Dehydrogenation of Alcohols to Carboxylic Acid Catalyzed by in Situ-Generated Facial Ruthenium- CPP Complex

Article abstract of DOI:10.1021/acs.joc.9b01100

A selective catalytic system for the dehydrogenation of primary alcohols to carboxylic acids using a facial ruthenium complex generated in situ from the [Ru(COD)Cl₂]_n and a hybrid N-heterocyclic carbene (NHC)-phosphine-phosphine ligand (CPP) has been first reported. The facial coordination model was unveiled by NMR analysis of the reaction mixture. Such a fac-ruthenium catalyst system exhibited high catalytic activity and stability, and a high turnover number of 20 000 could be achieved with catalyst loading as low as 0.002 mol %. The exceedingly high catalyst stability was tentatively attributed to both the anchoring role of NHC and the hemi-lability of phosphines. The catalytic system also features a wide substrate scope. In particular, the facial coordination of CPP ligands was found to be beneficial for sterically hindered alcohols, and ortho-substituted benzylic alcohols and bulky adamantanyl methanol as well as cholesterol were all found to be viable dehydrogenation substrates.

Full text of DOI:10.1021/acs.joc.9b01100

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Article
Dehydrogenation of Alcohols to Carboxylic Acid Catalyzed
by in-situ Generated Facial Ruthenium-CPP Complex
Hui-Min Liu, Lei Jian, Chao Li, Chunchun Zhang, Hai-yan Fu, Xue-Li Zheng, Hua Chen, and Rui-xiang Li
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b01100 • Publication Date (Web): 25 Jun 2019
Downloaded from http://pubs.acs.org on June 25, 2019
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Dehydrogenation of Alcohols to Carboxylic Acid Catalyzed by in-situ Generated
Facial Ruthenium-CPP Complex
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‡
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Hui-min Liu , Lei Jian , Chao Li , Chun-chun Zhang , Hai-yan Fu* , Xue-li Zheng ,
†
†
Hua Chen , and Rui-xiang Li *
†Key Laboratory of Green Chemistry & Technology, Ministry of Education College of
Chemistry, Sichuan University Chengdu 610064, P. R. China.
‡Analytical & Testing Center, Sichuan University, Chengdu, Sichuan 610064, P. R.
China.
Fax: (+86)-28-8541-2904; e-mail: liruixiang@scu.edu.cn; scufhy@scu.edu.cn
Anchoring effect
C
Provide wide open
coordination space
Hemilability
P
P
O
R
CH2OH
+
2 H2
KOH, then HCl
R
OH
=
Ru
N
The first example for facial-Ru complexes catalized
dehydrogenation of alcohols to acids
High reactivity and stability (TON up to 20000)
Broad substrate scope
PPh2
PPh2
C
P
N
=
N
Cl
P
Compatible with the sterically demanding alcohols
ABSTRACT: A selectively catalytic system for the dehydrogenation of primary
alcohols to carboxylic acids using a facial ruthenium complex generated in-situ from
the [Ru(COD)Cl ] and a hybrid NHC-phosphine-phosphine ligand (CPP) has been
2
n
first reported. The facial coordination model was unveiled by NMR analysis of the
reaction mixture. Such fac-ruthenium catalyst system exhibited high catalytic activity
and stability, and a high turnover number of 20000 could be achieved with a catalyst
loading as low as 0.002 mol%. The exceedingly high catalyst stability was tentatively
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attributed to both the anchoring role of the NHC and the hemi-lability of the phosphine.
The catalytic system also features a wide substrate scope. In particular, the facial
coordination of CPP ligand was found to be beneficial for the sterically hindered
alcohols, and the ortho-substituted benzylic alcohols and bulky adamantanyl-methanol
as well as the cholesterol were all viable dehydrogenation substrates.
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INTRODUCTION
The selective oxidation of primary alcohols to carboxylic acids is an important
1
transformation in both academic research and industrial production. Traditionally,
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either the stochiometric amount of toxic (in) organic oxidant or the hydrogen acceptor
3
reagents are required to accomplish this transformation. However, the low atom
efficiency and frequently generated heavy metal and organic wastes does not meet the
requirements of atom economy and environment concerns. In recent years, acceptorless
alcohol dehydrogenation system has emerged as a green alternative method, where
without any oxidant or hydrogen acceptor is required and the only by-product is the
molecule hydrogen which could be used as a fuel.4-18
A wide range of efficient catalytic system based on Ru,4-13 Rh, Ir, Fe, Ni and
Mn16,18 complexes have been investigated in such an acceptorless alcohol
dehydrogenation reaction. Among them, the most studied catalyst precursors are the
ruthenium-based complexes modified by different ligands. The first example of
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16
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homogeneously catalyzed transformation of alcohols to carboxylic acids was reported
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by Milstein et al. in 2013 by using the ruthenium complex with a PNN-type pincer
ligand. Since then, several other ruthenium complexes containing PNP and NNN8,9
pincer ligands, have also been successfully used in this reaction (Scheme 1). These
tridentate “pincer ligands” tend to coordinate in a meridional geometry around the metal
4
a
5-7
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center, and embrace a planar framework, which crosscuts the coordination sphere
around the metal center. Although such a meridional geometry offers an enhanced
stability to the resulting pincer complexes, which exhibited good catalytic performance
in the acceptorless alcohol dehydrogenation reaction, these mer-Ru complexes are too
rigid to reflect hemi-lability which is beneficial for the catalytic reactivity due to the
formation of two five-membered rings around the Ru center.
