Facile synthetic method for diverse polyfunctionalized imidazoles by means of pd-catalyzed C-H bond arylation of N -methyl-4,5-dibromoimidazole

Article abstract of DOI:10.1021/jo5013493

C-H bond-selective arylation reaction of 4,5-dibromoimidazole with aryl iodides, catalyzed by the palladium-1,10-phenanthroline complex [Pd(phen) ₂](PF₆)₂, has been developed. The process tolerates the presence of a variety of functional groups on the aryl halide substrates. The products formed in these reactions were transformed to a variety of polyfunctionalized imidazoles by taking advantage of selective reactions of remaining C-Br bonds.

Full text of DOI:10.1021/jo5013493

Article
pubs.acs.org/joc
Facile Synthetic Method for Diverse Polyfunctionalized Imidazoles by
Means of Pd-Catalyzed C−H Bond Arylation of N‑Methyl-4,5-
dibromoimidazole
Takayuki Yamauchi,† Fumitoshi Shibahara,*,† and Toshiaki Murai*,†,‡
†Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, Yanagido, Gifu 501-1193, Japan
‡JST, ACT-C, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan
S
* Supporting Information
ABSTRACT: C−H bond-selective arylation reaction of 4,5-dibromoimidazole with aryl iodides, catalyzed by the palladium-
1,10-phenanthroline complex [Pd(phen)2](PF6)2, has been developed. The process tolerates the presence of a variety of
functional groups on the aryl halide substrates. The products formed in these reactions were transformed to a variety of
polyfunctionalized imidazoles by taking advantage of selective reactions of remaining C−Br bonds.
Some conventional cross-coupling reactions of multihalo-
genated imidazoles have been employed to prepare poly-
functionalized derivatives, but site selectivities associated with
these processes are low, particularly C2- versus C5-positions.9
We envisioned that if conditions could be devised to enable
selective C−H bond arylation reactions of readily available
azoles, which possess both C−H and C−Br bonds, a novel and
concise method for preparation of polyfunctionalized imida-
zoles would become available (Scheme 1). Unfortunately,
conventional catalytic systems used for direct C−H bond
arylation reactions typically display low activities for C−H bond
INTRODUCTION
■
Polyfunctionalized azoles, particularly imidazoles, are an
important class of compounds owing to their unique bio-
activities1 and physical properties.2 Therefore, the development
of concise methods for the synthesis of members of this family
is highly important.3 Previously, such imidazoles were usually
synthesized by condensation and/or substitution cyclization of
functionalized carbonyl compounds and/or halides, and those
alternative methods.3,4 In these cases, functional groups have to
be introduced at early stage of synthesis. However, such early
stage functionalization strategies have a disadvantage for
synthesis of diverse derivatives since these often translate into
elaborate multistep syntheses. Thus, late-stage functionalization
methods are highly desired. Recently, transition-metal-catalyzed
direct C−H bond functionalization reactions of azoles have
received significant attention because they enable the
preparation of polyfunctionalized azoles from readily available
unsubstituted azoles in a straightforward and late-stage
functionalization manner.5,6 Generally, transition-metal-cata-
lyzed direct C−H functionalization reactions of imidazoles
display a position-dependent reactivity order of C2 ≈ C5 ≫
C45g,7 and a C2 versus C5 reactivity order that depends on the
catalytic system used.8 In addition, only few direct C4−H
functionalization reactions of azoles, and in particular
imidazoles, have been described due to the low reactivity at
this site.5,6 Thus, 5-unsubstituted 2,4-substituted imidazoles and
2-unsubstituted 4,5-substituted imidazoles as well as 2,4,5-
trisubstituted imidazoles are not readily prepared using direct
C−H functionalization reactions of unsubstituted imidazoles.
Scheme 1. New Synthetic Approach to Polyfunctionalized
Imidazoles
Received: June 17, 2014
Published: July 9, 2014
© 2014 American Chemical Society
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cleavage but high activities for oxidative addition of aryl
halides,10 and those catalytic systems often need some additives
such as silver salts and carboxylic acids or their salts to achieve
efficient C−H bond cleavage.5 As a result, these catalysts
cannot be utilized to promote C−H-selective reactions. In a
recent effort, we have shown that palladium complexes with
nitrogen-based ligands, and in particular [Pd(phen)2](PF6)2
(1) (phen: 1,10-phenanthroline), show excellent catalytic
activities in direct C−H arylation reactions of azoles even in
the absence of additives except base.11 Following this report,
direct C−H bond functionalizations of aromatic compounds
promoted by Pd−nitrogen-based ligand systems have been
extensively investigated and applied to the syntheses of
polyfunctionalized azoles.6 Most recently, Itami, Yamaguchi,
and co-workers developed rare C4-selective oxidative direct
arylation of thiazoles with boronic acids catalyzed by a Pd-1,10-
phenanthroline system, and they have realized synthesis of all
patterns of mono-, di-, triarylated thiazoles by combination of
their methods and previously reported direct C−H arylation
reactions.12 However, the C4-selective arylation reaction did
not take place with other azoles, in particular imidazoles, thus
further investigations for developing methods to construct
highly substituted imidazoles are still needed.
Table 1. Optimization of Conditions for Reaction of 6 with
7a
a
entry
Pd catalyst
ligand
temp (°C)
yield (%)
1
2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
1
150
150
150
150
150
150
130
150
150
150
150
130
110
37
38
18
14
PPh3
3
P(4-CF3C6H4)3
P(4-MeOC6H4)3
4
b
c
5
dppb
ND
6
t-Bu3P·HBPh4
PPh3
36
17
7
e
8
2,2′-bipyridyl
phen
36
e
9
45
d
e
10
11
12
13
14
phen
67
73
85
37
1
1
1
90
20
An important characteristic of Pd−nitrogen-based ligand
containing catalysts is that they display relatively low activity in
promoting reactions of aryl halides in contrast to C−H bond
cleavage reactions.11 By considering this feature, we envisaged
that C−H bond-selective arylation reactions of halogenated
imidazoles might be possible if highly reactive aryl iodides are
used as coupling partners. Importantly, in this case, halogen
atoms in the azoles would serve as protecting groups for
otherwise reactive C−H bonds. In fact, the results of a
preliminary investigation showed that C−I bond-selective
reaction takes place between benzoxazole 2 and bromoiodo-
benzene 3 when 1 is utilized as the catalyst (Scheme 2). This
a
b
c
d
Isolated yields. Diphenylphosphinobutane. Not detected. NaPF6
e
(10 mol %) was added. The yield was determined by using 1H NMR
with 1,1,2,2-tetrachloroethane as an internal standard.
complex product mixture from which the coupling product 8a
is isolated in only 37% yield and a significant amount of
unidentified side products is generated (entry 1). The addition
of PPh3 or its para-electron-withdrawing and -donating-group-
substituted analogues as ligands to the Pd(OAc)2 containing
reaction mixture does not improve the yield of the process
(entries 2−4). Moreover, 8a was not generated when the
bidentate phosphine ligand dppb was employed (entry 5), and
the addition of t-Bu3P does not cause an enhancement in the
efficiency of the reaction (entry 6). An attempt to suppress side
processes by carrying out reaction of 6 with 7a in the presence
of Pd(OAc)2 and PPh3 at lower temperature (130 °C) was not
successful (entry 7).
