Factors favoring efficient bifunctional catalysis. Study of a ruthenium(II) hydrogenation catalyst containing an N-heterocyclic carbene with a primary amine donor

Article abstract of DOI:10.1021/om300108p

An alcohol-assisted outer-sphere bifunctional mechanism is proposed for the H₂ hydrogenation of ketones catalyzed by the ruthenium(II) precatalyst [RuCp*(C-NH₂)py]PF₆ (2; Cp* = pentamethylcyclopentadienyl ligand, C-NH

Full text of DOI:10.1021/om300108p

Article
pubs.acs.org/Organometallics
Factors Favoring Efficient Bifunctional Catalysis. Study of a
Ruthenium(II) Hydrogenation Catalyst Containing an N-Heterocyclic
Carbene with a Primary Amine Donor
Wylie W. N. O, Alan J. Lough, and Robert H. Morris*
Davenport Laboratory, Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario M5S 3H6, Canada
S
* Supporting Information
ABSTRACT: An alcohol-assisted outer-sphere bifunctional mechanism is
proposed for the H2 hydrogenation of ketones catalyzed by the ruthenium(II)
precatalyst [RuCp*(C−NH2)py]PF6 (2; Cp* = pentamethylcyclopentadienyl
ligand, C−NH2 = N-heterocyclic carbene (NHC) with a tethered primary amine
donor, py = pyridine) when activated by an alkoxide base. It has a high activity
(turnover frequency (TOF) of up to 17 600 h−1) and selectivity for the H2
hydrogenation of ketones at 25 °C and 8 bar of H2 pressure in the presence of
alcohols. Computational studies of a model neutral ruthenium(II) hydride amine
complex, RuCp(C−NH2)H (Cp = cyclopentadienyl ligand), using density
functional theory (DFT) methods reveal a low free energy barrier for the transfer
of a proton/hydride couple to the ketone in the outer coordination sphere. In
contrast, the related iridium(III) hydride amine complex [IrCp(C−NH2)H]+ is
predicted to have a high barrier for hydride transfer to the ketone due to the poor
nucleophilicity of this cationic hydride. A 2-propanol molecule acts as a proton shuttle in the heterolytic splitting of the η2-H2
ligand on ruthenium according to deuterium labeling and computational studies. The carbonyl stretching wavenumbers of the
complexes [RuCp*(D−NH2)CO]X, including the new complexes [RuCp*(C−NH2)CO]PF6 (4) and [RuCp*(P−NH2)CO]-
PF6 (5; P−NH2 = 2-(diphenylphosphino)benzylamine), decrease as D is changed in the order phosphine, NHC, 2′-pyridine,
amine. Thus, the NHC complex 2 is more electron rich and more active as a hydrogenation catalyst than the phosphine complex
[RuCp*(P−NH2)py]PF6 (3). We conclude that complex 2 outperforms other ruthenium(II) NHC complexes and some other
phosphine−amine complexes for the H2 hydrogenation of ketones due to the following factors: (1) the ease of formation of a
highly reactive neutral hydride, (2) the presence of an NH2 donor ligand required for bifunctional catalysis, and (3) the presence
of an NHC donor to achieve the right balance of hydricity of the metal hydride and acidity of the protic amine group for the
efficient H+/H− transfer to the polar double bond.
coordinated η2-H2 ligand is rate determining.11d−f,i−l,12,13 The
key intermediates of the catalytic cycle, the trans-dihydride−
INTRODUCTION
Catalytic hydrogenation of unsaturated bonds using dihydrogen
■
is an attractive, atom-economical, chemical process.1 The
activation of dihydrogen by homogeneous catalysts is a process
of continuing interest.2 The use of an ancillary ligand such as an
amido3 or an amine donor4 to heterolytically split dihydrogen
has emerged as an effective strategy in the design of catalysts for
the hydrogenation of polar double bonds.5 This idea has been
extended to the development of catalysts for C−C,5e,6 C−O,7
and C−N8 bond formation to provide access to new synthetic
building blocks which are otherwise difficult to synthesize using
conventional methods.9
amine and the monohydrido−amido catalysts of RuXY-
(diamine)(phosphine)2 or RuXY(diamine)(diphosphine) sys-
tems (X = H, Cl; Y = H, BH4, OR), have been identified and
isolated.13,14 Ruthenium(II) alkoxide complexes have been
observed at low temperature prior to the formation of an amido
species,15 and one of these has been isolated recently.16 Under
optimum conditions, such catalysts allow hydrogenation to
occur under mild conditions: room temperature and low
hydrogen pressures with no added base.13,14,17 The importance
of the N−H group was demonstrated by the fact that metal
hydride amine systems that lacked the N−H were found to be
less active and selective and required forcing conditions in the
hydrogenation of ketones.18
The “NH effect”, which involves the bifunctional action of
M−H/N−H groups to attack a polar bond in the outer
coordination sphere, has been studied extensively both
experimentally10 and theoretically.11 The ketone hydrogenation
is proposed to proceed via a six-membered pericyclic transition
state involving hydrogen bonding of the N−H group with the
oxygen of the ketone and attack of the carbonyl group by the
metal hydride.3a,5c Many research groups,11e,12 including
ours,11k,13 have shown that the heterolytic splitting of a
The effect of alcohol on bifunctional catalysis with the “NH
effect” has also been well studied. Combined computational and
experimental studies on many catalyst systems have shown that
Received: February 9, 2012
Published: March 6, 2012
© 2012 American Chemical Society
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Figure 1. Late-transition-metal complexes containing a chelating N-heterocyclic carbene (NHC)−primary amine (C−NH2) or a chelating
phosphine−primary amine (P−NH2) ligand.
an alcohol molecule serves as a proton shuttle that assists in the
heterolytic splitting of the η2-H2 ligand.5f,11e,12a,13b,17b,18b,19 This
decreases the energy barrier for the activation of H2 but does
not significantly change the energy barrier for the transfer of a
proton/hydride couple to the ketone in a hydrogen-bonded
network.17b
Certain ruthenium(II) complexes bearing a phosphine−amine
(P−NH2) ligand, including the complexes trans-RuHCl((S)-
BINAP)(P−NH2)20 and RuCp*(κ2(P,N)-PPh2CH2CH2NH2)-
Cl21 (Figure 1), when activated with a base, catalyze efficiently
the hydrogenation of a variety of polar bonds, including those
of ketones,18h,20,22 imines,14b esters and lactones,23 epoxides,21
and cyclic imides.24 The notion of replacing a phosphine with
a more electron-donating N-heterocyclic carbene (NHC) donor
Figure 2. Inner sphere mechanism involving the decoordination of the
primary amine group proposed for the H2 hydrogenation of ketones
catalyzed by [Ru(p-cymene)(C-NH2)Cl]PF6 in the presence of an
alkoxide base.
is attractive with the promise of a reduction in the toxicity of
catalyst precursors and contaminants in the hydrogenated pro-
ducts leading to greener catalysis.25 Thus, the replacement of
phosphine by an NHC donor would give a donor-functionalized
NHC26 containing an NHC ligand and a primary amine donor
(C−NH2). Douthwaite and co-workers reported the synthesis of
the first palladium complex containing such a C−NH2 ligand
(Figure 1).27
We began to explore the use of a more conveniently pre-
pared C−NH2 ligand in metal complexes for the catalytic hydro-
genation of ketones using H2 or 2-propanol as the hydrogen
source. The complexes [M(p-cymene)(C−NH2)Cl]PF6 (M =
Ru,28 Os;29 Figure 1) were prepared by a transmetalation
reaction28 from a nickel(II) complex, [Ni(C−NH2)2](PF6)2 (1;
Figure 1), to the appropriate precursor complex. The hydride
complex [Ru(p-cymene)(C−NH2)H]PF6 was prepared, but this
failed to transfer its proton/hydride couple to acetophenone
in either stoichiometric or catalytic reactions. Experimental and
computational studies suggested that an outer-sphere bifunc-
tional mechanism was not viable for this cationic hydride−
amine complex and that an inner sphere mechanism involving
the decoordination of the primary amine group was more likely
to occur (Figure 2).29
with high turnover frequency (TOF) the hydrogenation of
a variety of ketones (up to 17 300 h−1 for the hydrogenation
of acetophenone), styrene oxide, an aromatic ester, and a
ketimine.31 The substrate to catalyst loading is high, and the
reaction conditions are very mild (8 bar of H2 pressure,
25 °C). This system has activity that is superior to that of the
related catalysts RuCp*(κ2(P,N)-PPh2CH2CH2NH2)Cl and
RuCp*(diamine)Cl.11e,18b,21 This complex (2) is, to date, the
most active ruthenium(II) catalyst containing an NHC for the
H2 hydrogenation of ketones.32 We believe that the unique
catalyst architecture for this complex is responsible for the very
high activity observed in the ketone hydrogenation and in the
activation of H2.
In the current study we show that when 2 is activated by an
alkoxide base, it follows an alcohol-assisted outer-sphere
bifunctional mechanism in the H2 hydrogenation of ketones
involving the action of a metal hydride and a protic amine
group. A structurally similar iridium(III) complex, [IrCp*(C−
NH2)Cl]PF6, when it is activated with an excess of alkoxide base
in 2-propanol, is a less active catalyst in ketone hydrogenation,
as described in the following paper.33 Herein, we will present
both experimental and theoretical evidence to support the two
elementary steps in the alcohol-assisted outer-sphere bifunc-
tional mechanism: (a) the heterolytic splitting of dihydrogen at
Although there are many metal complexes containing an
amine-functionalized NHC ligand,27,30 none were reported
to be useful for ketone hydrogenation30c,g,j apart from those in
our work.31 We have prepared the ruthenium(II) complex
[RuCp*(C−NH2)py]PF6 (2; Cp* = pentamethylcyclopenta-
dienyl ligand, py = pyridine; Figure 1) and found it to catalyze
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the active metal center, aided by a 2-propanol molecule acting
as a proton shuttle (step A in Scheme 1), and (b) the transfer
RESULTS AND DISCUSSION
■
Synthesis of Ruthenium(II) Complexes Containing
C−NH2 and P−NH2 Ligands. The ruthenium(II) complex,
[RuCp*(C−NH2)py]PF6 (2), was prepared by a transmetala-
tion reaction28,31 of 1 and RuCp*(cod)Cl in refluxing aceto-
nitrile followed by the addition of pyridine in tetrahydrofuran
(THF; Scheme 2). The characterization of this complex has
been reported previously.31 The diphenylphosphino-containing
complex [RuCp*(P−NH2)py]PF6 (3; P−NH2 = 2-(di-
phenylphosphino)benzylamine herein) was prepared by the
reaction of the P−NH2 ligand and RuCp*(cod)Cl. After the
crude reaction mixture was treated with AgPF6 in acetonitrile
followed by the addition of pyridine in THF, complex 3 was
isolated in good yields (Scheme 3).31
Scheme 1. Alcohol-Assisted Outer-Sphere Bifunctional
Mechanism of H2 Hydrogenation of Ketones Catalyzed by a
Ruthenium(II) Complex Containing a C−NH2 Ligand
We also set out to prepare the carbonyl complexes
[RuCp*(C−NH2)(CO)]PF6 (4) and [RuCp*(P−NH2)-
(CO)]PF6 (5) in order to compare their electronic properties
(Schemes 2 and 3). Both complexes 4 and 5 were characterized
by NMR and an X-ray diffraction study (Figures 3 and 4).
