Selective Hydrogenation of α,β-Unsaturated Aldehydes and Ketones by Air-Stable Ruthenium NNS Complexes

Article abstract of DOI:10.1002/chem.201700806

The selective hydrogenation of the carbonyl functionality of α,β-unsaturated aldehydes and ketones is catalysed by ruthenium dichloride complexes bearing a tridentate NNS ligand as well as triphenylphosphine. The tridentate ligand backbone is flexible, as evidenced by the equilibrium observed in solution between the cis- and trans-isomers of the dichloride precatalysts, as well as crystal structures of several of these complexes. The complexes are activated by base in the presence of hydrogen and readily hydrogenate carbonyl functionalities under mild conditions. Despite the activation by base, side reactions are negligible, even for aldehyde substrates, because of the low amount of base. Thus, the corresponding allylic alcohols can be isolated in very good yields on a 10–25 mmol scale. Turnover numbers up to 200 000 were achieved.

Full text of DOI:10.1002/chem.201700806

A Journal of
Accepted Article
Title: Selective hydrogenation of α,β-unsaturated aldehydes and
ketones by air-stable Ruthenium NNS complexes
Authors: Johannes Gerardus de Vries, Pim Puylaert, Richard van
Heck, Yuting Fan, Anke Spannenberg, Wolfgang Baumann,
Matthias Beller, Jonathan Medlock, Werner Bonrath, Lauren
Lefort, and Sandra Hinze
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Chem. Eur. J. 10.1002/chem.201700806
Link to VoR: http://dx.doi.org/10.1002/chem.201700806
Supported by

10.1002/chem.201700806
Chemistry - A European Journal
FULL PAPER
Selective hydrogenation of α,β-unsaturated aldehydes and
ketones by air-stable Ruthenium NNS complexes
Pim Puylaert,[a] Richard van Heck,[a] Yuting Fan,[a] Anke Spannenberg,[a] Wolfgang Baumann,[a]
Matthias Beller,[a] Jonathan Medlock,[b] Werner Bonrath,[b] Laurent Lefort,[c] Sandra Hinze,[a] and
Johannes G. de Vries*[a]
Abstract: The selective hydrogenation of the carbonyl functionality
of α,β-unsaturated aldehydes and ketones is catalysed by ruthenium
dichloride complexes bearing a tridentate NNS ligand as well as
triphenylphosphine. The tridentate ligand backbone is flexible, as
evidenced by the equilibrium observed in solution between the cis-
and trans-isomers of the dichloride precatalysts, as well as crystal
structures of several of these complexes. The complexes are
activated by base in the presence of hydrogen and readily
hydrogenate carbonyl functionalities under mild conditions. Despite
the activation by base, side reactions are negligible, even for
aldehyde substrates, because of the low amount of base. Thus, the
corresponding allylic alcohols can be isolated in very good yields on
ligands.[6] Later, it was shown that these complexes suffer from
product inhibition and the ligand was found to be quaternised by
the substrate to some extent.[7] Generally, the reduction of the
carbonyl moiety by ruthenium complexes containing amine or
picoline functionalities is considered to take place via
a
bifunctional metal-ligand mechanism.[8]
The development of cheaper and environmentally more
benign processes led to recent interest towards analogous Fe-,[9]
Co-[10], Mn-[11] and Cu-based[12] catalysts. One downside of these
catalysts is that the catalyst loadings are relatively high in
comparison to precious metal catalysts. In addition,
alkylphosphine ligands are often required, which are not cheap
a 10-25 mmol scale. Turnover numbers up to 200000 were achieved. and usually air-sensitive, thus largely off-setting the gain made
by using base metals. A further challenge in the hydrogenation
of aldehydes lies in the use of strong bases that are needed to
activate the catalyst, as aldehydes themselves are base-
sensitive. Dupau et al. showed that side reactions can be
Introduction
prevented by using ruthenium carboxylate rather than chloride
complexes as the former does not require addition of base.[13]
Selective catalytic hydrogenations and transfer hydrogenations
of the carbonyl functionality in α,β-unsaturated aldehydes and
Despite the vast body of work performed on catalytic
ketones are of great relevance for organic synthesis, as well as
hydrogenation, high activity paired with good selectivity towards
industrial application in, for instance, the production of flavours,
the carbonyl functionality, especially in the case of α,β-
unsaturated aldehydes, remains challenging.
fragrances, or vitamins.[1] Achieving a high selectivity for the
reduction of the carbonyl moiety is inherently difficult because
A promising alternative lies in the development of simple
the reduction of the carbon-carbon double bond is
ligands containing donor atoms other than phosphorus, such as
thermodynamically favoured by approximately 35 kJ/mol.[2]
nitrogen, carbon, or sulphur.[5g,14] For the selective
hydrogenation of α,β-unsaturated aldehydes and ketones, we
Although many different types of heterogeneous catalysts
have been tested,[3] their use has rarely led to more than 90%
developed ruthenium complexes with ligands of the NNS type,
selectivity to the desired allylic alcohols.[4]
as shown in Figure 1. The ligands are obtained in a simple two-
step procedure from readily available starting materials; they are
air- and moisture-stable, and derivatives are readily prepared by
using various substituted pyridines and 2-alkylthioethylamines.
These ruthenium complexes are highly active precatalysts in the
Typical homogeneous hydrogenation catalysts include the
complexes of precious metals such as Ru, Os, Rh and Ir, with
5]
diphosphine/diamine ligand pairs or pincer ligands.[1a,
In
industrial application, ruthenium is strongly preferred in view of
its lower cost. High selectivities towards the allylic alcohols were
obtained with ruthenium complexes based on water-soluble
H
H
H
Cl
Ru
Cl
Cl
Ru
Cl
Cl
Ru
Cl
N
N
S
S
N
S
N
N
PPh3
PPh3
N
PPh3
[a]
P. Puylaert, R. van Heck, Dr. Y. Fan, Dr. A. Spannenberg, Dr. Habil.
W. Baumann, Prof. Dr. M. Beller, Dr. S. Hinze, Prof. Dr. J.G. de
Vries
Leibniz Institut für Katalyse e. V. an der Universität Rostock
Albert-Einstein-Straße 29a, 18055 Rostock, Germany
E-mail: johannes.devries@catalysis.de
C1
C2
C3
H
H
H
Cl
Cl
Cl
Cl
Ru
Cl
N
S
N
N
N
S
S
S
Ru
Cl
Ru
Cl
Ru
Cl
N
PPh3
N
N
N
PPh3
PPh3
PPh3
[b]
[c]
Dr. J. Medlock, Dr. W. Bonrath,
O
Research and Development, Process Research, DSM Nutritional
Products, P.O. Box 2676, 4002 Basel, Switzerland
Dr. Laurent Lefort,
C7
C4
C5
C6
DSM Ahead R&D-Innovative Synthesis
P.O. Box 18, 6160 MD Geleen, The Netherlands
Figure 1. Ru-NNS complexes presented in this work.
Supporting information for this article is given via a link at the end of
the document.
This article is protected by copyright. All rights reserved.

10.1002/chem.201700806
Chemistry - A European Journal
FULL PAPER
chemoselective hydrogenation of α,β-unsaturated ketones and
aldehydes. Excellent selectivities were obtained even in
presence of base required for the activation of the precatalysts.
Structure and properties
1H- and 31P{1H}-NMR spectroscopy showed that the complexes
C1-C7 exist in solution as an equilibrium mixture of isomers. The
ratio between the major and minor isomers is approximately 4 to
1 at room temperature, based on integration of the 1H-NMR
1
signals. H- and 31P{1H}-VT-NMR spectra of C2 in [D8]-toluene
Results and Discussion
showed coalescence at 75 °C (Figure 2; VT-NMR spectra of C7
are available in the supporting information). Thus the equilibrium
is fast at elevated temperatures, and is not expected to influence
the catalyst activation. After storing the complexes under
Preparation of ligands and complexes
The ligands were obtained in good yields via reductive amination
of the corresponding aldehydes and ketones. Ligands L1-L5
were synthesised at room temperature via the intermediate
imine formed from the 2-alkylthio-ethylamines and (substituted)
2-pyridinecarboxaldehydes, followed by NaBH4 reduction
(Scheme 1a). Formation of L6 (Scheme 1b) was slow at room
temperature, and was therefore performed by overnight reflux in
toluene in the presence of 5 mol % of p-toluenesulfonic acid.
The N-methylated amine L7 was obtained via Eschweiler-Clarke
methylation of L2 (Scheme 1c).
ambient conditions for several weeks, the H- and 31P{1H}-NMR
1
spectra looked identical, showing that the complexes were air-
and moisture-stable.
a) 1H
δ 8.6, ∫1
δ 8.0, ∫3
25 °C
R1
a)
R1
S
H2N
2
R2
O
N
R2
50 °C
Na
r.t.,
2SO4
eq.
N
S
N
16 h
R1
DCM,
2
NaBH
eq.
4
H
N
R2
75 °C
25 °C
MeOH,
0 °C to
N
S
1 h
r.t.,
L1-L5
b) 31
P
δ 52.6 δ 51.6
b)
S
H2N
N
O
N
N
S
5% -TsOH
Toluene, reflux,
p
16 h
50 °C
75 °C
2
NaBH
4
H
N
eq.
