From esters to alcohols and back with ruthenium and osmium catalysts

Article abstract of DOI:10.1002/anie.201108956

There and back again: Hydrogenation of esters and the reverse reaction of dehydrogenative coupling of alcohols are efficiently catalyzed by dimeric complexes of Ru and Os under neutral conditions. The Os dimer (see picture) is an outstanding catalyst for the hydrogenation of alkenoates and triglycerides, and allows production of fatty alcohols from olive oil. This complex converts ethanol into ethyl acetate and hydrogen under reflux. Copyright

Full text of DOI:10.1002/anie.201108956

.
Angewandte
Communications
DOI: 10.1002/anie.201108956
Catalytic (De)Hydrogenation
From Esters to Alcohols and Back with Ruthenium and Osmium
Catalysts**
Denis Spasyuk, Samantha Smith, and Dmitry G. Gusev*
Hydrogenation is an attractive “green” method for the
A meaningful comparison of the efficiency of these
catalysts is currently problematic because of significant
differences in the employed reaction temperatures and
pressures. Available data for hydrogenation of benzoates
[
1–4]
reduction of esters.
The reaction shown in Scheme 1a is
mildly exergonic, for example, formation of ethanol from
(PhCOOR, R = Me, Et) serve to highlight the impressive
performance of catalysts 6 and 7, although a major drawback
of these systems is the need for 5–10 mol% NaOMe. Hydro-
genation of alkyl alkanoates proceeded slower compared to
benzoates, for example, a turnover frequency (TOF) of 690
for methyl octanoate versus 2200 for methyl benzoate was
[
2b,c]
reported for catalyst 6.
Little is known about selectivity and functional-group
tolerance of the existing ester hydrogenation catalysts. Testing
of complexes 1, 2, 4, and 5 was restricted to unfunctionalized
aliphatic and aromatic esters. Catalyst 3 performed well for
hydrogenation of methyl formate (TOF = 534 in 8 h) and
dimethyl carbonate (TOF = 314 in 14 h) at 1108C and p(H ) =
2
[
1b]
5
0 bar. Only complex 7 was studied with alkyl alkenoates
and showed an excellent C=O/C=C selectivity, except for
substrates with terminal C=C bonds, that is, methyl 10-
[
2]
Scheme 1. Hydrogenation of esters and dehydrogenation of alcohols.
undecanoate and the a,b-unsaturated methyl cinnamate.
[a] Under basic conditions. Dipp=2,6-Diisopropylphenyl, Mes=2,4,6-
Hydrogenation of cis alkenoates (common in plant oils) and
their stability with respect to cis/trans isomerization under
catalytic conditions have not been reported.
trimethylphenyl, S/M=molar ratio of substrate to metal, TOF=turn-
over frequency per hour for hydrogenation of PhCOOR (R=Me, Et).
Catalysts 8 and 10 have been successfully tested with
chiral esters of a-amino, a-hydroxy, b-amino, and b-hydroxy
acids. Good conversions and retention of the ee values were
À1 [5a]
[3]
ethyl acetate is favored by circa À5 kcalmol . The reverse
process of acceptorless dehydrogenative coupling (ADC,
observed by using 0.1–1 mol% catalyst without base at 808C
Scheme 1b) is feasible in an open system, because H gas is
and p(H ) = 50 bar. Complex 9 is exceptionally active for
2
2
sparcely soluble and can be efficiently expelled under reflux
conditions. Well-defined catalysts for reactions shown in
Scheme 1 have been developed in the past five years.
Milsteinꢀs complex 1, which was reported in 2005, gives
symmetrical esters from primary alcohols upon heating to
hydrogenation of methyl (R)-lactate at 278C when used with
12 mol% of NaOMe.