The carbonyl stretching wavenumbers of 4 and 5 are 1940 and
1952 cm−1, respectively.
General Features of the H2 Hydrogenation of Ketones
Catalyzed by Complexes 2 and 3. The ruthenium(II)
complex 2 catalyzed the H2 hydrogenation of a variety of
ketones and N-(1-phenylethylidene)aniline with high substrate
to catalyst loadings (catalyst to substrate (C/S) ratio up to
1/11 500) under very mild reaction conditions (8 bar of H2
pressure, 25 °C) using either THF or 2-propanol as the
reaction medium and potassium tert-butoxide (KOtBu) as the
base (catalyst to base (C/B) ratio 1/8). The solvent 2-propanol
is an excellent choice for achieving a TOF of 17 300 h−1 in the
H2 hydrogenation of acetophenone, under the same catalysis
conditions as above (Figure 5).31 The transfer hydrogenation
of acetophenone in 2-propanol has activity that is inferior to
that of hydrogenation using H2 (TOF = 1270 h−1, 25 °C under
argon). Significantly, complex 2 catalyzed the H2 hydrogenation
of an Ru−H/N−H couple to the ketone in the outer-sphere
(step B in Scheme 1). We also show here that the structurally
similar cationic iridium(III) system is unlikely to catalyze ketone
hydrogenation by this mechanism. A novel alternative
mechanism involving neutral iridium(I) intermediates will be
described in the accompanying paper.33 In addition, a
comparison between the C−NH2 and analogous P−NH2 ligand
in the ruthenium(II) catalyst allows us to evaluate the relative
merits of these ligands in the homogeneous hydrogenation of
ketones.
Scheme 2. Synthesis of Ruthenium(II) Complexes Containing a C−NH2 Ligand
Scheme 3. Synthesis of Ruthenium(II) Complexes Containing a P−NH2 Ligand
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conversion) and none of the saturated ketone 4-phenylbutan-
2-one within 1 h (C/B/S = 1/8/600). This corresponds to a
maximum TOF value of 938 h−1 in the conversion to trans-
4-phenyl-but-3-en-2-ol (Figure 5). The selectivity that 2 exhibits is
characteristic of an outer-sphere bifunctional mechanism,
although the reduction of the olefin might proceed via a
1,4-addition reaction utilizing the same mechanism.34
The catalytic activity for the hydrogenation of acetophenone
using H2 (C/B/S = 1/8/200) of the phosphine−amine
complex 3, on the other hand, is inferior to that of 2. It
produces a maximum conversion of 8% in 4 h under 25 bar of
H2 pressure in THF at 50 °C. Complex 2 is, by far, the most
active ruthenium(II) catalyst containing an NHC for the H2
hydrogenation of ketones.32
Effect of Alcohols and Other Additives on the H2
Hydrogenation of Acetophenone Catalyzed by Com-
plex 2. Reactions carried out in THF gave sigmoidal-type
reaction profiles with variable induction periods (10−60 min).
On the other hand, a reaction that was conducted in 2-propanol
did not show any sigmoidal behavior in the reaction profile
(Figure 6).
The effects of different additives on this induction period
were investigated. The addition of the product alcohol,
1-phenylethanol, at the beginning of the reaction (up to 0.4 M
in THF) decreased the induction period. In addition, the
induction period increased by roughly 6-fold when the pressure
of H2 was decreased from 8 to 2 bar. There was little effect on
changing the concentrations of acetophenone or the catalyst by
2-fold (see the Supporting Information, Figure S1). The addition
of pyridine to the reaction mixture retarded catalysis (Figure 6).
In addition, the possibility of ruthenium nanoparticle formation
was considered; the hydrogenation of 4′-chloroaccetophenone in
THF catalyzed by 2 with KOtBu added was not affected by the
addition of excess mercury, an indication that heterogeneous
Ru(0) particles are not the active species for catalyzed ketone
hydrogenation.31
Figure 3. ORTEP diagram of 4 ([RuCp*(C−NH2)CO]PF6) depicted
with thermal ellipsoids at 30% probability. The counteranion and most
of the hydrogens have been omitted for clarity. Selected bond
distances (Å) and bond angles (deg): Ru(1)−C(1), 2.065(4); Ru(1)−
N(3), 2.178(3); Ru(1)−C(22), 1.859(4); Ru(1)−C(15), 2.223(4);
C(22)−O(1), 1.149(5); C(1)−Ru(1)−N(3), 90.8(2); C(1)−Ru(1)−
C(22), 95.1(2); C(22)−Ru(1)−N(3), 91.7(2).
It appears that there exists a competition between H2 and
pyridine to coordinate to the catalytically active species. The
presence of alcohol selectively favors the binding and heterolytic
splitting of η2-H2 by acting as a proton shuttle.5f,11e,17b,18b,19a
This system will have a rate law different from that reported for
the amido complex RuH((S)-BINAP)(app) (app = 2-amido-2-
(2-pyridyl)propane), which displayed autocatalysis in the
presence of alcohols, because of competing coordination
between H2 and pyridine to the active species.17b
Deuterium Labeling Studies Using Complex 2 and
2-Propanol. In order to find evidence for an alcohol-assisted
mechanism in the hydrogenation of ketones catalyzed by complex
2, acetophenone was deuterated using D2 gas in 2-propanol
(OH) and 2-propanol-d1 (OD, Table 1). Full conversion to the
deuterated product was achieved in 30 min. Analysis of the
1H NMR spectra of the products revealed significant deuteration
at the α-carbon and the hydroxyl group of 1-phenylethanol when
both D2 and 2-propanol-d1 were used, but less when D2 and
2-propanol were used (Table 1). These results suggest significant
H/D scrambling took place at the active ruthenium species with
participation of the alcohol solvent. Further analysis of the
2H NMR spectra showed deuteration of the hydroxyl group of
2-propanol but not at its α carbon. On the other hand, the
hydroxyl deuterium of 2-propano1-d was not retained after
catalysis (lowered from 100% to 84% deuteration, Table 1),
further supporting the idea that H/D scrambling has taken place.
This is evidence that 2-propanol is acting as a proton shuttle.18b
Figure 4. ORTEP diagram of 5 ([RuCp*(P−NH2)(CO)]PF6)
depicted with thermal ellipsoids at 30% probability. The counteranion
and most of the hydrogens have been omitted for clarity. Selected
bond distances (Å) and bond angles (deg): Ru(1)−P(1), 2.320(1);
Ru(1)−N(1), 2.166(4); Ru(1)−C(30), 1.877(6); Ru(1)−C(24),
2.218(5); C(30)−O(1), 1.140(6); P(1)−Ru(1)−N(1), 87.3(1);
P(1)−Ru(1)−C(30), 88.6(2); C(30)−Ru(1)−N(1), 90.8(2).
of methyl benzoate to methanol and benzyl alcohol in THF,
reaching a TOF value of 209 h−1 at 25 °C and 838 h−1 at 50 °C
and 8 bar of H2 pressure (C/B/S = 1/8/1500; Figure 5).
Under similar reaction conditions to the hydrogenation of
ketones using KOtBu as the base (8 bar of H2 pressure, 25 °C),
complex 2 catalyzed the selective reduction of the polar bond
in trans-4-phenyl-but-3-ene-2-one to give trans-4-phenyl-but-3-
en-2-ol (89% conversion) and 4-phenylbutan-2-ol (4%
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Figure 5. Substrate scope and TOF value reported for the H2 hydrogenation of organic molecules with polar double bonds catalyzed by complex 2 in
the presence of KOtBu at 25 °C and 8 bar of H2 pressure. Details of the reaction conditions were reported in ref 31.
Observation and Reactivity of Hydride Complexes of
Ruthenium(II). Hydride intermediates have been proposed in
the catalytic cycles of the hydrogenation of polar bonds and the
racemization of chiral alcohols. The complex RuCp*(κ2(P,N)-
PPh2CH2CH2NH2)H, which was suggested to be present
during the catalytic hydrogenolysis of epoxides, has been observed
but not isolated.21 Hydride intermediates have been observed
spectroscopically in the racemization catalyst system containing
Ru(η5-Cp*)(ICy)Cl, NaOtBu, and (S)-1-phenylethanol (ICy =
1,3-dicyclohexylimidazol-2-ylidene).35 The complex Ru(η5-
C5Ph5)(CO)2H has been isolated, and this catalyzes the
racemization of (S)-1-phenylethanol36 via an inner-sphere
mechanism upon the dissociation of the carbonyl ligand.37
We sought to observe or isolate the hydride−amine complex
RuCp*(C−NH2)H, which can potentially transfer a proton/
Figure 6. Reaction profiles showing the effect of alcohols and pyridine
hydride couple from its Ru−H/N−H group to the ketone (step B
in Scheme 1).3a,5e,f Attempts to isolate such a complex were not
on the hydrogenation of acetophenone (S = substrate) catalyzed by
complex 2 (C = catalyst). All of the reactions were conducted with 8
successful. Reactions of excess or stoichiometric amounts of base
bar of H2 at 25 °C with KOtBu (B) added: (a) in THF, red circles; (b)
(KOtBu, NaOiPr, NaOMe, NaBH4, KOH, KH, or K-Selectride)
in 2-propanol, blue diamonds; (c) in THF, [1-phenylethanol] = 0.2 M,
with complex 2 in THF under a hydrogen atmosphere (up to
green squares; (d) in THF, [1-phenylethanol] = 0.4 M, orange
8 bar) or in 2-propanol solution gave intractable products.
triangles; (e) in THF, [pyridine] = 0.030 M, purple crosses. The C/B/S
ratio was 1/8/2515.