Recently, our group has developed two new hybrid N-heterocyclic carbene (NHC)
phosphine ligands, one is pincer type CNP and the another is tripodal CPP, their
structures are shown in Scheme 1. Due to their coordination sites are far away from
each other by 4 to 5 bonds, these ligands tend to form a more flexible six-, seven- or
even eight-membered ring upon coordination with the metal center. Such structural
features may enforce them forming a facial configuration,20,21 in which three chelating
atoms occupy one face of the octahedron. The facial configuration for the
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RuH(CO)(PPh )(κ -CNP)]Cl complex (Ru-CNP for short) has already been
3
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ambiguously confirmed by its X-ray structure in our previous work. In comparison
with the previously reported meridional Ru complexes, these facial Ru complexes own
both a more flexible framework backbone and an open wide coordination space around
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the metal center. We envisioned that such fac-Ru/NHC complexes would exhibit the
following advantages in the catalytic process: (1) the NHC moiety could anchor the
metal center by robust bonding; (2) the hemilabile phosphine/amine moiety could
stabilize the coordinatively unsaturated catalytic species; (3) the wide coordination
space could provide more opportunity to accommodate the substrate. Most likely
benefit from these advantages, the fac-Ru complexes showed excellent catalytic
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properties in our previous reported catalytic N-alkylation of aromatic amine and the
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acceperless-dehydrogention of alcohol. Encouragingly, the above-mentioned fac-Ru-
CNP complex has successfully enabled the cross-coupling dehydrogenative cross-
coupling of primary alcohols to form cross-esters, which is difficult to achieve and
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scarcely been reported in meridional Ru complex systems. Following our continuing
interest in the catalytic facial Ru complex, we herein demonstrate that they are also
efficient catalysts for the acceptor-less dehydrogenation of alcohol to carboxylic acid.
To the best of our knowledge, this is the first report of fac-ruthenium complexes in
acceptorless alcohol dehydrogenation to carboxylic acid.
Scheme 1. The Representative Pincer Type Ligands Used in the Ru-catalyzed
Dehydrogenation of Primary Alcohol to Acids
O
Ru complex
OH
OH
+
2 H2
Base, Water or Toluene
then HCl
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Previous report
Ru-PNN
Ru-PNP
Ru-NNN
Ru-NNN
H
R'
X
PPh3
X
Cl
HN
N
PtBu2
CO
N
N
N
P
N
N
L
N
Cl
L''
R
NH
Ru
Cl
Ru
H
Ru
Ru
Ru
N
R
N
P
CO
N
Cl
X'
N
L'
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R
R
X''
meridional
Milstein4
5
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7
Szymczak9
Gauvin, Prechtl, Beller
Peng8
This work
Ru-CNP21
Ru-CPP
L''
Ph2
P
X
L
H
Ph2
P
Cl
X
X'
X''
Ru
OC
Ru
X'
Ru
PPh2
L'
N
N
Ph3P
N
X''
N
N
N
facial
RESULTS AND DISCUSSION
Initially, the benzyl alcohol was chosen as the substrate to evaluate the catalytic
properties of the fac-Ru-complex in acceptorless dehydrogenation of alcohol to
carboxylic acid. In our previous report,21 we demonstrated that the fac-Ru-CNP
complex is an excellent catalyst for dehydrogenation of alcohol to ester. The
dehydrogenation of benzyl alcohol (1 mmol) catalyzed by 1 mol% fac-Ru-CNP in
toluene at 110 ℃ for 24 h in the presence of 0.5 of equiv Cs CO led to the selective
2
3
formation of benzyl benzoate in 94% yield. We supposed that the increase of the
basicity and the nucleophilicity of the base would be favorable to form the carboxylic
acid. As expected, a significant amount of benzoic acid was detected when using 0.5
equiv of KOH instead of Cs CO as the base. Increase the amount of KOH to 1.0 equiv
2
3
rapidly increased the carboxylic acid to 69% yield. We were pleased to find that the 1
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mol% of [Ru(COD)Cl ] /CPP (Ru-CPP for short) as the catalyst was even much
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superior to the fac-Ru-CNP, affording the benzoic acid in 85% and 99% yield, in the
presence of 1.0 equiv and 2.0 equiv KOH, respectively. Accordingly, the Ru-CPP was
selected as the catalyst in the following experiment (Table 1).
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The controlled experiments showed that other hydroxide type bases, such as NaOH
and CsOH were less efficient than KOH (entries 2 and 3). The ligand CPP play a key
role in maintaining the catalyst activity, since the absence of it only led to a lower yield
of 21%. Different kinds of solvents were also briefly investigated, and it was found that
besides the toluene, the dioxane is also a proper solvent for this reaction. Considering
the relatively low solubility of potassium carboxylate in toluene than that in dioxane,
we have chosen the toluene as the optimal solvent (Table 1).
Table 1. Optimization of Reaction Conditions for the Dehydrogenation of Benzyl
Alcohol to Carboxylic Acida
1
mol% [Ru(COD)Cl ] , 1 mol% CPP)
2 n
O
KOH (2.0 equiv), Toluene (4 mL)
OH
o
OH
1
20 C, 24 h
+
2 H2
then HCl
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Ph2
P
H
Cl
PPh2
PPh2
OC
N
Ru
[Ru(COD)Cl2]n
N
N
N
Ph3P
Cl
N
N
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Ru-CNP
Ru-CPP
Cs CO , 0.5 eq, trace
2
3
KOH, 0.5 eq, 4%
KOH, 1.0 eq, 69%
KOH, 2.0 eq, 72%
85%
>99%
Entry
Deviation from the standard condition
No change
Yield (%)
>99
73
1
2
3
4
5
6
NaOH instead of KOH
CsOH instead of KOH
65
in absence of CPP
21
DMF or DMSO instead of toluene
Dioxane instead of toluene
trace
97
a
Standard conditions: 1.0 mol% of [Ru(COD)Cl ] , 1 mol% of ligand CPP, benzyl
2
n
o
alcohol (1 mmol) and 2.0 equiv KOH in toluene (4 mL) at 120 C for 24 h under the
nitrogen atmosphere. Yields were determined by GC.
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The advantage of toluene as solvent is that it allows for the easy isolation of the product
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from the catalyst system. The generated potassium carboxylate was easily precipitated
due to the low solubility in toluene, which, after simple filtration, could be converted
into the acids by acidifying with aqueous HCl. While, the filtrate containing the catalyst
would be recycled. Then, we used the benzyl alcohol as the substrate to demonstrate
the catalyst recyclability, after the produced potassium benzoate was isolated by
filtration, and the remaining solution was subjected to the next catalytic cycle. The
outcome showed that the catalyst in the filtrate could be recycled for 5 times, albeit
with a remarkable decreased yield in the fifth cycle (see SI, Figure S1). In addition, to
test the efficiency and the stability of this catalytic system, two large scale experiments
were conducted with the substrate to catalyst ratio being 10000:1, and 50000:1,
respectively. As shown in Figure 1, in the former case the conversion of benzyl alcohol
increased gradually with the prolonged reaction time, even after six days. After six days,
benzyl alcohol has been converted into carboxylic acid. It should be mentioned that a
turnover number (TON) of 20000 for this Ru catalyst could be achieved by employing
0.002 mol% of catalyst after the reaction proceeded 3 days. This is so far the highest
TON value for the Ru catalyzed dehydrogenation of primary alcohol to acid. All
these results revealed that the Ru-CPP is a highly active and robust catalyst for the
acceptorless dehydrogenation of alcohol to carboxylic acid.
