Iridium-Catalyzed Direct Amidation of Imidazoles at the C-2 Position with Isocyanates in the Presence of Hydrosilanes Leading to Imidazole-2-Carboxamides

Article abstract of DOI:10.1055/a-1375-5283

Regioselective coupling reaction of N -substituted imidazoles with isocyanates in the presence of a stoichiometric amount of hydrosilanes catalyzed by Ir ₄(CO) ₁₂to give imidazole-2-carboxamides is reported. Imidazoles bearing an (O -silyl)carboximidate group at the 2-position appear to be initially formed in the reaction; these are then hydrolyzed to the final products in situ. The addition of the hydrosilane was essential for the catalytic reaction to proceed. Substituents on the imidazole ring had no effect on the reaction, except for certain bulky substituents such as ^tBu and Ph groups at the 4-position. Triazoles such as 4-methyl-4 H -1,2,4-triazole and 1-methyl-1 H -1,2,4-triazole were also applicable to this C-H amidation, and the latter reaction proceeded regioselectively at the carbon atom between the sp ³and sp ²nitrogen atoms of the ring, and not between the two sp ²nitrogen atoms.

Full text of DOI:10.1055/a-1375-5283

SYNTHESIS
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart
2021, 53, A–H
special topic
A
Bond Activation – in Honor of Prof. Shinji
Y. Fukumoto et al.
Special Topic
Synthesis
Iridium-Catalyzed Direct Amidation of Imidazoles at the C-2 Posi-
tion with Isocyanates in the Presence of Hydrosilanes Leading to
Imidazole-2-Carboxamides
Yoshiya Fukumoto*
R'
N
C
O
N
N
Motohiro Shiratani
Hikaru Noguchi
Naoto Chatani
cat. Ir4(CO)12
HSR''3
H
N
+
H
R'
N
R
N
R
O
N
Department of Applied Chemistry, Faculty of Engineering,
Osaka University, Suita, Osaka 565-0871, Japan
fukumoto@chem.eng.osaka-u.ac.jp
N
R'
OSiR''3
N
R
Dedicated to Professor Shinji Murai for his great contribution to
the chemistry of catalytic C–H bond activation.
initial product
Published as part of the Special Topic
Bond Activation – in Honor of Prof. Shinji Murai
Corresponding Author
Received: 11.12.2020
Accepted after revision: 27.01.2021
Published online: 27.01.2021
thoxyiodobenzene, catalyzed by a palladium complex, was
reported.5 Phenylglyoxylic acid6 and N-aroylsaccharins7
were also used in place of the combination of CO and ArI in
palladium-catalyzed C–H aroylation, both of which also af-
forded 2-aroylimidazoles. Intramolecular coupling using
isocyanides in place of CO leading to the formation of ring-
fused imidazoles was also reported.8 Nolan and co-workers
developed the Au-catalyzed carboxylation of imidazole C–H
bonds at the C-2 position with CO2 to produce imidazole-2-
carboxylic acids.9 Daugulis reported the selective, CuCN cat-
alyzed C–H cyanation of imidazoles with NaCN in the pres-
ence of a strong base.10
In 2002, we reported the regioselective C–H functional-
ization of imidazole derivatives with aldehydes at the C-2
position, catalyzed by Ir4(CO)12 in the presence of hydrosila-
nes, leading to the production of 2-[2-(siloxy)alkyl]imidaz-
oles.11 Since that report, the direct introduction of mixed al-
kyl-silyl acetals into imidazole derivatives at the 2-position
using formates appeared, one product of which was hydro-
lyzed under acidic conditions to form 2-formylimidazoles.12
The addition of hydrosilanes was found to be crucial for
both reactions to proceed. We report herein the direct C2-
functionalization of imidazoles with isocyanates13 to give
imidazole-2-carboxamides, catalyzed by Ir4(CO)12 with a
stoichiometric amount of hydrosilanes as a co-reactant
(Scheme 1).14 As is discussed below, the fact that the pres-
ent reaction also required the addition of a stoichiometric
amount of hydrosilane indicates that an imidazole 2-(O-si-
lyl)carboximidate A is probably formed initially, and subse-
quently hydrolyzed in situ to the final product. The imidaz-
ole-2-carboxamide moiety is contained in a number of bio-
logically active molecules, such as DNA-binding ligands
Lexitropsins,15 a colony-stimulating factor 1 receptor (CSF-
1R) inhibitor Edicotinib,16 and a direct renin inhibitor
Imarikiren17 (Scheme 2).
DOI: 10.1055/a-1375-5283; Art ID: ss-2020-f0637-st
Abstract Regioselective coupling reaction of N-substituted imidaz-
oles with isocyanates in the presence of a stoichiometric amount of hy-
drosilanes catalyzed by Ir4(CO)12 to give imidazole-2-carboxamides is re-
ported. Imidazoles bearing an (O-silyl)carboximidate group at the 2-
position appear to be initially formed in the reaction; these are then hy-
drolyzed to the final products in situ. The addition of the hydrosilane
was essential for the catalytic reaction to proceed. Substituents on the
imidazole ring had no effect on the reaction, except for certain bulky
substituents such as tBu and Ph groups at the 4-position. Triazoles such
as 4-methyl-4H-1,2,4-triazole and 1-methyl-1H-1,2,4-triazole were also
applicable to this C–H amidation, and the latter reaction proceeded re-
gioselectively at the carbon atom between the sp3 and sp2 nitrogen at-
oms of the ring, and not between the two sp2 nitrogen atoms.
Key words C–H bond functionalization, imidazoles, isocyanates, hy-
drosilanes, iridium catalysis, imidazole 2-carboxamides
The development of novel methods for the regioncon-
trolled synthesis of substituted imidazole derivatives is of
great importance, since it can be used for the construction
of highly substituted and functionalized target molecules.1
Among the large number of such reactions, transition-met-
al-catalyzed C–H functionalization has proven to be a pow-
erful tool over the past few decades. The focus of this study
was mainly on the regioselective C–H mono- and multi-
arylation with aryl halides or pseudohalides catalyzed by
various transition-metal complexes, especially, palladium
complexes.2 Only a limited number of reports have ap-
peared on the introduction of carbonyl and the related
groups into imidazole C–H bonds.3 Our group developed
the Ru3(CO)12-catalyzed regioselective acylation of an imid-
azole ring with CO and alkenes.4 The direct C–H aroylation
of imidazole derivatives at the 2-poition with CO and p-me-
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–H
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
Y. Fukumoto et al.
Special Topic
Synthesis
rently unclear (entry 5). In any case, two hydrogen atoms at
the 2-position of the imidazole ring and on silicon atom in
the hydrosilane would be released as H2, although there is
no direct evidence for this.