1
Nevertheless, a hydride peak in the H NMR spectrum was
observed at −9.23 ppm in THF-d8 when the reaction was carried
out under a hydrogen atmosphere in the presence of KOtBu.
Attempts to utilize such a reaction mixture upon removal of
excess KOtBu in the catalytic hydrogenation of acetophenone
(0.15 or 1.9 M) using 8 bar of H2 pressure at 25 °C in the
absence of base gave no conversion to the product alcohol.
However, reactions of complex 2 with sodium 2-propoxide
(2.6 equiv) or potassium 1-phenylethoxide (1.3 equiv) in THF-
d8 at 25 °C under argon gave a species showing a new hydride
Table 1. Deuteration of Acetophenone and 2-Propanol
Catalyzed by Complex 2
b
D content in 1-phenylethanol (%)
D content in
2-propanol (%)
OD group
b
OD
CDnH3−n group
(n = 1 − 3)
a
D
source α-CD group
D2/iPrOH
D2/iPrOD
42
80
11
76
−
71
27
84
1
peak at −9.47 ppm in the H NMR spectrum. The relative
a
Reactions were carried out in a 50 mL Parr hydrogenation reactor at
integration of this peak against the alkoxide suggested that 6%
of the starting material was converted to this hydride. A hydride
peak at −9.23 ppm was also observed in a smaller amount in
these two experiments. Acetone and acetophenone that were
produced from β-hydride elimination of the alkoxides were
observed as well with 2% and 8% conversion, respectively. After
the solutions were left for 1 day in sealed NMR tubes at 25 °C,
the hydride peaks disappeared and both samples contained less
than 2% of the ketone. These results suggest that the hydride-
containing species at −9.47 ppm in THF-d8 may represent the
true catalytically active species, instead of the one that was
observed at −9.23 ppm. These hydride complexes, however,
are difficult to identify due to the complexity of the reaction
mixture and their high reactivity.
8 bar of D2 pressure at 25 °C using the appropriate solvent (6 mL).
KOtBu was used as the base. The catalyst/base/substrate/solvent ratio
was 1/8/898/17 060. Complete conversion to the product alcohol was
b
achieved in 30 min. The deuterium content of 1-phenylethanol and
1
2
2-propanol were determined by H and H NMR.
Of note, deuteration of the methyl group of 1-phenylethanol was
observed when D2 and 2-propanol-d1 were used in catalysis. This
is expected, due to the base-catalyzed deuteration of enolizable
ketones as reported elsewhere.13b,29 These experiments support
the alcohol-assisted heterolytic splitting of η2-H2 on the active
ruthenium species starting from complex 2 when activated (step
A in Scheme 1).
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Scheme 4. Computed Outer-Sphere Bifunctional Mechanism for the Hydrogenation of Acetone Catalyzed by Complexes of
Ruthenium(II) and Iridium(III)
Conventional Non-Alcohol-Assisted Outer-Sphere
Bifunctional Mechanism. The catalytic cycles that involve
the outer-sphere bifunctional mechanism in the absence of
alcohol for the ruthenium(II) (complex 2) system was
investigated by density functional theory (DFT). The
MPW1PW91 functional was used, as this gives a better
prediction of energy barriers and transition states for 4d and 5d
metals.38 A catalytic cycle pertaining to a structurally similar
cationic iridium(III) system was also computed for comparison,
although the experimental results and the preferred, alternative
mechanism for this less active catalyst system will be reported
elsewhere.33 Simplifications were made to ease computation by
replacing the Cp* ligand with Cp; acetone and 2-propanol were
used to model the ketone and the product alcohol.
In the conventional outer-sphere mechanism that involves
the action of M−H and N−H groups (Scheme 4), the addition
of base to the precatalyst afforded the amido complex A, which
results from the deprotonation of the N−H group. Such a
complex is responsible for activating dihydrogen to yield the
metal hydride complex D via an H2 addition step to the metal
center (TSB,C) and subsequent heterolytic splitting at the metal
center (TSC,D). The activation of H2 at the amido complex
is rate-determining, and this should have the largest energy
barrier of the overall catalytic cycle. The fast, low barrier step
then follows for the transfer of H+/H− from D to the ketone
in the outer-sphere fashion to afford the product alcohol
and A.5f,11e,j,l,12a,13a,b,17b
splitting of H2) by the neutral ruthenium(II) and cationic
iridium(III) species are 14.1 (ΔH⧧ = 7.3 kcal/mol) and 22.6
kcal/mol (ΔH⧧ = 14.8 kcal/mol), respectively. The heterolytic
splitting of H2 leads to a more reactive ruthenium(II) hydride DRu
(−8.8 kcal/mol relative to ARu and H2) but a more thermodynami-
cally stable iridium(III) hydride DIr (−23.5 kcal/mol relative to AIr
and H2). The free energy barriers for the transfer of H+/H− from
DRu to acetone and to acetophenone are 16.9 (ΔH⧧ = 2.2 kcal/
mol) and 12.3 kcal/mol (ΔH⧧ = −1.7 kcal/mol), respectively
(see the Supporting Information, Figure S2). In contrast, it is
unfavorable to transfer H+/H− from DIr to acetone (ΔG⧧ = 36.7
kcal/mol; ΔH⧧ = 62.6 kcal/mol). In addition to a stronger Ir−H
bond that is formed due to relativistic effects on going from a 4d
(Ru) to a 5d (Ir) metal, the cationic charge of the iridium may
deactivate the metal hydride, as was observed for the [Ru(p-
cymene)(C−NH2)H]+ system.29
The computed results suggest well-balanced energy barriers
for the ruthenium(II) system. The hydride complex (DRu)
which is formed upon the activation of H2 by ARu is readily
consumed when it transfers its H+/H− to the ketone in the
outer sphere. This provides evidence to support a bifunctional
step involving the action of Ru−H/N−H outlined in step B
from Scheme 1. The replacement of an arene ligand (η6-C6H6)
in [Ru(η6-C6H6)(C−NH2)H]+ with the cyclopentadienyl ligand
(η5-Cp) to give Ru(η5-Cp)(C−NH2)H results in a significant
energy difference of the ground-state energies of the hydride−
amine complexes and the starting ruthenium amido complexes:
calculations using the same functional and basis sets suggest that
the cationic hydride−amine complex [Ru(η6-C6H6)(C−NH2)H]+
According to calculations (Figure 7), the free energy barriers
(ΔG⧧) for the activation of H2 (the coordination and heterolytic
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Figure 7. Free energy profile for the outer-sphere bifunctional mechanism in the H2 hydrogenation of acetone, starting from A and moving to the
right. The pathway in blue represents the ruthenium(II) system, and that in red represents the iridium(III) system. The gas-phase free energies
(1 atm, 298 K) are reported relative to A, H2, and acetone in kcal/mol.
Figure 8. Computed transition state structures for the heterolytic splitting of H2 (TSC,D) of the ruthenium(II) (left) and the iridium(III) system (right). The
bond lengths (Å) are given in the structures. Color code for the atoms: (orange) ruthenium; (yellow) iridium; (blue) nitrogen; (gray) carbon; (white) hydrogen.
is the resting state of the outer-sphere bifunctional mechanism
in the H2 hydrogenation of ketone (22.4 kcal/mol more stable
than the amido complex and H2). This supports the
experimental observation that the cationic hydride−amine
complex [Ru(η6-p-cymene)(C−NH2)H]PF6 does not react
with a ketone.29 On the other hand, the neutral complex Ru(η5-
Cp)(C−NH2)H is only 8.8 kcal/mol more stable than the
amido complex Ru(η5-Cp)(C−NH) (Figure 7). Our calculated
results also predict that the cationic iridium(III) hydride
complex (DIr), if formed during catalysis, is the resting state of
the catalytic cycle (23.5 kcal/mol more stable than the
iridium(III) amido complex and H2), and the transfer of H+/
H− to the ketone in the outer sphere will be very difficult. In
fact, we will show that the cationic hydride−amine complex
[Ir(η5-Cp*)(C−NH2)H]PF6 does not react with a ketone as
well.33 Of note, the neutral, well-defined hydride−amine
complexes containing a cyclometalated C−NH2 ligand and an
anionic carbon donor IrCp*(κ2(C,N)-2-C6H4CR2NH2)H39 and
Ru(η6-C6H6)(κ2(C,N)-2-C6H4CR2NH2)H40 react with aceto-
phenone by transferring their M−H/N−H couples to the
ketone in the absence of base. Their mechanisms have not yet
been explored computationally, however. It appears that the
charge of these hydride−amine complexes is an important
factor in determining the reactivity of the M−H/N−H couple
to a ketone.
Of interest, the geometric parameters for the optimized
transition state structures for the heterolytic splitting of H2
(TSC,D, Figure 8) and the transfer of H+/H− to acetone (TSE,F
,
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Figure 9) of both systems are surprisingly similar, except for a
longer O−H interaction in TSE,F (O−H···N distance: 1.61 Å for
ruthenium and 1.10 Å for iridium) for the ruthenium(II)
system.10h,11a,b,e,13a,17b An intrinsic reaction coordinate (IRC)
calculation41 that was performed on TS(Ru)E,F located a local
minimum, which revealed a 2-propoxide anion that is hydrogen
bonded via oxygen to the N−H group on the C−NH2 ligand,
along with an agostic C−H interaction of the 2-propoxide anion
with the ruthenium(II) center. Subsequent geometry optimiza-
tion and normal-mode analysis revealed that this structure
(FRu′) is 0.9 kcal/mol more stable than TS(Ru)E,F (ΔG =
7.2 kcal/mol relative to ARu, H2, and acetone). This has a O−H
distance of 1.39 Å, a C−H distance of 1.26 Å, and a Ru···H
distance of 1.85 Å (see Figure S4 in the Supporting
Information). These geometric parameters are similar to an
analogous structure reported by Gusev and co-workers.10h
A
QST3 or a QST2 calculation that was performed for the
protonation of the 2-propoxide anion by the N−H group on the
C−NH2 ligand, giving FRu, failed to locate a transition-
state structure. All these suggest that the transfer of a H+/H−
couple from the hydride−amine complex to the ketone in the
outer sphere for the ruthenium(II) system might occur in a
stepwise fashion.10h,15,42
Alcohol-Assisted Outer-Sphere Bifunctional Mechanism
for the Ruthenium(II) System. In the presence of 2-propanol
(Scheme 5), or when the concentration of the product alcohol
builds up during catalysis, the free energy barrier for the
activation of dihydrogen becomes lower. The highest barrier is
now ΔG⧧ = 11.1 kcal/mol measured from the energy of A in
the presence of alcohol, Aalc (or F in Scheme 4), to the
Figure 9. Computed transition state structures for the transfer of a
proton/hydride pair to acetone (TSE,F) from the ruthenium(II) (top)
and iridium(III) hydrides (bottom). The bond lengths (Å) are given in
the structures. Color code for the atoms: (orange) ruthenium;
(yellow) iridium; (blue) nitrogen; (blue) oxygen; (gray) carbon;
(white) hydrogen.
