Highly enantioselective imine hydrogenation catalyzed by ruthenium phosphane-phosphite diamine complexes

Article abstract of DOI:10.1002/chem.201203193

Mildly does it: A highly enantioselective catalyst for the hydrogenation of N-aryl imines is described (see scheme). This catalyst offers practical advantages because it operates under very mild conditions and is based on an Ru complex with a diamine as t

Full text of DOI:10.1002/chem.201203193

DOI: 10.1002/chem.201203193
Highly Enantioselective Imine Hydrogenation Catalyzed by Ruthenium
Phosphane–Phosphite Diamine Complexes
Mꢀnica Vaquero, Andrꢁs Suꢂrez, Sergio Vargas, Giovanni Bottari,
Eleuterio ꢃlvarez, and Antonio Pizzano*[a]
Dedicated to Professor Josꢀ Gimeno on the occasion of his 65th birthday
À
À
The
exceedingly
high
performance
of
A remarkable feature of [RuX2ACTHNGUTRENNU(G P P)ACHTUNGTREN(NUNG N N)] complexes is
[RuCl2(diphosphane)
A
the presence of four tunable, coordinating P and N groups,
which offer rather unlimited possibilities for catalyst optimi-
zation. Among the possible combinations, and particularly
appealing for practical reasons, are those based on only one
chiral ligand.[15] Moreover, most of the catalytic applications
described with these Ru complexes have been performed
with C2-symmetric diphosphane and diamine ligands. How-
ric hydrogenation of ketones[1] has led to a great interest in
the reactivity of RuII complexes based on phosphorus and
amino ligands. Thus, a wide diversity of structurally related
À
À
À
chiral complexes (e.g., [RuX2ACHTUGNTRENN(NGU P P)ACHTUNTRGEG(NNUN N N)], [RuX2(P)2ACHTNGUTRENN(UNG N
N)], [RuX
À
(P N)2]; X=anionic ligand) has been descri-
bed.[2] Most notably, these compounds have displayed a rich
reactivity, providing active catalysts for the hydrogenation
of different types of substrates.[3–5] In addition, applications
of these complexes in catalytic transfer hydrogenation,[6] cy-
cloaddition,[7] conjugate addition,[8] or hydrocyanation reac-
tions[9] have also been reported.
À
ever, the use of unsymmetric bidentate N N’ ligands
(Figure 1) has produced remarkable achievements in ketone
Due to the industrial importance of chiral amines, an in-
teresting application of the aforementioned Ru complexes is
the asymmetric catalytic hydrogenation of imines.[10] Be-
cause the best enantioselectivities for these substrates are
normally achieved with Ir catalysts,[11] a general goal in this
area is the development of catalysts based on less costly
metals.[12] In this regard, the group of Morris has reported
that several Ru hydrides give active catalysts for imine hy-
drogenation reactions, and BINAP complexes with DPEN
(1,2-diphenylethylenediACTHNURTGNEUaGN mine) or DACH (1,2-diaminocyclo-
hexane) diamines gave moderate enantioselectivities.[5]
Moreover, Cobley and co-workers, by following a systematic
optimization of both the diamine and diphosphane ligands,
found a highly enantioselective catalyst, based on Et-
DuPHOS and DACH, for the hydrogenation of N-(1-phe-
nylethylidene)aniline.[13] Very recently, Ohkuma et al. descri-
bed a highly efficient catalyst based on Xyl-skewphos and
DPEN ligands for the hydrogenation of a wide range of
imines.[14]
À
À
Figure 1. Some C1 symmetric N N’ and P P’ ligands.
hydrogenation.[16] In contrast, the application of phosphorus
ligands with two different P coordinating fragments (P P’)
is practically unexplored and is limited, to the best of our
knowledge, to the diastereoselective formation of a highly
active transfer hydrogenation catalyst based on a Josiphos
diphosphane, as reported by Baratta et al.[6c] In this contri-
À
À
bution we focus on the study of Ru derivatives based on P
P’ ligands. Thus, a practical and highly enantioselective cata-
lyst, based on an achiral phosphane–phosphite and DPEN,
for the catalytic hydrogenation of N-aryl imines is descri-
bed.