R'
N
C
O
N
N
cat. Ir4(CO)12
H
N
+
R'
HSiR''3
N
N
R
O
R
N
Table 1 Optimization of the Reaction Conditionsa
N
R'
OSiR''3
N
R
C6H13
N
C
O
N
N
A
cat. Ir4(CO)12
H
N
initial product
+
C6H13
HSiEt2Me
DMAD
N
N
Scheme 1 General scheme for the Ir4(CO)12-catalyzed reaction of imid-
O
Me
Me
azoles with isocyanates in the presence of hydrosilanes
1a
NH2
HN
Entry
Deviation from the previous conditions
Yield (%)
NH
1
2
3
4
5
none
75
0
NH
H2N
NH
without Ir4(CO)12
without HSiEt2Me
HSiEt2Me 0.1 mol
without DMAD
O
X
H
0
N
N
X'
X = N,
X' = CH Lexitropsin A
8
O
NH
Me
Lexitropsin B
X = CH, X' = N
N
74
Lexitropsin AB
X = N,
X' = N
O
Me
a Reaction conditions: 1-methylimidazole (1 mmol), hexyl isocyanate
(1 mmol), Ir4(CO)12 (0.02 mmol), HSiEt2Me (2 mmol), and DMAD
(0.16 mmol), in toluene (3 mL) at 110 °C for 6 h.
O
HN
N
We next examined the use of some hydrosilanes in the
reaction of 1-methylimidazole with hexyl isocyanate (Table 2).
As is the case with HSiEt2Me (entry 1), other trialkyl-substi-
tuted hydrosilanes, such as HSiEt3 (entry 2) and HSitBuMe2
(entry 3) also reacted to give 1a. However, the presence of a
bulkier substituent at the silicon gave a lower product yield.
While HSiMe2Ph also afforded 1a in 50% yield (entry 4), the
use of alkoxy-substituted hydrosilane (entry 5) or dihydro-
silane (entry 6) resulted in the starting 1-methylimidazole
being completely recovered. Unfortunately, A was not ob-
served in any of the cases, either by 1H NMR or GC/MS,
probably due to its susceptibility to hydrolysis. However,
the reaction required the addition of a stoichiometric
amount of hydrosilane for a satisfactory yield of product to
be obtained. In our previous reports, in which aldehydes
and formates were used in place of isocyanates, we ob-
tained products bearing the silyl group on the oxygen atom.
Based on these results, A is likely to be formed in the pres-
ent reaction.
A variety of imidazole derivatives were subjected to
these optimized conditions, and the results are summa-
rized in Table 3. Imidazole derivatives substituted with ben-
zyl, methoxymethyl, and phenyl groups at the nitrogen re-
acted with hexyl isocyanate to give the corresponding imid-
azole-2-carboxamides 1b–d (entries 2–4). In the case of N-
phenylimidazole, an elevated reaction temperature of 160
°C was required, since the reaction at 110 °C proceeded
slowly to afford 1d in 22% yield. Imidazoles bearing a bulky
substituent such as tert-butyl and phenyl groups at the 4-
position did not participate in the coupling reaction even at
160 °C (entries 5 and 6), while such groups at the 5-posi-
tion provided the products 1e and 1f (entries 7 and 8). On
N
O
H
N
N
NC
N
N
N
H
N
O
O
O
OMe
Edicotinib
Imarikiren
Scheme 2 Some biologically active molecules containing an imidazole-
2-carboxamide moiety
We initially examined the reaction of 1-methylimidaz-
ole (1 mmol) with hexyl isocyanate (1 mmol) and HSiEt2Me
(2 mmol) in the presence of Ir4(CO)12 (0.02 mmol) and
DMAD (dimethyl acetylenedicarboxylate, 0.16 mmol) in
toluene (3 mL) at 110 °C for 6 h, which are the conditions
generally used for aldehydes, and the desired product 1a
was obtained in 75% isolated yield (Table 1, entry 1). While
Papadopoulos reported that imidazoles coupled with isocy-
anates in nitrobenzene under reflux (bp 211 °C),18 in the
absence of Ir4(CO)12 (entry 2) or HSiEt2Me (entry 3) at the
lower temperature of 110 °C, neither of the reactions pro-
ceeded at all. The reaction using 0.1 equivalent of HSiEt2Me
resulted in a significant decrease in the product to 8% (entry
4). Other metal carbonyls, such as Mn2(CO)10, Fe3(CO)12,
Ru3(CO)12, and Co2(CO)8, showed no catalytic activity for the
present reaction. In our previous reports on the reaction
with aldehydes11 and formates,12 the addition of a catalytic
amount of DMAD, probably as a ligand, and not a hydrogen
scavenger, was found to dramatically improve the product
yields. On the other hand, the present reaction was not af-
fected by the addition of DMAD, in terms of the product
yield of 1a, although the reason for this difference is cur-
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–H

C
Y. Fukumoto et al.
Special Topic
Synthesis
Table 2 Screening of Hydrosilane for the Reaction of 1-Methylimidaz-
Table 3 Coupling Reaction of Azoles with Hexyl Isocyanatea
ole with Hexyl Isocyanatea
C6H13
N
C
O
N
N
R'
R'
cat. Ir4(CO)12
HSiEt2Me
H
C6H13
+
N
N
C
O
N
N
cat. Ir4(CO)12
hydrosilane
C6H13
H
N
R
N
R
+
N
O
C6H13
N
N
O
Me
Me
1a–m
1a
Entry Azole
1
Product
R
1
Yield
(%)
Entry
Hydrosilane
Yield (%)
Me
Bn
1a
1b
1c
1d
74b
1
2
3
4
5
6
HSiEt2Me
HSiEt3
74
51
29
50
0
N
N
H
2
3
4
5
68
58
52d
0d
N
C6H13
N
R
N
R
CH2OMe
Ph
HSitBuMe2
HSiPhMe2
HSi(OMe)3
H2SiPh2
O
tBu
R
R
N
N
H
0
N
0d
C6H13
6
Ph
N
N
a Reaction conditions: 1-methylimidazole (1 mmol), hexyl isocyanate
(1 mmol), hydrosilane (2 mmol), and Ir4(CO)12 (0.02 mmol) in toluene
(3 mL) at 110 °C for 6 h.
