Highly active iridium catalysts for the hydrogenation of ketones and aldehydes

Article abstract of DOI:10.1039/b815501a

The pressure hydrogenation capabilities of the iridium pincer complexes IrH₂Cl[(ⁱPr₂PC₂H₄) ₂NH] (1) and IrH₃[(ⁱPr₂PC ₂H₄)₂NH] (2) are described and compared to related results obtained previously in transfer hydrogenation. Complex 1 was shown to act as a convenient air-stable entry point to the active catalyst 2, in the presence of base and hydrogen gas. The catalysts are active in a range of solvents, including CH₂Cl₂ and CHCl₃, in contrast to related ruthenium systems. This class of iridium complexes is very effective for the direct hydrogenation of a wide range of carbonyl compounds including ketones, diketones, α,β-unsaturated ketones and aldehydes. A catalytic cycle is proposed for this system which involves an ionic heterolytic bifunctional hydrogenation mechanism. This journal is

Full text of DOI:10.1039/b815501a

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www.rsc.org/dalton | Dalton Transactions
Highly active iridium catalysts for the hydrogenation of ketones
and aldehydes†
Xuanhua Chen, Wenli Jia, Rongwei Guo, Todd W. Graham, Meredith A. Gullons and Kamaluddin Abdur-Rashid*
Received 5th September 2008, Accepted 8th December 2008
First published as an Advance Article on the web 13th January 2009
DOI: 10.1039/b815501a
i
The pressure hydrogenation capabilities of the iridium pincer complexes IrH
2
Cl[( Pr
2
PC
2
H ) NH] (1)
4
2
i
and IrH
3
[( Pr
2
PC
2
H ) NH] (2) are described and compared to related results obtained previously in
4
2
transfer hydrogenation. Complex 1 was shown to act as a convenient air-stable entry point to the active
catalyst 2, in the presence of base and hydrogen gas. The catalysts are active in a range of solvents,
including CH
2
Cl
2
and CHCl , in contrast to related ruthenium systems. This class of iridium complexes
3
is very effective for the direct hydrogenation of a wide range of carbonyl compounds including ketones,
diketones, a,b-unsaturated ketones and aldehydes. A catalytic cycle is proposed for this system which
involves an ionic heterolytic bifunctional hydrogenation mechanism.
Introduction
Catalytic hydrogenation of ketones and aldehydes is an in-
dispensable process for the synthesis of alcohols, which are
valuable end products and precursor chemicals in the phar-
maceutical, agrochemical, flavor, fragrance, material and fine
1
chemical industries. Noyori and co-workers have developed the
versatile RuCl
2
(PR
3
)
2
(diamine) and RuCl (diphosphine)(diamine)
2
hydrogenation catalyst systems that are highly effective for the
1,2
hydrogenation of ketones. It was subsequently discovered that
the Noyori catalysts are also very effective for the hydrogena-
3
tion of imines. It has been shown that in the presence of a
base and hydrogen gas the active catalyst species are ruthe-
nium dihydride complexes of the form RuH
2
(PR
3
)
2
(diamine)
3,4
and RuH
2
(diphosphine)(diamine). The mechanistic investiga-
Scheme 1 Catalyst activation.
tion included the synthesis, isolation and characterization of
the highly reactive amidoaminohydrido species that activates
4
a–c
hydrogen to regenerate the active dihydride catalysts.
It was
to hydrogen gas. On this premise, it is logical to postulate that
this class of iridium catalysts could also function as effective
clearly demonstrated that the carbonyl molecular recognition
motif of these catalysts is the mutually cis N–H and Ru–H moieties
in the dihydride catalysts, which facilitate hydrogenation through
hydrogenation catalysts in the presence of hydrogen gas. Since H
2
6
hydrogenation is generally preferred over transfer hydrogenation,
4
a–c,f,g
an outer-sphere hydrogen transfer process.
Catalysts that
6e,7
due to the typically higher loading capacity
and decreased
function via a related mechanism have also been reported by Shvo
et al. and Wills et al.