[a] M. Vaquero, Dr. A. Suꢀrez, Dr. S. Vargas, Dr. G. Bottari,
Dr. E. ꢁlvarez, Dr. A. Pizzano
Instituto de Investigaciones Quꢂmicas
Consejo Superior de Investigaciones Cientꢂficas and
Universidad de Sevilla, Avda Amꢃrico Vespucio 49
Isla de la Cartuja, 41092 Sevilla (Spain)
Fax : (+34)954460565
In recent years, we have studied the application of a
À
family of chiral phosphane–phosphites (P OP) in diverse
Rh, Ru, and Ir asymmetric catalytic hydrogenations.[17] The
highly modular structure of these ligands, the rich catalytic
E-mail: pizzano@iiq.csic.es
À
reactivity of [RuCl2(diphosphane)
the lack of phosphane–phosphite analogues in the literature
(N N)] complexes, and
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201203193.
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Chem. Eur. J. 2012, 18, 15586 – 15591

COMMUNICATION
led us to investigate the preparation of some derivatives
À
that contain P OP ligands. Initially, the reaction of [Ru(2-
[17f]
À
À
Me C3H4)
2A
with two equivalents of HCl and one
equivalent of (S,S)-DPEN yielded complexes 1a–1g. Alter-
natively, complexes 2a, 2c, and 2d were prepared by using
(R,R)-DPEN (Scheme 1a). The treatment of [Ru(Cl)2-
Scheme 2. Catalytic hydrogenation of N-aryl imines.
Table 1. Hydrogenation of 4a with complexes 1 and 2.[a]
À
P OP
À
N N
Entry
Conv.
[%]
ee
[%]
Config.
1
2
3
4
5
6
7
8
9
3a
3b
3c
3d
3e
3 f
3g
3a
3c
3d
U
39
47
55
72
67
97
78
39
24
70
80
32
58
73
90
93
72
90
12
54
R
R
R
R
R
R
R
S
S
S
10
[a] Reactions were carried out at 608C by using 0.1m solutions of sub-
strate and tBuOK as the base (B); S/C/B=100:1:100, reaction time=
72 h. Conversion was determined by 1H NMR spectroscopy and enantio-
meric excess by Chiral HPLC. Configuration was determined by compar-
ison of the sign of optical rotation with literature data (see the Support-
ing Information).
Scheme 1. Preparation of complexes 1 and 2.
ACHTUNGTRENNUNG(PPh3)3] with one equivalent of ligand 3, followed by a stoi-
chiometric amount of DPEN, provided easy access to the
desired compounds (Scheme 1b). Depending on the nature
gave a higher conversion. To examine matching effects be-
À
À
of the P OP and DPEN ligands, these reactions produced
tween diamine and P OP ligands, the diastereomeric com-
compounds 1 and 2 either as a single diastereomer or as
mixtures containing two or three isomers, from which the
major isomer was purified by column chromatography. In
addition, the major isomer can display either a cis- or trans-
dichloride coordination mode depending on the combina-
tion of the chelating ligands (see below).
plex 2a was also tested. This compound produced a similar
conversion and a higher enantioselectivity than 1a (90% ee;
Table 1, Entry 8). These results indicate that the chiral in-
duction is predominantly caused by the diamine ligand and
that the stereogenic axis of the phosphite has a secondary
role.
We next screened the performance of complexes 1 and 2
in the enantioselective hydrogenation of N-(1-phenylethyli-
dene)aniline (4a; Scheme 2, Table 1). As a first approach,
similar reaction conditions to those reported by Cobley
et al. were used (i.e., substrate/catalyst=100, iPrOH as sol-
Following this reasoning, we examined complex 1e, which
contains a conformationally flexible phosphite fragment. We
were pleased to observe that this compound produced the
same enantioselectivity as 2a with better conversion (90%
ee; Table 1, Entry 5). Interestingly, these results indicate that
an important variable is the phosphite flexibility, which can
enable a higher catalyst reactivity, whereas the use of a
more rigid phosphite fragment with a stereogenic axis re-
tards the reaction and does not improve enantioselectivity.