O
Me
Me
7
tBu
Ph
1e
1f
45
68
70
55
N
N
H
N
the other hand, a small methyl group did not significantly
affect the reaction, since 1,4,5-trimethylimidazole afforded
the tetrasubstituted imidazole 1i (entry 11). Substituents
such as p-methoxy (entry 9) and p-trifluoromethyl groups
(entry 10) on the phenyl ring at the 5-position of the imid-
azole had no effect on the reaction. N-Methylbenzimidazole
and imidazo[1,5-a]pyridine, which are imidazoles fused to
a benzene ring, also participated in the catalytic reaction to
give 1j and 1k, respectively (entries 12 and 13). Triazoles
were also applied to the regioselective reaction. When the
symmetric 4-methyl-4H-1,2,4-triazole was used as sub-
strate, the monoamidated triazole 1l was obtained as a ma-
jor product along with diamidated triazole 1l′ in 10% yield
(entry 14). The latter was also produced in 75% as the sole
product in the reaction when an excess amount of hexyl
isocyanate and HSiEt2Me were used (see Experimental Sec-
tion). The regioselective amidation of 1-methyl-1H-1,2,4-
triazole occurred at the carbon atom between the sp3 and
sp2 nitrogen atoms of the ring to afford 1m in 83% yield (en-
try 15).19 However, 1-methyl-1,2,3,4-tetrazole remained in-
tact under the reaction conditions. Other 1,3-azoles such as
benzoxazole and benzothiazole were also unreactive in the
present catalytic reaction.
8
R
R
C6H13
N
N
9
4-MeOC6H4 1g
O
Me
N
Me
N
10
4-F3CC6H4
1h
1i
H
11
12
N
40
67
C6H13
N
N
O
Me
Me
N
N
H
N
1j
C6H13
N
N
O
Me
Me
N
N
H
N
13
14
15
1k
1l
69b
C6H13
N
N
O
N
N
N N
H
N
70b,e
C6H13
N
N
O
Me
N
Me
N
N
H
N
N
N
1m
83b
C6H13
N
O
Me
Me
We explored some isocyanates for the reaction with 1-
methylimidazole and HSiEt2Me in the presence of Ir4(CO)12
and results were summarized in Table 4. While hexyl isocy-
anate (entry 1) and cyclohexyl isocyanate (entry 2) reacted
under the standard reaction conditions, the reaction of
bulkier adamantyl isocyanate required more severe reac-
tion conditions such as a larger amount of the Ir4(CO)12 cat-
alyst at 0.04 mmol and a higher reaction temperature of
160 °C (entry 3). An ester group itself was compatible with
this reaction (entry 5). The reaction of phenyl isocyanate
produced 6a in 24% yield, along with the formation of the
a Reaction conditions: azole (1 mmol), hexyl isocyanate (1 mmol), Ir4(CO)12
(0.04 mmol), and HSiEt2Me (2 mmol), in toluene (3 mL) at 110 °C for 15 h.
b Ir4(CO)12 (0.02 mmol).
c For 6 h.
d At 160 °C.
e 2,5-Bisamidated product 1l′ was also obtained in 10%.
reduction product of phenyl isocyanate, formanilide, in 48%
yield (entry 6). However, the reaction was retarded com-
pletely when electron-withdrawing groups are directly at-
tached to the nitrogen atom (entries 7 and 8).
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–H

D
Y. Fukumoto et al.
Special Topic
Synthesis
Table 4 Coupling Reaction of 1-Methylimidazole with Isocyanatesa
N
N
N
R'
OSiR''3
HSiR''3
H
N
R
N
R
R
N
C
O
N
N
Ir SiR''3
cat. Ir4(CO)12
HSiEt2Me
H
N
Ir
I
+
A
SiR''3
N+
R
N
N
VI
O
Me
Me
H
Ir–
H
R'
N
N
1a–6a
N
hydrolysis
N
R
Ir
OSiR''3
II
N
R
Entry
R
Time (h)
Product
Yield (%)
V
H2
H
1
3
3
4
5
6
7
8
C6H13
Cy
6
1a
2a
3a
4a
5a
6a
74
83
80b,c
66
66d
24
0
R'
SiR''3
N
N
N
C
O+
R'
N
R
N
15
15
10
15
6
Ir–
O
N
Ir
Ad
N
R
R''3Si
R
Bn
IV
R'
III
N
C
O
CH2CO2Et
Ph
CO2Et
Ts
15
15
Scheme 3 Proposed reaction mechanism
0
a Reaction conditions: 1-methylimidazole (1 mmol), isocyanate (1 mmol),
Ir4(CO)12 (0.02 mmol), and HSiEt2Me (2 mmol), in toluene (3 mL) at 110 °C.
b Ir4(CO)12 (0.04 mmol).
SiR''3
R'
R'
N
N
N
N
N
C O
SiR''3
c For 160 °C.
Ir
Ir
Ir
OSiR''3
N
R
N
R
N
R
d Isocyanate (1.5 mmol).
III
VII
V
A proposed reaction mechanism is shown in Scheme 3,
although it is somewhat speculative at the present stage.
From the fact that certain types of bulky substituents at the
4-position on the imidazole ring retarded the reaction,
probably due to steric factors, the sp2 nitrogen atom in the
imidazole ring would not be a spectator but, rather, be a
participant in the catalytic reaction. One explanation in-
volves the assumption that the imidazole acts as a base by
accepting a silyl group from I to form a silylimidazolium
species II, which is accompanied by the formation of an an-
ionic hydridoiridium species. The abstraction of an acidic
hydrogen on the C-2 carbon atom by the anionic hydridoir-
idium species then gives a N-silyl-substituted N-heterocy-
clic carbene species III,20 along with the generation of H2.
The transfer of the silyl group in III to the isocyanate oxy-
gen atom occurs, followed by attack of the iridium center in
the resulting IV on the carbon atom in the silylated isocya-
nate to form V. Reductive elimination from V affords the
initial product A, which is hydrolyzed to the final product.
Finally, oxidative addition of a hydrosilane to VI results in
the regeneration of I. As an alternative, the 1,3-transfer of
the silyl group in III from the nitrogen atom to the iridium
center to form VII and the subsequent insertion of the C=O
bond in the isocyanate into the Ir–Si bond to give V could
possibly be involved in the catalytic cycle (Scheme 4). Fur-
ther experiments will be required for the elucidation of the
reaction mechanism, including other possible scenarios.
