Amino acid-bearing ROMP polymers with a stereoregular backbone

Article abstract of DOI:10.1021/ja058801v

The ruthenium-catalyzed ring-opening polymerization (ROMP) of 1-cyclobutenecarbonyl glycine methyl ester provides translationally invariant, head-to-tail ordered polymers. This polybutadiene backbone contains (within the limits of detection) only E-trisub

Full text of DOI:10.1021/ja058801v

Published on Web 03/22/2006
Amino Acid-Bearing ROMP Polymers with a Stereoregular Backbone
Jae Chul Lee, Kathlyn A. Parker,* and Nicole S. Sampson*
Department of Chemistry, Stony Brook UniVersity, Stony Brook, New York 11794-3400
Received December 28, 2005; E-mail: kathlyn.parker@stonybrook.edu; nicole.sampson@stonybrook.edu
Scheme 1. Ring-Opening Metathesis One-mer Formation
“Living” polymerizations provide materials with well-defined
chain lengths and narrow molecular weight distributions (polydis-
persity indices or PDIs). They also allow the preparation of block
polymers. Among the general classes of living polymerizations,
ring opening metathesis polymerization (ROMP) has been broadly
applied for the synthesis of materials with interesting physical
properties1 and biological activities.2,3
Although ROMP polymers have been prepared from many
strained cycloalkenes and their derivatives,4 norbornenes and
oxanorbornenes are used for the preparation of peptide- and
carbohydrate-bearing multivalent ROMP polymers.3,5 These mono-
mers, substituted on the 5-position or on the 5- and 6-positions of
the norbornene ring, are the most synthetically accessible monomers
that metathesize efficiently. However, in these systems, stereocon-
trol of the polymerization reaction is not always possible. For
example, ruthenium-catalyzed polymerization of 5-substituted nor-
bornene and oxanorbornene monomers provides stereochemically
heterogeneous materials.6 Each monomeric unit contributes three
stereochemical variables that are not controlled in the chain
extension step.7 Therefore it is difficult to correlate the physical or
biological properties of these polymers with specific structural
features.
For our studies of bi- and multidentate binding to cell surfaces,3,8
we wished to employ multivalent peptide-bearing polymers in which
structural ambiguities were minimized. We considered the design
of a ROMP monomer that would provide polymers that were
translationally invariant. A desirable monomer might be an un-
bridged, strained cyclic olefin that contains no chiral centers. A
1-substituted cyclobutene suggested itself as a possible solution to
this problem. If the resulting polymer were to contain no head-to-
tail or E/Z double bond ambiguities, it would meet our criterion.
We postulated that cyclobutene carboxylic acid derivatives might
undergo ruthenium-catalyzed ROMP with high regiochemical and
geometric preferences. The literature offers several examples of
the ROMP and ROM (ring opening metathesis) of substituted
cyclobutenes9-12 including three examples in which the substrate
is a 1-substituted cyclobutene.12 Indeed, with the (CO)5WC(C6H5)2
catalyst, Katz and co-workers produced translationally invariant (all
head-to-tail, E-olefinic) polymers.12d Nonetheless, it was not obvious
that the more functional group-tolerant ruthenium catalysts would
give analogous results with related monomers.
ruthenium carbene adds to the substrate to form metallocyclobutene
4, which then undergoes ring opening to the carbonyl-substituted
ruthenium carbene 5. When ethyl vinyl ether is added, a second
metathesis cycle leads to the formation of Fischer carbene 6 and
1,1-disubstituted alkene 3 as a 1:1.4 mixture of Z and E styrene
olefins.
Next we performed an experiment designed to afford the 10-
mer 7. Catalyst was stirred with 10 equiv of substrate 1, and
1
quenching was effected by addition of ethyl vinyl ether. The H
NMR spectrum of the product exhibited a broad signal for the
aromatic group centered at 7.29 ppm, a broad signal of olefinic
protons centered at 6.22 ppm, and two small olefinic proton signals
centered at 5.56 and 5.39 ppm. Comparison to 1H NMR spectra of
model compounds (Supporting Information) revealed that the peak
at 6.22 ppm corresponds to the proton at the â-position of the
unsaturated amide and two styrenyl protons, and the peaks at 5.56
and 5.39 ppm correspond to the terminal vinyl group. The relative
intensities of the signals were 5:11:1:1 (7.29, 6.22, 5.56 and 5.39
ppm), a ratio that is fully consistent with the internally homogeneous
structure 7 in which the trisubstituted olefinic bonds have the E-
and not the Z-configuration. A contribution from protons on a 1,2-
dialkyl olefin, which would appear at 5.3-5.5 ppm, could not be
discerned.
Longer polymers, 18-mer (8), 35-mer (9), and 50-mer (10), were
prepared by similar experiments with different ratios of catalyst to
1
monomer. The H NMR spectrum of each showed a peak at 6.22
ppm, the integration of which increased in proportion to the length
of the polymer; no new vinyl peaks appeared.
Additional evidence for the structures of the polymers was
obtained by 13C NMR spectroscopy. In the case of 7, two amide-
substituted alkene carbon signals were observed at 136.4 and 136.2
ppm. Likewise, the 13C NMR spectra for longer polymers showed
two distinct peaks at 136.4 and 136.2 ppm. To clarify the identities
of the two peaks, an APT (Attached Proton Test) experiment was
performed on polymer 8. The carbon with a peak at 136.4 ppm
has a single hydrogen attached, and the carbon with a peak at 136.2
ppm bears no hydrogens. This experiment confirms that the structure
of the polymer is composed of repeating R,â unsaturated amide
units. In total the 1H NMR, 13C NMR, and APT spectra demonstrate
that the ROMP of cyclobutenecarboxylic amide 1 is highly regio-
In this communication, we describe the polymerization of
cyclobutene-1-carboxamide 1 with the Grubbs precatalyst 2, notable
for its fast initiation rates and the narrow dispersities of the materials
it provides.13 The polymers that we obtained, models for peptide-
bearing, multivalent tools for mechanistic studies, had low to
moderate PDIs and were translationally invariant.
A preliminary experiment indicated the regiochemistry of the
metathesis of the substrate with the ruthenium carbene 2. Thus,
substrate 1, when treated with 1.0 equiv of initiator 2, afforded the
ring-opened metathesis product 3 as a single regioisomer (Scheme
1). This result is consistent with a mechanism in which the
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10.1021/ja058801v CCC: $33.50 © 2006 American Chemical Society