Scheme 2. Preliminary Result of C−I Bond-Selective, Direct
C−H Bond Arylation Reaction
In contrast, addition of 2,2′-bipyridyl or 1,10-phenanthroline
as a ligand dramatically suppressed the side processes, and only
8a and substrates 6 and 7a were recovered with high mass
balance after the reaction, particularly with 1,10-phenanthroline
as a ligand, though the product yield did not improve (entries 8
and 9). These results obviously indicated that the use of
nitrogen-based ligands is critical for selective reaction with
brominated substrates. Catalytic activity increased by adding
NaPF6 as an additive (entry 10). In addition, as anticipated,
coupling reaction of 6 and 7a takes place with high efficiency to
form the C2-arylated product 8a when preformed [Pd(phen)2]-
(PF6)2 (1) is utilized as the catalyst (entry 11). Studies of the
effect of temperature (entries 11−14) showed that the use of
130 °C leads to an optimal yield of 8a (85%, entry 12). Further
lowering of the reaction temperature greatly affects the
conversion of 6, and the yields of 8a drop at 110 and 90 °C
(entries 13 and 14).
result prompted a general investigation of C−H bond-selective
arylation reactions of brominated imidazoles. Below, we
describe the results of this study, which have led to the
development of a novel and concise synthetic method for the
preparation of polyfunctional imidazoles, which employs C−H
bond-selective arylation reactions of 1-methyl-4,5-dibromo-
imidazole promoted by Pd−1,10-phenanthroline complexes as
a key step.
RESULTS AND DISCUSSION
■
Investigations of C−H-Selective Direct Arylation of a
4,5-Dibromoimidazole. In the initial phase of the studies,
reaction of 1-methyl-4,5-dibromoimidazole (6) and 1-iodo-4-
α,α,α-trifluoromethyltoluene (7a) was explored using several
different palladium complexes as catalysts (Table 1).11,13
Reaction promoted using Pd(OAc)2 was found to give a
In previous investigations, several C2-selective arylations of
N-protected imidazoles were observed to occur when additives
CuI8d and Ni(OAc)28b were employed. In a study exploring the
potential utility of these catalysts, we observed that C2-selective
reaction of 6 with phenyl iodide (7b) to form 8b does not take
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place, and in each case, a complex product mixture is produced
Table 2. Scope of Reaction of 6 with Aryl Iodides
(Scheme 3, conditions A−C). Also, the yield of the desired
Scheme 3. Reactions under Conventional C2-Selective
Arylation Conditions
product was low when the previously reported catalytic system
for 1-methyl-4,5-dichloroimidazole is employed to promote C−
H-selective reaction (conditions D).14 Again, the reaction
proceeds smoothly with catalyst 1 to give 8b in almost
quantitative yield (conditions E).
Scope of Substrates. Based on the findings described
above, the aryl iodide scope of the coupling reaction was
investigated next. As the results tabulated in Table 1 and
represented in Scheme 3 show, reaction of 6 with aryl iodides
7a and 7b, promoted by 1, give the corresponding arylated
imidazoles 8a and 8b in high yields (Table 2, entries 1 and 2).
Relatively electron-rich aryl iodides, which are generally less
reactive in oxidative addition processes, also react with 6 under
these conditions to form the corresponding products 8c and 8d
in high yields (entries 3 and 4). Steric hindrance in the aryl
halides has little effect on the efficiencies of this process as
exemplified by reactions with 1-naphthyl iodide 7e and o-tolyl
iodide 7f, which generate the corresponding coupling products
8e and 8f in respective yields of 90 and 61% (entries 5 and 6).
It should be noted that the use of Pd(phen)(OAc)2 instead of 1
as a catalyst gives higher yields for coupling reactions of these
substrates. Reaction of imidazole 6 with five-membered
heteroaromatic iodide 7g takes place to form arylation product
8g in low yield (entry 7), but in contrast, the six-membered
heteroaromatic iodide 7h couples with 6 with high efficiency
(entry 8). In addition, reactions of 6 with aryl iodides 7i−k,
containing strongly electron-withdrawing groups such as nitro,
cyano, and ethoxycarbonyl, form the corresponding adducts
8i−k in moderate to good yields (entries 9−11). Notably,
selective cleavage of the C−Br bond in the highly electron-
deficient 3,5-bis(trifluoromethylphenyl)bromide 9l takes place
in reaction with 6 while the C−Br bonds in the imidazole
remain undisturbed (entry 12).
a
b
c
Cs2CO3 was used. K2CO3 was used. Reaction was performed at 150
d
e
°C. Pd(phen)(OAc)2 was used as a catalyst. The yield was
determined by using H NMR with 1,1,2,2-tetrachloroethane as an
internal standard. Aryl bromide was used instead of iodide.
1
f
Scheme 4. Reactivity Order of Aryl Halides and an Aryl
Triflate
cases, unidentified insoluble materials, which probably contain
oligomerized imidazole, are formed in significant amounts.
Although arylated imidazole products are generated in reactions
using the more reactive aryl bromides such as bromo-α,α,α-
trifluorotoluene (9a), the yields are low. In contrast, highly
selective incorporation of aryl groups is achieved using aryl
iodides as substrates.
Synthetic Applications of the Selective Arylation
Reaction. In this effort, we also investigated synthetic
applications of the C2-arylated imidazoles 8 that are generated
in selective Pd-catalyzed C−H bond arylation reactions of 1-
methyl-4,5-dibromoimidazole. For example, 2,4-disubstituted
imidazoles 12−14, which are difficult to prepare from
unsubstituted imidazoles using conventional methods, are
produced by utilizing straightforward pathways (Scheme 5).
