Cooperative N-heterocyclic carbene/Br?nsted acid catalysis for the tail-to-tail (co)dimerization of methacrylonitrile

Article abstract of DOI:10.1021/jo500514e

The first tail-to-tail dimerization of methacrylonitrile (MAN) has been realized by the cooperative use of N-heterocyclic carbene (NHC) and Br?nsted acid catalysts, producing 2,5-dimethylhex-2-enedinitrile with the E/Z ratio of 24:76. Although the NHC alo

Full text of DOI:10.1021/jo500514e

Article
pubs.acs.org/joc
Cooperative N‑Heterocyclic Carbene/Brønsted Acid Catalysis for the
Tail-to-Tail (Co)dimerization of Methacrylonitrile
Terumasa Kato, Shin-ichi Matsuoka,* 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, Japan
S
* Supporting Information
ABSTRACT: The first tail-to-tail dimerization of methacrylonitrile (MAN) has been realized by the cooperative use of N-
heterocyclic carbene (NHC) and Brønsted acid catalysts, producing 2,5-dimethylhex-2-enedinitrile with the E/Z ratio of 24:76.
Although the NHC alone was not effective for the catalysis, the addition of alcohols resulted in the significant increase of the
dimer yield up to 82% in the presence of 5 mol % NHC. Detailed experimental studies including the ESI-MS analysis of the
intermediates, stoichiometric (co)dimerizations, and deuterium-labeling experiments revealed the mechanistic aspects of the
proton transfer, isomerization, umpolung, and rate-limiting steps, allowing us to observe several mechanistic differences between
the dimerization of MAN and that of methyl methacrylate. The stoichiometric reactions in the presence and absence of an
alcohol suggest that the alcohol additives play a role in promoting the intermolecular proton transfers from the deoxy-Breslow
intermediate to the regenerated NHC in the second half of the catalytic cycle. In addition, the codimerizations of MAN with n-
butyl methacrylate (n-BuMA) have been studied. While the dimerization of n-BuMA was sluggish in the presence of an alcohol,
the catalytic activity for the codimerization was enhanced by the cooperative systems.
offer interesting opportunities for the discovery of new
reactions.11 Since the first report by Scheidt et al.,12 various
Lewis acids, Mg(OtBu)2,12 Ti(OiPr)4,13 Fe(OTf)2,14 Sc-
INTRODUCTION
■
Bifunctional compounds, such as dicarboxylic acids and
diamines, are important monomers for the synthesis of
condensation polymers. The catalytic tail-to-tail (co)-
dimerizations of functionalized olefins are attractive routes to
access a variety of such monomers and are mostly promoted by
transition metal-based systems.1 For example, the precursors of
adipic acid and hexamethylendiamine can be synthesized from
the dimerizations of methyl acrylate and acrylonitrile,
respectively, catalyzed by a variety of Pd,2 Rh,3 Ru,4,5 and other
metal6 complexes, followed by hydrogenation. In contrast, the
dimerizations of disubstituted olefins are generally difficult.
Indeed, there are only a few reports on the dimerization of
methyl methacrylate (MMA) catalyzed by Pd7 and Ru8 and, to
our surprise, no example of that of methacrylonitrile (MAN).
Because the polymers made from methyl-substituted monomers
exhibit distinct properties from the nonsubstituted variants in
terms of thermal stability, crystallinity, and solubility, the
dimerization of such disubstituted olefins is an important issue
that needs to be addressed.
