A class of readily available optically pure 7,7′-disubstituted BINAPs for asymmetric catalysis

Article abstract of DOI:10.1016/j.tet.2009.03.066

A class of optically pure 7,7′-disubstituted BINAPs have been prepared starting with a catalytic asymmetric oxidative coupling reaction. A general, concise, and straightforward synthetic procedure has been established, and is suitable for all optically pure 7,7′-disubstituted BINAPs 1a-h, regardless of the substituents' structure in the 7,7′-positions. The catalytic potential of this class of ligands has been investigated in the highly enantioselective Rh-catalyzed 1,4-addition of aryl boronic acids to enones (up to 99.8% ee), and Ru-catalyzed asymmetric hydrogenation of simple aromatic ketones (up to S/C=100,000, up to 98% ee) and β-ketoesters (up to S/C=10,000, up to 99.8% ee), respectively.

Full text of DOI:10.1016/j.tet.2009.03.066

Tetrahedron 65 (2009) 4130–4141
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
A class of readily available optically pure 7,70-disubstituted
BINAPs for asymmetric catalysis
,
a
a
a
a,b,
*
Wei-Cheng Yuan a , Lin-Feng Cun , Ai-Qiao Mi , Yao-Zhong Jiang , Liu-Zhu Gong
*
a Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041, China
b Hefei National Laboratory for Physical Sciences at the Microscale and Department of Chemistry, University of Science and Technology of China, Hefei 230026, China
a r t i c l e i n f o
a b s t r a c t
A class of optically pure 7,70-disubstituted BINAPs have been prepared starting with a catalytic asym-
metric oxidative coupling reaction. A general, concise, and straightforward synthetic procedure has been
established, and is suitable for all optically pure 7,70-disubstituted BINAPs 1a–h, regardless of the sub-
stituents’ structure in the 7,70-positions. The catalytic potential of this class of ligands has been
investigated in the highly enantioselective Rh-catalyzed 1,4-addition of aryl boronic acids to enones (up
to 99.8% ee), and Ru-catalyzed asymmetric hydrogenation of simple aromatic ketones (up to
Article history:
Received 19 November 2008
Received in revised form 18 March 2009
Accepted 20 March 2009
Available online 1 April 2009
Keywords:
S/C¼100,000, up to 98% ee) and
b
-ketoesters (up to S/C¼10,000, up to 99.8% ee), respectively.
7,70-Disubstituted BINAPs
Oxidative coupling
Asymmetric catalysis
1,4-Addition
Ó 2009 Elsevier Ltd. All rights reserved.
Asymmetric hydrogenation
1. Introduction
of unsaturated carboxylic acids,7 and the chiral biaryl bisphosphine
ligand SEGPHOS provides greater enantioselectivities than BINAP in
Ru-catalyzed hydrogenation of a wide variety of carbonyl com-
pounds.8 In addition, 3,30-, 4,40-, 5,50-, and 6,60-disubstituted BINAPs
have been synthesized and exhibit different enantiocontrol ability
from mother BINAP in some catalytic asymmetric reactions.6b
The subtle modulation of the dihedral angle and electronic prop-
erties of BINAP maybe lead to an improvementof catalytic behavior of
the ligand. In principal, introducing substituents at 7,70-positions of
BINAP should alter the dihedral angle and electronic properties to
a certain degree. Therefore, we envisioned that the 7,70-disubstituted
BINAPs would exhibit different catalytic behavior from the mother
BINAP in asymmetric catalysis. However, in sharp contrast to nu-
merous studies on 3,30-, 4,40-, 5,50-, and 6,60-disubstituted BINAP
derivatives,6 there are few reports on synthesizing and usingoptically
pure 7,70-disubstituted BINAPs in catalytic asymmetric reactions so
far.9 This may be resulted from lacking convenient methods to syn-
thesize them. To the best of our knowledge, the preparation of 7,70-
disubstituted BINAPs mainly subjected to the indispensable tedious
resolution of 7,70-disubstituted BINOLs.9 Thus developing easily ac-
cessible approach to 7,70-disubstituted BINAPs is still a challenge.
Recently, we have discovered three types of chiral oxovanadium
complexes for catalytic asymmetric oxidative coupling of 2-naph-
thols, and very high enantioselectivity has been achieved.10 Based on
this procedure, a class of optically pure 7,70-disubstituted BINOLs
were conveniently prepared and applied in catalytic asymmetric
addition of phenylacetynylzincs to aldehdyes with excellent
Transition metal-catalyzed asymmetric transformation plays
a very important role in modern organic chemistry, in which
searching for highly efficient chiral ligands is the key objective to
obtain high reactivity and enantioselectivity.1 Over the past four
decades, thousands of chiral ligands have been synthesized for
a variety of catalytic asymmetric reactions in both academic re-
search and industrial production.1,2 Among them, chiral phosphorus
ligands have received much more attention since Knowles and
Sabacky3a and Horner and co-workers3b pioneered the asymmetric
hydrogenation with rhodium complexes of chiral phosphorus li-
gands in the late 1960s. In the history of chiral phosphorus ligands,
BINAP (2,20-bis(diphenylphosphino)-1,10-bi-naphthyl), discovered
by Noyori and co-workers in 1980,4a appears to be the most fre-
quently applied ligand for asymmetric catalysis.2,4 Indeed, many
asymmetric transformations can be carried out with metal com-
plexes of chiral BINAP ligand in very good enantioselectivity since
this particular ligand exhibits atropoisomerism.2,4,5 Many modified
BINAP derivatives have also been developed by fine-tuning both the
steric and electronic properties of BINAP scaffold in order to obtain
higher efficiency and selectivity.6 For example, H8-BINAP provides
better enantioselectivity than BINAP in Ru-catalyzed hydrogenation
* Corresponding authors. Fax: þ86 28 8522 3978.
E-mail address: yuanwc@cioc.ac.cn (W.-C. Yuan).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.03.066

W.-C. Yuan et al. / Tetrahedron 65 (2009) 4130–4141
4131
enantioselectivities.11 As a logical extension, we decided to prepare
7,70-disubstituted BINAPs (7,70-disubstituted-2,20-bis(diphenylphos-
phino)-1,10-binaphthyls) starting from optically pure 7,70-dis-
ubsituted BINOLs, and further investigate their catalytic potential in
asymmetric reactions.
We have previously communicated the syntheses of a series of
ligands 1a, 1e–h (Scheme 1) and their applications in Rh-catalyzed
highly enantioselective 1,4-additions of aryl boronic acids to
enones.12 In this article, we will give full details of the syntheses of
the optically pure 7,70-disubstituted BINAPs ligands and provide
a general, concise, and straightforward synthetic procedure suit-
able for all ligands 1a–h, regardless of the substituents’ structure in
the 7,70-positions. In addition to previously reported Rh-catalyzed
1,4-addition reactions of aryl boronic acids to enones, evaluations
of this class of 7,70-disubstituted BINAPs ligands in Ru-catalyzed
hydrogenation reaction of simple aromatic ketones and
obtained by recrystallization from dry toluene/methanol at 0 ꢀC
with an overall 56% yield from 5g. Unfortunately, partial racemi-
zation took place during the course of preparing ligands 1e, 1f, and
1h with the same process as described in Scheme 3.
The partial racemization was determined by 31P NMR spectrum
of the complexes formed from [RuCl2(benzene)]2, (R,R)-1,2-diphe-
nylenediamine (DPEN), and ligands 1e, 1f, and 1h, respectively. We
chose ligand 1h as one example to elaborate the partial racemiza-
tion (Fig. 1). The Ru-complex of optically pure ligand (R)-1g showed
sole peak at 46.00 ppm in 31P NMR spectrum (Fig. 1, C), and the
similar Ru-complex of racemic ligand (ꢁ)-1g showed a couple of
same absorption intensity peaks at 46.04 ppm and 45.69 ppm in
31P NMR spectrum (Fig. 1, B). However, one stronger peak at
46.04 ppm and one weaker peak at 45.70 ppm were showed in the
31P NMR spectrum of the Ru-complex of ligand 1g, this one ligand
was synthesized through the procedure as described in Scheme 3. It
can be seen from Figure 1 that the stronger peak (46.04 ppm, Fig. 1,
A), the left peak (46.04 ppm, Fig. 1, B), and the sole peak (46.00 ppm
Fig. 1, C) should be assigned to Ru-complex of (R)-isomer 1h.
Meanwhile, the weaker peak (45.70 ppm, Fig. 1, A), the right peak
(45.69 ppm, Fig. 1, B) belong to Ru-complex of (S)-isomer 1h. From
these, we concluded that ligand 1h had partial racemized during
the course of preparation, but the cause of partial racemization in
synthesizing ligands 1e, 1f, and 1h through the procedure as de-
scribed in Scheme 3 is unclear.
b
-ketoesters are also discussed.
O
O
RO
RO
PPh2
PPh2
PPh2
PPh2
O
O
PPh2
PPh2
H2C
O
n
n
1a, R = Me
1b, R = Et
1g, n = 1
1h, n = 2
1e, n = 6
1f, n = 8
Yokozawa and Saito recently developed the phosphination re-
action of BINOL ditriflate with diphenylphosphine catalyzed by
a Pd-complex generated in situ from Pd2(dba)3$CHCl3 and dppp,
and achieved optically active BINAP in high yield.9c Based on this
literature procedure,9c the phosphination reactions of 7,70-di-
substituted BINOL ditriflates 5e, 5f, and 5h with diphenylphosphine
were conducted in the presence of 5 mol % palladium catalyst
generated in situ from Pd2(dba)3$CHCl3 and dppp using DMF as
solvent at 100 ꢀC (Scheme 4). We were pleased to find that not only
this method smoothly provided the desired products but also this
approach tolerated a wide range of substrates regardless of the
substituents’ structure in the 7,70-positions. Thus, all the chiral li-
gands 1a–h were obtained in good yields without any racemization
(Scheme 4). This new family of optically pure 7,70-disubstituted
BINAPs were smoothly prepared from corresponding 7,70-di-
substituted BINOLs obtained from the catalytic asymmetric oxida-
tive coupling reaction. To the best of our knowledge, this synthetic
route is the most concise and straightforward to prepare 7,70-di-
substituted BINAPs ligand to date.
1c, R = n-Pr
1d, R = i-Pr
Scheme 1. The chiral ligands evaluated in this study.
2. Results and discussion
2.1. Synthesis of chiral 7,70-disubstituted BINAPs ligands 1a–h
Starting from an asymmetric oxidative coupling reaction of
readily accessible 7-alloxyl-2-naphthol 2 in the presence of 5 mol %
chiral oxovanadium catalyst,10 optically pure 7,70-disubstituted
BINOLs 4a–h wereconvenientlyobtained (Scheme 2).11 According to
the literature procedure,13 treatment of 4a–h with triflic anhydride
(Tf2O) and pyridine in CH2Cl2 afforded 7,70-disubstituted-binaph-
thols ditriflates 5a–h in almost quantitative yields. The ditriflates
5a–d were then coupled with diphenylphosphine in the presence of
10 mol % nickel(II) catalyst and DABCO as base in DMF at 100 ꢀC for
2–3 days afforded optically pure 7,70-disubstituted BINAPs ligands
1a–d in 73%, 70%, 61%, and 66% yields, respectively. However, ligands
1e–h were not obtained under the same conditions even for pro-
longed reaction time (Scheme 2). This difference between 5a–d and
5e–h presumably arises from the steric properties of the sub-
stituents at 7,70-positions. In the cases of preparing 1e–h, 7,70-po-
sitions of 5e–h are linked by an alkyl or crown ether forming cyclic
substituents, which maybe have some effects on the dihedral angle
of BINAP scaffold and thus inhibited the coupling reactions.
Since the phosphination steps of 5e–h with diphenylphosphine
in the presence of Ni(dppe)Cl2 failed to directly give the desired
products, an indirect synthetic pathway was attempted (Scheme
3).14 Monophosphination of 5g with diphenylphosphine oxide in
the presence of 5 mol % of palladium complex generated in situ
from palladium acetate and 1,4-bis(diphenylphosphino)butane
(dppb) gave compound 6, which was subsequently reduced into 7
with trichlorosilane (Cl3SiH). Compound 8 was obtained by the
phosphination of intermediate 7 with diphenylphosphine oxide
under similar conditions to those of the preparation of 6 from 5g,
and subsequently was reduced by Cl3SiH to afford the desired li-
gand 1g. Although this synthetic process included several steps, it
was noteworthy that the purification of all intermediates 6, 7, and 8
was normally unnecessary and the optically pure ligand 1g was
2.2. Rh-catalyzed 1,4-addition of aryl boronic acids to enones
Among the catalytic asymmetric carbon–carbon bond formation
reactions catalyzed by chiral transition metal complexes, the cata-
lytic asymmetric 1,4-addition reaction holds a prominent position
because it is frequently used in organic synthesis.15 Considerable
efforts have been recently made on the asymmetric 1,4-addition of
organometallic reagents to electron deficient olefins and the im-
portant progress has been achieved in this field.16 One of the sig-
nificant cases, Rh-catalyzed highly enantioselective 1,4-addition
addition of aryl boronic acids to enones was reported by Hayashi
and co-workers in 1998.17
To evaluate the catalytic potential of ligands 1a–h in the
asymmetric catalysis, we first explored Rh-catalyzed enantiose-
lective 1,4-addition of aryl boronic acids to enones. A model re-
action of cyclohexenone 9a with phenyl boronic acid 10a was
carried out in the presence of Ru-complex in situ generated from
Rh(acac)(C2H4)2 and either of ligands 1a–h according to the liter-
ature reaction conditions.17 As shown in Table 1, all the ligands were
excellent for the 1,4-addition reaction, good to excellent yields with
high enantioselectivities were obtained. High to 98% and 99% ees

