Expanding the scope of the tail-to-tail dimerization of vinyl compounds catalyzed by N-heterocyclic carbene

Article abstract of DOI:10.1246/bcsj.20150048

The tail-to-tail dimerization of vinyl compounds catalyzed by an N-heterocyclic carbene was found to show a very broad substrate scope and tolerance to various functional groups. The optimization of the dimerizations of 2-vinylpyridine and n-butyl acrylate, as low and high electrophilicity model substrates, indicates that high reaction temperatures around 150 °C are required for both substrates. In addition to methacrylates and methacrylonitrile, the applicable substrates range from an activated styrene and vinyl pyridines to highly reactive acrylonitrile, dimethyl acrylamide, and various functionalized acrylates. The alcohol additives significantly increase the catalytic turnover number to 18 for the dimerization of acrylates. Deuterium labeling experiments indicate that the alcohols promote the intermolecular proton transfers.

Full text of DOI:10.1246/bcsj.20150048

Expanding the Scope of the Tail-to-Tail Dimerization of Vinyl
Compounds Catalyzed by N-Heterocyclic Carbene
Shin-ichi Matsuoka,* Masanori Nakazawa, and Masato Suzuki
Department of Materials Science and Engineering, Graduate School of Engineering, Nagoya Institute of Technology,
Gokiso-cho, Showa-ku, Nagoya, Aichi 466-8555
E-mail: matsuoka.shinichi@nitech.ac.jp
Received: February 9, 2015; Accepted: April 17, 2015; Web Released: April 23, 2015
The tail-to-tail dimerization of vinyl compounds catalyzed by an N-heterocyclic carbene was found to show a very
broad substrate scope and tolerance to various functional groups. The optimization of the dimerizations of 2-vinylpyridine
and n-butyl acrylate, as low and high electrophilicity model substrates, indicates that high reaction temperatures around
150 °C are required for both substrates. In addition to methacrylates and methacrylonitrile, the applicable substrates range
from an activated styrene and vinyl pyridines to highly reactive acrylonitrile, dimethyl acrylamide, and various func-
tionalized acrylates. The alcohol additives significantly increase the catalytic turnover number to 18 for the dimerization
of acrylates. Deuterium labeling experiments indicate that the alcohols promote the intermolecular proton transfers.
The tail-to-tail dimerization of functionalized olefins is an
attractive procedure for the synthesis of bifunctional com-
pounds. A variety of metal-based complexes has catalyzed the
dimerization of acrylonitrile,1 acrolein,2 acrylates,3-6 acryl-
amides,7 methacrylates,8 and styrenes.9 Among them, particular
attention has been paid to the dimerizations of acrylates and
acrylonitrile, because these are promising synthetic routes for
adipic acid and hexamethylenediamine. Although such metal
catalysis has been investigated for a few decades, the increas-
ing of activity and selectivity, and expanding of the substrate
scope still need to be addressed. Among the acrylate deriva-
tives, for example, the substrate scope has been limited to
methyl and ethyl acrylates. In this context, we and others have
been exploring an alternative organocatalytic procedure.
Organocatalysis using N-heterocyclic carbenes10 (NHCs)
have received considerable attention for more than a decade
mainly because they promote the umpolung of aldehydes
leading to the access of various carbonyl compounds. A variety
of transformations of Michael acceptors by NHCs have also
been recently studied.11-29 In particular, the umpolung of them
has also become possible,11-25 potentially allowing a new bond
forming procedure between the Michael acceptors and electro-
philes. The most fundamental intermolecular reaction based on
this concept is the tail-to-tail dimerization,14,15,18,19,21,22 which
is analogous to the benzoin condensation. We14 and Glorius
et al.15 independently developed the dimerization of meth-
acrylates catalyzed by TPT, a 1,2,4-triazol-5-ylidene, at 80 °C.
Subsequently, mechanistic insights were revealed by exper-
imental18 and computational19 studies, in which the rate-
limiting steps involve the C-C bond-forming step between
the substrates as well as the catalyst elimination process.18 The
dimerization of methacrylonitrile (MAN) has also been realized
by the cooperative NHC/Brønsted acid system.21 The Michael
addition to MAN, a higher electrophilic substrate than meth-
acrylates, generally proceeds more readily than that to meth-
acrylates, but the optimal reaction temperature of the dimeri-
zation is as high as 100 °C. These previous studies suggest that
high temperatures would be required to allow the catalyst
elimination to proceed, irrespective of the electrophilicity of
the substrates. Very recently, the dimerizations of low electro-
philic substrates, such as activated styrenes and vinyl pyridines,
at 140 °C were reported.22 In addition, the umpolung reaction
has been applied to the polyaddition of dimethacrylates for the
synthesis of unsaturated polyesters.25 However, the scope is
still limited to these substrates. Indeed, there is no report on the
NHC-catalyzed dimerizations of highly reactive and represen-
tative Michael acceptors, such as acrylates, acrylamides and
acrylonitrile.
We previously found that the imidazol-2-ylidene NHCs, such
as IMes and IDipp, catalyzed the unprecedented cyclotetra-
merization of acrylates to produce trisubstituted cyclopente-
nones through the umpolung reaction,20 while TPT showed no
catalytic activity, indicating the difference in the catalytic
behavior between these two types of NHCs. In addition, we
recently reported the oxa-Michael addition polymerization of
alcohol functionalized acrylates,26g in which the NHCs were
found to act as nucleophiles even in the presence of alcohols.
These previous results allowed us to envision that use of
the TPT catalyst or TPT/alcohol cooperative systems at high
temperatures may lead to the dimerization of a wide variety
of Michael acceptors including acrylates. In this study, we
focus on expanding the substrate scope of the NHC-catalyzed
dimerization of vinyl compounds.