Recently, we reported the synthesis and characterization of the
amount of waste, we decided to examine this desirable facet of
iridium-based catalyst technology.
Herein we report that 2 is a very active base-free catalyst for
the pressure hydrogenation of ketones and aldehydes, whereas 1
is only active in the presence of a base, but serves as an air-stable
catalyst precursor.
4d
4e
i
series of iridium hydride complexes IrH
2
Cl[( Pr
PC
2
PC
2
H
4
)
2
NH] (1),
i
i
IrH
3
[( Pr
2
PC
2
5
H
4
)
2
NH] (2) and IrH
2
[( Pr
2
2
H
4 2
)
N] (3) illustrated
in Scheme 1. It was demonstrated that 2 and 3 are very active
catalysts for the base-free transfer hydrogenation of ketones in
-propanol, while 1 is air-stable and inactive as a catalyst in the
absence of a base. It was also reported that complex 3 rapidly
formed complex 2 upon exposure of a solution of the former
Reports on iridium aminophosphine catalyzed pressure hydro-
2
8
9a–c
genation of ketone are relatively scarce. Dahlenburg and G o¨ tz
have reported some hydrogenation results using a variety of
Ir(cod)(PN)]BF
[
4
salts (PN = 2-(diphenylphosphino)ethanamine
ligands with various substituents on the C–C backbone or on
N). The relatively low substrate to catalyst ratio of 100, long
Kanata Chemical Technologies Inc., 101 College Street, Office 230, MaRS
Centre, South Tower, Toronto, ON M5G 1L7, Canada. E-mail: kamal@
kctchem.com; Web: http://www.kctchem.com/
reaction times, high H pressures and high temperatures that were
used in the experiments suggest that these systems are not very
efficient. We are unaware of any reports on related iridium pincer
aminodiphosphine complexes being used as catalysts for pressure
hydrogenation of ketones.
2
†
Electronic supplementary information (ESI) available: Table for kinetic
runs for catalytic hydrogenation of acetophenone with 1/KO Bu and 2.
t
See DOI: 10.1039/b815501a
This journal is © The Royal Society of Chemistry 2009
Dalton Trans., 2009, 1407–1410 | 1407

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Table 1 Hydrogenation of acetophenone in methanol (10 atm H
2
) at
and RuH (diphosphine)(diamine) and their amido analogues are
2
a
room temperature
known to rapidly form the inactive species RuHCl(PR
3
2
) (diamine)
and RuHCl(diphosphine)(diamine), respectively, in the presence
of dichloromethane or chloroform.
Entry
Catalyst
S:C
Time/h
Conv (%)
4
1
2
3
4
5
2
2
1
1800
5000
1800
1800
5000
1
5
5
1
5
100
100
0
100
100
Table 3 summarizes the catalyst activity towards the hydro-
genation of a variety of ketones and aldehydes using 1/KO Bu as
t
the catalyst at room temperature. Acetophenone was converted
to phenylethanol (entries 1–3), even at high substrate to catalyst
ratios. Benzophenone was converted to benzhydrol (98% isolated
yield) under similarly mild reaction conditions (entry 4). The cat-
t
1/KO Bu
t
1/KO Bu
a
A weighed amount of the catalyst was added to a solution of the substrate
in methanol and the mixture was stirred for the allotted time under
hydrogen gas.
t
alytic activity of 1/KO Bu towards various dialkyl ketones was ex-
amined (entries 5–12). The reduction of 4-tert-butylcyclohexanone
resulted in a 1:2 non-thermodynamic mixture of the cis and trans
alcohols, respectively (entry 6). Unactivated dialkyl ketones were
readily converted to their respective alcohols, including sterically
congested and electronically deactivated pinacolone (entry 11).
The hydrogenation of conjugated ketones was also investigated.
For example, benzalacetone (entry 13) was converted to the allyl
alcohol (E)-4-phenylbut-3-en-2-ol as the only detectable product.
Only the carbonyl group of b-ionone (entry 14) was reduced to give
the alcohol product (E)-4-(2,6,6-trimethylcyclohex-1-enyl)but-3-
en-2-ol, whereas hydrogenation of 2-cyclohexen-1-one (entry 15)
resulted in a 1:1 mixture of the allyl and saturated alcohols.
