Access to Bicyclo[4.2.0]octene Monomers to Explore the Scope of Alternating Ring-Opening Metathesis Polymerization

Article abstract of DOI:10.1021/acs.joc.8b00054

Bicyclo[4.2.0]oct-1(8)-ene-8-carboxamides undergo alternating ring-opening metathesis polymerization (AROMP) with cyclohexene. Herein, a general method for the preparation of bicyclo[4.2.0]oct-(8)-ene-8-carboxy derivatives is described. The central 8-cyano intermediate provides entry to five different functional group substituents on the alkene. These monomers were tested as potential substrates for AROMP with cyclohexene. In addition to the carboxamide, the carboxynitrile and carboxaldehyde are also substrates for AROMP. In the case of the carboxaldehyde, the polymer is regioregular. However, the addition of carboxynitrile is stereoirregular and slow.

Full text of DOI:10.1021/acs.joc.8b00054

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Article
Access to bicyclo[4.2.0]octene monomers to explore the
scope of alternating ring-opening metathesis polymerization
Lei Chen, Liqiang Li, and Nicole S Sampson
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b00054 • Publication Date (Web): 06 Feb 2018
Downloaded from http://pubs.acs.org on February 6, 2018
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Page 1 of 18
The Journal of Organic Chemistry
Access to bicyclo[4.2.0]octene monomers to explore the scope of alternating ring-
opening metathesis polymerization
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Lei Chen, Liqiang Li and Nicole S. Sampson*
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Department of Chemistry, Stony Brook University, Stony Brook, NY 11794-3400.
*Corresponding Author: nicole.sampson@stonybrook.edu
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CONHR
CO2H
[Ru]
AROMP
CN
+
[Ru]
Slow and Stereoirregular
AROMP
CO2R
CHO
[Ru]
AROMP
+
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Abstract
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Bicyclo[4.2.0]oct-1(8)-ene-8-carboxamides undergo alternating ring-opening metathesis polymerization
(AROMP) with cyclohexene. Herein, a general method for the preparation of bicyclo[4.2.0]oct-(8)-ene-
8-carboxy derivatives is described. The central 8-cyano intermediate provides entry to five different
functional group substituents on the alkene. These monomers were tested as potential substrates for
AROMP with cyclohexene. In addition to the carboxamide, the carboxynitrile and carboxaldehyde are
also substrates for AROMP. In the case of the carboxaldehyde, the polymer is regioregular. However,
the addition of carboxynitrile is stereoirregular and slow.
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The Journal of Organic Chemistry
Introduction
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Alternating co-polymers are of interest for a multitude of applications ranging from the biological to
nanoelectronics and catalysis.1-8 Generally, alternating copolymers have been synthesized by radical
polymerization9-12 and metal-mediated routes, including CO2/epoxide copolymerizations13 and catalyst
transfer polymerizations of heterocycles.14 However the introduction of functionality can be limited by
reaction conditions. In addition, these polymerizations often provide broad molecular weight distribu-
tions. A more advanced method for the synthesis of alternating polymers is iterative chain extension,15
but lengths are limited by yield and purification steps.
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2
CONHR
CONHR
+
1
8
7
3
4
2
6
1'
5
1
3
Mes
N
N
Cl
Mes
Ph
2
CONHR
N Ru
Ph
Cl
N
Br
4
CONHR
Br
2
poly(1-alt-3)n
Scheme 1. Original route to monomer 1, which is used in AROMP with cyclohexene 3.