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Figure 1. The Influence of Reaction Time on the Conversion.
After the establishment of the robust catalytic system: 1 mol% of CPP, 1 mol% of
o
[
Ru(COD)Cl ] , and 2.0 equiv of KOH in toluene at 120 C for 24 h under the nitrogen
2 n
atmosphere, we next investigated the substrate scope in terms of alcohols. A wide range
of alcohols including aliphatic, (hetero)aromatic alcohols were studied (Table 2). The
catalytic system exhibited a wide substrate scope and all the tested alcohols could be
smoothly converted into the carboxylic acids under the optimal condition in 25-99%
isolated yields. In case of aliphatic alcohols, the yields of the reaction were generally
high ranging from 55-98% (Table 2, 2a-2f). Various benzylic alcohol derivatives also
reacted well in this system (Table 2, 2g-2x). For the benzylic alcohols bearing a
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substituent at the meta/para position of the aromatic ring, the yields were higher than
90%, regardless of the substituent is electron-rich or -poor (Table 2, 2h-2m). It is worth
mentioning that sterically demanding substrates, such as the adamantanyl-methanol and
the ortho-substituted benzylic alcohols, could also undergo this transformation
smoothly to afford corresponding carboxylic acids in good yields of 31-96% (Table 2,
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n-2s). So far, only few examples of sterically demanding alcohols have been
demonstrated in the dehydrogenation reaction.4a,15b,18 Take the adamantanyl-methanol
for example, there are only two catalytic systems being reported, which suffer from the
either low reactivity15b or forcing reaction conditions. These results showed that our
designed fac-Ru-CPP catalyst was advantageous for the alcohol with large steric
hindrance. However, for the aromatic alcohols bearing an electron-deficient group at
ortho-position, the reaction outcome is often complicated, possibly due to the
undesirable side-reactions. For example, when using 2-(2-nitrophenyl)ethan-1-ol as the
dehydrogenation substrate, we unexpectedly obtained the indole as the major product
in 35% GC yield (Table 2, 2t). The reason might be that the nitro group serve as the
hydrogen acceptor during the alcohol dehydrogenation process, and the resulted
23
2
4
aldehyde and amino functional groups would then condense to give the indole. Finally,
the 2-naphthalenemethanol was easily converted into 2-naphthoic acid in 90% yield
(
Table 2, 2u). Furthermore, heteroaryl alcohols, such as 3-thiophenylmethanol, 2-
furanylmethanol and 3-pyridinylmethanol were also well tolerated, and generating the
corresponding product in 25-92% yield (Table 2, 2v-x).
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1
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2
2
2
2
2
2
2
2
2
3
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3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
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9
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1
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9
0
Table 2. Dehydrogenation of Different Primary Alcohols to Carboxylic Acidsa
1 mol% CPP, 1 mol% [Ru(COD)Cl2]n
O
o
KOH, Toluene (4 mL), 120 C, 24 h
+
2 H2
R
OH
a-x
R
OH
2a-x
then HCl
1
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1
1
1
1
2
2
2
2
2
2
2
2
2
2
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3
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4
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O
O
O
O
n-C H
OH
n-C H
7
15
OH
n-C H
8 17
OH
OH
6
13
2
b 95%
2c 94%
2
a, 79%
2d 98%
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
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5
6
7
8
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1
2
3
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6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
O
O
O
O
n-C H
OH
OH
OH
OH
11
23
2
e 90%
2f 55%
2g 92%
2h 95%
O
O
O
O
MeO
OH
OH
OH
OH
MeO
F3C
Cl
2i 94%
2j 87%
2k 92%
2l 93%
O
O
O
O
F
OH
OH
OH
OH
OMe
2
m 94%
2n 72%
2o 96%
2p 31%
O
O
O
H
N
OH
OH
OH
Cl
2
q 75%
2r 73%
2s 68%
2t 35%
O
O
O
O
O
OH
OH
OH
OH
S
N
2
u 90%
2v 76%
2w 25%
2x 92%
a
Reaction conditions: [Ru(COD)Cl ] (1 mol%), ligand CPP (1 mol%), alcohol (1
2
n
o
mmol) and KOH (2.0 equiv) in toluene (4 mL) at 120 C for 24 h under the nitrogen
atmosphere; After of the reaction, the corresponding acid salts was converted to
carboxylic acids by treatment with hydrochloric acid (4 mmol); the isolated yield.
As noted earlier, the facial Ru-complex may provide a wide-open coordination space
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around the Ru center and hence is beneficial for the large molecules approaching. To
further confirm this, we selected a more sterically hindered molecule cholesterol as the
dehydrogenation substrate. To our pleasure, the facial-Ru catalytic system was proved
to be capable of dehydrogenation of the cholesterol and followed by double bond
isomerization to give cholest-4-en-3-one in 42% yield. The reason for the double bond
isomerization of the dehydrogenative product might be the presence of a base in the
system, since the base was believed to act a promoter in double bond isomerization to
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
2
5
the thermodynamically more stable products. The cholest-4-en-3-one is a potentially
26
27
bioactive compounds and often prepared from cholesterol under enzyme catalysis.
While the chemical oxidation of the cholesterol usually use the stochiometric amount
2
8
29
30
of toxic oxidation reagents such as Martin, PhI(OAc) , N-chlorosuccinimide, etc.
2
We herein present the first example of dehydrogenative oxidation of cholesterol
(
Scheme 2).