N
S
MeOH,
0 °C to
1 h
r.t.,
L6
c)
Formalin,
Formic acid
Figure 2. Variable temperature NMR spectra of C2 in [D8]-toluene a) 1H-
(pyridine signals) and b) 31P{1H}-NMR of C2.
H
N
N
16 h
70°C,
N
N
S
S
L7
Upon addition of freshly sublimed potassium tert-butoxide (2 eq.
relative to the Ru), the orange solution of C2 in [D8]-toluene,
[D8]-THF or C6D6 turned dark green immediately, The
characteristic 31P{1H}-NMR signals at δ 52.6 and 51.6 ppm
(major and minor isomer respectively) disappeared completely.
Two doublets at δ 60.7 and 54.4 ppm appeared, both with a J-
coupling value of 23 Hz, which must arise from coupling with
another phosphorus nucleus (Figure 3).
Scheme 1. Preparation of NNS Ligands L1-L5 (a), L6 (b), and L7 (c).
The corresponding RuCl2(NNS)(PPh3) complexes were
prepared in good yields from RuCl2(PPh3)3 by reflux in diglyme
in the presence of 1 equivalent of ligand, according to Scheme 2.
R2
H
Cl
Ru
Cl
N
S
L1-L7
1
eq.
δ 54.5
δ 60.7
RuCl
2(PPh3)3
2 h
reflux,
Diglyme,
N
PPh3
R1
50-90%
Figure 3. 31P{1H}-NMR spectrum (50-70 ppm) of C2 in [D8]-toluene after
addition of 2 eq. of KOtBu.
Scheme 2. Preparation of RuCl2(NNS)(PPh3) complexes.
This article is protected by copyright. All rights reserved.

10.1002/chem.201700806
Chemistry - A European Journal
FULL PAPER
b)
a)
c)
Figure 4: ORTEP drawings (30% probability ellipsoids, hydrogen atoms, except H1A for C2 and C3, are omitted for clarity.) Selected bond lengths (Å) and angles
(°): for complex C2 (a): Ru1-S1 2.3360(5), Ru1-N1 2.1252(17), Ru1-N2 2.0956(16), Ru1-P1 2.2960(5), Ru1-Cl1 2.4199(5), Ru1-Cl2 2.4273(5); S1-Ru1-N1
84.23(5), S1-Ru1-N2 162.42(5), N1-Ru1-N2 78.27(6), N1-Ru1-P1 175.62(5), Cl1-Ru1-Cl2 171.97(2), Cl1-Ru1-N1 84.80(5), Cl1-Ru1-N2 83.65(5), Cl1-Ru1-S1
93.239(18), C1-N1-C7 115.23(16), for complex C3 (b): Ru1-S1 2.3184(4), Ru1-N1 2.1184(14), Ru1-N2 2.1818(14), Ru1-P1 2.3161(4), Ru1-Cl1 2.4327(4), Ru1-
Cl2 2.4207(4), ; S1-Ru1-N1 84.05(4), S1-Ru1-N2 160.75(4), N1-Ru1-N2 76.94(5), N1-Ru1-P1 172.48(4), Cl1-Ru1-Cl2 171.162(15), Cl1-Ru1-N1 86.67(4), Cl1-
Ru1-N2 94.49(4), Cl1-Ru1-S1 87.308(15), C1-N1-C8 113.66(13).for complex C7 (c): Ru1-N1 2.215(2), Ru1-N2 2.069(2), Ru1-S1 2.3039(7), Ru1-Cl1 2.4445(7),
Ru1-Cl2 2.4535(7), Ru1-P1 2.2827(7); N1-Ru1-N2 78.47(9), N1-Ru1-S1 85.11(6), N2-Ru1-S1 93.72(6), N1-Ru1-P1 177.83(7), S1-Ru1-Cl2 172.07(3), N1-Ru1-
Cl2 87.79(6), N2-Ru1-Cl1 170.59(6), Cl1-Ru1-Cl2 94.14(2), C1-N1-C8 108.8(2), Cl1-Ru1-S1 82.65(3), N2-Ru1-Cl2 88.32(6), P1-Ru1-Cl2 94.35(2)
This suggests that upon deprotonation in the absence of a
hydride donor, the activated complex dimerises. This hypothesis
was supported by the appearance of signals at m/z 1117.170
and 1158.183 in the mass spectrum, with isotope patterns
corresponding to a complex possessing two ruthenium atoms,
although these signals are not readily assigned. So far, we have
been unable to isolate this species for further investigation.
Addition of 1 to 5 equivalents of isopropanol to these solutions
did not result in any hydride signals, and upon heating the
complex degraded, as evidenced by a brown precipitate and the
appearance of the signal for uncoordinated PPh3 around δ -5.
Hydride signals were not observed when the NMR experiments
were repeated under a pressure of up to 10 bar of H2.
Crystals of C2, C3 and the tertiary amine complex C7
suitable for X-ray diffraction analysis were obtained. The solid-
state structures were determined as the trans-(mer-) (C2 and
C3) and cis-(fac-) dichloride (C7) complexes (Figure 4).
Dissolving the crystalline material in deuterated solvent at -18 °C,
and subsequent measurement of the 31P{1H}-NMR spectra
showed the same signals as before, in the same ratios,
indicating that the equilibrium established readily. It is likely that
the two equilibrium forms of complexes C1-C7 observed in
solution by NMR correspond to the same fac- and mer- isomers.
Recent theoretical work by Chen et al. on Gusev’s Ru-SNS
hydrogenation catalysts supports this hypothesis, and showed
that the geometry of the isolated complexes does not
necessarily resemble the catalytic species. The flexibility of the
ligand may actually be an important factor for catalyst activity.[15]
amounts. It appears the starting material is first hydrogenated to
CA, which then reacts further to PP. Notably, when using freshly
sublimed potassium tert-butoxide, the reaction is faster and
more over hydrogenation is observed in these initial screening
Table 1. Screening of different bases and lewis acids for the
hydrogenation of trans-cinnamaldehyde to cinnamyl alcohol[a]
OH
O
OH
C2 base
,
H
30 bar H2 80 °C
,
CA
PP
#
Conversion
Base[a]
CA (%)[b]
PP (%)[b]
(%)[b]
100
100
100
100
7
1
2
LiOtBu
NaOtBu
75
76
88
51
0
7
5
3
KOtBu
3
4
KOtBu[c]
43
0
5
Al(iOPr)3
Ti(iOPr)4
CaCO3
6
15
0
0
7
11
0
0
8
Na(PhCOO)
K(PhCOO)
K3PO4
15
0
0
9
22
0
0
10
11
20
0
0
Hydrogenation reactions
Catalytic hydrogenations were performed at 80 °C with 30 bar H2
in isopropanol. A base screening was performed for the
overnight hydrogenation reaction of trans-cinnamaldehyde to
cinnamyl alcohol at 1 mmol scale with 0.05 mol% C2 as catalyst.
As shown in Table 1, full conversions were obtained with tert-
butoxide bases (Entries 1-4). In addition to cinnamyl alcohol
(CA), 3-phenylpropanol (PP) was also observed in small
2,6-Lutidine
25
0
0
[a] Reaction conditions: trans-cinnamaldehyde (1 mmol), dodecane (internal
standard, 200 µL), dry iPrOH (2 mL), C2 (0.05 mol%), base (1.25 mol%), 80 °C,
30 bar H2, 16 h. [b] Determined by GC using dodecane as internal standard. [c]
KOtBu sublimed and stored under Ar prior to reaction. KOtBu stored under
ambient conditions decomposes over time, which in turn leads to a lower actual
base loading, or side reactions catalysed by KOH or K2CO3.
This article is protected by copyright. All rights reserved.

10.1002/chem.201700806
Chemistry - A European Journal
FULL PAPER
Table 3. Substrate scope[a]
reactions that were run overnight. (Entry 4). The other bases
gave disappointing results. The yields of CA and PP did not
correspond to the total conversion, suggesting base-catalysed
side-reactions occurred in these initial screening reactions.
Lewis acid activation with Al(OiPr)3 and (Ti(OiPr)4 was also
investigated (Entries 5 and 6) but none of the expected products
(CA and PP) were observed
Entry
Substrate
O
Product
OH
Yield (%)
99
1
H
O
Under the same reaction conditions, the RuCl2(NNS)(PPh3)
complexes C1-C7 were tested in the catalytic hydrogenation of
trans-cinnamaldehyde in the presence of freshly sublimed
KOtBu (Table 2). In overnight reactions, all complexes reached
full conversion, with CA as the main product together with
varying amounts of PP. When the reaction time was shortened
to 1 h, only C2 gave full conversion and a yield of CA of 90%.
The fact that the amount of PP is higher after 16 h suggests CA
is the primary product of the reaction and PP is a secondary
product formed via hydrogenation of CA. Note that only 52%
conversion was reached after 1 h if 10 eq. of base were used
with respect to the catalyst, instead of the usual 25 eq. Again, it
was observed that the yields of both alcohols did not always add
up to 100%, which suggests that, in the case of slower catalysts,
base-catalysed side-reactions took place leading to unidentified
by-products which were not detected by GC.
