Hydrogenation of Nitriles and Ketones Catalyzed by an Air-Stable Bisphosphine Mn(I) Complex

Article abstract of DOI:10.1021/acs.orglett.8b03132

Efficient hydrogenations of nitriles and ketones with molecular hydrogen catalyzed by a well-defined bench-stable bisphosphine Mn(I) complex are described. These reactions are environmentally benign and atomically economic, implementing an inexpensive, earth-abundant nonprecious metal catalyst. A range of aromatic and aliphatic nitriles and ketones were efficiently converted into primary amines and alcohols, respectively, in good to excellent yields. The hydrogenation of nitriles proceeds at 100 °C with catalyst loading of 2 mol % and 20 mol % base (t-BuOK), while the hydrogenation of ketones takes place already at 50 °C, with a catalyst loading of 1 mol % and 5 mol % of base. In both cases, a hydrogen pressure of 50 bar was applied.

Full text of DOI:10.1021/acs.orglett.8b03132

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Hydrogenation of Nitriles and Ketones Catalyzed by an Air-Stable
Bisphosphine Mn(I) Complex
†
‡
,†
̈
Stefan Weber, Berthold Stoger, and Karl Kirchner*
†Institute of Applied Synthetic Chemistry, Vienna University of Technology, Getreidemarkt 9/163-AC, A-1060 Wien, Austria
‡X-Ray Center, Vienna University of Technology, Getreidemarkt 9/163, A-1060 Wien, Austria
S
* Supporting Information
ABSTRACT: Efficient hydrogenations of nitriles and ketones with molecular hydrogen
catalyzed by a well-defined bench-stable bisphosphine Mn(I) complex are described. These
reactions are environmentally benign and atomically economic, implementing an inexpensive,
earth-abundant nonprecious metal catalyst. A range of aromatic and aliphatic nitriles and
ketones were efficiently converted into primary amines and alcohols, respectively, in good to
excellent yields. The hydrogenation of nitriles proceeds at 100 °C with catalyst loading of 2 mol
% and 20 mol % base (t-BuOK), while the hydrogenation of ketones takes place already at 50
°C, with a catalyst loading of 1 mol % and 5 mol % of base. In both cases, a hydrogen pressure
of 50 bar was applied.
bisphosphine Mn(I) complex as shown in Scheme 1. To the
best of our knowledge, this is the only other example of a
he development of efficient and selective synthetic
Tmethods to obtain novel target molecules is one of the
fundamental research goals in modern organic chemistry.
Moreover, as the sustainable use of resources is a major issue, it
is important to perform organic reactions under catalytic
conditions utilizing earth-abundant nonprecious metal catalysts
based on, e.g., iron, cobalt, or manganese.1 In this context,
atom-efficient and clean processes that permit access to a green
synthesis of valuable alcohols and amines is the hydrogenation
of carbonyl compounds, imines, and nitriles with molecular
hydrogen. Iron-2 and cobalt-based3 catalysts and most recently
also manganese catalysts4−8 have turned out to be highly active
for such processes (Figure 1).
Scheme 1. Synthesis of fac-[Mn(nPr2PCH2CH2PnPr2)
(CO)3Br] (1) and Structural View of 1 Showing 50%
a
Ellipsoids (H Atoms Omitted for Clarity)
a
Selected bond distances (Å) and angles (deg): Mn1−Br1 2.5593(6),
Mn1−C15 1.776(4), Mn1−C17 1.824(4), Mn1−C16 1.829(4),
Mn1−P2 2.313(1), Mn1−P1 2.314(1), Mn2−P4 2.323(1), C16−
Mn1−P2 175.5(1), C17−Mn1−P1 173.8(1), C15−Mn1−Br1
178.3(1).
Inspired by recent discoveries of manganese-catalyzed
(de)hydrogenation reactions,4 we describe here the efficient
hydrogenation of nitriles and ketones catalyzed by an air-stable
manganese catalyst being able to hydrogenate nitriles.5 It has
to be further noted that nonpincer type Mn(I) complexes have
rarely been applied in hydrogenation catalysis.8d,f,g
The neutral Mn(I) complex fac-[Mn(nPr2PCH2CH2PnPr2)
(CO)3Br] (1) was obtained by treatment of the commercially
available [Mn(CO)5Br] with the ligand nPr2PCH2CH2PnPr2
in 71% isolated yield (Scheme 1). The resulting yellow-orange
complex was fully characterized by NMR and IR spectroscopy,
high resolution mass spectrometry, and elemental analysis (see
Supporting Information). The IR spectrum contains strong
CO stretching vibrations at 2003, 1935, and 1903 cm−1, which
Figure 1. Manganese catalysts for the hydrogenation of nitriles,
ketones, and aldehydes.
Received: October 1, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b03132
Org. Lett. XXXX, XXX, XXX−XXX