Scheme 5. Computed Reaction Pathway of the Activation of H2 by Complex A in the Presence of 2-Propanol
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Figure 10. Free energy profile for the outer-sphere bifunctional mechanism in the activation of H2, starting from A and moving to the right (blue
pathway), and in the presence of 2-propanol, starting from Aalc and moving to the right (red pathway). The gas-phase free energies (1 atm, 298 K)
are reported relative to A, H2, and 2-propanol for the red pathway and to A and H2 for the blue pathway, in kcal/mol.
Figure 11. Computed transition state structures for the heterolytic splitting of H2 (TSC,Dalc) by the ruthenium(II) system in the presence of 2-
propanol. The bond lengths (Å) are given in the structure. Color code for the atoms: (orange) ruthenium; (blue) nitrogen; (red) oxygen; (gray)
carbon; (white) hydrogen.
transition state for H2 coordination to Aalc (TSB,Calc, Figure 10).
This is lower than the 14.1 kcal/mol value for the case of no
alcohol present. Similarly the barrier for the heterolytic splitting
of H2 becomes lower (ΔG⧧ = ΔG(TSC,Dalc) − ΔG(Aalc) =
8.5 kcal/mol) in comparison to that with no alcohol present
(13.1 kcal/mol).
alcoholic oxygen are held in close proximity by the formation of
two hydrogen bonds via O···H interactions (H(2)−O = 1.74 Å,
H(3)−O = 1.36 Å; Figure 11). These results are supportive of
an alcohol-assisted mechanism where the alcoholic proton is
shuttled between the coordinated dihydrogen and the amido
nitrogen via a six-membered-ring transition state (step B in
Scheme 1).5f,11e,l,12a,13b,17b,18b,19 Andersson and co-workers
have calculated a similar transition state structure for the
The transition state structure of the alcohol-assisted hetero-
lytic splitting of H2 shows that the protons neighboring the
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Figure 12. Carbonyl stretching wavenumbers (cm−1 in KBr) of a series of ruthenium(II) complexes, [RuCp*(D−NH2)CO]+, where D is a donor
group. The complexes [RuCp*(κ2(N,N)-N(CH3)2CH2CH2NH2)CO]OTf, [RuCp*(κ2(N,N)-(2′-C5H4N)CH2NH2)CO]OTf, and [RuCp*-
(κ2(P,N)-PPh2CH2CH2NH2)CO]OTf were prepared by Ikariya and Ito. See refs 5f and 43.
alcohol-assisted heterolytic splitting of H2 of a structurally
similar RuCp*(diamine)X system; the effect of methanol on
the free energy barriers of H2 coordination and its activation are
pronounced.11e
an analogous C−NH2 ligand with an aniline-type N−H group
are not very active in the catalytic transfer hydrogenation of
ketones.30j The phosphine−amine complex 3 is a poor catalyst
for the hydrogenation of acetophenone when activated by base.31
This P−NH2 ligand is the least donating in the series, judging
from its carbonyl stretching wavenumber in complex 5.
In addition, the free energy barrier for the transfer of a
proton/hydride couple to acetone is 16.2 kcal/mol (ΔH⧧ =
2.6 kcal/mol) if a six-membered-ring transition state is assumed
(see the Supporting Information, Scheme S1 and Figures S4
and S6).17b The alcohol, therefore, has a minor effect on such
a transition state as the energy barriers with and without
alcohol were similar (ΔG⧧ = 16.9 kcal/mol), consistent with
our observations reported previously.17b On the other hand, the
induction period that was observed when an aprotic solvent
was used during catalysis can be explained by a competition
between pyridine and dihydrogen to coordinate to the amido
complex RuCp*(C−NH). The energy barriers for the
coordination of pyridine and hydrogen to A are very similar
(ΔG⧧ = 15.7 and 14.1 kcal/mol, respectively; ΔH⧧ = 4.6 and
7.3 kcal/mol, respectively; see the Supporting Information,
Scheme S2 and Figure S6), and the presence of alcohol
provides a lower energy pathway to effectively convert Aalc and
H2 to the hydride complex Dalc, which will be readily consumed
by transferring its H+/H− couple to acetone in the outer sphere.
This has the effect of driving the equilibrium between A plus
pyridine and its adduct, RuCp*(C−NH)(py), to the left.
Electronic Properties of Ruthenium(II) Complexes That
Relate to Their Reactivity in Catalytic Hydrogenation. The
electronic properties of a series of ruthenium(II) complexes
formulated as RuCp*(D−NH2)Cl, where D is a donor group,
have been probed by preparing the corresponding cationic
carbonyl complexes.5f,43 In particular, the carbonyl stretching
wavenumber of complex 4 containing the C−NH2 ligand lies
between those of the complex [RuCp*(κ2(P,N)-PPh2CH2CH2-
NH2)CO]OTf, in which the D−NH2 ligand is less donating,
and complexes containing nitrogen donors, which are more
electron donating (Figure 12). Of note, the complexes RuCp*
(κ2(N,N)-N(CH3)2CH2CH2NH2)Cl and RuCp*(κ2(N,N)-
(2′-C5H4N)CH2NH2)Cl are ketone and ester44 hydrogenation
catalysts upon activation by KOH, yet are poor catalysts for the
hydrogenolysis of epoxides; the complex RuCp*(κ2(P,N)-
PPh2CH2CH2NH2)Cl, on the other hand, shows the reverse
trend.18b,21 Ikariya and co-workers have attributed the facile
proton and hydride transfer to the polar bond to a greater
acidity of the coordinated NH2 group of the latter.5f A counter
example to this is the rhodium(I) amine complex [Rh(η4-diene)-
(C−NHR)]BF4 (C−NHR = 1-mesityl-3-(2-(mesitylamino)-
ethyl)imidazolylidene), which contains an acidic aniline-type
N−H group and is not active toward the catalytic transfer hydro-
genation of benzophenone.30c The iridium(III) and ruthenium-
(II) complexes prepared by Cross and co-workers that contain
The chelation effect of the phosphine−amine ligand that
forms a five-membered or a six-membered ring including the
metal may contribute to the difference in electronics at the metal
center.45 Overall, the hydricity of the hydride complex must also
contribute to the reactivity exhibited by these complexes;46,47
a
good balance of the hydricity of the hydride ligand and the
acidity of the protic amine group, which is dependent on the
donor strength of the D−NH2 ligand, is required to promote a
successful transfer of H+/H− to the polar bond of interest and,
therefore, result in a catalyst of high activity.3a,5e,f The rich
substrate scope and the high turnover frequencies of 2 as a
hydrogenation catalyst (ketones, an epoxide, a ketimine, and
an ester) suggests that a correct electronic balance is achieved
in such an NHC−amine system in contrast to its other
counterparts.
CONCLUSIONS
■
There are several pieces of evidence to support an alcohol-
assisted outer-sphere bifunctional mechanism for the ruthenium-
(II) complex 2 when activated by an alkoxide base in the
hydrogenation of ketones using hydrogen gas:
(a) the high selectivity for the reduction of the ketone over the
olefin in an α,β-unsaturated ketone, a characteristic feature
of a catalyst operating by the outer-sphere bifunctional
mechanism5e,f,11e,14b
(b) the pronounced effect of alcohols on increasing the rate
of catalysis, decreasing the period of activation of the
catalyst, and promoting H/D scrambling when deu-
terated alcohol or deuterium gas is used
(c) the low free energy barrier calculated for the transfer of a
proton/hydride couple from the neutral ruthenium(II)
hydride Ru(η5-Cp)(C−NH2)H to the ketone in the outer
sphere; in contrast, a high energy barrier is calculated for
this transfer to acetone from the cationic hydride complex
[Ir(η5-Cp)(C−NH2)H]+
(d) a significant decrease in the calculated free energy
barriers to the heterolytic splitting of the η2-H2 ligand on
Ru(η5-Cp)(C−NH) when a 2-propanol molecule acts a
proton shuttle by participating in a six-membered-ring
transition state5f,11e,12a,13b,17b,18b,19
The donor ability of the D−NH2 type ligand (D = NHC,
phosphine, amine, 2′-pyridine) was also investigated by use of
the carbonyl stretching wavenumbers of the complexes
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atmosphere using standard Schlenk-line and glovebox techniques.
Dry and oxygen-free solvents were always used. The syntheses of [1-
(2-aminomethylphenyl)-3-methylimidazol-2-ylidene](η5-pentamethyl-
cyclopentadienyl)(pyridine)ruthenium(II) hexafluorophosphate (2) and
[2-(diphenylphosphino)benzylamine](η5-pentamethylcyclopentadienyl)-
(pyridine)ruthenium(II) hexafluorophosphate (3) have been reported
previously.28,31 The syntheses of RuCp*(cod)Cl49 and 2-(diphenyl-
phosphino)benzylamine (P−NH2)50 were reported in the literature. All
other reagents and solvents were purchased from commercial sources and
were used as received. Deuterated solvents were purchased from
Cambridge Isotope Laboratories and Sigma Aldrich and degassed and
dried over activated molecular sieves prior to use. NMR spectra were
[RuCp*(D−NH2)CO]X to help explain the poorer perform-
ance in the catalytic H2 hydrogenation of ketones of the
phosphine−amine complex [RuCp*(P−NH2)py]PF6 (3) in
comparison to the C−NH2 analogue. The C−NH2 ligand was
found to be more donating than the P−NH2 ligand. We
conclude that a fine tuning of the Brønsted acidities of the N−H
and the M−H groups is required by choosing the right donor
ligand to achieve maximum activity of polar double bond
reduction by H2.