Results and Discussion
We had been performing the dimerization of vinylpyridines
and an activated styrene before the appearance of a report by
Glorius et al.,22 which deals with the dimerizations of these
substrates by triazolium salts with bases. In this paper, we
initially disclose the results of the dimerizations under our
Bull. Chem. Soc. Jpn. 2015, 88, 1093–1099 | doi:10.1246/bcsj.20150048
© 2015 The Chemical Society of Japan | 1093

original conditions in the bulk under microwave irradiation
using TPT or TPT-MeOH, the latter of which is converted to
TPT in situ by heating. The attempted dimerization of 2-
vinylpyridine (2-VP) by TPT-MeOH at 100 °C in the bulk was
unsuccessful (Table 1, Entry 1), but increasing the reaction
temperature to 150 °C using either TPT or TPT-MeOH resulted
in the formation of the dimer in high yields (Entries 2 and 3).
The dimerization is very rapid and complete within 10 min
(Entry 4). Even when the catalyst loading was decreased to
5 and 2 mol %, the yields remained moderate with a turnover
number (TON) of 6-7 (Entries 5 and 6). Under the high
temperature conditions at 150 °C, 4-vinylpyridine (4-VP) and
the ester functionalized styrene (CO2Me-St), a low electrophilic
substrate, also underwent the dimerization (Entries 8 and 9),
while 4-chlorostyrene (Cl-St) and styrene (St) did not (Entries
10 and 11). These results suggest the limitation for the NHC-
catalyzed dimerization of low electrophilic substrates.
for the TPT-catalyzed polyaddition of the dimethacrylate
increased the monomer conversion and the polymer molecular
weight.25 We then examined the dimerization of n-BuA in the
presence or absence of two equivalents (relative to the sub-
strate) of n-BuOH with the low catalyst loading of 2 mol %. As
expected, the addition of n-BuOH increased the yield from 9 to
46% (Entries 28 and 29). This positive effect of alcohol on the
dimerization is observed for MA, i-BuA, and t-BuA (Entries
31, 32, 34, 35, 37, and 38), but not for 2VP, DMAA, and AN
(Entries 6, 7, 46, 47, 52 and 53). The dimer of t-BuA was
obtained with high diastereoselectivity (trans/cis = 98:2) due
to the bulky t-butyl groups. The TON value of the dimerization
reached 18 (Entry 38), which is, at present, highest for the
NHC-catalyzed umpolung reactions of Michael acceptors. The
dimerization of n-BuA in the presence of CD3OD produced
the dimer with the deuterium incorporation at C-2, 3, and 5
positions, accompanied by the transesterification (Scheme 1),
indicating that the alcohol additives are effective promoters for
the intermolecular proton transfers.
Figure 1 shows the proposed catalytic cycle of the dimeri-
zation of acrylates. The key deoxy-Breslow intermediate30 II is
generated from the reaction of TPT with the substrate followed
by proton transfer, in which the electrophilic β-carbon of the
acrylate is converted to the nucleophilic site. This process is
in contrast to our previous report on the cyclotetramerization
of acrylates catalyzed by IMes, in which the zwitterionic
intermediate generated from IMes and the acrylate undergoes
further Michael addition to the acrylate followed by the proton
transfer to form the dimeric deoxy-Breslow intermediate. When
the H/D exchange in three proton transfer processes (I ¼ II,
III ¼ IV, and IV ¼ V) takes place, the deuteriums are
incorporated at the C-2, 3, and 5 positions of the dimer. This
is in good agreement with the result of the dimerization in the
presence of CD3OD (Scheme 1). We previously reported that
the rate-limiting steps in the dimerization of methyl methacry-
late (MMA) at 80 °C are both the Michael addition of the
deoxy-Breslow intermediate to MMA and final catalyst elimi-
nation. It is reasonable to assume that for the dimerization of
acrylates at higher temperatures both TPT and II smoothly react
with acrylates. Indeed, the crude mixtures from the reactions at
80 °C (Entry 12) and for 1 min (Entry 26) showed the ESI-MS
peak at m/z = 554 corresponding to III, IV or V, while the
peaks for the intermediates I and II were not detected. We thus
propose that the rate-limiting step is the second half of the
catalytic cycle (III ¼ TPT). In addition, it is reasonable that,
similar to the dimerization of methacrylonitrile, the alcohol
additives would effectively promote the intermolecular proton
transfer in these rate-limiting steps.
We then examined the dimerization of n-butyl acrylate
(n-BuA) as the highly electrophilic model substrate. The di-
merization by the TPT catalyst was initially attempted at 80 °C
in a 1,4-dioxane (1,4-DOX) solution (Entry 12), which are
suitable conditions for the dimerization of methacrylates, but
the corresponding dimer was not obtained. To our delight,
increasing the reaction temperature to 100, 120, 140, and
160 °C produced the dimer in low to good yields, with the best
yield obtained at 140 °C (Entries 13-17). The key to success is
to use relatively harsh conditions even for this highly electro-
philic substrate. The dimerizations in toluene, DMF and THF
solvents similarly proceeded (Entries 18-20), suggesting that
there are no significant solvent effects, while the bulk condition
lowered the yield due to the formation of other oligomers, such
as trimers (Entry 21). The dimerization in 1,4-dioxane using
t
another NHC precursor, IMesHCl, with bases, such as BuOK,
DBU, and Cs2CO3, gave the product in less than 10% yield
(Entries 22-24). With optimal conditions in hand, the di-
merizations of various acrylates were evaluated. The dimeriza-
tions of the acrylates bearing bulky substituents, such as t-
butyl, i-butyl, and tetrahydrodicyclopentadienyl, gave the
products in moderate isolated yields (Entries 33, 36, and 39).
The ether and trialkylamine-functionalized substrates, MEA,
THFA, and DMAEA, were also tolerant under these harsh con-
ditions to give the dimers, albeit in low isolated yields (Entries
40-42). Dimethylacrylamide (DMAA), a lower electrophilicity
substrate, also underwent the dimerization to give the dimer
in 78% yield (Entry 45). For all of these dimers, the trans-
isomers were predominantly formed. A highly reactive sub-
strate, acrylonitrile (AN), was found to be a difficult substrate
for the dimerization, but could be converted to the product in
low yields (Entries 48-53). In this case, the formation of the
cis-isomer was favored.