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Letter
clearly indicates the coordination of three CO ligands to the
metal center in a facial arrangement.9 The molecular structure
of 1 was determined by single-crystal X-ray diffraction. A
structural view with selected bond distances and angles is
depicted in Scheme 1.
Table 2. Hydrogenation of Various (Hetero)aromatic and
Aliphatic Nitriles Catalyzed by 1
a
The catalytic performance of complex 1 was then
investigated for the hydrogenation of 4-fluorobenzonitrile as
a model substrate. We tested the influence of various solvents,
addition of bases, and different temperatures. Selected
optimization experiments are depicted in Table 1. With a
Table 1. Optimization of the Reaction Conditions for the
a
Hydrogenation of 4-Fluorobenzonitrile.
b
entry
solvent
t (°C)
base
yield (%)
1
2
3
4
5
6
7
8
MeOH
EtOH
90
90
90
90
90
90
80
100
100
100
t-BuOK
t-BuOK
t-BuOK
t-BuOK
MeONa
DBU
t-BuOK
t-BuOK
t-BuOK
t-BuOK
<5
<5
<5
77
30
<5
35
95
47
>99
dioxane
toluene
toluene
toluene
toluene
toluene
toluene
toluene
c
9
10
d
a
Reaction conditions: 4-fluorobenzonitrile (0.72 mmol), t-BuOK (10
mol %), catalyst (2 mol %), 5 mL of anhydrous toluene, 50 bar H2, 18
b
c
h. Determined by 19F{1H} NMR spectroscopy. 1 mol % catalyst.
d
20 mol % t-BuOK.
catalyst loading of 2 mol % at 90 °C in the presence of 10 mol
% t-BuOK and a hydrogen pressure of 50 bar H2, no reaction
took place in the protic solvents MeOH and EtOH as well as in
dioxane (Table 1, entries 1 and 3) after 18 h of reaction time.
In toluene, 77% of 4-fluorobenzylamine was obtained (Table 1,
entry 4). Applying weaker bases such as MeONa or DBU (1,8-
diaza-bicyclo[5.4.0]undec-7-ene) resulted in small or no
conversions (Table 1, entries 5 and 6). In the absence of
base, no reaction took place. At lower temperature (80 °C) or
a lower catalyst loading (1 mol %), the catalytic activity
dropped significantly and lower yields of 4-fluorobenzylamine
were obtained (Table 1, entries 7 and 9). At 100 °C the yield
of 4-fluorobenzylamine increased to 95% (Table 1, entry 8). A
high catalytic activity was observed upon increasing the
concentration of t-BuOK from 10 to 20 mol %, affording 4-
fluorobenzylamine in essentially quantitative yield (Table 1,
entry 10). It has to be noted that in the absence of catalyst or
with [Mn(CO)5Br] as catalyst, no reaction took place.
The catalytically active manganese species may be the
hydride complex fac-[Mn(nPr2PCH2CH2PnPr2)(CO)3H],
which could be detected by 1H NMR from the reaction
mixture giving rise to a hydride triplet resonance at −9.16 ppm
(JHP = 48.8 Hz).
a
Reaction conditions: substrate (0.72 mmol), t-BuOK (20 mol %),
catalyst (2 mol %), 5 mL of anhydrous toluene, 100 °C 50 bar H2, 18
h. GC yield. Isolated yields as ammonium hydrochloride. Overall
yield with 10% of fully hydrogenated product. Reaction time 48 h.
b
c
d
e
Having established the best reaction conditions, the
applicability of catalyst 1 is demonstrated in the selective
hydrogenation of various nitriles, including substituted
aromatic, benzylic, aliphatic nitriles, and a dinitrile. These
results are shown in Table 2. In general, electron-donating and
electron-withdrawing substituents, e.g., chloride, bromide,
methyl, methoxy, and amino, as well as heterocycles such as
pyridine and thiophenes are well tolerated. No reaction was
observed in the case of 2-hydroxybenzonitrile (Table 2, entry
8), presumably due to possible chelating property of this
substrate. In the case of methyl-4-cyanobenzoate, the nitrile
B
DOI: 10.1021/acs.orglett.8b03132
Org. Lett. XXXX, XXX, XXX−XXX