Recently, advances have yielded several approaches to polymer sequence control using metathesis
and/or ring-opening methods.16-25 We reported the rapid initiation and alternating propagation of bicy-
clo[4.2.0]oct-1(8)-ene-8-carboxamides with cyclohexene and ruthenium catalysis leads to very long al-
ternating polymers of excellent dispersities (Scheme 1).26 Monomers 1 were obtained by Ru-catalyzed
(2) isomerization of bicyclo[4.2.0]oct-7-ene-7-carboxamides 1’ (Scheme 1). The isomerization and sub-
sequent polymerization can be carried out in a single pot reaction. However, any loss of catalyst via
decomposition during isomerization affected the ultimate molecular weight and molecular weight distri-
bution of the polymer obtained. Moreover, the isomerization is sensitive to functionality in the amide
side chain, and bulkier substituents led to incomplete isomerization. Thus, yields of monomers were
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affected by slow isomerization which necessitated isolating bicyclo[4.2.0]oct-1(8)-ene-8-carboxamide
before isomerization was complete to prevent loss of carboxamide to ring-opening metathesis.26 In ad-
dition, preparation of polymers of a specific molecular weight with narrow dispersities necessitated iso-
lation and purification of monomer 1, followed by initiation of polymerization with fresh catalyst 2. As an
additional consideration, preparation of the ester precursor to monomer 1’ requires an epoxidation step
to separate regioisomers chromatographically that limits the scale of the reaction.27
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Therefore, we sought a simpler and more direct route to monomer 1 that would facilitate preparation of
polymers with a greater diversity of substituents. Here, we describe the direct preparation of amide 1
from stable nitrile 4, which can be easily prepared in multi-gram quantities from cyclohexanone and
pyrrolidine (Scheme 2). A further advantage of the synthetic scheme is that the 1(8)-alkene in the bicy-
clo[4.2.0] scaffold is obtained through direct elimination. This approach provides entry to the nitrile 4,
aldehyde 10, and ester-substituted bicyclo[4.2.0]oct-1(8)-ene 9 that have never been tested as mono-
mers in AROMP (Scheme 3).
O
N
5
Toluene
Pentane
CN
N
CN
+
+
6
N
H
MeI
Et2O
2
5
N
CN
8
1
6
CN
3
4
NaOH
7
7
4
overall yield 41%
Scheme 2. Synthesis of bicyclo [4.2.0] oct-8-ene-8-carbonitrile
CO2H
CN
8'
KOH
+
CONHR1
CO2H
R1NH2
4
8
DIBAL/DCM
CHO
1
R2I
CO2R2
R1 = propyl
R2 = ethyl
10
9
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Scheme 3. Synthesis of potential AROMP monomers from 4.
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RESULTS and DISCUSSION
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Synthesis of AROMP monomers. The preparation of bicyclo[4.2.0]oct-1(8)-ene-8-carbonitrile 4 is based
on Harley-Mason’s approach.28 Cyclohexanone and pyrrolidine are condensed to provide 1-N-
pyrrolidinylcyclohexene 5. A 2+2 cycloaddition with acrylonitrile yields carbonitrile 6. Subsequent N-
methylation and Hoffman elimination produces bicyclo[4.2.0]oct-1(8)-ene-8-carbonitrile 4 in 41% overall
yield (Scheme 2). This synthetic route relies on isolation of solid intermediates that can be utilized with-
out additional purification steps and a single chromatographic step to purify nitrile 4. Thus, we routinely
prepared 4 on a five-gram scale.
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We envisioned nitrile 4 could be converted to a variety of potential AROMP monomers. First, we sought
conversion of nitrile 4 to carboxylic acid 8 through hydrolysis of nitrile 4 without addition of metal cata-
lyst and mild heating. Carboxylic acid 8 could then be coupled with an amine to provide the amide 1 or
with an alcohol or alkyl iodide to yield ester 9.
Initial attempts to hydrolyze nitrile 4 gave a very low yield of acid 8. Moreover, during hydrolysis, isom-
erization of the alkene occurred to form bicyclo[4.2.0]oct1(2)-ene-8-carboxylic acid 8’ (Scheme 3 and
Table 1). This alkene is approximately 1.5 kcal/mol more stable than 8.29 Therefore, we undertook op-
timization of this reaction to produce acid 8.
1
The nitrile hydrolysis reaction was monitored by H NMR spectroscopy to determine the degree of
isomerization and conversion under a variety of conditions. The product distribution was assessed by
comparing the 1H NMR integration of the 8’ hydrogen with a resonance at 3.92 ppm to the 8 hydrogen
with a resonance at 2.92 ppm (see for example, Figure S1). Bicyclo[4.2.0]oct-1(8)-ene-8-carbonitrile 4
does not dissolve well in water, and the hydrolysis reaction is necessarily biphasic. Thus, we tested for
possible cosolvents to improve the reaction yield and rate. Methanol, DMSO, DMF, THF, or ethylene
glycol were mixed with 2 M NaOH (1:1, v:v), nitrile 4 added, and the mixture heated to 50 °C for 1 day.
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Although the solutions were homogenous, none of the solvent mixtures improved selectivity or yield
compared to the purely aqueous system.
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8
Subsequently, temperature was studied (Table 1, entries 1, 2, 3, 4, 7). At 110 °C, the hydrolysis reac-
tion proceeded rapidly, but selectivity for the desired alkene isomer was low. At 40 °C, the reaction did
not proceed after 4 days. At 50 °C, the highest selectivity was obtained.