OH
O
O
2
99
H
OH
O
HO
O
O
3
4
5
93[b]
99
O
OH
O
H
O
OH
H
O
OH
H
99
OH
OH
O
O
6
7
94[c]
H
H
Table 2. Screening of C1-C7 for the hydrogenation of trans-cinnamaldehyde
96
to cinnamyl alcohol[a]
OH
O
OH
C1-C7
tBu
KO
,
H
30 bar H2 80 °C
,
O
OH
CA
PP
8
9
97
91
Entry
Complex
Conv.
1h
Yield 1h
Conv.
16h
Yield 16h
(CA:PP)
(%)[b]
O
OH
(CA:PP)[c]
(%)[b]
(%)[b]
1
2
3
4
5
6
7
8
9
C1
C2
C2[c]
C3
C4
C5
C6
C7
-
22
7 : 0
90 :10
52 : 0
65 : 2
36 : 23
12 : 0
11 : 3
37 : 16
n.d.
100
100
n.d.
100
100
98
70 : 12
51 : 43
n.d.
O
OH
100
52
10
84
86
66 : 5
80 :14
63 : 8
62 : 32
76 : 12
1:1
OH
O
59
11
12
13
99
93
99
O
O
21
O
OH
O
O
17
100
100
15
56
O
OH
n.d.
[a] Reaction conditions: trans-cinnamaldehyde (1 mmol), dodecane (internal
standard, 200 µL), dry isopropanol (2 mL), C1-C7 (0.05 mol %), KOtBu (1.4
mg, 1.25 mol %), 80 °C, 30 bar H2. [b] Determined by GC using dodecane as
internal standard. [c] 10 eq. base w.r.t. C2 (0.6 mg KOtBu, 0.5 mol %).
O
OH
14
97%[d]
O
O
The fact that N-methylated C7 also catalysed the
hydrogenation indicates that the NH functionality in the ligand is
not essential, although this does not rule out involvement of the
secondary amine in the reaction mechanism of the first 6
complexes. This is in accordance with recent reports by Ikariya,
Dub, Gordon and co-workers on the mechanism of the
asymmetric hydrogenation and transfer hydrogenation of
acetophenone.[8b, 16]
O
O
[a] Reaction conditions: substrate (10 mmol), dry isopropanol (20 mL), C2 (3.2
mg, 0.05 mol%), KOtBu (14 mg, 1.25 mol%), 80 °C, 30 bar H2, 1 h. Listed
yields are isolated yields. [b] 0.5 mol% catalyst, 5.0 mol% KOtBu. [c] 25 mmol
scale.[d] 2 mmol scale in 10 mL dry methanol; reaction time 3 h.
With these results in hand, it was apparent that the purity of
the base and short reaction times are crucial in obtaining both
This article is protected by copyright. All rights reserved.

10.1002/chem.201700806
Chemistry - A European Journal
FULL PAPER
high yields and selectivities. For further reactions, KOtBu was
sublimed and stored under argon atmosphere. Precatalyst C2
was then employed in the hydrogenation of a range of
aldehydes and ketones at a 10 mmol scale (Table 3).
highest abundant peak and are of the expected isotope pattern. X-ray
diffraction data were collected on
a Bruker Kappa APEX II Duo
diffractometer. The structures were solved by direct methods[19] and
refined by full-matrix least-squares procedures on F2.[20] CCDC 1532411-
1532413 contain the supplementary crystallographic data for this paper.
These data can be obtained free of charge from the Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
Next to representative α,β-unsaturated aldehydes and
ketones, Table
3 also includes furfural (Entry 2) and
hydroxymethylfurfural (HMF, Entry 3), which are of interest as
biomass-derived platform chemicals.[17] In entries 7 and 10, no
hydrogenation of the non-conjugated C=C bond was observed.
The substrate of Entry 14 contains both an aldehyde and an
ester functionality. Only the aldehyde was hydrogenated under
the reaction conditions. This reaction was performed in methanol
instead of isopropanol, to prevent transesterification. The
hydrogenation of trans-cinnamaldehyde was scaled up to 25
mmol leading to a slightly higher yield of the desired CA. The
hydrogenated products were isolated in high yields after 1 hour
reaction time, corresponding to TONs of 2000.
NNS ligand synthesis
2-(Ethylthio)-N-((6-methylpyridin-2-yl)methyl)ethan-1-amine [L3]: a)
6-Methylpyridine-2-carboxaldehyde (3.0 g, 25 mmol) and 2-
(ethylthio)ethylamine (2.63 g, 2.8 mL, 1 eq.) were dissolved in CH2Cl2 (75
mL), and Na2SO4 (7.1 g, 50 mmol) was added. The suspension was
stirred at room temperature overnight, and filtered. The filter cake was
washed with CH2Cl2, and the combined volatiles were removed in vacuo,
yielding 5.45 g of imine as a brown oil, which was used directly in the
following step without further purification. 1H-NMR (300 MHz, CDCl3): δ
8.34 (s, 1H, -CCH=N-), 7.74 (d, 1H, JH-H = 7.5, CHarom), 7.59 (t, 1H, JH-H
=
Workup typically consisted of filtration over a plug of silica
and distillation in vacuo. In some cases (Entry 6, 7, and 10),
slight overhydrogenation already occurred during cooldown of
the reaction vessel, and column chromatography was necessary
to obtain clean products. For the hydrogenation of HMF (Entry 3),
0.5 mol% of pre-catalyst was required. This can be ascribed to
impurities and decomposition products in liquid HMF, a known
problem in its chemistry.[18]
The hydrogenation of acetophenone was repeated with C2
loadings of 50 and 5 ppm, using stock solutions, 25 eq. base
w.r.t. precatalyst. Full conversion was reached overnight,
corresponding to TONs of > 200 000 after 16 h.
7.5, CHarom), 7.15 (d, 1H, JH-H = 7.5, CHarom), 3.83 (dt, 2H, JH-H = 7.2, JH-H
= 1.3), 2.84 (t, 2H, JH-H = 7.0), 2.56 (s, 3H), 2.56 (q, 2H, JH-H = 7.2) 1.23 (t,
3H, JH-H = 7.4). HRMS (ESI+): calculated for C11H16N2S: 208.1034; found
209.1109 (M+H). b) The imine (5.45 g) was dissolved in MeOH (50 mL),
and NaBH4 (2.6 g, 2 eq.) was added in portions at 0 ⁰C. The mixture was
then stirred at room temperature for another hour, after which the solvent
was removed in vacuo. CH2Cl2 (20 mL) and water (20 mL) were added,
and the aqueous layer was extracted three more times with DCM (20 mL).
The combined organic layers were washed with 20 mL of brine and dried
over Na2SO4. Evaporating the solvent and drying in vacuo yielded 4.95 g
(94%) of L3 as an orange oil, which could be used for complex synthesis
directly, or further purified by Kugelrohr distillation. 1H-NMR (300 MHz,
CDCl3): δ 7.45 (t, 1H, J = 7.6, CHarom), 7.07 (d, 1H, J = 7.8, CHarom), 6.96
(d, 1H, J = 7.5, CHarom), 3.84 (s, 2H), 2.80 (dt, 2H), 2.66 (dt, 2H), 2.48 (m,
5H), 1.23 (t, 3H, J = 7.4).13C-NMR (75 MHz, CDCl3): δ 158.9, 157.8,
136.5, 121.3, 118.9, 54.9, 48.2, 31.8, 25.6, 24.4. HRMS (ESI+):
calculated for C11H18N2S: 210.1191; found 211.1265 (M+H), 233.1082
(M+Na).
Conclusions
New air-stable Ru-NNS(TPP) dichloride complexes based on
tridentate, easy to prepare ligands have been synthesised in
good yields. The complexes are highly suitable as precatalysts
in the fast and selective hydrogenation of a range of aromatic
and α,β-unsaturated aldehydes and ketones. The need for in situ
catalyst activation by a strong base did not lead to significant
side reactions at the short reaction times that were used. Full
conversions corresponding to TONs of 2000 were obtained
invariably within 1 hour, and TONs > 200000 were achieved
overnight.