Conclusion
The dimerization of n-BuA was studied in more detail. The
reaction by TPT-MeOH was more rapid than TPT; the former
produced the dimer in 26% and 67% yields for 1 and 10 min,
respectively (Entries 25 and 26), while the latter took 10 min
for a 23% yield (Entry 27). This difference suggests that the
methanol generated from TPT-MeOH would accelerate the
dimerization. Indeed, we have previously reported that the
additive alcohol is effective for the dimerization of methacry-
lonitrile.21 Chen et al. also reported that phenol additives used
The dimerization catalyzed by TPT at the high temperatures
of 120-150 °C showed an exceptionally broad substrate scope
including a low electrophilicity styrene derivative, highly reac-
tive acrylonitrile and eight types of acrylates. Various func-
tional groups, such as bulky alkyl, ester, ether, amino, dialkyl
amide, cyano, and pyridyl groups, are tolerant. In general, the
electrophilicity of vinyl compounds can be estimated by the
13C NMR chemical shift of their β-carbons. The values of the
Michael acceptors applicable for the dimerization are found to
1094 | Bull. Chem. Soc. Jpn. 2015, 88, 1093–1099 | doi:10.1246/bcsj.20150048
© 2015 The Chemical Society of Japan

Table 1. Tail-to-Tail Dimerization of Vinyl Compounds Catalyzed by NHCa)
Ph
Ph
Mes
N
N
N
N
Cl
N
OMe
or
or
N
N
N
Ph
Ph
Ph
TPT-MeOH
Mes
Ph
TPT
IMesHCl
EWG
EWG
EWG
N
CO2i-Bu
i-BuA
CO2t-Bu
t-BuA
CO2Me
CO2n-Bu
n-BuA
N
Cl
Cl-St
CO2Me
2-VP
4-VP
CO2Me-St
St
MA
O
NMe2
OMe
O
O
O
O
O
CN
O
O
O
CONMe2
MEA
THFA
DMAEA
DMAA
AN
DCPA
Tempb)
/°C
Time
/h
Cat
Yield/%
Entry Substrate
Additive
Solvent
TONc) trans/cisd)
Type
mol %
Isolated NMR
1
2
3
4
5
6
7
8
9
2-VP
2-VP
2-VP
2-VP
2-VP
2-VP
2-VP
4-VP
TPT-MeOH
TPT-MeOH
TPT
TPT-MeOH
TPT-MeOH
TPT-MeOH
TPT-MeOH
TPT-MeOH
10
10
10
10
5
2
2
10
10
10
10
®
®
100
150
150
150
150
150
150
150
150
150
150
®
®
®
®
®
®
®
®
®
®
®
2
2
2
trace
81
72
®
®
4.1
3.6
3.8
6.4
6.8
5.5
2.5
0.7
®
>99/1
>99/1
>99/1
>99/1
>99/1
>99/1
>99/1
>99/1
®
®
®
10 min
76
®
®
2
2
2
2
2
2
2
49
64
27
22
n-BuOH
®
®
50
14
CO2Me-St TPT-MeOH
Cl-St
St
10
11
TPT-MeOH
TPT-MeOH
®
®
0
0
®
®
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
n-BuA
n-BuA
n-BuA
n-BuA
n-BuA
n-BuA
n-BuA
n-BuA
n-BuA
n-BuA
n-BuA
n-BuA
n-BuA
n-BuA
n-BuA
n-BuA
n-BuA
n-BuA
TPT
TPT-MeOH
TPT
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
2
®
®
80
100
120
120
140
160
140
140
140
140
140
140
140
140
140
140
140
140
1,4-DOX
1,4-DOX
1,4-DOX
1,4-DOX
1,4-DOX
1,4-DOX
toluene
DMF
2
2
2
2
2
2
2
2
2
2
2
2
2
0
21
66
61
69
46
58
58
61
15
9
trace
trace
67
26
23
9
®
1.1
3.3
3.1
3.5
2.3
2.9
2.9
3.1
0.8
0.5
®
®
88/12
88/12
94/6
87/13
93/7
90/10
96/4
90/10
90/10
86/14
®
®
®
TPT-MeOH
TPT-MeOH
TPT-MeOH
TPT-MeOH
TPT-MeOH
TPT-MeOH
TPT-MeOH
IMesHCl
®
®
®
®
®
®
THF
®
t-BuOK
DBU
Cs2CO3
®
1,4-DOX
1,4-DOX
1,4-DOX
1,4-DOX 10 min
1,4-DOX 1 min
1,4-DOX 10 min
IMesHCl
IMesHCl
®
®
TPT-MeOH
TPT-MeOH
TPT
TPT-MeOH
TPT-MeOH
3.4
1.3
1.2
2.3
11.5
93/7
92/8
81/19
97/3
93/7
®
®
®
n-BuOH
1,4-DOX
1,4-DOX
2
2
2
46
30
31
32
33
MA
MA
MA
i-BuA
TPT-MeOH
TPT-MeOH
TPT-MeOH
TPT-MeOH
10
2
2
®
®
140
140
140
140
1,4-DOX
1,4-DOX
1,4-DOX
1,4-DOX
2
2
2
2
41
14
24
55
2.1
3.5
6.0
2.8
86/14
97/3
98/2
MeOH
®
10
89/11
Continued on next page:
Bull. Chem. Soc. Jpn. 2015, 88, 1093–1099 | doi:10.1246/bcsj.20150048
© 2015 The Chemical Society of Japan | 1095

Continued:
Tempb)
/°C
Time
/h
Cat
Yield/%
Entry Substrate
Additive
Solvent
TONc) trans/cisd)
Type
mol %
Isolated NMR
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
i-BuA
i-BuA
t-BuA
t-BuA
t-BuA
DCPA
MEA
THFA
DMAEA
DMAA
DMAA
DMAA
DMAA
DMAA
AN
TPT-MeOH
TPT-MeOH
TPT-MeOH
TPT-MeOH
TPT-MeOH
TPT-MeOH
TPT-MeOH
TPT-MeOH
TPT-MeOH
TPT-MeOH
TPT-MeOH
TPT-MeOH
TPT-MeOH
TPT-MeOH
TPT-MeOH
TPT-MeOH
TPT
2
2
10
2
®
i-BuOH
140
140
140
140
140
140
140
140
140
100
120
140
140
