Ruthenium catalysts containing rigid chiral diamines and achiral diphosphanes for highly enantioselective hydrogenation of aromatic ketones

Article abstract of DOI:10.1002/chem.201100820

One chiral element is enough: A new ruthenium catalyst containing a rigid chiral diamine (BIDN) and a commercially available inexpensive achiral phosphane (DPPF) is highly efficient for the enantioselective hydrogenation of ketones (see scheme). High reactivity (S/C up to 100 000) and excellent enantioselectivities (up to 99 % ee) were obtained. Copyright

Full text of DOI:10.1002/chem.201100820

DOI: 10.1002/chem.201100820
Ruthenium Catalysts Containing Rigid Chiral Diamines and Achiral
Diphosphanes for Highly Enantioselective Hydrogenation of
Aromatic Ketones
[
a]
Qiming Zhu, Dengjian Shi, Chungu Xia, and Hanmin Huang*
The development of practical and efficient chiral catalytic
systems for asymmetric organic reactions is one of the most
We have recently introduced the chiral diamine 1a
((1S,1’S)-1,1’-biisoindoline, named BIDN), a new and intri-
guing structural motif as a chiral amine ligand, and demon-
strated that it can be more effective for some asymmetric re-
[1]
important subjects in synthetic organic chemistry. In gener-
al, conformationally rigid chiral ligands proved to be ex-
tremely useful for the construction of a good oriented and
fixed chiral environment around the metal center, which
could efficiently impart high enantioselectivity and activity
[7]
actions. The fused benzene rings not only make this amine
more conformationally rigid compared with DPEN, but also
render it more electron-deficient due to the p-electron ac-
[2]
[8]
to some important reactions.
ceptability of the fused benzene ring. Given that the con-
The catalytic asymmetric reduction of ketones is a funda-
mental transformation in organic synthesis for making chiral
alcohols. For asymmetric hydrogenation of simple aromatic
formationally rigid structure would have good chiral induc-
[2]
[5n]
tion ability and inspired by the elegant work of Mikami
[5o–p]
and Ding,
we envisaged that 1 could be evolved into a
ketones, the use of [(BINAP)Ru
catalytic systems pioneered by Noyori and co-workers is the
A
H
U
G
R
N
U
G
good chiral ruthenium catalyst for asymmetric hydrogena-
tion of ketones upon combination with an appropriate achi-
ral phosphane. Furthermore, the tunable modular structure
of this newly developed chiral diamine can provide us an
opportunity to systematically turn the electronic feature by
introducing different substituents, and thus investigate the
catalytic properties of the corresponding ruthenium catalyst
on the asymmetric hydrogenation of ketones. We expected
that this key modification, if successful, would not only es-
tablish a practical chiral catalyst for asymmetric hydrogena-
tion of ketones but also provide some new insights into the
mechanism for this reaction.
most powerful and reliable procedure. The general defini-
tive feature of this catalyst is that the ruthenium is coordi-
nated with a chiral diphosphane and a chiral diamine, form-
ing a good oriented chiral trans-octahedral complex. As the
excellent enantioselectivity was proposed to be a result of
the excellent chiral environment impact by synergistic effect
of the chiral diphosphane and chiral diamine ligands, tre-
mendous efforts have been dedicated to developing efficient
phosphane ligands such as chiral phosphane, chirally flexible
phosphane and even achiral bulky monophosphane ligands.
However, most phosphanes have been used in conjunction
with chiral DPEN and DAIPEN to mimic the Noyori cata-
To test this hypothesis, a series of rigid chiral diamines
1a–1h with different electronic features were successfully
[5]
[7]
lyst. There are very few reports focused on developing effi-
cient chiral diaminea that could be combined with commer-
cial available inexpensive achiral phosphane ligands to con-
struct an efficient Ru-catalyst for the asymmetric hydroge-
prepared according to our previously reported procedure
and a series of commercially available structurally similar
achiral diphosphane ligands 2a–2h with different bite angle
and steric hindrance were applied for pursuing the practical
catalysts for the asymmetric hydrogenation of ketones
(Scheme 1). Acetophenone was used as a model substrate
[4h,6]
nation of ketones,
although the nitrogen-containing li-
gands are more favorable in terms of preparation. Herein,
we report a ruthenium catalytic system consisting of a new
rigid chiral diamine and achiral commercially available di-
phosphane, which hydrogenates aromatic ketones with high
enantioselectivity and activity.
