Efficient Transfer Hydrogenation of Ketones Catalyzed by a Phosphine-Free Cobalt-NHC Complex

Article abstract of DOI:10.1002/ejoc.202000654

A simple phosphine-free cobalt-NHC pincer complex has been synthesized and utilized for the transfer hydrogenation of ketones with 2-propanol as hydrogen donor. A broad range of ketones varying from aromatic, aliphatic and heterocyclic were effectively reduced to their corresponding alcohols in moderate to excellent yields with good tolerance of functional groups.

Full text of DOI:10.1002/ejoc.202000654

European Journal of Organic Chemistry
Accepted Article
Accepted Article
Title: Efficient Transfer Hydrogenation of Ketones Catalyzed a
Phosphine-free Cobalt-NHC Complex
Authors: Jessica Juweriah Ibrahim, C. Bal Reddy, Xiaolong Fang, and
Yong Yang
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.202000654
Link to VoR: https://doi.org/10.1002/ejoc.202000654
01/2020

10.1002/ejoc.202000654
European Journal of Organic Chemistry
COMMUNICATION
Efficient Transfer Hydrogenation of Ketones Catalyzed a
Phosphine-free Cobalt-NHC Complex
Jessica Juweriah Ibrahim,[a,b] C. Bal Reddy,[a] Xiaolong Fang,[c]* and Yong Yang[a,d]
*
Dedication ((optional))
[a]
CAS Key Laboratory of Bio-Based Materials, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao 266101,
China
*E-mail: yangyong@qibebt.ac.cn
[b]
[c]
University of Chinese Academy of Sciences, Beijing 100049, China
Key Laboratory of Functional Molecule Design and Interface Process, College of Materials and Chemical Engineering, Anhui Jianzhu University, Hefei,
230601, China
*E-mail: xlfang@stu.xmu.edu.cn
[d]
Dalian National Laboratory for Clean Energy, Dalian 116023, China.
Supporting information for this article is given via a link at the end of the document. ((Please delete this text if not appropriate))
Abstract: A simple phosphine-free cobalt-NHC pincer complex has
been synthesized and utilized for the transfer hydrogenation of
ketones with 2-propanol as hydrogen donor. A broad range of ketones
varying from aromatic, aliphatic and heterocyclic were effectively
reduced to their corresponding alcohols in moderate to excellent
yields with good tolerance of functional groups.
aldehydes, alkenes and imines using pressurised H2 or 2-
propanol as hydrogen donors (Figure 1).[14]
Kempe and
coworkers then reported several PN3-5P ligand coordinated
cobalt(II) chloride complexes for the effective hydrogenation of
ketones with H2 (Figure 1).[15] In these cases, phosphine-based
ligands suffer from shorter shelf-lives and can be hard to prepare
on a large scale due to their moisture- and air-sensitivity, which
significantly limit its practical applicability. In 2019, Liu and
coworkers reported the first example of phosphine free NHC-Co
complex for the hydrogenation of ketones and aldehydes under
pressurised H2 condition.[16] We recently also developed a bench-
stable NNN pincer cobalt complex, which demonstrated the most
efficient cobalt-catalyzed regioselective hydrosilylation of terminal
alkynes.[17]
In the quest for simple and inexpensive catalytic systems, we
were looking for alternative phosphine free ligands for promoting
cobalt catalysis in transfer hydrogenation reactions. Herein, we
wish to report the use of Co-NHC pincer complex as a catalyst for
the transfer hydrogenation of ketones using 2-propanol as
hydrogen donor. A broad set of ketones ranging from aromatic,
heterocycles to aliphatic ones were effectively reduced to their
corresponding alcohols in moderate to excellent yields with good
functional groups tolerance.
The carbonyl reduction to their corresponding alcohols is a widely
used and important organic transformation for the production of
pharmaceuticals, cosmetics and agrochemicals.[1] Traditionally,
such a transformation was performed using stoichiometric
reducing agents such as metal hydrides. Later on, catalytic
hydrogenation and transfer hydrogenation methods, as an