4132
W.-C. Yuan et al. / Tetrahedron 65 (2009) 4130–4141
OH
OH
OH
RO
RO
ref. 10
ref. 11
O
O
O
OH
OH
2
3
4a-h
Ph2PH, Ni(dppe)Cl2
DABCO
Tf2O, pyridine
CH2Cl2, 0 °C
RO
OTf
OTf
RO
RO
PPh2
PPh2
DMF, 2-3 days
100 °C
RO
1a, R = CH3
5a-h
1b, R = CH2CH3
1c, R = CH2CH2CH3
1d, R = CH(CH3)2
Ph2PH, Ni(dppe)Cl2
DABCO
O
PPh2
PPh2
O
OTf
OTf
H2C
H2C
DMF, 2-3 days
100 °C
O
O
n
n
1e, n = 6
1f, n = 8
5e, n = 6
5f, n = 8
Ph2PH, Ni(dppe)Cl2
DABCO
O
O
PPh2
PPh2
OTf
OTf
O
O
O
O
DMF, 2-3 days
100 °C
n
n
1g, n = 1
1h, n = 2
5g, n = 1
5h, n = 2
Scheme 2. The synthesis of ligands 1a–d.
were obtained with 1b or 1c as chiral ligand, respectively (Table 1,
entries 2 and 3), but ligand BINAP gave 97% ee.17 Ligand 1g resulted
in the corresponding adduct in nearly quantitative yield and 97% ee
under the same condition (Table 1, entry 7). Ligands 1a, 1d–1f, and
1h all resulted in very high catalytic activity and enantioselectivity
(Table 1, entries 1, 4–6, and 8). These observations indicate that the
substituents at 7,70-positions of the ligands have some effect on the
ligand’s stereocontrol ability. Notably, decreasing the catalyst
loading from 3 mol % to 1 mol %, product 11a was obtained in 97%
ee and 92% yield (Table 1, entry 9). Further decreasing the catalyst
loading to 0.5 mol %, product 11a was obtained in 92% ee and 75%
yield with a slightly prolonged reaction time (Table 1, entry 10).
Electron-donating groups at 7 and 70 positions of BINAP scaffold
may increase the electron density of the phosphine atom compar-
ing that of mother BINAP. The electron rich phosphorus may
therefore contribute to the higher activity.
Ligand 1g was chosen to perform the further study because it
provided the very comparable results to BINAP under the same re-
action.17 The 1,4-additions of a range of aryl boronic acids bearing
either electron-donating or -withdrawing groups to cyclohexenone
O
Ph2(O)H, Pd(OAc)2
PPh2
dppb, iPr2NEt
DMSO, 100 °C
O
O
Cl3SiH, iPr2NEt
O
OTf
OTf
O
O
Toluene, 100 °C
O
OTf
5g
6
Ph2(O)H, Pd(OAc)2
dppb, iPr2NEt
PPh2
O
PPh2
Cl3SiH, iPr2NEt
toluene, 100 °C
O
O
O
PPh2
OTf
O
O
O
DMSO, 100 °C
8
7
O
O
PPh2
PPh2
O
1g
Scheme 3. The synthesis of ligand 1g.

W.-C. Yuan et al. / Tetrahedron 65 (2009) 4130–4141
4133
Table 1
1,4-Addition of phenyl boronic acid to cyclohexenone catalyzed by ligands 1–Rh(I)
complexesa
O
O
3 mol % Rh(acac)(C2H4)2
46.0433
1 (1 equiv to Rh)
46.0431
PhB(OH)
+
2
45.9856
45.6922
*
dioxane/H2O (10/1)
100 °C
Ph
a
a
10a
9a
45.7019
11aa
b
Entry
Ligand
Time (h)
Yieldb (%)
eec (%)
b
1
2
3
4
5
6
7
8
9
10
1a
1b
1c
1d
1e
1f
1g
1h
1g
1g
5
5
5
5
5
5
5
5
5
8
83
93
90
85
90
82
99
92
92
75
94
98
99
96
91
92
97
97
97d
92e
60
40
20
50
40
50
45
A
40
B
C
Figure 1. The 31P NMR spectra of Ru-complexes for different purity ligands 1h. A: The
ligand 1h synthesized by procedure as described in Scheme 3; (major R and minor S)-
1h–RuCl2–(RR)DPEN, peak a,
(RR)DPEN, peak a, z46.04 ppm; peak b,
single peak z46.00 ppm.
d
z46.04 ppm; peak b,
dz45.70 ppm. B: (rac)-1h–RuCl2–
z45.69 ppm. C: (R)-1h–RuCl2–(RR)DPEN,
d
d
d
a
For a general reaction procedure, see Experimental section.
Isolated yield based on cyclohexenone 9a.
The ee values were determined by HPLC and the absolute configuration was R
b
c
assigned by comparison of the sign of the optical rotation with reported data.17
were conducted. As shown in Table 2, excellent ee values ranging
from 94% to 99.8% were obtained and all the reactions successfully
proceeded in 5 h and gave the corresponding adducts in very high
yields. 4-tert-Butylboronic acid 10e and 4-trifluorometyhlboronic
acid 10f both underwent the catalytic asymmetric additions and the
resulting adducts were obtained in even over 99% ee (Table 2, entries
5 and 6). It is obvious from the results in Table 2 that the catalyst
Rh(I)–1g possesses very high activity and stereocontrol ability in the
1,4-addition of aryl boronic acids 10a–g to cyclohexenone 9a and
these results are comparable to BINAP in these reactions.17
d
In the presence of 1.0 mol % catalyst.
In the presence of 0.5 mol % catalyst.
e
catalytic asymmetric hydrogenation of prochiral simple aromatic
ketones appears to be the most facile route to produce enantio-
merically enriched secondary alcohols, which are important
building blocks for the synthesis of many natural products and
pharmaceutical compounds. This reaction has been also extensively
used as a model reaction to evaluate various diphosphine ligands in
asymmetric hydrogenation.19 Our further exploration of 7,70-di-
substituted BINAPs ligands 1a–h in asymmetric catalysis was fo-
cused on applying Ru-complex of this class of ligands to this
hydrogenation reaction. These reactions were performed with the
literature catalytic system developed by Noyori and co-workers.20
The catalysts were easily prepared according to the following
procedure. The reaction mixture of ligands 1a–h and 0.5 equiv
[RuCl2(benzene)]2 in anhydrous and degassed DMF was stirred for
10 min at 100 ꢀC, followed by addition of 1.0 equiv of (R,R)-1,2-
diphenylethylenediamine (DPEN) to the reddish solution at room
temperature. The resulting mixture was stirred for 3–4 h at room
temperature. The solvent was removed under high vacuum at 50 ꢀC
and the light brown complex was used for hydrogenation reaction
without further purification. All the catalysts showed single signal
The optimized protocol was then extended to different types of
-unsaturated ketones. The results were summarized in Table 3.
Rh(I)–1g exhibited high enantioselectivities for various -un-
a
,
b
a,b
saturated ketones. Comparing with cyclohexenone 9a (Table 2,
entry 1), cyclopentenone 9b and cycloheptenone 9c resulted in
slightly lower, but still high, up to 90% ee values, respectively (Table
2, entries 2 and 3), which were similar to the results provided with
BINAP served as catalyst in the same reaction.17 However, phenyl
boronic acid added to a linear enone substrate 9d furnishing 11da
in 88% yield and a 97% ee (Table 2, entry 4). This result also is similar
to that of Rh(I)–BINAP catalyzed same reaction.17
In term of all the results summarized in Tables 1–3, 7,70-di-
substituted BINAPs ligands 1a–h demonstrated the considerable
catalytic potential for catalytic asymmetric 1,4-addition reactions of
aryl boronic acids to both cyclic and linear enones with high ac-
tivities and enantioselectivites. These results were comparable to
the best results observed with BINAP as ligand in this reaction.
in the 31P NMR spectrum and the chemical shift values (
listed in Table 4.
d) were
Table 2
Asymmetric 1,4-addition of arylboronic acids to cyclohexenone catalyzed by ligands
Rh(I)–1g complexa
2.3. Ru-catalyzed enantioselective hydrogenation of simple
aromatic ketones
O
O
3 mol % Rh(acac)(C2H4)2
1g (1 equiv to Rh)
+
ArB(OH)2
Among the extraordinary advances achieved in catalytic asym-
metric reactions, asymmetric hydrogenation remains to be an at-
tractive method to prepare chiral material due to the fact that it
provides a powerful, efficient, and atom economic avenue for
biologically active compounds and advanced materials.2a,18 The
dioxane/H2O (10/1)
100 °C, 5 h
*
Ar
11aa-ag
9a
10a-g
Entry
ArB(OH)2
Ar
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
10a
10b
10c
10d
10e
10f
Ph
99
85
90
92
86
84
97
97
98
96
96
99
4-ClC6H4
4-MeOC6H4
3-MeOC6H4
4-tBuC6H4
4-CF3C6H4
4-CH3C6H4
Ph2PH, dppp
PPh2
PPh2
RO
RO
OTf
OTf
Pd2(dba)3 CHCl3
RO
RO
iPr2NEt, DMF
100 °C, 48 h
99.8
94
10g
a
For a general reaction procedure, see Experimental section.
Isolated yields based on cyclohexenone 9a.
The ee values were determined by HPLC and the absolute configuration was R
5
1e, 1f, 1h
1a-d and 1g also
b
c
assigned by comparison of the sign of the optical rotation with reported data.17
Scheme 4. The synthesis of ligands 1e, 1f, and 1h.