Hydrogenation of 1-tetralone (entry 16) resulted in the formation
of the expected alcohol. The hydrogenation of the diketone
benzil formed mainly the meso alcohol (entry 17, meso:rac =
Results and discussion
The iridium complexes 1 and 2 were prepared as previously
5
described. It was previously established that the trihydride
complex 2 is an exceptionally active catalyst for the transfer
hydrogenation of ketones in the hydrogen donating solvent
5
2
2
-propanol. Therefore, in order to investigate the effectiveness of
as a direct hydrogenation catalyst, the reactions were conducted
in the non-hydrogen donor solvent methanol.
The base-free hydrogenation of acetophenone in methanol using
2
as a catalyst and hydrogen gas (entries 1 and 2) is summarized in
Table 1. The results demonstrate the effectiveness of the iridium
trihydride complex as a hydrogenation catalyst.
Under similar conditions 1 was totally ineffective (entry 3) as
a catalyst. By contrast, the use of 1/KO Bu (1:10) as the catalyst
resulted in complete conversion of acetophenone to phenylethanol
3
:1), whereas 2,5-hexanedione resulted in only rac-2,5-hexanediol
t
(entry 18). A 6:1 mixture of endo:exo norborneol resulted from
the hydrogenation of norcamphor (entry 19). The ability of this
catalyst system to reduce diketones and related substrates leading
to diastereomeric products demonstrates the possible relevance of
chiral derivatives for asymmetric hydrogenation reactions.
(
entries 4 and 5). This suggests that the air-stable complex 1 serves
as an entry point to the active catalyst 2 in the presence of a base
and hydrogen gas.
The effectiveness of this new catalytic hydrogenation system in
Aldehydes are typically easier to hydrogenate than ketones. The
hydrogenation of benzaldehyde and valeraldehyde was examined
t
a variety of solvents was then investigated using 1/KO Bu (1:10)
t
using 1/KO Bu as the catalyst (Table 3, entries 20 and 21). In both
as the catalyst. The results are summarized in Table 2. These show
that hydrogenation with this catalytic system is possible in most
common laboratory solvents, including dichloromethane and
chloroform. However, no reaction was observed in acetonitrile.
Similar results were obtained using 2 as catalyst. This is in contrast
cases, complete conversion to the primary alcohol products was
observed.
A preliminary kinetic study of the hydrogenation of acetophe-
t
◦
none catalyzed by 1/KO Bu and 2 in methanol at 25 C was
investigated. The results are plotted in Fig. 1. These show that
both systems are effective as catalysts.
to the Noyori-type systems in which the RuH
2
(PR ) (diamine)
3
2
t
Table 2 Hydrogenation of acetophenone using 1/KO Bu (1:10) as cata-
a
2
lyst in various solvents (10 atm H ) at room temperature
Entry
Solvent
S:C
Time/h
Conv (%)
1
2
3
4
5
6
7
8
9
Methanol
Ethanol
2-Propanol
Ether
THF
Ethyl acetate
Hexane
450
450
450
450
450
450
450
450
450
450
450
0.5
1
0.5
1
0.5
0.5
0.5
1
100
100
100
100
100
100
100
100
100
100
0
Toluene
Dichloromethane
Chloroform
Acetonitrile
1
1
2
1
1
0
1
a
A weighed amount of the catalyst was added to a solution of the substrate
t
Fig. 1 Plot of the hydrogenation of acetophenone catalyzed by 1/KO Bu
in the solvent and the mixture was stirred for the allotted time under
hydrogen gas.
◦
(
᭜) and 2 (᭹) in methanol at 25 C. [ketone]initial = 1.67 M; H
2
= 10 atm;
-3
[
catalyst] = 1.8 ¥ 10 M.