C O M M U N I C A T I O N S
Scheme 2. Ring-Opening Metathesis Polymer Formation
Thus, the ROMP of cyclobutenecarboxamide 1 was regio- and
stereoselective and afforded functionalized polymers with polydis-
persities ranging from 1.2 to 1.6. Related polymers should provide
the basis for applications in both materials and chemical biology
when well-defined stereoregular structures are advantageous. Further
study is in progress to fully characterize the ROMP of cyclobutene
amides and other unexploited monomers.
Acknowledgment. This research was supported by NIH Grants
R01HD38519 (N.S.), S10RR021008 (N.S.), and R01CA87503
(K.A.P.) and NSF Grant CHE0131146 (NMR). We thank Dr. James
Marecek for his assistance with NMR spectroscopy.
Table 1. Polymerization Results
a
b
polymer
[M]o/[C]
calcd M n
h
PSS M n
h
rxn temp (°C)
PDI
% yieldc
7
8
9
10/1
18/1
35/1
50/1
1796
3149
6025
8563
5170
6532
10 445
16 966
24
24
24-40
24-40
1.18
1.30
1.52
1.56
57
59
59
64
Supporting Information Available: Experimental details including
synthetic procedures, spectroscopic data, gel permeation data, and
MALDI-TOF mass analysis. This material is available free of charge
via the Internet at http://pubs.acs.org.
10
a Number average molecular weight by NMR. b Number average mo-
lecular weight by GPC using polystyrene standards. c Isolated yield after
precipitation and silica column chromatography.
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and stereoselective and that it yields a head-to-tail ordered polymer
(Scheme 2) in which there are no ambiguities of tacticity.
Along with stereoregularity, polydispersity is an important
characteristic of well-defined polymers. We measured the polydis-
persity index (PDI) of each of our polymers by gel permeation
chromatography (GPC) with polystyrene standards (PSS). For each
of the polymers, the PSS Mhn was larger than the value calculated
from the NMR data. This result is consistent with the Benoit factor
for substituted 1,4-polybutadienes.10a For each polymer, the PDI
was low to moderate and the molecular weight distribution was
monomodal (Table 1 and data not shown). In the preparations of
larger polymers it was necessary to warm the reaction mixtures in
order to effect complete reaction; the higher temperature presumably
accounts for the larger PDIs. A plot of average molecular weight
versus monomer consumed was linear; this result was consistent
with a living polymerization and the absence of chain transfer (data
in Supporting Information).
Seeking more accurate molecular weight data for our polymers,
we examined the MALDI-TOF spectrum of polymer 7 (Figure 1).
The molecular ions and monomer repeats (+169) are consistent
with the assigned structure. The calculated Mhn indicates that the
average length of the polymer is that of an 11-mer, in close
agreement with our NMR data. The PDI is 1.15 in accord with the
GPC data.
(13) Love, J. A.; Morgan, J. P.; Trnka, T. M.; Grubbs, R. H. Angew. Chem.,
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