Comparative Study of Bifunctional Mononuclear and Dinuclear Amidoiridium Complexes with Chiral C?N Chelating Ligands for the Asymmetric Transfer Hydrogenation of Ketones

Article abstract of DOI:10.1002/asia.201600955

A series of new bifunctional C?N chelating Ir complexes possessing a metal/NH group was synthesized by cyclometalation of optically active primary benzylic amines such as O-silylated (S)-2-amino-2-phenylethanols (1 a and 1 a’), (R)-5-amino-6,7,8,9-tetrahydro-5H-benzocycloheptene (1 b), and (R)-1-phenyl-2,2-dimethylpropylamine (1 c). Although treatment of KOtBu with the amine complexes originating from 1 a and 1 a’ afforded amido-bridged dinuclear complexes (3 a and 3 a’), more sterically hindered complexes were solely transformed into the coordinatively unsaturated mononuclear amido complexes (3 b and 3 c), which can serve as real catalyst species in the asymmetric transfer hydrogenation. The structural difference in the C?N chelate framework markedly affected the catalytic performance. Among them, amido complex 3 c showed a pronounced ability to catalyze the transfer hydrogenation of acetophenone in 2-propanol, even at a low temperature of ?30 °C. A hydridoiridium complex (4 c) was also identified in the reaction of 3 c in 2-propanol, which provides mechanistic insights into the enantiodiscriminating step in the hydrogen transfer to prochiral ketones.

Full text of DOI:10.1002/asia.201600955

CHEMISTRY
AN ASIAN JOURNAL
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Accepted Article
Title: Comparative Study of Bifunctional Mononuclear and Dinuclear Amidoiridium
Complexes with Chiral C-N Chelating Ligands for the Asymmetric Transfer Hy-
drogenation of Ketones
Authors: Yasuhiro Sato; Yoshihito Kayaki; Takao Ikariya
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Chemistry - An Asian Journal
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Comparative Study of Bifunctional Mononuclear and Dinuclear
Amidoiridium Complexes with Chiral C–N Chelating Ligands for
the Asymmetric Transfer Hydrogenation of Ketones
[
a]
Yasuhiro Sato, Yoshihito Kayaki* and Takao Ikariya*
Abstract: A series of new bifunctional C–N chelating Ir complexes
possessing a metal/NH group was synthesized by cyclometalation of
optically active primary benzylic amines such as O-silylated (S)-2-
amino-2-phenylethanols (1a and 1a’), (R)-5-amino-6,7,8,9-
tetrahydro-5H-benzocycloheptene (1b), and (R)-1-phenyl-2,2-
to mononuclear amidoiridium and from hydrido(amine)iridium to
ketones is induced by the high basicity of the amido
[
4,6a]
complexes
hydrido ligand,
as well as by the enhanced nucleophilicity of the
[
6b]
that arises from the strong -donor nature of
the chelating carbon atom. Notably, these outstanding features
accommodate the dynamic kinetic resolution of racemic
t
dimethylpropylamine (1c). Although treatment of KO Bu with the
amine complexes originating from 1a and 1a’ afforded amido-
bridged dinuclear complexes (3a and 3a’), more sterically hindered
complexes were solely transformed into the coordinatively
unsaturated mononuclear amido complexes (3b and 3c), which can
serve as real catalyst species in asymmetric transfer hydrogenation.
The structural difference in the C–N chelate framework markedly
affected the catalytic performance. Among them, the amido complex
secondary
transesterification.
alcohols
by
combination
with
enzymatic
[
8]
NaOCOCH3
KOtBu
NH2
1
.1 equiv
1.1 equiv
1/2 [Cp*MCl2]2
+
R
M
M
R
R
R
R
R
CH3CN
N
Cl
CH2Cl2
rt
N
H
rt60 °C
H H
M = Ir, Rh
R = CH3, C6H5
M = Ir
3c
showed
a
pronounced ability to catalyze the transfer
R = CH3, C6H5
hydrogenation of acetophenone in 2-propanol, even at a low
temperature of –30 °C. A hydridoiridium complex (4c) was also
identified in the reaction of 3c in 2-propanol, which provides
mechanistic insights into the enantio-discriminating step in the
hydrogen transfer to prochiral ketones.
Scheme 1. Synthesis of C–N chelating complexes from achiral benzylic
amines.
Azametalacycles with a NH group are applicable to the
asymmetric transfer hydrogenation by introducing appropriate
[4,5a,9]
chirality into the C–N chelate frameworks.
Pfeffer and
Introduction
coworkers developed the related cationic C–N chelating Ru
complex that acted as a precatalyst for the asymmetric transfer
Group 8 and 9 metal complexes with multidentate protic amine
ligands have been utilized as efficient catalysts for hydrogen
transfer from alcohols and to carbonyl compounds. Since the
[9a,f]
hydrogenation of ketones and imines.
In a mechanistic study
2
6
of the Ru system, [Ru{(R)- (N,C)-1-(1-naphthyl)ethylamine}( -
benzene)(NCCH )](PF ), treatment of the catalyst precursor with
[
1]
3
6
discovery of well-defined Ru catalysts bearing N-
t
KO Bu in 2-propanol afforded a diastereomeric mixture of
[
2]
sulfonyldiamines (N–N chelates) two decades ago,
the
hydrido(amine) complexes with different configurations at the
metal/NH bifunctionality that allows the interconversion between
[9d]
ruthenium center.
The hydridoruthenium species presented
1
6e-amido and 18e-hydrido(amine) complexes has been widely
similar catalytic behavior to that of the precatalyst and generated
the corresponding mononuclear amidoruthenium species
accompanied with 1-phenylethanol in a stoichiometric reaction
+
–
credited as a powerful and versatile concept to facilitate H /H
delivery.
[
2,3]
The related C–N chelating Ir, Rh, and Ru complexes
derived from benzylic amines have also been successfully
synthesized (Scheme 1), and their marked catalytic abilities
with acetophenone. Although the coordinatively unsaturated
1
amido complex was observed in solution by
H NMR
[
4-9]
have been recognized.
We reported that the C–N chelating
spectroscopy, an attempt to isolate it from the reaction mixture of
complexes could offer a beneficial enhancement in the transfer
t
2 2
the precatalyst and KO Bu in CD Cl resulted in crystallization of
[
4]
hydrogenation of ketones using 2-propanol and in the aerobic
an amido-bridged dimer. For the relative chiral Rh and Ir
systems, the concomitant formation of catalytically less active
imine complexes via the dehydrogenation of benzylic amines
[
5]
oxidation of alcohols , compared to the original N–N chelating Ir
[
3]
and Rh complexes. The rapid hydrogen transfer from alcohols
[
9e]
during cyclometalation was reported.
Among these
derivatives, the 16e mononuclear chiral amido complexes have
not been synthesized; therefore, the catalytic asymmetric
hydrogen transfer requires a base additive such as KO Bu to
[
a]
Y. Sato, Prof. Dr. Y. Kayaki, and Prof. Dr. T. Ikariya
Department of Chemical Science and Engineering, School of
Materials and Chemical Technology
t
Tokyo Institute of Technology
generate
active
mononuclear
intermediates
of
the
2-12-1-E4-1 O-okayama, Meguro-ku, Tokyo 152-8552, Japan
hydrido(amine) and amido complexes from the precatalysts.
E-mail: ykayaki@o.cc.titech.ac.jp, tikariya@apc.titech.ac.jp
In this paper, we disclose the synthesis and characterization
of new azairidacycles from optically active benzylamine
derivatives possessing a chiral center at a position on the NH
Supporting information for this article can be found under
http://dx.doi.org/10.1002/asiaxxxxx.
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Chemistry - An Asian Journal
10.1002/asia.201600955
FULL PAPER
moiety and their deprotonation to isolate the amido complexes.
