Accelerated ring-opening metathesis polymerization of a secondary amide of 1-cyclobutene by hydrogen-bonding interaction

Article abstract of DOI:10.1021/ol2014363

A hydrogen-bond-assisted model is proposed for ring-opening metathesis polymerization (ROMP) of a secondary amide of 1-cyclobutene, resulting in the fastest reaction rate in a nonpolar solvent, toluene. This new model was supported by the investigation on

Full text of DOI:10.1021/ol2014363

ORGANIC
LETTERS
2011
Vol. 13, No. 15
3908–3911
Accelerated Ring-Opening
Metathesis Polymerization of a
Secondary Amide of 1-Cyclobutene
by Hydrogen-Bonding Interaction
Kil Sun Lee and Tae-Lim Choi*
Department of Chemistry, Seoul National University, 599 Gwanak-ro, Gwanak-gu,
Seoul, Korea, 151-747
tlc@snu.ac.kr
Received May 27, 2011
ABSTRACT
A hydrogen-bond-assisted model is proposed for ring-opening metathesis polymerization (ROMP) of a secondary amide of 1-cyclobutene,
resulting in the fastest reaction rate in a nonpolar solvent, toluene. This new model was supported by the investigation on how the solvent effect
affected the NMR spectra, ROMP kinetic studies, and the copolymerization of monomers 1 and 2.
Ring-opening metathesis polymerization (ROMP) has
attracted a great deal of attention because it provides a
versatile method for the synthesis of functional polymers1
such as hydrogels,2 biologically active polymers,3 and
liquid crystalline polymers.4 This versatility has been
mainly driven by the remarkable development of well-
defined transition-metal catalysts on the basis of W, Mo,
and Ru complexes,5 which readily polymerize many
strained cycloalkenes such as norbornene derivatives,
cyclobutene, cyclooctene, and dicyclopentadiene.6 In par-
ticular, Grubbs catalysts based on Ru complexes are
widely used in ROMP because they are tolerant to protic
functional groups, oxygen, and moisture.7 However, the
drawback of Grubbs catalysts is that they generally give
less stereoregular polymers than the catalysts based on Mo
and W complexes.8
Among the few studies on the stereoregular polymeriza-
tion by Grubbs catalysts,9 recent studies conducted by
Sampson and Parker caught our attention. Although
many examples of the ROMP of substituted cyclo-
butenes have been reported, these polymers have low
(1) (a) Komiya, Z.; Pugh, C.; Schrock, R. R. Macromolecules 1992,
25, 6586. (b) Lynn, D. M.; Mohr, B.; Grubbs, R. H. J. Am. Chem. Soc.
1998, 120, 1627. (c) Royappa, A. T.; Saunders, R. S.; Rubner, M. F.;
Cohen, R. E. Langmuir 1998, 14, 6207.
(2) Bell, B.; Hamilton, J. G.; Law, E. E.; Rooney, J. J. Macromol.
Rapid Commun. 1994, 15, 543.
(3) (a) Roberts, K. S.; Konkar, S.; Sampson, N. S. ChemBioChem
2003, 4, 1229. (b) Gordon, E. J.; Gestwicki, J. E.; Strong, L. E.; Kiessling,
L. L. Chem. Biol. 2000, 7, 9.
(4) (a) Singh, R.; Verploegen, E.; Hammond, P. T.; Schrock, R. R.
Macromolecules 2006, 39, 8241. (b) Xia, Y.; Verduzco, R.; Grubbs,
R. H.; Kornfield, J. A. J. Am. Chem. Soc. 2008, 130, 1735.
(5) (a) Bielawski, C. W.; Grubbs, R. H. Prog. Polym. Sci. 2007, 32, 1.
(b) Buchmeiser, M. R. Chem. Rev. 2000, 100, 1565.
(6) Black, G.; Maher, D.; Risse, W. Living Ring-Opening Olefin
Metathesis Polymerization; Wiley-VCH: Weinheim, 2003.
(7) Trnka, T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34, 18.
(8) (a) Flook, M. M.; Victor, W. L. N.; Schrock, R. R. J. Am. Chem.
Soc. 2011, 133, 1784. (b) Katz, T. J.; Lee, S. J.; Shippey, M. A. J. Mol.
Catal. 1980, 8, 219.
(9) For an early example of highly stereoregular polymers prepared
by Grubbs catalyst, see: Choi, T.-L.; Rutenberg, I. M.; Grubbs, R. H.
Angew. Chem., Int. Ed. 2002, 41, 3839.
r
10.1021/ol2014363
Published on Web 07/08/2011
2011 American Chemical Society