[3d]
Herein we report new Ru and Os catalysts capable of
efficient reduction of esters under neutral conditions. This
research is based upon our recent work with
[MH (CO)(HN(C H PiPr ) )] complexes (M = Ru, Os),
[
6]
[1,4a]
more than 1008C. All Milstein-type complexes 1–5
and
2
2
4
2 2
[2,3]
Noyori-type catalysts 6-10
are active in ester hydrogena-
which are catalysts for transfer dehydrogenation of ethanol
to ethyl acetate at room temperature and for acceptorless
tion (Scheme 1). These catalysts employ ligand cooperativity
by pyridine aromatization/dearomatization in 1–5 and cleav-
age/formation of NÀH bonds in 6–10.
dehydrogenation of primary alcohols (Scheme 1b) at temper-
[
1e,2a,3c]
[5b]
atures above 1208C.
Use of 0.05 mol% [RuH (CO)-
2
(
HN(C H PiPr ) )] gave a turnover frequency of 90 for
2 4 2 2
hydrogenation of methyl benzoate after 18 hours at 1008C
with p(H ) = 50 bar. We thought that replacement of the
2
[
*] Dr. D. Spasyuk, S. Smith, Prof. D. G. Gusev
Department of Chemistry, Wilfrid Laurier University
Waterloo, Ontario N2L 3C5 (Canada)
E-mail: dgoussev@wlu.ca
Homepage: http://wlu.ca/homepage.php?grp_id=366
PNHPiPr ligand by a hemilabile NNHPiPr system could
facilitate the hydrogenation, by analogy with the Milsteinꢀs
NNP complex 1, which is more efficient than its PNP
[
1a]
analogue.
The NNHPiPr= PyCH NHC H PiPr (Py = 2-pyridyl)
[
**] We are grateful to the NSERC of Canada and the SHARCNET
2
2
4
2
facilities (www.sharcnet.ca) for their support of this work.
ligand is easily assembled by condensation of the commer-
cially available picolinaldehyde and 2-(diisopropylphosphi-
no)ethanamine, followed by reduction with DIBAL. The
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201108956.
2
772
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Angewandte
Chemie
[
a]
hydrido carbonyl chlorides [MHCl(CO)(NNHPiPr)] (M = Os
11), Ru (13); Scheme 2) were prepared from the readily
available [MHCl(CO)(AsPh ) ] precursors by ligand meta-
Table 1: Catalytic hydrogenation of methyl benzoate.
(
3
3
[
b]
Entry
Cat.
Ester/Metal
T [8C]
t [h]
Conv. [%]
[
c]
1
2
3
4
5
6
7
8
9
10
11
1
13
11
2000
2000
2000
2000
2000
3000
10000
2000
2000
2000
2000
2000
10000
20000
100
40
60
1.5
22
7
2.2
1.5
3
19
1.7
17
2.2
1.2
1
100
28
82
76
99
100
80
100
82
71
88
12
12
12
12
12
12
80
100
100
100
100
40
60
80
100
100
100
Scheme 2. Complexes used in this communication.
[
d]
[
c]
13
14
14
14
14
14
14
thesis. Treatment of complexes 11 and 13 with tBuOK
afforded unusual dimers [MH(CO)(NNPiPr)]2 (M = Os
(12), Ru (14); Scheme 2), presumably via intermediate 16-
2
99
100
90
e amido species [MH(CO)(NNPiPr)], which is analogous to
[
5b]
14
17
the known [OsH(CO)(PNPiPr)]. Characterization of new
complexes 11–14 was accomplished by a combination of
spectroscopic methods and X-ray crystallography.
1
4
[
a] PhCOOMe (20 mmol) in THF (7 mL) was hydrogenated in a 75 mL
Parr pressure vessel. [b] Molar ratio of substrate to metal. [c] With tBuOK
1 mol%). [d] With PhCOOMe (120 mmol) in a 300 mL vessel.
Dimers 12 and 14 have similar structures, however, they
differ by the arrangements of the NNPiPr ligands, which are
spanning the Ru centers in 14, but coordinate individual Os
centers in 12. These dimers are lacking symmetry and produce
characteristic 1:1 hydride and phosphorus NMR resonances
at room temperature. In the temperature range of 40 to 808C,
a second minor 1:1 pattern appears in the hydride region and
(
0.05 mol% of the catalyst (Table 1, entry 9). Osmium dimer
12 is also an efficient catalyst for hydrogenation of methyl
benzoate, however, at a slower rate compared to 14. The
chlorides 11 and 13 are similarly active in the presence of
tBuOK.
