General and Phosphine-Free Cobalt-Catalyzed Hydrogenation of Esters to Alcohols

Article abstract of DOI:10.1002/cjoc.201900292

Catalytic hydrogenation of esters is essential for the sustainable production of alcohols in organic synthesis and chemical industry. Herein, we describe the first non-noble metal catalytic system that enables an efficient hydrogenation of non-activated esters to alcohols in the absence of phosphine ligands (with a maximum turnover number of 2391). The general applicability of this protocol was demonstrated by the high-yielding hydrogenation of 39 ester substrates including aromatic/aliphatic esters, lactones, polyesters and various pharmaceutical molecules.

Full text of DOI:10.1002/cjoc.201900292

Chinese Journal
of Chemistry
CJC
中 国 化 学 - An International Journal
Accepted Article
Title: General and Phosphine-Free Cobalt-Catalyzed Hydrogenation of Esters to
Alcohols
Authors: Zhihui Shao, Rui Zhong, Raffaella Ferraccioli, Yibiao Li, and Qiang Liu*
This manuscript has been accepted and appears as an Accepted Article online.
This work may now be cited as: Chin. J. Chem. 2019, 37, 10.1002/cjoc.201900292.
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published online in Early View: http://dx.doi.org/10.1002/cjoc.201900292.
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Chinese Journal
of Chemistry
phosphine-Free, cobalt, hydrogenation, esters, alcohols
Report
CJC
中
国 化 学 - An International Journal
General and Phosphine-Free Cobalt-Catalyzed Hydrogenation of Esters to
Alcohols
†
†
Zhihui Shao,a, Rui Zhong,a, Raffaella Ferraccioli,b Yibiao Li,c and Qiang Liu*,a
a Center of Basic Molecular Science (CBMS), Department of Chemistry Tsinghua University, Beijing 100084, China
b CNR, Istituto di Scienze e Tecnologie Molecolari (ISTM) Via C. Golgi 19, 20133 Milan, Italy
c School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, Guangdong Province 529090, China
†
Z. S and R. Z contributed equally to this work.
Cite this paper: Chin. J. Chem. 2019, 37, XXX—XXX. DOI: 10.1002/cjoc.201900XXX
Summary of main observation and conclusion Catalytic hydrogenation of esters is essential for the sustainable production of alcohols in organic
synthesis and chemical industry. Herein, we describe the first non-noble metal catalytic system that enables an efficient hydrogenation of non-activated
esters to alcohols in the absence of phosphine ligands (with a maximum turnover number of 2391). The general applicability of this protocol was
demonstrated by the high-yielding hydrogenation of 39 ester substrates including aromatic/aliphatic esters, lactones, polyesters and various
pharmaceutical molecules.
catalysts using earth-abundant metals alongside phosphine-free
ligands that are robust, easily-pepared and highly-tunable. As the
overall cost of the catalyst is also affected by the ligand, it should
also be a priority for the development of new ligands for the
non-noble metal catalysts.
Background and Originality Content
Reduction of esters to alcohols is
a
fundamental
transformation in organic chemistry, and is important for the
production of a wide range of bulk and fine chemicals. Compared
with traditional approaches using stoichiometric amounts of
metal hydride reagents, catalytic hydrogenation represents an
environmentally benign and atom economic alternative[1-2]. As
conventional heterogeneous catalysts require harsh reaction
N-heterocyclic carbenes (NHCs) are useful alternatives to
phosphine ligands due to their strong σ-donor and relatively weak
π-acceptor properties[45]. In this respect, several well-defined
NHC-Co complexes bearing rigid backbones have been applied for
o
the catalytic hydrogenation of alkenes, alkynes and nitriles[46-49]
.
conditions (>200 C, >200 bars), the development of more active
homogeneous catalysts for hydrogenation of esters is in high
demand[3-5]. Significant progress was achieved in 2006 by the
group of Milstein[6] and Firmenich SA[7], with the application of
Ru-based homogeneous catalysts for ester hydrogenation under
mild conditions. Since then, a variety of active homogeneous
ester hydrogenation catalysts based on Ru[8-15], Os[16-18], and
Ir[19-20] have been described.
