Ester hydrogenation catalyzed by Ru-CNN pincer complexes

Article abstract of DOI:10.1039/c1cc12601f

We report new Ru-CNN pincer catalysts for ester hydrogenation under mild conditions.

Full text of DOI:10.1039/c1cc12601f

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Ester hydrogenation catalyzed by Ru-CNN pincer complexesw
Yunshan Sun, Christian Koehler, Runyu Tan, Vincent T. Annibale and Datong Song*
Received 3rd May 2011, Accepted 5th June 2011
DOI: 10.1039/c1cc12601f
We report new Ru-CNN pincer catalysts for ester hydrogenation
under mild conditions.
good yields (see ESIw). Complexation can be achieved by
reacting [RuHCl(CO)(PPh3)3] with free carbenes 1a and 1b
(Scheme 1) that are generated in situ from the corresponding
imidazolium ligand precursors and LiHMDS (HMDS=
bis(trimethylsilyl)amide). The resulting Ru-CNN pincer
complexes are mixtures of [RuH(CNN)(CO)Br] (major B98%)
and [RuH(CNN)(CO)Cl] (minor B2%), which can be
converted into pure [RuH(CNN)(CO)Br], 2a and 2b by reacting
with LiBr.5
The reduction of esters to the corresponding alcohols is an
important chemical process that has found use in many areas.
In the total synthesis of natural products and drug candidates,
esters are usually reduced with a stoichiometric amount of
aluminum-hydride reagent (e.g. LiAlH4 and AlBu2H),1 which
requires tedious work-up procedures to handle the resulting
inorganic wastes. The catalytic hydrogenation of esters is
an attractive alternative, because it produces no byproduct.
In manufacturing industry, fatty esters are reduced to fatty
alcohols in the presence of heterogeneous catalysts at 200–300 1C
under 200–300 bar of H2 gas.2 The energy consumption and
safety issues associated with these processes call for the develop-
ment of better catalysts that can operate at a lower temperature
under a lower pressure of H2.
Complexes 2a and 2b are air stable in the solid state. They
are slightly soluble in benzene and slowly react with chloroform.
Because 2a and 2b show similar properties, we will use 2a as an
example for further discussions. In the 1H NMR spectrum of 2a
in C6D6, the four pyridylic protons display 4 doublets at 6.97 and
4.20 ppm (NHC-CH2Py), 3.79 and 3.36 ppm (PyCH2NEt2).
The hydride ligand exhibits a singlet at À14.21 ppm. The
structures of 2a and 2b have been unambiguously confirmed
with X-ray crystallography (Fig. 1). The pincer ligand adopts a
mer configuration. Each Ru(II) center adopts a distorted
octahedral coordination geometry with a CO ligand trans to
a pyridine nitrogen atom, and a hydride trans to a bromide.
The six-membered chelate ring involving the NHC donor
adopts a boat conformation, with the axial pyridylic proton
aligned with the bromide ligand. The axial pyridylic proton of
the amine arm is aligned with the hydride ligand. The Ru1–N1
bond (2.256(2) and 2.262(2) A for 2a and 2b, respectively)
is significantly longer than Ru1–N2 bond (2.134(2) and
2.135(2) A for 2a and 2b, respectively) as a result of the strong
trans-influence of the carbene donor.
Recently, Firmenich has reported homogeneous catalysts
for ester hydrogenation that operate at 100 1C with low
catalyst loadings, but require the use of high pressures
of H2 (e.g., 50 bar in most cases).3 Milstein and coworkers
have reported a Ru-pincer catalyst (Scheme 1a) for ester
hydrogenation that operates under a much lower pressure
(5.3 bar) of H2 and at 115 1C.4 Milstein’s catalyst is effective
for several esters, but the turn-over frequency (TOF) is generally
low. For the bulky tert-butyl acetate, in particular, 10.5%
yield has been observed after 24 h; the corresponding TOF is
0.44 hÀ1. Herein, we report new Ru-CNN pincer complexes
that catalyze ester hydrogenation under milder conditions
(105 1C and 5.3 bar) with a significantly higher performance
than Milstein’s catalyst. For example, the catalytic hydro-
genation of tert-butyl acetate with our catalytic system shows
a more than 100-fold increase in TOF at a lower temperature,
compared to Milstein’s catalytic system.