4134
W.-C. Yuan et al. / Tetrahedron 65 (2009) 4130–4141
Table 3
Table 5
Asymmetric 1,4-addition of phenyl boronic acids to enones 11 catalyzed by ligands
Enantioselective hydrogenation of 1-acetonaphthone (12a) to alcohol 13aa
1g–Rh(I) complexa
O
OH
O
3 mol % Rh(acac)(C2H4)2
O
Ph
*
[(1a-h)-RuCl2-DPEN](R,RR)
tBuOK, iPrOH, H2, rt.
1 (1 equiv to Rh)
R1
R2
+
PhB(OH)2
R2
R1
dioxane/H2O (10/1)
100 °C
9a-d
11aa-da
10a
12a
13a
Entry
Enones 9
Time (h)
Yieldb (%)
99
eec (%)
Entry
Ligand
S/Cb
2000
2000
2000
2000
2000
2000
2000
2000
5000
Time (h)
Convc (%)
eed (%)
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
1g
1h
1c
1c
1c
8
8
8
8
8
8
8
8
100
100
100
100
100
100
100
100
>99
>99
>99
96
96
98
96
92
96
91
94
97
97
97e
O
1
2
5
97
9a
O
5
5
90
82
90d
9
10
11
10
16
30
10,000
100,000
9b
a
Unless otherwise stated, the reaction was conducted at 25–28 ꢀC with a 1.0 M
solution of substrate (2 mmol) in 2-propanol in the presence of (CH3)3COK (base/
catalyst¼70:1). H2 pressure was 40 atm.
O
3
4
90
97
b
The molar ratio of substrate to catalyst.
Determined by GC on CP-Cyclodex
Determined by GC on CP-Cyclodex
c
b
b
-236M column or crude 1H NMR.
-236M column. Absolute configuration is S
d
9c
and assigned by the sign of rotation.
e
The solution concentration was 2.0 M. and temperature was 60 ꢀC.
O
5
88
9d
found that methyl ketone substrates containing an electron-
donating or -withdrawing group at ortho-position of phenyl ring
were the better substrates for asymmetric hydrogenation (Table 6,
entries 1, 12, and 16), while containing meta- or para-substituent
substrates gave lower enantioselectivites than that containing
ortho-substituent substrates. For instance, substrate 12m was hy-
drogenated to give the product in 94% ee, whereas 12n gave only
71% ee under the same conditions (Table 6, entries 12 and 13).
Analogous examples, substrates 12b and 12h gave the products in
90% and 81% ee under identical conditions, respectively (Table 6,
entries 1 and 7). The reduction of 20-acetonaphthone 12k gave only
77% ee (Table 6, entry 10), but the model substrate 10-acetonaph-
thone 12a afforded 98% ee (Table 5, entry 3). Comparing meta-
para-disubstituted substrate 12o with ortho-para-disubstituted
substrate 12p, the former afforded 77% ee but the latter afforded
90% ee under the same conditions. These results suggest the ortho-
substituted group has important effects on the enantioselectivity
(Table 6, entries 14 and 15). Interestingly, substrates 12f and 12g
bearing the same substituent group in the phenyl ring were
smoothly reduced under the same conditions but exhibited dif-
ferent enantioselectivity, which may be due to the different elec-
tronic effect resulted from the positions’ difference of substituents
in phenyl ring (Table 6, entries 5 and 6).
We also found that the size of the alkyl substituent in aromatic
ketones 12 was another factor to influence the enantioselectivity.
Only a slight drop was observed comparing propiophenone 12i
with benzylphenone 12e (Table 6, entries 8 and 4), but an apparent
ee value decrease from 88% to 73% was observed by comparing
isopropylphenone 12j with benzylphenone 12e (Table 6, entries 4
and 9). Since 1-ferrocenylethanol is a crucial starting material in the
synthesis of many chiral ferrocene compounds such as ferroceny-
lethylamines and ferrocenylphosphines,21 we subjected acetyl-
ferrocene 12l under the optimized conditions and it was reduced to
(S)-1-ferrocenylethanol in 79% ee at S/C¼1000 (Table 6, entry 11).
Based on all of the above observations, we can easily conclude
that Ru-complexes (RRR)-[(1a–h)–RuCl2–DPEN] are highly active
and efficient in catalytic asymmetric hydrogenation of simple aro-
matic ketones. Almost quantitative yields and moderate to excellent
enantioselectivities are furnished throughout all the substrates
a
b
c
For a general reaction procedure, see Experimental section.
Isolated yield based on unsaturated ketones 9a–d.
The ee values were determined by HPLC and the absolute configuration was R
assigned by comparison of the sign of the optical rotation with reported data.17
d
The ee value was determined by GC and the absolute configuration was R as-
signed by comparison of the sign of the optical rotation with reported data.17
With these optically active catalysts in hand, 1-acetonaphthone
12a was chosen as a model substrate to optimize ligands and re-
action conditions. The results were summarized in Table 5. As can
be seen in Table 5, 1-acetonaphthone 12a could be smoothly re-
duced to alcohol 13a in 8 h with very high enantioselectivies with
the catalysts formed from ligands 1a–h (Table 5, entries 1–8). The
best results, 100% conversion and 98% ee, were obtained with the
catalyst generated from ligand 1c under 40 atm of hydrogen pres-
sure and a catalyst loading of 0.05 mol % at room temperature
(Table 5, entry 3). This result is slight better than that obtained with
complex [RuCl2{(R)-BINAP}{(R,R)-DPEN}] as a precatalyst.20 To
further examine the catalytic potential, we found that more than
99% conversion and 97% ee were obtained in 10 h by decreasing the
catalyst loading to 0.02 mol % (Table 5, entry 9). The catalyst loading
was decreased to 0.01 mol % without loss of enantioselectivity, but
the reaction required prolonged time of 16 h (Table 5, entry 10). It is
noteworthy that the catalyst was further decreased to 0.001 mol %,
to get the same results, we only need to prolong the reaction to 30 h
and elevate the reaction temperature to 60 ꢀC (Table 5, entry 11).
The optimized protocol was then extended to a variety of
aromatic ketones in order to further examine the ligands. The hy-
drogenation reactions were conducted with 0.05% loading of Ru-
complex formed from ligand 1c under 40 atm of hydrogen pressure
at room temperature. The results are summarized in Table 6. It was
Table 4
The chemical shift values (
1a–h
d
) of 31P NMR signal of catalysts derived from ligands
Entry
Ligand
(ppm)
1
1a
45.70
2
1b
45.72
3
4
5
6
7
8
1c
1d
1e
1f
1g
1h
d
45.70
45.67
46.41
45.90
46.68
46.00

W.-C. Yuan et al. / Tetrahedron 65 (2009) 4130–4141
4135
Table 6
Table 8
Enantioselective hydrogenation reactions of aromatic ketones catalyzed by (RRR)-
1c–RuCl2–DPEN complexa
Asymmetric hydrogenation of b
-ketoesters with 1c as the liganda
O
O
OH
O
Ru(1c)(C6H6)Cl2
O
OH
*
R1
OR2
R1
OR2
1c-RuCl2-DPEN, H2
tBuOK, iPrOH, r.t.
C2H5OH, H2
14b-g
15b-g
Ar
R
12b-q
Ar
R
13b-q
Entry
1
Substrate
S/Cb
Time (h)
12
Convc (%)
eed (%)
96
Entry Ketone Ar
R
Time (h) Convb (%) eec (%)
O
O
1
2
3
4
5
6
7
8
12b
12c
12d
12e
12f
12g
12h
12i
o-CH3C6H5
C6H5
C6H5
CH3
CH3
(CH2)3CH3
CH2Ph
CH3
CH3
CH3
CH2CH3
CH(CH3)2
CH3
8
8
100
>99
>99
>99
100
>99
>99
100
>99
100
>99
100
100
>99
100
>99
90
81
87
88d
88
78
81
85
73
1000
>99
OtBu
8
8
8
8
8
8
8
(14b)
C6H5
m-CH3OC6H5
p- CH3OC6H5
p-CH3C6H5
C6H5
O
O
2
1000
12
>99
98
O
(14c)
9
12j
12k
12l
12m
12n
12o
12p
12q
C6H5
O
O
10
11
12
13
14
15
16
20-Naphthyl
Ferrocenyl
o-ClC6H5
m-ClC6H5
8
77
3
4
5
1000
5000
12
15
20
100
100
>99
99
98
98
CH3
CH3
CH3
12
10
10
8
79d,e
94
71
OCH3
OCH3
OCH3
(14d)
O
O
O
3,4-(CH3O)2C6H5 CH3
2,4-(Cl)2C6H5
o-BrC6H5
77
CH3
CH3
10
15
90
94e
(14d)
a
Unless otherwise stated, the reaction was conducted at 25–28 ꢀC with 1.0 M
O
solution of substrate (2 mmol) in 2-propanol in the presence of (CH3)3COK (base/
10,000
catalyst¼70:1). H2 pressure was 40 atm. The molar ratio of substrate to catalyst is
2000.
(14d)
b
Determined by GC on CP-Cyclodex
Determined by GC on CP-Cyclodex
b
b
-236 M column or 1H NMR.
-236 M column. Absolute configuration was
S and determined by the sign of rotation.
c
O
O
6
7
1000
1000
12
26
>99
>99
91e
85f
ClH2C
OC2H5
d
The ee values were determined by HPLC and the absolute configuration was S.
S/C¼1000. The solution concentration was 2.0 M and the temperature was 60 ꢀC.
(14e)
e
O
O
examined, in addition, these results obtained herein are slight better
or similar to those provided by their analogue complex RuCl2{(R)-
BINAP}{(R,R)-DPEN}] in the same hydrogenation reaction.20
Ph
OC2H5
(14f)
O
O
8
1000
12
100
99.8
OCH3
2.4. Ru-catalyzed enantioselective hydrogenation
(14g)
of
b-ketoesters
a
Unless otherwise stated, the reaction was carried out in EtOH with 1.0 M solu-
tion of substrate (2 mmol) and 30 atm of hydrogen pressure at 50 ꢀC.
Optically pure
b
-hydroxyl ester belongs to a very important class
b
The molar ratio of substrate to catalyst.
Determined by GC on a
Determined by GC on a
of compound, because they are widely used for natural products
synthesis.22 To the best of our knowledge, among the studies
reported, one of the most successful protocols is the asymmetric
c
b
-225 capillary column or crude 1H NMR.
-225 capillary column.
d
e
b
Product was acylated to 3-acetoxy-4-chloro-butyric acid ethyl ester 15e in
hydrogenation of
b-ketoesters using chiral Ru-complex of phos-
pyridine and acetic anhydride for ee value determination by GC analysis.
f
phine ligand as catalyst.1a,18a,23 Initially, Noyori and co-workers
successfully reported that the chiral ruthenium catalyst of BINAP
was efficient for this reaction.23a To further investigate the utility of
ligands 1a–h in the asymmetric catalysis, another asymmetric
The conversion and ee value were determined by HPLC on Chiralpak OD-H col-
umn. Additive is HI, substrate/[Ru(benzene)Cl2]/ligand/adductive¼1000:1:1.1:1.5.
hydrogenation reaction was examined with these ligands. Herein,
we present the results of apply ligands 1a–h in catalytic asym-
Table 7
metric hydrogenation of
according to the literature procedure.23a
Initial studies were aimed at determining the most optimal re-
action conditions for the asymmetric hydrogenation of -ketoesters
b-ketoesters to chiral b-hydroxyl esters
Asymmetric hydrogenation of ethyl acetoacetate with 1a–h as the ligandsa
O
O
OH
O
Ru(1a-h)(C6H6)Cl2
b
OC2H5
C2H5OH, H2
OC2H5
15a
using ethyl acetoacetate 14a as a standard substrate. The experi-
mental results are summarized in Table 7. It was found that all of
the catalysts, which were in situ generated from [RuCl2(benzene)]2
and 2 equiv of ligands 1a–h, exhibited high activity and gave ex-
cellent enantioselectivity under the mild conditions (S/C¼1000,
50 ꢀC, 30 atm, and EtOH as solvent) (Table 7, entries 1–8). Under the
optimized reaction conditions, we found that elevating tempera-
ture from 50 ꢀC to 85 ꢀC under 30 atm of H2 pressure (Table 7, entry
9) or increasing H2 pressure from 30 atm to 60 atm at 50 ꢀC (Table 7,
entry 10) both using 1c as ligand, the conversion and ee values were
maintained. Based on these preliminary results, we chose ligand 1c,
reaction temperature 50 ꢀC, S/C¼1000, and 30 atm of hydrogen
pressure as the set of optimized conditions.
14a
Entry
Ligand
T (ꢀC)
50
P (atm)
Convb (%)
eec (%)
1
2
3
4
5
6
7
8
9
10
1a
1b
1c
1d
1e
1f
1g
1h
1c
1c
30
30
30
30
30
30
30
30
30
60
100
100
100
100
100
100
100
100
100
100
98
97
98
97
97
97
96
98
98
98
50
50
50
50
50
50
50
85
50
a
Unless otherwise stated, the reaction was carried out in EtOH with 1.0 M solu-
tion of substrate (2 mmol) for 12 h. The molar ratio of substrate to catalyst was 1000.
b
Determined by GC on
Determined by GC on
b
-225 capillary column or crude 1H NMR.
-225 capillary column.
As a reasonable extension of the optimized procedure, hydro-
genation reactions of a variety of b-ketoesters were then performed
c
b