Because a variety of hydrogenation catalysts have exhibited
prominent enhancements in reactivity using metal-ligand
cooperation functionality based on the “N-H effect”[50-51], we
envisioned that a NHC-Co complex comprising an N-H moiety
would be able to catalyze the hydrogenation of less reactive
carbonyl groups[52]. Herein, we report the first general and
phosphine-free non-noble metal catalyzed hydrogenation of
non-activated esters using an in-situ formed catalytic system from
CoCl2 and a non-rigid aliphatic pincer NHC ligand (Scheme 1b).
In recent years, efforts on catalyst development have focused
on the replacement of noble metals by more economic and
ecologically-friendly base metals in terms of sustainability[21-28]
.
Since Milstein and co-workers developed the first iron-catalyzed
hydrogenation of activated esters to the corresponding alcohols
in 2014[29]
, remarkable advances have been made in the
application of non-noble metal catalysts based on Fe[30-32], Co[33-39]
and Mn[40-43] (Scheme 1a). Despite these impressive
achievements, almost all of the reported non-noble metal
catalysts for ester hydrogenation involve phosphine ligands,
which are typically expensive, air-sensitive and difficult to
prepare, thus restricting a broad application. To the best of our
knowledge, only one phosphine-free non-noble catalyst
(Knölker-type Fe complex[44]
) has been reported for the
hydrogenation
of
esters,
however,
only
activated
trifluoroacetates could be reduced[32]. Therefore, it is highly
desirable to develop general and practical ester hydrogenation
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10.1002/cjoc.201900292
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First author et al.
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Scheme 1 Non-noble metal catalyzed hydrogenation of esters.
Table
1
Screen of NHC ligands and metal precursors on the
hydrogenation of benzyl benzoate.a
non-noble
metal catalysts
/
esters:
R2 OH
for
of
Representative
O
hydrogenation
R1
(a)
L
mol%)
mol%),
tBuOK
[M] (2
NHC (2
mol%)
O
[M] (base)
-
H
2 (10
80 bar)
R2
OH
(10
solvent, 90-130 °C
R1
O
2
H
bar)
2 (30
Ph
OH
Ph
Ph
O
THF, 100
16 h
°C,
P tBu)
PiPr2
HBH3
Fe CO
Br
P tBu)
(
2
Br
2a
1a
H
(
2
H
N
PR2
CO
N
Mn CO
:
LNHC
H
N
H
Mn
Fe
CO
N
H
P
H
P
R2
CO
CO
P tBu)
N
R2
PiPr2
H
N
(
2
N
Milstein
2014
Beller/Guan
2014
Milstein
2016
Beller
2016
N
N
N
2Cl-
N
N
2Br-
R1 CF3
=
Cl-
N
Mes
N
R
N
R
TMS
PPh2
N
R
N
R
NH2
PPh2
PPh2
O
Ph2P
OC
N
L1-L4
L7
L5-L6
CO
Br
Mn
CO
tBu) P Co NHtBu
TMS
+
Fe
(
2
CO
CO
·6H2O
Cl
Cl
Co(BF4)2
CO
N
N
2Br-
N
N
N
Milstein
2015
=
Elsevier/de Bruin
2015
Pidko
2017
Lefort/Pignataro
2016
R1 CF3
=
2Cl-
N
N
N
N
R1 Alkyl
Mes
Dipp
Mes
Dipp
and
L8
LNHC
L9
A
N
cobalt catalyst
ester
This
for
general
phosphine-free
hydrogenation
work
(b)
b
Entry
[M]
Yield
(%)
H
N
H
N
Cl
•
•
catalytic
system
Phosphine-free
Easily-prepared
1
2
L1
L2
CoCl2
CoCl2
CoCl2
CoCl2
CoCl2
CoCl2
CoCl2
CoCl2
CoCl2
CoBr2
5
8
or
(R=Me)
(R=Ph)
N
N
N
&
Robust
2Cl
+
Co
Cl
N
R
N
R
• Metal-ligand
coorperation
N
Mes
N
3
L3
L4
89
4
(R=Mes)
(R=Dipp)
Mes
scope
• Broad
efficiency
&
High
CoCl2/Base
4
5
L5
L6
4
(R=Me)
6
4
(R=Mes)
L7
Remarkably, a broad scope of aromatic/aliphatic esters, lactones,
polyesters as well as pharmaceutical molecules were effectively
hydrogenated to afford the corresponding alcohols (39 examples)
with excellent functional group tolerance and high turnover
numbers (TONs) up to 2391.