The replacement of an arene ligand (η6-p-cymene) in
[Ru(η6-p-cymene)(C−NH2)H]+ with the pentamethylcyclo-
pentadienyl ligand (η5-Cp*) to give Ru(η5-Cp)(C−NH2)H
results in a significant energy difference of the ground state
energies of the hydride−amine complexes with respect to the
starting amido complexes. This is important in explaining their
reactivity toward polar double bonds. Our computational results
show that the cationic model complexes, [Ru(η6-C6H6)(C−
NH2)H]+ and [Ir(η5-Cp)(C−NH2)H]+, are the resting states of
the outer-sphere bifunctional mechanism in the H2 hydro-
genation of ketones. The high free energy barriers that were
calculated for these hydride−amine complexes prevent them
from transferring their proton/hydride couple to a ketone. This
is evident from our experimental studies.29,33 We also showed
that it is feasible for the neutral hydride−amine complex Ru(η5-
Cp)(C−NH2)H to transfer its proton/hydride couple to
a ketone in the outer sphere. Ikariya and Pfeffer have showed
that the neutral hydride−amine complexes of iridium(III) and
ruthenium(II) containing a cyclometalated C−NH2 ligand
react with acetophenone in the absence of base at ambient
temperature.39,40 It appears that the charge of these hydride−
amine complexes is an important factor in determining the
reactivity of the M−H/N−H pair.
1
recorded on a Varian 400 spectrometer operating at 400 MHz for H,
100 MHz for 13C, 161 MHz for 31P, and 376 MHz for 19F. The 1H and
13C{1H} NMR spectra were measured relative to partially deuterated
solvent peaks but are reported relative to tetramethylsilane (TMS). All
19F chemical shifts were measured relative to trichlorofluoromethane as
an external reference. All 31P chemical shifts were measured relative to
85% phosphoric acid as an external reference. All infrared spectra were
recorded on a Nicolet 550 Magna-IR spectrometer. The elemental
analysis was performed at the Department of Chemistry, University of
Toronto, on a Perkin-Elmer 2400 CHN elemental analyzer. Samples
were handled under argon where it was appropriate. Single-crystal X-ray
diffraction data were collected using a Nonius Kappa-CCD diffractometer
with Mo Kα radiation (λ = 0.710 73 Å). The CCD data were integrated
and scaled using the Denzo-SMN package. The structures were solved
and refined using SHELXTL V6.1. Refinement was by full-matrix least
squares on F2 using all data. Details are given in Table S1 (Supporting
Information).
Synthesis of [1-(2-Aminomethylphenyl)-3-methylimidazol-
2-ylidene]carbonyl(η5-pentamethylcyclopentadienyl)-
ruthenium(II) Hexafluorophosphate (4; [RuCp*(C−NH2)(CO)]-
PF6). A Schlenk flask was charged with 2 (32 mg, 0.049 mmol). It was
evacuated and back-filled with a CO atmosphere (1 atm) two times.
A solution of tetrahydrofuran (10 mL) saturated with Ar was injected
into the Schlenk flask against a flow of CO by means of a syringe and a
needle. The solution turned immediately from orange-yellow to pale
yellow upon dissolution. The solution was stirred at room temperature
(25 °C) for 3 h. The volume of the solvent was reduced (2 mL).
Addition of diethyl ether or hexanes (12 mL) to this and slow cooling
of the solution at −25 °C afforded a pale yellow crystalline solid, which
was filtered on a glass frit and dried in vacuo. Yield: 22 mg, 75%.
Suitable crystals for an X-ray diffraction study were obtained by slow
diffusion of hexanes into a saturated solution of 4 in tetrahydrofuran
The presence of an N-heterocyclic carbene ligand, an amine
group, and a pentamethylcyclopentadienyl ligand in our system,
therefore, provides the following unique features favoring
efficient bifunctional catalysis:
(a) an NH2 group required for bifunctional catalysis utilizing
the “NH effect”3a,5e
(b) the ability to form a highly reactive neutral hydride
(c) the use of an NHC ligand to achieve the right balance of
the hydricity of the metal hydride and the acidity of the
protic amine group for the efficient H+/H− transfer to
the polar double bond
1
under a nitrogen atmosphere. H NMR (CD2Cl2, δ): 7.62 (m, 3-CH
and 5-CH of Ph, 2H), 7.51 (m, 4-CH and 6-CH of Ph, 2H), 7.35 (d,
JHH = 2.07 Hz, 5-CH of imid, 1H), 7.29 (d, JHH = 2.07 Hz, 4-CH of
imid, 1H), 4.21 (td, JHH = 2.69, 11.53 Hz, CH2, 1H), 3.89 (s, CH3, 3H),
3.84 (br, NH2, 1H), 2.98 (m, CH2, 1H), 2.17 (m, br, NH2, 1H), 1.40
(s, CH3 of Cp*, 15H). 19F NMR (CD2Cl2, δ): −72.5 (d, JPF = 712 Hz).
13C{1H} NMR (CD2Cl2, δ): 207.1 (Ru−CCO), 181.8 (Ru−Ccarbene),
139.5 (CPh), 132.6 (CPh), 131.8 (CPh), 130.5 (CPh), 129.7 (CPh), 126.2
(CPh), 125.0 (Cimid), 124.7 (Cimid), 94.6 (CAr‑Cp*), 48.9 (CH2), 39.4
(CH3), 9.5 (CH3 of Cp*). IR (KBr, cm−1): 1940 (ν(CO)). MS (ESI,
methanol/water; m/z): 452.1 [M]+. HRMS (ESI, methanol/water;
m/z): calcd for C22H28N3ORu+ [M]+ 452.1270, found 452.1269.
Attempts at elemental analyses failed to give an acceptable carbon
content, while hydrogen and nitrogen contents are in the acceptable
range. Typical results are as follows. Anal. Calcd for C22H38F6N3OPRu:
C, 44.30; H, 4.73; N, 7.04. Found: C, 42.99; H, 4.64; N, 7.35.
Synthesis of [2-(Diphenylphosphino)benzylamine]carbonyl-
(η5-pentamethylcyclopentadienyl)ruthenium(II) Hexafluoro-
phosphate (5; [RuCp*(P−NH2)(CO)]PF6). A scintillation vial with
a threaded screw cap was charged with RuCp*(cod)Cl (50 mg, 0.13
mmol) in dry dichloromethane (5 mL) under a nitrogen atmosphere.
A solution of 2-(diphenylphosphino)benzylamine (40 mg, 0.13 mmol)
in dry dichloromethane (5 mL) was added to the aforementioned
yellow solution and stirred for 1 h at room temperature (25 °C),
whereupon the reaction mixture turned orange. Silver hexafluor-
ophosphate (33 mg, 0.13 mmol) in dry acetonitrile (1 mL) was added
These features make the present system outperform other
ruthenium(II) NHC complexes29,32 and some other phos-
phine−amine complexes12a,13a,b,18b,20,48 for the H2 hydro-
genation of ketones, judging from the reaction conditions and
the TOF values reported for some of these systems in ketone
hydrogenation (Table 2). Our results show that an alcohol-
assisted outer-sphere bifunctional mechanism accounts for such
a difference in catalytic activity.
We will further discuss the effect of the metal center on
ketone hydrogenation by comparing the catalytic activity of the
current ruthenium(II) system with that of a structurally similar
iridium(III) system in an accompanying article.33 The potential
for this ruthenium(II) system in the H2 hydrogenation of other
polar double bonds is currently being investigated by our
research group.
EXPERIMENTAL SECTION
Synthesis. All of the preparations and manipulations, except where
otherwise stated, were carried out under a nitrogen or argon
■
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Table 2. Reaction Conditions and Turnover Frequencies Reported for Some Ketone Hydrogenation Catalysts of Ruthenium(II)
a
cat.
ketone
reacn conditions
TOF/h−1
ref
13a
RuH(NH2CMe2CMe2NH)(PPh3)2
trans-RuH2(NH2CMe2CMe2NH2)- ((R)-BINAP)
RuHCl(P−NH2)2
RuHCl((R)-BINAP)(P−NH2)
RuCl2((S)-tol-BINAP)((S,S)-dpen)
RuCl2(ethP2(NH)2)
acetophenone
acetophenone
acetophenone
acetophenone
acetophenone
acetophenone
acetophenone
acetophenone
acetophenone
acetophenone
acetone
6 atm H2, 20 °C, C6D6
6 686
505
i
14 atm H2, 20 °C, PrOH
13a
20
b
i
2.0 atm H2, 5 °C, PrOH
2 500
b
i
2.0 atm H2, 5 °C, PrOH
1 250
20
b
45 bar H2, 30 °C, KOiPr/iPrOH
45 bar H2, 30 °C, KOiPr/iPrOH
4 atm H2, 30 °C, KOiPr/iPrOH
20 atm H2, 30 °C, KOH/iPrOH
1 atm H2, 30 °C, KOH/iPrOH
50 000
13b, 48
13b
12a
18b
18b
32a
32b
32c
29
b
3 300 000
37 440
RuH(η1-BH4)((S)-tol-BINAP)((S,S)-dpen)
RuCp*(NH2CH2CH2NMe2)Cl
RuCp*(P−NH2)Cl
b
1 170
b
16
b
RuH(η2-BH4)(IPr)2(CO)
10 atm H2, 75 °C, PrOH
11
i
b
[RuH(IMes)2(CO)]BArF
2 atm H2, 60 °C, C6D6
0.42
4
b
Ru(p-cymene)(C−O-carboxylate)Cl
[Ru(p-cymene)(C−NH2)Cl]PF6
[RuCp*(C−NH2)py]PF6
benzophenone
tert-butyl phenyl ketone
acetophenone
benzophenone
60 bar H2, 80 °C, THF/EtOH
25 bar H2, 50 °C, KOtBu/THF
8 bar H2, 25 °C, KOtBu/iPrOH
25 bar H2, 50 °C, KOtBu/THF
64
461
17 600
472
31
[IrCp*(C−NH2)Cl]PF6
33
a
b
TOF = turnover frequency, measured from the slope of the linear portion of [alcohol] versus time plot unless otherwise stated. TOF measured as
TON (turnover number) divided by time at a certain percentage conversion.
1
to the reaction mixture, and a yellow-brown suspension was obtained.
After the reaction mixture was stirred for 0.5 h, it was filtered through
a pad of Celite, and the solvent was collected into a Schlenk flask
under a nitrogen atmosphere. The solvent was then removed under
reduced pressure. The Schlenk flask containing the residue was
evacuated and back-filled with a CO atmosphere (1 atm) two times.