We further investigated hydrogenation of a group of
carbonyl compounds (Table 2) and representative alkenoates
(Scheme 3) at 1008C, under p(H ) = 50 bar. Catalyst 12 is
3
1
in the P NMR spectra of 12 and 14 because of slow
isomerization. No resonances of mononuclear species were
seen even at 808C, as well as no saturation transfer between
the hydrides, thus suggesting significant thermal and kinetic
stability of 12 and 14 in solution.
2
Exposing 12 and 14 to 2-propanol or H (1 atm) failed to
equally active for hydrogenation of ethyl, iso-butyl, and
methyl benzoates. However, hydrogenation of isopropyl 2-
bromobenzoate was unsuccessful, apparently because of
2
produce [MH (CO)(NNHPiPr)]. We obtained trans-
2
[
OsH (CO)(NNHPiPr)] (15) by treating 11 with Li(Et BH)
2
3
in THF. Characterization of the product in common solvents
was hampered by the lack of solubility (in C D and [D ]THF)
6
6
8
Table 2: Catalytic hydrogenation of esters A–I.
or rapid decomposition (in CD CN, CD Cl , and ethanol).
3
2
2
Surprisingly, 15 is soluble and stable in [D ]DMSO, in which
6
1
13
31
the H, C, and P NMR spectra are fully consistent with the
trans-dihydride structure analogous to the related trans-
[5b]
[
OsH (CO)(PNHPiPr)] complex. Experimental and com-
2
putational details for complexes 11–15 are provided in the
Supporting Information.
A stoichiometric reaction of dihydride 15 and methyl
[b]
Entry
Ester
Cat.
Ester/Metal
t [h]
Conv. [%]
benzoate in [D ]THF immediately produced methanol,
benzyl alcohol, and a mixture of the isomers of 12. The
8
1
2
3
4
A
B
C
D
D
D
D
E
F
F
G
H
I
12
12
12
12
12
14
14
12
12
14
12
12
14
2000
2000
2000
2000
3000
2000
10000
2000
2000
2000
2000
2000
2000
1.6
1.5
17
2
2.7
1.5
18
3
1.4
5
9
23
5.7
99
93
0
catalytic activity of complexes 11–14 under p(H ) = 50 bar
2
was first tested in a series of experiments with methyl
benzoate (Table 1). The ultimate performance was observed
with ruthenium dimer 14, which gave 18000 turnovers in
100
100
93
71
100
99
67
72
0
[
c]
5
6
7
8
9
1
1
1
7 hours at 1008C by using 0.005 mol% (50 ppm) of the
catalyst without base. Thus, this complex is one order of
magnitude more efficient than [RuH (CO)(PNHPiPr)],
2
0
1
which was mentioned above. At 808C, complex 14 gave
TOF = 1470 (Table 1, entry 11), which is 20 times faster than
12
13
[
3c]
the hydrogenation rate reported
for [RuHCl(CO)-
85
(
PNHPPh)] with 5 mol% NaOMe (catalyst 9, Scheme 1).
[a] Substrate (20 mmol) in THF (7 mL) was hydrogenated in a 75 mL
The efficiency of 14 increases markedly from 40 to 1008C, yet
a high conversion was achieved even at 408C by using only
pressure vessel at 1008C and p(H )=50 bar. [b] Molar ratio of substrate
to metal. [c] Substrate (120 mmol) in a 300 mL vessel.
2
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Substrates G and I are difficult to hydro-
genate and require longer reaction times. The
TOF of 160 for G (Table 2, entry 11) and 298 for I
(entry 13) compare well with the best reported
values under neutral conditions with catalysts 10
[
3c]
(
TOF = 62 in 16 h at 808C) and 3 (TOF = 314
[1b]
in 14 h at 1108C). No hydrogenation of methyl
oxalate (H) was observed with 12; this substrate
has not been studied with catalysts 1–10.