7
4
L8
L9
L3
L3
L3
L3
L3
L3
L3
L3
L3
L3
4
8
9
trace
76
54
22
11
5
10
11
12
13
14
15
16
17
18
19
20
21
22c
Co(OAc)2
Results and Discussion
Co(acac)2
CuCl2
Initially, three different types of NHC precursors L1-L7 with
both mono- and bis-NHC moieties were tested in the
hydrogenation of benzyl benzoate 1a. The catalytic systems were
easily generated in-situ by mixing the NHC precursor, CoCl2 and
tBuOK in THF (Table 1). These reactions were conducted in the
presence of 2 mol% cobalt catalyst under 30 bar H2 at 100 °C. The
pincer NHC ligand L3[53] bearing mesityl (Mes) substituents gave
the best result, with 89% yield of benzyl alcohol 2a (Table 1, entry
CuCl
MnCl2
3
Br
26
4
Mn(CO)5
FeCl2
·
6H2O
trace
3
Fe(BF4)2
NiCl2
-
L3
-
4
CoCl2
CoCl2
4
L3
99
a
Reaction conditions:0.5 mmol scale, 2 mol% LNHC, 2 mol% [M], 10 mol%
tBuOK in 2 mL of THF, under 30 bar H2 at 100 ℃ for 16 h. Yield was
determined by GC analysis using biphenyl as the internal standard. 5 mL
b
c
THF was used.
3). However, the other three analogue ligands with methyl (L1),
phenyl (L2) or 2,6-diisopropylphenyl (Dipp, L3) substituents
exhibited almost no reactivity (Table 1, entries 1, 2 and 4). Only
4% yield were obtained with the lutidine-derived pincer ligands L5
and L6 (Table 1, entries 5 and 6). Ligand L7 (Table 1, entry 7),
which could be regarded as a bidentate congener of L3, also
displayed very low reactivity. Additionally, the rigid pincer NHC
ligands L8 and L9, which had been applied in other
cobalt-catalyzed hydrogenation reactions[46-47], resulted in a very
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Running title
Chin. J. Chem.
low yield of 2a (Table 1, entries 8 and 9).The above results clearly
demonstrate the impact of the ligand structure on the catalytic
activity. Furthermore, the evaluation of metal precursors using
ligand L3 was conducted (Table 1, entries 10-19). CoBr2 afforded a
good yield of 76% (Table 1, entry 10), while another two cobalt
precursors Co(OAc)2 and Co(acac)2 gave rise to 54% and 22%
yield, respectively (Table 1, entries 11 and 12). The other metal
precursors mostly gave very low reactivity in this transformation
(Table 1, entries 13-19). The absence of either CoCl2 or L3 resulted
in very low conversion (Table 1, entries 20 and 21). A quantitative
yield was obtained by increasing the amount of THF solvent to 5
mL (Table 1, entry 22).
The influence of bases, solvents, hydrogen pressure, reaction
temperature were also examined (See Supporting Information for
more details, Tables S1-S4). Moreover, the ligand and mercury
poison experiments were further implemented. Different amounts
of PMe3, PPh3 and a drop of mercury were added to the reaction
system, respectively (See Supporting Information for more details,
Table S5). No significant inhibitory effect was detected, which
indicated the homogeneous nature of this cobalt catalysis system.
Encouraged by the excellent performance of the precatalyst
formed from CoCl2/L3 under basic conditions, we sought to
synthesize the corresponding well-defined NHC-Co complex.
Different from our previous work,[52] a basic cobalt metal reagent
[Co{N(SiMe3)2}2(THF)] featuring two equivalents of internal
base[54] reacted smoothly with L3 in THF to generate the desired
CNC pincer NHC-Co(II) chloride complex Co-1 in 42% isolated yield
(Scheme 2).
hydrogenation of benzoates 1b, 1c, 1h and methyl 2-furoate 1q
using only 1 mol% catalyst loading (Table 2, entries 1, 2, 7 and 16).