The efficiencies and selectivities of the C−H arylation
reactions of 6 are governed by the high reactivity of aryl halides
in transition-metal-catalyzed oxidative addition processes
(Scheme 4).15 In fact, reactions using less reactive aryl halides
such as phenyl triflate (10b) and phenyl bromide (9b) are
observed to result in formation of complex mixtures that
contain only trace amounts of coupling products 8. In these
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the highly substituted imidazole 20, which has been shown to
possess antiallergic properties (Scheme 7).1f In previous efforts,
Scheme 5. Synthesis of 2,4-Substituted Imidazoles
Scheme 7. Synthesis of 20
Treatment of dibromoimidazole 8b with an equivalent of n-
butyllithium at −78 °C followed by aqueous quenching gave
rise selectively to the debrominated imidazole 11c in high
yield.16 The remaining C4-bromo group in 11c can be used to
introduce aryl or acetylenic groups by employing conventional
cross-coupling reactions. For example, Suzuki−Miyaura cou-
pling of 11c with phenylboronic acid efficiently generates the
2,4-diarylated N-methylimidazole 12.17 Application of a
Sonogashira coupling enabled generation of 4-alkynyl-2-aryl-
imidazole 13 in good yield.18 Furthermore, cross-coupling
reaction of 11c with benzamide under conditions recently
described by Buchwald produces the C4-amidated imidazole 14
in 96% yield.19 The C5-selective debromination protocol can
be applied to other 2-aryl-3,4-dibromoimidazoles, as exempli-
fied by the debromination of the alkoxycarbonylated derivative
8k under Knochel’s conditions with i-PrMgCl·LiCl,20 which is
more tolerant of ester moieties than is butyllithium. Addition of
DMF to the crude reduction mixture formed in this manner
gives rise to formylimidazole 15 in excellent yield (Scheme 6).
20 was synthesized using conventional condensation strategies
that are difficult to apply for the preparation of derivatives. In
the strategy we devised, the naphthyl group in the target is
introduced in the first step through C−H arylation of 1-methyl-
4,5-dibromoimidazole that provides 8e (Table 2, entry 5).
Selective C5 lithiation of 8e followed by ethoxycarbonylation
with ethyl cyanoformate efficiently generates ester 17. The
remaining bromo group in 17 is then used to direct Suzuki−
Miyaura coupling with p-tolylboronic acid to give 18, which is
then transformed to 20 by hydrolysis followed by condensation
with 2-aminothiazole (19).
CONCLUSIONS
■
In conclusion, a method for direct C−H-selective arylation of a
dibromoimidazole with aryl iodides, using a Pd−1,10-phenan-
throline catalyst, was developed in the investigation described
above. The catalyst used for this process finely discriminates
C−Br bonds of the imidazole from bonds of the arylating
agents and consequently promotes reactions that chemo- and
regioselectively form 2-aryl-4,5-dibromoimadazole products in
high efficiencies. By employing this process, diversely function-
alized azoles can be readily produced, making 4,5-dibromo-
imidazoles versatile precursors in the preparation of highly
functionalized imidazoles. Selective C−H arylation reactions of
other brominated azoles and applications of the generated
functionalized imidazoles1,21 and respective reaction mecha-
nisms on each C−H bond as well as C−H bond-selective
reactions are the focus of our continuing investigations in this
area.
Scheme 6. Functionalization of Dibromoimidazole Bearing
an Alkoxycarbonyl Group
EXPERIMENTAL SECTION
■
1
General. H NMR (400 MHz), 13C NMR (100 MHz), and 19F
NMR (376 MHz) spectra were recorded in CDCl3. Chemical shifts of
1H and 13C are reported in δ values with reference to tetramethylsilane
and CDCl3 as internal standards, respectively. The 19F chemical shifts
are expressed in δ values deshielded with respect to CF3COOH as an
external standard. The mass spectra (MS) and high-resolution mass
spectra (HRMS) were obtained by ionizing samples via electron
ionization (EI) in positive mode with a magnetic sector analyzer. All
reactions were carried out in an argon atmosphere. Preparative
recycling gel permeation chromatography (GPC) was performed on
Japan Analytical Industry LC-908 or LC9201R/U recycling prepara-
These observations show that alkynyl and carbonyl groups,
particularly a formyl group, which are typically sensitive to a
variety of reagents, can be introduced at late stages of synthetic
pathways using the new protocol. In fact, the formylimidazole
derivative 15 can be coupled with a terminal alkyne by using
Sonogashira conditions in the last step to produce the highly
substituted imidazole 16 (Scheme 6).
To demonstrate the power of the new method developed in
the studies described above, we employed it in the synthesis of
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1
tive HPLC equipped with JAIGEL-1H and -2H columns (chloroform
as eluent).
969, 775, 735 cm−1; H NMR (CDCl3) δ 2.24 (s, 3H), 3.43 (s, 3H),
7.25−7.30 (m, 3H), 7.34−7.38 (m, 1H); 13C NMR (CDCl3) δ 19.8,
33.7, 104.3, 116.3, 125.9, 129.3, 130.1, 130.5, 130.6, 138.3, 148.2; MS
(EI) m/z (relative intensity %) 332 (36, M+ + 4), 330 (72, M+ + 2),
328 (40, M+); HRMS (EI) exact mass calcd for C11H1079Br2N2 (M+)
327.9211; found 327.9215.
Reaction of Benzoxazole (2) and 4-Bromoiodobenzene (3).
[Pd(phen)2](PF6)2 (1) (5 mol %, 19 mg), Cs2CO3 (1.5 equiv, 245
mg), benzoxazole (2) (0.5 mmol, 60 mg), 4-bromoiodobenzene (3)
(1.5 equiv, 212 mg), and DMA (1 mL) were added to a screw-capped
test tube. The reaction mixture was stirred for 20 h at 130 °C under
argon atmosphere. After the reaction completed, the mixture was
cooled to room temperature. The reaction mixture was filtered
through a Celite pad and concentrated in vacuo. The residue was
purified by flash column chromatography on silica gel (n-hexane/
EtOAc = 10:1, Rf = 0.63) to give 2-(4-bromophenyl)benzoxazole (4)22
2-(2-Benzothienyl)-4,5-dibromo-1-methylimidazole (8g):
36% yield (33 mg), yellow solid, mp 158.7−163.5 °C; Rf = 0.50 (n-
hexane/EtOAc = 4:1); IR (KBr) 1486, 1443, 938, 741, 723 cm−1, H
1
NMR (CDCl3) δ 3.89 (s, 3H), 7.37−7.40 (m, 2H), 7.56 (s, 1H),
7.80−7.86 (m, 2H); 13C NMR (CDCl3) δ 34.9, 106.9, 117.5, 122.3,
123.4, 124.3, 125.0, 125.6, 131.6, 139.5, 140.0, 142.8; MS (EI) m/z
(relative intensity %) 374 (42, M+ + 4), 372 (88, M+ + 2), 370 (42,
M+); HRMS (EI) exact mass calcd for C12H879Br2N2S 369.8775; found
369.8773.
