Ruthenium-Catalyzed meta-Selective CAr-H Bond Formylation of Arenes

Article abstract of DOI:10.1021/acs.joc.0c00007

The meta-C_Ar-H bond formylation of arenes has been achieved using CHBr₃ as a formyl source in the presence of [Ru(p-cym)(OAc)₂] as a catalyst. This method provides efficient access to the preparation of various meta-substituted aromatic compounds, such as alcohols, ethers, amines, nitriles, alkenes, halogens, carboxylic acids, and their derivatives, through transformation of the versatile formyl group. Furthermore, mechanistic studies show that the key active species is a pentagonal ruthenacycle complex.

Full text of DOI:10.1021/acs.joc.0c00007

Subscriber access provided by Murdoch University Library
Note
Ar
Ruthenium-catalyzed meta-selective C–H bond formylation of arenes.
Chunqi Jia, Nini Wu, Xiaofeng Cai, Gang Li, Lei Zhong, Lei Zou, and Xiuling Cui
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.0c00007 • Publication Date (Web): 05 Mar 2020
Downloaded from pubs.acs.org on March 6, 2020
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a service to the research community to expedite the dissemination
of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in
full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully
peer reviewed, but should not be considered the official version of record. They are citable by the
Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore,
the “Just Accepted” Web site may not include all articles that will be published in the journal. After
a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web
site and published as an ASAP article. Note that technical editing may introduce minor changes
to the manuscript text and/or graphics which could affect content, and all legal disclaimers and
ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or
consequences arising from the use of information contained in these “Just Accepted” manuscripts.
is published by the American Chemical Society. 1155 Sixteenth Street N.W.,
Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 8
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Ruthenium-catalyzed meta-selective CAr – H bond formylation of
arenes.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Chunqi Jia,† Nini Wu,‡ Xiaofeng Cai,‡ Gang Li,‡* Lei Zhong,‡ Lei Zou,‡ and Xiuling Cui†*
† Engineering Research Center of Molecular Medicine of Ministry of Education, Key Laboratory of Fujian Molecular
Medicine, Key Laboratory of Xiamen Marine and Gene Drugs, School of Biomedical Sciences, Huaqiao University,
Xiamen 361021, PR China
‡ College of Chemistry and Chemical Engineering, Henan Province Key Laboratory of New Optoelectronic Functional
Materials, Anyang Normal University, Anyang 455000, P. R. China.
Supporting Information Placeholder
ABSTRACT: The meta-CAr–H bond formylation of arenes has been achieved using CHBr3 as a formyl source in the presence
of [Ru(p-cym)(OAc)2] as catalyst. This method provides efficient access to the preparation of various meta-substituted
aromatic compounds, such as alcohols, ethers, amines, nitriles, alkenes, halogens, carboxylic acids, and their derivatives,
through transformation of the versatile formyl group. Furthermore, mechanism studies show that the key active species is a
pentagonal ruthenacycle complex.
Aromatic aldehydes are essential compounds, with their
versatile formyl groups employed for further
transformations into various other functional groups, such
as alcohols, carboxylic acids, amines, nitriles, and halogens,
that are widely present in bioactive natural molecules,
pharmaceuticals, agrochemicals, and many functional
materials.1 To date, numerous methods for the synthesis of
aromatic aldehydes have been reported. The most efficient
methods involve direct installation of a formyl group on
the aromatic ring. Conventional electrophilic aromatic
formylations, such as the Gattermann–Koch reaction,2 Duff
reaction,3 Reimer–Tiemann reaction,4 Rieche formylation,5
and Vilsmeier–Haack reaction,6 are perfectly suited to this
goal, avoiding prefunctionalization before formylation.
However, these transformations are not suitable for
electron-deficient aromatic substrates. Furthermore, the
functional group tolerance is low. With the development of
position relative to substituents. Accordingly, the efficient
meta-CAr–H formylation of arenes remains challenging.
In recent years, various TM-catalyzed meta-CAr – H bond
functionalizations have been achieved in the literature
using alternative strategies.8 Ruthenium complexes are
inexpensive, highly active, and distinctive catalysts that
can not only catalyze ortho-CAr–H bond activation,9 but also
meta-CAr – H bond activation through the Ru – CAr bond
ortho/para-directing effect.10 Herein, we have achieved the
meta-CAr–H bond formylation of arenes using CHBr3 as the
formyl source in the present of a ruthenium catalyst.
Initially, we selected readily available 2-phenylpyridine
and CHBr3 as representative reactants to explore favorable
conditions for the meta-CAr –H bond formylation of arenes
catalyzed by a ruthenium complex. The transformation
was conducted in a thick-walled Schlenk reaction tube at
120 ℃ for 24 h under an inert atmosphere (N2 gas), as
shown in Table 1. The target product was provided in 16%
yield in acetonitrile when [Ru(p-cym)(OAc)2], prepared in
our laboratory, and common K2CO3 were employed as
catalyst and base, respectively (Table 1, entry 1). Usually,
carboxylic acids are popular and efficient promoters of Ru-
catalyzed CAr – H bond activation.10d Carboxylic acid
screening showed that the formylation process was
transition-metal
(TM)-catalyzed
C-H
bond
functionalization in recent years, aromatic aldehydes have
been efficiently obtained by directing-group-assisted CAr–H
formylation in the presence of TMs.7 However, regardless
of whether electrophilic aromatic formylation or TM-
catalyzed aromatic C – H bond formylation is used, these
methods are limited to formylation at the ortho/para-
ACS Paragon Plus Environment

The Journal of Organic Chemistry
promoted by Ac-Leu-OH, providing the desired product in
Page 2 of 8
compatible with the transformation, offering potential
active sites for further functionalization (3d, 3e, 3j). The
electronic nature of the phenyl ring was also found to
influence the transformation efficiency. An electron-
donating substituent ( –OCH3, 3f) on the phenyl ring was
more favorable for formylation than an electron-
withdrawing ( – CF3, 3g) functional group. When 7,8-
benzoquinoline and 2-(2-naphthyl)pyridine were used as
substrates, the corresponding products were successfully
obtained (3k, 3l). An investigation of nitrogen-containing
chelating groups showed that pyrimidine was a leading
directing group, with good isolated yields obtained (3h–j).
The desired products were also obtained when pyridines
bearing a methyl group (3m), quinoline (3n), isoquinoline
(3o), and pyrazole (3p–r) were used as directing groups.
Notably, the ruthenium-catalyzed meta-CAr –H formylation
was also suitable for phenyl ring meta-position
modification and the functionalization of 6-phenyl purine
nucleobases as bioactive molecule (3s).