4136
W.-C. Yuan et al. / Tetrahedron 65 (2009) 4130–4141
and all the results are listed in Table 8. The results indicated that
very high enantioselectivities and almost complete conversions
were achieved with Ru-complex formed from ligand 1c in all cases
(Table 8). We also found that ligand 1c proceeded well in the
asymmetric reduction of alkyl acetoacetates regardless of the
bulkiness of the alkyl group (Table 8, entries 1–3). Ligand 1c
exhibited excellent stereocontrol ability in the asymmetric hydro-
4.2. General procedure for synthesis of 7,70-disubstituted-
binaphthols ditriflate 5a–h
To a solution of 4a–h (20.0 mmol) in 50 mL of CH2Cl2 was added
pyridine (3.9 g, 4.1 mL, 50.0 mmol) and followed by dropwise ad-
dition of triflic anhydride Tf2O (13.0 g, 7.8 mL, 46 mmol) at 0 ꢀC. The
mixture was stirred at room temperature for 5 h. The mixture was
diluted with CH2Cl2 and then washed with 2.0 M aqueous HCl,
saturated NaHCO3, and brine. The organic layer was extracted and
dried over anhydrous sodium sulfate, concentrated under reduced
pressure, then passed through a silica gel plug (eluted with CH2Cl2)
to give the corresponding products 5a–h.
genation of not only linear alkyl-substituted
14e (Table 8, entry 6) but also branched alkyl-substituted
b
-keto methyl ester
-keto
b
ethyl ester 14g with excellent 99.8% ee (Table 8, entry 8). Substrate
methyl acetoacetate (14d) was reduced in 99% ee value and 100%
conversion under the standard set of reaction conditions (Table 8,
entry 3). Notably, increasing the substrate-to-catalyst ratio to 5000
and 10,000, respectively, the reactions also proceeded smoothly
and afforded 98% ee values with slightly prolonging the reaction
times to 15 h and 20 h (Table 8, entries 4 and 5). When substrate 3-
oxo-3-phenyl-propionic acid ethyl ester 14f was subjected to hy-
drogenation reaction, the product was obtained in 85% ee, and HI
was required as an additive under the optimized reaction condi-
tions (Table 8, entry 7). This 85% ee value was same as what was
observed when BINAP used as ligand in this reacion.23a
4.2.1. (R)-Trifluoro-methanesulfonic acid 7,70-dimethoxy-20-
trifluoromethanesulfonyloxy-1,10-binaphthalenyl-2-yl ester (5a)
20
White foam solid, yield 97%. Mp 106.7–107.9 ꢀC. [
a
]
ꢂ292.3 (c
D
0.5, CH2Cl2). 1H NMR (300 MHz, CDCl3):
d 3.52 (s, 6H), 6.52 (d,
J¼2.4 Hz, 2H), 7.23 (dd, J¼9.0, 2.4 Hz, 2H), 7.46 (d, J¼9.0 Hz, 2H),
7.89 (d, J¼9.0 Hz, 2H), 8.04 (d, J¼9.0 Hz, 2H). 13C NMR (75 MHz,
CDCl3):
d 55.2, 105.0, 116.0, 116.7, 120.1, 122.2, 127.8, 129.9, 131.5,
134.5, 146.0, 159.1. IR (KBr) 3085.6, 2952.5, 2831.0, 1625.8, 1586.2,
1506.6, 1465.6, 1244.9, 1226.6, 992.3, 869.8 cmꢂ1. HRMS (ESI) calcd
for (C24H16F6O8S2þNa)þ: m/z 633.0191, found m/z 633.0199.
In summary, a series of 7,70-disubstituted BINAPs 1a–h were
applied in Ru-catalyzed enantioselective hydrogenation of aryl-
and alkyl-substituted
b-ketoesters. We found these catalysts
formed from ligands 1a–h behaved very well under mild and
concise reaction conditions, and these reactions afforded the cor-
responding reductive products in excellent conversions and very
good enantioselectivity up to 99.8% ee. These 7,70-disubstituted
BINAPs ligands showed the comparable catalytic activity and
enantiocontrol potential to BINAP ligand in the same hydrogena-
4.2.2. (R)-Trifluoro-methanesulfonic acid 7,70-diethoxy-20-
trifluoromethanesulfonyloxy-1,10-binaphthalenyl-2-yl ester (5b)
20
White foam solid, yield 98%. Mp 66.8–67.6 ꢀC. [
a]
ꢂ306.4 (c
D
0.5, CH2Cl2). 1H NMR (300 MHz, CDCl3):
d
1.23 (t, J¼6.9 Hz, 6H),
3.62–3.76 (m, 4H), 6.52 (d, J¼1.8 Hz, 2H), 7.23 (dd, J¼9.0,1.8 Hz, 2H),
7.43 (d, J¼9.0 Hz, 2H), 7.89 (d, J¼9.0 Hz, 2H), 8.04 (d, J¼9.0 Hz, 2H).
tion of
b
-ketoesters.23a
13C NMR (75 MHz, CDCl3):
d 14.3, 63.2, 105.7, 116.0, 116.6, 120.4,
122.2, 127.8, 129.8, 131.4, 134.6, 145.9, 158.4. IR (KBr) 3073.1, 2980.0,
2933.2, 1623.7, 1507.1, 1482.1, 1453.0, 1424.3, 1394.0, 1221.6, 1164.9,
1141.5, 1042.9, 916.7, 868.8, 839.0 cmꢂ1. HRMS (ESI) calcd for
(C26H20F6O8S2þNa)þ: m/z 661.0504, found m/z 661.0502.
3. Conclusion
In summary, starting from chiral oxovanadium complex cata-
lyzed asymmetric oxidative coupling reaction, a class of optically
pure 7,70-disubstituted BINAPs 1a–h have been prepared via dif-
ferent synthetic routes due to the 7,70-disubstitutents’ difference
from each other in their 7,70-positions. Furthermore, a general,
concise, and straightforward approach that is suitable to prepare all
optically pure 7,70-disubstituted BINAPs 1a–h, regardless of the
substituents’ structure in the 7,70-positions, has been successfully
developed for the first time. Their catalytic potential also has been
demonstrated in the highly enantioselective Rh-catalyzed 1,4-ad-
4.2.3. (R)-Trifluoro-methanesulfonic acid 7,70-dipropoxy-20-
trifluoromethanesulfonyloxy-1,10-binaphthalenyl-2-yl ester (5c)
20
Colorless oil, yield 98%. [
(300 MHz, CDCl3):
a
]
D
ꢂ310.7 (c 0.5, CH2Cl2). 1H NMR
d
0.87 (t, J¼6.3 Hz, 6H), 1.59–1.66 (m, 4H), 3.54–
3.67 (m, 4H), 6.52 (d, J¼1.5 Hz, 2H), 7.22–7.26 (m, 2H), 7.44–7.47 (m,
2H), 7.89 (d, J¼9.0 Hz, 2H), 8.04 (d, J¼9.0 Hz, 2H). 13C NMR (75 MHz,
CDCl3): d 10.3, 22.1, 69.3,105.7,116.0,116.6,120.3,120.4,122.2,127.8,
129.8, 131.4, 134.6, 146.0, 158.6. IR (film) 2968.6, 2939.5, 2880.3,
1623.5, 1585.2, 1506.5, 1451.6, 1421.7, 1389.4, 1246.8, 1223.9, 1165.0,
ditions of aryl boronic acids to
catalyzed asymmetric hydrogenation of both simple aromatic
ketones and -ketoesters with high activity and selectivity.
a,b-unsaturated ketones and Ru-
1140.8, 969.5, 879.8, 836.0 cmꢂ1
.
HRMS (ESI) calcd for
b
(C28H24F6O8S2þNa)þ: m/z 689.0817, found m/z 689.0811.
4. Experimental
4.2.4. (R)-Trifluoro-methanesulfonic acid 7,70-diisopropoxy-20-
trifluoromethanesulfonyloxy-1,10-binaphthalenyl-2-yl ester (5d)
20
4.1. General remarks
White foam solid, yield 93%. Mp 138.7–139.9 ꢀC. [
a
]
ꢂ379.8 (c
D
0.5, CH2Cl2). 1H NMR (300 MHz, CDCl3):
d
0.99 (d, J¼6.0 Hz, 6H),
All reactions and manipulations were performed in an argon-
filled glovebox or using standard Schlenk techniques. Ru-
(acac)(C2H4)2, enone, Ph2P(O)H, dppb, Pb(OAc)2, Ph2PH, Ni(dppe)Cl2,
1.15 (d, J¼6.0 Hz, 6H), 4.11–4.19 (m, 2H), 6.49 (d, J¼2.4 Hz, 2H), 7.19
(dd, J¼9.0, 2.4 Hz, 2H), 7.88 (d, J¼9.0 Hz, 2H), 8.02 (d, J¼9.0 Hz,
2H). 13C NMR (75 MHz, CDCl3):
d 21.1, 21.7, 69.8, 107.5, 116.0, 116.6,
aromatic ketones, and
b
-ketoesters and others were purchased
120.3, 121.0, 122.1, 127.6, 129.9, 131.4, 134.6, 145.9, 157.3. IR (KBr)
3049.5, 2962.4, 2933.3, 2874.7, 1618.1, 1584.4, 1501.9, 1432.3,
1387.2, 1267.6, 1219.0, 1106.9, 1067.1, 1024.8, 989.7, 838.4, 741.4,
from Aldrich or Acros chemical company. Anhydrous toluene and
dioxane were distilled from sodium benzophenone ketyl. CH2Cl2,
DMSO, iPrOH, and C2H5OH were freshly distilled from calcium
hydride. 1H, 13C, 31P NMR spectra were recorded on a Brucker-
300 MHz spectrometer. Optical rotations were measured on a Per-
kin–Elmer 241 Polarimeter. HPLC analysis was performed on
BECKMAN (110B Solvent Delivery Module and 168 Detector). GC
analysis was performed using a Hewlett Packard Model HP 6890
Series. IR spectra were recorded on NICOLET MX-1E FT-IR. ESI MS
spectra were recorded on Bruker BIO TPF Q.
694.4 cmꢂ1
.
HRMS (ESI) calcd for (C28H24F6O8S2þNa)þ: m/z
689.0817, found m/z 689.0800.
4.2.5. (R)-Trifluoro-methanesulfonic acid 7,70-cyclohexyloxy-20-
trifluoromethanesulfonyloxy-1,10-binaphthalenyl-2-yl ester (5e)
20
White foam solid, yield 94%. Mp 71.1–72.4 ꢀC. [
a
]
D
ꢂ259.4 (c
0.2, CH2Cl2). 1H NMR (300 MHz, CDCl3):
1.36 (m, 2H), 1.40–1.51 (m, 2H), 3.82–3.89 (m, 2H), 4.00–4.07 (m,
d 1.26–1.29 (m, 4H), 1.30–