In addition, these results allow a further optimization of the
vent, 20 bar H2, [4a]/ACTHNUTRGNEUNG
[tBuOK]=1, 608C).[13] Under these
conditions, compounds 1a and 1b gave moderate conver-
sions, and the diphenyl catalyst provided a significantly
better enantioselectivity (Table 1, Entries 1 and 2). More-
over, precatalysts with a smaller phosphite fragment (1c;
Table 1, Entry 3) and an ethane backbone (1d; Table 1,
Entry 4) were also examined. None of these improved on
the enantioselectivity provided by 1a, although the ethane-
bridged catalyst, probably due to a more flexible backbone,
À
catalyst by using other achiral P OP ligands that differ in
the phosphane group. Complexes 1 f and 1g with p-tolyl and
xylyl phosphane substituents were examined. While the
latter produced moderate levels of conversion and enantio-
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15587

A. Pizzano et al.
selectivity (Table 1, Entry 7), the catalyst precursor 1 f pro-
vided a higher enantioselectivity than 1a, with an important
improvement in the conversion (Table 1, Entry 6).
positions of the chloride ligands. In complex 2d, the two
chloride ligands occupy positions cis to one another, with
one of them trans to the phosphite group (Figure 2). In addi-
Most remarkably, the precatalyst 1 f showed a high reac-
tivity in toluene, enough to complete reactions under very
mild conditions with lower catalyst and base loadings (room
temperature, 4 bar H2, substrate/catalyst/base=500:1:10).
Under these conditions, a 93% ee for the hydrogenation of
4a was reached (Table 2, Entry 1). These results prompted
Table 2. Hydrogenation of imines 4 with complex 1 f.[a]
Entry
Substrate
H2
[bar]
Conv.
[%]
ee
[%]
Config.[b]
N
1
2
3
4
5
6
7
8
9
4a
4b
4c
4d
4e
4 f
4g
4g
4h
4h
4i
4
4
4
4
4
4
4
10
4
20
4
>99
>99
>99
>99
>99
>99
73
>99
26
>99
>99
>99
93
93
91
92
95
96
89
95
81
93
96
95
R
–
R
–
R
R
R
R
R
R
–
10[c]
11
12
4j
4
R
[a] Reactions were carried out at room temperature in toluene with
Figure 2. ORTEP view of complex 2d. Ellipsoids are presented at the
30% probability level.
tBuOK as the base (B); S/C/B=500:1:10, reaction time=24 h, and [S]=
1
1.0m, unless otherwise specified. Conversion was determined by H NMR
spectroscopy and enantiomeric excess by Chiral HPLC. [b] Configuration
was determined by comparison of the sign of optical rotation with litera-
ture data when available (see the Supporting Information), otherwise the
optical rotation sign is provided. [c] The reaction was performed at 608C
in iPrOH.