Based on the relative reactivity and stereoselectivity of the
isolated amido complexes in the hydrogen transfer from 2-
propanol, we also address the mechanistic aspects of the
asymmetric transfer hydrogenation of acetophenone to
understand how the chiral azairidacycles lead to asymmetric
induction.
was isolated as yellow crystals in 29% yield after
recrystallization from dichloromethane/diethyl ether (Scheme 3).
PF6
NH2
KPF6, 2 equiv
KOH, 1 equiv
1/2 [Cp*IrCl2]2
+
Ir
CH3CN
N
NCCH3
60 °C, 40 h
H H
1c
2c: 29% (recrystallized)
major : minor = 4 : 1
Results and Discussion
Scheme 3. Synthesis of the cationic azairidacycle 2c by cyclometalation of 1c.
Cyclometalation of Optically Active Benzylic Amines
The C–N chelating framework was prepared by selective ortho
[
10]
C–H activation of benzylamines.
Analogous to our previous
In contrast to the C–N chelating chloridoiridium complexes
2a, 2a’, and 2b, the H NMR spectrum of the cationic complex
1
report on the synthesis of an azairidacycle (2a) from TBDMS-
protected (S)-2-amino-2-phenylethanol (1a),
performed the cyclometalation of TIPS-protected (S)-2-amino-2-
phenylethanol (1a’) and (R)-5-amino-6,7,8,9-tetrahydro-5H-
[
4]
we newly
2c displayed broad signals at room temperature, as shown in
Figure 1. Lowering the temperature to –20 °C resulted in a peak
separation with a ratio of approximately 4:1. The dynamic
behavior is possibly due to the rapid stereochemical inversion at
the Ir center, as depicted in Scheme 4. The labile acetonitrile
[
11]
benzocycloheptene (1b)
Cp*IrCl (ligand:Ir = 1:1) with a slight excess of sodium acetate
in CH CN at 60 °C. After recrystallization, the corresponding C–
using a stoichiometric amount of
[
2 2
]
[7]
3
group in the cationic complex 2c readily dissociates in solution,
N chelating chlorido complexes (2a’, and 2b) were obtained as
allowing the interconversion between the diastereomers.
yellow crystals in 37% and 75% yields, respectively (Scheme 2).
1
The H NMR spectra of 2a, 2a’, and 2b in CDCl
3
display that the
signals due to the amine protons are shifted downfield compared
with those of the respective parent amines 1a, 1a’, and 1b. A
set of nonequivalent NH signals also indicates the chelating
2
structure of the amine ligand. Coordination of the chiral C–N
chelates led to the formation of diastereomers due to a central
chirality at the iridium center. The diastereomeric ratios were
1
determined to be 13:1 for 2a and 10:1 for 2a’ by H NMR
analysis at room temperature. Less than 4% of the minor
[
12]
diastereomer was observed for 2b.
NaOCOCH3
NH2
1
.1 equiv
OR
1/2 [Cp*IrCl2]2
+
Ir
RO
CH3CN
0 °C, 20 h
N
H H
Cl
6
1
a (R = TBDMS)
a' (R = TIPS)
2
a (R = TBDMS): 54% (recrystallized)
a' (R = TIPS): 37% (recrystallized)
1
2
1
Figure 1. H NMR spectra of 2c at –20 °C and room temperature.
NH2
NaOCOCH3
.1 equiv
1
PF6-
PF6-
1/2 [Cp*IrCl2]2
+
Ir
CH3CN
0 °C, 22 h
N
H H
Cl
6
Ir
Ir
NCCH3
NH2
CH3CN
H N
1b
2b: 75% (recrystallized)
2
Scheme 2. Synthesis of the azairidacycles 2a, 2a’, and 2b by cyclometalation
of 1a, 1a’, and 1b.
Scheme 4. Dynamic behavior of the cationic C–N chelating complex 2c.
Orthometalation of (R)-1-phenyl-2,2-dimethylpropylamine
(
1c) possessing a sterically demanding tert-butyl group did not
Synthesis of Amidoiridium Complexes via Deprotonation of
Amine Ligands
[
9a-c]
proceed with sodium acetate. Alternatively, Pfeffer’s method
proved to be feasible for the less reactive amine. Treatment of
c with a suspension of [Cp*IrCl , KOH, and excess KPF in
CH CN afforded the desired cationic azairidacycle (2c) which
Deprotonation of the precursor amine complexes was examined
for conversion into optically active amidoiridium complexes,
1
2
]
2
6
[
4]
3
according to the reported method.
As shown in Scheme 5,
t
addition of KO Bu to the C–N chelating chlorido complex 2a or
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Chemistry - An Asian Journal
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2a’ in dichloromethane turned the solution color from orange to
red at room temperature. The resulting amido complexes (3a
and 3a’) were isolated as orange crystals in 12% and 21% yield,
respectively, after purification by recrystallization from diethyl
ether at –20 °C.
OR
H
N
Ir
+
KOC(CH3)3
1-2 equiv
Ir
Ir
+ KCl + (CH3)3COH
RO
N
Cl
CH2Cl2
N
H
H
H
rt, overnight
2
2
a (R = TBDMS)
a' (R = TIPS)
RO
3a (R = TBDMS): 12% (recrystallized)
a' (R = TIPS): 21% (recrystallized)
3
2
Scheme 5. Synthesis of the dinuclear C–N chelating amido complexes 3a and
a’.
Figure 2. Molecular structure of [Cp*Ir{ (N,C)-(S)-(NHCH(CH OTIPS)-2-
2
3
C H )}] (3a’) with 50% probability ellipsoids. All hydrogens except those
6
4
2
attached to the chiral carbon and amine protons are omitted for clarity.
1
The H NMR spectra of the amido complexes 3a and 3a’ in
Cl exhibit a broad signal ascribed to the amido proton at
.89 and 2.77 ppm, respectively. These chemical shifts are
distinct from those of the mononuclear amidoiridium complexes,
OTBDMS
OTIPS
OTBDMS
CD
2
2
2
H
H
H
N
N
N
Ir
Ir
Ir
Ir
Ir
Ir
+
2
2
toluene-d8
Cp*Ir[κ (N,C)-(NHC(C
6
H
5
)
2
-2-C
6
H
4
)]
and
Cp*Ir[κ (N,C)-
N
H
N
H
N
H
[
4]
(
NHC(CH -2-C )] (8.00 and 8.47 ppm), possibly because
3
)
2
6 4
H
3
TBDMSO
TIPSO
3a'
TIPSO
not obserbed
the amido nitrogens in 3a and 3a’ are sp hybridized unlike the
mononuclear amido complexes. Single-crystal X-ray diffraction
of 3a’ possessing TIPS groups revealed that the amido ligand
3
a
Scheme 6. A crossover experiment using the amidoiridium dimers 3a and 3a’.