15
(OTf)2 and LiCl,16 have been employed to improve the
reactivity of the Breslow intermediates and/or substrate. In
addition to Lewis acids, a few examples of the cooperative NHC
and Brønsted acid catalytic systems have been reported by Rovis
and Chi. They propose that Brønsted acids, such as catechols and
carboxylic acids, promote proton transfer to form the Breslow
intermediate,17 the dual activation of the intermediate and
electrophilic substrates,18 and the intermediate transformation
from homoenolates to enolates.19
Previously, we20 and Glorius21 independently developed the
tail-to-tail dimerization of methacrylates catalyzed by NHC. This
catalysis involves the umpolung of Michael acceptors through the
deoxy-Breslow intermediates.22 Recently, the reaction mecha-
nism has been investigated both experimentally and computa-
tionally by us23 and Chen,24 in which we have revealed the
reversibility, proton transfer mechanism, and rate-determining
steps. Since the first report of the intramolecular reaction by Fu in
2006,25 several other examples involving the umpolung reaction
of Michael acceptors, such as the tautomerization of vinyl
N-Heterocyclic carbenes (NHCs)9 have received a great deal
of scientific attention as organocatalysts for the umpolung
reactions of aldehydes via the Breslow intermediates.10 The
cooperative NHC and Lewis acid catalysis, involving dual-
activation using metal and organic catalysts, has been found to
Received: March 4, 2014
Published: April 28, 2014
© 2014 American Chemical Society
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sulfones,26 the stoichiometric three-component reaction,27 and
the cyclotetramerization of acrylates,28 have appeared. However,
the reaction scope is still not broad, and in particular, the
substrate scope of the dimerization is limited to methacrylates.
Glorius et al. previously attempted the dimerization of MAN
catalyzed by the NHC precursor with DBU at 80 °C in 1,4-
dioxane, but they documented that MAN was not suitable for the
umpolung, not providing the homodimer.21 However, on the
basis of this negative reactivity, they carried out the selective
codimerizations of MAN and n-butyl methacrylate (n-BuMA) to
give a mixture of isomers of codimers with a low E/Z selectivity
through the double bond migration. Because MAN shows a
electrophilic reactivity only slightly higher than that of
methacrylates, we envisioned that the detailed survey of the
reaction conditions may lead to the first dimerization of MAN.
We now report the cooperative NHC and alcohol catalytic
systems for the (co)dimerization of MAN and the detailed
experimental mechanistic studies.
a
Table 1. Tail-to-Tail Dimerization of MAN
RESULTS AND DISCUSSION
■
Tail-to-Tail Dimerization of MAN by Cooperative NHC
and Alcohol Catalysts. We previously reported that the tail-to-
tail dimerization of MMA at 80 °C in bulk or in solutions affords
the corresponding dimer with an E/Z ratio of 95:5 in 86% yield.
Under similar conditions, the initial experiments for the
dimerization of MAN were carried out in bulk or in 1,4-dioxane
for 2 h using 5 mol % NHC (A) or NHC precursors (B−M)
(Table 1) using a sealed vial under microwave irradiation to
increase the reaction temperature above the boiling point of
MAN. Although the dimerization catalyzed by the isolated
triazole NHC A did not proceed at 60 °C (entry 1), increasing
the temperature to 80 and 100 °C resulted in the formation of the
tail-to-tail MAN dimer 1 in 8% and 9% yields, respectively, with
very low conversions (entries 2−4). The combinations of other
NHC precursors C−M and DBU or K2CO3, generating NHCs in
situ, did not give 1 (entries 5 and 6). This catalytic specificity was
also observed in the dimerization of MMA. It is noteworthy that
the methanol adduct B, which is converted to NHC A and
methanol by heating, increased the yield of 1 to 18% and 26%
yields (entries 7 and 8). This finding prompted us to add alcohols
to the reaction system. Expectedly, similar improvements were
found in the dimerizations in the presence of an equimolar
amount of various alcohols for A. (entries 9−11 in Table 1, and
entry 6 in Table S1, Supporting Information). The use of 5 and
10 equiv of alcohols enhanced the dimerization to give 1 in 62%
and 58% yields (72% and 63% conversions), respectively (entries
12 and 13 in Table 1; see also entries 7 and 8 in Table S1).
Further studies on the effects of the additives were then
performed. The phenols, such as 2-naphthol and hydroquinone,
as the additives gave 1 in nearly 20% yields (entries 15 and16).