Table 2 Hydrogenation of aromatic esters applying L3/CoCl2 or Co-1.a
L
3
mol%),
mol%)
CoCl
2 (2
(2
mol%)
O
tBuOK
(10
THF, 100
R2
R2
R1
H2
bar)
OH
OH
R1
O
°C,
16 h
1
2
3
(30
Entry
1
2
Yield
(%)
O
OH
R'
O
R'
1b R'
g
=
1
H
2a
2c
2d
2e
2f
96
99
(99 )
g
=
1c R' 4-OMe
2
(94 )
92b,f
=
1d R' 4-N(CH3 2
)
=
1e R' 2-Me
3
4
84
85c,f
91f
70d
=
1f R' 2-SMe
5
=
R'
6
3-OMe
1g
1h R' 4-F
2g
2h
(66g)
=
7
=
8
1i R' 4-Cl
2i
2j
68
88b
n.r.h
n.r.h
=
9
R' 4-
CF3
1j
1k R' 4-NO2
=
10
11
2k
2l
=
1l R' 4-CONH2
O
OH
O
75e
12
Ph
Ph
1m
O
2m
Scheme 2 Synthesis of pincer NHC-Co(II) chloride complex.
R2
O
OH
H
N
H
N
Cl
N
N
N
N
THF
-78 o
2Cl-
1n R2
1o R2
CH2CH3
2a
2a
92
94
=
=
Co
Cl
13
14
[Co{N(SiMe3)2}2(THF)]
C-RT
N
Mes
N
Mes
N
Mes
N
Mes
CH(CH3)2
O
L3
Co-1
(42%)
OH
OH
O
15
94
N
N
The results for the hydrogenation of aromatic esters using the
in-situ catalytic system and the well-defined catalyst Co-1 are
summarized in Table 2. A number of methyl benzoate derivatives
1p
O
2p
g
16
96
(98 )
O
1b-1j, 1m bearing
a
range of electron-donating and
O
O
electron-withdrawing substituents in the ortho-, meta- and
para-positions of the phenyl ring were reduced to alcohols in good
to excellent yields (Table 2, entries 1-9). A series of functional
groups, such as methoxyl, amino, methylthio, fluoro, chloro,
trifluoromethyl, and alkenyl groups were all well-tolerated.
However, nitro and amide substituted substrates were failed in
this reaction (Table 2, entries 10 and 11). Further variation of the
oxygen substituents from a methyl group to ethyl and more
sterically-hindered isopropyl groups did not affect the efficiency of
ester hydrogenation processes (Table 2, entries 13 and 14).
Additionally, heteroaromatic esters 1p and 1q were also
compatible in this catalytic system, leading to excellent yields of
the corresponding alcohol products 2p and 2q (Table 2, entries 15
and 16). The complex Co-1 showed comparable catalytic
performance to the in-situ catalytic system revealed by the
1q
2q
a
Reaction conditions:0.5 mmol scale, 2 mol% CoCl2, 2 mol% L3, 10 mol%
tBuOK in 5 mL of THF, under 30 bar H2 at 100 oC for 16 h;Yield was
b
determined by GC analysis using biphenyl as the internal standard. 60
bar H2. c 60 bar H2, 5 mol% L3, 5 mol% CoCl2, 25 mol% tBuOK. d 30 bar H2, 5
t
e
mol% L3, 5 mol% CoCl2, 20 mol% BuOK. 1 mol% L3, 1 mol% CoCl2, 5
t
f
g
mol% BuOK. Isolated yield. The reaction was perfomed using 1 mol%
well-defined complex Co-1 as the catalyst in the presence of 5 mol%tBuOK.
h n.r.: no reaction.
The hydrogenation of aliphatic esters, lactones and polyesters
were also investigated (Table 3). Linear aliphatic esters 4a-4g with
different chain lengths were all smoothly reduced in high yields
between 89%-99% (Table 3, entries 1-7). For cyclic esters with
varied steric bulk (4h-4j), the hydrogenation products were
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First author et al.