A solution of tetrahydrofuran (10 mL) saturated with Ar was injected
into the Schlenk flask against a flow of CO by means of a syringe and
needle. The solution turned immediately from orange-yellow to pale
yellow upon dissolution. The solution was stirred at room temperature
for 3 h. The volume of the solvent was reduced (2 mL). Addition of
diethyl ether (15 mL) afforded a yellow precipitate, which was filtered
and dried in vacuo to give a pale yellow solid. Yield: 72 mg, 78%.
Suitable crystals for an X-ray diffraction study were obtained by slow
diffusion of diethyl ether into a saturated solution of 5 in
dichloromethane under a nitrogen atmosphere. H NMR (CD2Cl2, δ):
7.56−7.49 (m, Ar-CH of Ph-PPh2, 6H), 7.47 (m, Ar-CH of Ph-PPh2,
1H), 7.45−7.36 (m, Ar-CH of Ph-PPh2, 5H), 7.32−7.25 (m, Ar-CH of
Ph-PPh2, 2H), 4.00 (m, CH2, 1H), 3.71 (br, NH2, 1H), 3.58 (m, CH2,
1H), 3.05 (br, NH2, 1H), 1.67 (s, CH3 of Cp*, 15H). 19F NMR
(CD2Cl2, δ): −72.6 (d, JPF = 712 Hz). 31P{1H} NMR (CD2Cl2, δ):
42.1 (s), −144.5 (sept, JPF = 712 Hz). 13C{1H} NMR (CD2Cl2, δ):
203.9 (d, JCP = 16.83 Hz, Ru−CCO), 140.7 (d, JCP = 15.08 Hz, CPh‑PPh),
134.1 (d, JCP = 12.48 Hz, CPh‑PPh), 133.4 (d, JCP = 10.93 Hz, CPh‑PPh),
132.5 (d, JCP = 22.03 Hz, CPh‑PPh), 132.3 (d, JCP = 31.09 Hz, CPh‑PPh),
131.8 (d, JCP = 2.20 Hz, CPh‑PPh), 131.6 (d, JCP = 2.11 Hz, CPh‑PPh), 131.4
(d, JCP = 2.51 Hz, CPh‑PPh), 131.3 (CPh‑PPh), 130.9 (d, JCP = 1.95 Hz,
CPh‑PPh), 129.7 (CPh‑PPh), 129.4 (d, JCP = 10.38 Hz, CPh‑PPh), 129.3 (d,
JCP = 10.51 Hz, CPh‑PPh), 129.1 (d, JCP = 7.11 Hz, CPh‑PPh), 96.8 (d, JCP
1.91 Hz, CAr−Cp*), 50.4, (d, JCP = 9.41 Hz, CH2), 9.7 (CH3 of Cp*). IR
=
2148
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Article
(KBr, cm−1): 1952 (ν(CO)). MS (ESI, methanol/water; m/z): 556.1
[M]+. HRMS (ESI, methanol/water; m/z): calcd for C30H33NOPRu+
[M]+ 556.1337, found 556.1355. Anal. Calcd for C30H33NF6OP2Ru: C,
51.43; H, 4.75; N, 2.00. Found: C, 51.10; H, 4.70; N, 1.91.
with the restricted hybrid mPW1PW91 functional.53 Ruthenium and
iridium were treated with the SDD54 relativistic effective core potential
and an associated basic set. All other atoms were treated with the
double-ζ basis set 6-31++G**, which includes diffuse functionals55 and
additional p orbitals on hydrogen as well as additional d orbitals
on carbon, nitrogen, and oxygen.56 All geometry optimizations were
conducted in the gas phase, and the stationary points were
characterized by normal-mode analysis. Reported free energies were
obtained at 1 atm and 298 K using unscaled vibrational frequencies.
The QST3 method was used to locate transition states. All transition
states reported were found to have a single imaginary frequency.
Representative Example of a Stoichiometric Reaction Using
High Pressure of H2. Complex 2 (10 mg, 15 μmol) and potassium
tert-butoxide (9 mg, 0.080 mmol) were dissolved separately in THF
(4 and 2 mL, respectively) under a nitrogen atmosphere. These
solutions were taken up by means of two separate syringes and needles
in a glovebox. The needles were stoppered, and the syringes were taken
to the reactor. The solutions were then injected into the reactor against
a flow of hydrogen gas. The hydrogen gas was adjusted to 8 bar, and
the reaction mixture was stirred at 25 °C. After 2 h of reaction, the
reactor was detached from the hydrogen source and a H2 pressure of
2−4 bar was maintained. The reactor was attached to a Schlenk line
and back-filled with argon gas using standard Schlenk-line techniques.
The reaction mixture was then transferred to an empty Schlenk flask
filled with argon by syringe and a needle, and the solvent was removed
under vacuum. The residue was taken up in diethyl ether (10 mL) and
filtered through a pad of Celite. The solvent was then evaporated, and a
1H NMR spectrum of the crude reaction mixture was measured in
ASSOCIATED CONTENT
* Supporting Information
■
S
CIF files giving X-ray structural data for complexes 4 and 5,
tables, text, and figures giving details for catalysis, Cartesian
coordinates, energies for all of the computed structures, and the
complete citations for refs 51 and 52, and AVI files giving
animations for loose vibration characterizing the computed
transition states. This material is available free of charge via the
Internet at http://pubs.acs.org.
THF-d8.
Catalysis. Oxygen-free tetrahydrofuran (THF) used for all of the
catalytic runs was stirred over sodium for 2−3 days under argon and
freshly distilled from sodium benzophenone ketyl prior to use.
Oxygen-free 2-propanol used for all catalytic runs was stirred over
magnesium turnings and a single crystal of iodine for several hours
under argon and freshly distilled prior to use. Acetophenone was
vacuum-distilled over phosphorus pentoxide (P2O5) and stored under
nitrogen prior to use. 2-Propanol-d (purchased from Cambridge
Isotope Laboratories) and 1-phenylethanol were vacuum-distilled,
dried over activated molecular sieves, and stored under nitrogen prior
to use. D2 gas was purchased from Cambridge Isotope Laboratories.
All of the hydrogenation reactions were performed at constant
pressures using a stainless steel 50 mL Parr hydrogenation reactor. The
temperature was maintained at 25 °C using a constant-temperature
water bath. The reactor was flushed several times with hydrogen gas at
2−4 bar prior to the addition of catalyst and substrate and of base
solutions.
In a typical run (Figure 6), catalyst 2 (3 mg, 4.6 μmol), aceto-
phenone (1.4 g, 11.6 mmol), and 1-phenylethanol (147 mg, 1.2 mmol)
and potassium tert-butoxide (4 mg, 0.036 mmol) were dissolved in
THF (4 and 2 mL, respectively) under a nitrogen atmosphere. The
catalyst/substrate and base solutions were taken up by means of two
separate syringes and needles in a glovebox. The needles were
stoppered, and the syringes were taken to the reactor. The solutions were
then injected into the reactor against a flow of hydrogen gas. The
hydrogen gas was adjusted to 25 bar. Small aliquots of the reaction
mixture were quickly withdrawn with a syringe and a needle under a flow
of hydrogen at timed intervals by venting the Parr reactor at reduced
pressure. Alternatively, small aliquots of the reaction mixture were
sampled from a stainless steel sampling dip tube attached to a modified
Parr reactor. The dip tube was 30 cm in length with an inner diameter of
0.01 in., and a swing valve was attached to the end of the sampling tube.
Other technical details were previously reported.11k Two small aliquots of
samples were thereby withdrawn quickly at timed intervals by opening
the swing valve, and the first two aliquots were discarded. All samples for
gas chromatography (GC) analyses were diluted to a total volume of
approximately 0.50 mL using oxygenated THF.
AUTHOR INFORMATION
Corresponding Author
*E-mail: rmorris@chem.utoronto.ca.
Notes
■
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
The NSERC of Canada is thanked for a Discovery Grant to
R.H.M. and a graduate scholarship to W.W.N.O.
■
REFERENCES
■
(1) (a) de Vries, J. G., Elsevier, C. J., Eds. The Handbook of
Homogeneous Hydrogenation; Wiley-VCH: Weinheim, Germany, 2004;
Vols. 1−3. (b) Kubas, G. J. Chem. Rev. 2007, 107, 4152−4205.
(2) (a) Samec, J. S. M.; Backvall, J. E.; Andersson, P. G.; Brandt, P.
̈
Chem. Soc. Rev. 2006, 35, 237−248. (b) Nixon, T. D.; Whittlesey,
M. K.; Williams, J. M. J. Dalton Trans. 2009, 753−762. (c) Gloaguen,
F.; Rauchfuss, T. B. Chem. Soc. Rev. 2009, 38, 100−108. (d) Conley,
B. L.; Pennington-Boggio, M. K.; Boz, E.; Williams, T. J. Chem. Rev.
2010, 110, 2294−2312.
(3) (a) Noyori, R.; Yamakawa, M.; Hashiguchi, S. J. Org. Chem. 2001,
66, 7931−7944. (b) Ito, M.; Endo, Y.; Ikariya, T. Organometallics
2008, 27, 6053−6055. (c) Kuwata, S.; Ikariya, T. Dalton Trans. 2010,
39, 2984−2992.
(4) (a) Lough, A. J.; Park, S.; Ramachandran, R.; Morris, R. H. J. Am.
Chem. Soc. 1994, 116, 8356−8357. (b) Chu, H. S.; Lau, C. P.; Wong,
K. Y.; Wong, W. T. Organometallics 1998, 17, 2768−2777. (c) Lee,
D. H.; Patel, B. P.; Clot, E.; Eisenstein, O.; Crabtree, R. H. Chem.
Commun. 1999, 297−298. (d) Ayllon, J. A.; Sayers, S. F.; Sabo-
Etienne, S.; Donnadieu, B.; Chaudret, B.; Clot, E. Organometallics
1999, 18, 3981−3990. (e) Henry, R. M.; Shoemaker, R. K.; DuBois,
D. L.; DuBois, M. R. J. Am. Chem. Soc. 2006, 128, 3002−3010.
(f) Grutzmacher, H. Angew. Chem., Int. Ed. 2008, 47, 1814−1818.
̈
(g) Kayaki, Y.; Ikeda, H.; Tsurumaki, J. I.; Shimizu, I.; Yamamoto, A.