2 2
bridges to dimerize, as shown in Figure 2. The Ir N core adopts
a slightly distorted geometry, which is corroborated by a small
dihedral angle of 24.936° between the triangle of Ir1-Ir2-N1 and
the triangle of Ir1-Ir2-N2. The Cp* ligands arrange in a mutually
In contrast, treatment of the C–N chelating (R)-amine
complexes 2b and 2c with a stoichiometric amount of KO Bu in
t
cis orientation, and
a
pseudo C2 symmetric axis lies
dichloromethane caused an immediate color change from yellow
to purple, which implies formation of the corresponding
mononuclear amido complexes (3b and 3c) with a similar
structure as the previously reported achiral complexes (Scheme
perpendicular to the Ir
bonding interactions is confirmed by a Ir–Ir distance of 3.3079(5)
Å, which is longer than those of the reported amido-bridged Ir(I)
2
complexes, for example, 2.8146(3) Å and 2.9577(4) Å in [Ir( -
2
N
2
core. The absence of metal-metal
[
4]
1
[13]
7). In the H NMR spectra of 3b and 3c in CD
NH signals appeared in lower fields at 8.21 and 8.36 ppm,
respectively, compared to the NH signals of the parent
complexes (3.46 and 4.99 ppm for 2b; 3.90 and 4.36 ppm for
c). This downfield shift is characteristic of the protons attached
2 2
Cl , the amido
NH
amido/imido-bridged Ir(III) complex,
NTs)IrCp*][OTf] (Tf = SO CF ); and 2.584(1) Å in a bis(amido)-
[Cp*Ir{( -NH) -1,8}IrCp*]. The
2
)L
2
]
2
(L
2
= cod and (CO)
2
);
2.837 Å (mean value) in an
[
14]
[Cp*Ir(
2
2
-NHTs)( -
2
2
15]
3
[
bridged Ir(II) complex,
2
2 10 6
C H
2
Ir–N bond lengths (2.127 Å, mean value) of 3a’ are distinct from
2
to nitrogen atoms with sp hybridization in coordinatively
unsaturated amido complexes. As illustrated in Figure 3, X-ray
crystallographic analysis indicates that the amido complex
possesses a monomeric structure with a planar geometry
around the metal center. The amido complex 3c has a relatively
short Ir–N bond (1.902(4) Å) compared with that of a general C–
that of the reported monomeric amidoiridium complex,
2
[4]
Cp*Ir[ (N,C)-(NHC(C
closer to the Ir-sulfonylamido bonds in [Cp*Ir(
NTs)IrCp*][OTf] (Tf = SO CF
6
H
5
)
2
-2-C
6
H
4
)] (1.903(2) Å),
and are
-NHTs)(
) (2.114(6) and 2.131(6) Å) or to
the Ir-arylamido bonds in [Cp*Ir{( -NH) -1,8}IrCp*] (2.02-
2
2
-
2
3
2
2 10 6
C H
[
15]
2.11 Å).
[
4]
N chelating chloroiridium complex (2.119 and 2.137 Å).
The
To verify whether the dimeric amido complexes are
substituents vicinal to the coordinating nitrogen are crucial for
the structure of the amido complex. The monomeric (R)-amido
complexes 3b and 3c possess a sterically constrained
accessible to the mononuclear amido species in solution, we
performed crossover experiments using the isolated
1
homodimers. H NMR monitoring of a 1:1 mixture of the amido
framework that hampers dimerization, as observed for the
reported complexes derived from achiral tritylamine and
complexes 3a and 3a’ in toluene-d
process took place, even when increasing the temperature up to
00 °C (Scheme 6). It was also confirmed that the amido-
8
revealed that no scrambling
[
4]
cumylamine.
1
bridging structure was maintained in other polar solvents
including 2-propanol.
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Chemistry - An Asian Journal
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FULL PAPER
complexes 3b and 3c was maintained with an increase in the
enantioselectivity. As summarized in Table 1, 3a, 3b, and 3c
provided the (S)-product in good ee of 61–69% (entries 1-3).
Gratifyingly, 3c effectively catalyzed the asymmetric transfer
hydrogenation, even at –30 °C, and (S)-1-phenylethanol was
smoothly produced within 4 h with an improved ee of 81% (entry
Ir
+
KOC(CH3)3
1.2 equiv
Ir
+
KCl
3 3
+ (CH ) COH
N
H
2
Cl
CH2Cl2
rt, 11 h
N
H
H
Ir
b
3b: 88% yield
PF6
+
4).
KOC(CH3)3
1.6 equiv
Ir
N
+
KCl
3 3
+ (CH ) COH
N
NCCH3
CH Cl
2
2
H
H
H
rt, 17 h
2c
3c: 55% yield (recrystallized)
Scheme 7. Synthesis of the mononuclear amido complexes 3b and 3c.
Figure 4. Time course of the yield of (S)-1-phenylethanol in the transfer
hydrogenation of acetophenone catalyzed by 3a, 3b, and 3c with
a
substrate/catalyst (S/C) ratio of 200.
2
Figure 3. Molecular structure of Cp*Ir[ (N,C)-(R)-{NHCH(C(CH
3 3
) )-2-C
6
H
4
}]
(3c) with 50% probability ellipsoids. All hydrogens except those attached to the
chiral carbon and amine are omitted for clarity.
Catalytic Behavior of Amidoiridium Complexes
In order to compare the catalytic behavior of the isolated chiral
amidoiridium complexes, asymmetric transfer hydrogenation of
acetophenone (0.1 M) was carried out in 2-propanol using 3a,
3b, and 3c with a substrate/catalyst (S/C) ratio of 200 at 30 °C.
In all cases, (S)-1-phenylethanol was selectively formed, even in
the absence of additional base; however, the catalytic activity of
the dinuclear complex 3a was remarkably lower than that of the
mononuclear complexes 3b and 3c, as shown in Figure 4. The
mononuclear amido complexes 3b and 3c exhibited outstanding
performance, reaching almost complete conversion within 30
min, whereas the enantiomeric excess (ee) of the product
decreased with time (Figure 5). Following the trend that the
catalytic ability in the hydrogen transfer between ketones and
alcohols is inherently associated with the ease of product
Figure 5. Time course of the optical purity of (S)-1-phenylethanol in the
transfer hydrogenation of acetophenone catalyzed by 3a, 3b, and 3c with a
substrate/catalyst (S/C) ratio of 200.
[
8d]
racemization,
reduction.
3c exhibits superior activity over 3b for the
When the transfer hydrogenation was conducted at a
reduced catalyst concentration and the the S/C was increased
from 200 to 1,000, the striking activity of the monomeric amido
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Chemistry - An Asian Journal
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FULL PAPER
atmosphere at –20 °C for several months. Pale yellow crystals
Table 1. Asymmetric transfer hydrogenation of acetophenone in 2-propanol
catalyzed by 3a, 3b, and 3c with a substrate/catalyst (S/C) ratio of 1000.
of 4c were successfully obtained in 30% yield after
1
crystallization from diethyl ether at –20 °C. In the H NMR
Entry
Catalyst
t [h]
Yield [%]
Ee [%]
8
spectrum of 4c in THF-d at room temperature, a mixture of two
diastereomers was observed at a ratio of 24:1. Preliminary X-
ray crystallographic analysis of 4c revealed a three-legged
piano-stool structure of a single diastereomer possessing an S
configuration at the iridium center, as shown in Figure S2, but
further structural refinement was not possible due to the poor
crystal quality. The chiral metal center is slightly fluxional in
solution, as evident from the fact that the obtained crystals
epimerized to the diastereomeric mixture upon dissolution in
1
2
3
3a
3b
3c
3c
27.5
79
88
83
78
61
63
69
81
1
1
4
[
a]
4
[
a] This reaction was performed at –30 °C.
8
THF-d .
The crystallographic structure of the amido and hydrido
complexes, 3c and 4c, could be rationalized with the
enantiomeric outcome of the hydrogen transfer process. The
Dehydrogenation
Complexes
of
2-Propanol
by
Amidoiridium
The excellent hydrogen transfer ability of the mononuclear
amidoiridium complexes 3b and 3c was also confirmed by the
dehydrogenation of 2-propanol to furnish the corresponding
hydrido(amine) complexes (4b and 4c). In sharp contrast to the
bridging amido complex 3a being inert in 2-propanol at room
SIr-isomer of 4c was favorably generated because 2-propanol
approached to the amido complex 3c away from the spatially
+
-
congested tert-butyl group as depicted in Figure 6a. The H /H
transfer from 4c to the Re face of acetophenone resulted in the
formation of (S)-1-phenylethanol. From the extensive theoretical
6
temperature, the amido complex 3b, formed in-situ from 2b and
studies on the bifunctional Ru( -arene) catalysts bearing
t
KO Bu in CD
2
Cl
2
, was completely converted into 4b by the
Two sets of signals
aminoalcohol and N-sulfonyldiamine ligands, a C-H/ attraction
6
addition of excess of 2-propanol.
between the  -arene ligand and the phenyl ring of
corresponding to the diastereomers of 4b were confirmed by the
acetophenone in a six-membered pericyclic transition structure
1
[16]
H NMR spectrum, in which the Ir–H resonances appeared at –
was realized as the main origin of the enantioselectivity.