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Table 1. Hydrolysis of bicyclo[4.2.0]oct-1(8)-ene-8-carbonitrile 4 in H2O.
Entry Time Temp % Yield 8:8’b % remaining 4b
(d)
1
(°C)
110
8+8’a
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2
3
4
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6
7
-
1:1
3.5:1
3:1
3:1
4:1
4:1
-
0
11%
10%
0
1
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40
17%
12%
25%
49%
52%
-
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2
4
0
9
0
4
100%
aIsolated yield of carboxylic acids 8 and 8’. bAs assessed
by 1H NMR spectroscopy of the quenched reaction.
The intermediate amide was also obtained as an undesired side product. We investigated extension of
reaction time to increase yield of 8 (Table 1 entries 4, 5, 6, 7). Doubling the reaction time from 2 to 4
days increased the yield of acid 8 from 25% to 50% (Table 1, entries 4, 5). Although an extended reac-
tion time of 9 days did not reduce selectivity, minimal improvements in yield were obtained.
With an inexpensive and simple synthesis of nitrile 4 and acid 8, we prepared amide 1 and ester 9 by
standard coupling methods (Scheme 3). In addition, reduction of nitrile 4 with DIBAL-H provides alde-
hyde 10 in 36% yield isolated as a solution to prevent self-condensation. Next, the propensity of the
[4.2.0] derivatives to undergo alternating ring opening metathesis polymerization (AROMP) was tested.
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The Journal of Organic Chemistry
1
Investigation of [4.2.0] derivative AROMP. Using H NMR spectroscopy, we followed the alternating
ring opening metathesis polymerization (AROMP) of each type of monomer (4, 8, 9, and 10) with cy-
clohexene 3. The alkene region of the spectrum was monitored to determine whether ring-opened pol-
ymer was obtained and the degree of region- and stereocontrol obtained (Figure 1). The AROMP of
amide 1 previously reported to form poly(1-alt-3)n26 was used as a positive control.
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Nitrile 4. Nitrile 4 underwent very slow initiation with catalyst 2. The slow initiation of 4 may be due to
the strong electron withdrawing cyano group. Upon addition of a 2-fold molar excess of cyclohexene 3,
only 30% of monomer 4 was consumed after 24 hours (Table 2, entry 1). Therefore, we used a large
molar excess (20-fold excess) of cyclohexene 3 to push the equilibrium toward ring-opening metathesis
polymerization. One hour after cyclohexene 3 addition, no AROMP product was detected as evidenced
by the lack of new alkene protons in the 1H NMR spectrum of the reaction. After 24 hours, all the nitrile
4 disappeared and AROMP product appeared (Figures 1 and S2, Table 2, entry 2).
Repeated attempts to purify the poly(4-alt-3)10 polymer by silica column chromatography only yielded
multiple decomposition products, which were not characterized further. Gel permeation chromatog-
raphy analysis of the crude poly(4-alt-3)10 polymer revealed that the expected molecular weight was
obtained (Mn = 2300). However, the dispersity index was 1.7 (Figure S3), which is high in comparison
to the narrower dispersity (1.1–1.2) poly(1-alt-3)n polymers obtained from amide 1.27 This high dispersi-
ty is consistent with the slow reaction times, suggesting that intermolecular chain transfer competes
with AROMP of nitrile 4.
1
Inspection of the alkene region of the H-NMR spectrum of poly(4-alt-3)10 revealed that two isomers
were formed during AROMP in approximately a 2:1 ratio (Figure 1). Previously, we established that the
1H resonance of the E-alkene is shifted downfield compared to the Z-isomer.30 Therefore, the major
isomer of poly(4-alt-3)10 formed is the E-alkene. The reduced selectivity for the E-alkene in the AROMP
of nitrile 4 is consistent with reduced allylic 1,3 steric and electronic strain in the case of substitution of
the alkene with the linear nitrile moiety. Thus, the carbonyl on the alkene amide substituent serves two
functions. First, the amide increases the rate of AROMP compared to the nitrile, despite the strong ni-
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trile dipole.31 Second, the amide carbonyl is required to destabilize formation of the Z-alkene during
1
2
3
metathesis of [4.2.0] monomer.