In summary, we report herein the Ir4(CO)12-catalyzed
regioselective coupling reaction of N-substituted imidaz-
oles with isocyanates in the presence of hydrosilanes, lead-
ing to the production of imidazole-2-carboxamides. Imid-
azole 2-(O-silyl)carboximidates appear to be initially
Scheme 4 An alternative pathway from III to V via the formation of VII
formed in the reaction, and are hydrolyzed to the final
products in situ. The addition of a stoichiometric amount of
hydrosilanes was crucial for the catalytic reaction to pro-
ceed. Substituents on the imidazole ring had negligible ef-
fects on the reaction, except for certain types of bulky
substituents such as tert-butyl and phenyl groups at the 4-
position. The reaction of 1,2,4-triazole proceeded regio-
selectively at the carbon atom between the sp3 and sp2 ni-
trogen atoms of the ring, and not between two sp2 nitrogen
atoms. Some functional groups such as an N,O-acetal, an
ether, a trifluoromethyl, and an ester groups were tolerated
under the reaction conditions used.
IR spectra were obtained with a Horiba FT-720 spectrophotometer
using the transmission method; absorption data are reported in re-
ciprocal centimeters. 1H NMR and 13C NMR spectra were recorded
with a JEOL JNM-ECS400 spectrometer using CDCl3 as the solvent.
Data are reported as follows: chemical shift in ppm (), multiplicity (s
= singlet, d = doublet, t = triplet, q = quartet, quint = quintet, m = mul-
tiplet, br = broad singlet, c = complex), coupling constant (Hz), and in-
tegration. Mass spectra (MS) were obtained with a Shimadzu GCMS-
QP 2010 instrument with an ionization voltage of 70 eV. Elemental
analyses and high-resolution mass spectra (HRMS) were performed
by the Elemental Analysis Section of Osaka University. Analytical GC
was carried out with a Shimadzu GC-2014 gas chromatograph,
equipped with a flame ionization detector. GPC was carried out with
a JAI LC-908 equipped with a RI detector, using chloroform as the sol-
vent. Flash column chromatography was performed with Silicycle
SiliaFlash F60 (230–400 mesh). Preparative TLC was performed with
Wako-gel B-5F. Liquid reagents such as isocyanates except 1-adaman-
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–H

E
Y. Fukumoto et al.
Special Topic
Synthesis
tyl isocyanate, hydrosilanes, and 1-methylimidazole, are commercial-
ly available and were purified by distillation prior to use. Solid re-
agents, including 1-adamantyl isocyanate, 1-methylbenzimidazole,
and Ir4(CO)12, were purchased and used without further purification.
1-Benzylimidazole,21 1-methoxymethylimidazole,22 1-phenylimidaz-
ole,23 4-tert-butyl-1-methylimidazole,24 4-phenyl-1-methylimidaz-
ole,25 5-tert-butyl-1-methylimidazole,26 5-phenyl-1-methylimidaz-
ole,27 5-(4-methoxy)phenyl-1-methylimidazole,27 5-(4-trifluoro-
methyl)phenyl-1-methylimidazole,27 1,4,5-trimethylimidazole,28 4-
methyl-4H-1,2,4-triazole,29 and 1-methyl-1H-1,2,4-triazole,30 were
prepared by following reported procedures.
IR (neat): 1666 cm–1
.
1H NMR (400 MHz, CDCl3):  = 7.46 (br, 1 H), 7.20 (s, 1 H), 7.06 (s, 1 H),
5.88 (s, 2 H), 3.36–3.41 (m, 5 H), 1.60 (quint, J = 7.2 Hz, 2 H), 1.28–1.41
(m, 6 H), 0.89 (t, J = 6.6 Hz, 3 H).
13C NMR (100 MHz, CDCl3):  = 158.8, 139.2, 128.0, 123.3, 77.9, 56.5,
39.0, 31.4, 29.4, 26.6, 22.5, 4.0.
MS (EI): m/z (%) = 239 (9) [M]+, 196 (77), 194 (14), 168 (25), 140 (18),
139 (43), 138 (58), 126 (21), 124 (17), 112 (29), 109 (68), 102 (16),
100 (100), 98 (35), 96 (18), 95 (52), 94 (15), 83 (10), 82 (87), 81 (31),
74 (14), 69 (31), 68 (23), 56 (12), 55 (14), 54 (15), 53 (11).
Anal. Calcd for C12H21N3O2: C, 60.23; H, 8.84; N, 17.56. Found: C,
60.16; H, 8.78; N, 17.67.
General Procedure
A 10-mL reaction flask, equipped with a reflux condenser, was dried
for 1 h in an oven at 150 °C and then purged with N2. After cooling to
room temperature, Ir4(CO)12 (22.0 mg, 0.02 mmol), the hydrosilane (2
mmol), toluene (3 mL), the isocyanate (1 mmol), and the azole (1
mmol) were placed in the flask. The reaction mixture was heated at
reflux in an oil bath. After cooling to room temperature, the volatiles
were removed in vacuo. The residue was passed through a silica-gel
column to isolate the desired azole-2-carboxyamide. An analytically
pure sample was obtained by GPC followed by bulb-to-bulb distilla-
tion.
N-Hexyl-1-phenyl-1H-imidazole-2-carboxyamide (1d)
Yield: 141 mg (52%); colorless oil; Rf = 0.10 (hexane/EtOAc = 4:1).
Bulb-to-bulb distillation (oven temp.): 170 °C/1 mmHg.
IR (neat): 1672 cm–1
.
1H NMR (400 MHz, CDCl3):  = 7.35–7.46 (m, 6 H), 7.13 (d, J = 2.7 Hz, 2
H), 3.31 (q, J = 6.9 Hz, 2 H), 1.55 (quint, J = 7.3 Hz, 2 H), 1.28–1.37 (m,
6 H), 0.87 (t, J = 6.9 Hz, 3 H).
13C NMR (100 MHz, CDCl3):  = 157.8, 139.4, 138.2, 128.5, 128.4,
127.8, 125.9, 125.6, 39.0, 31.3, 29.4, 26.5, 22.4, 13.9.
N-Hexyl-1-methyl-1H-imidazole-2-carboxamide (1a)
Yield: 155 mg (74%); colorless oil; Rf = 0.10 (hexane/EtOAc = 4:1).
Bulb-to-bulb distillation (oven temp.): 140 °C/8 mmHg.