tion, this structure displays a significant trans influence by
À
the phosphite group because the Ru Cl(2) bond is apprecia-
À
bly longer than that of Ru Cl(1) (2.475 and 2.409 ꢅ, respec-
tively). In contrast, the structure of compound 1e shows two
chloride atoms in mutually trans positions (Figure 3). A re-
markable feature of this compound is the existence of two
diastereomeric molecules in the crystal that differ in the
conformation of the biphenyl fragment. The dissimilarity be-
tween the two structures is not restricted to the phosphite
fragment because the change in biaryl conformation is cou-
pled with the opposing conformations of the benzene back-
bone and the phosphane group. Thus, if the diamine back-
bone is ignored, both structures are nearly enantiomers of
each other. In solution, however, only one set of signals that
is composed of two doublets centered at 146.1 and 38.7 ppm
us to investigate the scope of the latter catalytic system. We
were pleased to observe that diverse N-aryl imines 4 were
hydrogenated with high levels of conversion and enantiose-
lectivity under these reaction conditions (Scheme 2). In gen-
eral, N-phenyl imines gave somewhat lower enantioselectivi-
ties (91–93% ee, Table 2, Entries 1–4), than N-(p-anisyl)
imines, which provided values from 93 to 96% ee (Table 2,
Entries 5, 6, 8, and 10–12), in good accord with previous ob-
servations.[11g,14] During this screening, we observed that the
reactions of substrates 4g and 4h were incomplete under
these conditions. However, an increase in the hydrogen
pressure to 10 bar produced the amine 5g with full conver-
sion and a 95% ee (Table 2, Entry 8). In the case of the tri-
fluoromethyl-substituted imine 4h, the reaction in iPrOH at
20 bar showed full conversion with a 93% ee (Table 2,
Entry 10). Finally, N-(p-methoxyphenyl)-1-phenylpropyl-
[JACTHNUTRGNEUNG
(P,P)=73 Hz] was observed by 31P{1H} NMR at room tem-
perature. Upon cooling, the signals broadened and at
À908C two species were observed in a 2:1 ratio. The major
species appeared as two doublets centered at 149.5 and
37.3 ppm [J
ACHTUNGTRENNUNG
acterized by two doublets at 148.8 and 36.9 ppm [JACHTUNGTRENNUNG
A
73 Hz]. These observations are in accord with a fast ex-
change between the two diastereomers upon atropisomeri-
zation of the phosphite group at room temperature, as ob-
served in rhodium derivatives that contain this phosphite
fragment.[19] Therefore, the chiral diamine does not efficient-
ly favor a phosphite biaryl conformation, which has been
observed before in the case of complexes based on confor-
mationally flexible diphosphanes.[20]
version by hydrogenation of the corresponding imine 4j
(Table 2, Entry 12).
To gain additional information about the stereochemistry
of Ru complexes, representative compounds 2d and 1e
were structurally characterized by X-ray crystallography.[18]
Both compounds show a distorted octahedral structure and
it is noteworthy that they differ in the relative coordination
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Chem. Eur. J. 2012, 18, 15586 – 15591

Enantioselective Imine Hydrogenation Catalyzed by Ruthenium
COMMUNICATION
structures B and C, which differ
in the relative positions of the
P functionalities (only diaste-
AHCTUNGTERGrNNUN eomers corresponding to a D
Ru configuration are shown).
Among these structures, the di-
hydride B, which is structurally
similar to 2d, places the more
reactive hydride in a trans posi-
tion to the phosphite group, ac-
cording to the larger trans influ-
ence of the phosphite than that
of the amino ligand. This ar-
rangement would minimize the
influence of the phosphite con-
formation on asymmetric induc-
tion, in good accord with exper-
imental results. This proposal
finds further support in the ste-
AHCTUNGTERGrNNUN eochemical model proposed by
Ohkuma et al., which is based
on a cis-dihydride in which the
apical hydride, trans to a phos-
phane ligand, is transferred to
the N-aryl imine.[14] Moreover,
the stereochemical outcome
provided by complexes 1 and 2
is analogous to that rationalized
by the mentioned model (that
is, that catalysts based on (S,S)-
DPEN give R amines).
Therefore,
a new catalytic
system for the hydrogenation of
imines that is based on Ru com-
plexes with phosphane–phos-
phite and diamine ligands has
been described. From a ligand
screening, a practical catalyst
that possesses a conformation-
ally flexible phosphane–phos-
phite and a DPEN ligand has
Figure 3. ORTEP views of Sa (top) and Ra (bottom) conformers of 1e. Ellipsoids are presented at the 30%
probability level.
The high enantioselectivity provided by 1e, along with the
lack of control of the diamine on the conformation of the
phosphite, is a remarkable aspect that deserves further com-
ment. Assuming that the hydrogenation of N-aryl imines
proceeds in an analogous manner to ketone hydrogena-
tion,[21] several structures for the key dihydride compound
with cis-hydride and -amino ligands are possible.[22] Namely,
a trans-dihydride A (Figure 4) and the diastereomeric cis
been found. This catalyst operates under very mild condi-
tions and provides up to 96% ee in the hydrogenation of N-
aryl imines. Further studies aimed to identify the mechanism
of this reaction, as well as to analyze the scope of the pres-
ent Ru complexes in the hydrogenation of other imine
types, are currently in progress.