1
2
3
4
5
6
7
8
a 53% isolated yield (entry 2). Other carboxylic acids, such
as 2,4,6-trimethylbenzoic acid and 1-adamantane
carboxylic acid, showed inferior performance (entries 3
and 4). Formylation also proceeded in 1,4-dioxane and
THF as solvents, but lower yields were obtained (entries 5
and 6). No products were obtained in toluene and DMF
(entries 7 and 8). Na2CO3, KOAc, and Cs2CO3 were also
tested as bases in the formylation. The results
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 1. Condition Optimization of the Ru-Catalyzed
meta-CAr–H Formylation
Entry formyl source
catalyst
base
ligand
solvent yield (%)
1
CHBr3
CHBr3
CHBr3
CHBr3
CHBr3
CHBr3
CHBr3
CHBr3
CHBr3
CHBr3
CHBr3
CHI3
[Ru(p-cym)(OAc)2]
[Ru(p-cym)(OAc)2]
[Ru(p-cym)(OAc)2]
[Ru(p-cym)(OAc)2]
[Ru(p-cym)(OAc)2]
[Ru(p-cym)(OAc)2]
[Ru(p-cym)(OAc)2]
[Ru(p-cym)(OAc)2]
[Ru(p-cym)(OAc)2]
[Ru(p-cym)(OAc)2]
[Ru(p-cym)(OAc)2]
[Ru(p-cym)(OAc)2]
[Ru(p-cym)(OAc)2]
[Ru(p-cym)(OAc)2]
RuCl3
K2CO3
－
CH3CN
16
53
8
2
K2CO3 Ac-Leu-OH CH3CN
K2CO3 MesCOOH CH3CN
K2CO3 1-AdCOOH CH3CN
Scheme 1. Substrate Scope of the meta-CAr − H
Formylation Catalyzed by Ruthenium.
3
4
14
5
K2CO3 Ac-Leu-OH 1,4-Dioxane 28
6
K2CO3 Ac-Leu-OH
THF
18
0
7
K2CO3 Ac-Leu-OH toluene
8
K2CO3 Ac-Leu-OH
Na2CO3 Ac-Leu-OH
DMF
0
9
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
0
10
11
12
13
14
15
16
17
18
KOAc
Ac-Leu-OH
11
26
51
21
32
19
0
Cs2CO3 Ac-Leu-OH
K2CO3 Ac-Leu-OH
K2CO3 Ac-Leu-OH
K2CO3 Ac-Leu-OH
K2CO3 Ac-Leu-OH
K2CO3 Ac-Leu-OH
K2CO3 Ac-Leu-OH
K2CO3 Ac-Leu-OH
CHCl3
CHBr3
CHBr3
CHBr3
CHBr3
CHBr3
Ru3(CO)12
Pd(OAc)2
0
－
0
showed that the Na2CO3 was not compatible (Table 1,
entry 9), while KOAc and Cs2CO3 were effective, but gave
poor yields (entries 10 and 11). An examination of other
formylation reagents showed that CHI3 also provided the
target product in 51% yield (entry 12), while CHCl3
showed low efficiency (entry 13). [Ru(p-cym)Cl2]2 and
RuCl3 were also efficient catalysts for C – H bond
formylation (entries 14 and 15), although the yields were
inferior to those obtained using [Ru(p-cym)(OAc)2]. When
Ru3(CO)12, Pd(OAc)2, and no transition metal were
employed as catalysts in the process, no desired product
was obtained (entries 16–18).
To illustrate the versatile synthetic potential of the
arylaldehyde products, different transformations were
performed, as shown in Scheme 2. For example, carboxylic
acid11 and benzyl alcohol12 were synthesized from
arylaldehyde by a simple redox reaction (4, 5). Benzyl
alcohol reacts further with HCl to give benzyl chloride
(6).13 By means of the famous Wittig reaction, the reaction
of arylaldehydes with diethyl benzylphosphonate provided
olefins in excellent yields (7).14 The structure of product
Under the optimized conditions, the generality of meta-
CAr – H bond formylation catalyzed by the ruthenium
complex was investigated using various 2-phenylpyridine
derivatives as substrates, as shown in Scheme 1. Initially,
several 2-phenylpyridines bearing various groups on the
phenyl ring were employed as reactants. 2-
Phenylpyridines bearing alkyl or aryl groups reacted
successfully, providing the target products in moderate
yields (3b, 3c, 3i). Halogen substituents were also
ACS Paragon Plus Environment

Page 3 of 8
The Journal of Organic Chemistry
7b was confirmed by single-crystal X-ray diffraction.
(Scheme 3b). These results indicated that pentagonal
ruthenacycle I was a key active species in the formylation
process. Furthermore, when radical scavengers, such as
TEMPO (2,2,6,6-tetramethylpiperidin-1-yl)oxyl) and BQ
(1,4-benzoquinone), were added to the standard reaction,
no product was obtained, indicating that the formylation
involved a single-electron transfer process (Scheme 3c).
Next, to study the impact of electronic properties on the
1
2
3
4
5
6
7
8
Furthermore, benzonitrile was obtained by reacting
arylaldehydes with ammonium acetate (8).15
Scheme 2. Synthetic Utility of the Formylation.
formylation,
methoxyphenyl)pyridine
(trifluoromethyl)phenyl)pyridine,
a
scrambling
test
and
bearing
of
2-(4-
2-(4-
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
electron-
donating (–OCH3) and electron-withdrawing (–CF3) groups,
respectively, reacted with CHBr3 under the optimized
conditions to provide product 3f predominantly (Scheme
3d). This result indicated that the ruthenium-catalyzed
CAr–H formylation was an electrophilic substitution
process. Finally, after the reaction was complete, the gas
from the reaction system caused clarified lime water to
become turbid, showing that CO2 was a byproduct of the
process (Scheme 3e).
To gain insight into the Ru(II)-catalyzed meta-CAr – H
formylation mechanism, some test reactions were
performed, as shown in Scheme 4. First, under the
optimized conditions, 2-(2,6-dimethylphenyl)pyridine, in
which the two ortho-positions relative to the directing
group were occupied by two methyl groups, did not react
with CHBr3 (Scheme 3a).
Scheme 4. Proposed Catalytic Mechanism.
Scheme 3. Preliminary Mechanistic Probes.
From the aforementioned experimental results and
literature relating to ruthenium-catalyzed CAr–H bond
activation,9 a plausible mechanism was proposed for the
meta-CAr–H formylation process, as shown in Scheme 4.
Ortho-CAr–H bond metalation of 2-phenylpyridine by
[Ru(p-cym)OAc2] generates key pentagonal ruthenacycle
species A. The dibromomethyl radical, formed by a
ruthenium-complex-mediated single-electron transfer,
attacks active intermediate A at the pyridyl meta-position,
producing intermediate B. The deprotonation of active
intermediate B, aided by ruthenium and K2CO3, provides
complex C. Finally, complex C undergoes ligand exchange
with 2-phenylpyridine to give the recycled active catalyst
species and the meta-dibromomethylated product, which
further reacts with K2CO3 to give the final product, and KBr
and CO2 as byproducts.
