Non-Pincer-Type Manganese Complexes as Efficient Catalysts for the Hydrogenation of Esters

Article abstract of DOI:10.1002/anie.201701365

Catalytic hydrogenation of carboxylic acid esters is essential for the green production of pharmaceuticals, fragrances, and fine chemicals. Herein, we report the efficient hydrogenation of esters with manganese catalysts based on simple bidentate aminophosphine ligands. Monoligated Mn PN complexes are particularly active for the conversion of esters into the corresponding alcohols at Mn concentrations as low as 0.2 mol % in the presence of sub-stoichiometric amounts of KO^tBu base.

Full text of DOI:10.1002/anie.201701365

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Communications
Chemie
International Edition: DOI: 10.1002/anie.201701365
German Edition: DOI: 10.1002/ange.201701365
Hydrogenation Catalysts
Non-Pincer-Type Manganese Complexes as Efficient Catalysts for the
Hydrogenation of Esters
Robbert van Putten, Evgeny A. Uslamin, Marcel Garbe, Chong Liu, Angela Gonzalez-de-
Castro, Martin Lutz, Kathrin Junge, Emiel J. M. Hensen, Matthias Beller, Laurent Lefort, and
Evgeny A. Pidko*
Abstract: Catalytic hydrogenation of carboxylic acid esters is
essential for the green production of pharmaceuticals, fragran-
ces, and fine chemicals. Herein, we report the efficient hydro-
genation of esters with manganese catalysts based on simple
bidentate aminophosphine ligands. Monoligated Mn PN
complexes are particularly active for the conversion of esters
into the corresponding alcohols at Mn concentrations as low as
0.2 mol% in the presence of sub-stoichiometric amounts of
KOtBu base.
in such catalysts by cheaper, more abundant, and non-toxic
metals.[5] Among these, manganese can be regarded as one of
the most desirable candidates in view of its low price, rich
chemistry, and exceptional biocompatibility.[6] Yet, most
examples of non-noble metal homogeneous hydrogenation
catalysts are based on Fe[7] and Co,[8] while the respective
catalytic chemistry of Mn was not known until very recently.
In early 2016 Milstein and co-workers described the first MnI-
based catalyst A for the dehydrogenative coupling of alcohols
and amines (Scheme 1).[9a] Later, Kirchner and co-workers
showed that this reaction can also be catalyzed by a related
MnI PNP pincer complex.[9b] Shortly afterwards, the groups of
Beller[10] and Kempe[11] independently reported the hydro-
genation of ketones with pincer catalysts B and C. Complex B
is also active in the reduction of nitriles and aldehydes.
Reduction of less-reactive ester substrates remains a challenge
for Mn catalysts with only two examples reported to date.
Beller and co-workers described aliphatic MnI PNP-pincer
catalyst D that converts esters into alcohols under basic
conditions at 2 mol% catalyst loading (1108C/30 bar H2/
24 h).[12] Milstein and co-workers reported that lutidine-
derived MnI PNN-pincer catalyst E is active at 1 mol%, but
requires addition of KH as the base (1008C/20 bar H2/50 h).[13]
Despite the impressive progress witnessed in recent years in
catalytic hydrogenations with non-noble-metal complexes,
even the most active examples are efficient only at relatively
high catalyst loading of 1–3 mol%, significantly limiting their
utility as practical alternatives to the more active Ru-based
systems.[14] Herein we report the catalytic hydrogenation of
esters with three novel non-pincer-type Mn PN complexes,
T
he reduction of polar carbonyl moieties is a fundamental
organic transformation important for the production of a wide
variety of bulk- and fine chemicals, such as biofuels,
fragrances, and pharmaceuticals. Catalytic processes employ-
ing H2 as the reductant represent an atom-efficient and
sustainable alternative to conventional stoichiometric
approaches.[1] To date a wide range of versatile and highly
active homogeneous ester hydrogenation catalysts based on
Ru,[2] Os,[3] and Ir[4] have been described. Driven by economic
and environmental considerations, recent efforts have
focused on the replacement of the noble-metal component
[*] R. van Putten, E. A. Uslamin, C. Liu, Prof. Dr. E. J. M. Hensen,
Prof. Dr. E. A. Pidko
Inorganic Materials Chemistry Group
Department of Chemical Engineering and Chemistry
Eindhoven University of Technology
P.O. Box 513, 5600 MB, Eindhoven (The Netherlands)
E-mail: E.A.Pidko@tue.nl
M. Garbe, Dr. K. Junge, Prof. Dr. M. Beller
Leibniz-Institut fꢀr Katalyse e.V. an der Universitꢁt Rostock
Albert-Einstein Strasse 29a, 18059, Rostock (Germany)
Dr. A. Gonzalez-de-Castro, Dr. L. Lefort
DSM Ahead R&D B.V. Innovative Synthesis
P.O. Box 18, 6160 MD, Geleen (The Netherlands)
Dr. M. Lutz
Crystal and Structural Chemistry, Bijvoet Center for Biomolecular
Research, Utrecht University
Padualaan 8, 3584 CH, Utrecht (The Netherlands)
Prof. Dr. E. A. Pidko
ITMO University
Kronverskskiy pr., 49, 197101, St. Petersburg (Russia)
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under:
http://dx.doi.org/10.1002/anie.201701365.
