Asymmetric Hydrogenation of Ketones with Polymer-Bound BINAP/Diamine Ruthenium Catalysts

Article abstract of DOI:10.1002/1615-4169(20010430)343:4<369::AID-ADSC369>3.0.CO;2-3

The BINAP/1,2-diphenylethylenediamine RuCl₂ complexes bound to a polystyrene resin act as precatalysts for asymmetric hydrogenation of various simple ketones. The enantioselectivity, turnover number, and turnover frequency are comparable to those attained under homogeneous conditions.

Full text of DOI:10.1002/1615-4169(20010430)343:4<369::AID-ADSC369>3.0.CO;2-3

FULL PAPERS
Asymmetric Hydrogenation of Ketones with
Polymer-Bound BINAP/Diamine Ruthenium Catalysts
Takeshi Ohkuma, Hiroshi Takeno, Yuji Honda, Ryoji Noyori*
Department of Chemistry and Research Center for Materials Science, Nagoya University, Chikusa, Nagoya 464±8602, Japan
Fax: (+81)-52-783-4177, e-mail: noyori@chem3.chem.nagoya-u.ac.jp
Received February 16, 2001; Accepted March 29, 2001
Keywords: asymme-
tric
BINAP; ketone hydro-
genation; polymer-
bound catalyst.
hydrogenation;
Abstract: The BINAP/1,2-diphenylethylenediamine over number, and turnover
RuCl complexes bound to a polystyrene resin act frequency are comparable
2
as precatalysts for asymmetric hydrogenation of var- to those attained under
ious simple ketones. The enantioselectivity, turn- homogeneous conditions.
Introduction
Results and Discussion
Synthesis of Precatalysts
Homogeneous asymmetric catalysis provides a fun-
damental tool for the preparation of chiral building
blocks for biologically important substances and ad- The resin-supported Ru precatalysts 3 were prepared
[1]
vanced materials. Polymer-bound catalysts have in- by using (R)-BINAP ligands bound to polystyrene via
[
6]
6
herent operational and economical advantages: im- an amide-based spacer. [RuCl (h -benzene)] was
2
2
mobilization on solid matrices facilitates the reacted first with (R)-1a in N,N-dimethylacetamide
separation from reaction mixtures, recovery, and re- (DMA) (Ru:diphosphine = 3 : 1) at 80 °C for 24 h and
use of the expensive chiral compounds. Further, then with (R,R)-1,2-diphenylethylenediamine [(R,R)-
the solid-phase reaction offers a technical basis for di- DPEN] [(R,R)-2] (Ru : diamine = 1 : 5) in the same
versity-oriented combinatorial synthesis. Numer- medium at 80 °C for 24 h without stirring. At each
ous resin-supported (pre)catalysts have been devel- step, the unreacted materials were removed by wash-
oped along this line, though their practical ing with DMA. The P NMR analysis of the solid
application application is limited to only a few suggested that the resulting diphosphine/diamine
cases. Many of these are much less reactive than mixed-ligand Ru complex (R,RR)-3a was a 7 : 1 mix-
the homogeneous catalyst systems, and their stereo- ture of the trans-dichloro complex (singlet at
selectivity is often reduced, impeding practical use. 47.5 ppm) and its cis isomer (broad singlets at 50.0
We previously found that RuCl (phosphine) (1,2-dia- and 57.5 ppm) contaminated with unreacted (R)-1a
[
2]
[
3]
[7]
3
1
[8]
[
2]
2
2
mine) complexes, coupled with an alkaline base in 2- (±15.8 ppm) and some unknown compounds. The
propanol, hydrogenate a C=O function preferentially purity of the diphosphine/diamine Ru complex was
over coexisting conjugated or non-conjugated C=C ca. 81%. Both trans- and cis-RuCl [(R)-binap][(R,R)-
2
linkages, halogen atoms, various hetrocycles, and dpen] are known to be reactive for homogeneous hy-
[
4]
[8]
many other functional groups. The use of appropri- drogenation of ketones. As shown in Figure 1, the
ate chiral diphosphines and diamines results in rapid polymer beads are better swelled in DMF than in 2-
and productive asymmetric hydrogenation of a range propanol, which serves as a standard solvent of hy-
[
4]
of achiral and chiral ketones. Their high efficiency drogenation. DMA can also be used in place of
[
5]
prompted us and other groups to immobilize the BI- DMF. In a similar manner, the diastereomer (R,SS)-
3
1
NAP/diamine RuCl complexes. This report describes 3a [ P NMR, d = 46.9 ppm (trans) and 50.7 and
2
our study on asymmetric hydrogenation of simple ke- 57.1 ppm (cis)] was prepared from (R)-1a and (S,S)-
tones using polystyrene-anchored chiral Ru cata- 2. Reaction of 1a and racemic 2 proceeds without dis-
[
5]
lysts.
This reaction exhibits a turnover number crimination of the diamine chirality to result in a 1 : 1
(
TON) as high as 12,300/batch or a total of 33,000 by mixture of the R,RR and R,SS isomers [(R,RR/SS)-3a]
repeated use. The enantioselectivity, productivity, (Scheme 1). The analogue (R,RR)-3b was also ob-
and rate of hydrogenation using the polymer-bound tained by use of the N-propyl compound (R)-1b,
6
catalysts are comparable to those attained under (R,R)-2, and [RuCl(h -benzene)] in a similar proce-
2
homogeneous conditions.
dure.
Adv. Synth. Catal. 2001, 343, No. 4
Ó WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2001
1615-4150/01/34301-369±375 $ 17.50-.50/0
369