This supported that ortho-CAr–H metalation was
necessary in the ruthenium-catalyzed formylation. Next,
pentagonal ruthenacycle I was prepared by the reaction of
2-phenylpyridine with [Ru(p-cym)OAc2] in CH2Cl2 at room
temperature for 18 h. This experiment indicated that the
meta-CAr – H formylation was promoted by ruthenacycle
complex I to give product 3a in 56% isolated yield
In conclusion, we have achieved Ru-catalyzed meta-CAr–H
formylation using CHBr3 as the formyl source. Mechanistic
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 8
Preparation of Complex I: Complex I were prepared from
[Ru(p-cymene)(OAc)2] and 2-phenylpyridine according to
literature report.17
studies showed that a radical intermediate might be
involved in this process, and that pentagonal
1
2
3
4
5
6
7
8
a
ruthenacycle was the key active species. This provides an
efficient method for the synthesis of various meta-
substituted aromatic compounds via an active formyl
group, and allows further transformation to obtain many
other functional groups.
3-(pyridin-2-yl)benzaldehyde (3a, colorless oil, PE/EtOAc = 3:1
1
as eluent, 19.4mg, 53% yield): H NMR (400 MHz, CDCl3) δ
10.09 (s, 1H), 8.70 (d, J = 4.4 Hz, 1H), 8.49 (s, 1H), 8.27 (d, J =
7.7 Hz, 1H), 7.91 (d, J = 7.5 Hz, 1H), 7.81–7.73 (m, 2H), 7.62 (t,
J = 7.6 Hz, 1H), 7.27 (m, 1H).13C{1H} NMR (101 MHz, CDCl3) δ
192.2, 155.8, 149.8, 140.3, 137.0 (d), 132.7, 129.7, 129.5,
128.4, 122.8, 120.6. HRMS (ESI) m/z: [M+H]+ Calcd for
C12H10NO 184.0757; Found 184.0752.
9
EXPERIMENTAL SECTION
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Materials and Methods. All commercial reagents and
solvents were used directly without additional purification.
Column chromatography were performed on silica gel 200-
2-methyl-5-(pyridin-2-yl)benzaldehyde
(3b,
yellow
oil,
1
PE/EtOAc = 3:1 as eluent, 20.5mg, 52% yield): H NMR (400
MHz, CDCl3) δ 10.32 (s, 1H), 8.69 (d, J = 4.2 Hz, 1H), 8.42 (s,
1H), 8.12 (d, J = 7.9 Hz, 1H), 7.76 (d, J = 3.6 Hz, 2H), 7.35 (d, J =
7.9 Hz, 1H), 7.30 – 7.19 (m, 1H), 2.70 (s, 3H). 13C{1H} NMR
(101 MHz, CDCl3) δ 192.8, 155.9, 149.8, 141.2, 137.0, 134.4,
132.4, 131.6, 130.7, 122.5, 120.2, 19.5. HRMS (ESI) m/z:
[M+H]+ Calcd for C13H12NO 198.0914; Found 198.0913.
1
300 mesh. H NMR and 13C NMR spectra were registered on a
Bruker AscendTM 400 spectrometer (Germany). Chemical
shifts were reported in units (ppm) referenced to 0.0 ppm of
TMS in the 1H spectrum and 77.0 ppm of CDCl3 in the 13C
spectrum. All coupling constants were reported in Hertz (Hz).
HRMS data were obtained using Tof ESI-MS instrument on a
Waters LCT PremierxeTM (USA). Crystal (7b) grows in
CH2Cl2/PE system at room temperature. Single-crystal X-ray
crystallography was carried out on a Bruker Smart Apex II
diffractometer system. The pyridine derivatives were
prepared via Suzuki coupling of the corresponding
arylboronic acids and 2-bromopyridine according to literature
report.16
Typical Experimental Procedure of ruthenium-catalyzed
meta-selective C-H bond formylation of Arenes: 2-
Phenylpyridine (0.2 mmol), CHBr3 (0.6 mmol, 3.0 equiv.),
[Ru(p-cymene)(OAc)2], (0.01 mmol, 10 mol %), K2CO3 (0.4
mmol, 2.0 equiv), Ac-Leu-OH (30 mmol %), dry acetonitrile (1
mL) were charged into a pre-dried 30-mL pressure tube
sealed with rubber plugs under N2 atmosphere. The reaction
mixture was stirred at 120 °C oil bath for 24 h. The reaction
was cooled down to room temperature. The mixture was
passed through a short pad of celite, washing with a mixture
of EtOAc. The organic layer was concentrated under reduced
pressure to give a crude oil, which was purified by column
chromatography (PE/EtOAc as eluent) on silica gel to afford
the desired products.
1 mmol Scale Experimental Procedure of ruthenium-
catalyzed meta-selective C-H bond formylation of Arenes:
2-Phenylpyridine or 2-(4-methoxyphenyl)pyridine (1 mmol),
CHBr3 (3 mmol, 3.0 equiv.), [Ru(p-cymene)(OAc)2], (0.05
mmol, 10 mol %), K2CO3 (2 mmol, 2.0 equiv), Ac-Leu-OH (30
mmol %), dry acetonitrile (3 mL) were charged into a pre-
dried 75-mL pressure tube sealed with rubber plugs under N2
atmosphere. The reaction mixture was stirred at 120 °C oil
bath for 36 h. The reaction was cooled down to room
temperature. The mixture was passed through a short pad of
celite, washing with a mixture of EtOAc. The organic layer was
concentrated under reduced pressure to give a crude oil,
which was purified by column chromatography (PE/EtOAc as
eluent) on silica gel to afford the 3a and 3f products in 42%
(76.9 mg) and 48% (102.3 mg) isolated yields respectively.
4-(pyridin-2-yl)-[1,1'-biphenyl]-2-carbaldehyde (3c, yellow oil,
PE/EtOAc = 3:1 as eluent, 26mg, 56% yield): 1H NMR (400
MHz, CDCl3) δ 10.07 (s, 1H), 8.74 (d, J = 4.2 Hz, 1H), 8.60 (d, J
= 1.4 Hz, 1H), 8.45–8.34 (m, 1H), 7.87 (d, J = 7.8 Hz, 1H), 7.81
(t, J = 7.6 Hz, 1H), 7.59 (d, J = 8.0 Hz, 1H), 7.48 (m, 5H), 7.33–
7.25 (m, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ 192.3, 155.9,
149.9, 146.3, 138.9, 137.4, 137.0, 133.9, 131.9, 131.5, 130.1,
128.5, 128.3, 125.8, 122.7, 120.6. HRMS (ESI) m/z: [M+H]+
Calcd for C18H14NO 260.1070; Found 260.1075.
2-bromo-5-(pyridin-2-yl)benzaldehyde (3d, white solid,
1
PE/EtOAc = 3:1 as eluent, 24.4mg, 47% yield): H NMR (400
MHz, CDCl3) δ 10.44 (s, 1H), 8.72 (d, J = 4.7 Hz, 1H), 8.49 (d, J
= 2.2 Hz, 1H), 8.22 (m, 1H), 7.80 (m, 3H), 7.31 (m, 1H). 13C{1H}
NMR (101 MHz, CDCl3) δ 191.6, 155.0, 149.9, 139.3, 137.1,
134.4, 133.6, 127.9, 127.6, 123.0, 120.4. HRMS (ESI) m/z:
[M+H]+ Calcd for C12H9BrNO 261.9863; Found 261.9861.