Scheme 2. Ru-CPP Catalyzed Dehydrogenation of Cholesterol
R
R
2
mol% [Ru(COD)Cl ] , 2 mol% CPP
2 n
H
H
KOH (2.0 equiv), Tol (4 mL)
H
H
H
H
o
120 C, 24 h, N
2
O
HO
1y, R = (CH2)3CH(CH3)2
2y, 42% isolated yield
In order to get further information about the reaction mechanism, we performed the
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1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
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5
5
5
5
5
5
5
5
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following experiments. Firstly, in order to find out the oxygen source for the oxidation
1
8
of primary alcohols to acids, we reacted the benzyl alcohol with the O-labeled and
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
nonlabelled potassium hydroxide, respectively, then analyzed the produced potassium
benzoates using IR, ESI/MS and NMR. In the former case, a wave number of 1677 cm-1
-1
was detected in IR spectrum, which is obviously lower than 1693 cm for the potassium
benzoate obtained from the nonlabelled KOH (Table 3). In addition, the electro-spray
1
8
ionization/mass spectrum (ESI/MS) of the sample prepared from the O labeled KOH
display two major peaks at m/z = 125.04 and 123.04 and one minor peak at 121.03,
while only one peak at m/z = 121.03 was observed for the latter case. The peaks at m/z
1
8
=
123.04 and 125.04 correspond to the benzoic salts labeled with one and two O atoms,
1
8
respectively. The two O atoms incorporation is presumed to arise from the Cannizzaro
1
8
reaction of the intermediate benzaldehyde mediated by O-labled KOH (see SI, Figure
1
3
S2-7). Similarly, C NMR spectrum showed three resonance signals for carboxylic
group of potassium benzoate at 167.34, 167.32, 167.29 ppm in the former case, while
in contrast, only one peak at 167.34 ppm was shown in the latter case (see SI, Figure
S2). All of these results revealed that the oxygen atom incorporated into the carboxylic
acids originate from potassium hydroxide.
1
8
Table 3. Comparative Data of the Benzoic Acids Prepared From K OH and KOH
18
K OH
KOH
1693
-
1
IR(cm )
1677
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m/z
Chemical shift for C NMR
121.03, 123.04, 125.04
167.34, 167.32, 167.29
121.03
167.34
13
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Then, the evolution of H gas was measured by reacting 1.0 mmol of benzyl alcohol in
2
a Schlenk tube connected to a burette filled with water. A total volume of evolved
dihydrogen gas was 44.5 mL, corresponding to approximately 1.9 mmol, which was
calculated using the ideal gas law. The molar amount of which confirms that 2 equiv of
dihydrogen is released during the dehydrogenation reaction (Figure 2). This is in line
1
0
with Madsen’s previous report. It was shown from the H evolution experiments that
2
the rate of dehydrogenation of benzyl alcohol was fast and the reaction was completed
within 7 h, but in view of the relatively low reactivity of the aliphatic acohols (see SI,
Table S1), we prolonged the reaction time to 24 h when investigated the substrate scope
(see Table 2).
Figure 2. Evolution of Dihydrogen Over Time.
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1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
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3
3
3
3
3
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4
4
4
4
4
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5
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Reaction conditions: [Ru(COD)Cl ] (1 mol%), ligand CPP (1 mol%), benzyl alcohol
2
n
o
(1 mmol) and KOH (2.0 equiv) in toluene (4 mL) at 120 C for 7 h under the nitrogen
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
atmosphere.
Considering the intermediate benzaldehyde could undergo a Cannizzaro reaction in
the presence of KOH, two parallel experiments with and without the Ru-complex were
o
conducted in toluene at 120 C for 1 h, and after neutralization with aqueous HCl, the
benzoic acid was obtained in 55% and 98% yields, respectively (Scheme 3). These
results clearly demonstrated that both the Cannizzaro and the Ru-catalyzed
dehydrogenation pathway are operating in case of the benzylic alcohol derivatives as
substrates.10
Scheme 3. Cannizzaro and Dehydrogenation Reaction of Benzaldehyde
KOH (2.0 equiv), Tol (4 mL)
o
1
20 C, 1 h
OH
OH
+
+
OH
OH
then HCl
44%
55%
O
O
O
1 mol% Ru/CPP
KOH (2.0 equiv), Tol (4 mL)
H
o
1
20 C, 1 h
then HCl
trace
98%
3
1
Then, we conducted a mercury poisoning experiment under the standard reaction
condition, by adding 500 equivalents of mercury with respect to [Ru (COD)Cl ] . The
2
n
dehydrogenation yield of benzyl alcohol in the presence of mercury resulted in 78%
yield after 15 h, without significant decrease in activity. The result indicates that the
ruthenium nanoparticles are not formed during the catalytic cycle. Furthermore, the
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kinetic profile of hydrogen evolution did not exhibit S curve, and without inductive
time was observed, thus revealing that the reaction follows a homogenous catalytic
pathway.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
However, possibly due to the structural flexibility and fluxionality of the fac-Ru-
CPP complex, the attempt to isolate it was not successful. We therefore studied the
benzyl alcohol dehydrogenation process using the in-situ NMR experiments to get
further information on the coordination behavior of the CPP ligand (Figure 3). Firstly,
a deuterated toluene solution containing 0.5 mmol of benzyl alcohol, 10 mol% of CPP,
o
0.5 mmol of KOH and 10 mol% of [Ru(COD)Cl ] was heated to 120 C under the
2
n
1
nitrogen atmosphere for 1 h, then which was then submitted to H NMR analysis, the
spectrum displays two dd (doublet of doublets) peaks in the typical hydride region at
−6.35 ppm and −6.75 ppm, both of them share with the same coupling constants (2JH−P
=
15.2 Hz and 2JH−H = 2.4 Hz). This observation serves as a key evidence pointing to
the two facts: (1) A [RuH ] species is present in the catalytic system, which was
2
coordinated with only one P atom of the ligand CPP; (2) In this species, the two
hydrides and the P atom coordinates in a cis configuration to each other. This
2
2
conclusion is in good agreement with our previously report. Particularly, this typical
[
RuH ] species was only observed in the system with the presence of both the benzyl
2
alcohol and KOH, and it disappeared after removal of either of them. Apart from
RuH ], there also exist a singlet at 9.6 ppm, a characteristic peak of the benzaldehyde,
[
2
which probably produced from the dehydrogenation of the benzyl alcohol. These facts
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1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
indicated that the two hydrides most likely come from the benzyl alcohol via its
coordination to Ru-CPP complex followed by a KOH promoted β-hydride elimination
process.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
3
1
The sample taken from the above-mentioned solution was also analyzed by P NMR.
