1.4
12
12
39
51
68
77
94
96
75
11
18
16
63
6600 1.4
5700 1.3
[c]
–
152000 1.5
46200 1.3
25500 1.4
25100 1.2
12000 1.5
27600 1.4
2
2
2
2
2
PhH/HFIP (89:11)
PhH
PhH/HFIP (89:11)
OVE
73
[a] Determined by 1H NMR spectroscopy. [b] Determined by GPC at 258C using dichloromethane as the eluent against PMMA standards. [c] AIBN
(1 mol%) was used as the initiator; the experiment was conducted at 808C. [d] The experiment was conducted at 1008C.
a HFIPA conversion of 15% after one hour at 908C in
benzene (Table 1, entry 1). The incorporation ratio was
determined by 1H NMR spectroscopy, and the higher
amount of HFIPA compared to NBVE in the copolymer
was corroborated by ESI mass spectrometry. Upon doubling
the amount of NBVE in the monomer feed, we observed an
increase in NBVE incorporation (entry 2). For a HFIPA/
NBVE feed ratio of 1:4, we obtained a copolymer with
a monomer incorporation ratio of 50:50 (entry 3). As NBVE
does not undergo homopolymerization under these condi-
tions, a further increase in the amount of NBVE in the
monomer feed did not lead to a preferential incorporation of
NBVE in the polymer chain (entry 4). Attempts to system-
atically adjust the average molecular weight by variation of
the reaction time were not successful. However, performing
alternating polymerization in neat monomers and varying the
concentration of the alkoxyamine initiator from 0.5 to
20 mol% allowed for good control over the molecular
weight, which ranged from Mn = 5700 to 26500 gmolÀ1 with
PDIs between 1.3 and 1.4 and HFIPA conversions of 39–94%
(entries 5–9). Polymerization of HFIPA/NBVE (1:8) with
2 mol% of alkoxyamine 5 at 1008C for 30 minutes provided
poly(HFIPA-alt-NBVE) with Mn = 46200 gmolÀ1 and a PDI
of 1.3 (entry 11). When AIBN was used as the initiator,
gelation occurred after 20 minutes (entry 10). The isolated
highly viscous polymer also exhibited a 50:50 monomer
incorporation ratio. However, the average molecular weight
of 152000 gmolÀ1 as well as the increased PDI of 1.5 indicate
low control over the polymerization and cross-linking of the
material. By using HFIPA in large excess with respect to
NBVE (8:1) in benzene, a copolymer with a HFIPA/NBVE
ratio of 65:35 was formed (entry 12).
feed ratio, and the data were fitted to the Mayo–Lewis
copolymerization equation using the least-squares method
(see the Supporting Information),[14] providing reactivity
ratios r1 = 0.12 and r2 = 0.028. These values are close to zero,
which illustrates that the copolymerization occurs in an
alternating fashion.
We further analyzed copolymer 7 by 13C NMR spectros-
copy and compared the chemical shifts of the methylene
carbon atoms of poly(HFIPA-alt-NBVE) 7 with those of the
homopolymer [poly(HFIPA), see the Supporting Informa-
tion]. All signals of poly(HFIPA-alt-NVBE) 7 were unam-
biguously assigned, and signals at 41–42 ppm, which would be
expected if sequences of homo-HFIPA were present in the
copolymer, were not observed.
Careful MS analysis of a low-molecular-weight poly-
(HFIPA-alt-NBVE) sample (5200 gmolÀ1, PDI 1.2) revealed
that all polymer chains contained a styryl moiety as the
initiating unit as well as a nitroxide moiety as the terminating
unit (see structure 7 in Scheme 4). ESI mass spectrometry
further showed that for the major peak series the number of
HFIPA moieties exceeded the number of NBVE moieties by
one (for spectra see the Supporting Information). Consider-
ing that no homo-HFIPAwas formed (within the error limit of
13C NMR analysis), we can conclude that HFIPA must be the
initiating as well as the terminating monomer. MS-MS studies
further supported the structure of 7 (see the Supporting
Information). Although monomer incorporation ratios of
50:50 had been determined for these polymers within the
1
error limit of H NMR spectroscopy, ESI MS spectra also
showed a small peak series of polymer chains where the
number of HFIPA exceeded the number of NBVE by two.
This can only be explained with one single sequence error
along the chain where two HFIPA moieties were incorpo-
rated sequentially.