2-(Ethylthio)-N-(1-(pyridin-2-yl)ethyl)ethan-1-amine [L6]: To a solution
of 2-acetylpyridine (3.0 g, 25 mmol) and 2-(ethylthio)ethylamine (2.63 g,
2.8 mL, 1 eq.) in toluene (75 mL), Na2SO4 (7.1 g, 50 mmol) and p-
toluenesulfonic acid (210 mg, 5 mol%) were added, and the mixture was
heated to reflux overnight. The imine was then reduced to L6
analogously to L3 for an overall yield of 80%. 1H NMR (300 MHz,
CD2Cl2): δ 8.51 (ddd, 1H, JH-H = 4.8 Hz, JH-H = 1.9 Hz,3JH-H = 1.0 Hz,
CHarom), 7.64 (td, 1H, JH-H = 7.6 Hz, JH-H = 1.8 Hz, CHarom), 7.32 (dt, 1H,
JH-H = 7.8 Hz, JH-H = 1.1 Hz, CHarom), 7.14 (ddt, 1H, JH-H = 7.5 Hz, JH-H
=
4.8 Hz, JH-H = 1.2 Hz, CHarom), 3.84 (q, 1H, JH-H = 6.9 Hz, CH), 2.71 –
2.55 (m, 4H, CH2), 2.47 (q, 2H, JH-H = 7.4 Hz, CH2), 2.05 (d, 1H, J = 39.3
Hz, NH), 1.34 (d, 3H, JH-H = 6.9 Hz, CH3), 1.20 (d, 3H, JH-H = 7.5 Hz,
CH3). 13C NMR (75 MHz, CD2Cl2): δ 165.4, 149.7, 136.9, 122.3, 121.4,
59.7, 47.1, 32.7, 26.1, 23.2, 15.2. HRMS (ESI+): calculated for
C11H18N2S: 210.1191; (M+H), 211.1264; (M+Na): 233.1083; found
211.1265 (M+H), 233.1083 (M+Na).
Experimental Section
General
Reagents and solvents were obtained from commercial sources and
used as received unless noted otherwise. Dry solvents were obtained
from a solvent purification system (CH2Cl2, toluene, heptane,) purchased
water-free in a bottle with septum (isopropanol) or distilled before use
(diglyme, deuterated solvents, isopropanol.) GC analysis was carried out
on an Agilent 7890B GC system with a HP-5 normal-phase silica column,
using He as a carrier gas and dodecane as standard. NMR spectra were
recorded on a Bruker AV400, Bruker AV300 or Bruker Fourier300 NMR
spectrometer. 1H and 13C-NMR spectra were referenced w.r.t. the solvent
signal. NMR experiments under hydrogen pressures larger than 1 bar
were carried out in a Wilmad Labglass pressure NMR tube. All chemical
shifts are in ppm, coupling constants in Hz. HR-MS measurements were
recorded on an Agilent 6210 Time-of-Flight LC/MS (ESI) or Thermo
Electron MAT 95-XP (EI, 70 eV), peaks as listed correspond to the
2-(Ethylthio)-N-methyl-N-(pyridin-2-ylmethyl)ethan-1-amine [L7]: 2-
(Ethylthio)-N-(pyridin-2-ylmethyl)ethan-1-amine (L2, 850 mg, 3.75 mmol),
formalin (4 mL of 37 wt% formaldehyde in water) and formic acid (4 mL)
were heated to 70 ⁰C overnight. All volatiles were removed in vacuo. To
the sticky brown residue, CH2Cl2 (10 mL) was added and extracted with a
saturated NaHCO3 solution in water (10 mL). The aqueous layer was
extracted three more times with CH2Cl2 (10 mL). The organic layers were
washed with brine and then dried over Na2SO4. Removal of the solvent
yielded 754 mg (3.59 mmol, 96%) of L7 as an orange liquid. 1H NMR
(300 MHz, CD2Cl2): δ 8.51 (ddd, 1H, J = 4.8 Hz, J = 1.9 Hz, J = 1.0 Hz,
CHarom), 7.64 (td, 1H, J = 7.6 Hz, J = 1.8 Hz, CHarom), 7.32 (dt, 1H, J = 7.8
Hz, J = 1.1 Hz, CHarom), 7.14 (ddt, 1H, J = 7.5 Hz, J = 4.8 Hz, J = 1.2 Hz,
CHarom), 3.84 (q, 1H, J = 6.9 Hz, CH), 2.71 – 2.55 (m, 4H, CH2), 2.47 (q,
This article is protected by copyright. All rights reserved.

10.1002/chem.201700806
Chemistry - A European Journal
FULL PAPER
2H, J = 7.4 Hz, CH2), 2.05 (d, 1H, J = 39.3 Hz, NH), 1.34 (d, 3H, J = 6.9
Hz, CH3), 1.20 (d, 3H, J = 7.5 Hz, CH3). 13C NMR (75 MHz, CD2Cl2): δ
165.4, 149.7, 136.9, 122.3, 121.4, 59.7, 47.1, 32.7, 26.1, 23.2, 15.2.
HRMS (ESI+): calculated for C11H18N2S: 210.1191; (M+H), 211.1264;
(M+Na): 233.1083; found 211.1265 (M+H), 233.1083 (M+Na).
2H), 0.87 (t, 3H, J = 7.5). 31P-NMR (122 MHz, CD2Cl2): δ 48.8, 45.8.
HRMS (ESI+): calculated for C29H32Cl2N2PRuS (M+H): 644.0518; found
644.0518 (M+H), 667.0412 (M+Na). Elemental analysis (%) calculated
for C29H33Cl2N2PRuS: C 54.04; H 5.16, N 4.35, S 4.97; found C 53.72, H
5.09, N 4.17, S 5.27. Crystal data for C3: C29.5H34Cl3N2PRuS, M = 687.03,
triclinic, space group P1, a = 9.8567(3), b = 10.0175(3), c = 15.9263(5) Å,
α = 100.0358(7), β = 97.5261(7), γ = 99.4249(7)° V = 1506.85(8) Å3, T =
2-(Methylthio)-N-((pyridin-2-yl)methyl)ethan-1-amine [L1]: Pyridine-2-
carboxaldehyde and 2-(methylthio)ethylamine were converted to L1
analogously to L3 in a yield of 92%. 1H NMR (300 MHz, CD2Cl2) δ 8.43
(ddd, 1H, J = 4.9 Hz, J = 1.8 Hz, J = 0.9 Hz, CHarom), 7.57 (td, 1H, J = 7.7
Hz, J = 1.8 Hz, CHarom), 7.24 (d, 1H, J = 7.8 Hz, CHarom), 7.07 (dd, 1H, J
= 7.5 Hz, J = 5.0.7 Hz, CHarom), 3.81 (s, 2H), 2.75 (td, 2H, J = 6.5 Hz, J =
0.8 Hz, CH2), 2.58 (td, 2H, J = 6.5 Hz, J = 0.6 Hz, CH2), 1.99 (s, 3H, CH3).
13C NMR (75 MHz, CD2Cl2): δ 160.2, 149.1, 136.2, 121.9, 121.7, 54.8,
47.6, 34.4, 15.0. HRMS (ESI+): calculated for C9H14N2S: 182.0878
(M+H): 183.0950; found 183.0950 (M+H)
150(2) K,
Z = 2, 57859 reflections measured, 7259 independent
reflections (Rint = 0.0303), final R values (I > 2σ(I)): R1 = 0.0226,
wR2 = 0.0526, final R values (all data): R1 = 0.0290, wR2 = 0.0564, 358
parameters.
Ru(NNSMe)(PPh3)Cl2 [C1]: RuCl2(PPh3)2 and L1 (1 eq.) were converted
to C1 analogously to C3. C1 was obtained in 80% yield as an orange
powder. 1H-NMR (300 MHz, CD2Cl2): δ 8.47 (d, 1H, JH-H = 5.7), 7.72 (m,
1H), 7.56 (m, 6H), 7.32 (m, 10H), 6.86 (t, 1H, JH-H = 6.3), 5.45 (s, broad,
1H, NH), 5.20 (t, 1H, JH-H = 12.6), 4.38 (m, 1H), 3.41 (m, 3H), 3.26 (d, 1H,
JH-H = 11.1), 2.55 (m, 1H), 1.14 (m, 2H). 31P-NMR (122 MHz, CD2Cl2): δ
51.8, 50.7. HRMS (ESI+): calculated for C27H29Cl2N2PRuS: 616.0210
(M+); found 616.0197 (M+). Elemental analysis (%) calculated for
C27H29Cl2N2PRuS: C 52.60; H 4.74, N 4.54, S 5.20; found C 52.92, H
4.77, N 4.68, S 5.58.