2-fluoro-5-(pyridin-2-yl)benzaldehyde
(3e,
white
solid,
1
PE/EtOAc = 3:1 as eluent, 17.3mg, 43% yield): H NMR (400
MHz, CDCl3) δ 10.43 (s, 1H), 8.70 (d, J = 4.8 Hz, 1H), 8.45 (m,
1H), 8.36 (m, 1H), 7.82 –7.74 (m, 2H), 7.31–7.25 (m, 2H).
13C{1H} NMR (101 MHz, CDCl3) δ 187.0 (d), 166.4, 163.8,
155.1, 149.8, 137.0, 134.9 (d), 127.0 (d), 122.7, 120.3, 117.2,
117.0. HRMS (ESI) m/z: [M+H]+ Calcd for C12H9FNO 202.0663;
Found 202.0667.
2-methoxy-5-(pyridin-2-yl)benzaldehyde (3f, white solid,
1
PE/EtOAc = 3:1 as eluent, 22.6mg, 53% yield): H NMR (400
MHz, CDCl3) δ 10.53 (s, 1H), 8.67 (d, J = 4.7 Hz, 1H), 8.41 (d, J
= 2.4 Hz, 1H), 8.36 (m, 1H), 7.79 – 7.72 (m, 2H), 7.23 (d, J =
3.9 Hz, 1H), 7.12 (d, J = 8.8 Hz, 1H), 4.01 (s, 3H). 13C{1H} NMR
(101 MHz, CDCl3) δ 189.6, 162.4, 155.9, 149.6, 136.9, 134.5,
132.1, 126.8, 124.7, 122.0, 119.9, 112.1, 55.9. HRMS (ESI) m/z:
[M+H]+ Calcd for C13H12NO2 214.0863; Found 214.0867.
5-(pyridin-2-yl)-2-(trifluoromethyl)benzaldehyde (3g, white
1
solid, PE/EtOAc = 3:1 as eluent, 19.6mg, 39% yield): H NMR
(400 MHz, CDCl3) δ 10.47 (d, J = 2.0 Hz, 1H), 8.79 – 8.68 (m,
2H), 8.44 (d, J = 8.1 Hz, 1H), 7.94 – 7.83 (m, 3H), 7.35 (m, 1H).
13C{1H} NMR (101 MHz, CDCl3) δ 188.8, 154.5, 150.1, 143.30,
137.2, 134.1, 131.8, 127.3, 126.8, 125.0, 123.6, 121.0. HRMS
Preparation
of
[Ru(p-cymene)(OAc)2]:
[Ru(p-
cymene)(OAc)2] were prepared from [Ru(p-cymene)Cl2]2 and
KOAc according to literature report.17
ACS Paragon Plus Environment

Page 5 of 8
The Journal of Organic Chemistry
(ESI) m/z: [M+H]+ Calcd for C13H9F3NO 252.0631; Found
252.0632.
3-(isoquinolin-1-yl)benzaldehyde (3o, yellow solid, PE/EtOAc =
3:1 as eluent, 13mg, 28% yield): 1H NMR (400 MHz, CDCl3) δ
10.14 (s, 1H), 8.65 (d, J = 5.6 Hz, 1H), 8.24 (s, 1H), 8.03 (t, J =
12.4 Hz, 3H), 7.93 (d, J = 8.2 Hz, 1H), 7.77 – 7.70 (m, 3H), 7.59
(t, J = 7.3 Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ 192.0,
159.1, 142.3, 140.6, 136.9, 136.5, 135.8, 131.6, 130.3, 129.5,
129.2, 127.7, 127.2, 126.9, 126.5, 120.6. HRMS (ESI) m/z:
[M+H]+ Calcd for C16H12NO 234.0914; Found 234.0915.
1
2
3
4
5
6
7
8
3-(pyrimidin-2-yl)benzaldehyde (3h, white solid, PE/EtOAc =
1
3:1 as eluent, 24.7mg, 67% yield): H NMR (400 MHz, CDCl3)
δ 10.14 (s, 1H), 8.96 (s, 1H), 8.84 (d, J = 4.3 Hz, 2H), 8.72 (d, J
= 7.6 Hz, 1H), 8.02 (d, J = 7.3 Hz, 1H), 7.66 (t, J = 7.6 Hz, 1H),
7.26 (t, J = 4.6 Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ 192.2,
163.4, 157.4, 138.6, 136.9, 133.9, 130.6 (d), 129.4, 119.7.
HRMS (ESI) m/z: [M+H]+ Calcd for C11H9N2O 185.0710; Found
185.0712.
3-(1H-pyrazol-1-yl)benzaldehyde (3p, yellow oil, PE/EtOAc =
1
9
3:1 as eluent, 15.6mg, 45% yield): H NMR (400 MHz, CDCl3)
2-methyl-5-(pyrimidin-2-yl)benzaldehyde (3i, white solid,
δ 10.08 (s, 1H), 8.20 (s, 1H), 8.06 – 8.01 (m, 2H), 7.83 –
7.75 (m, 2H), 7.64 (t, J = 7.8 Hz, 1H), 6.58 – 6.49 (m, 1H).
13C{1H} NMR (101 MHz, CDCl3) δ 191.4, 141.7, 137.5, 130.3,
127.6, 126.8, 124.7, 119.1, 118.8, 108.3. HRMS (ESI) m/z:
[M+H]+ Calcd for C10H9N2O 173.0710; Found 173.0709.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
PE/EtOAc = 3:1 as eluent, 22.6mg, 57% yield): H NMR (400
MHz, CDCl3) δ 10.32 (s, 1H), 8.92 – 8.74 (m, 3H), 8.54 (d, J =
7.9 Hz, 1H), 7.39 (d, J = 7.9 Hz, 1H), 7.21 (d, J = 4.8 Hz, 1H),
2.73 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 193.0, 163.5,
157.3, 143.1, 136.0, 134.5, 133.0, 132.7, 132.3, 119.4, 20.0.
HRMS (ESI) m/z: [M+H]+ Calcd for C12H11N2O 199.0866;
Found 199.0867.
3-(3-methyl-1H-pyrazol-1-yl)benzaldehyde (3q, white solid,
1
PE/EtOAc = 3:1 as eluent, 15.6mg, 42% yield): H NMR (400
MHz, CDCl3) δ 10.07 (s, 1H), 8.15 (s, 1H), 7.98 (d, J = 8.1 Hz,
1H), 7.91 (d, J = 2.2 Hz, 1H), 7.76 (d, J = 7.5 Hz, 1H), 7.61 (t, J =
7.8 Hz, 1H), 6.31 (d, J = 2.1 Hz, 1H), 2.40 (s, 3H). 13C{1H} NMR
(101 MHz, CDCl3) δ 191.5, 151.3, 140.9, 137.5, 130.2, 127.3,
127.0, 124.2, 118.8, 108.4, 13.7. HRMS (ESI) m/z: [M+H]+
Calcd for C11H11N2O 187.0866; Found 187.0860.