Interestingly, no signal was shown in the typical range for free phosphine, which
usually resonates at upfield in a negative value. The reason was probably due to the
equilibrium between the intermediates a and b (Figure 3), which is so fast that, on the
3
3
NMR time scale, no free phosphorus can be detected. Indeed, the two doublets at 88
3
1
ppm and 71 ppm in P NMR, which have the same coupling constant of 30 Hz (Figure
3
), suggesting the presence of a Ru species with two P atoms arranged cis to each other
34
31
around the Ru center. In addition, no large P, P coupling was observed in P NMR
spectrum of the reaction mixture. These results revealed that ligand CPP most likely
adopts a facial coordination in the catalytic Ru species, which is in line with the
previous literature report by Venanzi, who demonstrated that a tripodal triphosphine
3
5
was prone to adopt a facial coordination with Ruthenium. In addition, two broad
signals centered at 31 ppm and 23 ppm further supported a fast equilibrium among all
the fluxional ruthenium species. The fluxionality of these ruthenium intermediates is
probably attributed to the presence of a hemilabile P-donor, which could dissociate and
coordinate in a hemilabile manner, thus both promoting for substrate binding and the
product dissociation steps. Furthermore, the hemilabile phosphorous in the CPP ligand
is constrained within close proximity of the Ru coordinating sphere due to the anchoring
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effect of NHC moiety, which may benefit greatly to the catalyst stability. Therefore,
the aforementioned high TON value for Ru catalyst could be obtained.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
31
Figure 3. H NMR (400 MHz, toluene-d ) and P NMR (162 MHz, toluene-d ) Spectra
8
8
Evidencing the Presence of RuH (a) and the Facial Ru-complexes (b) in the Reaction
2
Mixture.
1
0
On the basis of these results and the previous Madsen’s report, we proposed a
possible mechanism for the reaction in Scheme 4. First, the ligand CPP replaces the
cycloocta-1,5-diene when mixed with [Ru(COD)Cl ] to give the dichloride ruthenium
2
n
precatalyst I, which then occurs the dissociation of chlorine and coordination of
hydroxyl anion and the primary alcohol to generate Ru-CCP complex II. The catalytic
cycle is initiated by β-hydride elimination of the alkoxyl ligand, which deliver the
important Ru-H species III with concomitant formation of the aldehyde. At this stage,
the resulting aldehyde may dissociate or coordinated with the Ru center in an
equilibrium form. For the coordinated form, the cis hydroxide ligand readily undergoes
a nucleophilic attack to the carbonyl group of the aldehyde, producing a ruthenium
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1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
intermediate IV bearing a hemiacetal ligand, where another β-hydride elimination take
place to give a RuH species V. In this step the hemilabile P atom is dissociated to
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
provide the vacant site for β-hydride elimination. From the intermediate V, the first
molecule of H was released, simultaneously the free P atom dissociated in the previous
2
step coordinated back to stabilize the newly formed Ru-H species VI. The product
potassium carboxylate was generated from VI via the carboxylate group replacement
-
by OH , accompanied by the coordination of another primary alcohol to give Ru-H
species VII, upon which the second H is liberated, thus close the catalytic circle with
2
regeneration of the Ru complex II. It should be mentioned that in case of benzylic
alcohols, the intermediate aromatic aldehyde dissociated from III can also be
transformed into the carboxylic acid via the Cannizzaro reaction. Finally, the peak
displayed at m/z = 747.1711 in the ESI/MS spectra of the catalytic system evidence the
presence of the possible species II-V (the exact mass of them is 747.1717) (see SI,
Figure S3), thus indicating the rationality of the proposed mechanism.
Scheme 4. Proposed Catalytic Cycle
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N
Ph2
P
N
KOH
Ligand CPP + [Ru(COD)Cl2]n
N
Cl
Cl
Ru
P
Ph
2
I
KOH
R
OH
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
N
Ph2
P
N
N
OH
O
H2
Ru
P
Ph
R
2
II
N
Ph2
P
N
N
N
R = Aromatic
O
Ph2
P
N
OH
O
N
OH
Ru
R
OH
Ru
Cannizzaro reaction
R
OK
P
P
O
Ph
2
Ph
H
H
R
2
R
H
III
VII
R = Aromatic or Aliphatic carbon chain Entering the next
catalytic cycle
O
R
OK
KOH + R
OH
N
Ph2
N
H
O
O
N
P
Ru
R
P
N
Ph2
P
N
Ph
2
H
N
O
IV
Ru
R
P
O
Ph
N
Ph2
N
2
H
VI
N
P
H
Ru
H
H
H2
O
O
PPh2
R
V
CONCLUSIONS
In summary, a selectively catalytic dehydrogenation of primary alcohols to carboxylic
acids by using a new type facial Ru-CPP catalyst was presented. This novel efficient
system allows a simple and straightforward synthesis of carboxylic acids in good yields
and the only by-product is the molecular hydrogen. The plausible mechanism was
proposed on the basis of the controlled experiments and NMR studies. Benefit from the
anchoring role of NHC, hemi-lability of phosphine, and the facial coordination of CPP
ligand, the catalyst system featured a high catalytic activity and robust stability, as well
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as a broad substrate scope.
EXPERIMENTAL SECTION
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General Information: All reactions were carried out under nitrogen atmosphere unless
otherwise stated. All solvents were dealt with standard purification method. All
reagents were purchased from commercial suppliers and used as received, and moisture
1
13
31
sensitive compounds were stored in glovebox. H, C and P NMR spectra were
recorded on the Bruker AVANCE III HD-400 MHz in CDCl DMSO-d or toluene-d .