2-(Ethylthio)-N-((pyridin-2-yl)methyl)ethan-1-amine [L2]: Pyridine-2-
carboxaldehyde and 2-(ethylthio)ethylamine were converted to L2
analogously to L3 in a yield of 94%. 1H NMR (300 MHz, CD2Cl2): δ 8.51
(ddd, 1H, J = 4,8 Hz, J = 1.5 Hz, J = 0.9 Hz, CHarom), 7.64 (td, 1H, J = 7.5
Hz, J = 1.8 Hz, CHarom), 7.32 (d, 1H, J = 7,8 Hz, CHarom), 7.19 – 7.12 (m,
1H, CHarom), 3.88 (s, 2H, CH2), 2.85 – 2.79 (m, 2H, CH2), 2.72–2.66 (m,
2H, CH2), 2.52 (q, 2H, J = 7.5 Hz, CH2), 2.09 (d, 1H, J = 9.6 Hz, NH),
1.23 (t, 3H, J = 7.4 Hz, CH3). 13C NMR (75 MHz, CD2Cl2): δ 161.6, 149.7,
136.8, 122.5, 122.3, 55.4, 48.9, 32.5, 26.2, 15.3. HRMS (ESI+):
Ru(NNSEt)(PPh3)Cl2 [C2]: RuCl2(PPh3)2 and L2 (1 eq.) were converted
to C2 analogously to C3. C2 was obtained in in 84% yield as an orange
powder. Crystals suitable for X-ray diffraction analysis were grown by
recrystallisation of C2 from hot toluene. 1H-NMR (300 MHz, CD2Cl2): δ
8.45 (d, 1H, JH-H = 5.7), 7.72 (m, 1H), 7.57 (m, 6H), 7.34 (m, 10H), 6.86 (t,
1H, JH-H = 6.3), 5.49 (s, broad, 1H, NH), 5.22 (t, 1H, JH-H = 13.5), 4.40 (m,
1H), 3.47 (m, 2H), 3.36 (m, 1H), 2.80 (m, 1H), 2.52 (m, 1H), 1.27 (m, 2H),
1.19 (m, 1H), 0.95 (t, 3H, JH-H = 7.5). 31P-NMR (122 MHz, CD2Cl2): δ 51.8,
50.7. HRMS (ESI+): calculated for C28H31Cl2N2PRuS: 630.0366 (M+);
found 630.0388 (M+), 686.1116 (M+Na). Elemental analysis (%)
calculated for C28H31Cl2N2PRuS: C 53.33; H 4.96, N 4.44, S 5.08; found
C 53.12, H 4.80, N 4.52, S 5.47. Crystal data for C2: C35H39Cl2N2PRuS,
M = 722.68, monoclinic, space group P21/c, a = 17.6874(11), b =
12.4773(7), c = 15.0717(9) Å, β = 92.4695(11)°, V = 3323.1(3) Å3, T =
calculated for
C10H16N2S: 196.1034; (M+H): 197.1107; (M+Na):
219.0926; found 197.1108 (M+H), 219.0929 (M+Na).
2-(Ethylthio)-N-((6-methoxy-pyridin-2-yl)methyl)ethan-1-amine [L4]:
6-Methoxy-pyridine-2-carboxaldehyde and 2-(ethylthio) ethylamine were
converted to L4 analogously to L3 in a yield of 95%. 1H-NMR (300 MHz,
CDCl3): δ 7.54 (dd, 1H, J = 8.1, J = 7.4, CHarom), 6.87 (d, 1H, J = 7,2),
6.63 (d, 1H, J = 8.1), 4.55 (s, NH), 3.92 (s, 3H), 3.90 (m, NH), 3.80 (s,
2H), 2.83 (t, 2H, J = 6.5), 2.66 (t, 2H, J = 6.5), 2.52 (t, 2H, J = 7.5), 1.23 (t,
3H, J = 7.2). 13C-NMR (75 MHz, CDCl3): δ 163.8, 157.3, 138.8, 114.5,
108.7, 54.3, 53.2, 48.1, 32.0, 25.8, 14.8. HRMS (ESI+): calculated for
C11H18N2OS: 227.1213 (M+H); found 227.1217 (M+H), 227.1217 (M+Na).
150(2) K,
Z = 4, 43978 reflections measured, 7633 independent
reflections (Rint = 0.0419), final R values (I > 2σ(I)): R1 = 0.0280,
wR2 = 0.0594, final R values (all data): R1 = 0.0409, wR2 = 0.0651, 373
parameters.
2-(Ethylthio)-N-((quinolin-2-yl)methyl)ethan-1-amine [L5]: Quinolin-2-
carboxaldehyde and 2-(ethylthio)ethylamine were converted to L5
analogously to L3 in a yield of 82%. 1H NMR (300 MHz, CD2Cl2): δ 8.13
(d, 1H, J = 8.4 Hz, CHarom), 8.00 (d, 1H, J = 8.7 Hz, CHarom), 7.82 (dd, 1H,
J = 8.3 Hz, J = 1.5 Hz, CHarom), 7.69 (ddd, 3H, J = 8.5 Hz, J = 6.9 Hz, J =
1.5 Hz, CHarom), 7.55 – 7.45 (m, 2H, CHarom), 4.08 (s, 2H, CH2), 2.89 (td,
2H, J = 6.8 Hz, J = 1.2 Hz, CH2), 2.73 (td, 2H, J = 6.4 Hz, J = 0.9 Hz,
CH2), 2.55 (q, 2H, J = 7.4 Hz, CH2), 2.14 (d, 1H, J = 11.4 Hz, NH), 1.24 (t,
3H, J = 7.4 Hz, CH3). 13C NMR (75 MHz, CD2Cl2): δ 161.5, 136.7, 129.8,
129.5, 128.1, 127.9, 126.5, 121.0, 56.0, 49.1, 32.6, 26.2, 15.3. HRMS
(ESI+): calculated for C14H18N2S: 246.1191; (M+H): 247.1264; found
247.1267 (M+H)
Ru(6-MeONNSEt)(PPh3)Cl2 [C4]: RuCl2(PPh3)2 and L4 (1 eq.) were
converted to C4 analogously to C3. C4 was obtained in 88% yield as an
orange powder. 1H-NMR (400 MHz, CD2Cl2): δ 7.94 (m, 2H), 7.65 (m,
2H), 7.42-7.14 (m, 12H), 7.07 (d, 1H, JH-H = 7.6), 6.56 (d, 1H, JH-H = 8.4),
5.56-5.36 (m, 2H), 4.46 (m, 1H), 3.50-3.19 (m ,2H), 3.21 (dd, 1H, JH-H
=
11.0, JH-H = 2.2), 2. 87 (m, 1H), 2.83 (s, 3H,), 2.50 (m, 1H), 1.33 (m, 1H),
0.87 (t, 3H) 31P-NMR (122 MHz, CD2Cl2): δ 47.2, 45.9. HRMS (ESI+):
calculated for C29H32Cl2N2OPRuS (M+H): 660.0468; found: 660.0469
(M+H), 683.0363 (M+Na). Elemental analysis (%) calculated for
C29H33Cl2N2OPRuS: C 52.73; H 5.04, N 4.24, S 4.85; found C 52.45, H
5.01, N 4.35, S 5.16.
Synthesis of Ru(NNS)(PPh3)Cl2 complexes
Ru(QuinNSEt)(PPh3)Cl2 [C5]: RuCl2(PPh3)2 and L5 (1 eq.) were
converted to C5 analogously to C3. C5 was obtained in 58% yield as a
red powder. 1H-NMR (300 MHz, CD2Cl2): δ 8.12 (d, 2H JH-H = 8.4), 7.74-
6.66 (m, 19H), 5.90 (s, broad, NH), 5.74 (t, 1H, JH-H = 13.3), 4.72 (m, 1H),
3.58-3.40 (m, 3H), 3.05 (m, 1H), 2.72 (m, 1H), 1.66 (m, 1H), 0.95 (t, 3H,
JH-H = 7.5). 31P NMR (122 MHz, CD2Cl2): δ 48.9, 45.9. HRMS (ESI+):
calculated for C32H33Cl2N2PRuS: 680.0519 (M+); found 680.0500 (M+).
Ru(6-MeNNSEt)(PPh3)Cl2 [C3]: RuCl2(PPh3)3 (1g, 1.04 mmol) and ligand
(1 eq.) were placed in a 25 mL Schlenk tube under an argon atmosphere,
and dissolved in dry diglyme (2 mL). The reaction mixture was heated to
162 °C for 2 h, allowed to cool down to room temperature, and then
stored at -18 ⁰C overnight to precipitate further. While cooling on a dry
ice/isopropanol bath, cold Et2O (2 mL) was added, the precipitate was
filtered by cannula, and washed with Et2O (5 times 2 mL). The orange
powder was dried in vacuo, affording 530 mg (79%) of C3 as an orange
powder. Note that the complex exists as an equilibrium mixture of two
conformations in solution. Crystals suitable for X-ray diffraction analysis
were grown by slow diffusion of pentane into a concentrated solution of
C3 in CH2Cl2. 1H-NMR (300 MHz, CD2Cl2): δ 7.67-7.16 (m, 17H, CHarom),
7.01 (d, 1H, J = 7.8, CHarom), 5.65 (m, 2H), 4.47 (m, 1H), 3.5 (m, 1H),
3.34 (m, 1H), 3.22 (d, 1H, J = 11.1), 2.98 (m, 1H), 2.59 (m, 1H), 1.53 (m,
Ru(N-Me-NSEt)(PPh3)Cl2 [C6]: RuCl2(PPh3)2 and L6 (1 eq.) were
converted to C6 analogously to C3. C6 was obtained in 62% yield as a
pale yellow powder. 1H-NMR (300 MHz, CD2Cl2): δ 8.53 (d, 1H, JH-H
=
5.7), 7.72 (m, 1H), 7.57 (m, 6H), 7.33 (m, 10H), 6.85 (t, 1H, JH-H = 6.6),
5.35 (m, 1H), 4.93 (s, broad, NH), 3.68-3.31 (m, 3H), 2.81 (m, 1H), 2.53
(m, 1H), 1.80 (d, 3H, JH-H = 6.9), 1.25 (m, 1H), 0.97 (t, 3H, JH-H = 7.2). 31
P
This article is protected by copyright. All rights reserved.