2-chloro-5-(pyrimidin-2-yl)benzaldehyde (3j, white solid,
1
PE/EtOAc = 3:1 as eluent, 23.5mg, 54% yield): H NMR (400
MHz, CDCl3) δ 10.55 (s, 1H), 9.03 (d, J = 1.9 Hz, 1H), 8.84 (d, J
= 4.8 Hz, 2H), 8.63 (m, 1H), 7.59 (d, J = 8.4 Hz, 1H), 7.27 (d, J =
4.4 Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ 189.4, 162.8,
157.4, 139.8, 137.1, 134.2, 132.6, 130.9, 129.5, 119.8. HRMS
(ESI) m/z: [M+H]+ Calcd for C11H8ClN2O 219.0320; Found
219.0322.
3-(3,5-dimethyl-1H-pyrazol-1-yl)benzaldehyde (3r, yellow oil,
1
PE/EtOAc = 3:1 as eluent, 14.4mg, 36% yield): H NMR (400
MHz, CDCl3) δ 10.03 (s, 1H), 7.94 (d, J = 1.6 Hz, 1H), 7.83 (d, J
= 7.6 Hz, 1H), 7.76 – 7.69 (m, 1H), 7.60 (t, J = 7.8 Hz, 1H), 6.01
(s, 1H), 2.34 (s, 3H), 2.28 (s, 3H). 13C NMR (101 MHz, CDCl3) δ
191.3, 149.7, 140.8, 139.5, 137.2, 129.9 (d), 127.9, 124.9,
107.8, 13.4, 12.5. HRMS (ESI) m/z: [M+H]+ Calcd for
C12H13N2O 201.1023; Found 201.1022.
3-(9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)benzaldehyde
(3s, white solid, PE/EtOAc = 3:1 as eluent, 22.2mg, 36% yield):
1H NMR (400 MHz, CDCl3) δ 10.20 (s, 1H), 9.33 (s, 1H), 9.13
(d, J = 7.8 Hz, 1H), 9.07 (s, 1H), 8.39 (s, 1H), 8.08 (d, J = 7.6 Hz,
1H), 7.74 (t, J = 7.7 Hz, 1H), 5.89 (m, 1H), 4.23 (d, J = 10.6 Hz,
1H), 3.85 (m, 1H), 2.22 (d, J = 12.4 Hz, 1H), 2.14 (d, J = 10.1 Hz,
2H), 1.82 (m, 2H), 1.71 (d, J = 9.9 Hz, 1H). 13C{1H} NMR (101
MHz, CDCl3) δ 192.1, 153.2, 152.4, 151.5, 142.6, 136.8 (d),
135.6, 132.2, 131.3, 130.6, 129.4, 82.1, 68.9, 31.9, 24.9, 22.8.
HRMS (ESI) m/z: [M+H]+ Calcd for C17H17N4O2 309.1347;
Found 309.1348.
methyl 3-(pyridin-2-yl)benzoate (4a, yellow oil, PE/EtOAc =
3:1 as eluent, 87 mg, 82% yield): 1H NMR (400 MHz, CDCl3) δ
8.73 – 8.68 (m, 1H), 8.64 (d, J = 1.5 Hz, 1H), 8.23 (m, 1H), 8.12
– 8.05 (m, 1H), 7.80 – 7.74 (m, 2H), 7.55 (m, 1H), 7.28 –
7.21 (m, 1H), 3.94 (d, J = 1.9 Hz, 3H). 13C{1H} NMR (101 MHz,
CDCl3) δ 166.9, 156.3, 149.8, 139.7, 136.9, 131.3, 130.7, 130.0,
128.9, 128.0, 122.6, 120.6, 52.2. HRMS (ESI) m/z: [M+H]+
Calcd for C13H12NO2 214.0863; Found 214.0859.
benzo[h]quinoline-9-carbaldehyde (3k, white solid, PE/EtOAc
= 3:1 as eluent, 15.3mg, 37% yield): 1H NMR (400 MHz, CDCl3)
δ 10.34 (s, 1H), 9.79 (s, 1H), 9.08 (m, 1H), 8.23 (m, 2H), 8.01
(d, J = 8.3 Hz, 1H), 7.87 (s, 2H), 7.61 (m, 1H). 13C{1H} NMR
(101 MHz, CDCl3) δ 192.5, 149.7, 136.1, 146.5, 137.3, 134.9,
131.4, 130.6, 128. 8 (d), 127.2, 126.7, 125.3, 122.5. HRMS (ESI)
m/z: [M+H]+ Calcd for C14H10NO 208.0757; Found 208.0757.
3-(pyridin-2-yl)-1-naphthaldehyde (3l, 35 mg, colorless oil,
1
PE/EtOAc = 3:1 as eluent, 17.7mg, 38% yield): H NMR (400
MHz, CDCl3) δ 10.53 (s, 1H), 9.29 (d, J = 8.5 Hz, 1H), 8.80 (d, J
= 4.0 Hz, 1H), 8.76 – 8.69 (m, 2H), 8.04 (d, J = 8.1 Hz, 1H),
7.97 (d, J = 8.0 Hz, 1H), 7.87 (m, 1H), 7.76 – 7.69 (m, 1H), 7.64
(m, 1H), 7.36 (s, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ 193.7,
155.6, 150.0, 137.1, 135.6 (d), 134.1, 132.8, 132.0, 129.6,
129.2, 127.4, 125.0, 122.8, 120.5. HRMS (ESI) m/z: [M+H]+
Calcd for C16H12NO 234.0914; Found 234.0913.
3-(3-methylpyridin-2-yl)benzaldehyde
(3m,
yellow
oil,
1
PE/EtOAc = 3:1 as eluent, 18.5mg, 47% yield): H NMR (400
MHz, CDCl3) δ 10.10 (s, 1H), 8.56 (d, J = 4.4 Hz, 1H), 8.08 (s,
1H), 7.94 (d, J = 7.6 Hz, 1H), 7.83 (d, J = 7.6 Hz, 1H), 7.64 (t, J =
7.4 Hz, 2H), 7.25 (m, 1H), 2.39 (s, 3H). 13C{1H} NMR (101 MHz,
CDCl3) δ 192.1, 157.1, 147.3, 141.6, 138.8, 136.4, 135.0, 130.9,
130.6, 129.0, 122.7, 20.0. HRMS (ESI) m/z: [M+H]+ Calcd for
C13H12NO 198.0914; Found 198.0918.
3-(quinolin-2-yl)benzaldehyde (3n, white solid, PE/EtOAc = 3:1
methyl 3-(pyrimidin-2-yl)benzoate (4b, white solid, PE/EtOAc
1
as eluent, 19.1mg, 41% yield): H NMR (400 MHz, CDCl3) δ
1
= 3:1 as eluent, 83mg, 78% yield): H NMR (400 MHz, CDCl3)
10.18 (s, 1H), 8.70 (s, 1H), 8.53 – 8.46 (m, 1H), 8.29 (d, J = 8.6
Hz, 1H), 8.20 (d, J = 8.5 Hz, 1H), 8.00 (d, J = 7.6 Hz, 1H), 7.95 (d,
J = 8.6 Hz, 1H), 7.87 (d, J = 8.0 Hz, 1H), 7.80 – 7.75 (m, 1H),
7.71 (t, J = 7.7 Hz, 1H), 7.58 (m, 1H). 13C{1H} NMR (101 MHz,
CDCl3) δ 192.2, 155.7, 148.3, 140.6, 137.1, 133.3, 130.3, 129.6,
129.0, 127.5, 126.8, 118.6. HRMS (ESI) m/z: [M+H]+ Calcd for
C16H12NO 234.0914; Found 234.0916.