Bull. Chem. Soc. Jpn. 2008, 81, 1053−1061.
A Perkin−Elmer Clarus 400 chromatograph equipped with a chiral
column (CP chirasil-Dex CB 25 m × 2.5 mm) with an autosampling
capability was used for GC analyses. Hydrogen was used as the mobile
phase at a column pressure of 5 psi with a split flow rate of 50 mL/min.
The injector temperature was 250 °C, the FID temperature was
275 °C, and the oven temperature was 130 °C. Retention times
(tR/min): acetophenone, 4.56; (R)-1-phenylethanol, 7.58; (S)-1-
phenylethanol, 8.03. All of the conversions were reported as an average
of two GC runs. The reported conversions were reproducible.
Computational Details. All density functional theory (DFT)
calculations were performed using the Gaussian 0351 and 0952 packages
(5) (a) Jessop, P. G.; Morris, R. H. Coord. Chem. Rev. 1992, 121,
155−284. (b) Morris, R. H. Can. J. Chem. 1996, 74, 1907−1915.
(c) Clapham, S. E.; Hadzovic, A.; Morris, R. H. Coord. Chem. Rev.
2004, 248, 2201−2237. (d) Muniz, K. Angew. Chem., Int. Ed. 2005, 44,
6622−6627. (e) Ikariya, T.; Murata, K.; Noyori, R. Org. Biomol. Chem.
2006, 4, 393−406. (f) Ito, M.; Ikariya, T. Chem. Commun. 2007,
5134−5142.
(6) (a) Guo, R.; Morris, R. H.; Song, D. J. Am. Chem. Soc. 2005, 127,
516−517. (b) Ikariya, T.; Gridnev, I. D. Top. Catal. 2010, 53, 894−
2149
dx.doi.org/10.1021/om300108p | Organometallics 2012, 31, 2137−2151

Organometallics
Article
901. (c) Gridnev, I. D.; Watanabe, M.; Wang, H.; Ikariya, T. J. Am.
Chem. Soc. 2010, 132, 16637−16650.
(d) Ma, G. B.; McDonald, R.; Ferguson, M.; Cavell, R. G.; Patrick,
B. O.; James, B. R.; Hu, T. Q. Organometallics 2007, 26, 846−854.
(e) Lundgren, R. J.; Rankin, M. A.; McDonald, R.; Schatte, G.;
Stradiotto, M. Angew. Chem., Int. Ed. 2007, 46, 4732−4735. (f) Baratta,
W.; Ballico, M.; Esposito, G.; Rigo, P. Chem. Eur. J. 2008, 14, 5588−
5595. (g) Sandoval, C. A.; Shi, Q. X.; Liu, S. S.; Noyori, R. Chem. Asian
J. 2009, 4, 1221−1224. (h) Phillips, S. D.; Fuentes, J. A.; Clarke, M. L.
Chem. Eur. J. 2010, 16, 8002−8005. (i) Soni, R.; Cheung, F. K.;
Clarkson, G. C.; Martins, J. E. D.; Graham, M. A.; Wills, M. Org.
Biomol. Chem. 2011, 9, 3290−3294.
(19) (a) Casey, C. P.; Johnson, J. B.; Singer, S. W.; Cui, Q. J. Am.
Chem. Soc. 2005, 127, 3100−3109. (b) Heiden, Z. M.; Rauchfuss, T. B.
J. Am. Chem. Soc. 2009, 131, 3593−3600. (c) Casey, C. P.; Johnson,
J. B.; Jiao, X. D.; Beetner, S. E.; Singer, S. W. Chem. Commun. 2010,
46, 7915−7917.
(20) Guo, R.; Lough, A. J.; Morris, R. H.; Song, D. Organometallics
2004, 23, 5524−5529.
(21) Ito, M.; Hirakawa, M.; Osaku, A.; Ikariya, T. Organometallics
2003, 22, 4190−4192.
(22) Jia, W. L.; Chen, X. H.; Guo, R. W.; Sui-Seng, C.; Amoroso, D.;
Lough, A. J.; Abdur-Rashid, K. Dalton Trans. 2009, 8301−8307.
(23) (a) Saudan, L. A.; Saudan, C. M.; Debieux, C.; Wyss, P. Angew.
Chem., Int. Ed. 2007, 46, 7473−7476. (b) Clarke, M. L.; Diaz-
Valenzuela, M. B.; Slawin, A. M. Z. Organometallics 2007, 26, 16−19.
(c) Kuriyama, W.; Ino, Y.; Ogata, O.; Sayo, N.; Saito, T. Adv. Synth.
Catal. 2010, 352, 92−96.
(24) (a) Ito, M.; Sakaguchi, A.; Kobayashi, C.; Ikariya, T. J. Am.
Chem. Soc. 2007, 129, 290−291. (b) Ito, M.; Kobayashi, C.; Himizu,
A.; Ikariya, T. J. Am. Chem. Soc. 2010, 132, 11414−11415.
(25) (a) Lee, H. M.; Lee, C. C.; Cheng, P. Y. Curr. Org. Chem. 2007,
11, 1491−1524. (b) Hahn, F. E.; Jahnke, M. C. Angew. Chem., Int. Ed.
2008, 47, 3122−3172. (c) Diez-Gonzalez, S.; Marion, N.; Nolan, S. P.
Chem. Rev. 2009, 109, 3612−3676.
(26) (a) Normand, A. T.; Cavell, K. J. Eur. J. Inorg. Chem. 2008,
2781−2800. (b) Corberan, R.; Mas-Marza, E.; Peris, E. Eur. J. Inorg.
Chem. 2009, 1700−1716.
(27) Bonnet, L. G.; Douthwaite, R. E.; Hodgson, R.; Houghton, J.;
Kariuki, B. M.; Simonovic, S. Dalton Trans. 2004, 3528−3535.
(28) O, W. W. N.; Lough, A. J.; Morris, R. H. Organometallics 2009,
28, 6755−6761.
(29) O, W. W. N.; Lough, A. J.; Morris, R. H. Organometallics 2011,
30, 1236−1252.
(7) (a) Zhang, J.; Leitus, G.; Ben-David, Y.; Milstein, D. J. Am. Chem.
Soc. 2005, 127, 10840−10841. (b) Zweifel, T.; Naubron, J. V.;
Grutzmacher, H. Angew. Chem., Int. Ed. 2009, 48, 559−563.
(8) (a) Gunanathan, C.; Ben-David, Y.; Milstein, D. Science 2007,
317, 790−792. (b) Gnanaprakasam, B.; Milstein, D. J. Am. Chem. Soc.
2011, 133, 1682−1685.
(9) Milstein, D. Top. Catal. 2010, 53, 915−923.
(10) (a) Rosales, M. Coord. Chem. Rev. 2000, 196, 249−280.
(b) Maire, P.; Buttner, T.; Breher, F.; Le Floch, P.; Grutzmacher, H.
Angew. Chem., Int. Ed. 2005, 44, 6318−6323. (c) Friedrich, A.; Drees,
M.; auf der Gunne, J. S.; Schneider, S. J. Am. Chem. Soc. 2009, 131,
17552−17553. (d) Kass, M.; Friedrich, A.; Drees, M.; Schneider, S.
Angew. Chem., Int. Ed. 2009, 48, 905−907. (e) Picot, A.; Dyer, H.;
Buchard, A.; Auffrant, A.; Vendier, L.; Le Floch, P.; Sabo-Etienne, S.
Inorg. Chem. 2010, 49, 1310−1312. (f) Ohkuma, T.; Utsumi, N.;
Tsutsumi, K.; Murata, K.; Sandoval, C.; Noyori, R. J. Am. Chem. Soc.
2006, 128, 8724−8725. (g) Cheung, F. K.; Clarke, A. J.; Clarkson,
G. J.; Fox, D. J.; Graham, M. A.; Lin, C. X.; Criville, A. L.; Wills, M.
Dalton Trans. 2010, 39, 1395−1402. (h) Bertoli, M.; Choualeb, A.;
Gusev, D. G.; Lough, A. J.; Major, Q.; Moore, B. Dalton Trans. 2011,
40, 8941−8949.
(11) (a) Alonso, D. A.; Brandt, P.; Nordin, S. J. M.; Andersson, P. G.
J. Am. Chem. Soc. 1999, 121, 9580−9588. (b) Yamakawa, M.; Ito, H.;
Noyori, R. J. Am. Chem. Soc. 2000, 122, 1466−1478. (c) Petra, D. G. I.;
Reek, J. N. H.; Handgraaf, J. W.; Meijer, E. J.; Dierkes, P.; Kamer, P. C.
J.; Brussee, J.; Schoemaker, H. E.; van Leeuwen, P. Chem. Eur. J. 2000,
6, 2818−2829. (d) Handgraaf, J. W.; Reek, J. N. H.; Meijer, E. J.
Organometallics 2003, 22, 3150−3157. (e) Hedberg, C.; Kallstrom, K.;
Arvidsson, P. I.; Brandt, P.; Andersson, P. G. J. Am. Chem. Soc. 2005,
127, 15083−15090. (f) Di Tommaso, D.; French, S. A.; Catlow, C. R. A.
J. Mol. Struct. (THEOCHEM) 2007, 812, 39−49. (g) Handgraaf, J. W.;
Meijer, E. J. J. Am. Chem. Soc. 2007, 129, 3099−3103. (h) Chen, Y.;
Liu, S. B.; Lei, M. J. Phys. Chem. C 2008, 112, 13524−13527.
(i) Puchta, R.; Dahlenburg, L.; Clark, T. Chem. Eur. J. 2008, 14, 8898−
8903. (j) Chen, Y.; Tang, Y. H.; Lei, M. Dalton Trans. 2009, 2359−
2364. (k) Zimmer-De Iuliis, M.; Morris, R. H. J. Am. Chem. Soc. 2009,
131, 11263−11269. (l) Lei, M.; Zhang, W. C.; Chen, Y.; Tang, Y. H.
Organometallics 2010, 29, 543−548. (m) Li, H. X.; Lu, G.; Jiang, J. L.;
Huang, F.; Wang, Z. X. Organometallics 2011, 30, 2349−2363.
(12) (a) Sandoval, C. A.; Ohkuma, T.; Muniz, K.; Noyori, R. J. Am.