Report
chemoselectively obtained in 80-94% yield (Table 3, entries 8-10),
with the internal C-C double bond remaining untouched (Table 3,
entry 9). Lactones 4k-4m with different ring sizes were all
quantitatively reduced into the corresponding diols 5k-5m
(Table3, entries 11-13). The bio-feedstock, γ-valerolactone 4n,
were also successfully hydrogenated into 1,4-pentanediol 5n in
91% yield (Table 3, entry 14). Hydrogenation of the diester
substrate, dimethyl adipate 4o, produced the diol product 5m in
66% yield (Table 3, entry 15). Notably, this protocol could be
Table 3 Hydrogenation of aliphatic esters, lactones as well as diester and
polyester applying L3/CoCl2 or Co-1.a
L
3
mol%),
mol%)
CoCl
2 (2
tBuOK
(2
mol%)
O
(10
R2
R2
R1
H2
bar)
OH
OH2
R1
O
THF, 100
16 h
°C,
4
5
6
(30
Entry
1
4
5
Yield
99
(%)
OH
O
Ph
Ph
O
4a
applied for the depolymerization of polyesters[55]
. When
5a
5b
2a
O
polycaprolactone (PCL) 4p with a MW of 14000 was used as the
substrate, 1,6-hexanediol 5m was obtained in 97% yield(Table 3,
entry 16).
2
3
98
92
Ph
OH
Me
Ph
O
4b
O
Ph
OH
Ph
O
4c
O
OH
n
O
n
99(96e)
89d
93d
n
=
=
4
5
6
4d
4e
4f
1
7
5d
5e
5f
n
n
=
13
O
7
99
OH
O
4g
5g
O
OH
Me
Me
80
O
O
8
9
4h
O
5h
5i
OH
94c,d
4i
O
OH
OMe
86b,d
10
4j
5j
n
O
HO
O
OH
n
=
=
=
11
12
13
4k
4l
1)
5k
5l
99
99
99
(n
(n
2)
3)
4m
5m
(n
O
OH
O
91c,d
14
OH
4n
4o
5n
O
66c
97
HO
O
15
16
O
OH
OH
O
5m
O
HO
O
n
=
5m
14000)
4p
(MW
a
Reaction conditions:0.5 mmol scale, 2 mol% CoCl2, 2 mol% L3, 10 mol%
tBuOK in 5 mL of THF, under 30 bar H2 at 100 oC for 16 h; Yield was
determined by GC analysis using biphenyl as the internal standard. 60
bar H2, 5 mol% L3, 5 mol% CoCl2, 20 mol% BuOK. 60 bar H2. Isolated
yield. The reactioin was perfomed using 1 mol% well-defined complex
b
t
c
d
e
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Running title
Chin. J. Chem.
Co-1 as the catalyst in the presence of 5 mol% tBuOK.
acetate 4g.
L3
mol%),
mol%)
CoCl
To further highlight the the synthetic utility of this procedure,
it was applied to the direct hydrogenation of pharmaceutical
molecules of practical importance (Scheme 3). NSC153412 7a is a
useful pharmaceutical intermediate, while clofibrate 7b is an
antilipemic drug. These two aliphatic esters were reduced in high
efficiency. The reduction of pharmaceutical intermediates
containing cyclic aliphatic esters, menthyl acetate 7c and ethyl
chrysanthemumate 7d, and cerebrovascular expansion drug
vinpocetine 7g, also resulted in high yields of the alcohol products
(78-88%). Both the C-C double bonds in distal and conjugated
positions of ester group were preserved after the reaction (7d and
2 (0.03
(0.03
mol%)
O
tBuOK
(0.58
THF, 100
H2
bar)
2
OH
5g
80%
O
°C,
16 h
4g
(80
mmol
30
2.64 g
yield
=
TON 2391
The efficiency of this catalytic system was further evaluated in
the gram-scale hydrogenation of ethyl acetate 4g using a catalyst
loading of 0.03 mol% (Scheme 4). Remarkably, the hydrogenated
product ethanol 5g was obtained in a good yield of 80% with a
high TON of 2391, demonstrating the high stability and efficiency
of this NHC-Co catalyst.
To shed light on the reaction mechanism, we performed the
hydrogenation of benzyl benzoate 1a using N-methyl substituted
pincer NHC precursor L10 as the ligand (Scheme 5). This system
afforded a very low yield of 2a, in contrast to the excellent
reactivity (99% yield) of the ligand L3 containing an N-H group
(Table 1, entry 22). This result suggested that an outer-sphere
hydrogen transfer mechanism via metal-ligand cooperation based
on the “N-H effect” was a major reaction pathway for this
cobalt-catalyzed hydrogenation of esters.