To demonstrate the living character of the copolymeriza-
tion we showed that amidated polymers of type 7 can be used
as macroinitiators for the preparation of block copolymers
(see the Supporting Information). This further indicates that
We also determined the reactivity ratios for the copoly-
merization of HFIPA and NBVE mediated by 5. To this end,
we carried out copolymerization reactions with different
monomer feed ratios in benzene, and the reactions were
stopped at low conversion. The HFIPA content of the
copolymer was then plotted against the initial monomer
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the ultimate monomer unit in the majority of polymer chains
an alternating copolymer (HFIPA/HVE ratio = 60:40; r1 =
0.54, r2 = 0.0020). Again, copolymerization of HFIPA with
the corresponding saturated n-hexyl vinyl ether (NHVE)
occurred well controlled, and the monomers were incorpo-
rated in equal amounts (in a ratio of 50:50 according to NMR
analysis; r1 = 0.12, r2 = 0.0026; see the Supporting Informa-
tion).[18]
À
is a HFIPA moiety, as the C O bond dissociation energy in a-
alkoxy-alkoxyamines is too large for the bond to be homolyti-
cally cleaved at 1008C.[15] Despite the living nature of the vast
majority of polymer chains, ESI MS spectra also showed
a minor peak series where the numbers of incorporated
HFIPA and NBVE monomers are the same. In these cases,
À
the chain is terminated by NBVE, and the C O bond of the
We therefore studied the effect of additives on the
alternating polymerization of HFIPA/OVE and found lithium
salts to alter the ratio of the incorporated monomers.
However, results were not reproducible. We then switched
to hexafluoroisopropanol (HFIP) as an additive and noted
a dependence of the HFIPA/OVE ratio in the resulting
copolymer on the amount of HFIP.[19] Experiments were
conducted with OVE (2; 8.0 equiv), HFIPA (1.0 equiv), and
HFIP as the additive in benzene with alkoxyamine 5
(2 mol%) at 908C for one hour. With 3.4 vol% HFIP with
respect to benzene, the HFIPA/OVE ratio in the polymer
dropped from 63:37 to 55:45. A further stepwise increase of
the HFIP concentration to 11 vol% led to a HFIPA/OVE
ratio of 50:50 in the polymer (Table 1, entry 15; see the
Supporting Information). A similar influence of the HFIP
additive was also observed for the copolymerization of HVE
with HFIPA, which could be well controlled when using 11
vol% of HFIP with respect to benzene (HFIPA/HVE ratio in
the copolymer: 52:48; see the Supporting Information). With
the HFIPA/NBVE system, we were able to obtain NBVE-
enriched copolymers with a HFIPA/NBVE ratio of 45:55
(Table 1, entry 13), demonstrating the significance of HFIP as
an additive as the NBVE-enriched copolymers could not be
prepared under the standard conditions.
corresponding alkoxyamine cannot be cleaved thermally (see
the Supporting Information).[16] From these results, we
conclude that the copolymerization of HFIPA and NBVE is
to a large extent alternating and living.
For the preparation of alternating copolymers bearing two
reactive orthogonal functionalities, we replaced NBVE with
the electronically similar oct-7-enyl vinyl ether (OVE, 2)
bearing a terminal alkene, which can be chemically addressed
by thiol–ene reactions.[9] Copolymerization was performed
with OVE (8.0 equiv) and HFIPA (1.0 equiv) in benzene
using alkoxyamine 5 (2 mol% with respect to HFIPA) as the
initiator/regulator at 908C for one hour (Scheme 5; Table 1,
entry 14). Residual monomers and solvent were removed
under reduced pressure.[17]
Having identified suitable conditions for the preparation
of an alternating poly(HFIPA-alt-OVE) copolymer of type 3
with a narrow PDI (1.4) and a molecular weight of Mn =
27600 gmolÀ1, we studied its sequential orthogonal function-
alization using various thiols and amines (Table 2).
The thiol–ene reaction of the terminal alkene was
conducted under UV light irradiation (365 nm) of poly-
(HFIPA-alt-OVE) 3 (1.0 equiv) in the presence of a thiol
(5.0 equiv)
and
2,2-dimethoxy-2-phenylacetophenone
(DMPA, 0.2 equiv) as the photoinitiator at ambient temper-
ature in THF for three hours. Under these conditions,
functionalization degrees of > 95% were achieved for all
tested thiols, as determined by 1H NMR spectroscopy and ESI
mass spectrometry (see the Supporting Information). In the
second step, the resulting polymeric thioethers were ami-
dated. To this end, the monofunctionalized poly(HFIPA-alt-
OVE-SR) copolymer and the corresponding amine (5.0–
10 equiv) were heated in THF or DMF at 758C for 24–
72 hours, and the resulting dual-functionalized alternating
Scheme 5. Alternating NMP of HFIPA with OVE (2) and sequential
orthogonal chemical functionalization.