3
,
6
8
GC analysis was performed with Agilent 6890N (KB-1, 30 m × 0.32 mm × 0.25 μm)
and Agilent 6890N-GC/MSD (GC-Mass). HR-MS was measured on SHIMADZU
LCMS-IT-TOF mass spectrometer. CPP ligand and [Ru(COD)Cl ] were synthesized
2
n
according to the reported method.22
Typical catalytic procedure: [Ru(COD)Cl ] (0.01 mmol Ru, 2.8 mg), ligand CPP
2
n
(
0.01 mmol, 5.6 mg) and KOH (2.0 mmol, 112 mg) were added into a dried reaction
tube. After the tube was charged with N , benzyl alcohol (1 mmol, 108.1 mg) and
2
toluene (4 mL) were added to it. The Schlenk tube was placed in a preheated heating
mantle (T = 120 °C) for 24 h. At the end of the reaction, the mixture was cooled to
room temperature, 2 M HCl (4 mL) and ethyl acetate (4 mL) were added to it, and then
the mixture solution was extracted with ethyl acetate (5 ml×2), the combined organic
phase was washed with saturated aqueous HCl (25 ml×2), dried over MgSO , filtered,
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and purified by column chromatography to afford the desired product 2g as a white
solid in 92% yield (112 mg).
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Physical Data of 2a−2y.
4a
n-butanoic acid (2a). General procedure gave pale yellow oily liquid (70 mg, 79%).
1
H NMR (400 MHz, CDCl ): δ 8.14 (s, 1H), 2.34 (t, J = 7.4 Hz, 2H), 1.75 – 1.59 (m,
3
1
3
1
2
1
H), 0.97 (t, J = 7.4 Hz, 3H). C NMR { H} (101 MHz, CDCl ): δ 179.9, 35.9, 18.2,
3
3.6.
2
4
n-heptanoic acid (2b). General procedure gave pale yellow oily liquid (124 mg, 95%).
1
H NMR (400 MHz, DMSO-d ): δ 11.97 (s, 1H), 2.18 (t, J = 7.4 Hz, 2H), 1.54 – 1.42
6
1
3
1
(m, 2H), 1.33 – 1.16 (m, 6H), 0.85 (t, J = 6.8 Hz, 3H). C NMR { H} (101 MHz,
DMSO-d ): δ 174.9, 34.1, 31.5, 28.7, 24.9, 22.4, 14.3.
6
1
8
n-octanoic acid (2c). General procedure gave colorless oily liquid (135 mg, 94%).
1
H NMR (400 MHz, DMSO-d ): δ 11.99 (s, 1H), 2.18 (t, J = 7.4 Hz, 2H), 1.55 – 1.41
6
1
3
1
(m, 2H), 1.17 – 1.30 (m, 8H), 0.86 (t, J = 6.8 Hz, 3H). C NMR { H} (101 MHz,
DMSO-d ): δ 174.9, 34.1, 31.6, 28.9, 28.9, 24.9, 22.5, 14.4.
6
3
6
n-nonanoic acid (2d). General procedure gave colorless oily liquid (155 mg, 98%).
1
H NMR (400 MHz, DMSO-d ): δ 11.96 (s, 1H), 2.18 (t, J = 7.4 Hz, 2H), 1.57 – 1.41
6
13
1
(m, 2H), 1.37 – 1.16 (m, 10H), 0.86 (t, J = 6.8 Hz, 3H). C NMR { H} (101 MHz,
DMSO-d ): δ 174.8, 34.1, 31.8, 29.2, 29.1, 29.0, 24.9, 22.6, 14.3.
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1
2
2
2
2
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2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
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1
n-dodecanoic acid (2e). General procedure gave a white solid (180 mg, 90%). H
NMR (400 MHz, DMSO-d ): δ 11.96 (s, 1H), 2.18 (t, J = 7.4 Hz, 2H), 1.56 – 1.43 (m,
6
0
1
2
3
4
5
6
7
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2
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8
9
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2
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7
8
9
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3
1
2
H), 1.32 – 1.14 (m, 16H), 0.86 (t, J = 6.8 Hz, 3H). C NMR { H} (101 MHz, DMSO-
d6): δ 174.9, 34.1, 31.8, 29.5, 29.5, 29.4, 29.3, 29.2, 29.1, 24.9, 22.6, 14.3.
1
8
1
2
-ethylbutyric acid (2f). General procedure gave a oily liquid (64 mg, 55%). H NMR
(
400 MHz, CDCl ): δ 10.09 (s, 1H), 2.27 – 2.14 (m, 1H), 1.68 – 1.59 (m, 2H), 1.57 –
3
1
3
1
1.49 (m, 2H), 0.93 (t, J = 7.4 Hz, 6H). C NMR { H} (101 MHz, CDCl ): δ 182.7, 48.9,
3
2
4.8, 11.7.
1
0
1
Benzoic acid (2g). General procedure gave a white solid (112 mg, 92%). H NMR
(
400 MHz, DMSO-d ): δ 12.98 (s, 1H), 7.96 (d, J = 7.0 Hz, 1H), 7.63 (t, J = 7.4 Hz,
6
1
3
1
1H), 7.51 (t, J = 7.6 Hz, 1H). C NMR { H} (101 MHz, DMSO-d ): δ 167.8, 133.3,
6
1
31.2, 129.7, 129.0.
2
4
1
4
-methylbenzoic acid (2h). General procedure gave a white solid (129 mg, 95%). H
NMR (400 MHz, DMSO-d ): δ 12.79 (s, 1H), 7.85 (d, J = 8.1 Hz, 2H), 7.31 (d, J = 8.0
6
13
1
Hz, 2H), 2.37 (s, 3H). C NMR { H} (101 MHz, DMSO-d ): δ 167.8, 143.5, 129.1,
6
129.6, 128.5, 21.6.
27
4
-methoxybenzoic acid (2i). General procedure gave a white solid (143 mg, 94%).
1
H NMR (400 MHz, DMSO-d ): δ 12.63 (s, 1H), 7.91 (d, J = 8.9 Hz, 2H), 7.02 (d, J =
6
1
3
1
8
1
.9 Hz, 2H), 3.83 (s, 3H). C NMR { H} (101 MHz, DMSO-d ): δ 167.5, 163.3, 131.8,
6
23.4, 114.3, 55.9.
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-(trifluoromethyl)benzoic acid (2j).15a General procedure gave a white solid (165
1
mg, 87%). H NMR (400 MHz, DMSO-d ): δ 13.49 (s, 1H), 8.15 (d, J = 8.1 Hz, 2H),
6
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
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0
1
2
3
4
5
6
7
8
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3
1
7
.88 (d, J = 8.3 Hz, 2H). C NMR { H} (101 MHz, DMSO-d ): δ 166.7, 135.1, 132.9
6
(
q, J = 31.9 Hz), 130.8, 126.1 (q, J = 3.7 Hz), 125.1 (q, J =274.7 Hz).