Scheme 3 Direct hydrogenation of ester motifs on natural products and
pharmaceutical molecules using L3/CoCl2.a
O
L
3
mol%),
mol%)
CoCl
2 (2
(2
mol%)
tBuOK
R2
R2
(10
THF, 100
R1
R1
H2
bar)
OH
OH
O
O
°C,
16 h
7
8
9
(30
O
O
O
O
O
O
OEt
Cl
Scheme 5 Cobalt-catalyzed hydrogenation of benzyl benzoate 1a
using N-methyl substituted ligand L10.
7a
153412)
92%
7b
7c
acetate)
O
(NSC
(Clofibrate)
75%c
(Menthyl
88%
O
O
Me
O
H
L10 mol%)
H
N
(2
N
O
O
CoCl
mol%)
tBuOK
mol%)
(10
OEt
2 (2
N
N
nBu
H2
bar)
2
Ph
2a 9%
)
OH
Ph
Ph
N
O
1a
2Cl
H
THF, 100
16 h
°C,
N
Mes
N
Mes
H
(30
(
7d
7e
7f
L10
(Chrysanthemumate)
79%d
(Tetracaine)
(Sclareolide)
68%e
93%/87%c
O
Based on the experimental observation and results from the
N
Ph
literature, a proposed reaction mechanism is shown in scheme 6.
Initially, the reaction of precatalyst Co-1 with tBuOK would
generate the deprotonated cobalt(II) amido complex Co-2, which
could further react with H2 to afford cobalt(I) hydride species Co-3
under reductive conditions. The oxidative additon of H2 with Co-3
OMe
OMe
O
N
N
OMe
O
O
7h
7g (Vinpocetine)
78%b
(Trimebutin)
87%/85%b
8f
aReaction conditions:0.5 mmol scale, 2 mol% CoCl2, 2 mol% L3, 10 mol%
tBuOK in 5 mL of THF, under 30 bar H2 at 100 oC for 16 h; Isolated yields
were obtained by flash column chromatograpy. b 60 bar H2. c 60 bar H2,
t
130 oC, 5 mol% L3, 5 mol% CoCl2, 20 mol% BuOK. d 5 mol% L3, 5 mol%
t
CoCl2, 15 mol% BuOK. [e]80 bar H2, 5 mol% L3, 5 mol% CoCl2 , 15 mol%
tBuOK.
7g). The lactone molecule sclareolide 7f, which is a fragrance
ingredient, was smoothly converted to the diol 8f in 68% yield,
with complete retention of configuration. In addition, the
hydrogenation of aromatic esters tetracaine 7e and trimebutine
7h, which are used for the treatment of acute and chronic
abdominal pain, delivered the alcohol products in high isolated
yields. The amino groups on these two molecules were
compatible with these reaction conditions.
Scheme 4 The efficiency of cobalt-catalyzed hydrogenation of ethyl
Chin. J. Chem. 2019, 37, XXX－XXX
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First author et al.
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Scheme 6 Proposed reaction mechanism.
(300 mL) containing an alloy plate with wells glass vials. General
procedure for the reaction: Under the argen argon atmosphere
glovebox, Ligand (0.01 mmol, 2 mol%), CoCl2 (0.01 mmol, 2
mol%), t-BuOK (0.1 mmol, 10 mol%), THF（5 mL） and ester (0.5
mmol) were added sequentially to the vial with a magnetic stir
bar, which was capped with a septum equipped with a syringe.
The vial was placed in the alloy plate, which was then placed to
the predried autoclave. Once sealed, the autoclave was purged 3
times with hydrogen, then pressurized to given pressure and
heated at given temperature for 16 h. After reaction, the
autoclave was cooled to 0°C, depressurized, the reaction mixture
was diluted by 2 mL of CH2Cl2. The yield of product was
determined by GC with diphenyl as the internal standard or
isolated via column chromatography.