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group was selectively hydrogenated, while the ester moiety was
tolerated (Table 2, entry 9). Such a transformation cannot be
achieved with common reduction reagents such as LiAlH4. In
the case of cinnamyl nitrile and (E)-3-(4-chlorophenyl)-
acrylonitrile, 91 and 89% (E)-4-phenylbut-3-en-1-amine and
(E)-3-(4-chlorophenyl)prop-2-en-1-amine, respectively, were
obtained (Table 2, entries 13 and 14). It has to be emphasized
that the CC double bond was only reduced to an amount of
about 10%. Likewise, also 4-((trimethylsilyl)ethynyl)-
benzonitrile was converted into the respective amine in 67%
isolated yield without hydrogenating the CC triple bond
(Table 2, entry 15). Finally, linear aliphatic nitriles and
decanedinitrile were converted to the corresponding amines in
high yields (Table 2, entries 18−22).
hydrogenation of ketones based on well-defined manganese
catalysts.
In conclusion, we have reported an efficient hydrogenation
of nitriles and ketones with molecular hydrogen catalyzed by a
well-defined bench-stable bisphosphine Mn(I) complex where
metal−ligand cooperation is not possible and we believe that
an outer-sphere process without ligand participation is taking
place. These reactions are environmentally benign and atom
economic implementing an inexpensive, earth-abundant non-
precious metal catalyst. A range of (hetero)aromatic and
aliphatic nitriles and ketones were efficiently converted into
primary amines and alcohols, respectively, in good to excellent
isolated yields. The hydrogenation of nitriles proceeds at 100
°C with a catalyst loading of 2 mol % and 20 mol % base (t-
BuOK), while the hydrogenation of ketones takes place already
at 50 °C, with a catalyst loading of 1 mol % and 5 mol % base.
In both cases a hydrogen pressure of 50 bar was applied and
the reaction time was 18 h.
Apart from nitriles, complex 1 also efficiently catalyzes the
hydrogenation of ketones to the corresponding alcohols with 1
mol % of catalyst loading in the presence of 5 mol % t-BuOK
in toluene at 50 °C. We investigated the scope and limitations
of catalyst 1 using various substrates (Table 3). Bromide,
ASSOCIATED CONTENT
* Supporting Information
■
S
Table 3. Hydrogenation of Various (Hetero)aromatic and
a
Aliphatic Ketones Catalyzed by 1
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.8b03132.
Synthetic and hydrogenation procedures, optimization
reactions, 1H, 13C{1H}, and 31P{1H} NMR spectra
(PDF)
Accession Codes
CCDC 1866466 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/data_request/cif, or by emailing
data_request@ccdc.cam.ac.uk, or by contacting The Cam-
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
Corresponding Author
■
*K.K.: e-mail, karl.kirchner@tuwien.ac.at, tel, (+43) 1 58801
163611; fax, (+43) 1 58801 16399.
ORCID
Karl Kirchner: 0000-0003-0872-6159
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
Financial support by the Austrian Science Fund (FWF) is
gratefully acknowledged (Project No. P29584−N28).
■
REFERENCES
■
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D
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Org. Lett. XXXX, XXX, XXX−XXX