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8
Ester 9. Surprisingly, bicyclo[4.2.0]oct-1(8)-ene-8-carboxylate ester 9 failed to react within 24 hours un-
der AROMP conditions, even with a large excess of cyclohexene 3 (Figures 1 and S4, Table 2, entries
3 and 4). It is unclear why ester 9 reacts more slowly than amide 1. Based on 13C chemical shifts, the
electron density distribution on the alkene of ester 9 is similar to the alkene of amide 1 (124.1/163.9 vs.
126.7/161.0 ppm). This low efficiency was unexpected considering that the isomeric methyl bicy-
clo[4.2.0]oct-7-ene-7-carboxylate readily undergoes AROMP with cyclohexene 3 and catalyst 2, albeit
at a slower rate than amide 1.27
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Acid 8. Similarly, acid 8 did not form AROMP product with cyclohexene 3 (Table 2, entry 5). Even with
an excess of cyclohexene 3 after 24 hours no polymer was formed (Figures 1 and S5, Table 2, entry
6). Instead, the monomer decomposed under the reaction conditions, and further study was not pur-
sued.
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Figure 1. AROMP of 1, 4, 8, 9, 10 with cyclohexene 3. The alkene region is shown in the figure. (Full
spectra are included in the SI as Figures S2, S4-S6.) [4.2.0] Monomer A (0.25 M in CDCl3,10 equiva-
lents for amide 1, nitrile 4, acid 8 and ester 9; 1.25 M in CDCl3, 50 equivalents for aldehyde 10) was
added to a solution of catalyst 2 (0.1 M in CDCl3) and the reaction initiated at 40 °C for 1 hour, then cy-
clohexene 3 (monomer B, 200 equivalents) was added and the reaction allowed to proceed for 1 hour
(amide 1 and aldehyde 10) or 24 hours (nitrile 4, acid 8 and ester 9). For monomers 1, 4, 8 and 9, the
reaction was quenched with excess ethyl vinyl ether, solvent was removed, and the crude product was
re-dissolved in CDCl3 and a 1H NMR spectrum acquired of the unpurified product(s).
Aldehyde 10. Aldehyde 10 self-condenses if concentrated during distillation (b.p. ca. 70°C), to prevent
self-reaction it was stored as a hexane solution (60% w/w in hexane). Despite these challenges, alde-
hyde 10 was subjected to AROMP conditions. The aldehyde monomer reacts rapidly within 1 hour and
undergoes regioselective AROMP reaction with cyclohexene 3 as evidenced by the appearance of al-
kene proton resonances at 5.0 and 6.4 ppm (Figures 1 and S6, Table 2, entry 7). The high reactivity of
poly(10-alt-3)50 precluded further characterization of the polymer molecular weight or molecular weight
distribution by gel permeation chromatography.
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Table 2. AROMP of [4.2.0] Monomers with cyclohexene 3.a
Entry A [A]:[Bb]:[2] Time(h) Conv
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9
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4
9
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8
10:20:1
10:200:1
10:20:1
10:200:1
10:20:1
10:200:1
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24
24
24
1
30%
100%
–
–
–
–
10 50:200:1
100%
1
1
100:200:1 1
89% isolated yield26
100%
10:200:1
1
aAt 40 °C, [4.2.0] monomer is incubated with catalyst 2 in
CDCl3 for 1 hour before addition of 3, and time of reac-
tion after addition of 3 is measured. bCyclohexene 3.
CONCLUSION
In conclusion, we developed an efficient and scalable synthesis of bicyclo[4.2.0] acid 8 which provides
ready and direct access to amide monomers for AROMP reactions. Additionally, this synthesis provid-
ed an opportunity to explore the scope of the AROMP reaction. Although the nitrile monomer 4 under-
goes stereoirregular AROMP, the long-reaction times led to a high dispersity. Therefore, the utility of
this monomer is limited. The aldehyde monomer 10 is an interesting prospect for development based
on its excellent kinetic performance in the cyclohexene 3 AROMP reaction. Although the resulting al-
dehyde polymer was very reactive and difficult to isolate for full characterization, pursuit of pre- or post-
polymerization modification procedures will be pursued to introduce more complex functionality in the
future. Our results suggest that the AROMP reaction is very sensitive to subtle shifts in carbonyl orien-
tation and alkene substituent polarity. We conclude that a carbonyl on the alkene substituent is re-
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quired for rapid, regio- and stereoregular AROMP between [4.2.0] monomers and cyclohexene 3, but is
1
2
3
not sufficient to ensure reaction.