140
100
120
140
160
140
140
1,4-DOX
1,4-DOX
1,4-DOX
1,4-DOX
1,4-DOX
1,4-DOX
1,4-DOX
1,4-DOX
1,4-DOX
1,4-DOX
1,4-DOX
1,4-DOX
1,4-DOX
1,4-DOX
1,4-DOX
1,4-DOX
1,4-DOX
1,4-DOX
1,4-DOX
1,4-DOX
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
10
65
63
28
72
36
7
22
21
2.5
16.3
3.2
7.0
18.0
1.8
2.9
1.1
1.1
®
92/8
97/3
95/5
98/2
98/2
93/7
99/1
98/2
87/13
®
®
®
2
t-BuOH
®
®
10
10
10
10
10
10
10
2
57
®
®
®
®
trace
69
3.5
3.9
4.3
5.3
0.3
0.4
0.4
0.7
0.2
0.2
92/8
95/5
91/9
95/5
32/68
18/82
23/77
18/82
23/77
30/70
®
®
78
17
21
2
n-BuOH
®
®
10
10
10
10
10
10
5
8
7
14
3
3
AN
AN
AN
AN
®
®
TPT-MeOH
TPT-MeOH
TPT-MeOH
®
n-BuOH
AN
a) Reaction conditions: TPT-MeOH (0.30 or 0.060 mmol), substrate (3.0 mmol), alcohol additive (6.0 mmol), base additive
(0.33 mmol), solvent (1.2 mL). b) Under microwave irradiation. c) TONs of Entries 5 and 40 were calculated by the NMR yields.
1
d) Estimated by GC for the dimer of DMAA or by H NMR for the other dimers.
(D) (D)
D(73)
D(2) D(2)
TPT-MeOH (2 mol%)
CD3OD (2.0 equiv)
Ph
CO2R
n-BuO2C
(CD3)
(11)
RO2C
N
CO2n-Bu
(CD3(11))
N
140 °C,
CO2n-Bu
(D)
D
D
D(75)
1,4-DOX, 2h
CO2R
N
(22) (22)
N
Ph
18%
Ph
Ph
N
TPT
(D)
N
Scheme 1. The dimerization of n-BuA in the presence of
CD3OD. Values in parentheses indicate the percentage of
deuterium incorporation.
Ph
Ph
N
OR
N
Ph
OR
(D)
Ph
N
O
(D)
Ph
O
V
I
CO2R
range from 116 (CO2Me-St) to 138 (AN) ppm. It is noteworthy
that the NHC-catalyzed dimerization may potentially be pos-
sible for substrates meeting these wide requirements. For the
dimerizations of acrylates, the catalytic turnover increases
many-fold by the addition of alcohols, due to the assistance of
the intermolecular proton transfers. Compared to various metal-
catalyzed systems, this organocatalysis is the most general
procedure to synthesize the tail-to-tail dimers.
proton transfer
proton transfer
(CD3OD)
(CD3OD)
Ph
Ph
N
(D)
N
N
(D)
N
Ph
Ph
N
CO2R
N
CO2R
Ph
Ph
Ph
II
N
N
(D)
(D)
N
Ph
CO2R
CO2R
IV
Experimental
Ph
proton transfer
CO2R
General Methods. 1,4-DOX, DMF, n-BuOH, i-BuOH, and
t-BuOH were dried and distilled from CaH2 prior to use, and
MeOH was dried and distilled from Mg prior to use. Dry THF
and toluene were purchased and used as received. 2-VP, 4-VP,
Cl-St, St, n-BuA, MA, i-BuA, t-BuA, MEA, THFA, DMAEA,
DMAA, and AN were distilled from CaH2 prior to use, while
DCPA (Tokyo Chem. Industry Co., Ltd., >95% total of iso-
mers) was used as received. CO2Me-St was prepared according
the previous report.31 Characterization data of the dimers of
2-VP, 4-VP, and CO2Me-St were previously reported.22 The
dimer of 2-VP was purified by silica gel column chromatog-
raphy using acetone/triethylamine (>99:<1, Rf = 0.58) as the
eluent. The dimers of 4-VP and CO2Me-St were purified by
(CD3OD)
III
O
OR
Figure 1. The proposed mechanism of the dimerization of
acrylates.
recrystallization from hexane/ethanol and hexane/methanol,
respectively. Column chromatography was performed using
neutral silica gel (63-210 ¯m). NMR spectra were recorded at
1
1
400 MHz for H (100 MHz for 13C) at 25 °C in CDCl3. H and
13C NMR chemical shifts were reported using tetramethylsilane
(0.0 ppm) and CDCl3 (77.1 ppm) as the internal standards,
respectively. The assignment of NMR signals was confirmed
by 2D NMR (COSY and HMQC) and DEPT135 experiments.
1096 | Bull. Chem. Soc. Jpn. 2015, 88, 1093–1099 | doi:10.1246/bcsj.20150048
© 2015 The Chemical Society of Japan

Electrospray ionization or electron impact mass spectrometries
equipped with time-of-flight instruments were used as high-
resolution mass spectrometry. The dimers were analyzed by a
GC instrument equipped with a flame ionization detector and
a fused silica capillary column (30 m © 0.25 mm i.d. © 0.25
¯m film thickness). The cis/trans ratios of the dimers were
The Dimer of DCPA.