The new pyridine-based CNN pincer ligand precursors
with NHC and diethylamino arms can be synthesized from
2,6-bis(bromomethyl)pyridine via two successive nucleophilic
substitutions with appropriate imidazoles and diethylamine in
Davenport Chemical Research Laboratories, Department of
Chemistry, University of Toronto, 80 St. George Street, Toronto,
Ontario, Canada. E-mail: dsong@chem.utoronto.ca;
Fax: +1-416-978-7013; Tel: +1-416-978-7014
w Electronic supplementary information (ESI) available: Experimental
procedures and characterization details. CCDC 824073–824077. For
ESI and crystallographic data in CIF or other electronic format see
DOI: 10.1039/c1cc12601f
Scheme 1 (a) Milstein’s catalyst; (b) NHC-based CNN-pincer
ligands 1a, 1b and the corresponding Ru(II) complexes 2a, 2b.
c
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Chem. Commun., 2011, 47, 8349–8351 8349

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whose structure has been confirmed with X-ray crystallo-
graphy (Fig. 2). The C–C bond lengths of the C5N ring shows
the alternating short-long pattern, i.e., C6–C7 1.363(7),
C7–C8 1.419(7), C8–C9 1.360(7), C9–C10 1.445(7) A. The
C10–C11 bond length is 1.367(7) A, consistent with a typical
double bond. It is clear that the NHC arm is deprotonated and
the pyridine ring is dearomatized. The addition of PPh3 has
trapped the 5-coordinate species as a monomeric 6-coordinate
adduct.
Next, we studied the reactivity of 3a towards dihydrogen.
Under B3.8 atm of H2 at room temperature 3a can be
converted into 4a (Scheme 2). The H NMR spectrum of 4a
1
in C6D6 shows only one singlet in the hydride region at
À4.35 ppm, indicative for a trans-dihydride species.6 A singlet
(2H, NHC-CH2Py) at 4.66 ppm and a singlet (2H, PyCH2NEt2)
at 3.81 ppm can be attributed to the two methylene linker
groups, respectively. The resonances at 6.74, 6.41, and 6.33 ppm
can be attributed to the protons of the rearomatized pyridine
ring. Under an N2 atmosphere at room temperature 4a slowly
loses H2 in solution to regenerate 3a; Milstein’s Ru-PNN
trans-dihydride species displays a similar behavior.6 To gain
further insight into the H2 activation process (e.g., the fate of
each H atom in H2), we studied the reaction between 3a and
D2. At À78 1C a toluene solution of 3a reacts with 1 atm of D2
to afford instantaneously 4a-d2 (Scheme 4), in which deuterium
atoms are incorporated into the pyridylic position of the NHC
arm and on the metal center, as confirmed by 1H and 2H NMR
experiments. Interestingly, when the reaction mixture is
warmed to room temperature the pyridylic position of the
amine arm also gets deuterated. At room temperature over-
night, all four pyridylic protons and the two hydrides become
deuterated, affording 4a-d6. This indicates that the hydrogen
splitting and releasing processes are dynamic and that the
dearomatization–rearomatization process also involves the
amine arm. No parallel reactivity (i.e., the involvement of
both arms) was reported for Milstein’s PNN system. Interestingly,
X-ray crystallography shows that 4a exists as a dimer in the
solid state (Fig. 2S in ESIw), with two bridging hydrides
and dangling amine arms, indicating the labile nature of the
amine arm.
Fig. 1 Pov-Ray plots of the molecular structures of complexes 2a
(left) and 2b (right) with thermal ellipsoids plotted at 50%. All H
atoms are omitted for clarity except for hydrides.