attractive and sustainable alternative to stoichiometric approach,
have been frequently employed for this conversion. The direct
hydrogenation with pressurized H2 gas has drawbacks such as
the requirement of high pressure and temperature, safety issues
during transportation and storage, and it also increases the
demand for hydrogen as a feedstock for chemcial processes.[2] To
this end, transition-metal catalyzed transfer hydrogenation (TH) of
ketones to alcohols has gained much attention due to their
convenience in operation, efficacy and sustainability.[3,4] In this
approach, transition metal catalyst mediates the transfer of
hydrogen via the hydridic route,[5] in which an alcohol as hydrogen
donor was first transfered to form the metal-hydride with
subsequent transfer to the carbonyl of the ketone to form the
corresponding alcohol.[6]
Since the seminal contributions by Noyori and coworkers
detailing Ru-catalyzed transfer hydrogenation of pro-chiral
ketones,[7] a variety of precious metal-based catalysts, such as
Ru,[8] Ir,[9] Rh,[10] have been well investigated and demonstrated
outstanding catalytic efficiency in this transformation. However,
as global concerns for more sustainable and economical
reactions, the use of earth-abundant and inexpensive non-
precious metals are highly desirable. Accordingly, several non-
noble metal-based catalysts, e.g., Fe,[11] Co,[12] Mn[13] to replace
precious metals have been developed and made a rapid progress
recently, especially cobalt catalysis. For example, Hanson and
coworkers synthesized a cationic cobalt(II) alkyl complex with an
aliphatic PNP pincer ligand for the hydrogenation of ketones,
1
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10.1002/ejoc.202000654
European Journal of Organic Chemistry
COMMUNICATION
Figure 1. Cobalt catalysed hydrogenation/transfer hydrogenation of ketones.
Table 1: Optimization of reaction conditions.a
Entry
Catalyst (mol%)
Base (mol%)
H-source (mL)
Temp (oC)
Yield 3a (%)b
1
Co-1a
NaOtBu (10)
NaOtBu (10)
No base
iPrOH
iPrOH
iPrOH
iPrOH
iPrOH
iPrOH
iPrOH
iPrOH
iPrOH
iPrOH
iPrOH
iPrOH
iPrOH
iPrOH
iPrOH
iPrOH
iPrOH
MeOH
EtOH
85
85
85
85
70
85
85
85
85
85
85
85
85
85
85
80
60
85
85
90
40
21
40
11
81
68
3
2
Co-1b
3
Co-1a
4
No catalyst
No catalyst
Co-1a
NaOtBu (10)
NaOtBu (10)
KOtBu (10)
NaOH (10)
NaOCH3 (10)
K2CO3(10)
Na2CO3 (10)
NaOtBu (3)
NaOtBu (5)
NaOtBu
5
6
7
Co-1a
8
Co-1a
9
Co-1a
30
20
23
27
64
74
89
75
30
21
29
10
11
12
13
14
15
16
17
18
19
Co-1a
Co-1a
Co-1a
Co-1a (1)
Co-1a (2.5)
Co-1a (5)
Co-1a
NaOtBu
NaOtBu
NaOtBu
Co-1a
NaOtBu
Co-1a
NaOtBu
Co-1a
NaOtBu
aReaction conditions: acetophenone (0.5 mmol), Co-1a or Co-1b (3 mol%), NaOtBu (10 mol%), iPrOH (5 mL), 24 h. bYields were
determined by GC-FID using n-dodecane as an internal standard.
NHC pincer ligands (1a and 1b) were readily synthesized
from the reaction of commercially available R-substituted
imidazoles (R = Me and Mes) and bis(2-chloroethyl)amine
hydrochloride (see Supporting Information for details). The
reaction of 1a or 1b with CoCl2 in THF afforded the respective
Co-NHC pincer complexes (Co-1a and Co-1b) in good yields,
which were characterized by IR spectroscopy, mass
spectrometry, and elemental analysis. Electrospray ionization
high-resolution mass spectrometry (ESI-HRMS) of Co-1a
displayed a strong signal at an m/z value of 326.0578 (Figure
S1), strongly indicating that Co coordinates with two C atoms
in imidazole, one N and Cl as shown in Figure 1. We attempted
to grow the single crystal to identify the structure of Co-1a, but
failed because of the dynamic formation of mixed coordination
structured complex.[16]
acetophenone 2 as the model substrate in the presence of Co-
1a or Co-1b (3 mol%), NaOtBu (10 mol%), and 2-propanol as
H-source at 85°C for 24 h, and the results are compiled in
Table 1. From Table 1, we found that the complex Co-1a
bearing the methyl group substituent on the carbene gave the