1
Disappointingly, H NMR analysis revealed that HFIPA
was incorporated to a larger extent (HFIPA/OVE ratio =
63:37), and further increasing the amount of OVE with
respect to HFIPA did not change the ratio. Obviously, the
terminal alkene unit alters the kinetics of the polymerization.
The reactivity ratios determined for the HFIPA/OVE system
were r1 = 0.37 and r2 = 0.0011, indicating a higher tendency for
HFIPA incorporation compared to the HFIPA/NBVE
system. In fact, copolymerization of n-octyl vinyl ether
(NOVE), which lacks the alkene moiety, and HFIPA under
the same conditions delivered an alternating copolymer
containing equal amounts of the two monomers (r1 = 0.11,
r2 = 0.0030; see the Supporting Information). The same
outcome was also observed for the copolymerization of hex-
5-enyl vinyl ether (HVE) with HFIPA, which did not provide
1
polymers 4a–o were analyzed by H NMR spectroscopy and
GPC. For a poly(HFIPA-alt-OVE) sample, the stepwise
postmodification was also confirmed by ESI mass spectrom-
etry (see the Supporting Information). All relevant signals
were assigned to fully functionalized oligomers, and signals of
partially unfunctionalized oligomers could not be identified.
This two-step postmodification of 3 was successfully
conducted with various thiols and amines. Considering the
scope of the thiol–click process, the reaction worked well for
4
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Chemie
Table 2: Orthogonal functionalization of 3 using various thiols and
amines to give copolymers of type 4. The degrees of functionalization
were >95% for both postmodification reactions.
NBVE, delivered alternating poly(HFIPA-alt-NBVE) 7.
Careful MS and NMR analyses were conducted to character-
ize the polymers. Replacing NBVE with OVE (2) enabled the
[a]
Entry
HSR1
H2NR2
Mn,exp
PDI
Yield[b] [%]
(Product)
synthesis of alternating poly(HFIPA-alt-OVE)
3 using
[gmolÀ1
]
a slightly modified procedure. We showed that the monomer
incorporation can be adjusted with hexafluoroisopropanol
(HFIP) as an additive during NMP. Subsequent sequential
orthogonal functionalization of poly(HFIPA-alt-OVE) 3 with
thiols and amines provided alternating dual-functionalized
copolymers of type 4. The potential of the approach was
demonstrated by the successful synthesis of a small library of
15 dual-functionalized alternating polymers 4a–o, which were
obtained from a single precursor, polymer 3.
1
2
3
4
15600
18600
19500
11600
1.3
1.3
1.3
1.2
68 (4a)
65 (4b)
80 (4c)
78 (4d)
5
6
34900
30200
1.4
1.5
86 (4e)
66 (4 f)
Received: December 19, 2014
Published online: && &&, &&&&
7
8
9
22400
16000
16900
1.3
1.5
1.5
48 (4g)
36 (4h)
64 (4i)
Keywords: active esters · alternating polymerization ·
.
nitroxide-mediated polymerization ·
orthogonal functionalization · thiol–ene reactions
10
34500
1.4
92 (4j)
[c]
[c]
11
12
13
14
–
–
35 (4k)
57 (4l)
60 (4m)
51 (4n)
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1.5
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1.3
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15
25600
1.4
94 (4o)
[a] At 258C in THFagainst PMMA standards. [b] Yield of isolated product
over two steps after extraction and precipitation. [c] No GPC data
obtained owing to poor solubility.
thiols bearing ester groups, which were also inert to the
following amidation of the HFIPA moieties (Table 2,
entries 1–4, 7–11, and 15). Furthermore, fluorinated thiols
(entries 5 and 6), alkyl thiols (entries 13 and 14), and
a phenyl-substituted thiol (entry 12) were readily introduced.
Subsequent amidation with primary amines occurred with
> 95% conversion, and polymers 4a–o were isolated in 35–
94% yield over two steps after extraction and precipitation.