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8
EXPERIMENTAL SECTION
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General Materials and Methods. Solvents, e.g. CH2Cl2 and THF were purified with Pure Process
Technology (PPT).26 Deuterated solvents for all ring-opening reactions were degassed and filtered
through basic alumina before use. Catalyst Cl2(H2IMes)(PCy3)Ru=CHPh and poly(styrene) standards
were purchased from Aldrich. Freshly prepared catalyst (3-Br-Pyr)2Cl2(H2IMes)Ru=CHPh, 232 should
be used to minimize oxidative degradation. Heteronuclear singular quantum correlation (HSQC) was
used to establish atom connectivity and spatial relationships of acid 8. Molecular weights (Mn and Mw)
and polydispersity indices (Mw/Mn) were determined by gel permeation chromatography (GPC) using a
Phenogel 5µm 10E4A LC column (300 x 7.8mm, 500 KDa exclusion limit, Phenomenex) with tetrahy-
o
drofuran as the mobile phase at 30 C. Output was detected with a Brookhaven Instruments refractive
index and light scattering detector using an eluent flow rate of 0.7 mL/min and a 200 μL injection loop.
Mallinckrodt silica gel 60 (230-400 mesh) was used for column chromatography. Analytical thin layer
chromatography (TLC) was performed on precoated silica gel plates (60F254), flash chromatography on
silica gel-60 (230-400 mesh), and Combi-Flash chromatography on RediSep normal phase silica col-
umns (silica gel-60, 230-400 mesh). Rf values reported are measured by TLC in the same solvent sys-
tem used for column chromatography. Bruker Nanobay 400, Avance III 500, Avance III 700 NMR in-
struments were used for analysis. Chemical shifts were calibrated from residual undeuterated solvents;
they are denoted in ppm (δ). Functional groups for monomers and polymers were characterized using
Fourier transform infrared spectroscopy (Nicolet iS 10 spectrophotometer Thermo Scientific, Inc) and
are expressed in cm-1. GC/MS (Agilent LC-MSD, with a 1100 HPLC and G1956A mass spectrometer),
o
was performed with an injection volume of 15 μL, column temperature = 26-35 C and MSD gas tem-
perature = 300 oC.
Bicyclo[4.2.0]oct-1(8)-ene-8-carbonitrile, 4.28 A 250-mL round-bottomed flask containing 4Å molecu-
lar sieves and cyclohexanone (19.1 g, 195 mmol) in toluene (100 mL) was fitted with a Dean-Stark trap
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with reflux condenser and heating mantle. Pyrrolidine (30 mL, 365 mmol) was added to above solution.
The solution was heated to reflux for 18 h. The solvent was evaporated to yield crude 1-N-
pyrrolidinylcyclohexene 5 as a yellow oil (29 g, 97% yield) with spectra identical to the literature.33
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Crude 5 (crude, 5.5 mL, 70 mmol) in pentane (10 mL) was mixed with acrylonitrile (6.0 mL, 91 mmol) at
0 °C. The temperature was allowed to rise to rt (25 °C) over 1 h. The mixture was kept at 0 °C over-
night and then cooled to -78 °C. The suspension was filtered to provide 1-N-
pyrrolidinylbicyclo[4.2.0]octane-8-carbonitrile 628 as a yellow waxy solid (13.4 g, 94% yield from 5). The
crude product was used immediately in the next reaction without further purification.