better reaction efficiency, affording the desired phenyl ethanol
3a in 90% yield (entry 1), while Co-1b bearing the bulkier
mesityl group was less reactive under otherwise identical
conditions (entry 2). Subsequently, Co-1a was used as the
catalyst for further optimization of reaction conditions (entries
3-18). In the absence of either base or Co-1a, the reaction gave
poor reactivity (entries 3 and 4), indicating that a combination
of Co-1a and base is necessary for producing the desired
product in high yields. Next, a set of parameters covering
bases, reaction temperatures, catalyst loadings, and base
loadings were intensively screened. Among the investigated
bases including KOtBu, NaOH, NaOCH3, K2CO3 and Na2CO3
(entries 5-10), NaOtBu was found to be the best choice and
With Co-NHC complexes Co-1a and Co-1b in hand, we
started to test their catalytic performance for the transfer
hydrogenation of ketones. The reaction was carried out using
2
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10.1002/ejoc.202000654
European Journal of Organic Chemistry
COMMUNICATION
gave 3a in 90% yield with base loading of 10 mol% (entry 1).
Recent studies reveal that alkali bases alone with larger than
10 mol% (with respect to ketone), such as NaOH and KOH,
could efficiently catalyze the transfer hydrogenation of ketones
and aldehyde.[18].In our case, we also found that NaOtBu alone
indeed enabled the reaction
Scheme 1. Transfer Hydrogenation of various ketone substrates.a
aReaction conditions: ketone substrate (0.5 mmol), Co-1a (3 mol%), NaOtBu (10 mol%), iPrOH (5 mL) at 85oC for 24 h. bCo-1a (4
mol%). cCo-1a (5 mol%) and NaOtBu (15 mol%). dNaOtBu (15 mol%). Isolated yield are given.
and gave 40 (85oC) and 11 (70oC) GC yield of 3a, respectively
(entries 4 and 5), while a considerable increase to 90% was
accomplished upon together with Co-1a, indicating the essential
role of Co-1a. A reduction of base loading to 3 mol% or 5 mol%
resulted in a considerable decrease in product formation (entries
11 and 12). Similarly, lowering the catalyst loading also led to a
reduced reaction efficiency (entries 13 and 14), while increasing
the catalyst loading had a negligible effect on the formation of 3a
(entry 15). Furthermore, we found that the reaction was greatly
sensitive to the reaction temperatures, and a signficiant decrease
3
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10.1002/ejoc.202000654
European Journal of Organic Chemistry
COMMUNICATION
in reaction efficiency was observed at lower temperatures (60 or
80oC) (entries 16 and 17). In addition, other H-sources like
ethanol and methanol were also investigated, but affording poor
reactivity (entries 18 and 19).
Keywords: transfer hydrogenation • cobalt pincer complex•
ketones • alcohols
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Having identified the optimalized reaction conditions, we next
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Acknowledgements ((optional))
The authors would like to acknowledge the financial support from
DICP and QIBEBT, CAS (Grant No. DICP & QIBEBT UN201704),
and the Dalian National Laboratory for Clean En-ergy
(DNL)Cooperation Fund, CAS (Grant No. DNL201904). Y.Y also
appreciates the support from the Royal Society (UK) for a Newton
Advanced Fellowship (NAF-R2-180695). J. J. I acknowledges the
support from Chinese Academy of Science and The World
Academy of Science in the form of CAS-TWAS President’s
Fellowship Program. X. F thanks the support from Natural
Science Foundation of China (No. 21802010).
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5
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Entry for the Table of Contents
Transfer Hydrogenation
A Phosphine-free Cobalt-NHC Complex was synthesized for efficient transfer hydrogenation of aromatic, aliphatic and heterocyclic
ketones to their corresponding alcohols.
6
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