δ 9.08 (t, J = 1.4 Hz, 1H), 8.78 (d, J = 4.8 Hz, 2H), 8.66 – 8.57
(m, 1H), 8.17 – 8.08 (m, 1H), 7.54 (t, J = 7.8 Hz, 1H), 7.17 (t, J
= 4.8 Hz, 1H), 3.93 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ
166.8, 163.8, 157.3, 138.0, 132.4, 131.7, 130.7, 129.3, 128.7,
119.5, 52.1. HRMS (ESI) m/z: [M+H]+ Calcd for C12H11N2O2
215.0816; Found 215.0825.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 8
(3-(pyridin-2-yl)phenyl)methanol (5a, colorless oil, PE/EtOAc
= 2:1 as eluent, 88mg, 95% yield): H NMR (400 MHz, CDCl3)
7.78 (d, J = 7.6 Hz, 1H), 7.62 (t, J = 7.8 Hz, 1H), 7.29 (d, J = 4.8
Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ 162.6, 157.5, 138.8,
133.5, 132.2, 132.0, 129.4, 120.0, 118.7, 112.9. HRMS (ESI)
m/z: [M+H]+ Calcd for C11H8N3 182.0713; Found 182.0712.
Complex I (yellow solid, EtOAc/ EtOH = 5:1 as eluent, 326mg,
68% yield): H NMR (400 MHz, CDCl3) δ 9.75 (m, H), 8.65
(m, 1H), 8.33 (d, J = 7.1 Hz, 1H), 8.00 (m, 1H), 7.32 – 7.23 (m,
2H), 7.15 – 7.06 (m, 1H), 7.05 – 6.95 (m, 1H), 5.70 (m, 2H),
5.48 (d, J = 5.8 Hz, 1H), 5.25 (d, J = 5.6 Hz, 1H), 2.22 (m, 1H),
1.92 (s, 3H), 1.68 (s, 3H), 0.89 (m, 6H). 13C{1H} NMR (101 MHz,
CDCl3) δ 181.3, 178.9, 172.7, 163.6, 157.1, 142.0, 139.0,
131.0, 127.2, 123.2, 116.5, 100.5, 97.1, 90.1, 89.4, 86.5, 82.5,
31.0, 24.3, 22.3 (d), 18.7.
1
1
2
3
4
5
6
7
8
δ 8.67 (d, J = 4.5 Hz, 1H), 7.97 (s, 1H), 7.87 (d, J = 7.4 Hz, 1H),
7.74 (m, 2H), 7.49 – 7.38 (m, 2H), 7.31 – 7.19 (m, 1H), 4.75
(s, 2H). 13C{1H} NMR (101 MHz, CDCl3) δ 157.3, 149.5, 141.7,
139.5, 136.9, 128.9, 127.5, 126.1, 125.5, 122.2, 120.8, 65.1.
HRMS (ESI) m/z: [M+H]+ Calcd for C12H12NO 186.0914; Found
186.0911.
1
1
(3-(pyrimidin-2-yl)phenyl)methanol
(5b,
colorless
oil,
9
PE/EtOAc = 2:1 as eluent, 96mg, 96% yield): 1H NMR (400
MHz, CDCl3) δ 8.82 (d, J = 4.8 Hz, 2H), 8.44 (s, 1H), 8.38 (d, J =
6.9 Hz, 1H), 7.53 (s, 2H), 7.21 (s, 1H), 4.81 (s, 2H). 13C{1H}
NMR (101 MHz, CDCl3) δ 164.5, 157.2, 141.7, 137.5, 129.4,
128.8, 127.2, 126.6, 119.1, 64.7. HRMS (ESI) m/z: [M+H]+
Calcd for C11H11N2O 187.0866; Found 187.0866.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2-(3-(chloromethyl)phenyl)pyridine
(6a,
colorless
oil,
ASSOCIATED CONTENT
Supporting Information
PE/EtOAc = 5:1 as eluent, 86mg, 85% yield): 1H NMR (400
MHz, CDCl3) δ 8.72 (d, J = 4.5 Hz, 1H), 8.07 (s, 1H), 7.99 –
7.90 (m, 1H), 7.80 – 7.72 (m, 2H), 7.48 (d, J = 7.1 Hz, 2H), 7.29
– 7.21 (m, 1H), 4.69 (s, 2H). 13C{1H} NMR (101 MHz, CDCl3)
δ 156.8, 149.7, 139.9, 138.1, 136.8, 129.2 (d), 127.2, 126.9,
122.4, 120.6, 46.2. HRMS (ESI) m/z: [M+H]+ Calcd for
C12H11ClN 204.0575; Found 204.0572.
The Supporting Information is available free of charge on the
ACS Publications website at DOI:. Experimental procedures,
characterization data, NMR spectra of products, and crystal
structure (PDF).
AUTHOR INFORMATION
2-(3-(chloromethyl)phenyl)pyrimidine (6b, yellow solid,
PE/EtOAc = 5:1 as eluent, 90mg, 88% yield): 1H NMR (400
MHz, CDCl3) δ 8.83 (d, J = 4.8 Hz, 2H), 8.50 (s, 1H), 8.43 (d, J =
7.3 Hz, 1H), 7.53 (m, 2H), 7.22 (s, 1H), 4.70 (s, 2H). 13C{1H}
NMR (101 MHz, CDCl3) δ 164.2, 157.3, 138.0 (d), 130.9, 129.1,
128.3 (d), 119.3, 46.1. HRMS (ESI) m/z: [M+H]+ Calcd for
C11H10ClN2 205.0528; Found 205.0528.
Corresponding Author
E-mail: ligang@aynu.edu.cn; cuixl@hqu.edu.cn.
OCRID
Gang Li: 0000-0002-1609-449X
Xiuling Cui: 0000-0001-5759-766X
Notes
(E)-2-(3-styrylphenyl)pyridine (7a, white solid, PE/EtOAc = 6:1
1
as eluent, 121mg, 94% yield): H NMR (400 MHz, CDCl3) δ
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
8.76 (d, J = 4.3 Hz, 1H), 8.23 (s, 1H), 7.90 (d, J = 7.5 Hz, 1H),
7.76 (d, J = 12.9 Hz, 2H), 7.59 (t, J = 8.7 Hz, 3H), 7.49 (t, J = 7.6
Hz, 1H), 7.41 (d, J = 7.4 Hz, 2H), 7.31 (d, J = 7.3 Hz, 4H). 13C{1H}
NMR (101 MHz, CDCl3) δ 157.3, 149.7, 139.8, 137.9, 137.3,
136.8, 129.2 (d), 128.8, 128.5, 127.8, 127.1, 126.6, 126.2,
125.2, 122.3, 120.7. HRMS (ESI) m/z: [M+H]+ Calcd for
C19H16N 258.1278; Found 258.1279.