The
13.03 and –12.96 ppm with an integral ratio of 1:2.
enantioselection by 4c is also likely governed by a congeneric
5
[17]
C-H/ interaction involving the  -C
5
Me
5
ligand,
as shown in
OTBDMS
H
Figure 6b. The model can explain the preferential formation of
S)-alcohol via the unique Re face selection derived from the C-
(
N
H/ interaction, permitting a rather crowded transition state.
OH
Ir
Ir
+
no reaction
N
H
2-propanol
rt, 13 h
TBDMSO
3a
OH
O
Ir
+
Ir
+
N
H
CD2Cl2
N
H
H
rt
H
excess
3b
4b
1H NMR (CD2Cl2, rt)
-13.01, -12.92 ppm (each s, Ir-H) 1:2
Figure 6. Conceptual drawings based on the ORTEP structures of 3c and 4c:
OH
O
Ir
+
Ir
+
+
-
a) H /H delivery from 2-propanol to the amido complex 3c and b) subsequent
transfer from the hydrido complex (SIr)-4c to acetophenone to produce (S)-1-
phenylethanol.
N
H
2-propanol
rt, 11 h
N
H
H
H
3c
4c: 30% yield (recrystallized)
1H NMR (THF-d8, rt)
13.84, -13.14 ppm (each s, Ir-H) 24:1
-
Conclusions
Scheme 8. Attempts at the synthesis of the C–N chelating hydrido(amine)
complexes 4 from the C–N chelating amido complexes 3a, 3b, and 3c.
By changing the C–N chelating framework, mono- and dinuclear
amidoiridium complexes were specifically synthesized via
deprotonation of primary amine-Ir complexes derived from
optically active benzylamines possessing a chiral center at the
benzyl position. The coordinatively unsaturated amidoiridium
complexes 3b and 3c exhibited outstanding catalytic
Although attempts to isolate 4b were unsuccessful due to its
instability, the structurally well-defined (R)-amido complex 3c
could smoothly react in 2-propanol to yield the corresponding
hydrido complex (4c), which can be stored under an argon
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Chemistry - An Asian Journal
10.1002/asia.201600955
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performance in the asymmetric transfer hydrogenation of
acetophenone in 2-propanol to yield (S)-1-phenylethanol in good
enantioselectivities up to 81% ee, whereas the bis(amido)-
bridged diiridium complex 3a exhibited lower hydrogen transfer
ability. The catalytic utility of the mononuclear amido complex
was in accord with the facile and highly selective formation of
(m, 21H; OSi(CH(CH ) ) ), 1.96 (br, 2H; NH2), 3.61 (m, 1H;
3
2 3
OCH CHNH ), 3.81 (m, 1H; OCH CHNH ), 4.10 (m, 1H; OCH CHNH ),
2
2
2
2
2
2
13
1
7.23-7.39 (m, 4H; C H ); C{ H} NMR (100.5 MHz, CDCl , RT):  12.0
6
5
3
(
(
OSi(CH(CH
OCH CHNH
32NOSi [M+H]+: 294.2253. Found: 294.2247.
3
)
2
)
3
), 18.1 (OSi(CH(CH
3
)
2
)
3
), 58.0 (OCH
2
2
CHNH ), 69.9
2
2
), 127.0, 127.4, 128.4, 142.5 (C
6 5
H ). HRMS (ESI+) calcd
for C17
H
C
the hydrido complex (R , SIr)-4c from 3c in 2-propanol. The
enhanced enantioselectivity observed for 3c is attributable to the
effective collision between the tert-butyl group and the hydrogen
donor, 2-propanol, giving rise to highly diastereoselective
formation of hydridoiridium species, which should be strongly
contributed to the precise discrimination of the prochiral face of
the ketone substrate. Further studies on the intimate
stereochemical mechanism of this transfer hydrogenation are in
progress to develop a new series of chiral C–N chelating
ligands.
Synthesis of (R)-1-phenyl-2,2-dimethylpropylamine (1c): A mixture of
2
,2-dimethylpropiophenone (5.01 g, 30.9 mmol), (S)-1-phenylethylamine
-1
(7.51 g, 62.1 mmol), and trifluoroacetic acid (1.00×10 mL) was refluxed
in toluene (30 mL) for 14 h with azeotropic removal of water using a
Dean-Stark trap. The solvent and unreacted amine were removed under
reduced pressure, and toluene (20 mL) was added to the residue. The
resulting mixture was added dropwise to
a solution of sodium
borohydride (1.45 g, 38.4 mmol) in anhydrous ethanol (50 mL) at –20 °C.
After stirring at room temperature for 45 h, water was added to the
mixture and the solvents were evaporated to dryness. The residue was
extracted with diethyl ether, dried over sodium sulphate, and
concentrated under reduced pressure. The crude product was mixed
with Pd/C (0.62 g), acetic acid (6 mL), water (6 mL), and methanol (45
Experimental Section
General: All experiments were conducted under an argon atmosphere
using Schlenk techniques. All deuterated NMR solvents were dried and
degassed by appropriate methods. Solvents were purchased from Kanto
Chemical and Nacalai Tesque, and dried by refluxing over sodium
mL) and was then shaken at room temperature for 38
h under
atmospheric pressure of hydrogen. After filtration of the resulting mixture
through a plug of Celite, the solvents were removed under reduced
pressure, and the residue dissolved in chloroform. The organic phase
benzophenone
ketyl
(THF,
toluene,
diethyl
ether),
2 5
P O
3
was washed with an aqueous solution of NH and dried over sodium
(
dichloromethane, acetonitrile), or CaH
2
(hexane, pentane) and distilled
sulphate. After evaporation of the filtrate to dryness, the desired (R)-
amine 1c (3.76 g, 75% yield) was obtained as a pale yellow oil. The
[
18]
under argon.
[Cp*IrCl
2
]
2
,
(R)-5-amino-6,7,8,9-tetrahydro-5H-
[
11]
2
benzocycloheptene
NH CHCH OSi(CH
(1b),
and
Cp*IrCl[ (N,C)-(S)-
[19]
spectral data were in accord with those reported for the racemic 1c.
[
4]
(
2
2
3
)
2
(C(CH
3
)
3
)-2-C
6
H
4
)] (2a) were prepared according
25
D
[]
3
+48 (c 0.066, CHCl ), 96% ee (Chiralcel OD-H, 2-propanol/hexane
1
19
13
1
31
1
to the literature methods. H, F, C{ H}, and P{ H} NMR spectra
were recorded on JEOL JNM-LA300 and JNM-ECX400 spectrometers
and referenced to tetramethylsilane via the solvent resonance.