[
a] Q. Zhu, D. Shi, Prof. Dr. C. Xia, Prof. Dr. H. Huang
State Key Laboratory for Oxo Synthesis and Selective Oxidation
Lanzhou Institute of Chemical Physics
Chinese Academy of Sciences
Lanzhou, 730000 (P.R. China)
Fax : (+86)931-496-8129
E-mail: hmhuang@licp.cas.cn
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201100820.
Scheme 1. Chiral amines and achiral phosphanes.
7760
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 7760 – 7763

COMMUNICATION
for the asymmetric hydrogenation reaction. The correspond-
ing catalysts were prepared according to the reported proce-
dure with [Ru ACHTUNGTRENNUNG( benzene)Cl ] as a catalyst precursor. All re-
2 2
actions were carried out at room temperature, 50 atm of H2,
nPrOH as the solvent, tBuOK as the base and 1d was uti-
lized to find the best achiral phosphane ligand (Table 1). It
erties of the amine, chiral diamines 1a–1h were synthesized,
and their catalytic properties were compared. The details of
the results are summarized in Table 1, and clearly demon-
strate that the enantioselectivities of the reaction are signifi-
cantly influenced by the electronic effect, and an interesting
trend was observed that the amines with electron-withdraw-
ing substituents gave better enantioselectivities than those
with electron-donating groups (Table 1, entry 10 vs. entry 11
or entries 12–13 vs. entry 14). For example, with the unsub-
stituted parent 1a as an amine ligand, the desired alcohol
[
a]
Table 1. Optimized reaction conditions.
4
a was obtained with 94% ee (Table 1, entry 12), while in-
troduction of electron-withdrawing substituents such as
fluoro, bromo, or chloro groups in the arene of the diamine
backbone enhanced the enantioselectivity in the hydrogena-
tion reaction (97% ee for bromo, chloro, and fluoro,
Table 1, entries 9–11). Replacement of the haloid group with
electron-donating substituents such as OMe or phenyl
groups, however, resulted in decrease in enantioselectivity
[
b]
[c]
Entry
Amine
Phosphane
PH
2
[atm]
Conv.[%]
ee [%]
1
2
3
4
5
6
7
8
9
1d
1d
1d
1d
1d
1d
1d
1d
1d
1b
1c
1a
1e
1 f
1g
1h
3
2a
2b
2c
2d
2e
2 f
2g
2h
2g
2g
2g
2g
2g
2g
2g
2g
2g
50
50
50
50
50
50
50
50
10
10
10
10
10
10
10
10
10
>99
>99
>99
>99
85
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
57
64
70
68
49
95
97
67
97
97
97
94
92
88
88
95
64
(
Table 1, entries 13–15). Moreover, this tendency was further
evidenced by using the amines 1g and 1h as chiral ligands.
The only major difference of ligand 1g and 1h is that the 1h
10
11
12
13
14
15
16
17
contains an electron-withdrawing CF group in the substitut-
3
ed phenyl moieties, but the difference of enantioselectivities
resulted from these two ligands are very striking (88% ee vs.
95% ee, Table 1, entry 15 vs. entry 16). In contrast, the Ru-
catalyst composed with DPEN 3 and DPPF could also be
employed for this hydrogenation, but only 64% ee was ob-
tained (Table 1, entry 17), which suggested that the rigid
structure of the chiral diamine BIDN used here was impor-
tant for constructing highly efficient catalysts.