Purified by silica gel column
chromatography using hexane/ethyl acetate (2:1, Rf = 0.53)
as the eluent and obtained as a pale yellow liquid (Entry 39,
207 mg, 36%). 1H NMR (400 MHz): ¤ 6.90 (dt, J = 15.7,
6.4 Hz, 1H), 6.20 (Z-isomer, dt, J = 11.5, 7.3 Hz), 5.81 (d, J =
15.7 Hz, 1H), 4.59 (m, 2H), 2.45 (m, 4H), 2.03 (m, 4H), 1.91-
1.60 (m, 12H), 1.50-1.15 (m, 8H), 0.94 (m, 4H). 13C NMR
(100 MHz): ¤ 172.2, 166.2, 146.3, 122.7, 77.5, 77.0, 47.32,
47.28, 46.19, 46.16, 43.03, 42.98, 39.62, 39.60, 39.11, 39.05,
32.9, 32.05, 32.04, 31.70, 31.68, 29.44, 29.42, 27.8, 27.4.
HRMS-ESI (m/z): calcd for C26H36O4Na [M + Na]+ 435.2511,
1
analyzed by both H NMR and GC. The dimerizations were
performed under microwave irradiation using a Biotage Initi-
ator 2.5 instrument. The reaction temperatures were measured
by a surface sensor.
General Procedure for the Dimerization. To a 0.5-2 mL
microwave vial were added TPT-MeOH (100 mg, 0.30 mmol),
n-BuA (0.43 mL, 3.0 mmol), and 1,4-dioxane (1.2 mL), and
then the vial was sealed. The mixture was stirred and heated at
140 °C under microwave irradiation for 2 h. The Kugelrohr
distillation under reduced pressure (1 mmHg, 200 °C) gave
the product (Entry 16, 259 mg, 69% yield) as a transparent
liquid.
(E)-Dibutyl Hex-2-enedioate (the Dimer of n-BuA).
1H NMR (400 MHz): ¤ 6.95 (dt, J = 15.7, 6.4 Hz, 1H), 6.24
(Z-isomer, dt, J = 11.5, 7.5 Hz), 5.86 (dt, J = 15.7, 1.6 Hz, 1H),
4.13 (t, J = 6.6 Hz, 2H), 4.09 (t, J = 6.6 Hz, 2H), 2.49 (m, 4H),
1.62 (m, 4H), 1.39 (m, 4H), 0.93 (m, 6H). 13C NMR (100
MHz): ¤ 172.2, 166.3, 146.5, 122.1, 64.4, 64.1, 32.4, 30.63,
30.55, 27.2, 19.1, 19.0, 13.6, 13.6. HRMS-ESI (m/z): calcd for
C14H24O4Na [M + Na]+ 279.1572, found 279.1573. IR (NaCl):
found 435.2519. IR (NaCl): 2951, 2863, 1720, 1655, 1261,
1186, 1157, 1042, 1021, 982, 909, 733 cm
¹1
.
(E)-Bis(2-methoxyethyl) Hex-2-enedioate (the Dimer of
MEA). Purified by silica gel column chromatography using
hexane/ethyl acetate (1:2, Rf = 0.55) as the eluent followed
by Kugelrohr distillation under reduced pressure (0.5 mmHg,
210 °C) and obtained as a transparent liquid (Entry 40, 36 mg,
10%). 1H NMR (400 MHz): ¤ 6.98 (m, 1H), 6.28 (Z-isomer, dt,
J = 11.5, 7.3 Hz), 5.91 (d, J = 15.9 Hz, 1H), 4.26 (m, 4H), 3.61
(m, 4H), 3.39 (m, 6H), 2.53 (m, 4H). 13C NMR (100 MHz):
¤ 172.3, 166.4, 147.2, 122.0, 70.6, 70.5, 63.8, 63.5, 59.08,
59.06, 32.3, 27.3. HRMS-EI (m/z): calcd for C12H20O6 [M]+
260.1260, found 260.1297. IR (NaCl): 2930, 2892, 2822, 1735,
1655, 1263, 1179, 1130, 1038, 917, 732 cm
¹1
.
(E)-Bis[(tetrahydrofuran-2-yl)methyl] Hex-2-enedioate
(the Dimer of THFA). Purified by silica gel column chro-
matography using hexane/ethyl acetate (1:5, Rf = 0.63) as the
eluent and obtained as a pale yellow liquid (Entry 41, 101 mg,
2960, 2935, 2874, 1735, 1655, 1465, 1261, 1177, 1065, 1025,
¹1
976 cm
.
(E)-Dimethyl Hex-2-enedioate (the Dimer of MA).
Purified by the Kugelrohr distillation under reduced pressure
(1 mmHg, 145 °C) and obtained as a transparent liquid
1
22%). H NMR (400 MHz): ¤ 6.98 (dt, J = 15.7, 6.1 Hz, 1H),
5.90 (d, 15.7 Hz, 1H), 4.23-3.99 (m, 6H), 3.92-3.86 (m, 2H),
3.80 (m, 2H), 2.53 (m, 4H), 2.01 (m, 2H), 1.92 (m, 4H), 1.61
(m, 2H). 13C NMR (100 MHz): ¤ 172.1, 166.2, 147.1, 121.9,
76.5, 76.4, 68.4, 66.6, 66.4, 32.2, 28.0, 27.9, 27.2, 25.61,
25.59. HRMS-ESI (m/z): calcd for C16H24O6Na [M + Na]+
1
(Entry 32, 60 mg, 24%). H NMR (400 MHz): ¤ 6.95 (dt, J =
15.8, 6.4 Hz, 1H), 6.26 (Z-isomer, dt, J = 11.5, 7.3 Hz), 5.87
(dt, J = 15.8, 1.5 Hz, 1H), 3.73 (s, 3H), 3.69 (s, 3H), 2.51 (m,
4H). 13C NMR (100 MHz): ¤ 172.7, 166.8, 146.9, 121.9, 51.8,
51.6, 32.3, 27.3. HRMS-ESI (m/z): calcd for C8H12O4Na
335.1471, found 335.1471. IR (NaCl): 2952, 2874, 1733, 1655,
1448, 1363, 1264, 1175, 1085, 1025, 992 cm .