1
in 56% yield (38 mg) as a colorless solid: H NMR (CDCl3) δ 7.34−
7.38 (m, 2H), 7.55−7.60 (m, 1H), 7.66 (d, J = 8.8 Hz, 2H), 7.74−7.79
(m, 1H), 8.12 (d, J = 8.8 Hz, 2H).
4,5-Dibromo-1-methyl-2-(3-pyridyl)imidazole (8h): 74% yield
General Procedure for the C−H-Selective Arylation of 4,5-
Dibromoimidazole. [Pd(phen)2](PF6)2 (1) (5 mol %, 10 mg),
Cs2CO3 (1.5 equiv, 122 mg) or K2CO3 (1.5 equiv, 52 mg), 4,5-
dibromo-1-methylimdazole (6) (0.25 mmol, 60 mg), aryl iodides 7
(1.5 equiv), and DMA (0.5 mL) were added to a screw-capped test
tube. The reaction mixture was stirred for 20 h at 130−150 °C under
an argon atmosphere. After the reaction completed, the mixture was
cooled to room temperature. The reaction mixture was filtered
through a Celite pad and concentrated in vacuo. The residue was
purified by flash column chromatography on silica gel to give 2-
arylated 4,5-dibromoimidazole 8.
(59 mg), brown oil; Rf = 0.04 (n-hexane/EtOAc = 1:1); IR (KBr)
1
1570, 1487, 1413, 1374, 1228, 1092, 1020, 971, 813, 711 cm−1; H
NMR (CDCl3) δ 3.73 (s, 3H), 7.41−7.44 (m, 1H), 7.96 (d, J = 7.6 Hz,
1H), 8.68 (brd, J = 3.1 Hz, 1H), 8.83 (s, 1H); 13C NMR (CDCl3) δ
34.8, 106.9, 117.6, 123.8, 126.1, 136.4, 145.5, 148.9, 150.3; MS (EI)
m/z (relative intensity %) 319 (57, M+ + 4), 317 (100, M+ + 2), 315
(50, M+); HRMS (EI) NMR exact mass calcd for C9H779Br2N3
314.9007; found 314.9005.
4,5-Dibromo-1-methyl-2-(4-nitrophenyl)imidazole (8i): 45%
yield (41 mg), yellow solid, mp 177.2−178.4 °C; Rf = 0.43 (n-hexane/
EtOAc = 4:1); IR (KBr) 1594, 1521, 1483, 1347, 970, 856, 708 cm−1;
1H NMR (CDCl3) δ 3.79 (s, 3H), 7.81 (d, J = 8.8 Hz, 2H). 8.33 (d, J
4,5-Dibromo-1-methyl-2-(4-(trifluoromethyl)phenyl)-
imidazole (8a): 85% yield (82 mg), colorless solid, mp 97.0−97.6 °C;
Rf = 0.33 (n-hexane/EtOAc = 10:1); IR (KBr) 1619, 1494, 1449, 1409,
= 8.8 Hz, 2H); 13C NMR (CDCl3) δ 35.1, 107.9, 118.0, 124.1, 129.3,
135.4, 146.1, 148.1; MS (EI) m/z (relative intensity %) 363 (53, M+ +
4), 361 (100, M+ + 2), 359 (46, M+); HRMS (EI) exact mass calcd for
C10H779Br2N3O2 (M+) 358.8905; found 358.8900.
1
1330, 1167, 1124, 1092, 1014, 971, 848 cm−1; H NMR (CDCl3) δ
3.74 (s, 3H), 7.73 (br s, 4H); 13C NMR (CDCl3) δ 34.8, 106.9, 117.4,
123.8 (q, JC−F = 272.5 Hz), 125.8 (q, JC−F = 3.8 Hz), 128.0, 131.5 (q,
JC−F = 32.9 Hz), 132.9, 147.0 (Ar); 19F NMR (CDCl3) δ −50.5; MS
(EI) m/z (relative intensity %) 386 (45, M+ + 4), 384 (100, M+ + 2),
382 (49, M+); HRMS (EI) exact mass calcd for C11H779Br2F3N2 (M+)
381.8928; found 381.8932.
4,5-Dibromo-2-(4-cyanophenyl)-1-methylimidazole (8j): 79%
yield (67 mg), colorless solid, mp 190.3−192.6 °C; Rf = 0.10 (n-
hexane/EtOAc = 4:1); IR (KBr) 2224, 1604, 1487, 1448, 969, 843
cm−1; 1H NMR (CDCl3) δ 3.75 (s, 3H), 7.72 (d, J = 8.5 Hz, 2H), 7.76
(d, J = 8.5 Hz, 2H); 13C NMR (CDCl3) δ 35.0, 107.6, 113.2, 117.7,
118.3, 129.1, 132.6, 133.6, 146.4; MS (EI) m/z (relative intensity %)
343 (44, M+ + 4), 341 (86, M+ + 2), 339 (50, M+); HRMS (EI) exact
mass calcd for C11H779Br2N3 (M+) 338.9007; found 338.9010.
4,5-Dibromo-2-(4-ethoxycarbonylphenyl)-1-methyl-
imidazole (8k): 70% yield (68 mg), colorless solid, mp 128.2−129.6
°C; Rf = 0.15 (n-hexane/EtOAc = 10:1); IR (KBr) 2923, 1713, 1281,
4,5-Dibromo-1-methyl-2-phenylimdazole (8b):23 99% yield
(78 mg), colorless solid; Rf = 0.29 (n-hexane/EtOAc = 10:1); 1H
NMR (CDCl3) δ 3.69 (s, 3H), 7.43−7.48 (m, 3H), 7.54−7.57 (m,
2H).