10.1002/chem.201700806
Chemistry - A European Journal
FULL PAPER
NMR (122 MHz, CD2Cl2): δ 51.5, 50.3. HRMS (ESI+): calculated for
C29H33Cl2N2PRuS: 644.0518 (M+); found 644.0513 (M+). Elemental
analysis (%) calculated for C29H33Cl2N2OPRuS: C 54.04; H 5.16, N 4.35,
S 4.97; found C 54.19, H 5.19, N 4.35, S 5.30.
13C NMR (101 MHz, CDCl3): δ 154.0, 142.6, 110.4, 107.8, 57.5. HRMS
(ESI+): calculated for C5H6O2: 121.026 (M+Na); found 121.0255.[22]
2,5-Di(hydroxymethyl)furan (Table 3, Entry 3): 5-(Hydroxymethyl)
furfural (1.26 g, 10 mmol) was hydrogenated to 1.20 g (93%) of 2,5-
di(hydroxymethyl)furan which was isolated as a white crystalline solid.
Note that the catalyst loading was increased to 0.5 % (31 mg), and the
KOtBu loading to 5 % (70 mg). 1H NMR (300 MHz, DMSO-d6) δ 6.21 (s,
2H), 5.19 (t, 2H, JH-H = 5.7), 4.38 (d, 1H, JH-H = 5.7). 13C NMR (101 MHz,
CDCl3): δ 155.1, 107.9, 56.2. HRMS (ESI+): calculated for C6H8O3:
151.03657 (M+Na); found 151.03606 (M+Na).[11b]
Ru(NNMeSEt)(PPh3)Cl2 [C7]: RuCl2(PPh3)2 and L7 (1 eq.) were converted
to C7 analogously to C3, but with a reaction time of 14 h, yielding 54% of
C7 as an orange powder. Crystals suitable for X-ray diffraction analysis
were grown by slow diffusion of pentane into a concentrated solution of
C7 in dichloromethane. 1H-NMR (300 MHz, CD2Cl2): δ 8.11 (d, 1H, JH-H
=
5.7), 7.92 (m, 6H), 7.47 (dt, 1H, JH-H = 7.5, JH-H = 1.5), 7.30 (m, 10H),
6.56 (t, 1H, JH-H = 7.5), 5.67 (d, 1H, JH-H = 14.4), 3.87 (d, 1H, JH-H = 14.4),
3.15 (s, 3H), 2.86 (m, 1H), 2.70 (m, 1H), 2.30 (m, 2H), 0.74 (m, 1H), 0.67
3-(2-Furyl)-2-propen-1-ol (Table 3, Entry 4): 3-(2-Furyl)acrolein (1.22 g,
10 mmol) was hydrogenated to 1.23 g (99%) of 3-(2-furyl)-2-propen-1-ol
which was isolated as a colourless oil (mixture of isomers). Note that the
allylic alcohol obtained turns bright orange over time when exposed to air.
1
(t, 3H, JH-H = 6.9), 0.42 (m, 1H). 31P-NMR (122 MHz, CD2Cl2): δ 51.4,
50.4. HRMS (ESI+): calculated for C29H33Cl2N2PRuS: 644.0518 (M+);
found 644.0505 (M+). Crystal data for C7: C29H33Cl2N2PRuS, M = 644.57,
monoclinic, space group P21, a = 8.8469(3), b = 15.1574(5), c =
10.3199(3) Å, β = 102.3524(9)°, V = 1351.82(8) Å3, T = 150(2) K, Z = 2,
22735 reflections measured, 6528 independent reflections (Rint = 0.0206),
final R values (I > 2σ(I)): R1 = 0.0188, wR2 = 0.0433, final R values (all
data): R1 = 0.0199, wR2 = 0.0438, 327 parameters.
1H NMR (300 MHz, CD2Cl2): δ 8.42 (d, 1H, JH-H = 2.1), 7.47 (t, 1H, JH-H
1.5) 7.44 (dd, 1H, JH-H = 1.8, JH-H = 1.5), 7.30 (m, 2H), 4.03 (t, 2H, JH-H
=
=
4.8). 13C NMR (75 MHz, CD2Cl2): δ 153.0, 142.4, 128.1, 119.1, 111.7,
108.2, 63.1. HRMS (ESI+): calculated for C7H8O2: 147.04165 (M+Na);
found 147.04175 (M+Na). [23]
Hydrogenation screening reactions (1 mmol scale)
1-Cyclohexene-1-methanol (Table 3, Entry 5): 1-Cyclohexene-1-
carboxaldehyde (1.10 g, 10 mmol, 1.2 mL) was hydrogenated to 1.10 g
(99%) of 1-cyclohexenemethanol as a colourless oil. 1H-NMR (300 MHz,
CDCl3) δ 5.62 (m, 1H), 3.91 (d, 2H, JH-H = 4.8), 1.95 (m, 4H), 1.56 (m,
4H), 1.21 (m, broad, 1H). 13C NMR (75 MHz, CDCl3) δ 137.6, 123.1,
67.8, 25.6, 24.9, 22.6, 22.5. HRMS (ESI+): calculated for C7H12O:
135.0780 (M+Na); found 135.0779. [24]
In a typical reaction, 4 mL glass reaction vials and stirring bars were
dried in the oven at 110°C. The reaction vessels were charged with base
(0.0125 mmol), closed with PTFE/rubber septa, placed in a multiple
reactor inlet suitable for a pressure vessel, and brought under argon
atmosphere by three vacuum-argon cycles. With a syringe the reaction
vessels were charged with C2 as a stock solution in dry isopropanol (1
mL, 0.5 mM, 0.05 mol%), followed by dodecane (200 µL), and a solution
of cinnamaldehyde in dry isopropanol (1 mL, 1 M). The reaction vessels
were transferred to an argon-filled pressure vessel, which was flushed
with three nitrogen and three hydrogen cycles, then pressurised to 30 bar
hydrogen, heated to 80°C and stirred for 16h.
Cinnamyl alcohol (Table 3, Entry 6): Cinnamalydehyde (3.30 g, 25
mmol, 3.3 mL) was hydrogenated in isopropanol (50 mL), with C2 (7.8
mg) and KOtBu (35 mg). The resulting yellow oil was purified by column
chromatography (SiO2; pentane:ethyl acetate 4:1), yielding 3.16 g (94%)
of cinnamyl alcohol as white crystals. 1H NMR (300 MHz, CDCl3): δ 7.41-
7.22 (m, 5H), 6.62 (d, 1H), 6.37 (m, 1H), 4.33 (m, 2H), 1.49 (s, broad,
1H). 13C NMR (75 MHz, CDCl3): δ 136.7, 131.1, 128.6, 128.6, 127.7,
126.5, 63.7. HRMS (EI): calculated for C9H10O: 134.0726 (M); found
134.0727.[22]
For the screening of the different precatalysts C1-C7, appropriate
amounts of complex and base were added to the reaction vials in the
glovebox, and dry isopropanol (2 mL), cinnamaldehyde (1 mmol), and
dodecane (200 µL) were added by syringe.
Perrilyl alcohol (Table 3, Entry 7): Perillaldehyde (1.50 g, 10 mmol,
1.58 mL) was hydrogenated to 1.48 g (96%) of perillyl alcohol as a
colourless liquid. The product was isolated by column chromatography
(SiO2; heptane:ethyl acetate 5:1). 1H NMR (300 MHz, CDCl3): δ 5.63
(broad, 1H), 4.65 (m, 2H), 3.93 (s, 2H), 2.10-1.70 (m, 5H), 1.67 (s, 3H),
1.50 (s, broad, 1H), 1.43 (m, 1H). 13C NMR (75 MHz, CDCl3): δ 149.8,
137.2, 122.4, 108.6, 67.2, 41.1, 30.4, 27.5, 26.1, 20.8. HRMS (ESI+):
calculated for C10H16O: 153.12739 (M+H); found 153.12757 (M+H),
175.10946 (M+Na).[11b]
Substrate scope
Aldehydes and ketones, except for HMF, were distilled in vacuo from
PPh3 prior to use. Reactions were performed in a 100 mL hastelloy
autoclave vessel, to which substrate (usually 10 mmol), dry isopropanol
(20 mL), C2 (0.05 mol%), and KOtBu (1.25 mol%), were added under a
flow of argon. For the hydrogenation of HMF 0.5 mol% of C2 and 5.0
mol% of KOtBu were employed. The vessel was flushed three times with
30 bar of N2, and then pressurised with 30 bar of H2, and heated to 80 ⁰C
for 1 h. After cooling to room temperature and depressurising, the orange
solutions were filtered over SiO2, and concentrated in vacuo. Unless
otherwise noted, the product was then obtained by vacuum distillation in
1-Phenylethanol (Table 3, Entry 8): Acetophenone (1.20 g, 10 mmol,
1.17 mL) was hydrogenated to 1.18 g (97%) of benzyl alcohol (colourless
liquid). 1H NMR (300 MHz, CDCl3): δ 7.17 (m, 5H), 4.78 (m, 1H), 1.88 (d,
1H, JH-H = 3.3), 1.38 (d, 3H, JH-H = 6.3). 13C NMR (75 MHz, CDCl3): δ
145.8, 128.5, 127.5, 125.4, 70.4, 25.2. HRMS (EI): calculated for C8H10O:
122.0726 (M); found 122.0727.[21]
a
Kugelrohr apparatus. Analytical data of the isolated alcohols
correspond to those found in literature.