However, the addition of H2O, carboxylic acids, bases, and Lewis
acids, which were previously employed in the cooperative NHC
catalysis,11−13,15,16 were not effective (entries 14 and 17−24; see
also entries 9−12 in Table S1). This suggests that the cyano
group in MAN was not activated by the Lewis acids. Collectively,
we hypothesized that alcohol additives would promote
intermolecular proton transfers to lead to an efficient catalytic
turnover.
b
c
d
entry NHC
additive (equiv )
solvent temp (°C) yield (%)
1
2
3
4
5
6
7
8
9
A
−
60
0
A
−
80
8
A
−
100
100
100
100
80
9
A
DOX
DOX
DOX
−
8
e
e
C−M
C−M
B
DBU (1.0)
0
K2CO3 (1.0)
0
18
26
31
21
38
62
58
0
B
−
−
−
−
−
−
−
−
−
−
−
−
−
−
−
−
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
A
i-PrOH (1.0)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
A
t-BuOH (1.0)
n-BuOH (1.0)
n-BuOH (5.0)
n-BuOH (10.0)
H2O (1.0)
A
A
A
A
A
2-naphthol (1.0)
hydroquinone (1.0)
benzoic acid (1.0)
adipic acid (0.5)
LiCl (1.0)
21
20
5
A
A
A
5
A
10
0
A
Sc(OTf)3 (1.0)
Mg(OTf)2 (1.0)
Mg(OtBu)2 (1.0)
DBU (1.0)
A
10
<1
0
A
A
A
K2CO3 (1.0)
−
13
a
5.5 mmol of MAN and 5 mol % of NHC or NHC precursors,
microwave irradiation for 2 h. Equivalent relative to NHC. 1.0 mL of
1,4-dioxane or in bulk. Isolated yield. For 6 h.
b
c
d
e
alcohols afforded 1 in good yields (entries 2−5 in Table 2, see
also entries 1−9 in Table S2, Supporting Information). With the
catalyst loading of 2.5 mol %, 1 was obtained in 48% yield,
however, with the higher TON of 10.6 (entry 6). We varied the
reaction temperature, time, and amount of alcohols, but further
improvements were not achieved (entries 7−10 in Table 2 and
When the combination of aliphatic alcohols and phenols was
used as additives, the catalytic activities were improved (Table 2).
The addition of 5.0 equiv of i-PrOH and 0.2 equiv of 2-naphthol
for A provided 1 in 82% yield, in which the turnover number
(TON) of the NHC catalyst was 8.2. A variety of combinations of
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a
Table 2. Optimization of the Tail-to-Tail Dimerization of MAN in the Presence of Alcohols
b
b
c
d
entry
B (mol %)
ROH (5.0 equiv )
ArOH (0.2 equiv )
temp (°C)
heating
time (h)
yield (%)
f
1
5.0
5.0
5.0
5.0
5.0
2.5
5.0
5.0
5.0
5.0
5.0
5.0
i-PrOH
EtOH
2-naphthol
100
100
100
100
100
100
100
100
80
MW
MW
MW
MW
MW
MW
MW
MW
MW
MW
OB
2
2
2
2
2
2
2
6
2
2
2
2
82 (89 )
2
2-naphthol
70
75
77
82
3
t-BuOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
2-naphthol
4
4-methoxyphenol
hydroquinone
2-naphthol
5
f
6
48 (53 )
e
7
2-naphthol
62
59
51
55
64
75
8
2-naphthol
2-naphthol
2-naphthol
2-naphthol
2-naphthol
9
10
11
12
120
100
120
OB
a
b
c
5.5 mmol of MAN, 0.27 mmol of B, 1.4 mmol of ROH, amd 0.05 mmol of ArOH in bulk for 2 h. Relative to B. MW: microwave, OB: oil bath
d
e
f
1
heating. Isolated yield. 1.0 equiv to B. Conversion of MAN determined by H NMR.
Table S2). We then performed the reaction by oil bath heating in
the same type of microwave vial. The reaction smoothly
proceeded and produced 1 in good yields, i.e., 64% at 100 °C
and 75% at 120 °C (entries 11 and 12). Therefore, nonthermal
microwave effects were not observed in this reaction. The E/Z
ratios of 1 were almost constant at 24:76, irrespective of the
reaction conditions, while our previous report showed that those
of the methacrylates were E/Z = 88−98:2−12.20 The DFT
calculations support that the Z isomer is favored (see Supporting
Information).