Elemental analyses were carried out using a PE2400 Series II CHNS/O
Analyzer (PerkinElmer). Analytical gas chromatography was performed
=
5/95; 30 ºC, 1 mL/min, detection at 254 nm; t
R
5.1 min (R form) and 8.6
1
min (S form)). H NMR (399.8 MHz, CDCl
3 3 3
, RT):  0.90 (s, 9H; C(CH ) ),
13
1
1.50 (br, 2H; NH
2 2 6 5
), 3.70 (s, 1H; CHNH ), 7.25-7.29 (m, 4H; C H ); C{ H}
NMR (100.5 MHz, CDCl
3
, RT):  26.6 (C(CH
3
)
3
), 35.1 (C(CH
3
)
3
), 65.4
(
CHNH
2 6 5
), 126.8, 127.6, 128.3, 143.9 (C H ).
with
a Shimadzu GC-17A gas chromatograph equipped with an
INNOWAX capillary column (30 m × 0.25 mm i.d.) purchased from
Agilent Technologies. Mass spectra (MS) were obtained with a JEOL
JMS-SX102A instrument. High performance liquid chromatography
2
Synthesis of Cp*IrCl[ (N,C)-(S)-(NH
2
CHCH
2
OSi(CH(CH
3
)
2
)
3
-2-C
6
H
4
)]
(
2a’): A mixture of [Cp*IrCl
2
]
2
(0.39 g, 0.49 mmol), (S)-2-triisopropylsiloxy-
1
-phenylethylamine (1a’) (0.28 g, 0.96 mmol), and NaOAc (85 mg, 1.0
(HPLC) analysis was performed using a system comprised of a JASCO
mmol) in CH
3
CN (20 mL) was stirred at 60 °C for 20 h. The solvent was
column oven: CO-1565, a low-pressure gradient unit: LG-1580-02, a
pump: PU-1580, a degasser: DG 1580-53, a UV/VIS detector: UV-1570,
and a CD detector: CD-2095. Analytical chiral HPLC was performed on a
Chiralcel OD column (4.6 mm × 25 cm) purchased from Daicel Chemical
Industries, Ltd. with hexane/2-propanol as the eluent where baseline
separation was obtained.
removed under reduced pressure. After the residue diluted with CH
2
Cl ,
2
the resulting mixture was filtered through a Celite pad. Evaporation of
the filtrate to dryness gave the iridacycle product 2a’. Orange crystals
were obtained by slow diffusion of hexane into the solution in toluene.
1
Yield: 37% (0.23 g, 0.36 mmol) as a 10:1 mixture of diastereomers.
NMR (399.8 MHz, CDCl
OSi(CH(CH ), 1.74 (s, 15H;
OSi), 3.73-3.76 (m, 1H; NH
OSi), 4.46, 4.75 (each br, 1H; NH
H
3
, RT, major diastereomer):  1.07-1.20 (m, 21H;
(CH ), 3.12-3.17 (dd, 1H;
CHCH OSi), 4.16-4.20 (m, 1H;
CHCH OSi), 6.79-7.50 (m,
, RT, major diastereomer): 
), 17.8, 18.1 (OSi(CH(CH ), 66.0
O), 86.8 (C (CH ), 120.6, 122.3,
). Anal. Calcd for C27 45ClIrNOSi: C,
3
)
2
)
3
C
5
3 5
)
Synthesis of (S)-2-triisopropylsiloxy-1-phenylethylamine (1a’): To a
solution of (S)-2-phenylglycinol (3.52 g, 25.7 mmol), triethylamine (3.12
g, 30.9 mmol), and 4-(dimethylamino)pyridine (0.323 g, 2.65 mmol) in
NH
2
CHCH
2
2
2
2
NH
2
CHCH
2
2
13
1
4
H; C
.4 (C
CHCH
27.7, 136.7, 147.4, 155.8 (C
H
6 4
); C{ H} NMR (100.5 MHz, CDCl
(CH ), 12.0 (OSi(CH(CH
OSi), 67.6 (NH CHCH
3
CH
After stirring for 3 days, the reaction mixture was diluted with water, and
extracted with CH Cl The combined organic layer was dried over
2 2
Cl (35 mL) was added triisopropylsilyl chloride (5.09 g, 26.4 mmol).
9
5
3
)
5
3
)
2
)
3
3 2 3
) )
(NH
2
2
2
2
5
3 5
)
2
2
.
1
4
6
H
4
H
sodium sulphate, filtered, and concentrated under reduced pressure.
The crude product was purified by flash chromatography (hexane/
9.48; H, 6.92; N, 2.14. Found: C, 49.66; H, 6.92; N, 2.31.
2
5
CH
2
Cl
2
), giving the amine 1a’ (0.456 g, 6% yield) as a colorless oil. []
D
2
Synthesis of Cp*IrCl[κ (N,C)-(R)-{NH
2
CH(CH
2
)
4 6 3
-2-C H }] (2b):
A
1
+
170 (c 0.045, CHCl
3
). H NMR (399.8 MHz, CDCl
3
, RT):  1.04-1.05
2 2
mixture of [Cp*IrCl ] (0.81 g, 1.0 mmol), (R)-5-amino-6,7,8,9-tetrahydro-
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Chemistry - An Asian Journal
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5
H-benzocycloheptene (1b) (0.33 g, 2.0 mmol), and NaOAc (0.17 g, 2.1
mmol) in CH CN (20 mL) was stirred at 60 °C for 22 h. The solvent was
removed under reduced pressure. After the residue diluted with CH Cl
for C48
H
76Ir
2
2 2
N O Si
2
: C, 49.97; H, 6.64; N, 2.43. Found: C, 49.93; H,
3
7.10; N, 2.61.
2
2
,
2
the resulting mixture was filtered through a Celite pad. Evaporation of the
Synthesis of [Cp*Ir{ (N,C)-(S)-(NHCHCH
2
OSi(CH(CH
3
)
2
)
3
-2-C
6
H
4
)}]
2
2
filtrate to dryness gave the iridacycle product 2b. Orange crystals were
(3a’): A mixture of Cp*IrCl[ (N,C)-(S)-(NH CHCH OSi(CH(CH ) ) -2-
2
2
3 2 3
obtained by slow diffusion of hexane into the solution in CH
5% (0.79 g, 1.5 mmol) as a >25:1 mixture of diastereomers. H NMR
399.8 MHz, CDCl , RT, major diastereomer):  1.19-1.29 (m, 1H;
), 1.49-2.03 (m, 5H; NH CH(CH ), 1.70 (s, 15H;
), 2,61-2.76 (m, 2H; NH CH(CH ), 4.50 (m, 1H;
), 3.46, 4.99 (each br, 1H; NH CH(CH ), 6.54-
); C{ H} NMR (100.5 MHz, CDCl , RT):
CH(CH ), 65.8
), 123.0, 127.1, 134.4, 135.6, 152.0,
29ClIrN: C, 48.21; H, 5.59; N, 2.68.
2
Cl
2
.
Yield:
C
6
H
4
)] (2a’) (0.21 g, 0.33 mmol) and KOC(CH
3 3
) (61 mg, 0.54 mmol) in
1
7
CH
2
Cl (5 mL) was stirred at room temperature for 11 h. The solvent was
2
(
3
removed under reduced pressure. After the residue was dissolved in
diethyl ether, insoluble material was removed by filtration. Evaporation of
the filtrate to dryness gave the product. Recrystallization from diethyl
NH
2
CH(CH
2
)
4
C
6
H
3
2
2 4 6 3
) C H
C
5
(CH
NH CH(CH
.32 (m, 3H; NH
9.4 (C (CH
CH(CH
53.3 (C
3
)
5
2
2 4 6 3
) C H
2
2
)
C
4 6
H
3
2
2
)
4
6
C H
3
ether at –20 °C afforded orange crystals. Yield: 21% (43 mg, 35 mol).
1
3
1
1
7
2
CH(CH
2
)
4
C
6
H
3
3
H
NMR (399.8 MHz, CD
2
Cl
2
,
RT):

1.04-1.08 (m, 42H;

5
3
)
5
), 27.6, 29.9, 36.5, 37.1 (NH
), 86.7 (C (CH
). Anal. Calcd for C21
2
2
)
4
6
C H
3
OSi(CH(CH ) ) ), 1.64 (s, 30H; C (CH ) ), 2.55 (m, 2H; NHCHCH ), 2.74
3
2
3
5
3
5
2
(NH
2
2
)
4
C
6
H
3
5
3
)
5
(br, 2H; NHCHCH
2
), 2.97, 3.81 (each m, 2H; NHCHCH
); C{ H} NMR (100.5 MHz, CD Cl
12.3 (OSi(CH(CH ), 18.0, 18.1 (OSi(CH(CH
7.0 (NHCHCH O), 85.2 (C (CH ), 119.4, 120.6, 124.3, 133.3, 155.7,
156.9 (C ). Anal. Calcd for C54 Si : C 52.39, H 7.17, N 2.26.
