Template-assisted selective radical addition toward sequence-regulated polymerization: Lariat capture of target monomer by template initiator

Article abstract of DOI:10.1021/ja1070575

Surprisingly high monomer selectivity was demonstrated in competitive radical addition with two kinds of methacrylates carrying sodium and ammonium cation. Crucial is size-specific recognition by a lariat crown ether embedded close to the reactive halide in a designer template initiator. Especially, a combination with an active ruthenium catalyst led to outstanding selectivity at low temperature. This template system will open the way to unprecedented sequence-regulated polymerization.

Full text of DOI:10.1021/ja1070575

Published on Web 10/01/2010
Template-Assisted Selective Radical Addition toward Sequence-Regulated
Polymerization: Lariat Capture of Target Monomer by Template Initiator
Shohei Ida, Makoto Ouchi,* and Mitsuo Sawamoto*
Department of Polymer Chemistry, Graduate School of Engineering, Kyoto UniVersity, Katsura,
Nishikyo-ku, Kyoto 615-8510, Japan
Received August 6, 2010; E-mail: ouchi@living.polym.kyoto-u.ac.jp; sawamoto@star.polym.kyoto-u.ac.jp
monomer additions, as we recently demonstrated;2,3b moreover,
living radical polymerization is suitable for template-assisted
propagation because the growing radicals are highly tolerant of polar
Abstract: Surprisingly high monomer selectivity was demon-
strated in competitive radical addition with two kinds of meth-
acrylates carrying sodium and ammonium cation. Crucial is size-
specific recognition by a lariat crown ether embedded close to
the reactive halide in a designer template initiator. Especially, a
combination with an active ruthenium catalyst led to outstanding
selectivity at low temperature. This template system will open the
way to unprecedented sequence-regulated polymerization.
functionalities within the monomers and templates.
Our first study along these lines3a in fact demonstrated a clear
template effect in a selective radical addition8 of methacrylic acid
(MAA) over methyl methacrylate with an amino-functionalized
template initiator, 2 (Scheme 1b). Specifically, the built-in amino
group recognized the acid monomer over the ester derivative via
ionic interactions and thereby enhanced the former’s radical
reactivity by more than an order of magnitude relative to the
The repeat-unit sequence, or monomer sequence, in proteins,
genes, and other natural polymers is perfectly controlled by template
molecules that carry predetermined sequence information through
which substrate monomers are selectively recognized and connected
(“sequence-regulated” polymerization). Sequence regulation in
macromolecules implies that functional groups are placed at specific
positions in a polymeric framework in order to express specific
structures (conformations) and, in turn, particular functions. Thus,
sequence-regulated macromolecules may work as autonomous
single molecules that function without depending on assembly,
aggregates, or other multimolecular architectures.
corresponding nontemplated systems. In order to achieve a truly
sequence-controlled polymerization, however, this heralding finding
should be generalized, i.e., the substrate-template “recognition
combination” should be diversified beyond the acid-amine pair.
Scheme 1. (a) Conceptual Sequence-Regulated Radical
Polymerization with a Template Initiator (1) Carrying Two Reactive
C-Cl Bonds for Living Cationic and Radical Polymerizations; (b)
Selective Radical Addition of MAA with an Amino-Functionalized
Template Initiator (2) via Ionic Recognition
In contrast, with repeat units just randomly and averagely
incorporated, conventional synthetic polymers (e.g., plastics in the
solid state) mostly work as multimolecular assemblies where simple
amplification of intermolecular interactions among repeat units leads
to superior mechanical properties. If the repeat-unit sequence is
precisely controlled in artificial polymers, more sophisticated and
perhaps unprecedented functions or properties may emerge, rivaling
natural polymers. Therefore, sequence regulation is no doubt one
of the most challenging subjects in contemporary polymer science,
and some efforts, including ours,1-4 have now been directed to
achieve this ultimate goal, although it has not yet been perfectly
achieved.
Quite recently, we have started to examine the possibility of
template-assisted5 sequence regulation in chain-growth polymeriza-
tions (Scheme 1a).3a Therein we have utilized living polymeriza-
tions6,7 with “template initiators” that carry not only an initiating
site but also a built-in template for sequence regulation. Such
initiators may be synthesized from a heterobifunctional precursor
(1) carrying two carbon-chlorine bonds ortho to each other in a
rigid benzene framework: the haloether part is for embedding of a
template molecule by living cationic polymerization or related
reactions, and the haloester is for metal-assisted living radical
propagation toward sequence control. Obviously, the close proxim-
ity of the template and the radical-growing sites within the rigid
aromatic framework is designed to maximize the so-called “template
effect” in sequence regulation.
In this work, a crown ether moiety was newly embedded as an
alternative recognition site in the template initiator (CEI; Figure
1) to recognize ionic monomers according to their cation size.9
Thus, a crown ether alcohol, 2-hydroxymethyl-15-crown 5-ether,
was allowed to react with the haloether C-Cl bond in 1 at room
temperature in the presence of triethylamine to give the target
initiator CEI in high yield (Figure 1).
While starting with the same precursor 1 as before, we
incorporated the recognition site via electrophilic substitution of
the haloether C-Cl bond rather than electrophilic addition across
a CdC bond as done previously.3a It should be noted that the latter
is a propagation model for cationic polymerization, whereas the
As illustrated in Scheme 1a, living cationic polymerization is
promising for template synthesis, as it allows precise single-
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10.1021/ja1070575  2010 American Chemical Society