ꢂ 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co.
KGaA. This is an open access article under the terms of the Creative
Commons Attribution Non-Commercial License, which permits use,
distribution and reproduction in any medium, provided the original
work is properly cited, and is not used for commercial purposes.
Scheme 1. Mn-based (de)hydrogenation catalysts.
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based on simple and easily accessible bidentate aminophos-
phine ligands. They show good performance at an unprece-
dented loading of only 0.2 mol%, bringing Mn-catalyzed
hydrogenation a step closer to practical implementation.
The use of P,N ligands for Ru-catalyzed ester hydro-
genation was first reported by Saudan et al.[15] We prepared
complexes 1 to 3 by reaction of Mn(CO)5Br with 1 or
2 equivalents of the corresponding P,N ligand in toluene at
1008C for 24 h. The isolated complexes were fully charac-
decreased substantially at higher temperatures owing to
formation of methyl benzyl ether (Table 1, entries 2,4,5).
Increasing the amount of KOtBu led to improved yields
(Table 1, entries 6–8). Ultimately, quantitative BnOH yield
was obtained with 0.75 equivalents of KOtBu relative to the
substrate (Table 1, entry 8).
After full conversion was achieved, we sought to optimize
crucial process parameters such as solvents, bases, reaction
temperature and H2 pressure to enable use of 2 at reduced
catalyst loading. With 0.5 mol% of 2 in THF a BnOH yield of
87% could be achieved in just 3 h. Importantly, 2 could also
be formed in situ without significant loss of activity, thus
eliminating the need for catalyst isolation (Table S1 in the
Supporting Information). Mercury poisoning did not evi-
dence inhibition, suggesting the homogeneous nature of
catalysis with 2 (Table S1).[18] Replacement of THF for 1,4-
dioxane resulted in a higher product yield, while the use of 2-
methyl-THF and MTBE led to inferior performance
(Table S2). KOtBu was found to be the superior base for the
current catalytic system (Table S3). An increase in temper-
ature and reduction in H2 pressure resulted in lower BnOH
yields (Table S4).
1
terized by H/31P-NMR, ESI-MS, FTIR, elemental analysis,
and single-crystal X-ray structure analysis (see Supporting
Information). Single-crystal X-ray structure determination
revealed the cis-coordination of the N-donor groups of the
P,N ligands and CO ligands in 1, with the two phosphine
moieties bound trans to each other (Figure 1). Their chemical
Next, we expanded the scope of the substrates and further
decreased the catalyst loading to 0.2 mol%. Under the
optimized conditions, 2 was able to convert aromatic and
aliphatic esters into their corresponding alcohols in good to
excellent yields (Scheme 2). Reduction of hexanoate esters
A1–A3 led to good yields of 1-hexanol with hexyl hexanoate
as the only by-product. Interestingly, more sterically hindered
esters (A4–A6) were almost quantitatively hydrogenated,
whereas these are typically more difficult to reduce than their
methyl and ethyl analogues.[1] Aromatic benzoate esters with
varied steric bulk or electronic properties were all hydro-
genated to benzyl alcohol in high yield (B1–B4). Similar to
aliphatic esters, the reduction of bulky tert-butyl benzoate was
more efficient than the less-sterically hindered substrates.