Chem. Soc. 2003, 125, 13490−13503. (b) Hamilton, R. J.; Leong,
C. G.; Bigam, G.; Miskolzie, M.; Bergens, S. H. J. Am. Chem. Soc. 2005,
127, 4152−4153. (c) Sandoval, C. A.; Ohkuma, T.; Utsumi, N.;
Tsutsumi, K.; Murata, K.; Noyori, R. Chem. Asian J. 2006, 1, 102−110.
(13) (a) Abdur-Rashid, K.; Clapham, S. E.; Hadzovic, A.; Harvey,
J. N.; Lough, A. J.; Morris, R. H. J. Am. Chem. Soc. 2002, 124, 15104−
15118. (b) Rautenstrauch, V.; Hoang-Cong, X.; Churlaud, R.; Abdur-
Rashid, K.; Morris, R. H. Chem. Eur. J. 2003, 9, 4954−4967. (c) Abbel,
R.; Abdur-Rashid, K.; Faatz, M.; Hadzovic, A.; Lough, A. J.; Morris, R.
H. J. Am. Chem. Soc. 2005, 127, 1870−1882.
(14) (a) Abdur-Rashid, K.; Faatz, M.; Lough, A. J.; Morris, R. H.
J. Am. Chem. Soc. 2001, 123, 7473−7474. (b) Abdur-Rashid, K.; Guo,
R. W.; Lough, A. J.; Morris, R. H.; Song, D. T. Adv. Synth. Catal. 2005,
347, 571−579.
(15) (a) Hamilton, R. J.; Bergens, S. H. J. Am. Chem. Soc. 2008, 130,
11979−11987. (b) Takebayashi, S.; Dabral, N.; Miskolzie, M.;
Bergens, S. H. J. Am. Chem. Soc. 2011, 133, 9666−9669.
(16) Bertoli, M.; Choualeb, A.; Lough, A. J.; Moore, B.; Spasyuk, D.;
Gusev, D. G. Organometallics 2011, 30, 3479−3482.
(17) (a) Clapham, S. E.; Morris, R. H. Organometallics 2005, 24,
479−481. (b) Hadzovic, A.; Song, D.; MacLaughlin, C. M.; Morris, R.
H. Organometallics 2007, 26, 5987−5999.
(18) (a) Standfest-Hauser, C.; Slugovc, C.; Mereiter, K.; Schmid, R.;
Kirchner, K.; Xiao, L.; Weissensteiner, W. Dalton Trans. 2001, 2989−
2995. (b) Ito, M.; Hirakawa, M.; Murata, K.; Ikariya, T. Organo-
metallics 2001, 20, 379−381. (c) Leong, C. G.; Akotsi, O. M.;
Ferguson, M. J.; Bergens, S. H. Chem. Commun. 2003, 750−751.
(30) (a) Arnold, P. L.; Mungur, S. A.; Blake, A. J.; Wilson, C. Angew.
Chem., Int. Ed. 2003, 42, 5981−5984. (b) Douthwaite, R. E.;
Houghton, J.; Kariuki, B. M. Chem. Commun. 2004, 698−699.
(c) Jong, H.; Patrick, B. O.; Fryzuk, M. D. Can. J. Chem. 2008, 86,
803−810. (d) Busetto, L.; Cassani, M. C.; Femoni, C.; Macchioni, A.;
Mazzoni, R.; Zuccaccia, D. J. Organomet. Chem. 2008, 693, 2579−
2591. (e) Wei, W.; Qin, Y.; Luo, M.; Xia, P.; Wong, M. S.
Organometallics 2008, 27, 2268−2272. (f) Arnold, P. L.; McMaster, J.;
Liddle, S. T. Chem. Commun. 2009, 818−820. (g) Dyson, G.; Frison,
J. C.; Whitwood, A. C.; Douthwaite, R. E. Dalton Trans. 2009, 7141−
7151. (h) Cross, W. B.; Daly, C. G.; Ackerman, R. L.; George, I. R.;
Singh, K. Dalton Trans. 2011, 40, 495−505. (i) Jong, H.; Patrick,
B. O.; Fryzuk, M. D. Organometallics 2011, 30, 2333−2341. (j) Cross,
W. B.; Daly, C. G.; Boutadla, Y.; Singh, K. Dalton Trans. 2011, 40,
9722−9730.
(31) O, W. W. N.; Lough, A. J.; Morris, R. H. Chem. Commun. 2010,
46, 8240−8242.
(32) (a) Chantler, V. L.; Chatwin, S. L.; Jazzar, R. F. R.; Mahon,
M. F.; Saker, O.; Whittlesey, M. K. Dalton Trans. 2008, 2603−2614.
(b) Lee, J. P.; Ke, Z. F.; Ramirez, M. A.; Gunnoe, T. B.; Cundari, T. R.;
Boyle, P. D.; Petersen, J. L. Organometallics 2009, 28, 1758−1775.
(c) Gandolfi, C.; Heckenroth, M.; Neels, A.; Laurenczy, G.; Albrecht,
M. Organometallics 2009, 28, 5112−5121. (d) Casbai, P.; Joo, F.
Organometallics 2004, 23, 5640−5643.
(33) O, W. W. N.; Lough, A. J.; Morris, R. H. Organometallics 2012,
DOI: 10.1021/om300071v.
2150
dx.doi.org/10.1021/om300108p | Organometallics 2012, 31, 2137−2151

Organometallics
Article
(34) (a) Ito, M.; Kitahara, S.; Ikariya, T. J. Am. Chem. Soc. 2005, 127,
6172−6173. (b) Ikariya, T.; Gridnev, I. D. Chem. Rec. 2009, 9, 106−
123.
(35) Bosson, J.; Poater, A.; Cavallo, L.; Nolan, S. P. J. Am. Chem. Soc.
2010, 132, 13146−13149.
́
(36) Martín-Matute, B.; Edin, M.; Bogar, K.; Kaynak, F. B.; Backvall,
̈
J.-E. J. Am. Chem. Soc. 2005, 127, 8817−8825.
(37) Warner, M. C.; Verho, O.; Backvall, J. E. J. Am. Chem. Soc. 2011,
̈
133, 2820−2823.
(38) Lynch, B. J.; Truhlar, D. G. J. Phys. Chem. A 2001, 105, 2936−
2941.
(39) Arita, S.; Koike, T.; Kayaki, Y.; Ikariya, T. Organometallics 2008,
27, 2795−2802.
(40) (a) Sortais, J. B.; Ritleng, V.; Voelklin, A.; Holuigue, A.; Smail,
H.; Barloy, L.; Sirlin, C.; Verzijl, G. K. M.; Boogers, J. A. F.; de Vries,
A. H. M.; de Vries, J. G.; Pfeffer, M. Org. Lett. 2005, 7, 1247−1250.
(b) Sortais, J. B.; Barloy, L.; Sirlin, C.; de Vries, A. H. M.; de Vries,
J. G.; Pfeffer, M. Pure Appl. Chem. 2006, 78, 457−462. (c) Pannetier,
N.; Sortais, J. B.; Dieng, P. S.; Barloy, L.; Sirlin, C.; Pfeffer, M.
Organometallics 2008, 27, 5852−5859.
(41) (a) Bosch, E.; Moreno, M.; Lluch, J. M.; Bertran, J. Chem. Phys.
Lett. 1989, 160, 543−548. (b) Koseki, S.; Gordon, M. S. J. Phys. Chem.
1989, 93, 118−125.
(42) Hamilton, R. J.; Bergens, S. H. J. Am. Chem. Soc. 2006, 128,
13700−13701.
(43) Ito, M. Pure Appl. Chem. 2008, 80, 1047−1053.
(44) Ito, M.; Ootsuka, T.; Watari, R.; Shiibashi, A.; Himizu, A.;
Ikariya, T. J. Am. Chem. Soc. 2011, 133, 4240−4242.
(45) Bassetti, M. Eur. J. Inorg. Chem. 2006, 4473−4482.
(46) (a) Abdur-Rashid, K.; Fong, T. P.; Greaves, B.; Gusev, D. G.;
Hinman, J. G.; Landau, S. E.; Lough, A. J.; Morris, R. H. J. Am. Chem.
Soc. 2000, 122, 9155−9171. (b) Belkova, N. V.; Epstein, L. M.;
Shubina, E. S. Eur. J. Inorg. Chem. 2010, 3555−3565.
(47) Chen, S. T.; Rousseau, R.; Raugei, S.; Dupuis, M.; DuBois,
D. L.; Bullock, R. M. Organometallics 2011, 30, 6108−6118 and
references therein.
(48) Doucet, H.; Ohkuma, T.; Murata, K.; Yokozawa, T.; Kozawa,
M.; Katayama, E.; England, A. F.; Ikariya, T.; Noyori, R. Angew. Chem.,
Int. Ed. 1998, 37, 1703−1707.
(49) Boren, B. C.; Narayan, S.; Rasmussen, L. K.; Zhang, L.; Zhao,
H. T.; Lin, Z. Y.; Jia, G. C.; Fokin, V. V. J. Am. Chem. Soc. 2008, 130,
8923−8930.
(50) Cahill, J. P.; Bohnen, F. M.; Goddard, R.; Kruger, C.; Guiry, P. J.
Tetrahedron: Asymmetry 1998, 9, 3831−3839.
(51) Frisch, M. J., et al. Gaussian 03, Revision C.02; Gaussian Inc.:
Wallingford, CT, 2004.
(52) Frisch, M. J., et al. Gaussian 09, Revision A.1; Gaussian Inc.:
Wallingford, CT, 2009.
(53) (a) Burke, K.; Perdew, J. P.; Wang, Y. Electronic Density
Functional Theory: Recent Progress and New Directions; Plenum: New
York, 1997. (b) Adamo, C.; Barone, V. J. Chem. Phys. 1998, 108, 664−
675.
(54) (a) Andrae, D.; Haussermann, U.; Dolg, M.; Stoll, H.; Preuss, H.
Theor. Chim. Acta 1990, 77, 123−141. (b) Leininger, T.; Nicklass, A.;
Stoll, H.; Dolg, M.; Schwerdtfeger, P. J. Chem. Phys. 1996, 105, 1052−
1059.
(55) (a) Clark, T.; Chandrasekhar, J.; Spitznagel, G. W.; Schleyer,
P. v. R. J. Comput. Chem. 1983, 4, 294−301. (b) Lynch, B. J.; Zhao, Y.;
Truhlar, D. G. J. Phys. Chem. A 2003, 107, 1384−1388.
(56) Frisch, M. J.; Pople, J. A.; Binkley, J. S. J. Chem. Phys. 1984, 80,
3265−3269.
2151
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