asc.wiley-vch.de
system using RuCl [(R)-binap][(R,R)-dpen] in 2-pro-
2
[
8,9]
panol.
The catalyst was recovered by removing
the solution phase by cannula, and reused for hydro-
genation.
Figure 1. Polystyrene beads possessing (R)-BINAP/(R,R)-
DPEN RuCl units observed under a microscope (´ 200).
2
Scheme 2. Asymmetric hydrogenation of ketones.
The durability of the catalyst was tested by hydroge-
nation of 4 with S/C = 2470/batch by repeating the
above procedure. The results are summarized in Ta-
ble 1. The product ee remained consistently high, 97±
9
8%, even after the 14th experiment. The catalytic
Scheme 1. Structures of compounds 1, 2, and 3.
activity was gradually decreased after the tenth ex-
periment, then required a longer reaction period.
The total TON achieved in 14 experiments was
Asymmetric Hydrogenation
3
3,000. Notably, use of a 0.02 M t-C H OK solution is
4 9
necessary in the reuse of the recovered catalyst; reac-
tion was very slow without the strong base. Thus, the
Aromatic Ketones
The polymer-bound Ru complexes 3 are excellent catalytic efficiency of the polymer-supported Ru com-
precatalysts for asymmetric hydrogenation of aro- plex 3a was evaluated as acceptable for some labora-
matic ketones giving the chiral secondary alcohols tory syntheses. During the repeated runs, a new poly-
(Scheme 2). When 1'-acetonaphthone (4) (2.46 mmol, mer-bound Ru complex(es) is formed at the expense
1
.0 M), (R,RR)-3a (0.40 mM), and t-C H OK (20 mM) of the starting RuCl complex (R,RR)-3a. This com-
4
9
2
3
1
(S/C = 2470), in a 1 : 1 2-propanol±DMF mixture plex, showing a broad P NMR signal centered at
[
10]
placed in a glass autoclave, was stirred with a mag- 69 ppm,
netic stirrer gently at ca. 500 rpm under 8 atm of aid of t-C H OK.
acted as a hydrogenation catalyst with the
[
7]
4
9
H and 26 °C for 26 h, the chiral alcohol, (S)-5, was ob-
Hydrogenation of 4 on a 20-g scale with a catalyst
tained in 98% ee with 99% conversion. The ee value molar ratio (S/C) of 12,300 gave (S)-5 in 97% ee with
2
was identical to that obtained in the homogeneous 96% conversion. The second run with such a high S/C
370
Adv. Synth. Catal. 2001, 343, 369±375