As shown in Table 2, various amines can be readily
introduced by this approach. Hydroxy groups, which can be
used for subsequent crosslinking of the resulting polymer 4n,
were readily incorporated by amide bond formation
(entry 14). Notably, alternating copolymers of poly(N-isopro-
pyl acrylamide) (PNIPAM) were readily obtained by reacting
HFIPA moieties with isopropylamine (entry 7). Linear
(entries 1, 2, and 5), and a-branched (entries 4, 7, 10, and
15) amines were introduced as well as amines bearing methyl
ether (entries 3, 6, 12, and 13) or imidazole (entry 11) entities.
Allyl and propargyl groups (entries 8 and 9), which are
amenable to further functionalization, could also be incorpo-
rated into the polymer, documenting the potential of our
novel approach.
[4] a) D. Benoit, C. J. Hawker, E. E. Huang, Z. Lin, T. P. Russell,
Macromolecules 2000, 33, 1505 – 1507; b) G.-Q. Chen, Z.-Q. Wu,
J.-R. Wu, Z.-C. Li, F.-M. Li, Macromolecules 1999, 32, 232 – 234;
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Fairbanks, G. Moad, R. G. Mulder, E. Rizzardo, S. H. Thang,
Polym. Chem. 2015, 6, 228 – 232.
In summary, we have developed a novel method for the
preparation of various alternating copolymers. NMP of two
electronically distinct monomers, namely HFIPA (1) and
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[5] B. Kırcı, J.-F. Lutz, K. Matyjaszewski, Macromolecules 2002, 35,
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[14] M. Buback, A. Feldermann, C. Barner-Kowollik, I. Lacik,
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thoki-Uprety, J. F. Reuther, B. M. Novak, Macromolecules 2012,
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[8] For recent examples of amidations with active esters, see:
a) A. C. Engler, J. M. W. Chan, D. J. Coady, J. M. OꢀBrien, H.
Sardon, A. Nelson, D. P. Sanders, Y. Y. Yang, J. L. Hedrick,
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[15] S. Marque, H. Fischer, E. Baier, A. Studer, J. Org. Chem. 2001,
66, 1146 – 1156. Indeed, a model compound mimicking a polymer
bearing a NBVE moiety as the ultimate monomer did not
À
undergo C O bond homolysis at 1008C (see the Supporting
Information).
[16] As ESI MS can only visualize the low-molecular region, a sample
of larger poly(HFIPA-alt-NBVE) with a higher average molec-
ular weight (Mn = 8200 gmolÀ1, PDI 1.4) clearly showed a peak
series of NBVE-terminated polymer chains (see the Supporting
Information). Therefore, for larger polymers, the dead NBVE-
terminated chains are enriched in the MS-visible low-molecular
region.
[17] In some cases, when the polymerization was run without or with
less benzene as the solvent, we observed gelation after 15–
30 minutes, and the material obtained was hardly soluble in any
organic solvent, likely because of cross-linking. We attribute this
cross-linking behavior to the participation of the terminal
alkene, which can undergo intramolecular radical cyclization at
the chain end as well as chain transfer to the monomer.
However, when the reaction was run in an adequate amount of
benzene, we did not find any indication for the participation of
the terminal alkene in the polymerization.
[18] The reason for the difference in the kinetic properties of the
saturated and unsaturated systems could not be elucidated thus
far. We hypothesize that it might be caused by a change in the
monomer aggregation state. This is known for acrylate mono-
mers, but has not be reported for vinyl ethers; see: A. P.
Haehnel, M. Schneider-Baumann, L. Arens, A. M. Misske, F.
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[19] HFIP as an additive is known to affect the selectivity of acrylate
polymerization and to enhance the alternating polymerization of
a-olefins and acrylates; see: a) K. Yamada, T. Nakano, Y.
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Angewandte
Chemie
Communications
Sequence-Controlled Polymerization
M. Tesch, J. A. M. Hepperle, H. Klaasen,
M. Letzel, A. Studer*
&&&& — &&&&
Alternating Copolymerization by
Nitroxide-Mediated Polymerization and
Subsequent Orthogonal
Alternating through double click: The title
reaction of A with hexafluoroisopropyl
acrylate (HFIPA) provides alternating
polymer B, which can be chemically
modified using two orthogonal polymer-
analogous reactions. With this method,
a small library of fifteen functionalized
alternating copolymers was prepared.
Functionalization
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ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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7
These are not the final page numbers!