This dramatic effect of electronic properties of the chiral
diamine was further demonstrated by the kinetic reaction
profiles shown in Figure 1. While the catalyst derived from
the diamine 1 f with electronic-donating substituents OMe
on the arene of amine backbone gave less than 40% conver-
sion after a 90 min reaction time, the conversion affected by
the corresponding electron-withdrawing bromo was over
[
0
a] Reaction conditions: 4a (2.5 mmol), catalyst (0.0025 mmol,
.1 mol%), tBuOK (0.25 mmol), solvent (2.5 mL). All of the reactions
were carried out under H atmosphere at room temperature for 12 h
unless otherwise noted. [b] The conversion was determined by GC.
c] The ee values were determined by GC with a Supleco beta-120
2
[
column.
was found that the bite angle of the ligands had significant
impact on the reactivity and enantioselectivity. With 2a as a
phosphane ligand which possesses a smallest bite angle, the
desired alcohol was obtained with 57% ee (Table 1, entry 1).
Increasing the bite angle by using the 2b and 2c as phos-
phane ligands, the enantioselectivities increased to 64% and
74% ee (Table 1, entries 2 and 3), respectively. However, a
further increase of the bite angle and the use of 2d and 2e
as ligands led to a decrease of the reactivity and of the enan-
tioselectivity. The phosphane ligands 2 f (DPEphos) or 2g
(
DPPF) with appropriate bite angles provided a break-
through in reactivity and enantioselectivity: full conversion
and high enantioselectivities up to 95% ee and 97% ee were
obtained, respectively. The steric more hindered Xantphos
2
h with larger bite angle than 2 f proved to be ineffective,
which further suggested that the steric property of the phos-
phine ligands was important for the catalytic behavior. The
reaction can be performed under 10 atm of H pressure with
2
same enantioselectivity (Table 1, entry 9).
After having defined the best achiral phosphane ligand
for the Ru-catalyst, we sought to explore the nature of
chiral diamine BIDN with 2g (DPPF) as an achiral phos-
phane ligand. To determine the influence of electronic prop-
Figure 1. Effect of the electronic properties on the rate of hydrogenation
of 4a in nPrOH under 10 atm of H at room temperature in the presence
2
of 0.1% mol of catalyst. The Ru-catalyst was composed with DPPF and
the corresponding amine (see the Supporting Information for details).
Chem. Eur. J. 2011, 17, 7760 – 7763
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
7761

H. Huang et al.
[
a]
98% (97% ee). These results obviously demonstrated that
Table 2. Substrate scope of aromatic ketones.
the amines with electron-withdrawing substituents shown
higher reactivity than those with electron-donating groups.
The above-mentioned preliminary investigation on the
ligand structure/enantioselectivity/reactivity relationship has
clearly indicated that the rigid structure of the diamine and
the electron-withdrawing group on the fused benzene ring
of the diamine are important for attaining high reactivity
and enantioselectivity. We speculate that the rigid chiral dia-
mine combined with the achiral phosphane ligand (DPPF)
with proper steric properties could craft good oriented
chiral environment, and the chiral information would be ef-
ficiently impart to the hydrogenation product from the rigid
chiral diamine. The electron-withdrawing substituent on the
scaffold of the chiral diamine might enhance the NÀH acidi-
ty and the RuÀH nucleophilicity, which will facilitate the
[
b]
Entry
Ar
R
Product
ee [%]
1
2
3
C
6
H
5
CH
CH
CH
CH
3
3
3
3
5a
5b
5c
5d
5e
5 f
5g
5h
5i
5j
5k
5l
5m
5n
5o
5p
5q
5r
97 (S)
96 (S)
95 (S)
95 (S)
95 (S)
95 (S)
95 (S)
88 (S)
94 (S)
92 (S)
98 (S)
99 (S)
95 (S)
98 (S)
99 (S)
94 (S)
98 (S)
94 (S)
98 (S)
97 (S)
4-CH
4-CH
3-CH
3
3
3
C
OC
6
H
4
6
H
4
[c]
4
C
6
H
4
5
6
7
8
9
4-ClC H
6
4
CH3
4-BrC
4-FC
2-CH
1-naphthyl
2-naphthyl
6
H
4
CH
CH
CH
CH
3
3
3
3
6
H
4
[
c]
3
C
6
H
4
[c]
10
11
CH3
CH
(CH
C
C
C
C
6
6
6
6
H
H
H
H
5
5
4
4
2
CH
CH
3
12
13
14
15
A
H
U
G
R
N
N
2
)
7
3
[
[
d]
e]
-(CH
-(CH
-(CH
CH3
CH
CH
CH
CH
2
2
2
)
)
)
2
-
3
-
3
-
capture of the carbonyl of a ketonic substrate by the charge-
d+
dÀ
d+
dÀ
alternating H -N -Ru -H via the NH—O=C hydrogen
bond, thus the rate of proton (NÀH) and hydride (RuÀH)
[e]
4-MeOC
2-thienyl
2-furyl
6 3
H
16
[9]
1
1
1
2
7
8
9
0
3
2
2
3
transfer would be accelerated. Furthermore, the enhanced
NÀH acidity can enhance the hydrogen bond interaction be-
tween the NÀH group and the ketone, which will allure the
[
[
c]
c]
2-thienyl
CH
CH
2
N(Me)
N(Me)
2
2
C
C
6
H
H
5
2
5s
5a
[f]
6
5
ketone substrate closer to the metal center to improve enan-
tioselectivity.