1
4
1
4
-chlorobenzoicacid (2k). General procedure gave a white solid (144 mg, 92%). H
NMR (400 MHz, DMSO-d ): δ 13.20 (s, 1H), 7.95 (d, J = 8.6 Hz, 2H), 7.58 (d, J = 8.5
6
1
3
1
Hz, 2H). C NMR { H} (101 MHz, DMSO-d ): δ 166.9, 138.3, 131.6, 130.1, 129.2.
6
3
-methoxybenzoic acid (2l).15a General procedure gave a white solid (141 mg, 93%).
1
H NMR (400 MHz, DMSO-d ): δ 13.03 (s, 1H), 7.56 (d, J = 7.6 Hz, 1H), 7.47 (s, 1H),
6
1
3
1
7
.43 (t, J = 7.9 Hz, 1H), 7.20 (d, J = 8.2 Hz, 1H), 3.82 (s, 3H). C NMR { H} (101
MHz, DMSO-d ): δ 167.6, 159.7, 132.6, 130.2, 122.0, 119.3, 114.3, 55.7.
6
3
8
1
3
-fluorobenzoic acid (2m). General procedure gave a white solid (132 mg, 94%). H
NMR (400 MHz, DMSO-d ): δ 13.31 (s, 1H), 7.80 (d, J = 7.6 Hz, 1H), 7.67 (d, J = 9.6
6
1
3
1
Hz, 1H), 7.55 – 7.60 (m, 1H), 7.53 – 7.46 (m, 1H). C NMR { H} (101 MHz, DMSO-
d6): δ 166.7, 162.4 (d, J = 244.7 Hz), 133.7 (d, J = 7.2 Hz), 131.3 (d, J = 8.0 Hz), 125.9
(d, J = 2.8 Hz), 120.3 (d, J = 21.2 Hz), 116.2 (d, J = 22.6 Hz).
1
-adamantane carboxylic acid (2n).15b General procedure gave a white solid (130 mg,
1
72%). H NMR (400 MHz, DMSO-d ): δ 11.99 (s, 1H), 2.00 – 1.90 (m, 3H), 1.85 –
6
1
3
1
1
3
.73 (m, 6H), 1.72 – 1.60 (m, 6H). C NMR { H} (101 MHz, CDCl ): δ 183.8, 40.5,
3
8.6, 36.4, 27.8.
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1
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1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
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4
1
2
-methylbenzoic acid (2o). General procedure gave a white solid (131 mg, 96%). H
NMR (400 MHz, DMSO-d ): δ 12.78 (s, 1H), 7.82 (d, J = 7.8 Hz, 1H), 7.44 (t, J = 7.5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
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4
5
6
7
8
9
0
1
3
1
Hz, 1H), 7.44 (t, J = 7.5 Hz, 2H), 2.53 (s, 3H). C NMR { H} (101 MHz, DMSO-d ):
6
δ 169.1, 139.4, 132.1, 131.9, 130.9, 130.6, 126.2, 21.7.
1
4
2
-methoxybenzoic acid (2p). General procedure gave a white solid (47 mg, 31%).
1
H NMR (400 MHz, DMSO-d ): δ 12.57 (s, 1H), 7.61 (d, J = 5.8 Hz, 1H), 7.47 (t, J =
6
1
3
8.0 Hz, 1H), 7.09 (d, J = 8.1 Hz, 1H), 6.96 (t, J = 7.0 Hz, 1H), 3.78 (s, 3H). C NMR
{1
H} (101 MHz, DMSO-d ): δ 167.8, 158.5, 133.5, 131.1, 121.7, 120.4, 112.8, 56.1.
6
3
9
2,3-dimethylbenzoic acid (2q). General procedure gave a white solid (113 mg, 75%).
1
H NMR (400 MHz, DMSO-d ): δ 12.79 (s, 1H), 7.50 (d, J = 7.4 Hz, 1H), 7.28 (d, J =
6
1
3
1
7.4 Hz, 1H), 7.12 (t, J = 7.6 Hz, 1H), 2.35 (s, 3H), 2.24 (s, 3H). C NMR { H} (101
MHz, DMSO-d ): δ 170.2, 138.0, 136.7, 132.9, 132.5, 127.5, 125.6, 20.5, 16.7.
6
4
0
2
,4-dimethylbenzoic acid (2r). General procedure gave a white solid (110 mg, 73%).
1
H NMR (400 MHz, DMSO-d ): δ 12.62 (s, 1H), 7.72 (d, J = 7.8 Hz, 1H), 7.08 (d, J =
6
13
1
4
.4 Hz, 1H), 7.05 (s, 1H), 2.46 (s, 3H), 2.28 (s, 3H). C NMR { H} (101 MHz, DMSO-
d6): δ 168.9, 142.2, 139.7, 132.6, 130.9, 127.7, 126.9, 21.8, 21.3.
41
4
-chloro-2-methylbenzoic acid (2s). General procedure gave a white solid (116 mg,
1
68%). H NMR (400 MHz, DMSO-d ): δ 13.00 (s, 1H), 7.83 (d, J = 8.4 Hz, 1H), 7.42
6
1
3
1
(
s, 1H), 7.35 (d, J = 6.6 Hz, 1H), 2.52 (s, 3H). C NMR { H} (101 MHz, CDCl ): δ
3
1
34.7, 126.8, 123.1, 119.7, 118.8, 109.9, 101.6, 28.7.
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Indole (2t).30b General procedure gave a white solid (41 mg, 35%) H NMR (400 MHz,
1
CDCl ): δ 8.08 (s, 1H), 7.58 (d, J = 7.6 Hz, 1H), 7.33 (d, J = 8.1 Hz, 1H), 7.16 – 7.10
3
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
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5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
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1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
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7
8
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2
3
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5
6
7
8
9
0
1
3
1
(
m, 2H), 7.05 (t, J = 7.0 Hz, 1H), 6.51 – 6.48 (m, 1H). C NMR { H} (101 MHz,
CDCl ): δ 134.7, 126.8, 123.1, 120.9, 119.7, 118.8, 109.9, 101.6.