2
), 6.00-7.13 (m,
13
1
1
6
H
3
H
8H; C
H
6 4
2
2
5 3
, RT):  9.44 (C (CH )
5
),
Found: C, 48.28; H, 5.71; N, 2.71.
3
)
2
)
3
3
)
2
)
3
), 69.1 (NHCHCH
2
O),
7
2
5
3 5
)
2
Synthesis of [Cp*Ir{κ (N,C)-(R)-(NH
2
CHC(CH
3
)
3
-2-C
6
H
4
)}(CH
3
CN)]PF
6
H
6 4
H88Ir
N O
2 2 2
2
(
2c): Optically acitve (R)-amine 1c (0.68 g, 4.18 mmol) was added to a
suspension of [Cp*IrCl (1.57 g, 1.97 mmol), KOH (0.23 g, 4.11 mmol),
and KPF (1.53 g, 8.29 mmol) in CH CN (20 mL), and the resulting
Found: C 52.75, H 7.17, N 2.26.
2 2
]
2
6
3
Synthesis of Cp*Ir[κ (N,C)-(R)-{NHCH(CH
2
)
4
6 3
-2-C H }] (3b): A mixture
2
mixture was stirred at 60 °C under Ar atmosphere for 95 h. The solvent
was removed under reduced pressure. After the residue diluted with
of Cp*IrCl[κ (N,C)-(R)-{NH
2
CH(CH
2
)
4
-2-C
6
H
3
}] (2b) (0.45 g, 0.86 mmol)
and KOC(CH
3
)
3
(0.11 g, 1.0 mmol) in CH
2
Cl
2
(10 mL) was stirred at room
CH
2
Cl
2
, the resulting mixture was filtered through a Celite pad. The
temperature for 11 h. The solvent was removed under reduced pressure.
After the residue was dissolved in diethyl ether, insoluble material was
removed by filtration. Evaporation of the filtrate to dryness gave the
filtrate was evaporated under reduced pressure. The residue was
washed with hexane and diethyl ether and dried under vacuum.
Recrystallization from CH
2
Cl
2
and diethyl ether afforded yellow crystals in
product 3b. Recrystallization from diethyl ether at –20 °C afforded purple
1
1
29% yield (0.77 g, 1.1 mmol) as a 4:1 mixture of diastereomers. H NMR
crystals in 88% yield (0.37 g, 0.76 mmol). H NMR (399.8 MHz, CD
2
Cl
2
,
(
399.8 MHz, CDCl
3
,
–20 °C, major diastereomer):
), 1.72 (s, 15H; C (CH ), 2.42 (s, 3H; CH CN), 3.41-3.44 (m,
CH), 3.87-3.93, 4.34-4.36 (each br, 1H; NH ), 6.99-7.48 (m, 4H;
, –20 °C, minor diastereomer):  1.00
(CH ), 2.30 (br, 3H; CH CN), 3.97-
), 6.91-7.48
–20 °C, major
), 27.1 (C(CH ), 35.2
), 117.8 (CH CN), 123.3, 124.5,
). Anal. Calcd for C23 PF : C,

1.23 (s, 9H;
5 3 5 2 4 6 3
RT):  1.93 (s, 15H; C (CH ) ), 0.81-2.76 (m, 9H; NHCH(CH ) C H ),
C(CH
3
)
3
5
3
)
5
3
6.54-7.88 (m, 3H; NHCH(CH ) C H ), 8.19 (br, 1H; NHCH(CH ) C H );
2
4
6
3
2
4
6
3
13
1
1
H; NH
2
2
C{ H} NMR (100.5 MHz, CD
2
Cl
2 5 3 5
, RT):  10.0 (C (CH ) ), 28.2, 31.2,
1
C
H
6 4
); H NMR (399.8 MHz, CDCl
), 1.76 (s, 15H; C
.98 (m, 1H; NH
3
33.9, 37.6 (NHCH(CH ) C H ), 82.4
2 4 6 3
(NHCH(CH ) C H ), 87.0
2
4
6
3
(s, 9H; C(CH
3
)
3
5
3
)
5
3
5 3
(C (CH )
5 6 3
), 123.2, 124.8, 134.5, 136.0, 159.0, 163.6 (C H ). Anal. Calcd
3
2
CH), 3.79-3.82, 5.21-5.26 (each br, 1H; NH
2
for C21H28IrN: C, 51.83, H 5.80, N 2.88. Found: C 51.43, H 5.96, N 2.87.
13
1
(
m, 4H;
diastereomer):  4.3 (CH
C(CH ), 76.4 (CHNH ), 89.3 (C
27.5, 137.0, 146.6, 152.7 (C
C
6
H
4
); C{ H} NMR (399.8 MHz, CDCl
CN), 9.2 (C (CH
(CH
3
,
2
3
5
3
)
5
3
)
3
Synthesis of Cp*Ir[κ (N,C)-(R)-(NHCHC(CH ) -2-C H )] (3c): A mixture
3
3
6
4
2
(
3
)
3
2
5
3
)
5
3
2 3 3 6 4 3 6
of [Cp*Ir{κ (N,C)-(R)-(NH CHC(CH ) -2-C H )}(CH CN)]PF (2c) (0.21 g,
1
4
6
H
4
H34IrN
2
6
2 2
0.32 mmol) and KOC(CH3)3 (56 mg, 0.50 mmol) in CH Cl (15 mL) was
0.88; H, 5.07; N, 4.15. Found: C, 40.67; H, 5.06; N, 4.02.
stirred at room temperature for overnight. The solvent was removed
under reduced pressure. After the residue was dissolved in diethyl ether,
insoluble material was removed by filtration. Evaporation of the filtrate to
2
Synthesis
)}]
CHCH
KOC(CH
of
[Cp*Ir{κ (N,C)-(S)-(NHCHCH
2
OSi(CH
Cp*IrCl[ (N,C)-(S)-
)] (2a) (0.34 g, 0.55 mmol) and
Cl (5 mL) was stirred at room
3 2 3 3
) (C(CH ) )-2-
2
C
H
6 4
2
(3a):
A
mixture
)-2-C
of
dryness gave the product.
Dark red crystals suitable for X-ray
(NH
2
2
OSi(CH
3
)
2
(C(CH
3
)
3
6
H
4
crystallography were obtained by cooling the ethereal solution at –20 °C
1
3
)
3
(75 mg, 0.67 mmol) in CH
2
2
in 55% yield (85 mg, 0.17 mmol). H NMR (399.8 MHz, CD
2
Cl
2
, RT): 
3
temperature for 11 h. The solvent was removed under reduced pressure.
After the residue was dissolved in diethyl ether, insoluble material was
removed by filtration. Evaporation of the filtrate to dryness gave the
product 3a. Recrystallization from diethyl ether at –20 °C afforded
0.80 (s, 9H; C(CH
NHCH) , 6.74-8.04 (m, 4H; C
MHz, CD Cl , RT):  10.0 (C
86.7 (NHCH), 88.6 (C (CH ) ), 121.2, 122.0, 124.4, 136.1, 157.1, 166.2
3
)
3
), 1.93 (s, 15H; C
5 3
(CH )
5
), 2.36 (d, JHH = 3.1 Hz, 1H;
13
1
H
6 4
), 8.36 (br, 1H; NH); C{ H} NMR (100.5
2
2
5
(CH ), 27.1 (C(CH ), 32.4 (C(CH ),
3
)
5
3
)
3
3 3
)
5
3 5
1
orange crystals. Yield: 12% (37 mg, 32 mol). H NMR (399.8 MHz,
6 4
(C H ). Anal. Calcd for C21H30IrN: C 51.61, H 6.19, N 2.87. Found: C
CD
OSi(CH
.86 (br, 2H; NHCHCH
2
Cl
2
, RT):  0.03, 0.04 (each s, 6H; OSi(CH
C(CH ), 1.63 (s, 30H; C (CH ), 2.44 (m, 2H; NHCHCH
), 2.89, 3.74 (each m, 2H; NHCHCH ), 6.02-7.12
); C{ H} NMR (100.5 MHz, CD Cl , RT):  -5.4, -5.1
), 18.6 (OSi(CH C(CH ), 26.0
CHCH O), 76.4 (NH CHCH O), 85.3
). Anal. Calcd
3
)
2
C(CH
3
)
3
), 0.90 (s, 18H;
51.51, H 6.14, N 3.00.