Figure 1. ORTEP diagrams of 1 (left) and 2 (right). Thermal ellipsoids
are set at 30% probability. Hydrogen atoms have been omitted for
clarity.
equivalence was also detected in solution by 31P NMR,
revealing a single resonance for 1 at d = 79.3 ppm. Complex
2 contains a single P,N ligand. The amine and Brꢀ in 2 are
bound in a cis fashion, providing a favorable environment for
heterolytic H2 activation across the Mn–N moiety.[16]
Complexes 1–3 are active catalysts for ester hydrogena-
tion. Table 1 summarizes the results of the initial catalytic
tests using methyl benzoate as a model substrate. Mono-
ligated complex 2 was found to be considerably more active
than 1 and 3 (Table 1, entries 1–3). This is remarkable as the
related Ru-PN catalyst is biligated.[15] Reaction at 80–1008C
gave similar benzyl alcohol (BnOH) yields, while the yield
Table 1: Hydrogenation of methyl benzoate with 1–3.[a]
Entry Catalyst KOtBu [mol%] T [8C] Conv. [%] YBnOH [%][17]
1
2
3
4
5
6
7
8
1
2
3
2
2
2
2
2
10
10
10
10
10
25
50
75
100
100
100
80
120
100
100
100
43
75
13
74
57
86
96
99
24
66
3
65
43
80
91
98
Scheme 2. Hydrogenation of various esters with 2. Conditions: 1 mmol
substrate, 75 mol% KOtBu, 0.2 mol% 2, 2 mL 1,4-dioxane, 1008C,
50 bar H2, 16 h. [a] 0.5 mol% 2, 6 h.
[a] Conditions: 1 mmol methyl benzoate, 10–75 mol% KOtBu, 1.0 mol%
Mn, 2 mL THF, 80–1208C, 50 bar H2, 20 h. Yield determined by GC.
2
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Hydrogenation of functionalized esters B5 and B6 gave high
yields of the corresponding alcohols with the functional group
being preserved and only trace amount of the methyl ether
side products detected by GC-MS. Hydrogenation of unsatu-
rated esters with 2 was fully chemoselective for substrates
=
with the C C bond distant from the ester moiety, such as fatty
acid methyl esters C1 and C2. Methyl cinnamate (C3),
however, was fully converted into hydrocinnamyl alcohol. No
products associated with the Claisen condensation were
observed for the enolizable substrates.
To get better insight into the effect of the base in catalysis
with 2 we carried out additional catalytic tests using four
different benzoate substrates at varied base concentration
(Figure 2). For all substrates, the elevated base loading
Figure 3. Kinetic traces of methyl benzoate hydrogenation with 2.
Conditions: 15 mmol methyl benzoate, 10–75 mol% KOtBu, 0.5 mol%
2, 28 mL THF, 1008C, 50 bar H2.
Gibbs free energies for elementary steps, DG8373Ksolv, are
summarized in Figure 4. Prior to the catalytic reaction, 2 is
activated via a base-assisted hydrogenolysis to produce
hydrido complex I (see Supporting Information). The cycle
starts with an exergonic complexation of MeOAc with I to
give H-bonded intermediate II, which then converts into an
activated gem-acetal III via a hydride attack with a free
energy barrier of 97 kJmolꢀ1. The addition of H2 to III yields
s-complex IV, which after hydrogenolysis produces CH3OH
and CH3CHO. Methanol elimination gives VI, from which the
final stage of the catalytic cycle, that is, aldehyde hydro-
genation, proceeds. This step is significantly more favorable
than the initial ester activation. The first hydride transfer is
exergonic by ꢀ8 kJmolꢀ1 and shows a free energy barrier of
only 29 kJmolꢀ1 (VI!VII). The resulting alkoxy anion is
stabilized by a partial deprotonation of the NH2-moiety of the
ligand, thereby resulting in a trigonal bipyramidal configu-
ration of Mn in VII. The interaction with the basic ethoxide
facilitates complexation with H2 to form VIII that is followed
Figure 2. Effect of ester alkoxy group and KOtBu amount on the degree
of hydrogenation (equal to sum of benzyl alcohol, methyl benzyl ether,
and 1= benzyl benzoate yields).