Experimental Section
General procedure: In a glovebox, a Fischer–Porter vessel (80 mL) was
charged with the appropriate imine
4 (0.88 mmol), Ru complex 1
(1.8 mmol), tBuOK (2.0 mg, 0.018 mmol) and toluene (0.88 mL). The re-
actor was purged three times with H2 and then pressurized at 4 bar. After
the desired reaction time, the reactor was slowly depressurized and the
solution that was obtained was evaporated. The resulting residue was an-
alyzed by 1H NMR spectroscopy for the determination of conversion,
Figure 4. Structures of the dihydride complexes.
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15589

A. Pizzano et al.
then dissolved in CH2Cl2 (2 mL), treated with a 2m aqueous solution of
HCl (2 mL), and the resulting mixture was stirred for 20 min. The mix-
ture was treated with NaHCO3 (3 mL, saturated aqueous solution), the
phases were separated, and the organic layer was dried over magnesium
sulfate. Evaporation of the resulting solution yielded amine 5. Enantio-
meric excess was analyzed by chiral HPLC.
[6] a) J.-X. Gao, T. Ikariya, R. Noyori, Organometallics 1996, 15, 1087–
1089; b) R. Guo, C. Elpelt, X. Chen, D. Song, R. H. Morris, Chem.
Commun. 2005, 3050–3052; c) W. Baratta, G. Chelucci, E. Herdt-
weck, S. Magnolia, K. Siega, P. Rigo, Angew. Chem. 2007, 119,
7795–7798; Angew. Chem. Int. Ed. 2007, 46, 7651–7654; d) C.
Wang, X. F. Wu, J. L. Xiao, Chem. Asian J. 2008, 3, 1750–1770.
[7] C. Schotes, A. Mezzetti, Angew. Chem. 2011, 123, 3128–3130;
Angew. Chem. Int. Ed. 2011, 50, 3072–3074.
[8] a) R. Guo, R. H. Morris, D. Song, J. Am. Chem. Soc. 2005, 127,
516–517; b) R. Guo, X. Chen, C. Elpelt, D. Song, R. H. Morris, Org.
Lett. 2005, 7, 1757–1759; c) F. Santoro, M. Althaus, C. Bonaccorsi,
S. Gischig, A. Mezzetti, Organometallics 2008, 27, 3866–3878.
[9] a) N. Kurono, N. Nii, Y. Sakaguchi, M. Uemura, T. Ohkuma, Angew.
Chem. 2011, 123, 5655–5658; Angew. Chem. Int. Ed. 2011, 50, 5541–
5544; b) N. Kurono, T. Yoshikawa, M. Yamasaki, T. Ohkuma, Org.
Lett. 2011, 13, 1254–1257; c) M. Uemura, N. Kurono, T. Ohkuma,
Org. Lett. 2012, 14, 882–885.
[10] a) H.-U. Blaser, C. Malan, B. Pugin, F. Spindler, H. Steiner, M.
Studer, Adv. Synth. Catal. 2003, 345, 103–151; b) N. Fleury-Brꢃgeot,
V. de La Fuente, S. Castillꢆn, C. Claver, ChemCatChem 2010, 2,
1346–1371; c) J.-H. Xie, S.-F. Zhu, Q.-L. Zhou, Chem. Rev. 2011,
111, 1713–1760; d) T. C. Nugent, M. El-Shazly, Adv. Synth. Catal.
2010, 352, 753–819.
Acknowledgements
We acknowledge MINECO (CTQ2009–11867 and CONSOLIDER-IN-
GENIO CSD2007–00006, FEDER support) and Junta de Andalucꢂa
(2008/FQM-3830) for financial support. M.V. thanks MINECO for a FPI
fellowship and G.B. for a Marie Curie Postdoctoral Contract (PITN
2008–215193).
Keywords: asymmetric catalysis · hydrogenation · imines ·
P-ligands · ruthenium
[11] For representative examples, see: a) C. Moessner, C. Bolm, Angew.