[8]
Activity and selectivity of complexes 12–14
were tested with substrates containing C=C
bonds. The results show significant differences
for ruthenium and osmium catalysts (Scheme 3).
Hydrogenation of a,b-unsaturated methyl 2-non-
enoate was not selective with 13 and afforded
nonanol, which is not surprising with regard to
the poor selectivity of 7 with methyl cinnama-
[
2a]
te. Unexpectedly, reduction of methyl 2-non-
enoate with 12 quantitatively afforded methyl
nonanoate. Such unusual selectivity and the lack
of further conversion to nonanol in this case are
puzzling. Osmium dimer 12 successfully cata-
lyzed reduction of methyl 3-nonenoate to 3-
nonenol, whereas ruthenium dimer 14 proved
inactive in this reaction. Methyl oleate was
hydrogenated with 12 with retention of the C=C
Scheme 3. Hydrogenation of alkenoates at 1008C and p(H )=50 bar, S/M=molar
bond to give (Z)-octadec-9-enol. The same
reaction was very sluggish and required more
catalyst with 12; the reaction also lacked selec-
tivity and afforded a mixture of octadecanol and
2
ratio of alkenoate groups to metal. [a] With tBuOK (0.5 mol%). [b] Conversion. [c] A
mixture of triglycerides of oleic (ca. 85%), linoleic (ca. 2–3%), and palmitic acids as
the main components in our samples. [d] Total yield of isolated alcohol mixture,
containing approximately 85% of oleyl alcohol.
(E)- and (Z)-octadec-9-enols.
We further tested osmium dimer 12 for
catalyst deactivation. None of the catalysts shown in
Scheme 1 have been tested with halogenated substrates,
except 6, which gave 88% conversion for methyl 4-chlor-
obenzoate by using 0.05 mol% catalyst with 10 mol%
reduction of glyceryl trioleate and a sample of domestic
olive oil, which is a natural mixture of triglycerides of oleic
(ca. 85%), linoleic (ca. 2–3%), and palmitic acids (main
components). Hydrogenation of the trioleate quantitatively
afforded neat (Z)-octadec-9-enol (oleyl alcohol) after aque-
[2b,c]
NaOMe at 1008C and p(H ) = 50 bar.
2
1
13
Complexes 12 and 14 gave 100% and 93% reduction for
methyl hexanoate in 2 and 1.5 hours, respectively. This
compares favourably with the reduction of methyl octanoate
with catalyst 6 (by using the same reaction temperature,
pressure, and catalyst loading), for which 86% conversion was
reported after 2.5 hours of reaction in the presence of
ous washing, based on comparison of the H and C NMR
spectra of the product with those of an authentic sample of the
alcohol. A similar product containing mostly oleyl (85%) and
palmityl alcohols was obtained after hydrogenation of olive
oil followed by aqueous washing. The reduction appeared
1
close to quantitative, although we noted that the H NMR
spectra of the product were missing the characteristic C11-
[
2b,c]
1
0 mol% NaOMe.
For ethyl acetate, the reduction with
1
2 was finished in three hours (Table 2, entry 8). The same
CH resonance of linoleyl alcohol (expected at 2.77 ppm in
2
reaction under p(H ) = 5 bar required a 20 times higher
CDCl ). Hydrogenation of esters of polyunsaturated acids
2
3
catalyst loading to reach 96% conversion in two hours with
will need to be studied further.
[
4a]
[1a]
5
and 86% conversion in 12 hours with 1, both at the
We finally tested the activity of the NNHPiPr catalysts for
dehydrogenative coupling of alcohols. Two complexes were
selected for this study, the ruthenium hydrido chloride 13 and
osmium dimer 12 (Table 3). We found the catalytic activity of
12 particularly impressive in ethanol and propanol at 788 and
968C respectively, as conversions of these alcohols to ethyl
acetate and propyl propionate with high yields have never
been observed below 1008C. The previously reported best
ADC catalyst 1 was inactive for ethanol and propanol and
required heating to more than 1008C to produce esters from
butanol and higher-boiling alcohols. The exceptional activity
of 12 for ester synthesis naturally correlates with the excellent
slightly higher temperatures of 105 and 1158C, respectively.