[M + Na]+ 195.0633, found 195.0634. IR (NaCl): 3001, 2954,
¹1
¹1
1725, 1660, 1437, 1273, 1200, 1173, 977, 858 cm
.
(E)-Bis[2-(dimethylamino)ethyl] Hex-2-enedioate (the Di-
mer of DMAEA). Purified by Kugelrohr distillation under
reduced pressure (0.5 mmHg, 220 °C) and obtained as a trans-
parent liquid (Entry 42, 92 mg, 21%). 1H NMR (400 MHz):
¤ 6.96 (m, 1H), 6.26 (Z-isomer, m), 5.89 (d, J = 15.9 Hz,
1H), 4.20 (m, 4H), 2.55 (m, 8H), 2.28 (m, 12H). 13C NMR
(100 MHz): ¤ 172.4, 166.4, 147.0, 122.0, 62.4, 62.2, 57.9,
57.8, 45.74, 45.72, 32.4, 27.2. HRMS-ESI (m/z): calcd
for C14H27N2O4 [M + H]+ 287.1971, found 287.1980. IR
(E)-Diisobutyl Hex-2-enedioate (the Dimer of i-BuA).
Purified by Kugelrohr distillation under reduced pressure
(1 mmHg, 200 °C) and obtained as a transparent liquid
(Entry 35, 241 mg, 65%). 1H NMR (400 MHz): ¤ 6.95 (m,
1H), 6.24 (Z-isomer, m), 5.87 (m, 1H), 3.88 (m, 4H), 2.50 (m,
4H), 1.93 (m, 2H), 0.92 (m, 12H). 13C NMR (100 MHz): ¤
172.3, 166.4, 146.6, 122.3, 70.8, 70.5, 32.5, 27.8, 27.7, 27.3,
19.1. HRMS-ESI (m/z): calcd for C14H24O4Na [M + Na]+
279.1572, found 279.1575. IR (NaCl): 2963, 2875, 1735, 1656,
(NaCl): 2951, 2827, 2779, 1720, 1655, 1458, 1269, 1175,
1032 cm .
¹1
¹1
1470, 1378, 1261, 1174, 1023, 733 cm
.
(E)-Di-tert-butyl Hex-2-enedioate (the Dimer of t-BuA).
Purified by Kugelrohr distillation under reduced pressure
(2 mmHg, 180 °C) and obtained as white solid with mp 27-
(E)-N,N,N¤,N¤-Tetramethylhex-2-enediamide (the Dimer
of DMAA). Purified by silica gel column chromatography
using acetone (Rf = 0.30) as the eluent and obtained as a pale
1
1
30 °C (Entry 38, 286 mg, 72%). H NMR (400 MHz): ¤ 6.83
yellow solid. mp 38-41 °C (Entry 45, 240 mg, 78%). H NMR
(td, J = 15.6, 6.3 Hz, 1H), 6.13 (Z-isomer, td, J = 11.5, 7.5 Hz),
5.77 (td, J = 15.6, 1.8 Hz, 1H), 2.46 (m, 2H), 2.57 (m, 2H),
1.47 (s, 9H), 1.45 (s, 9H). 13C NMR (100 MHz): ¤ 171.6,
165.7, 145.6, 123.7, 80.5, 80.0, 33.7, 28.1, 28.0, 27.3. HRMS-
ESI (m/z): calcd for C14H24O4Na [M + Na]+ 279.1572, found
(400 MHz): ¤ 6.83 (m, 1H), 6.33 (d, J = 15.2 Hz, 1H), 3.07
(s, 3H), 3.01 (m, 3H), 2.99 (m, 3H), 2.95 (m, 3H), 2.55 (m,
2H), 2.46 (t, J = 6.9 Hz, 2H). 13C NMR (100 MHz): ¤ 171.4,
166.5, 144.2, 121.2, 37.2, 37.0, 35.5, 35.3, 31.9, 27.8. HRMS-
ESI (m/z): calcd for C10H18N2O2Na [M + Na]+ 221.1266,
279.1578. IR (NaCl): 2978, 2933, 1716, 1654, 1456, 1368,
found 221.1273. IR (NaCl): 2933, 1638, 1498, 1399, 1261,
1144, 1082, 981, 849 cm .
¹1
¹1
1291, 1257, 1149, 977, 849 cm
.
Bull. Chem. Soc. Jpn. 2015, 88, 1093–1099 | doi:10.1246/bcsj.20150048
© 2015 The Chemical Society of Japan | 1097

Chem. Lett. 2004, 33, 728.
Hex-2-enedinitrile (the Dimer of AN).
Purified by
8
a) G. Oehme, J. Prakt. Chem. 1984, 326, 779. b) G. Oehme,
Kugelrohr distillation under reduced pressure (2 mmHg,
150 °C) and obtained as a transparent liquid (Entry 51, 25
mg, 14%). 1H NMR (400 MHz): ¤ 6.69 (E-isomer, dt, J = 16.4,
6.6 Hz, 0.3H), 6.55 (Z-isomer, dt, J = 11.0, 7.3 Hz, 0.7H), 5.55
(d, J = 11.0 Hz, 1H), 2.78 (m, 2H), 2.57 (m, 2H). 13C NMR
(100 MHz): ¤ 149.9, 149.2, 103.4, 103.2, 28.8, 27.2, 16.4, 14.7.
HRMS-EI (m/z): calcd for C6H6N2 [M]+ 106.0531, found
I. Grassert, H. Mennenga, H. Baudisch, J. Mol. Catal. 1986, 37,
53. c) M. Hirano, Y. Hiroi, N. Komine, S. Komiya, Organo-
metallics 2010, 29, 3690.
9
a) W. P. Kretschmer, S. I. Troyanov, A. Meetsma, B.