Chem. 2005, 117, 7736–7739; Angew. Chem. Int. Ed. 2005, 44, 7564–
7567; b) T. Imamoto, N. Iwadate, K. Yoshida, Org. Lett. 2006, 8,
2289–2292; c) S.-F. Zhu, J.-B. Xie, Y.-Z. Zhang, S. Li, Q.-L. Zhou, J.
Am. Chem. Soc. 2006, 128, 12886–12891; d) C. Li, C. Wang, B.
Villa-Marcos, J. Xiao, J. Am. Chem. Soc. 2008, 130, 14450–14451;
e) W. Li, G. Hou, M. Chang, X. Zhang, Adv. Synth. Catal. 2009, 351,
3123–3127; f) Z. Han, Z. Wang, X. Zhang, K. Ding, Angew. Chem.
2009, 121, 5449–5453; Angew. Chem. Int. Ed. 2009, 48, 5345–5349;
[1] a) H. Doucet, T. Ohkuma, K. Murata, T. Yokozawa, M. Kozawa, E.
Katayama, A. F. England, T. Ikariya, R. Noyori, Angew. Chem.
1998, 110, 1792–1796; Angew. Chem. Int. Ed. 1998, 37, 1703–1707;
b) T. Ohkuma, M. Koizumi, H. Doucet, T. Pham, M. Kozawa, K.
Murata, E. Katayama, T. Yokozawa, T. Ikariya, R. Noyori, J. Am.
Chem. Soc. 1998, 120, 13529–13530; c) T. Ohkuma, D. Ishii, H.
Takeno, R. Noyori, J. Am. Chem. Soc. 2000, 122, 6510–6511; d) J.
Wu, J.-X. Ji, R. Guo, C.-H. Yeung, A. S. C. Chan, Chem. Eur. J.
2003, 9, 2963–2968; e) M. J. Burk, W. Hems, D. Herzberg, C. Malan,
A. Zanotti-Gerosa, Org. Lett. 2000, 2, 4173–4176; f) T. Ohkuma,
C. A. Sandoval, R. Srinivasan, Q. Lin, Y. Wei, K. MuÇiz, R. Noyori,
J. Am. Chem. Soc. 2005, 127, 8288–8289; g) S. Liu, J.-H. Xie, L.-X.
Wang, Q.-L. Zhou, Angew. Chem. 2007, 119, 7650–7652; Angew.
Chem. Int. Ed. 2007, 46, 7506–7508; h) W. Li, X. Sun, L. Zhou, G.
Hou, S. Yu, X. Zhang, J. Org. Chem. 2009, 74, 1397–1399; i) J.-H.
Xie, S. Liu, W.-L. Kong, W.-J. Bai, X.-C. Wang, L.-X. Wang, Q.-L.
Zhou, J. Am. Chem. Soc. 2009, 131, 4222–4223.
[2] For examples of some ketone hydrogenation catalysts based on al-
ternative formulations to [RuCl2(diphosphane)diamine], see: a) T.
Ohkuma, M. Koizumi, K. MuÇiz, G. Hilt, C. Kabuto, R. Noyori, J.
Am. Chem. Soc. 2002, 124, 6508–6509; b) Y. Xu, N. W. Alcock, G. J.
Clarkson, G. Docherty, G. Woodward, M. Wills, Org. Lett. 2004, 6,
4105–4107; c) W. Baratta, G. Chelucci, S. Magnolia, K. Siega, P.
Rigo, Chem. Eur. J. 2009, 15, 726–732; d) M. B. Dꢂaz-Valenzuela,
S. D. Phillips, M. B. France, M. E. Gunn, M. L. Clarke, Chem. Eur. J.
2009, 15, 1227–1232; e) B. Stegink, L. van Boxtel, L. Lefort, A. J.
Minnaard, B. L. Feringa, J. G. de Vries, Adv. Synth. Catal. 2010, 352,
2621–2628; f) S. D. Phillips, J. A. Fuentes, M. L. Clarke, Chem. Eur.
J. 2010, 16, 8002–8005; g) K. Matsumura, N. Arai, K. Hori, T. Saito,
N. Sayo, T. Ohkuma, J. Am. Chem. Soc. 2011, 133, 10696–10699.
[3] For examples of the hydrogenation of esters and imides, see: a) W.