W.-C. Yuan et al. / Tetrahedron 65 (2009) 4130–4141
4137
2H), 6.66 (d, J¼2.4 Hz, 2H), 7.26 (dd, J¼9.0, 2.4 Hz, 2H), 7.45 (d,
J¼9.0 Hz, 2H), 7.90 (d, J¼9.0 Hz, 2H), 8.03 (d, J¼9.0 Hz, 2H). 13C NMR
103.5 mg), 1,3-bisdiphenylphosphinopropane (0.22 mmol, 90.7 mg),
diisopropylethylamine (3.0 mmol, 0.52 mL) added Ph2PH (4.4 mmol,
0.82 g, 0.77 mL) through syringe at 100 ꢀC and the mixture was
stirred for 48 h at the same temperature. After the solution was
cooled to room temperature, the solvent was removed under reduced
pressure. The residue was purified by flash chromatography on silica
gel (eluted with hexane/ether¼15:1) to afford corresponding prod-
ucts 1a–h as white powder solid.
(75 MHz, CDCl3):
d 23.0, 27.3, 66.8, 109.7, 116.1, 117.2, 120.0, 122.0,
1278.0, 130.1, 131.6, 134.1, 146.2, 157.6. IR (KBr) 3033.5, 2934.2,
2861.9, 1623.6, 1582.3, 1504.4, 1452.0, 1422.2, 1245.4, 1214.7, 1140.5,
984.7, 870.8 cmꢂ1. HRMS (ESI) calcd for (C28H22F6O8S2þNa)þ: m/z
687.0660, found m/z 687.0665.
4.2.6. (R)-Trifluoro-methanesulfonic acid 7,70-cyclooctyloxy-20-
trifluoromethanesulfonyloxy-1,10-binaphthalenyl-2-yl ester (5f)
4.4.1. (R)-2,20-Bis-diphenylphosphanyl-7,70-dimethoxy-1,10-
20
White foam solid, yield 93%. Mp 64.0–65.7 ꢀC. [
a
]
ꢂ259.5 (c
binaphthalenyl (1a)
D
0.2, CH2Cl2). 1H NMR (300 MHz, CDCl3):
d
1.06–1.08 (m, 2H), 1.17–
White powder solid, yield 73%. Mp 269.0–270.0 ꢀC. [ 20 251.0
a]
D
1.19 (m, 2H), 1.26–1.53 (m, 8H), 3.70–3.78 (m, 2H), 3.83–3.88 (m,
2H), 6.60 (d, J¼2.4 Hz, 2H), 7.24 (dd, J¼9.0, 2.4 Hz, 2H), 7.44 (d,
J¼9.0 Hz, 2H), 7.90 (d, J¼9.0 Hz, 2H), 8.03 (d, J¼9.0 Hz, 2H). 13C NMR
(c 0.1, CH2Cl2). 1H NMR (300 MHz, CDCl3):
d 3.12 (s, 6H), 6.05 (d,
J¼2.4 Hz, 2H), 7.02 (dd, J¼9.0, 2.5 Hz, 2H), 7.12–7.20 (m, 20H),
7.38–7.41 (m, 2H), 7.74 (d, J¼9.0 Hz, 2H), 7.83 (d, J¼9.0 Hz, 2H).
(75 MHz, CDCl3):
d
24.1, 27.0, 27.1, 66.6, 107.0, 116.0, 116.9, 119.9,
13C NMR (75 MHz, CDCl3):
d 54.6, 105.6, 119.1, 127.4, 127.8, 128.0,
122.1, 127.8, 130.0, 131.5, 134.3, 146.1, 158.1. IR (KBr) 3083.7, 2933.8,
2860.0, 1623.4, 1505.1, 1422.0, 1245.4, 1217.5, 1140.1, 957.8,
128.1, 128.3, 128.6, 128.8, 129.2, 132.5, 132.6, 132.7, 134.4, 134.5,
134.7, 134.8, 144.3, 157.4. 31P NMR (121 MHz, CDCl3):
ꢂ14.50
(s). IR (KBr) 3069.2, 2998.8, 2966.0, 2916.9, 2848.4, 1617.1,
d
873.3 cmꢂ1
.
HRMS (ESI) calcd for (C30H26F6O8S2þNa)þ: m/z
715.0973, found m/z 715.0960.
1549.5, 1501.2, 1431.9, 1264.2, 1220.5, 1029.1, 746.9, 696.5 cmꢂ1
.
HRMS (ESI) calcd for (C46H36O2P2þH)þ: m/z 683.2191, found m/z
4.2.7. (R)-Trifluoro-methanesulfonic acid 7,70-2crown-20-
683.2199.
trifluoromethanesulfonyloxy-1,10-binaphthalenyl-2-yl ester (5g)
20
White foam solid, yield 90%. Mp 121.7–122.3 ꢀC. [
a]
ꢂ263.7 (c
4.4.2. (R)-2,20-Bis-diphenylphosphanyl-7,70-diethoxy-
D
0.5, CH2Cl2). 1H NMR (300 MHz, CDCl3):
d
3.44–3.55 (m, 4H), 3.83–
1,10-binaphthalenyl (1b)
3.89 (m, 2H), 4.29–4.34 (m, 2H), 7.03 (d, J¼2.4 Hz, 2H), 7.20 (dd,
White powder solid, yield 71%. Mp 268.6–269.6 ꢀC. [ 20 250.8 (c
a]
D
J¼9.0, 2.4 Hz, 2H), 7.40 (d, J¼9.0 Hz, 2H), 7.84 (d, J¼9.0 Hz, 2H), 8.00
0.3, CH2Cl2). 1H NMR (300 MHz, CDCl3):
d
1.10 (t, J¼6.9 Hz, 6H),
(d, J¼9.0 Hz, 2H). 13C NMR (75 MHz, CDCl3):
d
65.9, 73.1, 108.2, 117.0,
3.08–3.30 (m, 4H), 6.05 (d, J¼2.1 Hz, 2H), 7.02 (dd, J¼9.0, 2.4 Hz,
2H), 7.13–7.38 (m, 20H), 7.74 (d, J¼9.0 Hz, 2H), 7.83 (d, J¼8.4 Hz,
120.3, 121.6, 122.1, 127.9, 129.5, 131.5, 134.0, 146.2, 158.5. IR (KBr)
3069.2, 2956.4, 2868.6,1623.4,1504.7,1422.6,1245.6,1215.1,1140.9,
992.9, 862.7 cmꢂ1. HRMS (ESI) calcd for (C26H18F6O9S2þNa)þ: m/z
675.0296, found m/z 675.0290.
2H). 13C NMR (75 MHz, CDCl3):
d 14.3, 62.7, 106.6, 118.4, 119.3, 127.3,
127.7, 127.9, 128.2, 128.4, 128.7, 129.1, 132.5, 132.6, 132.7, 134.4,
134.5, 134.7, 135.1, 136.1, 137.8, 138.7, 143.8, 144.4, 156.9. 31P NMR
(121 MHz, CDCl3):
d
ꢂ14.58 (s). IR (KBr) 3046.1, 2980.7, 2927.5,
4.2.8. (R)-Trifluoro-methanesulfonic acid 7,70-3crown-20-
1617.7, 1501.8, 1477.3, 1433.1, 1391.2, 1266.6, 1219.0, 1107.9, 1088.9,
1048.7, 1025.8, 975.6, 839.9, 696.1 cmꢂ1. HRMS (ESI) calcd for
(C48H40O2P2þH)þ: m/z 711.2504, found m/z 711.2508.
trifluoromethanesulfonyloxy-1,10-binaphthalenyl-2-yl ester (5h)
20
White foam solid, yield 91%. Mp 79.5–80.9 ꢀC. [
a
]
ꢂ276.0 (c
D
0.2, CH2Cl2). 1H NMR (300 MHz, CDCl3):
d 3.43–3.62 (m, 8H), 3.91–
3.98 (m, 4H), 6.61 (d, J¼2.4 Hz, 2H), 7.29 (dd, J¼9.0, 2.4 Hz, 2H), 7.45
4.4.3. (R)-2,20-Bis-diphenylphosphanyl-7,70-dipropoxy-
(d, J¼9.0 Hz, 2H), 7.90 (d, J¼9.0 Hz, 2H), 8.04 (d, J¼9.0 Hz, 2H). 13C
1,10-binaphthalenyl (1c)
NMR (75 MHz, CDCl3):
d
67.9, 69.0, 71.1, 107.0, 116.0, 117.1, 120.5,
White powder solid, yield 60%. Mp 100.1–101.3 ꢀC. [ 20 242.9 (c
a]
D
122.1, 127.9, 130.1, 131.6, 134.1, 146.1, 158.0. IR (KBr) 3069.2, 2924.6,
2869.6,1623.6,1585.2,1505.2, 1446.0, 1421.4, 1246.0,1220.3,1164.0,
0.4, CH2Cl2). 1H NMR (300 MHz, CDCl3):
d
0.84 (t, J¼7.5 Hz, 6H),
1.47–1.54 (m, 4H), 3.01–3.25 (m, 4H), 6.08 (d, J¼2.1 Hz, 2H), 7.05
(dd, J¼9.0, 2.4 Hz, 2H), 7.03–7.40 (m, 20H), 7.76 (d, J¼9.0 Hz, 2H),
1139.7, 911.4, 867.2, 837.7 cmꢂ1
.
HRMS (ESI) calcd for
(C28H22F6O10S2þNa)þ: m/z 719.0559, found m/z 719.0548.
7.84 (d, J¼8.4 Hz, 2H). 13C NMR (75 MHz, CDCl3):
d 10.4, 22.2, 68.5,
105.7,106.6,119.3,127.3,127.7,128.0,128.2,128.5,128.7,129.1,132.5,
132.6, 132.7, 134.3, 134.5, 134.6, 136.0, 137.8, 138.6, 143.9, 144.4,
4.3. A general procedure for synthesis of 7,70-disubstituted
BINAPs ligands 1a–d catalyzed by NiCl2(dppe)
157.1. 31P NMR (121 MHz, CDCl3):
d
ꢂ14.60 (s). IR (KBr) 3048.5,
2961.6, 2931.9, 2874.0, 1617.7, 1501.6, 1477.5, 1477.5, 1432.3, 1387.0,
1267.5, 1218.5, 1106.9, 1067.0, 1024.8, 989.7, 838.4, 741.3,
694.4 cmꢂ1. HRMS (ESI) calcd for (C50H44O2P2þH)þ: m/z 739.2817,
found m/z 739.2811.
A solution of [NiCl2(dppe)] (0.4 mmol, 106 mg) in anhydrous
DMF (3.0 mL) was degassed. Ph2PH (1.5 mmol, 0.26 mL) was added
and the mixture was heated at 100 ꢀC for 1 h. A degassed solution
containing the bistriflate of 5a–d (2 mmol) and DABCO (8 mmol,
0.9 g) in DMF (5.0 mL) was added to the mixture solution. The
mixture was heated at 100 ꢀC and three additional portions of
Ph2PH (1.5 mmol, 0.26 mL) were added after 1, 3, and 7 h. The re-
action was maintained at 100 ꢀC for 3 days. After the solution was
cooled to room temperature, the solvent was removed under re-
duced pressure. The residue was purified by flash chromatography
on silica gel (eluted with hexane/ether¼15:1) to afford the corre-
sponding products 1a–d as white powder solid.
4.4.4. (R)-2,20-Bis-diphenylphosphanyl-7,70-diisopropoxy-
1,10-binaphthalenyl (1d)
20
White powder solid, yield 70%. Mp 239.3–240.7 ꢀC. [
a]
267.2
D
(c 0.3, CH2Cl2). 1H NMR (300 MHz, CDCl3):
d
0.74 (d, J¼6.0 Hz, 6H),
1.05 (d, J¼6.0 Hz, 6H), 3.71–3.75 (m, 2H), 6.06 (d, J¼2.4 Hz, 2H),
6.99 (dd, J¼9.0, 2.4 Hz, 2H), 7.08–7.34 (m, 20H), 7.72 (d, J¼9.0 Hz,
2H), 7.80 (d, J¼8.4 Hz, 2H). 13C NMR (75 MHz, CDCl3):
d 20.4, 22.3,
69.0, 107.4, 108.5, 119.7, 127.4, 127.7, 127.9, 128.0, 128.4, 128.5, 129.1,
129.9, 131.4, 132.6, 132.7, 132.9, 134.1, 134.2, 134.4, 134.5, 138.3,
4.4. A general procedure for synthesis of 7,70-disubstituted
BINAPs ligands catalyzed by Pd2(dba)3$CHCl3
143.4, 155.5. 31P NMR (121 MHz, CDCl3):
d
ꢂ14.27 (s). IR (KBr)
3049.7, 2974.8, 2926.9, 1616.0, 1499.9, 1477.0, 1432.9, 1382.6,
1268.0, 1218.4, 1138.4, 1113.7, 1218.4, 1138.4, 1113.7, 982.2, 838.8,
741.8, 695.8 cmꢂ1. HRMS (ESI) calcd for (C50H44O2P2þH)þ: m/z
739.2817, found m/z 739.2825.
Under a nitrogen atmosphere, to a DMF solution containing
the bistriflate of 5a–h (2.0 mmol), Pd2(dba)3$CHCl3 (0.1 mmol,