regio- and stereoselectivity in general.10,11 On the other
hand, Sampson and Parker synthesized regioregular head-
to-tail polymers that strictly had an E-olefin geometry by
using third-generation Grubbs catalyst with secondary
amides of 1-cyclobutenes as monomers.12 Moreover, the
ROMP allowed controlled polymerization to give poly-
mers with a low to moderate polydispersity index (PDI) as
well. These polymers might find applications both as
materials and in chemical biology, where well-defined
stereoregular structures would be advantageous. Parker
and Sampson demonstrated the origin of the regio- and
stereoselectivity of the polymers using computational ana-
lysis and schematic models. However, one distinct draw-
back of the ROMP was that during homopolymerization,
1-cyclobutenecarboxylic acid ester underwent stoichio-
metric ring-opening metathesis with only one turnover,
and they proposed the chelation model of ester oxygen
coordinated to the ruthenium center, which resulted in the
deactivation of the catalyst and hence hindered further
propagation.13
amides of 1-cyclobutenes, which are the best monomers for
ROMP among the cyclobutene-1-carboxylic acid deriva-
tives, require an elevated temperature to produce regiore-
gular polymers with a degree of polymerization (DP) of 35
or higher.12 Furthermore, the catalyst fails to homopoly-
merize the 1-cyclobutenecarboxylic acid esters and the
tertiary amides.13a
We began our investigation to improve the efficiency of
this ROMP by inspecting the monomer structures, and we
realized that the presence of a secondary amide might
prove important. This led to a proposal that the hydrogen
of secondary amides in the enoic carbene intermediate
might have hydrogen-bonding interaction with the carbo-
nyl oxygen of an incoming monomer (Figure 1). If this
hypothesis was correct, then one could increase the ROMP
activity by enhancing the hydrogen bonding interaction,
which could be achieved by simply changing the polarity of
the solvent. To support this hypothesis, monomers 1 and 2
were synthesized (see the Supporting Information).13
Herein, we propose a new model of hydrogen bond-
assisted ROMP of the secondary amide of a 1-cyclobutene
monomer to explain why the secondary amides of 1-cyclo-
butenes are the most active monomers among the 1-cyclo-
butenecarboxylic acid derivatives. To verify this model, a
study on the solvent effect is conducted and a copolymer-
ization experiment is performed. To the best of our knowl-
edge, this is the first example of hydrogen bond-assisted
ROMP between monomers that results in faster polymer-
ization in a nonpolar solvent.14,15
Although highly strained cyclobutene derivatives are
good monomers for ROMP, the secondary amides of
1-cyclobutene are not good monomers for ROMP as
compared to 3-substituted cyclobutenes and norbornene
monomers.12,13 This is because they contain challenging
trisubstituted R,β-unsaturated carbonyl olefins that are
not only sterically hindered but also electron deficient.
Moreover, the inevitable formation of energetically un-
stable enoic carbenes as propagating species16 decreases
the ROMP activity even further. Therefore, the secondary
Figure 1. Proposed model for hydrogen-bond-assisted ROMP.17
To study the solvent effect on the hydrogen-bonding
interaction, dichloromethane (DCM), which was used in
the original report, and two other solvents were chosen:
tetrahydrafuran (THF) for interrupting the hydrogen
bonding and toluene as a nonpolar solvent. First, we
characterized 1 in these solvents by 1H NMR so as to shed
light on the interaction between 1 and the various solvents
(Figure S1, Supporting Information). When the 1H NMR
spectra of 1 in non-hydrogen bonding solvents were taken,
chemical shifts for the NÀH amide peak were observed at
6.06 ppm and 6.02 ppm in DCM-d2 and toluene-d8,
respectively. On the other hand, the N-H peak shifted
downfield to 7.14 ppm when recorded in the hydrogen-
bonding solvent, THF-d8, indicating that THF interacted
with 1 by hydrogen bonding and perhaps the ROMP
activity might be influenced by the choice of solvents.
In order to obtain more direct evidence to support the
proposed model (Figure 1), kinetic studies of ROMP in
three different solvents were conducted by monitoring the
conversion of 1 in NMR tube reactions. As shown in
Figure 2, the initial rate of ROMP in nonpolar toluene
was much faster than that in more polar DCM. Moreover,
(10) (a) Weck, M.; Mohr, B.; Grubbs, R. H. Macromolecules 1997,
30, 257. (b) de Fremont, P.; Montembault, V. R.; Fontaine, L. Macro-
mol. Chem. Phys. 2004, 205, 1238. (c) Grubbs, R. H. Macromolecules
1995, 28, 3502. (d) Maughon, B. R.; Grubbs, R. H. Macromolecules
1997, 30, 3459. (e) Perrott, M. G.; Novak, B. M. Macromolecules 1996,
29, 1817. (f) Snapper, M. L.; Tallarico, J. A.; Randall, M. L. J. Am.
Chem. Soc. 1997, 119, 1478.
(11) (a) McGinnis, J.; Altus, C. J. Am. Chem. Soc. 1976, 98, 606. (b)
Wilson, S. R.; Schalk, D. E. J. Org. Chem. 1976, 41, 3928. (c) Feng, J.;
Szeimies, G. Eur. J. Org. Chem. 2002, 2002, 2942.
(12) Lee, J. C.; Parker, K. A.; Sampson, N. S. J. Am. Chem. Soc. 2006,
128, 4578.
(13) (a) Song, A.; Lee, J. C.; Parker, K. A.; Sampson, N. S. J. Am.
Chem. Soc. 2010, 132, 10513. (b) For the related A,B-alternating ROMP,
see: Song, A.; Parker, K. A.; Sampson, N. S. J. Am. Chem. Soc. 2009,
131, 3444.
(14) For a templated assisted ROMP, see: South, C. R.; Weck, M.
Macromolecules 2007, 40, 1386.
(15) For a hydrogen-bond-assisted olefin metathesis reaction for the
synthesis of small molecules, see: Hoveyda, A. H.; Lombardi, P. J.;
O’Brien., R. V.; Zhugralin, A. R. J. Am. Chem. Soc. 2009, 131, 8378.
(16) (a) Ulman, M.; Grubbs, R. H. J. Org. Chem. 1999, 64, 7202. (b)
Choi, T.-L.; Lee, C. W.; Chatterjee, A. KJ.; Grubbs, R. H. J. Am. Chem.
Soc. 2001, 123, 10417.
(17) Similar models were used for the synthesis of A,B-alternating
€
Shiotsuki, M.; Masuda, T.; Sanda, F. J. Am. Chem. Soc. 2009, 131,
10546.
copolymers by Bronsted acidÀbase interaction; see: Sutthasupa, S.;
Org. Lett., Vol. 13, No. 15, 2011
3909