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Crude 6 (crude, 1.0 g, 5 mmol) in dry diethyl ether (3 mL) was cooled to 0 °C. Methyl iodide (1.0 mL, 16
mmol) was added dropwise. The flask was stoppered and stored at rt for 7 days. Solvent was evapo-
rated to give methyl iodide 7 as amorphous solid. Crude methyl iodide 7 in water (5 mL) was mixed
with 10% sodium hydroxide (4 mL), then the mixture was extracted with diethyl ether (20 mL x 3). The
organic phase was dried over Na2SO4, filtered, and concentrated by rotary evaporator. The residue
was purified by silica column chromatography (EA/hexane=1:100, Rf = 0.1) to provide bicyclo[4.2.0]oct-
1(8)-ene-8-carbonitrile 4 as a yellow oil (0.54 g, 45% yield from 6). The NMR, IR and UV spectra were
identical to the literature.28
Bicyclo[4.2.0]oct-8-ene-8-carboxylic acid, 8. Nitrile 4 (200 mg, 1.5 mmol) was mixed with 20% po-
tassium hydroxide (20 mL) in a 25 mL flask. The reaction was heated to 50°C for 4 days under an N2
atmosphere. The cooled mixture was extracted with CH2Cl2 (20 mL x 3). The organic phase was dried
over Na2SO4 to give bicyclo[4.2.0]oct-1(8)-ene-8-carboxamide as a yellow amorphous solid (97 mg,
43% yield from 4).28 1H NMR (500 MHz, CDCl3): δ 5.65 (s, 1H), 5.41 (s, 1H), 2.82 (dd, J= 3.8, 14.0 Hz,
1H), 2.72 (dt, J= 3.8, 12.1 Hz, 1H), 2.39 (m, 1H), 2.22 (ddd, J= 1.2, 3.0, 12.1 Hz, 1H), 2.17-2.05 (m,
2H), 1.98-1.92 (m, 1H), 1.80-1.74 (m, 1H), 1.37-1.31 (m, 2H), 1.19-1.10 (m, 1H). 13C NMR (125 MHz,
CDCl3): 165.9, 163.0, 126.0, 37.9, 34.2 32.9, 27.4, 26.8, 24.6. HRMS (ESI-TOF) m/z: [M+H] + Calcd for
C9H14NO 152.1075; Found 152.1072.
The aqueous phase was acidified to pH=1 with HCl (2 M) then extracted with CH2Cl2 (3 x 30 mL). The
organic phase was dried over Na2SO4, filtered, and concentrated by rotary evaporator. The oily residue
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was purified by silica column chromatography (CH2Cl2, Rf = 0.8) to yield 8 as a 4:1 mixture with 8’. The
product was further purified by combined recrystallization (hexane) to give 8 as a white solid (87 mg,
38% yield from starting material 4), m.p. 72– 74 °C. 1H NMR (500 MHz, CDCl3): δ 10.75 (br, 1 H), 2.93
(dd, J= 3.2 Hz, 1H), 2.76 (dt, 1H), 2.41 (m, 1H), 2.28 (dd, J= 15.4 Hz, 1H), 2.17 (m, J= 2.3 Hz, 1H),
2.08 (m, J= 6.6 Hz, 1H), 1.98 (m, 1H), 1.76 (m, J= 2.2 Hz, 1H), 1.40-1.28 (m, J= 2.0, 2H), 1.20-1.11 (m,
J= 11.24 Hz, 1H). 13C NMR (125 MHz, CDCl3): 171.4, 168.4, 123.4, 38.8, 34.2 33.1, 27.8, 26.9, 24.5.
HRMS (ESI-TOF) m/z: [M+H] + Calcd for C9H13O2 153.0916; Found 153.0911.
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N-Propyl bicyclo[4.2.0]oct-8-ene-8-carboxamide, 1. Bicyclo[4.2.0]oct-8-ene-8-carboxylic acid 8 (66.
5 mg, 0.5 mmol) was dissolved in 0.8 mL dry CH2Cl2 in a 4-mL vial. The solution was stirred and cooled
to 0 ºC for 30 min. Oxalyl dichloride (2.0 mmol, 175 μL) was added. The mixture was allowed to react
for 1 h at rt and the vial was evacuated for 30 min under high vacuum to evaporate solvent and residu-
al oxalyl dichloride. N-Propylamine (57.5 μL, 0.7 mmol) and DIPEA (280 μL, 1.6 mmol) were dissolved
in 0.5 mL dry CH2Cl2. The solution was stirred at 0 ºC for 1 h then transferred to the vial containing acid
chloride at 0 ºC. The mixture was stirred for an additional 16 h. The reaction mixture was washed se-
quentially with 5% NaHCO3 (3 x 20 mL), 1N HCl (3 x 20 mL) and brine (2 x 20 mL) and dried over an-
hydrous Na2SO4. The solvent was filtered and removed by evaporation. The crude product was purified
by silica column chromatography (CH2Cl2/Methanol=10:1, Rf = 0.7) to give amide 1 as a white solid (82
mg, 85% yield). IR 3303, 2925, 2845, 1675, 1627, 1533, 1431 cm-1. The 1H NMR and 13C NMR spectra
were identical to those previously reported from the synthesis of 1 via a different route.34
Ethyl bicyclo[4.2.0]oct-1(8)-ene-8-carboxylate, 9. Acid 8 (76 mg, 0.5 mmol) was dissolved in 1 mL
DMF. Potassium carbonate (84 mg, 0.6 mmol) and ethyl iodide (100 μL, 1.2 mmol) were added at rt
(25 °C) and the solution was stirred for 24 h at rt. The solution was diluted with water (10 mL) and ex-
tracted with EtOAc (20 mL). The organic phase was washed with brine (3 x 20 mL) and dried over
Na2SO4. The solvent was removed to give ester 9 as a clear oil (85 mg, 94% yield). 1H NMR (500 MHz,
CDCl3): δ 4.20 (q, J=5 Hz, 2H), 2.87 (dd, J=3, 13.5 Hz, 1H), 2.75 (td, J=3.5, 12.5 Hz, 1H), 2.34-2.41 (m,
1H), 2.24 (ddd, J=1, 3, 12.5 Hz, 1H), 2.11-2.18 (m, 1H), 1.91-1.98 (m, 1H), 1.74-1.79 (m, 1H), 1.28-
1.35 (m, 5H), 1.10-1.18 (m, 1H). 13C NMR (125 MHz, CDCl3): 167.2, 163.9, 124.1, 59.6, 38.4, 34.4,
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+
+
33.0, 27.5, 26.9, 24.6, 14.4. HRMS (ESI-TOF) m/z: [M+H] Calcd for C11HO2 [M+H] 181.1229;
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Found 181.1218.