3
)
2
3
)
3
5
3
)
5
2
),
2
2
2
2
Synthesis
of
Cp*IrH[κ (N,C)-(R)-(NH CHC(CH ) -2-C H )]
(4c):
2
3
3
6
4
1
3
1
2
(
(
(
(
m, 8H; C
6
H
4
2
2
Cp*Ir[κ (N,C)-(R)-(NHCHC(CH ) )] (3c) (56 mg, 0.12 mmol) dissolved in
3
3
OSi(CH
3
)
)
2
C(CH
3
)
)
3
), 9.4 (C
5
(CH
)
3 5
3
)
2
3
)
3
2-propanol (3 mL) was stirred at room temperature for 12 h. The solvent
was removed under reduced pressure. The residue was washed with
pentane and dried under reduced pressure. Pale yellow crystals suitable
OSi(CH
3
2
C(CH
3
3
), 68.9 (NH
2
2
2
2
C (CH
5
3
)
5
), 119.4, 120.5, 124.3, 133.6, 155.7, 157.0 (C
6
H
4
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Chemistry - An Asian Journal
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FULL PAPER
for X-ray crystallography were obtained by cooling the solution in diethyl
This work was financially supported by JSPS KAKENHI Grant
Numbers 24350079 and 26621043 and in part by a grant for
Basic Science Research Projects from The Sumitomo
Foundation.
ether at –20 °C. Yield 30% (17 mg, 35 mol) as a 24:1 mixture of
1
diastereomers. H NMR (399.8 MHz, THF-d
8
, RT, major diastereomer): 
CHC(CH ), 1.85 (s, 15H;
CHC(CH ), 5.68 (br, 1H;
), 6.49-7.30 (m, 4H; NH CHC(CH ). Anal.
32IrN: C 51.40, H 6.57, N 2.85. Found: C 51.52, H 6.48, N
–
13.84 (s, 1H; IrH), 0.92 (s, 9H; NH
(CH ), 3.35 (br, 2H; NH
NH2CHC(CH
Calcd for C21
.96.
2
3 3 6 4
) C H
C
5
3
)
5
2
3 3 6 4
) C H
3
)
3
C
H
6 4
2
3
)
C H
3 6 4
Keywords: asymmetric catalysis • cooperative effects •
H
hydrogen transfer • iridium • ketones
2
NMR Monitoring of a Mixture of 3a and 3a’: An NMR tube equipped
with a J-Young valve was charged with 3a (4.3 mg, 3.7 mol) and 3a’
[1]
a) K. Muñiz, Angew. Chem. 2005, 117, 6780-6785; Angew. Chem. Int.
Ed. 2005, 44, 6622-6627; b) T. Ikariya, A. J. Blacker, Acc. Chem. Res.
2007, 40, 1300-1308; c) T. Ikariya, Bull. Chem. Soc. Jpn. 2011, 84, 1-
(
4.7 mg, 3.8 mol) in 0.5 mL of toluene-d
8
at room temperature. The
1
reaction mixture was analyzed by H NMR spectra after heating at 60
and 100 °C.
16; d) B. Zhao, Z. Han, K. Ding, Angew. Chem. 2013, 125, 4844-4889;
Angew. Chem. Int. Ed. 2013, 52, 4744-4788; e) A. Bartoszewicz, N.
Ahlsten, B. Martín-Matute, Chem. Eur. J. 2013, 19, 7274-7302; f) D.
Wang, D. Astruc, Chem. Rev. 2015, 115, 6621-6686; g) F. Foubelo, C.
Nájera, M. Yus, Tetrahedron: Asymmetry 2015, 26, 769-790.
General Procedure of Transfer Hydrogenation of Acetophenone in 2-
Propanol Catalyzed by Amidoiridium Complexes: A 100-mL Schlenk
flask was charged with an appropriate amount of the iridium catalyst (3a,
[2]
a) S. Hashiguchi, A. Fujii, J. Takehara, T. Ikariya, R. Noyori, J. Am.
Chem. Soc. 1995, 117, 7562-7563; b) A. Fujii, S. Hashiguchi, N.
Uematsu, T. Ikariya, R. Noyori, J. Am. Chem. Soc. 1996, 118, 2521-
3
b, and 3c), durene (0.11 g, 0.83 mmol; an internal standard) and 2-
propanol (100 mL) under Ar atmosphere. After addition of acetophenone
1.2 g, 10 mmol), the reaction mixture was stirred at 30 °C for an
2522; c) N. Uematsu, A. Fujii, S. Hashiguchi, T. Ikariya, R. Noyori, J.
(
Am. Chem. Soc. 1996, 118, 4916-4917; d) K.-J. Haack, S. Hashiguchi,
A. Fujii, T. Ikariya, R. Noyori, Angew. Chem. 1997, 109, 297-300;
Angew. Chem. Int. Ed. Engl. 1997, 36, 285-288; e) S. Hashiguchi, A.
Fujii, K.-J. Haack, K. Matsumura, T. Ikariya, R. Noyori, Angew. Chem.
1997, 109, 300-303; Angew. Chem. Int. Ed. Engl. 1997, 36, 288-290.
a) K. Mashima, T. Abe, K. Tani, Chem. Lett. 1998, 27, 1119-1200; b) K.
Mashima, T. Abe, K. Tani, Chem. Lett. 1998, 27, 1201-1202; c) K.
Murata, T. Ikariya, J. Org. Chem. 1999, 64, 2186-2187.
appropriate period. The yield of (S)-1-phenylethanol was determined by
GC analysis and the optical purity was determined by HPLC analysis
(Chiralcel OD, 2-propanol/hexane = 5/95; 30 ºC, 0.5 mL/min, detection at
2
54 nm; t 8.0 min (R isomer) and 9.0 min (S isomer)).
R
[
3]
X-ray Structure Determination of 3a’, 3b, 3c, and 4c: X-ray diffraction
studies were conducted using a Rigaku Saturn 70 CCD area detector
equipped with graphite-monochromated Mo-K radiation ( = 0.71070 Å)
under a nitrogen stream at 193 K. Indexing was performed from seven
images. The crystal-to-detector distance was 45.05 mm. Data were
collected to a maximum 2 value of 55.0°. A total of 720 oscillation
images were collected. A sweep of the data was carried out by using 
scans from –110.0 to 70.0˚ in 0.5˚ steps at  = 45.0˚ and  = 0.0˚. A
second sweep was performed by using  scans from –110.0 to 70.0˚ in
[
4]
5]
S. Arita, T. Koike, Y. Kayaki, T. Ikariya, Organometallics 2008, 27, 2795-
2802.
[
a) S. Arita, T. Koike, Y. Kayaki, T. Ikariya, Angew. Chem. 2008, 120,
2481-2483; Angew. Chem. Int. Ed. 2008, 47, 2447-2449; b) S. Arita, T.
Koike, Y. Kayaki, T. Ikariya, Chem. Asian J. 2008, 3, 1479-1485.