We gratefully acknowledge the Program of Science and
Technology
Innovation
Talents
of
Henan
Province(19HASTIT035), the National Natural Science
Foundation of China (NSFC, No. 21102005) for financial
support of this work.
(E)-2-(3-styrylphenyl)pyrimidine (7b, white solid, PE/EtOAc =
1
6:1 as eluent, 119mg, 92% yield): H NMR (400 MHz, CDCl3)
δ 8.85 (d, J = 4.8 Hz, 2H), 8.65 (s, 1H), 8.38 (d, J = 7.7 Hz, 1H),
7.66 (d, J = 7.6 Hz, 1H), 7.57 (d, J = 7.4 Hz, 2H), 7.53 (d, J = 7.8
Hz, 1H), 7.40 (t, J = 7.5 Hz, 2H), 7.30 (d, J = 7.1 Hz, 1H), 7.26 (d,
J = 6.4 Hz, 2H), 7.22 (t, J = 4.8 Hz, 1H). 13C{1H} NMR (101 MHz,
CDCl3) δ 164.6, 157.3, 137.9 (d), 137.3, 129.2, 129.0, 128.9,
128.7, 128.4, 127.7, 127.4, 126.6, 126.2, 119.2. HRMS (ESI)
m/z: [M+H]+ Calcd for C18H15N2 259.1230; Found 259.1233.
3-(pyridin-2-yl)benzonitrile (8a, white solid, PE/EtOAc = 3:1 as
eluent, 79mg, 88% yield): 1H NMR (400 MHz, CDCl3) δ 8.72 (s,
1H), 8.33 (s, 1H), 8.24 (d, J = 7.5 Hz, 1H), 7.80 (d, J = 7.4 Hz,
1H), 7.72 (m, 2H), 7.62 – 7.53 (m, 1H), 7.36 – 7.22 (m, 1H).
13C{1H} NMR (101 MHz, CDCl3) δ 154.9, 150.0, 140.5, 137.1,
132.2, 131.0, 130.6, 129.6, 123.2, 120.5, 118.7, 113.0. HRMS
(ESI) m/z: [M+H]+ Calcd. For C12H9N2 181.0761; Found
181.0760.
REFERENCES
(1) (a) Larock, R. C. Comprehensive Organic Transformation: A
Guide to Functional Group Preparation, 2nd ed; Wiley-VCH:
New York, 1999. (b) Tokuyama, H.; Yokoshima, S.; Lin, S.-
C.; Li, L.; Fukuyama, T. Reduction of ethanethiol esters to
aldehydes. Synthesis, 2002, 1121-1123. (c) Carey, F. A.;
Sundberg, R. J. Advanced Organic Chemistry; Springer:
Heidelberg, Germany, 2007. (d) Lawrence, N. J. Aldehydes
and ketones. J. Chem. Soc. Perkin Trans. 1998, 1, 1739-1750.
(e) Larock, R. C. Comprehensive Organic Transformations;
Wiley-55 VCH: New York, 1988.
(2) (a) Aldabbagh, F. Compr. Org. Funct., Group Transform. II.
2005, 3, 99-133. (b) Gattermann, L.; Koch, J. A. New
Synthesis of Aromatic Aldehydes. Ber. 1897, 30, 1622-1624.
(c) Truce, W. E. The Gattermann Synthesis of Aldehydes. Org.
React. 1957, 9, 37-72.
3-(pyrimidin-2-yl)benzonitrile (8b, white solid, PE/EtOAc = 3:1
as eluent, 91mg, 82% yield): 1H NMR (400 MHz, CDCl3) δ
8.85 (d, J = 4.8 Hz, 2H), 8.81 (s, 1H), 8.71 (d, J = 7.9 Hz, 1H),
ACS Paragon Plus Environment

Page 7 of 8
The Journal of Organic Chemistry
(3) (a) Duff, J. C.; Bills, E. J. Reactions between
Bag, S.; Jayarajan, R.; Dutta, U.; Chowdhury, R.; Mondal, R.;
Maiti, D. Remote meta‐C–H Cyanation of Arenes Enabled
by a Pyrimidine‐Based Auxiliary, Angew. Chem. Int. Ed.
2017, 56, 12538-12542.
1
2
3
4
5
6
7
8
hexamethylenetetramine and phenolic compounds. Part I. A
new method for the preparation of 3- and 5-aldehydosalicylic
acids. Chem, J. Soc. 1932, 1987-1988. (b) Duff, J. C. A new
method for the preparation of p-dialkylaminobenzaldehydes.
Chem, J. Soc. 1945, 276-277.
(9) (a) Ackermann, L. Carboxylate-Assisted Ruthenium-
Catalyzed Alkyne Annulations by C–H/Het–H Bond
Functionalizations. Acc. Chem. Res. 2014, 47, 281-295. (b)
Arockiam, P. B.; Bruneau, C.; Dixneuf, P. H. Ruthenium(II)-
Catalyzed C–H Bond Activation and Functionalization. Chem.
Rev. 2012, 112, 5879-5918.
(4) (a) Reimer, K.; Tiemann, F. Ueber die Einwirkung von
Chloroform auf Phenole und besonders aromatische
Oxysäuren in alkalischer Lösung. Ber. Dtsch. Chem. Ges.
1876, 9, 1268-1278. (b) Wynberg, H. The Reimer-Tiemann
Reaction. Chem. Rev. 1960, 60, 169-184. (c) Wynberg, H.;
Meijer, E. W. The Reimer−Tiemann Reaction. Organic
Reactions; John Wiley and Sons: New York, 1982, 28, 1-36.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(10) For representative examples, see: (a) Barlow, H. L.; Teskey,
C. J.; Greaney, M. F. Ruthenium-Catalyzed meta-
Carboxylation. Org. Lett. 2017, 19, 6662-6665. (b) Li, G. B.;
Li, D. Z.; Zhang, J.; Shi, Y. D.-Q.; Zhao, Y. S. Ligand-
Enabled Regioselectivity in the Oxidative Cross-coupling of
Arenes with Toluenes and Cycloalkanes Using Ruthenium
Catalysts: Tuning the Site-Selectivity from the ortho to meta
Positions. ACS Catal. 2017, 7, 4138-4143. (c) Jing, K.; Li, Z.-
Y.; Wang, G.-W. Direct Decarboxylative Meta-Selective
Acylation of Arenes via an Ortho-Ruthenation Strategy. ACS
Catal. 2018, 8, 11875-11881. (d) Li, J.; Warratz, S.; Zell, D.;
De, S. S.; Ishikawa, E. E.; Ackermann, L. N-Acyl Amino
Acid Ligands for Ruthenium(II)-Catalyzed meta-C–H tert-
Alkylation with Removable Auxiliaries. J. Am. Chem. Soc.
2015, 137, 13894-13901. (e) Gandeepan, P.; Koeller, J.;
(5) Bennasar, M. L.; Zulaica, E. D.; Alonso, S. Facile synthesis of
azocino[4,3-b]indoles by ring-closing metathesis. Tetrahedron,
2007, 63, 861-866.
(6) (a) Vilsmeier, A.; Haack, A. Vilsmeier-Haack reaction. Bull.