4,5-Dibromo-1-methyl-2-(4-methylphenyl)imidazole (8c):
76% yield (63 mg), colorless solid, mp 99.5−100.0 °C; Rf = 0.28
(n-hexane/EtOAc = 10:1); IR (KBr) 1496, 1455, 1377, 1236, 1096,
1
968, 822, 721, 496 cm−1; H NMR (CDCl3) δ 2.40 (s, 3H), 3.67 (s,
1
1110, 775, 714 cm−1; H NMR (CDCl3) δ 1.40 (t, J = 7.2 Hz, 3H),
3H), 7.26 (d, J = 8.5 Hz, 2H), 7.45 (d, J = 8.5 Hz, 2H); 13C NMR
(CDCl3) 21.5, 34.7, 105.3, 116.7, 126.8, 128.7, 129.5, 139.8, 148.8; MS
(EI) m/z 332 (59, M+ + 4), 330 (100, M+ + 2), 328 (69, M+); HRMS
(EI) exact mass calcd for C11H1079Br2N2 327.9211; found 327.9217.
4,5-Dibromo-1-methyl-2-(4-methoxyphenyl)imidazole (8d):
66% yield (57 mg), colorless solid, mp 126.4−129.6 °C; Rf = 0.15 (n-
hexane/EtOAc = 10:1); IR (KBr) 1608, 1495, 1464, 1437, 1372, 1252,
1175, 1020, 968, 831 cm−1; 1H NMR (CDCl3) δ 3.65 (s, 3H), 3.83 (s,
3H), 6.95 (d, J = 9.0 Hz, 2H), 7.46 (d, J = 9.0 Hz, 2H); 13C NMR
(CDCl3) δ 34.7, 55.5, 105.1, 114.2, 116.4, 122.0, 130.2, 148.6, 160.6;
MS (EI) m/z (relative intensity %) 348 (27, M+ + 4), 346 (55, M+ +
2), 344 (27, M+); HRMS (EI) exact mass calcd for C11H1079Br2N2O
(M+) 343.9160; found 343.9161.
4,5-Dibromo-1-methyl-2-(1-naphthyl)imidazole (8e): 90%
yield (82 mg), colorless solid, mp 119.3−120.6 °C; Rf = 0.25 (n-
hexane/EtOAc = 10:1); IR (KBr) 1502, 1453, 1369, 1235, 1095, 987,
956, 797, 775 cm−1; 1H NMR (CDCl3) δ 3.43 (s, 3H), 7.50−7.55 (m,
4H), 7.64−7.67 (m, 1H), 7.89−7.93 (m, 1H), 7.95−7.99 (m, 1H); 13C
NMR (CDCl3) δ 34.2, 105.0, 116.7, 125.1 (2C), 126.6, 127.1, 127.4,
128.6, 129.1, 130.6, 132.1, 133.6, 147.5; MS (EI) m/z (relative
intensity %) 368 (54, M+ + 4), 336 (100, M+ + 2), 364 (49, M+);
HRMS (EI) exact mass calcd for C14H1079Br2N2 (M+) 363.9211; found
363.9216.
3.73 (s, 3H), 4.39 (q, J = 7.2 Hz, 2H), 7.67 (d, J = 8.1 Hz, 2H), 8.12
(d, J = 8.1 Hz, 2H); 13C NMR (CDCl3) δ 14.4, 34.9, 61.4, 106.8,
117.4, 128.5, 130.0, 131.3, 133.5, 147.5, 166.0; MS (EI) m/z (relative
intensity %) 390 (57, M+ + 4), 388 (100, M+ + 2), 386 (47, M+);
HRMS (EI) exact mass calcd for C13H1279Br2N2O2 (M+) 385.9266;
found 385.9268.
2-(3,5-Bis(trifluoromethyl)phenyl)-4,5-dibromo-1-methyl-
imidazole (8l): 97% yield (109 mg), colorless solid, mp 96.9−97.1
°C; Rf = 0.25 (n-hexane/EtOAc = 10:1); IR (KBr) 1482, 1354, 1277,
1183, 1134, 902 cm−1; 1H NMR (CDCl3) δ 3.80 (s, 3H), 7.97 (s, 1H),
8.10 (s, 2H); 13C NMR (CDCl3) δ 34.9, 107.8, 117.9, 123.0 (q, JC−F
=
273.4 Hz), 123.1 (q, JC−F = 3.8 Hz), 128.6, 131.6, 132.5 (q, JC−F = 33.8
Hz), 145.4; 19F NMR (CDCl3) −62.9; MS (EI) m/z (relative intensity
%) 454 (45, M+ + 4), 452 (100, M+ + 2), 450 (49, M+); HRMS (EI)
exact mass calcd for C12H679Br2F6N2 449.8802; found 449.8801.
4-Bromo-1-methyl-2-(4-methylphenyl)imidazole (11c). A
solution of n-BuLi in n-hexane (1.5 M, 1.1 equiv) was added dropwise
to a solution of 4,5-dibromo-1-methyl-2-(4-methylphenyl)imidazole
(8c) (0.25 mmol, 83 mg) in anhydrous THF (1 mL) under an argon
atmosphere at −78 °C. The mixture was stirred at −60 °C for 1 h. The
reaction solution was quenched with cold H2O then was warmed to
room temperature and extracted with EtOAc. The organic layer was
dried over Na2SO4, filtered, and concentrated in vacuo. The residue
was purified by flash column chromatography on silica gel (n-hexane/
EtOAc = 4:1; Rf = 0.54) to give 4-bromo-1-methyl-2-(4-methyl-
phenyl)imidazole (11c) in 73% yield (46 mg) as a colorless solid: mp
4,5-Dibromo-1-methyl-2-(2-methylphenyl)imidazole (8f):
61% yield (50 mg), yellow solid, mp 82.9−86.2 °C; Rf = 0.23 (n-
hexane/EtOAc = 10:1); IR (KBr) 2923, 1493, 1442, 1378, 1221, 1086,
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96.3−98.0 °C; IR (KBr) 3110, 1505, 1461, 1447, 1390, 1250, 951, 770,
chromatography on silica gel (n-hexane/EtOAc = 4:1, Rf = 0.54) to
give 4-bromo-2-(4-ethoxycarbonylphenyl)-5-formyl-1-methylimidazole
(15) in 90% yield (167 mg) as a colorless solid: mp 95.6−98.2 °C, IR
(KBr) 1720, 1664, 1181, 1108, 720 cm−1; 1H NMR (CDCl3) δ 1.41 (t,
J = 7.2 Hz, 3H), 4.00 (s, 3H), 4.41 (d, J = 7.2 Hz, 2H), 7.73 (d, J = 8.3
Hz, 2H), 8.17 (d, J = 8.3 Hz, 2H), 9.83 (s, 1H). 13C NMR (CDCl3) δ
14.4, 34.8, 61.6, 128.1, 129.4, 130.0, 130.9, 131.7, 132.4, 152.2, 165.8,
179.8; MS (EI) m/z (relative intensity %) 338 (91, M+ + 2), 336 (100,
M+); HRMS (EI) exact mass calcd for C14H1379BrN2O3 (M+)
336.0110; found 336.0109.