4138
W.-C. Yuan et al. / Tetrahedron 65 (2009) 4130–4141
4.4.5. (R)-2,20-Bis-diphenylphosphanyl-7,70-cyclohexyloxy-
mixture was then stirred at 100 ꢀC for 5 h. The solution was cooled
to room temperature and dissolved in 5 mL ethyl acetate. The so-
lution was washed with saturated sodium bicarbonate and the
aqueous layer is extracted with ethyl acetate (3 mLꢃ3), the organic
layer is dried over anhydrous Na2SO4, then concentrate the solvent
and chromatography on silica gel (petroleum ether/EtOAc¼15:1) to
give 3-phenylcyclohexanone as colorless oil.
1,10-binaphthalenyl (1e)
White powder solid, yield 54%. Mp 245.0–247.0 ꢀC. [ 20 276.8 (c
a]
D
0.5, CH2Cl2). 1H NMR (300 MHz, CDCl3):
d 0.89–1.01 (m, 4H), 1.14–
1.18 (m, 4H), 3.59–3.64 (m, 2H), 3.81–3.88 (m, 2H), 6.04 (d, J¼2.1 Hz,
2H), 6.97–7.01 (m, 10H), 7.05–7.07 (m, 2H), 7.28–7.32 (m, 8H), 7.39–
7.43 (m, 4H), 7.68 (d, J¼9.0 Hz, 2H), 7.78 (d, J¼9.0 Hz, 2H). 13C NMR
(75 MHz, CDCl3):
d 23.2, 27.2, 66.9, 110.3, 119.7, 127.8, 127.9, 128.1,
128.4, 128.5, 129.0, 129.4, 133.2, 133.3, 133.5, 134.1, 134.5, 134.7,
4.5.1. (R)-3-Phenylcyclohexanone (11aa)
134.8, 137.7, 138.3, 155.6. 31P NMR (121 MHz, CDCl3):
d
ꢂ11.39 (s). IR
Yield 99%, 97% ee. 1H NMR (300 MHz, CDCl3):
d
1.80–1.89 (m,
2H), 2.07–2.16 (m, 2H), 2.39–2.58 (m, 4H), 3.01 (m, 1H), 7.21–7.25
(m, 3H), 7.33–7.35 (m, 2H). 13C NMR (75 MHz, CDCl3):
25.7, 32.9,
41.3, 44.9, 49.1, 126.7, 126.8, 128.5, 144.5, 211.2. HPLC analysis
(Chiralcel OJ-H column, 2-propanol/hexane 15:85, flow rate 1.0 mL/
(KBr) 3052.8, 2928.9, 2886.0, 1618.6, 1583.7, 1499.3, 1432.3, 1266.4,
1223.6, 1205.0, 1195.6, 887.1, 842.0, 741.8, 693.6 cmꢂ1. HRMS (ESI)
calcd for (C50H42O2P2þH)þ: m/z 737.2660, found m/z 737.2669.
d
20
4.4.6. (R)-2,20-Bis-diphenylphosphanyl-7,70-cyclooctyloxy-
min, tR (major)¼7.36 min, tR (minor)¼8.39 min). [
a
]
20.1 (c 0.69,
D
1,10-binaphthalenyl (1f)
CHCl3).
White powder solid, yield 61%. Mp 251.0–253.2 ꢀC. [ 20 254.0 (c
a]
D
0.5, CH2Cl2). 1H NMR (300 MHz, CDCl3):
d
1.04–1.08 (m, 4H), 1.18–
4.5.2. (R)-3-Phenyl-cyclopentanone (11ba)
1.29 (m, 8H), 3.46–3.51 (m, 2H), 3.59–3.64 (m, 2H), 6.01 (d,
J¼2.4 Hz, 2H), 6.99–7.04 (m, 12H), 7.21–7.36 (m, 12H), 7.70 (d,
J¼9.0 Hz, 2H), 7.78 (d, J¼9.0 Hz, 2H). 13C NMR (75 MHz, CDCl3):
Yield 90%, 90% ee. 1H NMR (300 MHz, CDCl3):
d
1.67–2.04 (m,
1H), 2.32–2.51 (m, 4H), 2.65–2.74 (m, 1H), 3.50 (m, 1H), 7.24–7.29
(m, 3H), 7.34–7.39 (m, 2H). 13C NMR (75 MHz, CDCl3):
31.3, 39.0,
-DEX
d
d
24.3, 27.1, 27.2, 66.1, 107.3, 119.4, 127.5, 127.7, 127.8, 128.0, 128.1,
42.4, 45.9, 126.9, 128.8, 143.2, 218.5. GC analysis (GAMMA b
128.4, 128.5, 129.2, 132.8, 132.9, 133.0, 134.2, 134.3, 134.5, 134.6,
225 column, column temperature¼155 ꢀC, H2¼12 psi. N2 flow
142.9, 156.1. 31P NMR (121 MHz, CDCl3):
d
ꢂ13.20 (s). IR (KBr)
2 mL/min, tR (minor)¼9.47 min, tR (major)¼9.63 min). [
a]
20 89.1 (c
D
3065.3, 2926.8, 2855.1,1617.4,1584.3,1500.4,1432.2,1259.4,1216.6,
1202.2, 1025.0, 837.8, 740.9, 694.5 cmꢂ1. HRMS (ESI) calcd for
(C52H46O2P2þH)þ: m/z 765.2973, found m/z 765.2988.
0.94, CHCl3).
4.5.3. (R)-3-Phenyl-cycloheptanone (11ca)
Yield 82%, 90% ee. 1H NMR (300 MHz, CDCl3):
d
1.72–1.76 (m,
3H), 2.07–2.17 (m, 3H), 2.57–2.67 (m, 3H), 2.94 (m, 2H), 7.16–7.22
(m, 3H), 7.26–7.32 (m, 2H). 13C NMR (75 MHz, CDCl3):
24.3, 29.4,
4.4.7. (R)-2,20-Bis-diphenylphosphanyl-7,70-2crown-[1,10]-
binaphthalenyl (1g)
d
20
White powder solid, yield 60%. Mp 254.7–255.9 ꢀC. [
a
]
D
ꢂ238.3
39.3, 42.9, 44.1, 51.4, 126.5, 126.6, 128.8, 147.1, 213.7. HPLC analysis
(Chiralcel OJ-H column, 2-propanol/hexane 5:95, flow rate 1.0 mL/
(c 0.3, CH2Cl2). 1H NMR (300 MHz, CDCl3):
d
3.22–3.37 (m, 4H),
20
3.66–3.70 (m, 2H), 3.91–3.99 (m, 2H), 6.39 (d, J¼2.4 Hz, 2H), 6.84–
6.91 (m, 10H), 6.93–6.94 (m, 2H), 7.19–7.39 (m, 12H), 7.60 (d,
J¼9.0 Hz, 2H), 7.72 (d, J¼8.4 Hz, 2H). 13C NMR (75 MHz, CDCl3):
min, tR (major)¼12.37 min, tR (minor)¼13.22 min). [
a
]
59.8 (c
D
0.83, CHCl3).
d
66.1, 73.1, 109.4, 120.3, 127.6, 127.7, 128.0, 128.3, 128.4, 128.7, 128.8,
4.5.4. (R)-5-Methyl-4-phenyl-hexan-2-one (11da)
133.3, 133.5, 133.6, 133.8, 134.5, 134.6, 134.8, 138.2, 141.5, 156.3. 31P
NMR (121 MHz, CDCl3):
Yield 88%, 97% ee. 1H NMR (300 MHz, CDCl3):
d
0.74 (d, J¼6.6 Hz,
d
ꢂ9.74 (s). IR (KBr) 3049.0, 2973.7, 2855.1,
3H), 0.94 (d, J¼6.6 Hz, 3H), 1.77–1.86 (m, 1H), 1.97 (s, 3H), 2.78–2.80
1618.6, 1585.2, 1500.5, 1432.8, 1214.8, 1204.4, 1126.5, 1089.8, 1067.9,
1026.9, 965.0, 955.7, 839.3, 694.8 cmꢂ1. HRMS (ESI) calcd for
(C48H38O3P2þH)þ: m/z 725.2296, found m/z 725.2301.
(m, 2H), 2.88–2.95 (m, 1H), 7.12–7.20 (m, 3H), 7.24–7.29 (m, 2H). 13C
NMR (75 MHz, CDCl3):
d 20.5, 20.9, 30.7, 33.5, 47.8, 48.2, 126.4,
128.3, 128.4, 143.4, 208.5. HPLC analysis (Chiralcel OJ-H column, 2-
propanol/hexane 1:99, flow rate 1.0 mL/min, tR (major)¼7.93 min,
20
4.4.8. (R)-2,20-Bis-diphenylphosphanyl-7,70-3crown-
tR (minor)¼11.40 min). [
a]
32.7 (c 0.79, CHCl3).
D
1,10-binaphthalenyl (1h)
White powder solid, yield 62%. Mp 251.1–253.0 ꢀC. [ 20 275.7 (c
a]
D
4.5.5. (R)-3-(4-Chloro-phenyl)-cyclohexanone (11ab)
Yield 85%, 98% ee. 1H NMR (300 MHz, CDCl3):
1.77–1.84 (m, 2H),
0.5, CH2Cl2). 1H NMR (300 MHz, CDCl3):
d 3.21–3.36 (m, 4H), 3.42–
d
3.49 (m, 4H), 3.78–3.80 (m, 2H), 3.89–3.90 (m, 2H), 6.10 (d,
J¼2.4 Hz, 2H), 7.11–7.13 (m, 10H), 7.14–7.15 (m, 2H), 7.37–7.44 (m,
12H), 7.82 (d, J¼9.0 Hz, 2H), 7.91 (d, J¼8.4 Hz, 2H). 13C NMR
2.01–2.26 (m, 2H), 2.43–2.55 (m, 4H), 2.99 (m, 1H), 7.15 (d, J¼8.4 Hz,
2H), 7.29 (d, J¼8.5 Hz, 2H). 13C NMR (300 MHz, CDCl3):
d 25.5, 32.8,
41.2, 44.2, 48.9, 128.1, 128.9, 132.4, 142.8, 210.6. HPLC analysis (Chir-
(75 MHz, CDCl3):
d 66.9, 68.4, 70.9, 107.1, 119.6, 127.7, 127.8, 127.9,
alcel OJ-H column, 2-propanol/hexane 5:95, flow rate 1.0 mL/min, tR
major¼11.43 min, tR (minor)¼12.99 min). [
128.1, 128.2, 128.4, 129.3, 132.8, 132.9, 133.1, 134.5, 134.7, 142.6,
a]
20 19.3 (c 0.97, CHCl3).
D
155.7. 31P NMR (121 MHz, CDCl3):
d
ꢂ12.58 (s). IR (KBr) 3066.3,
2959.3, 2917.3, 2849.2, 1619.2, 1584.0, 1501.2, 1432.6, 1261.4, 1217.2,
1208.6, 1138.9, 1106.6, 1093.0, 1061.9, 1025.5, 836.8, 801.2, 742.9,
695.7 cmꢂ1. HRMS (ESI) calcd for (C50H42O4P2þH)þ: m/z 769.2558,
found m/z 769.2562.
4.5.6. (R)-3-(4-Methoxy-phenyl)-cyclohexanone (11ac)
Yield 90%, 96% ee. 1H NMR (300 MHz, CDCl3):
1.76–1.84 (m,
d
2H), 2.05–2.14(m, 2H), 2.42–2.56 (m, 4H), 2.96 (m, 1H), 3.80 (s, 3H),
6.87 (d, J¼6.6 Hz, 2H), 7.14 (d, J¼6.6 Hz, 2H). 13C NMR (75 MHz,
4.5. The typical experiment for the 1,4-addition
of aryl boronic acids to enones
CDCl3): d 25.6, 33.1, 41.3, 44.1, 49.4, 55.4, 114.1, 127.6, 136.7, 158.4,
211.4. HPLC analysis (Chiralcel OJ-H column, 2-propanol/hexane
5:95, flow rate 1.0 mL/min, tR (major)¼19.72 min, tR (minor)¼
To a Schlenk tube charged with Rh(acac)(C2H4)2 (3.1 mg,
26.80 min). [a]
20 18.6 (c 0.89, CHCl3).
D
12 mmol), 1g (9.3 mg, 12.6 mmol), and PhB(OH)2 (244 mg,
2.00 mmol) was added 1,4-dioxane (1.0 mL) and the solution was
flushed with argon. After the mixture was stirred for 15 min at
4.5.7. (R)-3-(3-Methoxy-phenyl)-cyclohexanone (11ad)
Yield 92%, 96% ee. 1H NMR (300 MHz, CDCl3):
1.81–1.89 (m,
2H), 2.06–2.18 (m, 2H), 2.40–2.60 (m, 4H), 3.00 (m, 1H), 3.82 (s, 3H),
6.78–6.84 (m, 3H), 7.28 (m, 1H). 13C NMR (75 MHz, CDCl3):
25.7,
d
room temperature, 100
mL water was added and followed by ad-
dition of 2-cyclohexenone (39 mg, 40
mL, 0.40 mmol). The resulting
d