Soc. Chim. France. 1962, 1989-1999. (b) Lauchli, R.; Shea, K.
J. A Synthesis of the Welwistatin Core. Org. Lett. 2006, 8,
5287-5289. (c) Coldham, I.; Dobson, B. C.; Fletcher, S. R.;
Franklin, A. I. Intramolecular Dipolar Cycloaddition
Reactions to Give Substituted Indoles – A Formal Synthesis
of Deethylibophyllidine. Eur. J. Org. Chem. 2007, 16, 2676-
2686. (d) Vilsmeier, A.; Haack, A. Über die Einwirkung von
Halogenphosphor auf Alkyl ‐ formanilide. Eine neue
Methode zur Darstellung sekundärer und tertiärer p ‐
Alkylamino‐benzaldehyde. Ber. Dtsch. Chem. Ges. 1927, 60,
119-122. (e) Jones, G.; Stanforth, S. P. The Vilsmeier
Reaction of Non-Aromatic Compounds. Org. React. 2000, 56,
355-659.
Korvorapun,
K.;
Mohr,
J.;
Ackermann,
L.
Visible‐Light‐Enabled
Ruthenium‐Catalyzed
meta‐C−H Alkylation at Room Temperature. Angew. Chem.,
Int. Ed. 2019, 58, 9820-9825. (f) Clark, A. M.; Rickard, C. E.
F.; Roper, W. R.; Wright, L. J. Electrophilic Substitution
Reactions at the Phenyl Ring of the Chelated 2-(2‘-
Pyridyl)phenyl Ligand Bound to Ruthenium(II) or
Osmium(II). Organometallics, 1999, 18, 2813-2820. (g)
Wang, X.-G.; Li, Y. K.; Liu, H.-C.; Zhang, B.-S.; Gou, X.-Y.;
Wang, Q. ; Ma, J. W.; Liang, Y.-M. Three-Component
Ruthenium-Catalyzed Direct Meta-Selective C–H Activation
of Arenes: A New Approach to the Alkylarylation of Alkenes.
J. Am. Chem. Soc. 2019, 141, 13914-13922. (h) Sagadevan,
A.; Greaney, M. F. meta ‐ Selective C−H Activation of
Arenes at Room Temperature Using Visible Light: Dual ‐
Function Ruthenium Catalysis. Angew. Chem., Int. Ed. 2019,
58, 9826-9830.
(7) (a) Zhu, C.; Pinkert, T. S.; Greßies, s.; Glorius, F. One-Pot C–
H Formylation Enabled by Relay Catalysis of Manganese(I)
and Iron(III). ACS Catal. 2018, 8, 10036-10042. (b) Masahito,
K. O.; Takayuki, Y. A Direct and Mild Formylation Method
for Substituted Benzenes Utilizing Dichloromethyl Methyl
Ether–Silver Trifluoromethanesulfonate. J. Org. Chem. 2013,
78, 3438-3444.
(8) For representative examples, see: (a) Li, J.; De Sarkar, S.;
Ackermann, L. Top. Organomet. Chem. 2015, 55, 217-257. (b)
Cheng, C.; Hartwig, J. F. Rhodium-Catalyzed Intermolecular
C–H Silylation of Arenes with High Steric Regiocontrol.
Science, 2014, 343, 853-857. (c) Ye, M.; Gao, G.-L.; Yu, J.-Q.
Ligand-Promoted C-3 Selective C–H Olefination of Pyridines
with Pd Catalysts. J. Am. Chem. Soc. 2011, 133, 6964-6967.
(d)Tang, R.-Y.; Li, G.; Yu, J.-Q. Conformation-induced
remote meta-C–H activation of amines. Nature 2014, 507,
215-220. (e) Wang, X.-C.; Gong, W.; Fang, L.-Z.; Zhu, R.-Y.;
Li, S.; Engle,K. M.; Yu, J.-Q. Ligand-enabled meta-C–H
activation using a transient mediator. Nature, 2015, 519, 334-
338. (f) Dong, Z.; Wang, J.; Dong, G. Simple Amine-Directed
Meta-Selective C–H Arylation via Pd/Norbornene Catalysis. J.
Am. Chem. Soc. 2015, 137, 5887-5890. (g) Phipps,R. J.;
Gaunt, M. J. A Meta-Selective Copper-Catalyzed C–H Bond
Arylation. Science, 2009, 323, 1593-1597. (h) Dey, A.; Sinha,
S. K.; Achar, T. K.; Maiti, D. Accessing Remote meta‐ and
para‐C(sp2)−H Bonds with Covalently Attached Directing
Groups, Angew. Chem. Int. Ed. 2019, 58, 10820-10843. (i)
(11) (a) Hazra, S.; Deb, M.; Elias, A. J. Iodine catalyzed oxidation
of alcohols and aldehydes to carboxylic acids in water: a
metal-free route to the synthesis of furandicarboxylic acid and
terephthalic acid. Green Chem. 2017, 19, 5548-5552. (b) Zou,
L.-H.; Reball, J.; Mottweiler, J.; Bolm, C. Transition metal-
free direct C–H bond thiolation of 1,3,4-oxadiazoles and
related heteroarenes. Chem. Commun. 2012, 48, 11307-11309.
(12) Ali, M. A.; Yao, X. Y.; Sun, H.; Lu, H. J. [RhCp*Cl2]2-
Catalyzed Directed N-Boc Amidation of Arenes “on Water”.
Org. Lett. 2015, 17, 1513-1516.
(13) Becker, J.; Gupta, P.; Angersbach, F.; Tuczek, F.; Näther,
C.; Holthausen, M. C.; Schindler, S. Selective Aromatic
Hydroxylation with Dioxygen and Simple Copper Imine
Complexes. Chem. – Eur. J. 2015, 21, 11735-11744.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 8
(17) Li, Z.-Y.; Li, L.; Li, Q.-L.; Jing, K.; Xu, H.; Wang, G.-
(14) Wadsworth, D. H.; Schupp, O. E.; Seus, E. J.; Ford, J. A. Jr.
The stereochemistry of the phosphonate modification of the
Wittig reaction. J. Org. Chem. 1965, 30, 680-685.
1
2
W. Ruthenium-Catalyzed meta-Selective C-H Mono- and
Difluoromethylation of Arenes through ortho-Metalation
Strategy. Chem. - Eur. J. 2017, 23, 3285-3290.
3
4
5
6
(15) Fang, C. J.; Li, M. C.; Hu, X. Q.; Mo, W. M.; Hu, B. X.; Sun,
N.; Jin, L. Q.; Shen, Z. L. A practical iodine-catalyzed
oxidative conversion of aldehydes to nitriles. RSC Adv. 2017,
7, 1484-1489.
7
(16) Li, G.; Jia, C.; Chen, Q.; Sun, K.; Zhao, F.; Wu, H.; Wang,
Z.; Lv, Y.; Chen, X. Copper(I)-Catalyzed Dehydrogenative
Amidation of Arenes Using Air as the Oxidant. Adv. Synth.
Catal. 2015, 357, 1311-1315
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ACS Paragon Plus Environment