2
resulted in a higher product yield. The hydrogenation of
methyl- and ethyl benzoates was more sensitive to changes in
the base concentration than for the tert-butyl- and benzyl
benzoate substrates. We attribute this to catalyst inhibition by
the short-chain alcohols produced in the reaction. This effect
is in line with the lower activity achieved with KOMe and
KOEt bases (Table S3). Product inhibition via metal-alkoxide
formation is well-known for P,N-type complex catalysts and is
consistent with both the lower observed rates for methyl- and
ethyl esters as well as the increased TON at reduced catalyst
loading.[19]
Dedicated kinetic experiments were next carried out to
further study the role of the base (Figure 3).[21] Near-complete
hydrogenation was achieved with 0.75 equiv. KOtBu, while in
the presence of 0.1 equiv. base the reaction progress was
limited to around 20%. Remarkably, catalytic activity could
be instantaneously restored upon addition of 0.65 equiv.
KOtBu. Regardless of the base loading sequence, nearly
identical initial rates of about 1100 hꢀ1 were observed (see
Figure S14). This is consistent with our hypothesis on Mn-
alkoxide inhibition, which upon reaction with KOtBu convert
into the catalytically active manganese amide. A similar
mechanism of in situ catalyst regeneration has been proposed
previously for related Ru-based catalysts.[20]
Next, the reaction mechanism with 2 was studied by
density functional theory (DFT) calculations at the PBE0/6-
311G(d)//6-31G(d) level (Gaussian09 D.01).[22] Methyl ace-
tate (MeOAc) was chosen as the model substrate. The
proposed mechanism, along with the reaction and activation
Figure 4. Proposed catalytic cycle for methyl acetate hydrogenation by
H2 and 2 (DG and G° stand for the reaction and activation Gibbs free
energy changes in kJmolꢀ1 at 373 K).
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In summary, we have synthesized and fully characterized
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complex 2 is a highly active catalyst for the hydrogenation of
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We acknowledge the Netherlands Center for Multiscale
Catalytic Energy Conversion (MCEC), an NWO Gravitation
program funded by the Ministry of Education, Culture and
Science of the Netherlands. E.A.P. thanks the Government of
the Russian Federation (Grant 074-U01) for support through
the ITMO Fellowship and Professorship Program. Super-
computer resources were provided by NWO. We thank Dr.
Anke Spannenberg for crystal-structure determination of 1.
The X-ray diffractometer at Utrecht University has been
financed by NWO.
Conflict of interest
[17] Bn- and tBu benzoate account for the residual mass balance.
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The authors declare no conflict of interest.
Keywords: alcohols · esters · homogeneous catalysis ·
hydrogenation · manganese
[21] A different (larger) autoclave was used for these experiments.
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Manuscript received: February 7, 2017
Final Article published: && &&, &&&&
4
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Communications
Hydrogenation Catalysts
It’s SuperMn! A bidentate MnI P,N com-
plex is a highly active catalyst for the
hydrogenation of esters under mild con-
ditions. Quantitative yields of alcohols
are obtained for a variety of aliphatic and
aromatic esters, while showing complete
chemoselectivity for ester reduction in the
presence of internal and terminal alkene
functionalities.
R. van Putten, E. A. Uslamin, M. Garbe,
C. Liu, A. Gonzalez-de-Castro, M. Lutz,
K. Junge, E. J. M. Hensen, M. Beller,
L. Lefort, E. A. Pidko*
&&&& — &&&&
Non-Pincer-Type Manganese Complexes
as Efficient Catalysts for the
Hydrogenation of Esters
Angew. Chem. Int. Ed. 2017, 56, 1 – 5
ꢀ 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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