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Bicyclo[4.2.0]oct-1(8)-ene-8-carboxaldehyde, 10.35,36 Nitrile 4 132 mg (1.0 mmol) in dry CH2Cl2 (0.9
mL), was cooled to -78 °C. DIBAL-H 1.05 mL (1.05 mmol, 1.0 M in hexane) was added. The mixture
was stirred for 30 min at -78 °C, and for 2 h at -40 °C until 4 was completely consumed as determined
by GC/MS analysis. The system was cooled to -78 °C, 0.5 mL EtOAc was added over 10 min. After
stirring for 30 min, the temperature was raised to rt and the reaction was stirred for another 30 min. The
solution was diluted with 30 mL Et2O and was washed with 1M HCl (3 x 20 mL) and dried over Na2SO4.
The solvent was removed carefully by distillation to give crude 10 as a clear oil (36% yield，60% in
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hexane w:w). 1H NMR (400 MHz, CDCl3): δ 9.64 (s, 1H), 2.87 (td, J=3.75, 10.67 Hz, 1H), 2.69-2.75 (td,
J=3.11, 1H), 2.43-2.48 (m, 1H), 2.04-2.35 (m, J=0.99, 10.43 Hz, 3H), 2.11-2.18 (m, 1H), 1.93-2.03 (m,
1 J=1.59 Hz, 1H), 1.71-1.78 (m, 2H), 1.29-1.38 (m, 2H), 1.07-1.28 (m, 3H), 0.81-0.98 (m, J=6.91 Hz,
2H). 13C NMR (100 MHz, CDCl3): 185.3, 172.8, 134.2, 39.6, 33.2, 32.8, 27.2, 26.9, 22.6. HRMS (ESI-
TOF) m/z: [M+H] + Calcd for C9H13O 137.0966; Found 137.0943.
General Procedure for NMR Scale AROMP Reactions. All experiments were performed under N2 at-
mosphere. A solution of [4.2.0] monomer A in 400 μL CDCl3 was added to the NMR tube, then catalyst
2 in 100 μL CDCl3 was added to the NMR tube. The NMR tube was heated in a water bath at 40 °C.
Cyclohexene 3 (monomer B) was added after the catalyst was consumed as judged by the disappear-
ance of the Ru alkylidene resonance at 19.1 ppm, or 1 h after the catalyst was added, whichever was
1
shorter. After all monomer A was consumed as judged by the disappearance of the H-NMR peak
around 2.9 ppm, or after 24 h, the reaction was quenched with excess ethyl vinyl ether for 30 min. The
solvent was evaporated and the crude product was re-dissolved in CDCl3 for NMR characterization.
AROMP of N-Propyl bicyclo[4.2.0]oct-8-ene-8-carboxamide 1. Amide 1 (19 mg, 0.1 mmol, 10 eq) was
dissolved in 400 μL CDCl3. Subsequently, a solution of catalyst 2 (8.9 mg, 0.01 mmol, 1 eq) in 100 μL
CDCl3 was added. After 1 h, 200 μL 3 (200 eq) was added. After 1 h 50 μL ethyl vinyl ether was added
and the reaction was stirred for 30 min. The solvent was evaporated and characterized in CDCl3 by
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1
NMR spectroscopy, and regioirregular polymer product poly(1-alt-3)10 was obtained. The H NMR and
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13C NMR spectra were identical to those previously reported.34 IR 3305, 2923, 2853, 1653, 1616 cm-1.