Kuriyama, Y. Ino, O. Ogata, N. Sayo, T. Saito, Adv. Synth. Catal.
2010, 352, 92–96; b) L. A. Saudan, C. M. Saudan, C. Debieux, P.
Wyss, Angew. Chem. 2007, 119, 7617–7620; Angew. Chem. Int. Ed.
2007, 46, 7473–7476; c) S. Takebayashi, J. M. John, S. H. Bergens, J.
Am. Chem. Soc. 2010, 132, 12832–12834.
ˇ ´
g) N. Mrsic, A. J. Minnaard, B. L. Feringa, J. G. de Vries, J. Am.
Chem. Soc. 2009, 131, 8358–8359; h) A. Baeza, A. Pfaltz, Chem.
Eur. J. 2010, 16, 4003–4009; i) G. Hou, R. Tao, Y. Sun, X. Zhang, F.
Gosselin, J. Am. Chem. Soc. 2010, 132, 2124–2125.
[12] For examples, see: a) C. A. Willoughby, S. L. Buchwald, J. Am.
Chem. Soc. 1994, 116, 11703–11714; b) C. A. Willoughby, S. L.
Buchwald, J. Am. Chem. Soc. 1994, 116, 8952–8965; c) R. Kuwano,
M. Kashiwabara, Org. Lett. 2006, 8, 2653–2655; d) S. Zhou, S.
Fleischer, K. Junge, M. Beller, Angew. Chem. 2011, 123, 5226–5230;
Angew. Chem. Int. Ed. 2011, 50, 5120–5124; e) F. Chen, Z. Ding, J.
Qin, T. Wang, Y. He, Q.-H. Fan, Org. Lett. 2011, 13, 4348–4351.
[13] C. J. Cobley, J. P. Henschke, Adv. Synth. Catal. 2003, 345, 195–201.
[14] N. Arai, N. Utsumi, Y. Matsumoto, K. Murata, K. Tsutsumi, T.
Ohkuma, Adv. Synth. Catal. 2012, 354, 2089–2095.
[15] a) C. G. Leong, O. M. Akotsi, M. J. Ferguson, S. H. Bergens, Chem.
Commun. 2003, 750–751; b) D. G. Genov, D. J. Ager, Angew. Chem.
2004, 116, 2876–2879; Angew. Chem. Int. Ed. 2004, 43, 2816–2819;
c) Q. Jing, X. Zhang, J. Sun, K. Ding, Adv. Synth. Catal. 2005, 347,
1193–1197; d) K. Mikami, K. Wakabayashi, K. Aikawa, Org. Lett.
2006, 8, 1517–1519; e) Q. Zhu, D. Shi, C. Xia, H. Huang, Chem.
Eur. J. 2011, 17, 7760–7763.
[16] a) N. Arai, H. Ooka, K. Azuma, T. Yabuuchi, N. Kurono, T. Inoue,
T. Ohkuma, Org. Lett. 2007, 9, 939–941; b) N. Arai, K. Azuma, N.
Nii, T. Ohkuma, Angew. Chem. 2008, 120, 7567–7570; Angew.
Chem. Int. Ed. 2008, 47, 7457–7460; c) C. A. Sandoval, Y. Li, K.
Ding, R. Noyori, Chem. Asian J. 2008, 3, 1801–1810; d) A. M.
Palmer, A. Zanotti-Gerosa, H. Nedden, Tetrahedron: Asymmetry
2008, 19, 1310–1327; e) Y. Li, K. Ding, C. A. Sandoval, Org. Lett.
2009, 11, 907–910; f) W. Li, G. Hou, C. Wang, Y. Jiang, X. Zhang,
Chem. Commun. 2010, 46, 3979–3981; g) Y. Li, Y. Zhou, Q. Shi, K.
Ding, R. Noyori, C. A. Sandoval, Adv. Synth. Catal. 2011, 353, 495–
500.
[4] For examples of enantioselective reactions involving the hydrogena-
tion of aldehydes, see: a) J.-H. Xie, Z.-T. Zhou, W.-L. Kong, Q.-L.