Mechanistic Studies of the Dimerization of MAN. We
evaluated the effect of alcohols on the dimerization of n-butyl
methacrylate (n-BuMA). The reaction of n-BuMA with 5 mol %
A for 2 h gave dimer 2 with an E/Z ratio of 95:5 in 64% yield,
while in the presence of n-BuOH (5.0 equiv related to A), the
reaction was sluggish and produced 2 in 34% yield for 2 h
(Scheme 1). This result is in contrast to the dimerization of MAN
(entries 3 and 12 in Table 1). Although the dimerization of MMA
has been proved to proceed through intermolecular proton
transfers,23 the alcohol additive, in this case, exerts detrimental
effects on the catalytic turnover. This interesting difference in the
effect of alcohols between these two major substrates prompted
us to investigate in detail the mechanistic aspects of the
dimerization of MAN and the codimerization of MAN with n-
BuMA.
When the dimerizations of MAN were performed under the
optimal conditions for 10 and 20 min and then quenched by HCl,
dimer 1 was obtained in 30% and 46% isolated yields,
respectively. The ESI-MS spectra of both crude product mixtures
showed signals corresponding to the proton adducts of
intermediates II and IV (Scheme 2). When the dimerization
Scheme 2. ESI-MS/MS Fragmentation of Intermediates II and
IV
Scheme 1. Dimerization of n-BuMA in the Presence or
a
Absence of n-BuOH
was not quenched by HCl, the peak due to IV was not observed,
suggesting that IV was relatively unstable. The MS/MS spectra of
the [II + H]+ and [IV + H]+ showed corresponding fragments of
[A + CH]+ and [A + C2H3]+, respectively, in a way similar to the
MS analysis of the MMA dimerization. Thus, the dimerization of
MAN proceeds through intermediates similar to those for the
dimerization of MMA.
When the reaction of MAN with 100 mol % A in 1,4-dioxane
was carried out by oil bath heating at 80 °C for 5 min, followed by
the addition of HCl, the adduct of the deoxy-Breslow
a
5.0 equiv of n-BuOH relative to A was used. The values in
parentheses indicate the yields in the dimerization in the presence of n-
BuOH.
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intermediates 3 was obtained in 95% yield (Scheme 3). The
addition of CF3CO2D instead gave the adduct 4 with the
(5.0 equiv relative to A) (Scheme 4). Dimer 5 was obtained in
20% yield with the deuterium incorporation at C3, C4, and C5,
Scheme 3. Stoichiometric Reaction of MAN with A Quenched
by HCl or CF3CO2D
Scheme 4. Dimerization of MAN in the Presence of CD3OD
through Double-Bond Migration
a
a
The values in parentheses indicate the percentage of deuterium
incorporations.
indicating intermolecular proton transfers without exchanges
between the α-methyl and alkenyl protons of MAN. We
previously reported that the deuterium incorporations at C3
and C5, but not C4, were observed in the dimerization of MMA
under similar conditions. This indicates that the double-bond
migration in the MAN dimer consisting of the migrations of the
allylic and α-protons (or deuteriums) resulted in the deuterium
incorporation at C4 under these conditions.29
Codimerization of MAN with n-BuMA and Effects of
Alcohol Additives. Glorius et al. previously demonstrated the
codimerization of MAN and n-BuMA at a molar ratio of MAN/n-
BuMA = 2:1. We then performed the codimerizations of MAN
with an equimolar amount of n-BuMA in the presence or absence
of n-BuOH to elucidate the role of alcohols and to compare the
reactivity of the two substrates (Scheme 5). The codimerization
in the presence of 10 mol % A produced homodimers 1 and 2 and
codimers 6 and 7. It is noteworthy that the alcohol additive was
also found to improve the catalysis. Indeed, the addition of n-
BuOH increased the yields of all dimers from 30% to 87%. In
particular, the yields of 1 and 6 increased from 3% and 13% to
24% and 37%, respectively. Because the double-bond isomer-
ization of 6 or 7 was not observed in the stoichiometric reactions
(See Schemes 7 and 8), we assumed that the isomerization would
not take place under the catalytic conditions.