Benzyl alcohol (Table 3, Entry 1): 1.06 g of benzaldehyde (10 mmol,
1.01 mL) was hydrogenated to 1.08 g (99%) of benzyl alcohol as a
colourless liquid. 1H-NMR (300 MHz, CDCl3): δ 7.19 (m, 5H), 4.58 (s, 2H),
1.80 (s, 1H). 13C-NMR (75 MHz, CDCl3): δ 140.9, 128.6, 127.7, 127.0,
54.3. HRMS (EI): calculated for C7H8O: 108.05697 (M); found
108.05651.[21]
β-Ionol (Table 3, Entry 9): β-Ionone (1.92 g, 10 mmol, 2.0 mL) was
hydrogenated to 1.76 g (91%) of β-ionol (colourless oil). 1H-NMR (300
MHz, CDCl3): δ 6.09 (d, 1H, JH-H = 14.7), 5.53 (dd, 1H, JH-H = 15.9; JH-H
=
6.8), 4.41 (quint, 1H, JH-H = 6.3), 2.02 (t, 1H, JH-H = 6.3), 1.71 (d, 3H, JH-H
= 0.9), 1.63 (m, 2H), 1.53 (s, broad, 1H), 1.49 (m, sH), 1.36 (d, 3H, JH-H
=
6.3), 1.03 (s, 6H). 13C-NMR (75 MHz, CDCl3): δ 137.8, 136.8, 128.9,
127.7, 69.7, 39.5, 34.1, 32.8, 28.8, 23.7, 21.5, 19.4. HRMS (EI):
calculated for C13H22O: 194.1665 (M); found 194.1666.[25]
Furfuryl alcohol (Table 3, Entry 2): Furfural (960 mg, 10 mmol, 0.83
mL) was hydrogenated to 950 mg (99%) of furfuryl alcohol as a pale
yellow liquid. 1H NMR (400 MHz, CDCl3) δ 7.32 (m, 1H), 6.27 (m, 1H),
6.22 (d, 1H, JH-H = 3.2), 4.53 (d, 2H, JH-H = 5.2), 1.90 (t, 1H, JH-H = 5,8).
Carveol (Table 3, Entry 10): L-carvone (1.56 g, 10 mmol) was
hydrogenated to carveol, which was isolated as
a mixture of two
This article is protected by copyright. All rights reserved.

10.1002/chem.201700806
Chemistry - A European Journal
FULL PAPER
diastereomers. After 1h reaction time, some hydrogenation of the C=C
double bond had already occurred. Thus, the product was isolated by
column chromatography (SiO2; heptane:ethyl acetate 20:1), yielding 1.28
[4]
[5]
Y. Zhu, H. Qian, B. A. Drake, R. Jin, Angew. Chem. Int. Ed. 2010, 49,
1295-1298.
a) T. Ohkuma, M. Koizumi, K. Muñiz, G. Hilt, C. Kabuto, R. Noyori, J.
Am. Chem. Soc. 2002, 124, 6508; b) L. Diab, T. Smejkal, J. Geier, B.
Breit, Angew. Chem. Int. Ed. 2009, 48, 8022-8026; c) S. Hashiguchi,
Akio Fujii, J. Takehara, T. Ikariya, R. Noyori, J. Am. Chem. Soc. 1995,
117, 7562-7563; d) X. Tan, G. Wang, Z. Zhu, C. Ren, J. Zhou, H. Lv, X.
Zhang, L. W. Chung, L. Zhang, X. Zhang, Org. Lett. 2016, 18, 1518-
1521; e) X. Wu, C. Corcoran, S. Yang, J. Xiao, ChemSusChem 2008, 1,
71-74; f) K. E. Jolley, A. Zanotti-Gerosa, F. Hancock, A. Dyke, D. M.
Grainger, J. A. Medlock, H. G. Nedden, J. J. M. Le Paih, S. J.
Roseblade, A. Seger, V. Sivakumar, I. Prokes, D. J. Morris, M. Wills,
Adv. Synth. Catal. 2012, 354, 2545-2555; g) D. Spasyuk, C. Vicent, D.
G. Gusev, J. Am. Chem. Soc. 2015, 137, 3743-3746
g
(84%) of a
colourless oil. 1H NMR (300 MHz, CDCl3, major
diastereomer): δ 5.52 (m, 1H), 4.66 (m, 2H), 4.12 (s, broad, 1H), 3.95,
2.30-1.38 (m, 14H). 13C NMR (75 MHz, CDCl3): δ 149.2, 149.0, 136.2,
134.3, 125.4, 123.9, 109.2, 109.0, 70.9, 68.6, 40.5, 38.0, 36.8, 35.2, 31.1,
31.0, 21.0, 20.9, 20.7, 19.0. HRMS (EI): calculated for C10H16O:
152.1196 (M); found 152.1198.[26]
4,5,6,7-Tetrahydro-4-benzofuranol (Table 3, Entry 11): 4,5,6,7-
Tetrahydro-4-benzofuranone (1.36 g, 10 mmol, 1.2 mL) was
hydrogenated to 1.37
(colourless liquid). 1H-NMR (300 MHz, CDCl3): δ 7.31 (m, 1H), 6.44 (d,
1H, JH-H = 2.0), 4.77 (t, 1H, JH-H = 4.4), 2.60 (m, 2H), 2.09-1.81 (m, 5H).
13C-NMR (75 MHz, CDCl3): δ 152.6, 141.1, 120.0, 109.1, 64.1, 32.7, 23.0,
19.0. HRMS (ESI+): calculated for C8H10O2: 139.07536 (M+H); found
139.07548 (M+H), 161.05749 (M+Na).[27]
g (99%) of 4,5,6,7-tetrahydro-4-benzofuranol
[6]
a) J. M. Grosselin, C. Mercier, G. Allmang, F. Grass, Organometallics
1991, 10, 2126-2133.
[7]
[8]
M. Hernandez, P. Kalck, J. Mol. Catal. A 1997, 116, 131-146.
a) P. A. Dub, J. C. Gordon, Dalton Trans. 2016, 45, 6756-6781; b) P. A.
Dub, N. J. Henson, R. L. Martin, J. C. Gordon, J. Am. Chem. Soc. 2014,
136, 3505-3521; c) T. Zell, D. Milstein, Acc.Chem. Res. 2015, 48, 1979-
1994.
4-(2-Furanyl)-3-buten-2-ol (Table 3, Entry 12): 4-(2-Furanyl)-3-buten-2-
one (1.36 g, 10 mmol) was hydrogenated to 1.28 g (93%) of 4-(2-
furanyl)-3-buten-2-ol. Note that the allylic alcohol obtained turns bright
orange over time when exposed to air. 1H NMR (300 MHz, CD2Cl2): δ
[9]
a) S. Elangovan, B. Wendt, C. Topf, S. Bachmann, M. Scalone, A.
Spannenberg, H. Jiao, W. Baumann, K. Junge, M. Beller, Adv. Synth.
Catal. 2016, 358, 820-825; b) B. Butschke, M. Feller, Y. Diskin-Posner,
D. Milstein, Catal. Sci. Technol. 2016, 6, 4428-4437; c) R. H. Morris,
Acc.Chem. Res. 2015, 48, 1494-1502; d) T. Zell, Y. Ben-David, D.
Milstein, Catal. Sci. Technol. 2015, 5, 822-826; e) P. O. Lagaditis, P. E.
Sues, J. F. Sonnenberg, K. Y. Wan, A. J. Lough, R. H. Morris, J. Am.
Chem. Soc. 2014, 136, 1367-1380; f) G. Wienhöfer, F. A. Westerhaus,
K. Junge, M. Beller, J. Organomet. Chem. 2013, 744, 156-159; g) S.
Fleischer, S. Zhou, K. Junge, M. Beller, Angew. Chem. Int. Ed. 2013,
52, 5120-5124; h) G. Wienhöfer, F. A. Westerhaus, K. Junge, R.
Ludwig, M. Beller, Chem. Eur. J. 2013, 19, 7701-7707; i) C. P. Casey,
H. Guan, J. Am. Chem. Soc. 2007, 129, 5816-5817; j) R. Langer, G.
Leitus, Y. Ben-David, D. Milstein, Angew. Chem. Int. Ed. 2011, 50,
2120-2124; k) C. Sui-Seng, F. N. Haque, A. Hadzovic, A.-M. Putz, V.
Reuss, N. Meyer, A. J. Lough, M. Z.-D. Iuliis, R. H. Morris, Inorg. Chem.
2009, 48, 735-743; l) S. Mazza, R. Scopelliti, X. Hu, Organometallics
2015, 34, 1538-1545. m) S. Werkmeister, J. Neumann, K. Junge, M.
Beller, Chem. Eur. J. 2015, 21, 12226-12250.