MS (EI): m/z (%) = 271 (6) [M]+, 200 (30), 172 (22), 171 (100), 158 (19),
145 (12), 144 (53), 117 (37), 116 (38), 106 (15), 100 (45), 91 (14), 90
(15), 89 (16), 77 (36), 51 (15).
IR (neat): 1664 cm–1
.
Anal. Calcd for C16H21N3O: C, 70.82; H, 7.80; N, 15.49. Found: C, 70.53;
H, 7.76; N, 15.27.
1H NMR (400 MHz, CDCl3):  = 7.42 (br, 1 H), 6.99 (s, 1 H), 6.95 (s, 1 H),
4.06 (s, 3 H), 3.37 (q, J = 6.9 Hz, 2 H), 1.59 (quint, J = 7.3 Hz, 2 H), 1.28–
1.47 (m, 6 H), 0.89 (t, J = 6.6 Hz, 3 H).
13C NMR (100 MHz, CDCl3):  = 159.1, 139.1, 127.3, 125.3, 39.0, 35.6,
31.5, 29.6, 26.6, 22.5, 14.0.
5-tert-Butyl-N-hexyl-1-methyl-1H-imidazole-2-carboxamide (1e)
Yield: 119 mg (45%); colorless oil; Rf = 0.10 (hexane/EtOAc = 4:1).
IR (neat): 1662 cm–1
.
MS (EI): m/z (%) = 209 (2) [M]+, 138 (28), 110 (20), 109 (100), 100 (30),
96 (15), 82 (38), 81 (12), 54 (16).
1H NMR (400 MHz, CDCl3):  = 7.48 (br, 1 H), 6.77 (s, 1 H), 4.17 (s, 3 H),
3.36 (q, J = 6.7 Hz, 2 H), 1.58 (quint, J = 7.2 Hz, 2 H), 1.28–1.43 (m, 15
H), 0.88 (t, J = 6.9 Hz, 3 H).
Anal. Calcd for C11H19N3O: C, 63.13; H, 9.15; N, 20.08. Found: C, 62.84;
H, 9.04; N, 20.14.
13C NMR (100 MHz, CDCl3):  = 159.7, 144.5, 140.0, 123.9, 39.0, 34.3,
31.5, 31.1, 29.6, 29.4, 26.6, 22.5, 14.0.
MS (EI): m/z (%) = 265 (11) [M]+, 250 (18), 222 (12), 194 (39), 166 (22),
165 (94), 152 (19), 149 (13), 139 (15), 138 (100), 123 (27), 122 (27),
100 (23), 95 (10), 80 (12), 67 (12), 57 (17), 55 (13).
1-Benzyl-N-hexyl-1H-imidazole-2-carboxamide (1b)
Yield: 194 mg (68%); white solid; mp 81.0–81.5 °C; Rf = 0.17 (hex-
ane/EtOAc = 4:1).
Bulb-to-bulb distillation (oven temp.): 170 °C/0.9 mmHg.
HRMS (EI): m/z [M]+ calcd for C15H27N3O: 265.2154; found: 265.2151.
IR (neat): 1664 cm–1
.
N-Hexyl-1-methyl-5-phenyl-1H-imidazole-2-carboxamide (1f)
Yield: 194 mg (68%); colorless oil; Rf = 0.13 (hexane/EtOAc = 8:1).
1H NMR (400 MHz, CDCl3):  = 7.52 (br, 1 H), 7.22–7.35 (m, 5 H), 7.02
(s, 1 H), 6.97 (s, 1 H), 5.75 (s, 2 H), 3.38 (q, J = 6.7 Hz, 2 H), 1.60 (quint,
J = 7.3 Hz, 2 H), 1.28–1.41 (m, 6 H), 0.88 (t, J = 7.1 Hz, 3 H).
IR (neat): 1666 cm–1
.
13C NMR (100 MHz, CDCl3):  = 159.0, 138.7, 136.9, 128.7, 127.9,
127.8, 127.7, 124.1, 39.5, 31.5, 29.5, 26.6, 22.5, 14.0, one signal is ob-
scured by overlap with other signals.
1H NMR (400 MHz, CDCl3):  = 7.53 (br, 1 H), 7.26–7.49 (m, 5 H), 7.06
(s, 1 H), 4.01 (s, 3 H), 3.41 (q, J = 6.7 Hz, 2 H), 1.62 (quint, J = 7.3 Hz, 2
H), 1.29–1.41 (m, 6 H), 0.89 (t, J = 7.1 Hz, 3 H).
MS (EI): m/z (%) = 285 (11) [M]+, 186 (19), 185 (39), 157 (51), 100 (23),
13C NMR (100 MHz, CDCl3):  = 159.2, 139.7, 137.6, 129.0, 128.8,
91 (100), 65 (15).
128.6, 128.4, 126.5, 39.0, 33.6, 31.4, 29.5, 26.5, 22.4, 13.9.
HRMS (EI): m/z [M]+ calcd for C17H23N3O: 285.1841; found: 285.1840.
MS (EI): m/z (%) = 285 (13) [M]+, 242 (15), 214 (28), 186 (25), 185 (91),
172 (16), 159 (13), 158 (75), 157 (15), 117 (14), 116 (100), 103 (15),
102 (60), 100 (33), 89 (19), 77 (15).
N-Hexyl-1-methoxymethyl-1H-imidazole-2-carboxyamide (1c)
Yield: 139 mg (58%); colorless oil; Rf = 0.10 (hexane/EtOAc = 4:1).
Bulb-to-bulb distillation (oven temp.): 160 °C/8 mmHg.
HRMS (EI): m/z [M]+ calcd for C17H23N3O: 285.1841; found: 285.1836.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–H

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Y. Fukumoto et al.
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Synthesis
N-Hexyl-5-(4-methoxyphenyl)-1-methyl-1H-imidazole-2-carbox-
amide (1g)
MS (EI): m/z (%) = 259 (18) [M]+, 216 (10), 188 (41), 160 (22), 159 (88),
146 (20), 133 (18), 132 (100), 131 (38), 104 (29), 100 (42), 90 (11), 77
(33).
Yield: 221 mg (70%); pale-yellow solid; mp 62.5–63.1 °C; Rf = 0.09
(hexane/EtOAc = 5:1).
HRMS (EI): m/z [M]+ calcd for C15H21N3O: 259.1685; found: 259.1676.
IR (neat): 1664 cm–1
.
N-Hexylimidazo[1,5-a]pyridine-3-carboxamide (1k)
Yield: 169 mg (69%); colorless oil; Rf = 0.13 (hexane/EtOAc = 8:1).