selective deuterium incorporation at the β-carbon, supporting
the formation of II in situ. These experiments indicated that the
reaction of MAN with A to form II is more rapid than the
subsequent Michael addition (II → III in Figure 1). This kinetics
The catalytic codimerizations of MAN with n-BuMA were
performed for 1 min and quenched by the addition of HCl
(Scheme 6). Adducts 3 and 8 were obtained in 45% and 28% 1H
NMR yields based on A, respectively, without the formation of
the dimers. Adduct 3 was produced more rapidly than 8 because
of the higher electrophilicity of MAN than n-BuMA. Although
the yield of 3 slightly increased in the presence of n-BuOH, no
significant difference was found. Thus, we reason that the alcohol
additives hardly affect the first half of the catalytic cycle (A → II
in Figure 1).
We then performed the stoichiometric reactions of
intermediates II or VII, which are quantitatively formed in situ
(Scheme 3 and ref 23), with MAN or n-BuMA.29 The reaction of
II with an equimolar amount of n-BuMA gave codimer 6 in 24%
yield, and the addition of n-BuOH improved the yield to 48%
(Scheme 7). The regenerated A catalyzed the homodimerization
of the unreacted n-BuMA to give 2 in 17% and 15% yields,
respectively, in the presence and absence of n-BuOH.
Interestingly, the reaction of II with MAN gave only a trace
amount of 1, but the addition of n-BuOH significantly increased
the yield to 46%. In contrast, no significant effects of the alcohol
in the reactions of intermediate VII, generated from n-BuMA,
Figure 1. Reaction mechanism.
in the first half of the catalytic cycle is similar to that of the
dimerization of MMA. On the basis of the results of the ESI-MS
analysis and the stoichiometric reactions, we propose the
reaction mechanism shown in Figure 1.
To gain insight into the proton transfer mechanisms, we
performed the dimerization of MAN in the presence of CD3OD
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Scheme 5. Catalytic Codimerizations of MAN and n-BuMA
Scheme 6. Short-Time Reaction of MAN and n-BuMA with 10 mol % of A
Scheme 7. Stoichiometric Reactions of II with MAN or n-BuMA
Scheme 8. Stoichiometric Reactions of VII with MAN or n-BuMA
were found (Scheme 8). These results indicated that the alcohol
contributes to the second half of the catalytic cycle in the
dimerization of MAN (II → A in Figure 1). During the catalytic
codimerization, intermediate II is formed more rapidly than VII,
but, in the absence of the alcohol, the subsequent reaction of II
with MAN or n-BuMA is slow, resulting in the low overall
catalytic activity. It is reasonable to assume that the alcohols
promoted the proton transfer processes (III → V) to regenerate
A, leading to the efficient catalytic turnover. We speculated that
the reaction of intermediates III or IV with alcohols gives
intermediary species VI, which subsequently undergoes the
elimination of the alcohol to form V (Scheme 9).
Scheme 9. Speculative Mechanism of the Proton Transfer
Assisted by Alcohol in the Dimerization of MAN
of the optimization of the reaction conditions, a three-
component catalyst system of aliphatic alcohols and phenols (5
and 0.2 equiv for NHC, respectively) with 5 mol % of the triazole
NHC was found to afford the dimer in 82% yield. The
cooperative system is also effective for the codimerization of
MAN with n-BuMA. We propose that alcohol additives promote
CONCLUSIONS
■
We have shown that the first dimerization of MAN was achieved
by the cooperative NHC and alcohol catalyst. During the course
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δ: 15.3, 17.4, 24.7, 32.4, 113.3, 115.6, 119.7, 141.7, (Z) δ: 17.6, 20.2, 24.9,
35.2, 113.6, 117.3, 121.6, 141.7. HRMS (ESI) m/z: calcd for C8H11N2
[M + H]+ 135.0922, found 135.0923. IR (neat, cm−1): 2987, 2943, 2241,
2218, 1644, 1454, 1384, 1327, 1120, 1048, 910, 867.