[
a] Reaction conditions: 4 (2.5 mmol), catalyst (0.0025 mmol, 0.1 mol%),
tBuOK (0.05 mmol), solvent (2.5 mL). All of the reactions were carried
out under 10 atm of H2 at room temperature for 12 h unless otherwise
noted. The conversion of the substrates was determined to be>99% by
To explore the synthetic utility of this catalyst, we have in-
vestigated the substrate scope. A series of aromatic ketones
bearing different substituent groups on the phenyl ring, het-
eroaromatic ketones and functionalized ketones were sub-
jected to this hydrogenation process under the catalysis of
1
GC or by H NMR. [b] The ee value was determined by chiral GC or
HPLC. [c] 50 atm of H
2
, 30 h. [d] tBuOK (0.025 mmol, S/B=100/1).
[
e] With DPEphos. [f] The S/C=100000, 50 atm of H , and 48 h.
2
[
RuCl ACHTUNGTRENNUNG( DPPF) ACHTUNGTRENNUNG( 1d)] or [RuCl AHCTUNGTRENNNUG( DPEphos) ACHTNUGTRENNUNG( 1d)]. Full conver-
2
2
[10]
sions were observed for all substrates in 0.1 mol% catalyst
Nisoxetine).
The high catalytic capability of the present
loading, with ee values ranging from 88% to>99%
catalyst system was further evidenced at even lower catalyst
loading (0.001%). The acetophenone substrate 4a was
smoothly hydrogenated within 48 h with almost no ee value
erosion (97% ee; Table 2, entry 20). These results suggest
that this ruthenium catalyst composed with chiral diamine
and commercially available inexpensive achiral phosphane
ligand is practically useful to prepare a variety of chiral al-
cohols under mild conditions.
(
Table 2). Acetophenone derivates, which bear substituted
groups such as methyl, methoxyl, chloro, bromo, and fluoro
at para or meta positions, all reacted smoothly to afford the
desired corresponding secondary alcohol in high to excellent
ee values (Table 2, entries 2–7), except in the case of hydro-
genation of highly hindered ortho substituted acetophenone
(
Table 2, entry 8). The results indicated that there is no
major electronic effect on the substitution pattern of the
acetophenones. Hydrogenation of 1-naphthyl and 2-naphthyl
derivatives also gave excellent ee values. Prolonging the
alkyl chain of the primary alkyl phenyl ketones increased
the enantiomeric excess up to 99%. Cyclic aromatic ketones
such as 4m, 4n, and 4o were efficiently converted into the
corresponding chiral alcohols in 95 to 99% ee (Table 2, en-
tries 13–15). Meanwhile, heteroaromatic ketones were also
suitable for this hydrogenation. When 2-acetylfuran and 2-
acetylthiophene were used as substrates, the corresponding
alcohols were attained in 94 and 98% ee (Table 2, entries 16
and 17), respectively. In addition to the reduction of simple
ketones, we also examined the hydrogenation of functional-
ized ketones. Utilizing the optimized conditions b-amino ke-
tones 4r and 4s can be efficiently converted to the corre-
sponding b-amino alcohol 5s and 5t with up to 98% ee
In summary, a new type of efficient ruthenium catalysts
containing rigid chiral diamines and achiral diphosphanes