3
2
4
2
-naphthalenecarboxylic acid (2u). General procedure gave a white solid (155 mg,
1
9
0%). H NMR (400 MHz, DMSO-d ): δ 13.11 (s, 1H), 8.63 (s, 1H), 8.13 (d, J = 7.9
6
1
3
1
Hz, 1H), 8.06 – 7.97 (m, 3H), 7.60 – 7.69 (m, 2H). C NMR { H} (101 MHz, DMSO-
d6): δ 167.9, 135.4, 132.6, 130.9, 129.8, 128.8, 128.6, 128.5, 128.1, 127.3, 125.6.
Thiophene-3-carboxylic acid (2v).18 General procedure gave a colourless needle
1
crystal (97 mg, 76%). H NMR (400 MHz, DMSO-d ): δ 12.73 (s, 1H), 8.27 (m, 1H),
6
1
3
1
7.66 – 7.58 (m, 1H), 7.50 – 7.41 (m, 1H). C NMR { H} (101 MHz, DMSO-d ): δ
6
1
64.1, 134.8, 133.8, 128.2, 127.7.
3
d
2
-furancarboxylic acid (2w). General procedure gave a white solid (28 mg, 25%).
1
H NMR (400 MHz, CDCl ): δ 9.58 (s, 1H), 7.65 – 7.50 (m, 1H), 7.33 – 7.21 (m, 1H),
3
13
1
6
.53 – 6.43 (m, 1H). C NMR { H} (101 MHz, CDCl ): δ 162.6, 146.4, 142.8, 119.1,
3
111.3.
18
3
-pyridinecarboxylic acid (2x). General procedure gave a colourless needle crystal
1
(113 mg, 92%). H NMR (400 MHz, DMSO-d ): δ 13.47 (s, 1H), 9.07 – 9.08 (m, 1H),
6
1
3
1
8
.78 – 8.80 (m, 1H), 8.26 – 8.29 (m, 1H), 7.53 – 7.56 (m, 1H). C NMR { H} (101
MHz, DMSO-d ): δ 166.8, 153.8, 150.7, 137.4, 127.0, 124.3.
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1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
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6
Cholest-4-en-3-one (2y). General procedure gave pale yellow oily liquid (162 mg,
1
42%). H NMR (400 MHz, CDCl ) δ 5.72 (s, 1H), 2.40 (ddd, J = 18.7, 15.4, 4.6 Hz,
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
3
1
–
H), 2.33 – 2.22 (m, 1H), 2.06 – 1.97 (m, 2H), 1.90 – 1.77 (m, 2H), 1.74 – 1.19 (m,
2H), 1.17 (s, 3H), 1.16 – 1.14 (m, 1H), 1.14 – 1.10 (m, 3H), 1.09 – 1.06 (m, 1H), 1.06
0.96 (m, 3H), 0.90 (d, J = 6.5 Hz, 3H), 0.86 (dd, J = 6.6, 1.8 Hz, 6H), 0.70 (s, 3H).
1
3
1
C NMR { H} (101 MHz, CDCl ): δ 199.8, 171.9, 123.8, 56.2, 56.0, 53.9, 42.5, 39.7,
3
39.6, 38.7, 36.2, 35.7, 35.8, 35.7, 34.1, 33.1, 32.1, 28.3, 28.1, 24.3, 23.9, 23.0, 22.7,
+
+
2
1.1, 18.8, 17.5, 12.1. HRMS (ESI-MS) calcd for C H O (M + H ) 385.3470, found
27 45
3
85.3468.
ASSOCIATED CONTENT
Supporting Information
The supplementary experimental data. Contained figures of Catalyst recycling,
1
8
1
13
Labeling experiments with K OH and H and C NMR spectra for all products (PDF).
ACKNOWLEDGMENT
The authors thank the financial support from the National Natural Science Foundation
of China (21572137 and 21871187) and the Key Program of Sichuan Science and
Technology Project (Nos. 2018GZ0312, 2019YFG0146). We are grateful to the
comprehensive training platform of specialized laboratory, College of Chemistry, and
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Page 29 of 38
The Journal of Organic Chemistry
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Chunchun Zhang from the Centre of Testing & Analysis, Sichuan University, for NMR
measurements.
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REFERENCES
(1) (a) Weber, M. A.; Ford, P. C. Catalytic dehydrogenation of 1,2- and 1,3-diols. J.
Mol. Catal. A: Chem. 2016, 416, 81‒87. (b) Tseng, K. N. T.; Kampf, J. W.; Szymczak,
N. K. Mechanism of N,N,N-Amide Ruthenium(II) Hydride Mediated Acceptorless
Alcohol Dehydrogenation: Inner-Sphere β-H Elimination versus Outer-Sphere
Bifunctional Metal−Ligand Cooperativity. ACS Catal. 2015, 5, 5468‒5485. (c)
Chakraborty, S.; Piszel, P. E.; Brennessel, W. W.; Jones, W. D. A Single Nickel
Catalyst for the Acceptorless Dehydrogenation of Alcohols and Hydrogenation of
Carbonyl Compounds. Organometallics. 2015, 34, 5203‒5206. (d) Campos, J.;
Sharninghausen, L. S.; Manas, M. G.; Crabtree, R. H. Methanol Dehydrogenation by
Iridium N-Heterocyclic Carbene Complexes. Inorg. Chem. 2015, 54, 5079‒5084.
(2) (a) Muzart. J. Chromium-Catalyzed Oxidations in Organic Synthesis. Chem. Rev.
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992, 92, 113‒140. (b) Punniyamurthy, T.; Velusamy, S.; Iqbal, J. Recent Advances in
Transition Metal Catalyzed Oxidation of Organic Substrates with Molecular Oxygen.
Chem. Rev. 2005, 105, 2329‒2363. (c) Patel, S.; Mishra, B. K. Chromium(VI) oxidants
having quaternary ammonium ions: studies on synthetic applications and oxidation
kinetics. Tetrahedron. 2007, 63, 4367‒4406.
(3) (a) Trincado, M.; Grützmacher, H.; Vizza, F.; Bianchini, C. Domino
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