HoveydaÀGrubbs catalyst led toa 66% conversion, which
was the highest DP reported among the ROMP of this
family of monomers. These results again indicate that the
ROMP of the secondary amide of 1-cyclobutene was a
challenging reaction.
Table 1. Polymerization Resultsa
convc
(%)
b
temp time
Mn
entry [M]0/[C] cat. (°C)
(h)
(g/mol)
PDIb
1
2
3
4
5
10
20
A
A
A
B
B
rt
rt
<1
5
2600
2800
6400
6500
7100
1.10
1.16
1.13
1.17
1.21
>99
>99
86
50
45
45
60
24
24
24
50
90
100
66
Figure 2. TimeÀconversion plots for ROMP of 1 in various
solvents: [M] = 0.2 M, cat. = A, [M]/[C] = 10, 25 °C, benzoic
acid = 25 mol %.
a Reaction conditions: [M] = 0.15 M in toluene. b Determined by
THF-SEC calibrated by PS standards. c Conversion calculated by crude
1H NMR.
the rate of ROMP was slowest in the hydrogen-bonding
solvent, THF, even though it was reported that the pro-
pagation rate for typical ROMP was faster in THF than in
toluene and DCM.18 On the other hand, the activity of
Grubbs catalysts is known to increase by the addition of
catalytic amount of acids.19 Contrary to these reports,
when we added 25 mol % of benzoic acid in toluene, the
polymerization rate decreased. The results of theses kinetic
studies indicate that the ROMP of 1 was accelerated by the
hydrogen-bonding interaction between the propagating
carbenes and the monomers, and this effect was the max-
imum in nonpolar toluene, whereas THF and benzoic acid
as the additive slowed down the ROMP because of the
competing hydrogen bonding between them and the pro-
pagating carbenes.
To further verify the acceleration of the ROMP of 1
in toluene, the reaction time for the ROMP of various
[M]0/[C] values in toluene was compared with that in
dichloromethane. According to the previousreport, ittook
3 h to achieve an 85% conversion for [M]0/[C] = 10 in
DCM,13 but in toluene, the reaction was completed within
1 h (Table 1, entry 1). The reaction in toluene was
completed in 5 h for DP of 20 (Table 1, entry 2), whereas
it required more than 20 h to achieve 100% conversion
when [M]0/[C] was 18 in DCM.12 These results clearly
indicate that the rate of the ROMP of 1 was enhanced
in toluene because of the hydrogen-bonding interaction.
To obtain a polymer with a higher molecular weight, the
ROMP with a higher DP at an elevated temperature was
required. For [M]0/[C] = 50, the polymerization was
carried out at 45 °C, but the conversion was incomplete
in toluene even after 24 h. Under similar conditions, we
achieved a slightly higher conversion rate (86% to 90%
conversion, Table 1, entries 3 and 4) by changing the
catalyst to the more stable HoveydaÀGrubbs catalyst B
[(IMesH2)RuCl2(dCH-o-OiPrC6H4)]. Consequently, the
ROMP for [M]0/[C] = 100 at 60 °C in toluene using the
Based on the hydrogen bond-assisted ROMP model, we
investigatedhow the solventsinfluenced not only the initial
rates but also the final conversion of the polymerization.
Using catalystB, wechosea challenging reaction condition
of [M]0/[C] = 50 to directly compare the effect of a solvent
on the conversion. The reaction temperature was set to
40 °C owing to the low boiling point of DCM, and in all
cases, the conversion did not increase after 24 h. Based on
the results presented in Table 2, we can conclude that the
highest conversionand molecularweight wereobtainedfor
the ROMP in toluene, thus confirming that toluene was the
best solvent for the ROMP of the secondary amide of the
1-cyclobutene monomer.
Table 2. Solvent Screening Resultsa
convc
(%)
b
temp
Mn
entry
[ M]0/[C] solvent
(°C)
(g/mol)
PDIb
1
2
3
50
50
50
THF
40
40
40
3400
3200
4100
1.21
1.16
1.22
47
54
67
DCM
toluene
a Reaction conditions: [M] = 0.15 M, cat. = B, 24 h. b Determined by
THF-SEC calibrated by PS standards. c Conversion calculated by crude
1H NMR.
After improving the conditions for the ROMP of 1, we
focused our attention to the polymerization of 2, the ester
of 1-cyclobutenecarboxylic acid, which was reported to
undergo a stoichiometric ring-opening metathesis reaction
withonlyoneturnover. Itwasproposed thatthe ester enoic
ruthenium carbene formed an intramolecular chelate,
(18) Slugovc, C. Macromol. Rapid Commun. 2004, 25, 1283.
(19) Kim, S.; Hwang, W.; Lim, I. S.; Kim, S. H.; Lee, S.-g.; Kim,
B. M. Tetrahedron Lett. 2010, 51, 709.
3910
Org. Lett., Vol. 13, No. 15, 2011