Zhou, J. Am. Chem. Soc. 2007, 129, 1868–1869; b) Z.-T. Zhou, J.-H.
Xie, Q.-L. Zhou, Adv. Synth. Catal. 2009, 351, 363–366.
[17] a) A. Suꢀrez, M. A. Mꢃndez-Rojas, A. Pizzano, Organometallics
2002, 21, 4611–4621; b) S. Vargas, M. Rubio, A. Suꢀrez, D. del Rio,
E. ꢁlvarez, A. Pizzano, Organometallics 2006, 25, 961–973; c) M.
Rubio, S. Vargas, A. Suꢀrez, E. ꢁlvarez, A. Pizzano, Chem. Eur. J.
2007, 13, 1821–1833; d) I. Arribas, S. Vargas, M. Rubio, A. Suꢀrez,
[5] For examples of imine hydrogenation, see: a) K. Abdur-Rashid,
A. J. Lough, R. H. Morris, Organometallics 2000, 19, 2655–2657;
b) K. Abdur-Rashid, A. J. Lough, R. H. Morris, Organometallics
2001, 20, 1047–1049; c) K. Abdur-Rashid, R. Guo, A. J. Lough,
R. H. Morris, D. Song, Adv. Synth. Catal. 2005, 347, 571–579.
15590
www.chemeurj.org
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Chem. Eur. J. 2012, 18, 15586 – 15591

Enantioselective Imine Hydrogenation Catalyzed by Ruthenium
COMMUNICATION
C. Domene, E. ꢁlvarez, A. Pizzano, Organometallics 2010, 29,
5791–5804; e) M. ꢁ. Chꢀvez, S. Vargas, A. Suꢀrez, E. ꢁlvarez, A.
Pizzano, Adv. Synth. Catal. 2011, 353, 2775–2794; f) M. Vaquero, S.
Vargas, A. Suꢀrez, S. E. Garcꢂa-Garrido, E. ꢁlvarez, M. Mancera,
A. Pizzano, Organometallics 2012, 31, 3551–3564.
[20] a) K. Mikami, T. Korenaga, M. Terada, T. Ohkuma, T. Pham, R.
Noyori, Angew. Chem. 1999, 111, 517–519; Angew. Chem. Int. Ed.
1999, 38, 495–497; b) T. Korenaga, K. Aikawa, M. Terada, S. Ka-
wauchi, K. Mikami, Adv. Synth. Catal. 2001, 343, 284–288.
[21] a) K. Abdur-Rashid, S. E. Clapham, A. Hadzovic, J. N. Harvey, A. J.
Lough, R. H. Morris, J. Am. Chem. Soc. 2002, 124, 15104–15118;
b) C. A. Sandoval, T. Ohkuma, K. MuÇiz, R. Noyori, J. Am. Chem.
Soc. 2003, 125, 13490–13503.
[22] a) R. Abbel, K. Abdur-Rashid, M. Faatz, A. Hadzovic, A. J. Lough,
R. H. Morris, J. Am. Chem. Soc. 2005, 127, 1870–1882; b) K.
Abdur-Rashid, R. Abbel, A. Hadzovic, A. J. Lough, R. H. Morris,
Inorg. Chem. 2005, 44, 2483–2492.
[18] CCDC-894893 (1e) and CCDC-894894 (2d) contain the supplemen-
tary crystallographic data for this paper. These data can be obtained
free of charge from The Cambridge Crystallographic Data Centre
via www.ccdc.cam.ac.uk/data_request/cif.
[19] a) G. J. H. Buisman, M. E. Martin, E. J. Vos, A. Klootwijk, P. C. J.
Kamer, P. W. N. M. van Leeuwen, Tetrahedron: Asymmetry 1995, 6,
719–738; b) M. Rubio, A. Suꢀrez, D. del Rio, A. Galindo, E. ꢁlvar-
ez, A. Pizzano, Organometallics 2009, 28, 547–560.
Received: September 7, 2012
Published online: November 7, 2012
Chem. Eur. J. 2012, 18, 15586 – 15591
ꢄ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
15591