(DPPF or DPEphos) has been developed, which affords ex-
cellent enantioselectivities (up to 99% ee) and reactivities
(up to S/C=100000) in asymmetric hydrogenation of simple
aromatic ketones and functionalized ketones. The rigid
structure and electron-withdrawing nature of the chiral dia-
mines appear to be the key feature to enable the achiral
phosphane ligands to be applicable to construct highly effi-
cient ruthenium catalysts for asymmetric hydrogenation of
ketones. The tunable modular structure of the chiral dia-
mine enables us for the first time to observe a significant
electronic effect of the amine moiety which affects catalytic
performance. In contrast to many reports on the modifica-
tion of chiral phosphane ligands to mimic the Noyori cata-
lyst, the present work firstly demonstrated that high enan-
tioselective ruthenium catalysts could be established from
simple inexpensive achiral phosphanes and rigid chiral dia-
[11]
(
Table 2, entries 18 and 19), which are important chiral drug
intermediates (for Duloxetine, Fluoxetine, Tomoxetine, and
7762
www.chemeurj.org
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 7760 – 7763

Highly Enantioselective Hydrogenation of Aromatic Ketones
COMMUNICATION
mines. The results obtained in this work should stimulate
the search for simple and practical catalysts for enantiose-
lective hydrogenation of ketones with commercially avail-
able diphosphane ligands.
Ohkuma, K. Muniz, R. Noyori, J. Am. Chem. Soc. 2003, 125, 13490;
f) S. E. Clapham, A. Hadzovic, R. H. Morris, Coord. Chem. Rev.
2
004, 248, 2201; g) R. J. Hamilton, C. G. Leong, G. Bigam, M. Mis-
kolzie, S. H. Bergens, J. Am. Chem. Soc. 2005, 127, 4152; h) W. P.
Hems, M. Groarke, A. Zanotti-Gerosa, G. A. Grasa, Acc. Chem.
Res. 2007, 40, 1340; i) C. A. Sandoval, Y. Li, K. Ding, R. Noyori,
Chem. Asian J. 2008, 3, 1801.
[
5] For selected examples using chiral phosphane other than BINAP as
ligands, see: a) P. Cao, X. Zhang, J. Org. Chem. 1999, 64, 2127;
b) M. J. Burk, W. Hems, D. Herzberg, C. Malan, A. Zanotti-Gerosa,
Org. Lett. 2000, 2, 4173; c) J.-H. Xie, L.-X. Wang, Y. Fu, S.-F. Zhu,
B.-M. Fan, H.-F. Duan, Q.-L. Zhou, J. Am. Chem. Soc. 2003, 125,
Experimental Section
General procedure for the asymmetric hydrogenation of ketones: In a
glove box, the precatalyst [RuCl ACHNUTGTRENNUNG( DPPF) ACHNUTGTRENNNUG( 1d)] (0.0025 mmol), and
2
tBuOK (0.05 mmol), nPrOH were added to a test tube containing a stir-
ring bar. The resulting mixture was stirred at room temperature for
0 min before the aromatic ketone 4 (2.5 mmol) was introduced. The test
tube was then transferred to a stainless autoclave and then sealed it.
After taking the autoclave out of the glove box, the autoclave was
2 2
(10 atm) for three times and charged with H (10 atm)
carefully. The reaction mixture was then stirred at RT for 12 h, and H
4
404; d) J. Wu, J.-X. Ji, R. Guo, C.-H. Yeung, A. S. C. Chan, Chem.
Eur. J. 2003, 9, 2963; e) J. P. Henschke, A. Zanotti-Gerosa, P.