Stoichiometric Reaction of MAN and NHC A (Scheme 3). To a
solution of A, generated from B (100 mg, 0.30 mmol) in 1,4-dioxane
(0.6 mL), was added MAN (20 mg, 0.30 mmol) at 80 °C, and the
mixture was stirred for 5 min. The reaction was quenched by HCl in 1,4-
dioxane (1.0 mL, 3.0 mol/L). The crude product was purified by silica
gel column chromatography using CH2Cl2/MeOH (7:1) as the eluent
to give 3 (0.11 g, 0.29 mmol) in 95% yield.
the intermolecular proton transfers in the second half of the
catalytic cycle. Similar to the dimerization of methacrylates, that
of MAN involves (1) the key deoxy-Breslow and dimeric
intermediates (II and VI) and (2) intermolecular proton
transfers. In addition, (3) the reaction of the deoxy-Breslow
intermediate with MAN to form the C−C bond is the rate-
limiting step. The differences are as follows: (1) the double-bond
migration in the MAN dimer is involved, (2) the E/Z selectivity
is much lower, and most interestingly, (3) the alcohol additive
promotes the catalytic turnover. The cooperative systems
involving the umpolung can create new opportunities for the
bond-forming process of a wide variety of Michael acceptors.
5-(2-Cyanopropyl)-1,3,4-triphenyl-4H-1,2,4-triazol-1-ium Chlor-
1
ide (3). Mp = 108−110 °C. H NMR (400 MHz, CDCl3) δ: 1.14 (d,
J = 7.1 Hz, 3H), 2.53−2.56 (m, 1H), 3.34 (dd, J = 10.9, 10.7 Hz, 1H),
4.19 (dd, J = 5.6, 5.6 Hz, 1H), 7.47−8.53 (m, 15H). 13C NMR (100
MHz, CDCl3) δ: 18.2, 22.4, 30.5, 120.0, 122.3, 126.6, 128.9, 129.4,
130.3, 131.4, 132.1, 132.2, 134.7, 152.5, 153.6. HRMS (ESI) m/z: calcd
for C24H21N4 [M − Cl]+: 365.1766, found: 365.1768. IR (neat, cm−1):
3353, 3052, 2243, 2175, 1556, 1377, 1294, 1260, 927, 760, 739, 694
Dimerization of MAN in the Presence of CD3OD (Scheme 4).
NHC B (97 mg, 0.29 mmol), CD3OD (0.21 g, 5.8 mmol), and MAN (0.
39 g, 5.8 mmol) were added into a 0.5−2.0 mL microwave vial, which
was then sealed and heated with microwave irradiation at 100 °C for 2 h.
Kugelrohr distillation under reduced pressure gave 5 (78 mg, 0.58
mmol) in 20% isolated yield. 1H NMR (400 MHz, CDCl3) δ: 1.37 (d, J =
6.2 Hz, 3.0H), 2.01 (s, 3.0H), 2.58−2.63 (m, 1.0H), 2.73−2.80 (m,
0.61H), 6.22 (brs, 0.50H). 13C NMR (100 MHz, CDCl3) δ: 17.5, 20.2,
24.5, 24.6, 24.7, 24.8, 34.7, 35.0, 35.1, 35.2, 113.5, 117.3, 121.5, 141.1,
141.3, 141.5, 141.6, 141.7. HRMS (ESI) m/z; calcd for C8H11N2 [M +
H]+ 135.0916, found 135.0913; calcd for C8H10DN2 [M + H]+
136.9079, found 136.0980; calcd for C8H9D2N2 [M + H]+ 137.1040,
found 137.1041; calcd for C8H8D3N2 [M + H]+ 138.1108, found
138.1103; calcd for C8H7D4N2 [M + H]+ 139.1169, found 139.1160.