1
695 cm−1; H NMR (CDCl3) δ 2.39 (s, 3H), 3.69 (s, 3H), 6.90 (s,
1H), 7.24 (d, J = 8.1 Hz, 2H), 7.48 (d, J = 8.1 Hz, 2H); 13C NMR
(CDCl3) δ 21.4, 34.7, 114.8, 121.0, 126.6, 128.7, 129.3, 139.3, 148.1;
MS (EI) m/z (relative intensity %) 252 (95, M+ + 2), 250 (100, M+);
HRMS (EI) exact mass calcd for C11H1179BrN2 250.0106; found
250.0103.
1-Methyl-2-(4-methylphenyl)-4-phenylimidazole (12). A sol-
ution of 4-bromo-1-methyl-2-(4-methylphenyl) imidazole (11c) (0.25
mmol, 63 mg), PhB(OH)2 (2 equiv, 61 mg), Cs2CO3 (2 equiv, 163
mg), and Pd(PPh)4 (10 mol %, 29 mg) in 1,2-dimethoxyethane (1
mL) and water (1 mL) was stirred at reflux under an argon
atmosphere for 21.5 h. The mixture was diluted with citric acid (1 M)
and extracted with EtOAc. The combined organic layer was dried over
Na2SO4, filtered, and concentrated in vacuo. The residue was purified
by flash column chromatography on silica gel (n-hexane/EtOAc = 4:1,
Rf = 0.59) to give 1-methyl-2-(4-methylphenyl)-4-phenylimidazole
(12) in 77% yield (48 mg) as a brown solid: mp 99.3−101.4 °C; IR
2-(4-Ethoxycarbonylphenyl)-5-formyl-4-(4-methylphenyl-
ethynyl)-1-methylimidazole (16). To a solution of 4-bromo-2-(4-
ethoxycarbonylphenyl)-5-formyl-1-methylimidazole (15) (0.1 mmol,
34 mg) in MeCN (0.5 mL) were added PdCl2(NCPh)2 (5 mol %, 2
mg), t-Bu3P·HBPh4 (10 mol %, 5 mg), CuI (5 mol %, 1 mg), 4-
ethynyltoluene (1.5 equiv, 24 μL), and i-Pr2NEt (2 equiv, 33 μL)
under an argon atmosphere. The resulting mixture was stirred at 80 °C
for 9.5 h. The resulting mixture was filtered through a Celite pad and
concentrated in vacuo. The residue was purified by flash column
chromatography on silica gel (n-hexane/EtOAc = 4:1, Rf = 0.38) to
give 2-(4-ethoxycarbonylphenyl)-5-formyl-4-(4-methylphenylethynyl)-
1-methylimidazole (16) in 76% yield (28 mg) as a brown solid: mp
1
(KBr) 1464, 1383, 827, 753, 729, 695 cm−1; H NMR (CD3COCD3)
δ 2.37 (s, 3H), 3.81 (s, 3H), 7.14−7.18 (m, 1H), 7.28−7.33 (m, 4H),
7.54 (s, 1H), 7.64 (d, J = 8.5 Hz, 2H), 7.83 (d, J = 8.5 Hz, 2H); 13C
NMR (CDCl3) 21.5, 34.7, 117.9, 125.0, 126.9, 127.1, 128.6, 128.9,
129.4, 133.8, 139.0, 140.6, 148.3; MS (EI) m/z 248 (M+); HRMS (EI)
exact mass calcd for C17H16N2 248.1313; found 248.1313.
1
165.1−168.5 °C; IR (KBr) 1718, 1660, 1279, 1108, 722 cm−1; H
NMR (CDCl3) δ 1.47 (t, J = 7.2 Hz, 3H), 2.37 (s, 3H), 4.02 (s, 3H),
4.41 (q, J = 7.2 Hz, 2H), 7.17 (d, J = 8.1 Hz, 2H), 7.48 (d, J = 8.1 Hz,
2H), 7.77 (d, J = 8.5 Hz, 2H), 8.18 (d, J = 8.5 Hz, 2H), 10.07 (s, 1H);
13C NMR (CDCl3) δ 14.4, 21.7, 34.7, 61.5, 79.6, 95.4, 118.8, 129.3,
1-Methyl-2-(4-methylphenyl)-4-(4-tolylethynyl)imidazole
(13). To a solution of 4-bromo-1-methyl-2-(4-methylphenyl)imidazole
(11c) (0.25 mmol, 63 mg) in MeCN (1.2 mL) were added
PdCl2(NCPh)2 (10 mol %, 10 mg), Pt-Bu3·HBPh4 (20 mol %, 26
mg), CuI (10 mol %, 5 mg), 4-ethynyltoluene (2 equiv, 70 μL), and i-
Pr2NEt (3 equiv, 130 μL) under an argon atmosphere. The resulting
mixture was stirred at 80 °C for 20 h. The resulting mixture was
filtered through a Celite pad and concentrated in vacuo. The residue
was purified by flash column chromatography on silica gel (n-hexane/
EtOAc = 10:1, Rf = 0.09) to give 1-methyl-2-(4-methylphenyl)-4-(4-
tolylethynyl)imidazole (13) in 57% yield (41 mg) as a brown solid:
mp 142.6−144.3 °C; IR (KBr) 2212, 1503, 1470, 1449, 1390, 822,
129.4, 130.0, 131.9, 132.2, 132.3, 133.2, 137.7, 139.7, 152.5, 165.8,
179.8; MS (EI) m/z (relative intensity %) 372 (M+); HRMS (EI)
exact mass calcd for C23H20N2O3 372.1474; found 372.1475.