We further investigated hydrogenation of e-caprolactone,
a substrate that is known to undergo ring opening polymer-
[7]
ization (ROP) in the presence of tBuOK and similar bases.
Indeed, polymeric material was formed in an attempted
reduction of e-caprolactone with 13 in the presence of tBuOK.
When catalyzed by 14 without base, the hydrogenation
proceeded without polymerization, but stopped at 67%
conversion as if the catalyst was deactivated at that time.
Rapid reduction of e-caprolactone was achieved with osmium
dimer 12 (Table 2, entry 9).
2
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Chemie
Table 3: Catalytic acceptorless dehydrogenation of alcohols.
18000 turnovers in 17 hours for methyl benzoate and 7100
turnovers in 18 hours for methyl hexanoate. Osmium dimer
2 has proved to be a particularly useful catalyst for hydro-
1
[
a]
[b]
genation of esters with C=C bonds. To the best of our
knowledge, complex 12 is the first homogenous catalyst
efficient for hydrogenation of triglycerides, allowing produc-
tion of fatty alcohols directly from olive oil. Complex 12 is
also uniquely distinguished by effecting conversion of alco-
hols to esters, for example, ethanol into ethyl acetate, at
temperatures below 1008C.
Entry
R
T [8C]
Cat.
ROH/Metal
t [h]
Conv. [%]
1
2
3
4
5
6
7
8
9
Me
Me
Me
Me
Et
Et
Pr
Pr
i-Amyl
i-Amyl
Hexyl
Hexyl
Hexyl
78
78
78
78
96
12
1000
1000
1000
1000
1000
1000
1000
1000
1000
1000
1000
4000
1000
24
8
8
7.5
8.5
8
3
3
3
2.5
1.3
1.3
1
7
61
96
30
86
73
93
78
86
92
97
71
86
[
[
[
c]
12
12
13
12
13
12
13
12
13
12
12
13
c,d]
d]
[
[
[
d]
d]
d]
96
118
118
131
131
158
158
158
Received: December 19, 2011
Published online: February 8, 2012
1
1
1
1
0
1
2
3
Keywords: dehydrogenation · ester reduction · hydrogenation ·
.
[
d]
osmium · ruthenium
[
a] Neat substrate (52 mmol). [b] Molar ratio of substrate to metal. [c] In
toluene (3 mL). [d] With tBuOK (0.5 mol%).
[
1] a) J. Zhang, G. Leitus, Y. Ben-David, D. Milstein, Angew. Chem.
2006, 118, 1131 – 1133; Angew. Chem. Int. Ed. 2006, 45, 1113 –
1
115; b) E. Balaraman, C. Gunanathan, J. Zhang, L. J. W. Shimon,
activity of this catalyst for the reverse reaction, the reduction
of esters under hydrogen pressure.
Both the Noyori-type outer-sphere and the classical inner-
sphere hydrogenation mechanisms are possible with the
NNHPiPr complexes (Scheme 4). The superior activity of 12
D. Milstein, Nat. Chem. 2011, 3, 609 – 614; c) E. Fogler, E.
Balaraman, Y. Ben-David, G. Leitus, L. J. W. Shimon, D. Milstein,
Organometallics 2011, 30, 3826 – 3833; d) J. Zhang, E. Balaraman,
G. Leitus, D. Milstein, Organometallics 2011, 30, 5716 – 5724; e) C.
Gunanathan, D. Milstein, Acc. Chem. Res. 2011, 44, 588 – 602.
2] a) L. A. Saudan, C. M. Saudan, C. Debieux, P. Wyss, Angew.
Chem. 2007, 119, 7617 – 7620; Angew. Chem. Int. Ed. 2007, 46,
[
7473 – 7476; b) L. Saudan, P. Dupau, J.-J. Riedhauser, P. Wyss
(Firmenich SA), WO 2006106483, 2006; c) L. Saudan, P. Dupau,
J.-J. Riedhauser, P. Wyss (Firmenich SA), US 2010280273, 2010.