In the presence of KOtBu or KHMDS, 2a catalyzes the
H2-hydrogenation of esters with high efficiencies at 105 1C,
under 5.3 bar of H2. As shown in Table 1, a variety of
unactivated aliphatic and aromatic esters can be hydrogenated
into the corresponding alcohols in excellent to quantitative
yields within 2 or 3 h (entries 1–7). The simple ethyl acetate can
be hydrogenated in quantitative yield within 2 h (entry 4),
while with Milstein’s catalyst, 86% yield takes 12 h to achieve.
Remarkably, even the bulky ester tert-butyl acetate can be
hydrogenated in 93% yield within 2 h (entry 6), while Milstein’s
catalyst gives 10.5% yield in 24 h. A diester diethyl succinate
can be hydrogenated into the corresponding diol in quantitative
yield within 2 h (entry 7). Complexes 3a and 4a can also
catalyze the hydrogenation of esters under similar conditions
as shown above with similar efficiencies. The activities of 2b
and its derivatives are slightly lower.
To probe the mechanism of the catalytic cycle, we conducted
stoichiometric reactivity studies. When 2a is reacted with
1 equiv of KHMDS in solution (Scheme 2), the clean formation
of 3a can be observed via NMR experiments. In the 1H NMR
spectrum of 3a in C6D6, the hydride ligand displays a singlet at
À22.69 ppm. The two doublets from the pyridylic protons of
the NHC arm of 2a are replaced by a singlet integrated as
1 proton at 6.13 ppm; the corresponding carbon resonates at
95.6 ppm in the 13C NMR spectrum. The pyridine proton para
to the NHC arm shows a significant upfield shift upon
deprotonation: from 6.37 ppm in 2a to 5.48 ppm in 3a,
indicating the dearomatization of the pyridine ring. The other
two protons of the pyridine ring show smaller upfield shifts.
The two pyridylic protons of the amine arm remain inequivalent,
displaying two doublets at 3.38 and 2.71 ppm, respectively. No
deprotonation at the amine arm was observed. Our DFT
calculations show that the observed deprotonation product
3a is 9.5 kcal molÀ1 more stable than its isomer with a
deprotonated amine arm in terms of free energy, consistent
with the observation that 3a is the only observable product of
deprotonation (see ESIw for details). Under similar conditions,
the deprotonation of 2b does not proceed cleanly. Presumably,
the labile amine-arm of the pincer ligand may dissociate from the
metal center and the less bulky mesityl group of the ligand may
allow for aggregation of the resulting 5-coordinate complex.
However, when 1 equiv. of PPh3 is added to the reaction mixture
(Scheme 3), everything cleanly converts to one species, 3b,
Using acetophenone as the model substrate, we studied the
hydrogenation in a stepwise manner (Scheme 5). When trans-
dihydride 4a is treated with 1.05 equiv. of acetophenone in
C6D6 at ambient temperature under N2 a dynamic reaction
mixture is achieved, as evidenced by the broad signals in the
1H NMR spectrum. Alternatively, the same reaction mixture
can be achieved by reacting 3a with 1 equiv. of 1-phenylethanol
1
at ambient temperature. At 60 1C, the H NMR spectrum of
the reaction mixture becomes cleaner (i.e., with one dominant
species, 5a) and the signals are sharper. The appearance of the
characteristic signal at 5.47 ppm indicates a dearomatized
ligand backbone; no free 1-phenylethanol is present. Therefore,
the quartet and doublet at 4.62 and 1.32 ppm, respectively, are
tentatively assigned to a coordinating 1-phenylethanol in 5a.