W.-C. Yuan et al. / Tetrahedron 65 (2009) 4130–4141
4139
32.9, 41.3, 44.9, 49.1, 55.4,111.8,112.9,119.1,129.8,146.2,160.0, 211.1.
HPLC analysis (Chiralcel OJ-H column, 2-propanol/hexane 5:95,
flow rate 1.0 mL/min, tR (major)¼15.04 min, tR (minor)¼19.52 min).
4.7.2. (S)-1-o-Tolyl-ethanol (13b)
Conversion 100%, 90% ee. S/C¼2000, base/catalyst¼70:1, the
substrate concentration was 1.0 M in 2-propanol. GC analysis (CP-
[
a]
20 15.1 (c 0.87, CHCl3).
cyclodex b
-236 M, column temperature 125 ꢀC, inject temperature
D
240 ꢀC, N2 flow 2 mL/min), tR1¼5.3 min, tR2¼6.5 min.
4.5.8. (R)-3-(4-tert-Butyl-phenyl)-cyclohexanone (11ae)
Yield 86%, 99% ee. 1H NMR (300 MHz, CDCl3):
1.29 (s, 9H), 1.76–
d
4.7.3. (S)-1-Phenyl-ethanol (13c)
1.85 (m, 2H), 2.04–2.13 (m, 2H), 2.36–2.56 (m, 4H), 2.99 (m, 1H),
Conversion >99%, 81% ee. S/C¼2000, base/catalyst¼70:1, the
7.13 (d, J¼8.4 Hz, 2H), 7.33 (d, J¼8.4 Hz, 2H). 13C NMR (75 MHz,
substrate concentration was 1.0 M in 2-propanol, GC analysis (CP-
CDCl3):
d
25.7, 31.5, 32.9, 41.3, 44.4, 49.1, 125.7, 126.3, 141.4, 149.6,
cyclodex b
-236 M, column temperature 115 ꢀC, inject temperature
220 ꢀC, N2 flow 2 mL/min), tR1¼5.0 min, tR2¼5.3 min.
211.4. HPLC analysis (Chiralcel OJ-H column, 2-propanol/hexane
1:99, flow rate 1.0 mL/min, tR (major)¼9.03 min, tR (minor)¼
9.92 min). [
a
]
20 11.9 (c 0.68, CHCl3).
4.7.4. (S)-1-Phenyl-pentanol (13d)
D
Conversion >99%, 87% ee. S/C¼2000, base/catalyst¼70:1, the
4.5.9. (R)-3-(4-Trifluoromethyl-phenyl)-cyclohexanone (11af)
Yield 84%, 99.8% ee. 1H NMR (300 MHz, CDCl3):
1.81–1.89 (m,
substrate concentration was 1.0 M in 2-propanol, GC analysis (CP-
d
cyclodex b
-236M, column temperature 150 ꢀC, inject temperature
240 ꢀC, N2 flow 2 mL/min), tR1¼24.1 min, tR2¼24.3 min.
2H), 2.09–2.11 (m, 2H), 2.45–2.59 (m, 4H), 3.11 (m, 1H), 7.33 (d,
J¼8.1 Hz, 2H), 7.58 (d, J¼8.1 Hz, 2H). 13C NMR (300 MHz, CDCl3):
d
25.5, 32.6, 41.2, 44.6, 48.7, 125.8, 125.8, 125.9, 127.1, 148.3, 210.4.
4.7.5. (S)-1,2-Diphenyl-ethanol (13e)
HPLC analysis (Chiralcel OJ-H column, 2-propanol/hexane 5:95,
Conversion >99%, 88% ee. S/C¼2000, base/catalyst¼70:1, the
substrate concentration was 1.0 M in 2-propanol, HPLC analysis (OD
column, 2-propanol/hexane 5:95, room temperature, flow rate
1.0 mL/min), tR1¼11.7 min, tR2¼14.5 min.
flow rate 1.0 mL/min, tR (major)¼12.87 min, tR (minor)¼16.17 min).
[a]
20 10.1 (c 0.79, CHCl3).
D
4.5.10. (R)-3-p-Tolyl-cyclohexanone (11ag)
Yield 97%, 94% ee. 1H NMR (300 MHz, CDCl3):
d
1.79–1.86 (m,
4.7.6. (S)-1-(3-Methoxy-phenyl)-ethanol (13f)
2H), 2.05–2.16 (m, 2H), 2.33 (s, 3H), 2.36–2.57 (m, 4H), 2.98 (m, 1H),
Conversion 100%, 88% ee. S/C¼2000, base/catalyst¼70:1, the
7.34 (d, J¼8.4 Hz, 2H), 7.59 (d, J¼8.4 Hz, 2H). 13C NMR (75 MHz,
substrate concentration was 1.0 M in 2-propanol. GC analysis (CP-
CDCl3):
d
21.1, 25.7, 33.1, 41.4, 44.5, 49.2, 126.6, 129.5, 136.4, 141.6,
cyclodex b
-236M, column temperature 150 ꢀC, inject temperature
240 ꢀC, N2 flow 2 mL/min), tR1¼4.4 min, tR2¼4.6 min.
211.4. HPLC analysis (Chiralcel OJ-H column, 2-propanol/hexane
5:95, flow rate 1.0 mL/min, tR (major)¼10.87 min, tR (minor)¼
12.24 min). [
a
]
20 18.2 (c 0.84, CHCl3).
4.7.7. (S)-1-(4-Methoxy-phenyl)-ethanol (13g)
D
Conversion >99%, 78% ee. S/C¼2000, base/catalyst¼70:1, the
4.6. General procedure for preparation of [(RRR)-
(1a–h)–RuCl2–DPEN] precatalysts
substrate concentration was 1.0 M in 2-propanol, GC analysis (CP-
cyclodex b
-236M, column temperature 140 ꢀC, inject temperature
240 ꢀC, N2 flow 2 mL/min), tR1¼5.1 min, tR2¼5.4 min.
Ligands 1a–h (0.031 mmol) and [(C6H6)RuCl2]2 (0.015 mmol,
7.5 mg) were dissolved in anhydrous and degassed DMF (3 mL)
under nitrogen. The reaction mixture was heated to 100 ꢀC for
20 min, then the reaction mixture was slowly cooled to room
temperature followed by the addition of 1,2-diphenylethylenedi-
amine (RR-DPEN) (0.031 mmol, 6.6 mg). The solvent was stirred at
room temperature for 4 h. The solvent DMF was removed under
high vacuum at 50 ꢀC and the residue was used for asymmetric
hydrogenation of simple aromatic ketones as precatalyst without
further purification.
4.7.8. (S)-1-p-Tolyl-ethanol (13h)
Conversion >99%, 81% ee. S/C¼2000, base/catalyst¼70:1, the
substrate concentration was 1.0 M in 2-propanol. GC analysis (CP-
cyclodex CB, column temperature 125 ꢀC, inject temperature
240 ꢀC, N2 flow 2 mL/min), tR1¼5.4 min, tR2¼6.5 min.
4.7.9. (S)-1-Phenyl-propan-1-ol (13i)
Conversion 100%, 85% ee. S/C¼2000, base/catalyst¼70:1, the
substrate concentration was 1.0 M in 2-propanol, GC analysis (CP-
cyclodex b
-236M, column temperature 150 ꢀC, inject temperature
240 ꢀC, N2 flow 2 mL/min), tR1¼4.8 min, tR2¼5.0 min.
4.7. General procedure for asymmetric hydrogenation
simple aromatic ketones
4.7.10. (S)-2-Methyl-1-phenyl-propan-1-ol (13j)
To a vial were added the precatalyst [(RRR)-1c–RuCl2–DPEN]
(0.001 mmol), tBuOK (0.029 mmol, 3.2 mg), and substrate simple
aromatic ketone (2 mmol), then quickly adding new distilled and
degassed iPrOH (1 mL) to the vial and putting the vial into a hydro-
genation vessel. The vessel was purged with high purity hydrogen by
pressurizing to 10 atm and releasing the pressure. This procedurewas
repeated five times successively. The vessel was purged with hy-
drogen and pressurized to 40 atm then making the mixture to stir at
room temperature for certain hours. The reaction was stopped and
the reaction mixture was filtered through a pad of silica gel and
eluted with ethyl acetate to afford the corresponding desired product.
Conversion >99%, 73% ee. S/C¼2000, base/catalyst¼70:1, the
substrate concentration was 1.0 M in 2-propanol. GC analysis (CP-
cyclodex b
-236M, column temperature 150 ꢀC, inject temperature
240 ꢀC, N2 flow 2 mL/min), tR1¼17.5 min, tR2¼18.6 min.
4.7.11. (S)-1-Naphthalen-2-yl-ethanol (13k)
Conversion 100%, 77% ee, S/C¼2000, base/catalyst¼70:1, the
substrate concentration was 1.0 M in 2-propanol. GC analysis (CP-
cyclodex b
-236M, column temperature 170 ꢀC, inject temperature
240 ꢀC, N2 flow 2 mL/min), tR1¼5.0 min, tR2¼5.2 min.
4.7.1. (S)-1-Naphthalen-1-ethanol (13a)
4.7.12. (S)-1-Ferrocenylethanol (13l)
Conversion 100%, 98% ee. S/C¼2000, base/catalyst¼70:1, the
Conversion >99%, 79% ee, S/C¼1000, base/catalyst¼70:1, the
substrate concentration was 1.0 M in 2-propanol. HPLC analysis on
AS column, 2-propanol/hexane 5:95, room temperature, flow rate
1.0 mL/min, tR1¼11.3 min, tR2¼13.7 min.
substrate concentration was 1.0 M in 2-propanol, GC analysis (CP-
cyclodex b
-236 M, column temperature 160 ꢀC, inject temperature
240 ꢀC, N2 flow 2 mL/min), tR1¼11.2 min, tR2¼12.0 min.

4140
W.-C. Yuan et al. / Tetrahedron 65 (2009) 4130–4141
4.7.13. (S)-1-(2-Chloro-phenyl)-ethanol (13m)
analysis (column, CP-cyclodex b-225, N2 flow 2 mL/min, column
Conversion 100%, 94% ee, S/C¼2000, base/catalyst¼70:1, the
substrate concentration was 1.0 M in 2-propanol. GC analysis (CP-
cyclodex CB, column temperature 160 ꢀC, inject temperature
250 ꢀC, N2 flow 2 mL/min), tR1¼2.2 min, tR2¼2.4 min.
temperature 70 ꢀC, inject temperature 240 ꢀC), tR1¼16.2 min,
tR2¼16.7 min.
4.8.4. (R)-3-Hydroxy-butyric acid methyl ester (15d)
Conversion 100%, 99% ee, S/C¼1000. 1H NMR (300 MHz, CDCl3):
4.7.14. (S)-1-(3-Chloro-phenyl)-ethanol (13n)
d
1.16 (d, J¼6.3 Hz, 3H), 1.87–1.95 (m, 2H), 3.22 (br, 1H), 3.63 (s, 3H),
Conversion 100%, 71% ee, S/C¼2000, base/catalyst¼70:1, the
4.08–4.15 (m, 1H). 13C NMR (75 MHz, CDCl3):
d 22.4, 42.6, 51.5, 64.1,
substrate concentration was 1.0 M in 2-propanol. GC analysis (CP-
173.0. GC analysis (column, CP-cyclodex b-225, N2 flow 2 mL/min,
column temperature 70 ꢀC, inject temperature 240 ꢀC),
tR1¼13.8 min, tR2¼15.0 min.
cyclodex
b
-236M, column temperature 140 ꢀC, inject temperature
240 ꢀC, N2 flow 2 mL/min), tR1¼8.8 min, tR2¼9.2 min.
4.7.15. (S)-1-(3,4-Dimethoxy-phenyl)-ethanol (13o)
4.8.5. (R)-4-Chloro-3-hydroxy-butyric acid ethyl ester (15e)
Conversion >99%, 91% ee, S/C¼1000. 1H NMR (300 MHz, CDCl3):
Conversion >99%, 77% ee, S/C¼2000, base/catalyst¼70:1, the
substrate concentration was 1.0 M in 2-propanol. GC analysis (CP-
cyclodex CB, column temperature 140 ꢀC, inject temperature
240 ꢀC, N2 flow 2 mL/min), tR1¼17.0 min, tR2¼17.5 min.
d
1.18 (t, J¼7.5 Hz, 3H), 2.47–2.54 (m, 2H), 3.50 (d, J¼5.1 Hz, 2H),
3.66 (br, 1H), 4.05 (q, J¼7.5 Hz, 2H), 4.07–4.14 (m, 1H). 13C NMR
(75 MHz, CDCl3):
d 13.8, 38.5, 47.9, 60.6, 67.6, 171.4. GC analysis
(column, CP-cyclodex b-225, N2 flow 2 mL/min, column tempera-
ture 110 ꢀC, inject temperature 240 ꢀC), tR1¼8.5 min, tR2¼8.8 min.
4.7.16. (S)-1-(2,4-Dichloro-phenyl)-ethanol (13p)
Conversion 100%, 90% ee, S/C¼2000, base/catalyst¼70:1, the
substrate concentration was 1.0 M in 2-propanol, GC analysis (CP-
4.8.6. (S)-3-Hydroxy-3-phenyl-propionic acid ethyl ester (15f)
Conversion >99%, 85% ee, S/C¼1000. 1H NMR (300 MHz, CDCl3):
cyclodex b
-236M, column temperature 180 ꢀC, inject temperature
240 ꢀC, N2 flow 2 mL/min), tR1¼4.4 min, tR2¼4.6 min.
d
1.23 (t, J¼7.2 Hz, 3H), 2.63–2.72 (m, 2H), 3.45 (br, 1H), 4.13 (q,
J¼7.2 Hz, 2H), 5.10 (dd, J¼4.2, 8.7 Hz, 1H), 7.25–7.36 (m, 5H). 13C
4.7.17. (S)-1-(2-Bromo-phenyl)-ethanol (13q)
NMR (75 MHz, CDCl3): d 13.9, 43.3, 60.6, 70.1, 125.5, 127.5, 128.3,
Conversion >99%, 94% ee, S/C¼1000, base/catalyst¼70:1, the
142.6, 172.1. HPLC analysis (column, AD column, eluent 2-propanol/
hexane¼2:98, temperature, room temperature, flow rate 1.0 mL/
min, 254 nm light), tR1¼6.5 min, tR2¼7.7 min.
substrate concentration was 2.0 M in 2-propanol. GC analysis (CP-
cyclodex b
-236M, column temperature 180 ꢀC, inject temperature
240 ꢀC, N2 flow 2 mL/min), tR1¼3.4 min, tR2¼3.5 min.
4.8.7. (R)-3-Hydroxy-4-methyl-pentanoic butyric acid methyl
ester (15g)
4.8. General procedure for asymmetric hydrogenation
of
b-ketoesters
Conversion 100%, 99.8% ee, S/C¼1000. 1H NMR (300 MHz,
CDCl3):
d
0.84 (d, J¼6.9 Hz, 6H), 1.54–1.65 (m, 1H), 2.26–2.43 (m,
To a Schlenk tube were added [(C6H6)RuCl2]2 (0.02 mmol,
2H), 3.07 (br, 1H), 3.59 (s, 3H), 3.65–3.71 (m, 1H). 13C NMR (75 MHz,
CDCl3): 17.4, 18.1, 33.0, 38.3, 51.4, 72.5, 173.5. GC analysis (column,
10.0 mg), ligand 1c (0.042 mmol), and freshly distilled and
degassed EtOH/CH2Cl2 (3 mL/3 mL). The solution was stirred at
50 ꢀC for 1 h. The catalyst was dried under reduced pressure and
dissolved in degassed EtOH (20 mL). The solution (1 mL) including
d
CP-cyclodex CB, N2 flow 2 mL/min, column temperature 50 ꢀC,
preserving 5 min, then 2.0 ꢀC/min to 150 ꢀC, inject temperature
240 ꢀC), tR1¼23.7 min, tR2¼23.9 min.
catalyst was added to each vial containing b-ketoesters (2 mmol),
and these vials were taken into a Parr bomb. The reactions were
carried out at the desired hydrogen pressure and temperature for
12 h. Taking out the vials and removing the solvent under reduced
pressure, the residue was passed through a pad of silica gel and
eluted with ethyl acetate to afford the corresponding product.
Acknowledgements
We are grateful for financial support from the National Natural
Science Foundation of China (No. 20802074).
4.8.1. (R)-3-Hydroxy-butyric acid ethyl ester (15a)
Supplementary data
Conversion 100%, 98% ee, S/C¼1000. 1H NMR (300 MHz, CDCl3):
d
1.19 (d, J¼6.6 Hz, 3H), 1.26 (t, J¼7.2 Hz, 3H), 2.34–2.48 (m, 2H),
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2009.03.066.
2.93 (br, 1H), 4.17 (q, J¼7.2 Hz, 2H). 13C NMR (75 MHz, CDCl3):
d 14.1,
22.4, 42.8, 60.6, 64.2, 172.8. GC analysis (column, CP-cyclodex b-
225, N2 flow 2 mL/min, column temperature 70 ꢀC, inject temper-
ature 240 ꢀC), tR1¼18.0 min, tR2¼18.9 min.
References and notes
1. For selected reviews, see: (a) Noyori, R. Asymmetric Catalysis in Organic Syn-
thesis; Wiley: New York, NY, 1994; (b) Comprehensive Asymmetric Catalysis;
Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer: Berlin, 1999; (c) Ojima, I.
Catalytic Asymmetric Synthesis; Wiley: New York, NY, 2000; (d) Lin, G. Q.; Li, Y.
M.; Chan, A. S. C. Principles and Applications of Asymmetric Synthesis; Wiley:
New York, NY, 2001.
2. For selected reviews, see: (a) Noyori, R. Angew. Chem., Int. Ed. 2002, 41, 2008 and
references therein; (b) Knolwes, W. S. Adv. Synth. Catal. 2003, 345, 3; (c) Tang,
W. J.; Zhang, X. M. Chem. Rev. 2003, 103, 3029 and references therein.
3. (a) Knowles, W. S.; Sabacky, M. J. J. Chem. Soc., Chem. Commun. 1968, 1445; (b)
Horner, L.; Siegel, H.; Bu¨the, H. Angew. Chem., Int. Ed. Engl. 1968, 7, 941.
4. (a) Miyashita, A.; Yasuda, A.; Takaya, H.; Toriumi, K.; Ito, T.; Souchi, T.; Noyori, R.
J. Am. Chem. Soc. 1980, 102, 7932; (b) Noyori, R.; Takaya, H. Acc. Chem. Res. 1990,
23, 345; (c) Noyori, R. Chem. Soc. Rev. 1989, 18, 187.
4.8.2. (R)-3-Hydroxy-butyric acid tert-butyl ester (15b)
Conversion >99%, 96% ee, S/C¼1000. 1H NMR (300 MHz, CDCl3):
d
1.07 (d, J¼6.3 Hz, 3H), 1.33 (s, 9H), 2.23–2.32 (m, 2H), 2.35 (br, 1H),
3.97–4.07 (m, 1H). 13C NMR (75 MHz, CDCl3):
80.7, 171.9. GC analysis (column, CP-cyclodex
d
22.2, 27.8, 43.8, 64.1,
-120, N2 flow 2 mL/
b
min, column temperature 100 ꢀC, inject temperature 240 ꢀC),
tR1¼9.2 min, tR2¼9.5 min.
4.8.3. (R)-3-Hydroxy-butyric acid isopropoyl ester (15c)
Conversion >99%, 98% ee, S/C¼1000. 1H NMR (300 MHz, CDCl3):
d
1.04 (d, J¼6.3 Hz, 3H), 1.10 (d, J¼6.3 Hz, 6H), 2.56–2.29 (m, 2H),
5. For selected reviews see: (a) Noyori, R. Science 1990, 248, 1194; (b) Rosini, C.;
Franzini, L.; Raffaellii, A.; Salvadori, P. Synthesis 1992, 503; (c) Noyori, R. Adv.
Synth. Catal. 2003, 345, 15.
3.28 (br, 1H), 4.00–4.08 (m, 1H), 4.84–4.93 (m, 1H). 13C NMR
(75 MHz, CDCl3): 21.4, 22.2, 24.9, 43.1, 63.6, 64.0, 67.7, 171.9. GC
d