Bulb-to-bulb distillation (oven temp.): 155 °C/1.5 mmHg.
1H NMR (400 MHz, CDCl3):  = 7.47 (br, 1 H), 7.26–7.32 (m, 2 H), 6.98–
7.00 (m, 3 H), 3.97 (s, 3 H), 3.86 (s, 3 H), 3.40 (q, J = 6.7 Hz, 2 H), 1.61
(quint, J = 7.3 Hz, 2 H), 1.32–1.39 (m, 6 H), 0.89 (t, J = 6.9 Hz, 3 H).
13C NMR (100 MHz, CDCl3):  = 159.8, 159.4, 139.5, 137.6, 130.5,
126.3, 121.2, 114.2, 55.3, 39.0, 33.5, 31.5, 29.6, 26.6, 22.5, 14.0.
MS (EI): m/z (%) = 315 (29) [M]+, 272 (12), 244 (25), 216 (27), 215
(100), 202 (19), 189 (14), 188 (85), 146 (58), 133 (11), 132 (84), 117
(15), 108 (14), 103 (11), 100 (21), 91 (11), 89 (14).
IR (neat): 1652 cm–1
.
1H NMR (400 MHz, CDCl3):  = 9.48 (d, J = 7.3 Hz, 1 H), 7.55 (dd, J = 8.9,
1.1 Hz, 1 H), 7.45 (s, 1 H), 7.37 (br, 1 H), 6.96 (s, 1 H), 6.81 (t, J = 6.9 Hz,
1 H), 3.47 (q, J = 6.7 Hz, 2 H), 1.64 (quint, J = 7.4 Hz, 2 H), 1.30–1.44 (m,
6 H), 0.89 (t, J = 7.1 Hz, 3 H).
HRMS (EI): m/z[M]+ calcd for C18H25N3O2: 315.1947; found: 315.1945.
13C NMR (100 MHz, CDCl3):  = 159.6, 133.4, 129.8, 125.5, 121.3,
120.1, 117.8, 114.4, 39.0, 31.5, 29.7, 26.6, 22.5, 14.0.
N-Hexyl-1-methyl-5–4-(trifluoromethyl)phenyl-1H-imidazole-2-
carboxamide (1h)
MS (EI): m/z (%) = 245 (23) [M]+, 174 (14), 146 (14), 145 (73), 132 (10),
119 (16), 118 (100), 117 (39), 100 (37), 91 (18), 90 (28), 78 (12), 64
(12), 63 (14).
Yield: 194 mg (55%); white solid, mp 65.3–65.9 °C; Rf = 0.14 (hexane/
EtOAc = 5:1).
HRMS (EI): m/z [M]+ calcd for C14H19N3O: 245.1528; found: 245.1527.
Bulb-to-bulb distillation (oven temp.): 160 °C/1 mmHg.
IR (neat): 1643 cm–1
.
N-Hexyl-1-methyl-1H-1,2,4-triazole-5-carboxamide (1l)
Yield: 147 mg (70%); colorless oil; Rf = 0.07 in hexane/EtOAc = 1:1.
Bulb-to-bulb distillation (oven temp.): 200 °C/8 mmHg.
1H NMR (400 MHz, CDCl3):  = 7.73 (d, J = 8.2 Hz, 2 H), 7.56 (br, 1 H),
7.52 (d, J = 8.2 Hz, 2 H), 7.12 (s, 1 H), 4.04 (s, 3 H), 3.42 (q, J = 6.9 Hz, 2
H), 1.62 (quint, J = 7.3 Hz, 2 H), 1.30–1.40 (m, 6 H), 0.90 (t, J = 7.1 Hz, 3
H).
13C NMR (100 MHz, CDCl3):  = 159.1, 140.5, 136.3, 132.6, 130.5 (q, J =
32.6 Hz), 129.3, 127.9, 125.8 (q, J = 3.8 Hz), 123.8 (q, J = 271.1 Hz),
39.1, 33.8, 31.5, 29.6, 26.6, 22.6, 14.0.
IR (neat): 1680 cm–1
.
1H NMR (400 MHz, CDCl3):  = 8.16 (s, 1 H), 7.50 (br, 1 H), 4.04 (s, 3 H),
3.42 (q, J = 6.9 Hz, 2 H), 1.61 (quint, J = 7.2 Hz, 2 H), 1.25–1.38 (m, 6 H),
0.89 (t, J = 6.4 Hz, 3 H).
13C NMR (100 MHz, CDCl3):  = 157.1, 146.7, 39.2, 33.3, 31.3, 29.3,
26.5, 22.5, 14.0, one signal is obscured by overlap with other signals.
MS (EI): m/z (%) = 210 (1) [M]+, 139 (73), 111 (16), 110 (100), 100 (89),
97 (16), 84 (14), 83 (28), 56 (23), 55 (15).
HRMS (EI): m/z [M]+ calcd for C10H18N4O: 210.1481; found: 209.1480.
MS (EI): m/z (%) = 353 (7) [M]+, 282 (29), 254 (21), 253 (100), 240 (17),
226 (50), 225 (15), 184 (24), 100 (73).
Anal. Calcd for C18H22F3N3O: C, 61.18; H, 6.27; F, 16.13; N, 11.89.
Found: C, 61.09; H, 6.20; F, 16.07; N, 11.73.
N-Hexyl-1,4,5-trimethyl-1H-imidazole-2-carboxamide (1i)
Yield: 95 mg (40%); colorless oil; Rf = 0.10 (hexane/EtOAc = 4:1).
N3,N5-Dihexyl-4-methyl-4H-1,2,4-triazole-3,5-dicarboxamide (1l′)
The reaction was carried out using 4-methyl-4H-1,2,4-triazole (83.1
mg, 1 mmol), hexyl isocyanate (318.0 mg, 2.5 mmol), Ir4(CO)12 (27.6
mg, 0.025 mmol), and HSiEt2Me (511.3 mg, 5 mmol) in toluene (3 mL)
at 110 °C for 6 h. The product was isolated by preparative TLC (Rf =
0.61; hexane/EtOAc = 1:1) in 75% yield. An analytically pure sample
was obtained by GPC in 45% yield (163 mg).
IR (neat): 1662 cm–1
.