Catalytic Codimerization of MAN and n-BuMA (Scheme 5). To
a 0.5−2.0 mL microwave vial were added NHC A, generated from B (80
mg, 0.24 mmol), and a mixture of MAN (0.16 g, 2.4 mmol), n-BuMA
(0.34 g, 2.4 mmol), and n-BuOH (89 mg, 1.2 mmol) at room
temperature. The vial was sealed and heated with microwave irradiation
at 100 °C for 2 h. Biphenyl (40 mg, 0.26 mmol) was then added as a GC
standard. The yields and the E/Z ratios of dimers 1, 2, 6, and 7 were
determined from GC analysis.
Short-Time Reaction of MAN and n-BuMA with A under
Catalytic Condition (Scheme 6). NHC A (72 mg, 0.24 mmol) was
added to a mixture of MAN (0.16 g, 2.4 mmol), n-BuMA (0.34 g, 2.4
mmol), and n-BuOH (89 mg, 1.2 mmol) under oil bath heating at 100
°C. The reaction mixture was stirred for 1 min and then quenched with
HCl in 1,4-dioxane. The mixture was dried in vacuo and subjected to 1H
NMR measurement in CDCl3. The yields of 3 and 8 were determined
from the integration ratio of the aromatic signals to the methylene
signals.
Stoichiometric Reactions of II with n-BuMA (Scheme 7). To a
solution of A, generated from B (100 mg, 0.30 mmol), in 1,4-dioxane
(0.6 mL) was added MAN (20 mg, 0.30 mmol) at 80 °C, and the
mixture was stirred for 10 min. After the volatiles were removed under
reduced pressure, n-BuMA (43 mg, 0.30 mmol), n-BuOH (45 mg, 0.60
mmol), and 1,4-dioxane (0.3 mL) were added at room temperature. The
mixture was transferred to a 0.2−0.5 mL microwave vial, which was then
sealed and heated with microwave irradiation at 100 °C for 2 h.
Kugelrohr distillation under reduced pressure gave 6 (30 mg, 0.14
mmol) in 48% isolated yield. The reactions shown in Scheme 8 were
similarly conducted. For the 1H and 13C NMR, HRMS, and IR data of 6
and 7, see ref 21.
EXPERIMENTAL SECTION
■
General. All reactions were performed under nitrogen atmosphere.
Under the microwave heating, the reaction temperature was measured
by a surface sensor. NHC precursors were prepared according to
previous literature (A,30 B,30 C,31 D,32 E,33 F,34 G,34 H,34 I,34 J,35 L,36
M36). MAN was distilled from CaCl2 and subsequently from CaH2
under reduced pressure and stored over 3 Å molecular sieves. n-BuMA,
n-BuOH, tert-butyl alcohol and 1,8-diazabicyclo[5.4.0]undec-7-ene
(DBU) were distilled from CaH2 under reduced pressure. Triethyl-
amine, i-PrOH, and 1,4-dioxane were distilled from CaH2. Methanol was
distilled from Mg. 2-Naphtol, hydroquinone, 4-methoxyphenol,
biphenyl, and benzoic acid were recrystallized from the mixture of
ethanol and toluene before use. Other chemicals were used as received.
Microwave irradiation experiments were performed using a Biotage
Initiator 2.5 instrument, under the following menu selections;
prestirring: off, absorption level: very high, fixed hold on time: on. 1H
and 13C NMR spectra were recorded on 600 MHz (600 MHz for H,
1
150 MHz for 13C) or 400 MHz (400 MHz for 1H, 100 MHz for 13C)
NMR spectrometers. Chemical shift values in 1H and 13C NMR spectra
1
are relative to internal TMS standard (0.0 ppm for H) or CDCl3
resonance (77.1 ppm for 13C). Electrospray ionization mass
spectrometry (ESI-MS) and tandem mass spectrometry (ESI-MS/
MS) were performed on a tandem quadrupole orthogonal acceleration
time-of-flight instrument equipped with a Z-spray nanoelectrospray
ionization source. GC analysis was carried out on an instrument
equipped with a flame ionization detector and a Zebron ZB-5 fused silica
capillary column (30 m × 0.25 mm i.d. × 0.25 μm film thickness,
Phenomenex). All of the dimers were characterized by GC. The GC
yields of the products and the conversions of substrates were estimated
using biphenyl as an internal standard. The (co)dimers (1, 2, 5−7) were
obtained as transparent liquids purified by Kugelrohr distillation under
reduced pressure (<1 Torr) at 110 °C for 1and 5, 180 °C for 2, 130 °C
for 6, and 230 °C for 7.