Hessen, J. H. Teuben, Organometallics 1998, 17, 284. b) T.
Kondo, D. Takagi, H. Tsujita, Y. Ura, K. Wada, T. Mitsudo, Angew.
Chem., Int. Ed. 2007, 46, 5958. c) S. Shimura, H. Miura, S.
Tsukada, K. Wada, S. Hosokawa, M. Inoue, ChemCatChem 2012,
4, 2062.
106.0503. IR (NaCl): 3073, 2961, 2939, 2874, 1637, 1427,
¹1
1328, 1105, 964, 749 cm
.
10 NHC (TPT) developed by Enders, see: a) D. Enders, K.
Breuer, G. Raabe, J. Runsink, J. H. Teles, J.-P. Melder, K. Ebel,
S. Brode, Angew. Chem., Int. Ed. Engl. 1995, 34, 1021. b) D.
Enders, K. Breuer, J. Runsink, J. H. Teles, Liebigs Ann. 1996,
2019. c) D. Enders, K. Breuer, J. H. Teles, K. Ebel, J. Prakt.
Chem./Chem.-Ztg. 1997, 339, 397. d) D. Enders, K. Breuer, U.
Kallfass, T. Balensiefer, Synthesis 2003, 1292. e) J. H. Teles, J.-P.
Melder, K. Ebel, R. Schneider, E. Gehrer, W. Harder, S. Brode, D.
Enders, K. Breuer, G. Raabe, Helv. Chim. Acta 1996, 79, 61.
Nucleophilic reactivities of NHCs, see; f) B. Maji, M. Breugst, H.
Mayr, Angew. Chem., Int. Ed. 2011, 50, 6915.
This work was partially supported by Hibi Science
Foundation.
Supporting Information
1
2
Copies of H, 13C, and H NMR spectra. This material is
available free of charge on J-STAGE.
References
1
For selected examples of the dimerization of acrylonitrile,
see: a) K. Kashiwagi, R. Sugise, T. Shimakawa, T. Matuura, M.
Shirai, F. Kakiuchi, S. Murai, Organometallics 1997, 16, 2233.
b) A. Fukuoka, T. Nagano, S. Furuta, M. Yoshizawa, M. Hirano, S.
Komiya, Bull. Chem. Soc. Jpn. 1998, 71, 1409. c) K. Kashiwagi,
R. Sugise, T. Shimakawa, T. Matuura, M. Shirai, J. Mol. Catal. A:
Chem. 2007, 264, 9. d) K. Kashiwagi, R. Sugise, T. Shimakawa, T.
Matuura, M. Shirai, Chem. Lett. 2006, 35, 186. e) K. Kashiwagi,
R. Sugise, T. Shimakawa, T. Matuura, Chem. Lett. 2007, 36, 1384.
f) K. Kashiwagi, R. Sugise, T. Shimakawa, T. Matuura, M. Shirai,
J. Mol. Catal. A: Chem. 2008, 286, 120.
11 For reviews, see; a) X. Bugaut, F. Glorius, Chem. Soc. Rev.
2012, 41, 3511. b) S. J. Ryan, L. Candish, D. W. Lupton, Chem.
Soc. Rev. 2013, 42, 4906. c) X.-Y. Chen, S. Ye, Org. Biomol.
Chem. 2013, 11, 7991.
12 C. Fischer, S. W. Smith, D. A. Powell, G. C. Fu, J. Am.
Chem. Soc. 2006, 128, 1472.
13 L. Zhao, X. Y. Chen, S. Ye, Z.-X. Wang, J. Org. Chem.
2011, 76, 2733.
14 S. Matsuoka, Y. Ota, A. Washio, A. Katada, K. Ichioka, K.
Takagi, M. Suzuki, Org. Lett. 2011, 13, 3722.
2
Y. Ohgomori, S. Ichikawa, N. Sumitani, Organometallics
15 A. T. Biju, M. Padmanaban, N. E. Wurz, F. Glorius, Angew.
Chem., Int. Ed. 2011, 50, 8412.
1994, 13, 3758.
3
For selected examples of the Pd-catalyzed dimerization
16 R. L. Atienza, H. S. Roth, K. A. Scheidt, Chem. Sci. 2011,
2, 1772.
17 S. Matsuoka, Y. Tochigi, K. Takagi, M. Suzuki, Tetrahe-
dron 2012, 68, 9836.
18 T. Kato, Y. Ota, S. Matsuoka, K. Takagi, M. Suzuki, J. Org.
Chem. 2013, 78, 8739.
19 Y. Zhang, M. Schmitt, L. Falivene, L. Caporaso, L.
Cavallo, E. Y.-X. Chen, J. Am. Chem. Soc. 2013, 135, 17925.
20 S. Matsuoka, S. Namera, A. Washio, K. Takagi, M. Suzuki,
Org. Lett. 2013, 15, 5916.
of acrylates, see: a) I. Guibert, D. Neibecker, I. Tkatchenko,
J. Chem. Soc., Chem. Commun. 1989, 1850. b) G. M. DiRenzo,
P. S. White, M. Brookhart, J. Am. Chem. Soc. 1996, 118, 6225.
c) J. Zimmermann, P. Wasserscheid, I. Tkatchenko, S. Stutzmann,
Chem. Commun. 2002, 760. d) M. Aresta, A. Dibenedetto, E.
Amodio, I. Tommasi, Eur. J. Inorg. Chem. 2002, 2188. e) D.
Ballivet-Tkatchenko, M. Picquet, M. Solinas, G. Franciò, P.
Wasserscheid, W. Leitner, Green Chem. 2003, 5, 232. f) J.
Zimmermann, I. Tkatchenko, P. Wasserscheid, Adv. Synth. Catal.
2003, 345, 402.
21 T. Kato, S. Matsuoka, M. Suzuki, J. Org. Chem. 2014, 79,
4484.