Moran, P. Harrison, B. Mullen, G. Casy, I. C. Lennon, Tetrahedron
Lett. 2003, 44, 4379; f) A. Hu, H. L. Ngo, W. Lin, Org. Lett. 2004, 6,
1
2
937; g) D. G. Genov, D. J. Ager, Angew. Chem. 2004, 116, 2876;
purged with H
Angew. Chem. Int. Ed. 2004, 43, 2816; h) R. Guo, R. H. Morris, D.
Song, J. Am. Chem. Soc. 2005, 127, 516; i) J.-H. Xie, Z.-T. Zhou, W.-
L. Kong, Q.-L. Zhou, J. Am. Chem. Soc. 2007, 129, 1868; j) W. Li,
X. Sun, L. Zhou, G. Hou, S. Yu, X. Zhang, J. Org. Chem. 2009, 74,
2
was carefully released. The reaction solution was removed and the con-
1
version was determined by GC or H NMR analysis. The residue was pu-
rified by flash silica gel column, and the enantiomeric excess of the prod-
uct was determined by chiral GC or HPLC.
1
397; For using racemic BINAP or chirally flexible diphosphane li-
gands: k) T. Ohkuma, H. Doucet, T. Pham, K. Mikami, T. Korenaga,
M. Terada, R. Noyori, J. Am. Chem. Soc. 1998, 120, 1086–1087;
l) K. Mikami, T. Korenaga, M. Terada, T. Ohkuma, T. Pham, R.
Noyori, Angew. Chem. 1999, 111, 517–519; Angew. Chem. Int. Ed.
Acknowledgements
1
999, 38, 495–497; m) K. Mikami, T. Korenaga, T. Ohkuma, R.
Noyori, Angew. Chem. 2000, 112, 3854–3857; Angew. Chem. Int. Ed.
000, 39, 3707–3710; n) K. Mikami, K. Wakabayashi, K. Aikawa,
This work was supported by the Chinese Academy of Sciences and the
National Natural Science Foundation of China (20802085).
2
Org. Lett. 2006, 8, 1517; o) Q. Jing, C. A. Sandoval, Z. Wang, K.
Ding, Eur. J. Org. Chem. 2006, 3606. For using a bulky achiral
monophosphane as ligand, see: p) Q. Jing, X. Zhang, J. Sun, K.
Ding, Adv. Synth. Catal. 2005, 347, 1193.
Keywords: achiral phosphanes
·
enantioselectivity
·
hydrogenation · ketones · ruthenium
[6] Although many kinds of chiral diamines have been exploited in
II
[
(bisphosphane)Ru ACHTUNGTERNNUN(G diamine)] complexes for asymmetric hydroge-
nation of ketones, to get high enantioselectivity and reactivity, the
chiral phosphane or special achiral ligand is required; see: a) ref.
[
1] For reviews, see: a) R. Noyori, Asymmetric Catalysis in Organic Syn-
thesis, Wiley, New York, 1994; b) Comprehensive Asymmetric Catal-
ysis, Vols. 1–3 (Eds.: E. N. Jacobsen, A. Pfaltz, H. Yamamoto),
Springer, Berlin, 1999; c) Catalytic Asymmetric Synthesis, 2nd ed.
[
4h]; some phosphorus free chiral amine-ruthenium catalysts have
been reported, see: b) M. Ito, M. Hirakawa, K. Murata, T. Ikariya,
Organometallics 2001, 20, 379; c) I. Karame, M. Jahjah, A. Messaou-
di, M. L. Tommasino, M. Lemaire, Tetrahedron: Asymmetry 2004,
(Ed.: I. Ojima), Wiley-Blackwell, New York, 2000; d) G.-Q. Lin, Y.-
1
5, 1569; d) T. Ohkuma, N. Utsumi, K. Tsutsumi, K. Murata, C. A.
M. Li, A. S. C. Chan, Principles and Applications of Asymmetric
Synthesis, Wiley-Blackwell, New York, 2001.
2] a) X. Zhang, Enantiomer 1999, 4, 541; b) W. Tang, X. Zhang, Chem.
Rev. 2003, 103, 3029; c) M. McCarthy, P. J. Guiry, Tetrahedron 2001,
Sandoval, R. Noyori, J. Am. Chem. Soc. 2006, 128, 8724; e) H.