7.38 (d, 1H, JH-H = 1.8), 6.41 (m, 2H), 6.26 (m, 2H), 4.49 (qd, 1H, JH-H
=
6.3), 2.06 (s, broad, 1H), 1.38 (d, 3H, JH-H = 6.6). 13C NMR (75 MHz,
CD2Cl2): δ 152.4, 141.9, 132.3, 117.7, 111.3, 108.0, 68.4, 23.4. HRMS
(ESI+): calculated for C8H10O2: 161.0573 (M+H); found 161.05774
(M+H).[28]
1-(cyclohex-1-en-1-yl)ethan-1-ol (Table 3, Entry 13): 1-(1-Cyclohexen-
1-yl)-ethanone (1.24 g, 10 mmol) was hydrogenated to 1.25 g (99%) of 1-
(cyclohex-1-en-1-yl)ethan-1-ol (colourless liquid). 1H NMR (300 MHz,
CDCl3): δ 5.57 (s, broad, 1H), 4.06 (q, 1H, JH-H = 6.3), 2.15 (s, 1H), 1.93
(m, 4H), 1.53 (m, 4H), 1.16 (d, 3H, JH-H = 6.3). 13C NMR (75 MHz,
CDCl3): δ 141.3, 121.3, 72.0, 24.9, 23.6, 22.6, 22.6, 21.5. HRMS (ESI+):
calculated for C8H14O: 149.09369 (M+Na); found 149.09364 (M+Na).[29]
Methyl 4-(hydroxymethyl)benzoate (Table 3, Entry 14): methyl 4-
formylbenzoate (0.33 g, 2 mmol) was dissolved in 10 mL of methanol to
0.32 g (97%) of methyl 4-(hydroxymethyl)benzoate (white powder). 1H
[10] a) C. Hou, J. Jiang, Y. Li, Z. Zhang, C. Zhao, Z. Ke, Dalton Trans. 2015,
44, 16573-16585; b) S. Rosler, J. Obenauf, R. Kempe, J. Am. Chem.
Soc. 2015, 137, 7998-8001; c) G. Zhang, B. L. Scott, S. K. Hanson,
Angew. Chem. Int. Ed. 2012, 51, 12102-12106.
NMR (300 MHz, CDCl3): δ 7.94 (d, 2H, JH-H = 8.1), 7.37 (d, 2H, JH-H
=
8.1), 4.68 (d, 2H, JH-H = 4.2), 3.88 (s, 3H), 3.52 (t, 1H, JH-H = 4.2). 13C
NMR (75 MHz, CDCl3) δ 167.2, 146.3, 129.7, 128.9, 126.4, 64.3, 52.1.
HRMS (EI): calculated for C9H10O: 166.06245 (M); found 166.06298
(M).[30]
[11] a) F. Kallmeier, T. Irrgang, T. Dietel, R. Kempe, Angew. Chem. Int. Ed.
2016, 55, 11806-11809; b) S. Elangovan, C. Topf, S. Fischer, H. Jiao,
A. Spannenberg, W. Baumann, R. Ludwig, K. Junge, M. Beller, J. Am.
Chem. Soc. 2016, 138, 8809-8814.
[12] a) J.-X. Chen, J. F. Daeuble, D. M. Brestensky, J. M. Stryker,
Tetrahedron, 2000, 56, 2153-2166. b) J.-X. Chen, J. F. Daeuble, J. M.
Stryker, Tetrahedron, 2000, 56, 2789-2798.
Acknowledgements
We thank Dr. C. Fischer, A. Koch, S. Buchholz, S. Schareina, A.
Lehmann, and S. Rosmeisl at the LIKAT analytical department
for their indispensable support. We thank the State of
Mecklenburg-Vorpommern and Royal DSM n.v. for financial
support.
[13] a) P. Dupau, L. Bonomo, L. Kermorvan, Angew. Chem. Int. Ed. 2013,
52, 11347-11350; b) L. Bonomo, L. Kermorvan, P. Dupau,
ChemCatChem 2015, 7, 907-910.
[14] a) D. Spasyuk, S. Smith, D. G. Gusev, Angew. Chem. Int. Ed. 2013, 52,
2538-2542; b) P. A. Dub, B. L. Scott, J. C. Gordon, Organometallics
2015, 34, 4464-4479; c) G. A. Filonenko, E. Cosimi, L. Lefort, M. P.
Conley, C. Copéret, M. Lutz, E. J. M. Hensen, E. A. Pidko, ACS Catal.
2014, 4, 2667-2671.
Keywords: homogeneous catalysis • hydrogenation • ruthenium
[15] X. Chen, Y. Jing, X. Yang, Chem. Eur. J.2016, 22, 1950-1957.
[16] a) P. A. Dub, T. Ikariya, J. Am. Chem. Soc. 2013, 135, 2604-2619. b) P.
A. Dub, B. L. Scott, J. C. Gordon, J. Am. Chem. Soc. 2017, 139, 1245-
1260.
• ligand • alcohols
[1]
a) The Handbook of Homogeneous Hydrogenation Vol. 1-3 (J. G. de
Vries, C. J. Elsevier, eds.), Wiley-VCH Verlag, Weinheim, 2007; b) P.
Gallezot, D. Richard, Catal. Rev. 1998, 40, 81-126. b) D. J. Ager, A. H.
M. de Vries J. G. de Vries, Chem. Soc. Rev., 2012, 41, 3340–3380.
C. J. Kliewer, M. Bieri, G. A. Somorjai, J. Am. Chem. Soc. 2009, 131,
9958-9966.
[17] a) R. J. van Putten, J. C. van der Waal, E. de Jong, C. B. Rasrendra, H.
J. Heeres, J. G. de Vries, Chem. Rev. 2013, 113, 1499-1597; b) P. J.
Deuss, K. Barta, J. G. de Vries, Catal. Sci. Technol. 2014, 4, 1174-
1196.
[2]
[3]
A. Stolle, T. Gallert, C. Schmöger, B. Ondruschka, RSC Adv. 2013, 3,
2112-2153.
This article is protected by copyright. All rights reserved.

10.1002/chem.201700806
Chemistry - A European Journal
FULL PAPER
[18] K. I. Galkin, E. A. Krivodaeva, L. V. Romashov, S. S. Zalesskiy, V. V.
Kachala, J. V. Burykina, V. P. Ananikov, Angew. Chem. Int. Ed. 2016,
55, 8338-8342.
[19] G. M. Sheldrick, Acta Crystallogr., Sect. A: Found.Ccrystallogr. 2008,
64, 112-122.
[20] G. M. Sheldrick, Acta Crystallogr., Sect. C: Struct. Chem. 2015, 71, 3-8.
[21] F. Jiang, D. Bezier, J.-B. Sortais, C. Darcel, Adv. Synth. Catal. 2011,
353, 239-244.
[22] I.R. Cabrita, P.F. Florindo, A.C. Fernandes, Tetrahedron 2017, 73,
1511-1516.
[23] A.B. Charette, C. Molinaro, C. Brochu, J. Am. Chem. Soc. 2001, 123,
12168-12175.
[24] G. Majetich, J. S. Song, C. Ringold, G. A. Nemeth, M. G. Newton, J.
Org. Chem. 1991, 56, 3973–3988.
[25] S. Akai, R. Hanada, N. Fujiwara, Y. Kita, M. Egi, Org. Lett. 2010, 12,
4900–4903.
[26] S. Dhulut, A. Bourin, M.-I. Lannou, E. Fleury, N. Lensen, E. Chelain, A.
Pancrazi, J. Ardisson, J. Fahy, Eur. J. Org. Chem 2007, 5235-5243.
[27] K. Krohn, K. Khanbabaee, U. Flörke, P. G. Jones, A. Chrapkowski, Eur.
J. Org. Chem. 1994, 471–477.
[28] X. Li, L. Li, Y. Tang, J. Org. Chem. 2010, 75, 2981.
[29] D. R. Li, A. He and J. R. Falck, Org. Lett. 2010, 12, 1756–1759.
[30] A.P. Dieskau, J.-M. Begouin, B. Plietker, Eur. J. Org. Chem. 2011,
5291–5296
This article is protected by copyright. All rights reserved.

10.1002/chem.201700806
Chemistry - A European Journal
FULL PAPER
FULL PAPER
Cheap yet noble. New, easily
prepared tridentate NNS ligands and
their ruthenium complexes are
described. The complexes are
activated by base and selectively
Pim Puylaert, Richard van Heck, Yuting
Fan, Anke Spannenberg, Wolfgang
Baumann, Matthias Beller, Jonathan
Medlock, Werner Bonrath, Laurent
Lefort, Sandra H, and Johannes G. de
Vries*
O
OH
H/R'
H
2, Ru-NNS
R
H/R'
R
catalyse
carbonyl
the
hydrogenation
in
of
the
•
•
•
Highly selective
Cheap and versatil
Mild conditions
functionalities
Page No. – Page No.
presence of conjugated carbon-
carbon double bonds.
Selective hydrogenation of α,β-
unsaturated aldehydes and ketones
by air-stable Ruthenium NNS
complexes
This article is protected by copyright. All rights reserved.