4
For selected examples of the Rh-catalyzed dimerization of
acrylates, see: a) W. A. Nugent, R. J. McKinney, J. Mol. Catal.
1985, 29, 65. b) M. Brookhart, S. Sabo-Etienne, J. Am. Chem. Soc.
1991, 113, 2777. c) Y. Kaneko, T. Kanke, S. Kiyooka, K. Isobe,
Chem. Lett. 1997, 23.
22 M. Schedler, N. E. Wurz, C. G. Daniliuc, F. Glorius, Org.
Lett. 2014, 16, 3134.
23 W. N. Ottou, D. Bourichon, J. Vignolle, A.-L. Wirotius, F.
Robert, Y. Landais, J.-M. Sotiropoulos, K. Miqueu, D. Taton,
Chem.®Eur. J. 2014, 20, 3989.
5
For selected examples of the Ru-catalyzed dimerization of
acrylates, see: a) R. Sustmann, H. J. Hornung, T. Schupp, B.
Patzke, J. Mol. Catal. 1993, 85, 149. b) B. Patzke, R. Sustmann,
J. Organomet. Chem. 1994, 480, 65. c) P. Pertici, V. Ballantini,
P. Salvadori, M. A. Bennett, Organometallics 1995, 14, 2565.
d) M. Hirano, Y. Sakate, N. Komine, S. Komiya, M. A. Bennett,
Organometallics 2009, 28, 4902.
24 Tail-to-tail dimerization of vinylphosphonates by PMe3-
catalyzed umpolung, see; X.-B. Wang, Y. Saga, R. Shen, H. Fujino,
M. Goto, L.-B. Han, RSC Adv. 2012, 2, 5935.
25 M. Hong, E. Y.-X. Chen, Angew. Chem., Int. Ed. 2014, 53,
11900.
26 Michael additions catalyzed by NHCs, see, a) E. M.
Phillips, M. Riedrich, K. A. Scheidt, J. Am. Chem. Soc. 2010, 132,
13179. b) S. Matsuoka, S. Shimakawa, K. Takagi, M. Suzuki,
Tetrahedron Lett. 2011, 52, 6835. c) T. Boddaert, Y. Coquerel, J.
Rodriguez, Chem.®Eur. J. 2011, 17, 2266. d) Q. Kang, Y. Zhang,
Org. Biomol. Chem. 2011, 9, 6715. e) M. Hans, L. Delaude, J.
6
The reductive dimerization of acrylates, phenyl vinyl
sulfone, acrylonitrile, and N,N-diethyl acrylamide catalyzed by
Co complex, see: C.-C. Wang, P.-S. Lin, C.-H. Cheng, Tetrahedron
Lett. 2004, 45, 6203.
7
M. Higashimura, K. Imamura, Y. Yokogawa, T. Sakakibara,
1098 | Bull. Chem. Soc. Jpn. 2015, 88, 1093–1099 | doi:10.1246/bcsj.20150048
© 2015 The Chemical Society of Japan

Rodriguez, Y. Coquerel, J. Org. Chem. 2014, 79, 2758. f) L. He,
H. Guo, Y.-Z. Li, G.-F. Du, B. Dai, Chem. Commun. 2014, 50,
3719. g) S. Matsuoka, S. Namera, M. Suzuki, Polym. Chem. 2015,
6, 294.
Zhang, E. Y.-X. Chen, Angew. Chem., Int. Ed. 2012, 51, 2465.
c) Y. Zhang, G. M. Miyake, M. G. John, L. Falivene, L. Caporaso,
L. Cavallo, E. Y.-X. Chen, Dalton Trans. 2012, 41, 9119. d) J. He,
Y. Zhang, E. Y.-X. Chen, Synlett 2014, 25, 1534.
27 Morita-Baylis-Hillman type reactions catalyzed by NHCs,
see; a) L. He, T.-Y. Jian, S. Ye, J. Org. Chem. 2007, 72, 7466.
b) L. He, Y.-R. Zhang, X.-L. Huang, S. Ye, Synthesis 2008, 2825.
c) R. L. Atienza, K. A. Scheidt, Aust. J. Chem. 2011, 64, 1158.
d) X.-Y. Chen, F. Xia, S. Ye, Org. Biomol. Chem. 2013, 11, 5722.
e) P. Verma, P. Verma, R. B. Sunoj, Org. Biomol. Chem. 2014, 12,
2176.
28 Cyclizations by NHCs, see; a) A. E. Raveendran, R. R.
Paul, E. Suresh, V. Nair, Org. Biomol. Chem. 2010, 8, 901.
b) X.-Y. Chen, L.-H. Sun, S. Ye, Chem.®Eur. J. 2013, 19, 4441.
29 Polymerizations by NHCs, see; a) Y. Zhang, G. M. Miyake,
E. Y.-X. Chen, Angew. Chem., Int. Ed. 2010, 49, 10158. b) Y.
30 For the deoxy-Breslow intermediates formed from NHCs
and alkyl harides, see; a) C. E. I. Knappke, J. M. Neudörfl, A. J.
von Wangelin, Org. Biomol. Chem. 2010, 8, 1695. b) C. E. I.
Knappke, A. J. Arduengo, III, H. Jiao, J.-M. Neudörfl, A. J.
von Wangelin, Synthesis 2011, 3784. c) A. Berkessel, S. Elfert,
Adv. Synth. Catal. 2014, 356, 571. For their nucleophilic
reactivities, see; d) B. Maji, M. Horn, H. Mayr, Angew. Chem.,
Int. Ed. 2012, 51, 6231. e) H. Mayr, S. Lakhdar, B. Maji, A. R.
Ofial, Beilstein J. Org. Chem. 2012, 8, 1458.
31 M. Schedler, D.-S. Wang, F. Glorius, Angew. Chem., Int.
Ed. 2013, 52, 2585.
Bull. Chem. Soc. Jpn. 2015, 88, 1093–1099 | doi:10.1246/bcsj.20150048
© 2015 The Chemical Society of Japan | 1099