1H NMR (400 MHz, CDCl3):  = 7.40 (br, 1 H), 3.93 (s, 3 H), 3.35 (q, J =
6.9 Hz, 2 H), 2.17 (s, 3 H), 2.15 (s, 3 H), 1.58 (quint, J = 7.2 Hz, 2 H),
1.25–1.38 (m, 6 H), 0.88 (t, J = 6.9 Hz, 3 H).
13C NMR (100 MHz, CDCl3):  = 159.1, 136.5, 132.6, 127.9, 38.9, 32.2,
31.4, 29.5, 26.6, 22.5, 14.0, 12.3, 8.8.
MS (EI): m/z (%) = 237 (11) [M]+, 166 (19), 138 (21), 137 (83), 124 (19),
111 (11), 110 (100), 109 (14), 56 (44), 55 (11).
HRMS (EI): m/z [M]+ calcd for C13H23N3O: 237.1841; found: 237.1845.
White solids; mp 105.5–106.0 °C.
IR (neat): 1672 cm–1
.
1H NMR (400 MHz, CDCl3):  = 7.43 (bs, 2 H), 4.39 (s, 3 H), 3.43 (q, J =
6.8 Hz, 4 H), 1.62 (quint, J = 7.1 Hz, 4 H), 1.26–1.42 (m, 12 H), 0.89 (t,
J = 7.1 Hz, 6 H).
N-Hexyl-1-methyl-1H-benzo[d]imidazole-2-carboxamide (1j)
Yield: 174 mg (67%); colorless oil; Rf = 0.18 (hexane/EtOAc = 8:1).
Bulb-to-bulb distillation (oven temp.): 127 °C/0.9 mmHg.
13C NMR (100 MHz, CDCl3):  = 156.7, 148.6, 39.2, 33.7, 31.2, 29.1,
26.3, 22.3, 13.8.
MS (EI): m/z (%) = 337 (1) [M]+, 266 (33), 237 (31), 110 (12), 100 (100),
IR (neat): 1672 cm–1
.
83 (11).
HRMS (DART): m/z [M]+ calcd for C17H32N5O2: 338.2551; found:
338.2549.
1H NMR (400 MHz, CDCl3):  = 7.77 (d, J = 7.2 Hz, 2 H), 7.33–7.46 (m, 3
H), 4.24 (s, 3 H), 3.45 (q, J = 6.9 Hz, 2 H), 1.65 (quint, J = 7.3 Hz, 2 H),
1.33–1.43 (m, 6 H), 0.89 (t, J = 6.4 Hz, 3 H).
N-Hexyl-4-methyl-4H-1,2,4-triazole-3-carboxamide (1m)
Yield: 175 mg (83%); colorless oil; Rf = 0.10 (hexane/EtOAc = 4:1).
Bulb-to-bulb distillation (oven temp.): 160 °C/8 mmHg.
13C NMR (100 MHz, CDCl3):  = 159.6, 143.5, 140.8, 136.9, 124.4,
123.4, 120.4, 110.4, 39.3, 32.0, 31.4, 29.5, 26.6, 22.5, 14.0.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–H

G
Y. Fukumoto et al.
Special Topic
Synthesis
IR (neat): 1660 cm–1
.
Ethyl 2-(1-Methyl-1H-imidazole-2-carboxamido)acetate (5a)
1H NMR (400 MHz, CDCl3):  = 7.82 (s, 1 H), 7.35 (br, 1 H), 4.28 (s, 3 H),
3.41 (q, J = 6.7 Hz, 2 H), 1.61 (quint, J = 7.2 Hz, 2 H), 1.29–1.39 (m, 6 H),
0.89 (t, J = 6.6 Hz, 3 H).
13C NMR (100 MHz, CDCl3):  = 157.0, 149.2, 146.2, 39.3, 38.2, 31.4,
29.3, 26.5, 22.5, 14.0.
Yield: 139 mg (66%); white solid; mp 92.0–93.0 °C; Rf = 0.10 (hexane/
EtOAc = 4:1).
Bulb-to-bulb distillation (oven temp.): 180 °C/8 mmHg.
IR (neat): 1749, 1670 cm–1
.
1H NMR (400 MHz, CDCl3):  = 7.84 (br, 1 H), 7.03 (s, 1 H), 6.98 (s, 1 H),
4.24 (q, J = 7.2 Hz, 2 H), 4.15 (d, J = 5.9 Hz, 2 H), 4.05 (s, 3 H), 1.30 (t, J =
7.1 Hz, 3 H).
MS (EI): m/z (%) = 210 (1) [M]+, 139 (67), 111 (15), 110 (77), 100 (100),
97 (17), 84 (30), 83 (41), 56 (24), 55 (14).
13C NMR (100 MHz, CDCl3):  = 169.4, 159.3, 138.4, 127.7, 125.5, 61.3,
40.8, 35.4, 14.1.
Anal. Calcd for C10H18N4O: C, 57.12; H, 8.63; N, 26.64. Found: C, 57.07;
H, 8.46; N, 26.55.
MS (EI): m/z (%) = 259 (3) [M]+, 231 (57), 216 (19), 215 (10), 214 (53),
202 (18), 150 (12), 136 (11), 120 (12), 109 (100), 96 (38), 93 (10), 91
(14), 83 (36), 82 (30), 81 (24), 79 (14), 77 (12), 55 (11), 54 (21).
N-Cyclohexyl-1-methyl-1H-imidazole-2-carboxamide (2a)
Yield: 172 mg (83%); white solid; mp 73.4–74.0 °C; Rf = 0.10 (hexane/
EtOAc = 4:1).
Anal. Calcd for C9H13N3O3: C, 51.18; H, 6.20; N, 19.89. Found: C, 51.17;
H, 6.01; N, 19.82.
Bulb-to-bulb distillation (oven temp.): 160 °C/8 mmHg.
IR (neat): 1668 cm–1
.
1-Methyl-N-phenyl-1H-imidazole-2-carboxamide (6a)
1H NMR (400 MHz, CDCl3):  = 7.30 (br, 1 H), 6.99 (s, 1 H), 6.95 (s, 1 H),
4.06 (s, 3 H), 3.83–3.90 (m, 1 H), 1.98 (c, 2 H), 1.76 (c, 2 H), 1.64 (c, 1
H), 1.18–1.45 (m, 5 H).
13C NMR (100 MHz, CDCl3):  = 158.1, 139.0, 127.1, 125.1, 47.8, 35.4,
32.9, 25.3, 24.7.
MS (EI): m/z (%) = 207 (4) [M]+, 179 (13), 164 (26), 150 (43), 110 (15),
109 (98), 98 (100), 97 (12), 96 (18), 83 (12), 82 (56), 81 (28), 56 (13),
55 (15), 54 (30).