Under B4.3 atm of H2 at 60 1C 5a converts into 4a and
1-phenylethanol cleanly within minutes. In this process, 3a
could not be observed, presumably because of the fast
conversion of 3a to 4a under H2. Further experiments and
DFT calculations will be carried out to help elucidate the
c
8350 Chem. Commun., 2011, 47, 8349–8351
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Table 1 Hydrogenation of esters to alcohols catalyzed by complex 2a in the presence of KOtBua
Entry
Substrate
t (h)
Conv. (%)b
Yield (%)d
1c
2
3
4
PhCOOEt
2
2
2
2
3
2
2
99.6
99.7
96
99
90
PhCH2OH (97.7) EtOH (99)
PhCH2CH2OH (99.7) EtOH (98)
EtOH (96) MeOH (96)
EtOH (99)
PhCH2COOEt
CH3COOCH3
CH3COOEt
CH3COOCH2Ph
CH3COOCMe3
(CH2COOEt)2
5
PhCH2OH (90) EtOH (87)
EtOH (93) BuOH (92)
HO(CH2)4OH (99) EtOH (99)
t
6
93
99
7e
a
b
Ester (1 mmol), complex 2a (0.01 mmol), KOtBu (0.08 mmol) and toluene (2 mL), 105 1C, 5.3 bar of H2. Conversions were determined by GC
with mesitylene as the internal standard. 0.01mmol of KOtBu was used. Yields were determined by H NMR with mesitylene as the internal
e
standard. 0.02 mmol of 2a was used.
c
d
1
Scheme 2 Syntheses of 3a and 4a.
Scheme 5 Stepwise hydrogenation study.
energetics of different species in the reaction system as well as
the mechanism of the catalytic reaction.
In summary, we have synthesized and characterized two
new NHC-based CNN-pincer ligands and the corresponding
ruthenium (II) complexes 2. Complex 2a can be deprotonated
Scheme 3 Synthesis of 3b.
by a strong base to form a 5-coordinate species 3a with
dearomatized pyridine moiety in the ligand backbone.
Compound 3a can split H2 to form a trans-dihydride species
4a with a rearomatized pyridine moiety in the ligand back-
bone. Interestingly, the D2 experiment reveals that both pincer
arms participate in the H2 activation and releasing processes.
Complexes 2 in the presence of KOtBu or KHMDS catalyze
the H2-hydrogenation of unactivated esters under mild
conditions. Even the bulky ester tert-butyl acetate, which
cannot be effectively hydrogenated by the Ru-PNN system,
can be converted into the corresponding alcohols in excellent
yield. Our work represents a rare example of a phosphorus-free
pincer system that displays the dearomatization–rearomatization
type of metal–ligand cooperation. The detailed mechanism
and the scope of polar bond hydrogenation as well as other
reactivities of this new Ru-CNN system are being investigated
in our laboratory.
Notes and references
Fig. 2 Pov-Ray plot of the molecular structure of 3b with thermal
ellipsoids plotted at 50%. All H atoms are omitted for clarity except
for hydrides and pyridilic protons. The phenyl groups of PPh3 and the
mesityl group of the NHC arm are omitted for clarity.
1 S. N. Ege, Organic Chemistry, D. C. Heath and Company,
Lexington, 1989, p. 596.
2 Y. Pouilloux, F. Autin and J. Barrault, Catal. Today, 2000, 63, 87,
and references therein.
3 L. A. Saudan, C. M. Saudan, C. Debieux and P. Wyss, Angew.
Chem. Int. Ed., 2007, 46, 7473–7476.
4 J. Zhang, G. Leitus, Y. Ben-David and D. Milstein, Angew. Chem.,
Int. Ed., 2006, 45, 1113–1115.
5 The mixture of [RuH(CNN)(CO)Br] and [RuH(CNN)(CO)Cl] can
be used for reactivity studies directly, because the deprotonation of
both species gives the same 5-coordinate species. For details, see
ESIw.
6 J. Zhang, G. Leitus, Y. Ben-David and D. Milstein, J. Am. Chem.
Scheme 4 Deuterium scrambling experiments.
Soc., 2005, 127, 10840–10841.
c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 8349–8351 8351