4-Bromo-5-ethoxycarbonyl-1-methyl-2-(1-naphthyl)-
imidazole (17). A solution of n-BuLi in n-hexane (1.5 M, 1.1 equiv,
0.18 mL) was added dropwise to a solution of 4,5-dibromo-1-methyl-
2-(1-naphthyl)imidazole (8e) (0.25 mmol, 92 mg) in anhydrous THF
(0.5 M, 0.50 mL) under an argon atmosphere at −78 °C. The mixture
was stirred at −60 °C for 1 h, and ethyl cyanoformate (2 equiv, 49 μL)
was then added. The reaction mixture was warmed to room
temperature. After 2 h, the reaction was quenched with H2O and
extracted with EtOAc. The organic layer was dried over Na2SO4,
filtered, and concentrated in vacuo. The residue was purified by flash
column chromatography on silica gel (n-hexane/EtOAc = 1:4, Rf =
0.43) to give 4-bromo-5-ethoxycarbonyl-1-methyl-2-(1-naphthyl)-
imidazole (17) in 76% yield (68 mg) as a colorless oil: IR (KBr)
1
768, 732 cm−1; H NMR (CDCl3) δ 2.33 (s, 3H), 2.39 (s, 3H), 3.71
(s, 3H), 7.11 (d, J = 7.6 Hz, 2H), 7.17 (s, 1H), 7.25 (d, J = 7.6 Hz,
2H), 7.41 (d, J = 8.1 Hz, 2H), 7.53 (d, J = 8.1 Hz, 2H); 13C NMR
(CDCl3) δ 21.5, 21.6, 34.9, 82.1, 89.9, 120.3, 123.4, 125.8, 126.6,
128.8, 129.1, 129.4, 131.5, 138.2, 139.4, 148.3; MS (EI) m/z 286
(M+); HRMS (EI) exact mass calcd for C20H18N2 286.1470; found
286.1469.
1
1707, 1244, 1125, 1108, 781 cm−1; H NMR (CDCl3) δ 1.45 (t, J =
4-Benzamido-1-methyl-2-(4-methylphenyl)imidazole (14). A
solution of 4-bromo-1-methyl-2-(4-methylphenyl)imidazole (11c)
(0.25 mmol, 63 mg), benzamide (2 equiv, 61 mg), Cs2CO3 (2
equiv, 163 mg), [Pd(allyl)Cl]2 (2.5 mol %, 2 mg), and Di-Ad-
BrettPhos (10 mol %, 16 mg) in 2-methyl-2-butanol (0.5 M, 0.5 mL)
was stirred under an argon atmosphere for 20 h at 100 °C. The
mixture was diluted with CH2Cl2, filtered through Celite pad, and
concentrated in vacuo. The residue was purified by flash column
chromatography on silica gel (n-hexane/EtOAc = 1:1, Rf = 0.50) to
give 4-benzamido-1-methyl-2-(4-methylphenyl)imidazole (14) in 96%
yield (70 mg) as a brown solid: mp 85.4−93.1 °C; IR (KBr) 1657,
7.2 Hz, 3H), 3.67 (s, 3H), 4.42 (q, J = 7.2 Hz, 2H), 7.51−7.57 (m,
5H), 7.91−7.93 (m, 1H), 7.99−8.01 (m, 1H); 13C NMR (CDCl3) δ
14.4, 35.2, 61.1, 121.5, 124.0, 125.0, 125.1, 126.3, 126.6, 127.5, 128.6,
129.2, 130.8, 132.0, 133.6, 150.7, 160.1; MS (EI) m/z (relative
intensity %) 360 (100, M+ + 2), 358 (91, M+); HRMS (EI) exact mass
calcd for C17H1579BrN2O2 (M+) 358.0317; found 358.0318.
5-Ethoxycarbonyl-1-methyl-4-(4-methylphenyl)-2-(1-
naphthyl)imidazole (18).1f To a solution of 4-bromo-5-ethoxy-
carbonyl-1-methyl-2-(1-naphthyl)imidazole (17) (1.1 mmol, 382 mg)
in DMF were added 4-methylphenylboronic acid (1.5 equiv, 216 mg),
KOH (2 equiv, 118 mg), Pd(dba)2 (10 mol %, 61 mg), and Pt-Bu3·
HBPh4 (20 mol %, 111 mg) under an argon atmosphere, and the
mixture was stirred at 80 °C for 8.5 h. The resulting mixture was
filtered through a Celite pad and concentrated in vacuo. The residue
was purified by GPC to give 5-ethoxycarbonyl-1-methyl-4-(4-methyl-
phenyl)-2-(1-naphthyl)imidazole (18) in 70% yield (285 mg) as a
1
1546, 1462, 826, 731, 694 cm−1; H NMR (CDCl3) δ 2.39 (s, 3H),
3.73 (s, 3H), 7.25 (d, J = 7.6 Hz, 2H), 7.41−7.52 (m, 5H), 7.55 (s,
1H), 7.92 (d, J = 7.6 Hz, 2H), 9.35 (br s, 1H); 13C NMR (CDCl3) δ
21.4, 34.9, 110.3, 125.8, 127.3, 128.5, 128.8, 129.6, 131.9, 133.5, 136.2,
139.6, 143.1, 164.3; MS (EI) m/z 291 (M+); HRMS (EI) exact mass
calcd for C18H17N3O 291.1372; found 291.1378.
4-Bromo-2-(4-ethoxycarbonylphenyl)-5-formyl-1-methyl-
imidazole (15). A solution of i-PrMgCl·LiCl in THF (1.2 M, 1.1
equiv, 0.50 mL) was added dropwise to a solution of 4,5-dibromo-2-
(4-ethoxycarbonylphenyl)-1-methylimidazole (8k) (0.55 mmol, 215
mg) in anhydrous THF (2.2 mL) under an argon atmosphere at −40
°C. The mixture was stirred for 1.5 h, and DMF (8 mL) was then
added. The reaction mixture was stirred at room temperature for 30
min and quenched with H2O. The crude mixture was extracted with
EtOAc. The organic layer was dried over Na2SO4, filtered, and
concentrated in vacuo. The residue was purified by flash column
1
colorless oil: n-hexane/EtOAc = 4:1, Rf = 0.44; H NMR (CDCl3) δ
1.27 (t, J = 7.2 Hz, 3H), 2.38 (s, 3H), 3.69 (s, 3H), 4.31 (q, J = 7.2 Hz,
2H), 7.21 (d, J = 8.1 Hz, 2H), 7.49−7.66 (m, 5H), 7.69 (d, J = 8.1 Hz,
2H), 7.91−7.93 (m, 1H), 8.00 (d, J = 8.1 Hz, 1H).