The calculations of 1 (E and Z) were carried out with the density
functional theory (DFT) in the Gaussian 09 program.37 Geometry
optimizations and vibrational frequencies (to make zero-point
corrections) were calculated using the B3LYP38,39 method at the 6-
31+G(d,p) level. A series of single-point calculations were performed
with the basis sets B3LYP/6-311+G(3df,2p), B3LYP/6-311++G(d,p),
and B3LYP/6-31+G(d, p) on the optimized geometry.
Tail-to-Tail Dimerization of Methacrylonitrile (Table 1, Entry
12). In a two-necked flask equipped with a three-way stopcock, NHC
precursor B (90 mg, 0.27 mmol) was heated at 100 °C for 12 h under
vacuum conditions to produce NHC A. MAN (0.36 g, 5.4 mmol) and n-
BuOH (100 mg, 1.35 mmol) were then added to this flask at room
temperature. The mixture was transferred to a 0.5−2 mL microwave vial,
which was then sealed and heated with microwave irradiation at 100 °C
for 2 h. The reaction mixture was subjected to Kugelrohr distillation
under reduced pressure to give 1 (0.22 g, 1.7 mmol) in 62% isolated
yield.
ASSOCIATED CONTENT
■
1
2,5-Dimethylhex-2-enedinitrile (1) (E/Z = 24:76). H NMR (600
S
* Supporting Information
MHz, CDCl3) (E) δ: 1.54 (d, J = 7.4 Hz, 3H), 1.94 (s, 3H), 2.46−2.52
(m, 2H), 3.03−3.04 (m, 1H), 6.35 (dd, J = 7.7, 7.5 Hz, 1H), (Z) δ: 1.38
(d, J = 7.1 Hz, 3H), 2.01 (s, 3H), 2.62−2.67 (m, 2H), 2.77−2.79 (m,
1H), 6.22 (dd, J = 7.6, 7.8 Hz, 1H). 13C NMR (100 MHz, CDCl3); (E)
Supplementary tables, results of DFT calculations, and copies of
1H, 13C, and 2D NMR spectra. This material is available free of
charge via the Internet at http://pubs.acs.org.
4489
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The Journal of Organic Chemistry
Article
H.; Melder, J.-P.; Ebel, K.; Schneider, R.; Gehrer, E.; Harder, W.; Brode,
S.; Enders, D.; Breuer, K.; Raabe, G. Helv. Chim. Acta 1996, 79, 61.
(10) For reviews, see: (a) Enders, D.; Balensiefer, T. Acc. Chem. Res.
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AUTHOR INFORMATION
Corresponding Author
*Tel: +81-52-735-7254. Fax: +81-52-735-7254. E-mail:
matsuoka.shinichi@nitech.ac.jp.
Notes
■
́
2007, 107, 5606. (c) Marion, N.; Díez-Gonzalez, S.; Nolan, S. P. Angew.
Chem., Int. Ed. 2007, 46, 2988. (d) Rovis, T. Chem. Lett. 2008, 37, 2.
(e) Nair, V.; Vellalath, S.; Babu, B. P. Chem. Soc. Rev. 2008, 37, 2691.
(f) Phillips, E. M.; Chan, A.; Scheidt, K. A. Aldrichim. Acta 2009, 42, 54.
(g) Moore, J. L.; Rovis, T. Top. Curr. Chem. 2010, 291, 77. (h) Vora, H.
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Scheidt, K. A. Angew. Chem., Int. Ed. 2012, 51, 11686. (n) Sarkar, S. D.;
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The authors declare no competing financial interest.
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