[
6]
a) A. Ueno, Y. Kayaki, T. Ikariya, Organometallics 2014, 33, 4479-4485.
b) A. Matsunami, S. Kuwata, Y. Kayaki, ACS Catal. 2016, 6, 5181-5185.
Y. Sato, Y. Kayaki, T. Ikariya, Organometallics 2016, 35, 1257-1264.
a) R. M. Haak, F. Berthiol, T. Jerphagnon, A. J. A. Gayet, C. Tarabiono,
C. P. Postema, V. Ritleng, M. Pfeffer, D. B. Janssen, A. J. Minnaard, B.
L. Feringa, J. G. de Vries, J. Am. Chem. Soc. 2008, 130, 13508-13509;
b) T. Jerphagnon, A. J. A. Gayet, F. Berthiol, V. Ritleng, N. Mršić, A.
Meetsma, M. Pfeffer, A. J. Minnaard, B. L. Feringa, J. G. de Vries,
Chem. Eur. J. 2009, 15, 12780-12790; c) T. Jerphagnon, R. Haak, F.
Berthiol, A. J. A. Gayet, V. Ritleng, A. Holuigue, N. Pannetier, M. Pfeffer,
A. Voelklin, L. Lefort, G. Verzijl, C. Tarabiono, D. B. Janssen, A. J.
Minnaard, B. L. Feringa, J. G. de Vries, Top. Catal. 2010, 53, 1002-
[
7]
8]
[
0.5° steps at  = 45.0˚ and  = 90.0°. Intensity data were collected for
the Lorentz-polarization effects as well as for the absorption. Structure
solution and refinement were performed using the CrystalStructure
program package. The heavy-atom positions were determined by a
direct-program method (SIR2002), and the remaining non-hydrogen
atoms were determined by the subsequent use of Fourier techniques
(DIRDIF99). An empirical absorption correction based on equivalent
reflections was applied to all data. All non-hydrogen atoms were refined
1008; d) Y. Sato, Y. Kayaki, T. Ikariya, Chem. Commun. 2012, 48, 3635-
2
anisotropically by full-matrix least-squared techniques based on F . The
3637.
low-temperature data collection enabled a hydrogen attached to the
iridium center in 4c to be located from the Fourier difference map and
refined isotropically. All other hydrogen atoms were constrained to be
attached to their parent atom. The relevant crystallographic data are
compiled in Table S1. CCDC 1487515 (3a’), CCDC 1487554 (3b),
CCDC 1487552 (3c), and CCDC 1487553 (4c) contain the
supplementary crystalographic data for this paper. These data are
provided free of charge by The Cambridge Crystallographic Data Centre.
[9]
a) J.-B. Sortais, V. Ritleng, A. Voelklin, A. Holuigue, H. Smail, L. Barloy,
C. Sirlin, G. K. M. Verzijl, J. A. F. Boogers, A. H. M. de Vries, J. G. de
Vries, M. Pfeffer, Org. Lett. 2005, 7, 1247-1250; b) J.-B. Sortais, N.
Pannetier, A. Holuigue, L. Barloy, C. Sirlin, M. Pfeffer, N. Kyritsakas,
Organometallics 2007, 26, 1856-1868; c) J.-B. Sortais, N. Pannetier, N.
Clément, L. Barloy, C. Sirlin, M. Pfeffer, N. Kyritsakas, Organometallics
2007, 26, 1868-1874; d) N. Pannetier, J.-B. Sortais, P. S. Dieng, L.
Barloy, C. Sirlin, M. Pfeffer, Organometallics 2008, 27, 5852-5859; e) L.
Barloy, J.-T. Issenhuth, M. G. Weaver, N. Pannetier, C. Sirlin, M. Pfeffer,
Organometallics 2011, 30, 1168-1174; f) N. Pannetier, J.-B. Sortais, J.-
T. Issenhuth, L. Barloy, C. Sirlin, A. Holiigue, L. Lefort, L. Panella, J. G.
de Vries, M. Pfeffer, Adv. Synth. Catal. 2011, 353, 2844-2852; g) E.
Féghali, L. Barloy, J.-T. Issenhuth, L. Karmazin-Brelot, C. Bailly, M.
Acknowledgements
For internal use, please do not delete. Submitted_Manuscript

Chemistry - An Asian Journal
10.1002/asia.201600955
FULL PAPER
Pfeffer, Organometallics 2013, 32, 6186-6194; h) S. Sabater, M. Baya,
J. A. Mata, Organometallics 2014, 33, 6830-6839.
C. A. Sandoval, T. Ohkuma, N. Utsumi, K. Tsutsumi, K. Murata, R.
Noyori, Chem. Asian. J. 2006, 1, 102-110; d) J. Václavík, M. Kuzma, J.
Přech, P. Kačer, Organometallics 2011, 30, 4822-4829; e) P. A. Dub, T.
Ikariya, J. Am. Chem. Soc. 2013, 135, 2604-2619; f) A. Matsuoka, C. A.
Sandoval, M. Uchiyama, R. Noyori, H. Naka, Chem. Asian. J. 2015, 10,
112-115; g) P. A. Dub, J. C. Gordon, Dalton Trans. 2016, 45, 6756-
6781.
[
10] Y.-F. Han, G.-X. Jin, Chem. Soc. Rev. 2014, 43, 2799-2823.
11] A. L. Gutman, M. Etinger, G. Nisnevich, F. Polyak, Tetrahedron:
Asymmetry 1998, 9, 4369-4379.
[
[
[
[
[
[
12] The relative ratio could not be precisely determined for 2b owing to
overlapping NMR signals.
13] I. Mena, E. A. Jaseer, M. A. Casado, P. García-Orduña, F. J. Lahoz, L.
A. Oro, Chem. Eur. J. 2013, 19, 5665-5675.
[17] a) M. Nordin, R.-Z. Liao, K. Ahlford, H. Adolfsson, F. Himo,
ChemCatChem 2012, 4, 1095-1104; b) D. Madrigal, A. L. Cooksy, R.
Somanathan, Comput. Theor. Chem. 2012, 999, 105-108.
[18] J. W. Kang, K. Moseley, P. M. Maitlis, J. Am. Chem. Soc. 1969, 91,
5970-5977.
14] K. Ishiwata, S. Kuwata, T. Ikariya, Organometallics 2006, 25, 5847-
5849.
15] H. Matsuzaka, K. Ariga, H. Kase, T. Kamura, M. Kondo, S. Kitagawa, M.
Yamazaki, Organometallics 1997, 16, 4514-4516.
[19] D. R. J. Hose, M. F. Mahon, K. C. Molloy, T. Raynham, M. Wills, J.
Chem. Soc., Perkin Trans. 1 1996, 691-703.
16] a) M. Yamakawa, I. Yamada, R. Noyori, Angew. Chem. 2001, 113,
2900-2903; Angew. Chem. Int. Ed. 2001, 40, 2818-2821; b) R. Noyori,
M. Yamakawa, S. Hashiguchi, J. Org. Chem. 2001, 66, 7931-7944; c)
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Entry for the Table of Contents (Please choose one layout)
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Yasuhiro Sato, Yoshihito Kayaki* and
Takao Ikariya*
Page No. – Page No.
Comparative Study of Bifunctional
Mononuclear and Dinuclear
Amidoiridium Complexes with Chiral
C–N Chelating Ligands for the
Asymmetric Transfer Hydrogenation
of Ketones
Hunting the Actual Catalyst: Mono- and di-nuclear chiral amidoiridium complexes
were specifically synthesized by changing the substituents on the C–N chelating
ligand. The isolated mononuclear amido complex based on (R)-1-phenyl-2,2-
dimethylpropylamine was easily accessible to the hydrido(amine) complex in 2-
propanol with excellent diastereoselectivity and served as an efficient catalyst for
the asymmetric transfer hydrogenation of acetophenone.
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