1
408 | Dalton Trans., 2009, 1407–1410
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t
Table 3 Hydrogenation of ketones and aldehydes using 1/KO Bu (1:10)
Table 3 (Contd.)
a
2
as catalyst in methanol (10 atm H ) at room temperature
Isolated h
yield (%)
Isolated
yield (%)
Entry
Substrate
S:C
900
Time/h
1
Conv (%)
100
h
Entry
1
Substrate
S:C
Time/h
1
Conv (%)
g
1
9
96
900
6000
30000
500
100
100
100
100
97
2
2
a
0
1
1000
750
2.5
1.5
100
100
98
2
3
4
5
5
12
1
n.d.
n.d.
98
n.d.
Catalyst samples were obtained from a stock solution of known
t
catalyst/KO Bu concentration, in a 1:10 mol ratio, and were added to
a solution of the substrate in MeOH; the mixture was then stirred at room
temperature under hydrogen gas. Yields based on the amount of substrate.
b
c
d
Ratio of cis:trans alcohol = 1:2. Only carbonyl group is reduced. Ratio
e
f
of saturated:allyl alcohol = 1:1. Ratio of meso:rac alcohol = 3:1. rac-
g
h
alcohol is the only product. Ratio of endo:exo = 6:1. n.d. = not
determined.
1100
700
1.5
1
100
100
93
99
t
The rate seems to be somewhat slower for 1/KO Bu. The delay
may be due to the need for activation of 1 to form the active
trihydride species.
b
6
7
8
9
1400
1200
900
2
2
100
100
100
100
100
74
Owing to the requirement of base for the hydrogenation to
occur with compound 1 we propose the involvement of an
ionic heterolytic bifunctional hydrogenation mechanism involving
mutually cis Ir–H and N–H moieties, as illustrated in Scheme 2.
The concerted outer sphere transfer of a hydride and NH
proton to the carbonyl carbon and oxygen of the substrate,
respectively, results in the formation of the alcohol product and the
highly reactive 16-electron amidodihydride species 3. Subsequent
heterolytic activation of hydrogen gas results in the regeneration
of the active trihydride catalyst. Further evidence for this was
substantiated by mixing a stoichiometric mixture of the trihydride
86
2
96
1
1
0
1
1000
1050
2
87
72
n.d.
2
(50 mg, 0.11 mmol) and acetophenone (10 ml, 0.08 mmol) in
1
1
2
3
160
360
1
1
100
100
98
99
dichloromethane (2 ml). A gas chromatogram of the reaction
mixture showed the formation of the phenylethanol product.
Although this does not eliminate the possibility of an insertion
mechanism, it provides support for an ionic heterolytic hydrogen
transfer. Further studies to evaluate this proposed mechanism
are underway. A similar heterolytic bifunctional hydrogenation
c
c
1
4
300
3
100
95
d
1
1
1
5
6
7
1100
360
2
100
100
100
n.d.
98
2
e
f
500
0.5
99
1
8
600
2
100
95
Scheme 2 Proposed hydrogenation mechanism.
Dalton Trans., 2009, 1407–1410 | 1409
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mechanism has been proposed for analogous ruthenium catalyst
systems.
100 ml Parr Pressure reactor. The pressure was adjusted to the
desired value and the reaction progress was monitored by assaying
aliquots of the reaction mixture using TLC or NMR spectroscopy,
or in two cases GC chromatography. After completion of the
reaction, the solvent was removed by evaporation under reduced
pressure. The alcohols were isolated and purified by filtering a
hexanes/ethyl acetate (3:1) solution of the crude product through
a pad of silica gel, and then removing the solvent under reduced
pressure. The conversion and purity of the alcohol products was
assessed using NMR spectroscopy.
4
a–c,f
Conclusions
In summary, this work has shown that iridium pincer amin-
odiphosphine complexes represent a very effective class of cat-
alysts for hydrogenation of carbonyl substrates under very mild
reaction conditions. In contrast to our previous report on transfer
hydrogenation catalysis utilizing this class of catalyst, it was shown
that hydrogen donor solvents such as 2-propanol are not required
for efficient reaction rates and high degrees of substrate conversion
under pressure hydrogenation conditions.
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410 | Dalton Trans., 2009, 1407–1410
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