H
N
Cl
N
N
N
N
N
tBuOK
Co
Co
-
HCl
N
Mes
N
Mes
N
Mes
N
Mes
Cl
Co-2
Cl
Co-1
tBuOK H2
H
N
N
N
Co
N
N
Mes
H
Mes
Co-3
H2
General procedure for the synthesis of Co-1：Slow addition
of the suspension of one equivalent of L3 (2 mmol) in THF (15 mL)
to the [Co{N(SiMe3)2}2(THF)] (2 mmol) solution in THF (5 mL) at
-78℃ under argon protection. The reaction mixture was slowly
warm to room temperature then stirring of the mixture at room
temperature for another 24 hours, resulted in the formation of a
blue suspension. The insoluble product was isolated and
re-crystallized for three times to eventually obtained the desired
CNC pincer product Co-1 as the bright blue powder in 42% yields.
Elemental analysis calcd (%) for C, 58.85; H, 6.17; N, 12.26; found:
C, 57.60; H, 6.23; N, 11.81; HR ESI-MS (positive ion): 535.1893
([M-Cl-]+, calcd 535.1913) m/z; Magnetic susceptibility: 4.2 μB; IR
ν (cm-1): 3141, 3042, 2961, 2924, 1610, 1558, 1488, 1459, 1409,
1377, 1303,1263, 1192, 935, 814, 799, 774, 735, 700, 639, 602,
582, 564, 451cm-1.
H
N
H
N
N
Mes
Co
H
N
O
H
N
Co-4
Mes
Ph
Ph
O
PhCHO
2a'
1a
H2
HO
Ph
OH
2a
N
Ph
Ph
C
H
1a'
O
PhCHO
2a'
N
2a
N
Co
Mes
Co-5
N
H
H
N
Mes
will lead to the formation of cobalt (III) trihydride Co-4. Similar
reactivities of the corresponding PNP pincer cobalt(II) complexes
with BuOK and H2 have been reported by the groups of Arnold
Supporting Information
t
and Schneider[56-58], supporting the feasibility for the speculated
precatalyst activation process. Moreover, complex Co-4 closely
correlates with a homologous trihydride iridium complex, which is
an effectivie ester hydrogenation catalyst[19]. Accordlingly, the
ester 1a could be hydrogenated via a concerted transfer of the
hydride from the cobalt center and the proton from the amino
group in complex Co-4 to generate the corresponding hemiacetal
1a‘ and the cobalt(II) amido dihydride speicies Co-5. Next, the
hemiacetal 1a‘ dissociated into benzyl alcohol 2a and
benzaldehyde 2a‘, while Co-4 is regenerated from Co-5 by
addition of H2 to complete the catalytic cycle. Finally, 2a‘ is
hydrogenated to 2a in the same manner.
The supporting information for this article is available on the
WWW under https://doi.org/10.1002/cjoc.2018xxxxx.
Acknowledgement
We are grateful for the financial supports from the National
Natural Science Foundation of China (21822106 and 91845107)
and the Beijing Municipal Commission of Science and Technology
(Z181100005118001).
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www.cjc.wiley-vch.de
© 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2019, 37, XXX－XXX
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Running title
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(The following will be filled in by the editorial staff)
Manuscript received: XXXX, 2019
Manuscript revised: XXXX, 2019
Manuscript accepted: XXXX, 2019
Accepted manuscript online: XXXX, 2019
Version of record online: XXXX, 2019
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www.cjc.wiley-vch.de
© 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2019, 37, XXX－XXX
This article is protected by copyright. All rights reserved.

Running title
Chin. J. Chem.
Entry for the Table of Contents
Page No.
General and Phosphine-Free Cobalt-Catalyzed
Hydrogenation of Esters to Alcohols
O
CoCl2/NHC/tBuOK
R2
R1
to 2391 TON
examples, up
H2
R2
OH
OH
THF, 100 °C
R1
O
0 bar)
39
(3
H
N
H
N
Cl
•
•
Phosphine-free
or
N
N
N
N
&
Robust
Easily-prepared
2Cl
+
Co
Cl
N
R
N
R
• Metal-ligand
coorperation
N
Mes
N
Mes
scope
• Broad
&
TON
High
CoCl2/Base
Zhihui Shao,a,† Rui Zhong,a,† Raffaella Ferraccioli,b
Yibiao Li,c and Qiang Liu*,a
Chin. J. Chem. 2019, 37, XXX－XXX
© 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
This article is protected by copyright. All rights reserved.