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AROMP of bicyclo[4.2.0]oct-8-ene-8-carboxylic acid 8. Acid 8 (15 mg, 0.1 mmol, 10 eq) was dissolved
in 400 μL CDCl3. Subsequently, a solution of catalyst 2 (8.9 mg, 0.01 mmol, 1 eq) in 100 μL CDCl3 was
added. After 1 h, 200 μL 3 (200 eq) was added. After 24 h, AROMP product was not observed in the 1H
NMR spectrum and 50 μL ethyl vinyl ether was added and the reaction was stirred for 30 min. The sol-
vent was evaporated and characterized in CDCl3 by NMR spectroscopy, and no polymer was obtained.
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AROMP of bicyclo[4.2.0]oct-1(8)-ene-8-carbonitrile 4. Nitrile 4 (13 mg, 0.1 mmol, 10 eq) was dissolved
in 400 μL CDCl3. Subsequently, a solution of catalyst 2 (8.9 mg, 0.01 mmol, 1 eq) in 100 μL CDCl3 was
added. After 1 h, 200 μL 3 (200 eq) was added. After 24 h, 50 μL ethyl vinyl ether was added and the
reaction was stirred for 30 min. The solvent was evaporated, and characterized NMR and IR spectros-
1
copy. Regioirregular polymer product poly(4-alt-3)10 was obtained. H NMR (700 MHz, CDCl3): δ 6.37
(t, J=14.28, 0.54 H), 6.11 (s, 0.33 H), 5.00-5.20 (m, J=7.35, 1H), 2.41-2.62 (M, 2H), 2.36 (m, 2H), 1.96-
2.27 (m, J=6.65, 7H), 1.27-1.75 (m, J=9.59, 7.14, 10H). 13C NMR (125 MHz, CDCl3): 148.7, 140.5,
129.0, 120.3, 114.2, 42.9, 42.8, 42.7, 42.2, 37.0, 32.7, 31.4, 29.6, 29.4, 28.6, 28.3, 28.2, 28.1, 28.0,
27.8, 26.8, 26.7, 25.6, 23.6, 15.3. IR 2923, 2852, 2213, 1447, 1263 cm-1. MnGPC =2.3K. ĐM =1.70.
AROMP of bicyclo[4.2.0]oct-1(8)-ene-8-carboxylate 9. Ester 9 (18 mg, 0.1 mmol, 10 eq) was dissolved
in 400 μL CDCl3. Subsequently, a solution of catalyst 2 (8.9 mg, 0.01 mmol, 1 eq) in 100 μL CDCl3 was
added. After 1 h, 200 μL 3 (200 eq) was added. After 24 h, AROMP product was not observed in the 1H
NMR spectrum and 50 μL ethyl vinyl ether was added and the reaction was stirred for 30 min. The sol-
vent was evaporated and characterized in CDCl3 by NMR spectroscopy, and no polymer was obtained.
AROMP of bicyclo[4.2.0]oct-1(8)-ene-8-carboxaldehyde 10. Aldehyde 10 (68.0 mg, 0.5 mmol, 50 eq)
was dissolved in 400 μL CDCl3. Subsequently, a solution of catalyst 2 (8.9 mg, 0.01 mmol, 1 eq) in 100
μL CDCl3 was added to the NMR tube. After 1 h, the Ru alkylidene resonance at 19.1 ppm disappeared
and 200 μL 3 (200 eq) was added. AROMP product poly(10-alt-3)50 was the sole product observed in
1
the H NMR spectrum after 1 h. 50 μL ethyl vinyl ether was added and the reaction was stirred for 30
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min. Repeated attempts to isolate the aldehyde polymer were unsuccessful. Crude material showed
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regions of interest via 1H NMR (700 MHz, CDCl3): δ 9.29 (s, 1H), 6.41 (s, 1 H), 5.01 (s, 1H).
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ACKNOWLEDGMENT
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We acknowledge funding from NSF CHE1609494 and NIH-NIGMS GM097971. We thank Guofang Li
for help in initiating these experiments.
SUPPORTING INFORMATION
Supplemental figures and spectra of compounds synthesized. The Supporting Information is available
free of charge on the ACS Publications website.
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