deactivating the catalyst from further ROMP. By using
our hydrogen-bond-assisted ROMP model, we predicted
that if ester 2and amide 1were subjected to copolymerization
in toluene, ester monomer 2 would undergo random
ROMP with more than one turnover because the hydro-
gen-bonding between the carbonyl oxygen of ester 2 and
the NH of amide 1 would enhance the ROMP activity
(Figure 3). On the other hand, if the hydrogen-bond-
assisted ROMP was not operative, the copolymer would
incorporate only 1 equiv of 2 or the ROMP would be
inhibited by the chelation.
Scheme 1. Random Ring-Opening Metathesis Polymerization
Table 3. Random ROMP Resultsa
entry solvent temp (°C) Mnb (g/mol) PDIb Polymer a:b ratioc
1
2
3
toluene
DCM
THF
45
40
45
3900
3200
3000
1.42
1.60
1.61
10:4
10:2
10:1
Figure 3. Model for activity 2 during random copolymerization.
a Reaction conditions: [M] = 0.2 M, cat. = B, 12 h. b Determined by
To test this premise, a mixture of 10 equiv of 1 and
20 equiv of 2 was added to catalyst B in toluene at 45 °C.
After 24 h, complete consumption of 1 and 20% incor-
poration of 2 was observed by 1H NMR (a:b = 2.5:1) after
purification of the copolymer, implying that on average,
the obtained copolymer contained 10 units of 1 and 4 units
of 2 (Scheme 1, Table 3, entry 1). When more polar DCM
used in the reaction, the obtained copolymer contained 10
units of 1 and 2 units of 2 (Table 3, entry 2). On the other
hand, the reaction incoporated only 1 unit of 2 and 10
units of 1 after the ROMP in hydrogen-bonding sol-
vent, THF (Table 3, entry 3). Although the low incor-
poration of 2 in non-hydrogen-bonding solvents might
not appear to be significant, these results further vali-
dated the hydrogen-bond-assisted ROMP model, in
which the nonactive monomer 2 was incorporated into
the copolymer by an amount greater than the stoichio-
metric amount, whereas only one turnover of 2 oc-
curred as expected in THF.
chloroform-SEC calibrated by PS standards. c Ratio determined by 1H
NMR analysis of the copolymers.
In conclusion, we demonstrated the accelerated ROMP
of 1 in a nonpolar solvent, toluene. This rate enhancement
was explained by the hydrogen-bond-assisted model which
was strongly supported by the results of the kinetic studies
of the ROMP and the copolymerization experiment. Our
findings should expand the scope and utility of the synth-
esis of regio- and stereoregular polymers.
Acknowledgment. Financial support from the National
Research Foundation of Korea (BRL), BK21, and Chun-
gam Fellowship is acknowledged.
Supporting Information Available. Experimental pro-
cedures and NMR characterization data for new com-
pounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
Org. Lett., Vol. 13, No. 15, 2011
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