1-Methyl-4-(4-methylphenyl)-2-(1-naphthyl)-5-((2-thiazolyl)-
aminocarbonyl)imidazole (20).1f To a solution of 5-ethoxy-
carbonyl-1-methyl-4-(4-methylphenyl)-2-(1-naphthyl)imidazole (18)
(0.17 mmol, 63 mg) in EtOH (10 mL) was added 1 M NaOHaq
(20 equiv, 3.4 mL), and the mixture was stirred at 80 °C for 4 h. The
reaction mixture was neutralized by addition of 5% HCl(aq) and
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The Journal of Organic Chemistry
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extracted with CH2Cl2. The organic layer was dried over Na2SO4 and
concentrated in vacuo. To a solution of the crude product in DMF
(3.4 mL) were added 2-aminothiazole (19) (2 equiv, 34 mg), 1-ethyl-
3-(3-(dimethylamino)propyl)carbodiimide hydrochloride (3 equiv, 98
mg), and 1-hydroxybenzotriazole (4 equiv, 92 mg) and stirred at room
temperature overnight. The mixture was diluted with EtOAc and
washed with H2O twice. The organic layer was dried over Na2SO4 and
concentrated in vacuo. The residue was purified by flash column
chromatography on silica gel (n-hexane/EtOAc = 4:1, Rf = 0.33) to
give 1-methyl-4-(4-methylphenyl)-2-(1-naphthyl)-5-((2-thiazolyl)-
aminocarbonyl)imidazole (20) in 63% yield (45 mg) as a colorless
solid: 1H NMR (CDCl3) δ 2.36 (s, 3H), 3.77 (s, 3H), 7.26 (d, J = 8.1
Hz, 2H), 7.40−7.45 (m, 2H), 7.52−7.64 (m, 3H), 7.69−7.74 (m, 2H),
7.87 (d, J = 8.1 Hz, 2H), 7.94−7.97 (m, 1H), 8.03−8.08 (m, 2H).
Ellman, J. A. Chem. Rev. 2010, 110, 624. (i) Satoh, T.; Miura, M.
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1074.
(6) For a review of C−H bond functionalization with Pd−nitrogen-
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2013, 2, 624.
(7) Joo, J. M.; Toure, B. B.; Sames, D. J. Org. Chem. 2010, 75, 4911.
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You, J. Chem.Eur. J. 2012, 18, 10830. (b) Yamamoto, T.; Muto, K.;
Komiyama, M.; Canivet, J.; Yamaguchi, J.; Itami, K. Chem.Eur. J.
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2011, 17, 6904. (d) Do, H.-Q.; Kashif Khan, R. M.; Daugulis, O. J. Am.
Chem. Soc. 2008, 130, 15185. (e) Bellina, F.; Calandri, C.; Cauterccio,
S.; Rossi, R. Tetrahedron 2007, 63, 1970. For direct arylation at C5,
see: (f) Liu, X.-W.; Shi, J.-L.; Yan, J.-X.; Wei, J.-B.; Peng, K.; Dai, L.; Li,
C.-G.; Wang, B.-Q.; Shi, Z.-J. Org. Lett. 2013, 15, 5774. (g) Kumar, P.
V.; Lin, W.-S.; Shen, J. S.; Nandi, D.; Lee, H. W. Organometallics 2011,
30, 5160. (h) Bellina, F.; Cauteruccio, S.; Fiore, A. D.; Rossi, R. Eur. J.
Org. Chem. 2008, 5436. (i) Parisien, M.; Valette, D.; Fagnou, K. J. Org.
Chem. 2005, 70, 7578. For switchable direct arylation at C2 and C5,
see: (j) Tamba, S.; Okuba, Y.; Tanaka, S.; Moriguchi, D.; Mori, A. J.
Org. Chem. 2010, 75, 6998. (k) Strotman, N. A.; Chobanian, H. R.;
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ASSOCIATED CONTENT
■
S
* Supporting Information
1
1
Copies of H and 13C NMR for all new compounds and H
NMR for known compounds. This material is available free of
charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Authors
*E-mail: fshiba@gifu-u.ac.jp.
*E-mail: mtoshi@gifu-u.ac.jp.
(9) (a) Recnick, L.-M.; Hameid, M. A. E.; Haider, M.; Schnurch, M.;
̈
Notes
Mihovilovic, M. D. Synthesis 2013, 45, 1387. (b) Strotman, N. A.;
Chobanian, H. R.; He, J.; Guo, Y.; Dormer, P. G.; Jones, C. M.; Steves,
J. J. Org. Chem. 2010, 75, 1733.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
(10) (a) Liu, B.; Wu, N.; Li, M.; You, J.; Lan, J. Chem.Eur. J. 2012,
18, 1599. (b) Huang, J.; Chan, J.; Chen, Y.; Borths, C. J.; Baucom, K.
D.; Larsen, R. D.; Faul, M. M. J. Am. Chem. Soc. 2010, 132, 3674.
(c) Tamba, S.; Okubo, Y.; Tanaka, S.; Monguch, D.; Mori, A. J. Org.
Chem. 2010, 75, 6998. (d) Roger, J.; Doucet, H. Org. Biomol. Chem.
2008, 6, 169. (e) Chiong, H. A.; Dagulis, O. Org. Lett. 2007, 9, 1449.
(11) (a) Shibahara, F.; Yamauchi, T.; Yamaguchi, E.; Murai, T. J. Org.
Chem. 2012, 77, 8815. (b) Shibahara, F.; Yamaguchi, E.; Murai, T. J.
Org. Chem. 2011, 76, 2680. (c) Yamaguchi, E.; Shibahara, F.; Murai, T.
Chem. Lett. 2011, 40, 939. (d) Shibahara, F.; Yamaguchi, E.; Murai, T.
Chem. Commun. 2010, 46, 2471.
(12) Tani, S.; Uehara, T. N.; Yamaguchi, J.; Itami, K. Chem. Sci. 2014,
5, 123.
(13) (a) Blanchot, M.; Candito, D. A.; Larnaud, F.; Lautens, M. Org.
Lett. 2011, 13, 1486. (b) Larivee, A.; Mousseau, J. J.; Charette, A. B. J.
́
Am. Chem. Soc. 2008, 130, 52. (c) Verrier, C.; Martin, T.; Hoarau, C.;
Marsals, F. J. Org. Chem. 2008, 73, 7383. (d) Harayama, T.; Hori, A.;
Serban, G.; Morikami, Y.; Matsumoto, T.; Abe, H.; Takeuchi, Y.
Tetrahedron 2004, 60, 1064. (e) Pivsa-Art, S.; Satoh, T.; Kawamura, Y.;
Miura, M.; Nomura, M. Bull. Chem. Soc. Jpn. 1998, 71, 467.
We are grateful to have been supported by a Grant-in-Aid for
Scientific Research on InnovativeAreas “Molecular Activation
Directed toward Straightforward Synthesis”.
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