Yield: 48 mg (24%); colorless oil; Rf = 0.54 (hexane/EtOAc = 5:1).
IR (neat): 1680 cm–1
.
1H NMR (400 MHz, CDCl3):  = 9.24 (br, 1 H), 7.65 (d, J = 7.8 Hz, 2 H),
7.36 (t, J = 8.0 Hz, 2 H), 7.13 (t, J = 7.5 Hz, 1 H), 7.07 (s, 1 H), 7.02 (s, 1
H), 4.12 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 156.9, 138.8, 137.5, 128.9, 127.6,
126.1, 124.1, 119.5, 47.8, 35.8.
MS (EI): m/z (%) = 201 (60) [M]+, 200 (51), 109 (35), 106 (11), 83 (14),
82 (100), 81 (100), 77 (12), 65 (14), 56 (26), 55 (21), 54 (39), 51 (12).
Anal. Calcd for C11H17N3O: C, 63.74; H, 8.27; N, 20.27. Found: C, 63.46;
H, 8.01; N, 20.29.
HRMS (EI): m/z [M]+ calcd for C11H11N3O: 201.0902; found: 201.0894.
N-(1-Adamantyl)-1-methyl-1H-imidazole-2-carboxamide (3a)
Yield: 207 mg (80%); white solids; mp 115.0–115.5 °C; Rf = 0.17
(hexane/EtOAc = 4:1).
Funding Information
Bulb-to-bulb distillation (oven temp.): 170 °C/8 mmHg.
We wish to thank Osaka University for providing financial assistance.
IR (neat): 1673 cm–1
1H NMR (400 MHz, CDCl3):  = 7.17 (br, 1 H), 6.96 (s, 1 H), 6.92 (s, 1 H),
.
Osak
a
U
niversiyt()
4.03 (s, 3 H), 2.11 (br, 9 H), 1.67–1.74 (m, 6 H).
13C NMR (100 MHz, CDCl3):  = 158.1, 139.0, 127.1, 125.1, 51.8, 41.5,
36.2, 35.7, 29.3.
Acknowledgment
We wish to express our thanks to the Instrumental Analysis Center,
Faculty of Engineering, Osaka University, for assistance with HRMS
and elemental analyses.
MS (EI): m/z (%) = 259 (3) [M]+, 231 (57), 216 (19), 215 (10), 214 (53),
202 (18), 150 (12), 136 (11), 120 (12), 109 (100), 96 (38), 93 (10), 91
(14), 83 (36), 82 (30), 81 (24), 79 (14), 77 (12), 55 (11), 54 (21).
Anal. Calcd for C15H21N3O: C, 69.47; H, 8.16; N, 16.20. Found: C, 69.56;
H, 8.08; N, 16.16.
Supporting Information
Supporting information for this article is available online at
N-Benzyl-1-methyl-1H-imidazole-2-carboxamide (4a)
https://doi.org/10.1055/a-1375-5283. Su
p
p
orti
n
gInformatio
n
Su
p
p
ortingInformatio
n
Yield: 207 mg (66%); white solid; mp 102.0–102.4 °C; Rf = 0.10
(hexane/EtOAc = 4:1).
Bulb-to-bulb distillation (oven temp.): 170 °C/8 mmHg.
References
IR (neat): 1662 cm–1
.
(1) For recent reviews on the synthesis of imidazoles, see:
(a) Shabalin, D. A.; Camp, J. E. Org. Biomol. Chem. 2020, 18, 3950.
(b) Kerru, N.; Bhaskaruni, S. V. H. S.; Gummidi, L.; Maddila, S. N.;
Maddila, S.; Jonnalagadda, S. B. Synth. Commun. 2019, 49, 2437.
(c) Rossi, R.; Angelici, G.; Casotti, G.; Manzini, C.; Lessi, M. Adv.
Synth. Catal. 2019, 361, 2737.
(2) For selected reviews on the direct arylation of imidazoles, see:
(a) Rossi, R.; Bellina, F.; Lessi, M.; Manzini, C.; Perego, L. A. Syn-
thesis 2014, 46, 2833. (b) Shibahara, F.; Murai, T. Asian J. Org.
1H NMR (400 MHz, CDCl3):  = 7.75 (br, 1 H), 7.26–7.34 (m, 5 H), 6.99
(s, 1 H), 6.96 (s, 1 H), 4.57 (d, J = 5.9 Hz, 2 H), 4.08 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 159.0, 138.9, 137.9, 128.6, 127.7,
127.5, 127.3, 125.4, 42.9, 35.6.
MS (EI): m/z (%) = 215 (2) [M]+, 172 (36), 109 (24), 106 (100), 91 (17),
82 (77), 81 (29), 79 (11), 65 (11), 54 (15).
Anal. Calcd for C12H13N3O: C, 66.96; H, 6.09; N, 19.52. Found: C, 66.88;
H, 6.05; N, 19.52.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–H

H
Y. Fukumoto et al.
Special Topic
Synthesis
Chem. 2013, 2, 624. (c) Roger, J.; Gottumukkala, A. L.; Doucet, H.
ChemCatChem 2010, 2, 20. (d) Bellina, F.; Rossi, R. Tetrahedron
2009, 65, 10269. (e) Lewis, J. C.; Bergman, R. G.; Ellman, J. A. Acc.
Chem. Res. 2008, 41, 1013.
(14) One preliminary result that the use of 1-methylimidazole,
propyl isocyanate, and HSiEt2Me resulted in the formation of 1-
methylimidazole-2-(N-propyl)carboxamide has been provided.
See ref. 11.
(3) For recent reviews on the catalytic C–H bond functionalization
with compounds bearing C=O and C=N groups, including isocy-
anates, see: (a) Hummel, J. R.; Boerth, J. A.; Ellman, J. A. Chem.
Rev. 2017, 117, 9163. (b) Yang, L.; Huang, H. Chem. Rev. 2015,
115, 3468.
(4) (a) Chatani, N.; Fukuyama, T.; Tatamidani, H.; Kakiuchi, F.;
Murai, S. J. Org. Chem. 2000, 65, 4039. (b) Fukuyama, T.; Chatani,
N.; Tatsumi, J.; Kakiuchi, F.; Murai, S. J. Am. Chem. Soc. 1998, 120,
11522. (c) Chatani, N.; Fukuyama, T.; Kakiuchi, F.; Murai, S.
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