C O M M U N I C A T I O N S
former is for cation quenching, thus showing the versatility of the
haloether function in template construction.
°C via coupling with Ru(Ind)Cl(PPh3)2 (Ind ) η5-C9H7), one of
the active catalysts for radical addition10 and living radical
polymerization11 (Scheme 2). Figure 2a shows time-conversion
curves during the initial 4 h. NaMA was smoothly consumed, while
an induction period was observed for the consumption of ACMA
during which only the sodium monomer was specifically incorpo-
rated into the radical site of CEI. The apparent rate constants (k′)
of the two monomers were calculated from the initial slopes of
first-order plots and found to have the values k′NaMA ) 0.186 h-1
and k′ACMA ) 5.10 × 10-3 h-1. These results show that NaMA
reacted ∼36 times faster than ACMA (k′NaMA/k′ACMA ) 36.4).
1
Figure 1. Synthetic scheme and H NMR spectrum of CEI in CDCl3.
Sodium methacrylate (NaMA) was selected as a targeting
monomer for the 15-crown-5-ether site, as sodium cation is known
to be specifically recognized by this crown ether via its ion-fitting
size. Methacryloyloxyethyltrimethylammonium chloride (ACMA)
was examined as a competing ionic monomer carrying an unfitted
larger cation. First, the size-specific recognition by 15-crown-5 was
Figure 2. Time-conversion curves for the competitive radical addition
of NaMA and ACMA with (a) CEI and (b) ECPA in EtOH at 40 °C.
Conditions: [NaMA]0 ) [ACMA]0 ) [initiator]0 ) 50 mM; [Ru(Ind)-
Cl(PPh3)2]0 ) 4.0 mM; [15-crown-5]0 ) 50 mM (only when ECPA was
used as the initiator).
1
monitored by H NMR spectroscopy in EtOH-d6 at 40 °C (Figure
S-1 in the Supporting Information). When NaMA was mixed with
an equimolar amount of the ether ([NaMA] ) [15-crown-5] ) 50
mM), the methylene peak d of the latter was clearly shifted
downfield from 3.64 to 3.70 ppm, and those of the NaMA olefin
(a) were shifted upfield from 5.73/5.13 to 5.70/5.10 ppm (Figure
S-1a,c,d). These shifts show some interaction between the two
components and most likely indicate capture of the sodium cation
into the cyclic ether moiety. On the other hand, such peak shifts
were not observed with ACMA (Figure S-1b,c,e), indicating that
no recognition or capture of the ammonium cation occurred. More
importantly, and relevant to competitive reactions with the two
monomers (see below), the selective recognition of NaMA occurred
even in the presence of ACMA (Figure S-1f).
As a control experiment, a similar competitive reaction was
performed with a template-free initiator, ethyl 2-chloro-2-pheny-
lacetate (ECPA), in the presence of 15-crown-5 (Figure 2b).
Importantly, a definitely opposite tendency was observed: NaMA
consumption was slower than that of ACMA (k′NaMA ) 4.28 ×
10-2 h-1, k′ACMA ) 0.119 h-1, k′NaMA/k′ACMA ) 0.359), and thus,
the selectivity enhancement by the template was more than 2 orders
of magnitude (36.4/0.359 ) 101.4). From these results, the crown
ether moiety on the initiator was found to selectively accelerate
the addition of NaMA via specific recognition (template effect) by
the crown ether, which approximates the substrate to the radical
reaction site (or its dormant C-Cl form).
Scheme 2. Ruthenium-Catalyzed Competitive Radical Addition of
NaMA and ACMA with Crown Template Initiator or Template-Free
Initiator (ECPA)
Figure 3. Monomer selectivity in competitive radical addition of NaMA
and ACMA with CEI or ECPA in EtOH at (a) 80, (b) 60, and (c) 40 °C.
Conditions: [NaMA]0 ) [ACMA]0 ) [initiator]0 ) 50 mM; [Ru(Ind)-
Cl(PPh3)2]0 ) 4.0 mM; [15-crown-5]0 ) 50 mM (only when ECPA was
used as the initiator).
Here we expediently define the ratio of k′NaMA/k′ACMA with CEI
(templated) to k′NaMA/k′ACMA with ECPA (nontemplated) as the
“template effect factor” (TE). Thus, TE was evaluated as 101.4 for
the above-described competition reactions at 40 °C. As expected,
Encouraged by these findings, we carried out a competitive
radical addition of NaMA and ACMA with CEI in ethanol at 40
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C O M M U N I C A T I O N S
decreasing the reaction temperature increased TE (Figure 3
and Table S1 in the Supporting Information), but at all of the
temperatures examined, the template effect was indeed operable
(TE . 1) and beyond the experimental error.
therefore crucial for the observed size-specific molecular recognition
(Figure 5), and the proximity effect allows surprisingly high
substrate selectivity (TE > 100) in comparison with the nontem-
plated system. We are now further developing this concept toward
sequence-regulated oligomerization and polymerization, which will
be presented in the near future.
Acknowledgment. This research was partially supported by the
Ministry of Education, Science, Sports, and Culture through a Grant-
in-Aid for Creative Science Research (18GS0209) for which the
authors are grateful.
Supporting Information Available: Experimental details, 1H NMR
spectra, and kinetic analysis data. This material is available free of
charge via the Internet at http://pubs.acs.org.
References
Figure 4. Time-conversion curves in competitive radical addition of
NaMA and ACMA with CEI in EtOH at (a) 40 and (b) 0 °C. Conditions:
[NaMA]0 ) [ACMA]0 ) [CEI]0 ) 50 mM; [Ru(Cp*)Cl(PPh3)2]0 ) 4.0
mM.
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Figure 5. Size-selective monomer recognition by lariat capture of CEI.
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In summary, we have demonstrated a highly selective radical
addition with a template initiator (CEI) that carries a crown ether
embedded close to a radical initiating site. Such a “lariat capture”
of the sodium cation monomer (NaMA) by a crown macrocycle is
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