3] a) W. Kuriyama, Y. Ino, O. Ogata, N. Sayo, T. Saitoa, Adv. Synth.
Catal. 2010, 352, 92 – 96; b) Y. Ino, W. Kuriyama, O. Ogata, T.
Matsumoto, Top. Catal. 2010, 53, 1019 – 1024; c) W. Kuriyama, T.
Matsumoto, Y. Ino, O. Ogata, N. Saeki (Takasago Int. Co.), WO
[
2011048727, 2011; d) W. Kuriyama, T. Matsumoto, O. Ogata, Y.
Ino, K. Aoki, S. Tanaka, K. Ishida, T. Kobayashi, N. Sayo, T. Saito,
Org. Process Res. Dev. 2012, 16, 166 – 171.
[
4] a) Y. Sun, C. Koehler, R. Tan, V. T. Annibale, D. Song, Chem.
Commun. 2011, 47, 8349 – 8351; b) F. Stempfle, D. Quinzler, I.
Heckler, S. Mecking, Macromolecules 2011, 44, 4159 – 4166;
c) M. J. Hanton, S. Tin, B. J. Boardman, P. Miller, J. Mol. Catal.
A 2011, 346, 70 – 78; d) W. W. N. O, A. J. Lough, R. H. Morris,
Chem. Commun. 2010, 46, 8240 – 8242; e) T. Touge, T. Hakamata,
H. Nara, T. Kobayashi, N. Sayo, T. Saito, Y. Kayaki, T. Ikariya, J.
Am. Chem. Soc. 2011, 133, 14960 – 14963; f) M. Ito, T. Ootsuka,
R. Watari, A. Shiibashi, A. Himizu, T. Ikariya, J. Am. Chem. Soc.
2
011, 133, 4240 – 4242; g) S. Takebayashi, S. H. Bergens, Organo-
Scheme 4. Outer-sphere (a) and inner-sphere (b) hydrogenation.
Py=pyridine.
metallics 2009, 28, 2349 – 2351; h) M. C. van Engelen, H. T.
Teunissen, J. G. de Vries, C. J. Elsevier, J. Mol. Catal. A 2003,
206, 185 – 192; i) H. Teunissen, C. J. Elsevier, J. Chem. Soc. Chem.
Commun. 1988, 1367 – 1368; j) H. T. Teunissen, C. J. Elsevier,
Chem. Commun. 1997, 667 – 668.
versus [RuH (CO)(PNHPiPr)] for hydrogenation of methyl-
2
benzoate suggests an important role of hemilability of the
NNHPiPr-coordinated catalysts. Continuing work in our
group with XNHP ligands that are modified in order to
disfavor dimerization and to enhance lability of the X group
of the product complexes may shed more light on the
mechanistic details of the reactions catalyzed by complexes
[5] a) M. Bertoli, A. Choualeb, D. G. Gusev, A. J. Lough, Q. Major,
B. Moore, Dalton Trans. 2011, 40, 8941 – 8949; b) M. Bertoli, A.
Choualeb, A. J. Lough, B. Moore, D. Spasyuk, D. G. Gusev,
Organometallics 2011, 30, 3479 – 3482.
[
6] J. Zhang, G. Leitus, Y. Ben-David, D. Milstein, J. Am. Chem. Soc.
005, 127, 10840 – 10841.
7] M. Labet, W. Thielemans, Chem. Soc. Rev. 2009, 38, 3484 – 3504.
2
[
1
1–14.
In conclusion, this communication presents outstanding
[8] Reduction of dimethyl oxalate to ethylene glycol was reported by
using 0.2 mol% of a catalyst prepared from [Ru(acac) ] and
3
MeC(CH PPh ) . It took 16 hours at 1208C and p(H ) = 80 bar to
versatile catalysts for reduction of esters and for dehydrogen-
ative coupling of alcohols. Ruthenium dimer 14 has shown an
unmatched efficiency under neutral conditions by giving
2
2
3
2
[
4h,j]
achieve full conversion.
Angew. Chem. Int. Ed. 2012, 51, 2772 –2775
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
2775