Huang, T. Okuno, K. Tsuda, M. Yoshimura, M. Kitamura, J. Am.
Chem. Soc. 2006, 128, 8716; f) J. Ito, S. Ujie, H. Nishiyama, Chem.
Commun. 2008, 1923.
7] Q. Zhu, H. Huang, D. Shi, Z. Shen, C. Xia, Org. Lett. 2009, 11, 4536.
8] D. Liu, X. Zhang, Eur. J. Org. Chem. 2005, 646.
9] M. Kitamura, H. Nakatsuka, Chem. Commun. 2011, 47, 842.
10] a) S. I. Ankier, Prog. Med. Chem. 1986, 23, 121; b) D. W. Robertson,
J. H. Krushinski, R. W. Fuller, J. D. Leander, J. Med. Chem. 1988,
[
5
7, 3809.
[
[
[
[
3] For reviews, see: a) M. Kitamura, R. Noyori in Ruthenium in Organ-
ic Synthesis (Ed.: S.-I. Murahashi), Wiley-VCH, Weinheim, Germa-
ny, 2004, Chapter 2; b) R. Noyori, T. Ohkuma, Angew. Chem. 2001,
[
1
13, 40; Angew. Chem. Int. Ed. 2001, 40, 40; For Leading example:
c) T. Ohkuma, H. Ooka, S. Hashiguchi, T. Ikariya, R. Noyori, J. Am.
Chem. Soc. 1995, 117, 2675; d) T. Ohkuma, H. Ooka, T. Ikariya, R.
Noyori, J. Am. Chem. Soc. 1995, 117, 10417; e) H. Doucet, T.
Ohkuma, K. Murata, T. Yokozawa, M. Kozawa, E. Katayama, A. F.
England, T. Ikariya, R. Noyori, Angew. Chem. 1998, 110, 1792;
Angew. Chem. Int. Ed. 1998, 37, 1703; f) T. Ohkuma, M. Koizumi,
H. Doucet, T. Pharm, M. Kozawa, K. Murata, E. Katayama, T. Yo-
kozawa, T. Ikariya, R. Noyori, J. Am. Chem. Soc. 1998, 120, 13529.
4] For the mechanism of asymmetric hydrogenation of ketones cata-
lyzed by the Noyori catalyst, see: a) M. Yamakawa, H. Ito, R.
Noyori, J. Am. Chem. Soc. 2000, 122, 1466; b) R. Noyori, M. Yama-
kawa, S. Hashiguchi, J. Org. Chem. 2001, 66, 7931; c) R. Hartmann,
P. Chan, Angew. Chem. 2001, 113, 3693; Angew. Chem. Int. Ed.
3
1, 1412; c) J. Deeter, J. Frazier, G. Staten, M. Staznak, L. Weigel,
Tetrahedron Lett. 1990, 31, 7101–7104.
[
11] For some reactions, electron-poor phosphane ligands are more effi-
cient, for selected examples, see: a) S. Jeulin, S. Duprat de Paule, V.
Ratovelomanana-Vidal, J. GenÞt, N. Champion, P. Dellis, Angew.
Chem. 2004, 116, 324–329; Angew. Chem. Int. Ed. 2004, 43, 320;
b) C. Y. Legault, A. B. Charette, J. Am. Chem. Soc. 2005, 127, 8966;
c) C. K. Jana, A. Studera, Angew. Chem. 2007, 119, 6662; Angew.
Chem. Int. Ed. 2007, 46, 6542; d) K. Tani, D. C. Behenna, R. M.
McFadden, B. M. Stoltz, Org. Lett. 2007, 9, 2529; e) T. Korenaga, K.
Osaki, R. Maenishi, T. Sakai, Org. Lett. 2009, 11, 2325.
[
2
001, 40, 3581; d) K. Abdur-Rashid, M. Faatz, A. J. Lough, R. H.
Received: March 17, 2011
Morris, J. Am. Chem. Soc. 2001, 123, 7473; e) C. A. Sandoval, T.
Published online: May 26, 2011
Chem. Eur. J. 2011, 17, 7760 – 7763
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
7763