Clickable initiators, monomers and polymers in controlled radical ...

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Published on 20 September 2010 on http://pubs.rsc.org | doi:10.1039/C0PY00168F
74). The pyridyl disulfide end groups allowed straightforward
conjugation with oligonucleotides and peptides. 267
6.1.2.7 NMP – Conventional modification and possibilities.
Only a few examples are described dealing with the exchange of
the nitroxide moiety on the polymer. The first study was conducted
by Rizzardo, reducing the TEMPO to a hydroxy group
with a mixture of zinc/acetic acid. 282 A radical-cleavage approach
towards more versatile functional end groups was presented by
Hawker and coworkers. Thereby, the propagating radical was
trapped at the polymerization temperature by N-functionalized
maleimides as non-self-polymerizing monomers, while the
TIPNO nitroxide decomposed at elevated temperatures resulting
in the maleimide-functionalized polymer. 283 The transformation
yield for polystyrene, polyisoprene and poly(n-butylacrylate) was
typically 90 to 95%, while no changes in molar masses and the
polydispersity indices were observed.
This approach offers the possibility to introduce clickable
units at the u-terminus by using functionalized maleimides.
Following this strategy, Lutz and coworkers synthesized
a library of functional maleimides and used them in the
copolymerization with styrene via ATRP, while the maleimide
was incorporated at a specific place in the polymer chain. 216
Among those, N-pentafluorophenyl maleimide or N-propargyl
maleimide could be incorporated into the polymer, while the
latter one had to be protected due to pronounced side reactions
(Entry 51, 62). In principle, clickable u-functionalized polymers
should be accessible using these monomers in the radicalcleavage
procedure by Hawker as well.
6.1.2.8 NMP – Modification towards alkyne functionality. In
contrast to the thermal cleavage of the alkoxyamine-terminated
polymer, oxidative cleavage under much milder thermal conditions
can be achieved by single electron oxidation with ceric
ammonium nitrate (CAN). 247,284 After the oxidation the alkoxamine
cleaves heterolytically into a nitroxide and the cationterminated
polymer that can be trapped by nucleophiles. Braslau
and coworkers treated TIPNO-terminated polystyrene with
CAN and propargyl alcohol as nucleophile at room temperature
under anhydrous conditions to obtain alkyne-functionalized PS
(Entry 76) with an end-group fidelity of 65% as determined by
UV-vis experiments. 247 Investigating PhEt-TEMPO as a model
compound for TEMPO-terminated polymers, a heterolytic
cleavage similar to the TIPNO counterpart was obtained. It
could be shown that this method can also be used for TEMPOterminated
polymers. In contrast, polyacrylates terminated with
TIPNO or TEMPO also undergo oxidative cleavage, but the
cation-terminated polymer interferes with CAN by forming
nitrate ester and prohibit further attachment of functional
groups via the addition of nucleophiles. 284
The modification of polystyrene that was prepared by NMP
with commercially available b-phosphonylated alkoxyamine
BlocBuilder Ò cannot be performed via the described oxidative
cleavage with CAN due to the electronic and steric nature of
SG1. 285
6.1.2.9 NMP – Modification towards azide functionality.
Terminal azide-functionalized polystyrene could be obtained
starting from the nitroxide-terminated polymer through the
reaction with ethanesulfonyl azide (EtSO 2 N 3 ) that was introduced
by Renaud and Ollivier 286 as an azidation method for carbon
radicals. Braslau and coworkers showed that polystyrene
prepared by NMP reacts in the presence of an excess of EtSO 2 N 3
in N-methyl-2-pyrrolidinone at 120 C to the azido-functionalized
PS (Entry 77), although the azidation was incomplete as judged by
labelling experiments with an alkyne-functionalized dye analyzed
via UV-vis experiments. 247 Using PhEt-TIPNO as a model
compound, the treatment with EtSO 2 N 3 led to less than 30% of the
desired transformation. 247 This was explained by the weak electrophilic
character of the styryl radical, since only electron-rich
radicals can efficiently add onto EtSO 2 N 3 . 287 This also explains
why polyacrylates could not be modified with this method.
The azidation reaction of nitroxide-terminated polystyrene
was further studied by Bertin and coworkers for polystyrenes
prepared with the commercial available BlocBuilder Ò . 285
Thereby, a one-step as well as a two-step approach towards the
terminal azido-functionalized polymer were performed (Entry 81).
In the one-step approach EtSO 2 N 3 was used under optimized
reaction conditions using a large excess (50 eq.) at 90 C. In the
two-step approach the alkoxyamine was reacted at 75 C in
a radical exchange reaction with 2-bromoisobutyrate as solvent as
well as the bromination agent to obtain the exchange of the
nitroxide by bromine. Furthermore, this bromo-functionalized
polymer was reacted with sodium azide following the well-known
ATRP postmodification procedure at room temperature in DMF.
For both approaches the azide-functionalization degree was
around 70%.
6.1.3 Heteromodification on both termini
6.1.3.1 NMP. Since the azide group is stable against the mild
conditions of the oxidative exchange of the nitroxide against
propargyl alcohol by ceric ammonium nitrate (Section 4.1.1),
alkyne-azide-functionalized heterotelechelic polystyrene could
be efficiently synthesized in a two step synthesis as demonstrated
by Braslau et al. (Entry 78). 247 At first the chloro group of the
a-functionalized polystyrene prepared by NMP was transformed
into the azide followed by the oxidative cleavage reaction with
CAN at room temperature and the in situ nucleophilic addition
of propargyl alcohol.
6.2 Side-group modification
In contrast to the terminal functionalization, the modification of
pendant groups is more influenced by steric or electronic effects,
in particular for homopolymers, where every repeating unit has
to be modified. Nonetheless, this method represents a convenient
alternative route to multiple click-functionalized polymers, if the
direct polymerization of these monomers is relatively more
difficult and/or side reactions occur during the polymerization.
6.2.1 ATRP
Modification towards alkyne functionality. In Entry 82 the
alkyne moiety could be selectively introduced by quaternization of
the amine of 2-(dimethylamino)ethyl methacrylate (DMAEMA)
with propargyl bromide at room temperature (Menschutkin
reaction). 288 Due to sterical hindrance, the DMAEMA is more
reactive towards quaternization than DEAEMA allowing for the
selective modification of a terpolymer containing DEGMA,
This journal is ª The Royal Society of Chemistry 2010 Polym. Chem., 2010, 1, 1560–1598 | 1589