W.-C. Yuan et al. / Tetrahedron 65 (2009) 4130–4141
4141
6. (a) McCarthy, M.; Guiry, P. J. Tetrahedron 2001, 51, 3809; (b) Berthod, M.;
Mignani, G.; Woodward, G.; Lemaire, M. Chem. Rev. 2005, 105, 1801 and refer-
ences therein.
7. (a) Zhang, X.; Mashima, K.; Sayo, N.; Kumobayashi, H.; Akutagawa, S.; Takaya, H.
Tetrahedron Lett. 1991, 32, 7283; (b) Zhang, X.; Mashima, K.; Sayo, N.;
Kumobayashi, H.; Akutagawa, S.; Takaya, H. J. Chem. Soc., Perkin Trans. 1 1994, 2309.
8. (a) Saito, T.; Yokozawa, T.; Zhang, X.; Sayo, N. U.S. Patent 5,872,273, 1999; (b)
Saito, T.; Yokozawa, T.; Ishizaki, T.; Moroi, T.; Sayo, N.; Miura, T.; Kumobayashi,
H. Adv. Synth. Catal. 2001, 343, 264.
9. (a) Che, D.; Andersen, N. G.; Lau, S. Y. W.; Parvez, M.; Keay, B. A. Tetrahedron:
Asymmetry 2000, 11, 1919; (b) Cai, D. W. (Merck & Co., Inc.). Japanese Patent
08311090, 1996; U.S. Patent 6,333,435, 2001; (c) Yokozawa, T.; Saito, K. (Taka-
sago International Corp.). European Patent Appl. 1371655, 2003.
10. (a) Luo, Z.-B.; Liu, Q.-Z.; Gong, L.-Z.; Mi, A.-Q.; Cui, X.; Jiang, Y.-Z. Chem. Commun.
2002, 914; (b) Luo, Z.-B.; Liu, Q.-Z.; Gong, L.-Z.; Mi, A.-Q.; Cui, X.; Jiang, Y.-Z.
Angew. Chem., Int. Ed. 2002, 41, 4532; (c) Guo, Q.-X.; Wu, Z.-J.; Luo, Z.-B.; Liu, Q.-Z.;
Ye, J.-L.; Luo, S.-W.; Cun, L.-F. J. Am. Chem. Soc. 2007, 129, 13927.
Synthesis 2001, 171; (e) Bolm, C.; Hildebrand, J. P.; Muˆniz, K.; Hermanns, N.
Angew. Chem., Int. Ed. 2001, 40, 3284; (f) Hayashi, T. Synlett 2001, 879; (g)
Hayashi, T. Bull. Chem. Soc. Jpn. 2004, 77, 13; (h) Reetz, M. T.; Moulin, K.; Gos-
berg, A. Org. Lett. 2001, 3, 4083; (i) Boiteau, J. G.; Imbos, R.; Minnaard, A. J.;
Feringa, B. L. Org. Lett. 2003, 5, 681; (j) Boiteau, J. G.; Minnaard, A. J.; Feringa,
B. L. J. Org. Chem. 2003, 68, 9481; (k) Shintani, R.; Ueyama, K.; Yamada, I.;
Hayashi, T. Org. Lett. 2004, 6, 3425; (l) Fischer, C.; Defieber, C.; Suzuki, T.;
Carreira, E. M. J. Am. Chem. Soc. 2004, 126, 1628; (m) Defieber, C.; Paquin, J. F.;
Serna, S.; Carreira, E. M. Org. Lett. 2004, 6, 3873; (n) Tokunaga, N.; Otomaru, Y.;
Okamoto, K.; Ueyama, K.; Shintani, R.; Hayashi, T. J. Am. Chem. Soc. 2004, 126,
13584; (o) Shintani, R.; Okamoto, K.; Otomaru, Y.; Ueyama, K.; Hayashi, T. J. Am.
Chem. Soc. 2005, 127, 54.
17. Takaya, Y.; Ogasawara, M.; Hayashi, T.; Sakai, M.; Miyaura, N. J. Am. Chem. Soc.
1998, 120, 5579.
18. (a) Noyori, R.; Ohkuma, T. Angew. Chem., Int. Ed. 2001, 40, 40; (b) Knowles, W. S.
Angew. Chem., Int. Ed. 2002, 41, 1998; (c) Pfaltz, A.; Blankenstein, J.; Hilgraf, R.;
Hormann, E.; Mcintyre, S.; Menges, F.; Schonleber, M.; Smidt, S. P.; Wustenberg,
B.; Zimmermann, N. Adv. Synth. Catal. 2003, 345, 33; (d) Crepy, K. V. L.; Im-
amoto, T. Adv. Synth. Catal. 2003, 345, 79; (e) Blaser, H. U.; Malan, C.; Pugin, B.;
Spindler, F.; Steiner, H.; Studer, M. Adv. Synth. Catal. 2003, 345, 103; (f) Geneˆt,
J. P. Acc. Chem. Res. 2003, 36, 908.
11. Liu, Q.-Z.; Xie, N.-S.; Lou, Z.-B.; Cui, X.; Cun, L.-F.; Gong, L.-Z.; Mi, A.-Q.; Jiang, Y.-Z.
J. Org. Chem. 2003, 68, 7921.
12. Yuan, W.-C.; Cun, L.-F.; Gong, L.-Z.; Mi, A.-Q.; Jiang, Y.-Z. Tetrahedron Lett. 2005,
46, 509, and corrigendum: Tetrahedron Lett. 2006, 47, 4979.
13. (a) Cai, D. W.; Payack, J. F.; Bender, D. R.; Hughes, D. L.; Verhoeven, T. R.; Reider,
P. J. J. Org. Chem. 1994, 59, 7180; (b) Cai, D.W. (Merck). U.S. Patent 252,306, 1994;
U.S. Patent 5,399,771, 1995.
14. Sayo, N.; Zhang, X.; Omoto, T.; Yokozawa, T.; Yamasaki, T.; Kumobayashi, H.
European Patent Appl. 0754696, 1997.
19. (a) Ohkuma, T.; Ooka, H.; Hashiguchi, S.; Ikariya, T.; Noyori, R. J. Am. Chem. Soc.
1995, 117, 2675; (b) Ohkuma, T.; Ikehira, H.; Ikariya, T.; Noyori, R. Synlett 1997,
467; (c) Ohkuma, T.; Doucet, H.; Pham, T.; Mikami, K.; Korenaga, T.; Terada, M.;
Noyori, R. J. Am. Chem. Soc. 1998, 120, 1086; (d) Ohkuma, T.; Koizumi, M.;
Doucet, H.; Pham, T.; Kozawa, M.; Murata, K.; Katayama, E.; Yokozawa, T.;
Ikariya, T.; Noyori, R. J. Am. Chem. Soc. 1998, 120, 13529.
20. (a) Ohkuma, T.; Ooka, H.; Ikariya, T.; Noyori, R. J. Am. Chem. Soc. 1995, 117, 10417;
(b) Doucet, H.; Ohkuma, T.; Murata, K.; Yokozawa, T.; Kozawa, M.; Katayama, E.;
England, A. F.; Irariya, T.; Noyori, R. Angew. Chem., Int. Ed. 1998, 37, 1703.
21. (a) Du¨bner, F.; Knochel, P. Angew. Chem., Int. Ed. 1999, 38, 379; (b) Schwink, L.;
Knochel, P. Chem.dEur. J. 1998, 4, 950; And for review, see: Togni, A. Angew.
Chem., Int. Ed. 1996, 35, 1475.
22. For selective examples, see: (a) Guzzo, P. R.; Miller, M. J. J. Org. Chem. 1994, 59,
4862; (b) Pommier, A.; Pons, J. M. Synthesis 1994, 1294; (c) Case-green, S. C.;
Davies, S. G.; Hedgecock, C. J. R. Synlett 1991, 781; (d) Taber, D. F.; Silverberg, L.
J.; Robinson, E. D. J. Am. Chem. Soc. 1991, 113, 6639.
23. For selective examples, see: (a) Noyori, R.; Ohkuma, T.; Kitamura, M.; Takaya,
H.; Sayo, N.; Kumobayashi, H.; Akutagawa, S. J. Am. Chem. Soc. 1987, 109, 5856;
(b) Kitamura, M.; Tokunaga, M.; Ohkuma, T.; Noyori, R. Tetrahedron Lett. 1991,
32, 4163; (c) Kumobayashi, H.; Miura, T.; Sayo, N.; Saito, T.; Zhang, X. Synlett
2001, 1055; (d) Wan, X.; Sun, Y.; Luo, Y.; Li, D.; Zhang, Z. J. Org. Chem. 2005,
70, 1070.
15. For selected reviews on 1,4-addition reactions, see: (a) Schmalz, H. G. In Compre-
hensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford,1991; (b)
Perlmutter, P. Conjugate Addition Reactions in Organic Synthesis; Pergamon: Oxford,
1992; (c) Rossiter, B. E.; Swingle, N. M. Chem. Rev. 1992, 92, 771; (d) Hayashi, T.; Ya-
masaki, K. Chem. Rev. 2003, 103, 2829; (e) Hayashi, T.; Ueyama, K.; Tokunaga, N.;
Yoshida, K. J. Am. Chem. Soc. 2003,125,11508; (f) Otomaru, Y.; Okamoto, K.; Shintani,
R.; Hayashi, T. J. Org. Chem. 2005, 70, 2503; (g) Shintani, R.; Kimura, T.; Hayashi, T.
Chem. Commun. 2005, 3213; (h) Hayashi, T.; Tokunaga, N.; Okamoto, K.; Shintani, R.
Chem. Lett. 2005, 1480; (i) Shintani, R.; Okamoto, K.; Hayashi, T. Org. Lett. 2005, 7,
4757; (j) Paquin, J. F.; Defieber, C.; Stephenson, C. R. J.; Carreira, E. M. J. Am. Chem. Soc.
2005,127,10850; (k) Paquin, J. F.; Stephenson, C. R. J.; Defieber, C.; Carreira, E. M. Org.
Lett. 2005, 7, 3821.
16. For selected reviews and examples, see: (a) Tomioka, K.; Nagaoka, Y. In Com-
prehensive Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.;
Springer: Berlin, 1999; (b) Kanai, M.; Shibasaki, M. In Catalytic Asymmetric
Synthesis, 2nd ed.; Ojima, I., Ed.; Wiley: New York, NY, 2000; (c) Sibi, M. P.;
Manyem, S. Tetrahedron 2000, 56, 8033; (d) Krause, N.; Hoffmann-Roder, A.