FULL PAPERS
Table 1. Asymmetric hydrogenation of 1'-acetonaphthone
Table 2. Sequential asymmetric hydrogenation of different
aromatic ketones.
[
a]
[a]
(4) with (R,RR)-3a.
[b]
[c]
[c]
[b]
Reusing run
Time [h]
Conversion [%]
ee of (S)-5 [%]
Reusing run
Ketone Time [h] Conversion
ee of S alcohol
[%]
[c]
[c]
[%]
1
2
3
4
5
6
7
8
9
26
20
27
24
24
25
36
28
30
84
50
52
48
86
99
100
100
100
100
100
100
99
99
100
99
97
96
98
97
97
97
97
98
98
98
98
98
97
98
97
97
1
2
3
4
4
7
13
22
24
100
100
100
99
97
95
84
84
6a
6b
6c
[
[
a]
b]
[a]
See footnote of Table 1.
See footnote of Table 1.
See footnote of Table 1.
[b]
[c]
[c]
1
1
1
1
1
0
1
2
3
4
(
(
R,RR)-3a was also examined by using acetophenone
6d), which gave 7d in 77±79% ee.
93
[
11]
Hydrogenation
[
a]
Reactions were conducted at 8 atm of H
2
and at 25 °C
of 6d with (R,RR)-3a in a 1 : 1 2-propanol±DMF mix-
using a 1.0 M solution of the ketone (2.4±2.5 mmol) in a 1 : 1
-propanol±DMF mixture containing t-C OK and the
polymer-bound complex (R,RR)-3a. Substrate:catalyst:t-
OK = 2470 : 1 : 50.
Number of times the catalyst was used. See experimental
section for details.
Conversion and ee were determined by chiral GC analy-
sis. Absolute configuration was determined by the sign of ro-
tation.
ture at 8 atm of H and 25 °C ([6d] = 1.0 M, ketone :
2
2
4 9
H
Ru:t-C H OK = 2000 : 1 : 40) showed a TOF of 510 at
4
9
4
0±90% conversion, which was only slightly lower
than the value of 604 (1 : 1 2-propanol±DMF) or 572
pure 2-propanol), observed with the homogeneous
(R)-BINAP/(R,R)-DPEN catalyst under otherwise
4 9
C H
[b]
(
[c]
[
12]
identical conditions.
Although the polymer-bound
catalyst showed a somewhat longer induction period
than that of the homogenous system, the high TOF
was sustained over at least eight repeated runs. DMF
did not retard the hydrogenation.
significantly lowered the conversion, probably due to
deterioration of the Ru catalyst.
Matching the chirality of the diphosphine and the
diamine is important to achieve a high level of enan-
tioselectivity. The diastereomeric catalyst (R,SS)-3a
was less reactive and stereoselective than (R,RR)-3a
in hydrogenation of 4, leading to (S)-5 in only 8% ee.
The complex (R,RR)-3b possessing a modified linker,
coupled with t-C H OK as a cocatalyst, hydrogenated
a,b-Unsaturated Ketones
Hydrogenation of b-ionone (8), a dienone, using
(
R,RR)-3a with S/C = 2470 at 8 atm and 25 °C oc-
curred selectively at the carbonyl function to give
4
9
Table 3. Asymmetric hydrogenation of b-ionone (8) with
4
in a 1 : 1 2-propanol±DMF mixture (S/C = 2000,
[a]
(R,RR)-3a.
8
atm, 25 °C, 42 h) to afford 5 in the same 96% ee. This
catalyst was somewhat less reactive than 3a.
[b]
[c]
[d]
Reusing run
Time [h]
Conversion [%]
ee of (S)-9 [%]
In addition, different kinds of ketonic substrates, 4
and 6a±c, can be hydrogenated sequentially in the
same flask without changing the polymer-supported
catalyst. The result obtained by using (R,RR)-3a with
S/C = 2470/batch at 8 atm and 25 °C is illustrated in
Table 2. The extent of enantioselectivity was very si-
milar to that obtained by the individual reaction using
1
2
3
4
5
6
7
8
9
15
20
24
23
26
30
45
47
25
78
72
75
100
100
100
100
100
100
99
84
84
83
83
83
83
84
85
86
86
87
RuCl [(R)-binap][(R,R)-dpen] in
a
homogeneous
2
100
100
99
phase.
1
1
1
0
1
2
100
87
Reaction Rate
[e]
±
Hydrogenation of 4 using the polymer-bound catalyst
R,RR)-3a with S/C of 2470 at 8 atm and 25 °C (the first
run of Table 1) gave an initial turnover frequency
TOF defined as moles of product/mole of catalyst ´ h)
of 390. The TOF was increased to 1520 when the reac-
tion was conducted at 50 °C, whereas the ee of 5 was
decreased from 98 to 93%. The catalytic activity of
[
[
a]
b]
[a]
See footnote of Table 1.
(
[b]
See footnote of Table 1.
[c]
1
Conversion was determined by H NMR analysis. No con-
jugate reduction products were observed.
(
[
d]
The ee was determined by chiral HPLC analysis. Absolute
configuration was determined by the sign of rotation.
[
e]
Not determined.
Adv. Synth. Catal. 2001, 343, 369±375
371

asc.wiley-vch.de
[
9]
Table 4. Asymmetric hydrogenation of 2,4,4-trimethyl-2-cy-
clohexenone (10) with (R,SS)-3a.
R/S,S combined system. In contrast, reaction of the
cyclohexenone 10 is better effected by an (R)-BINAP/
[
a]
[
15,17]
[b]
[c]
[c]
(S,S)-2 combination.
These phenomena have
Reusing run
Time [h]
Conversion [%]
ee of (S)-11 [%]
been utilized in the asymmetric activation of a race-
mic BINAP Ru complex with an enantiomerically
1
2
3
4
5
6
7
8
9
22
24
24
26
27
25
71
48
49
99
99
99
99
99
98
100
94
85
93
94
93
93
94
94
94
94
95
[
17,18]
pure diamine ligand.
As expected from the
homogeneous chemistry, when 4 was hydrogenated
with a polymer catalyst, (R,RR/SS)-3a, that had been
formed from (R)-1a and racemic 2 (S/C = 2940,
atm, 25 °C, 9 h), (S)-5 was obtained in 87% ee in
00% yield. On the other hand, reaction of the enone
10 with the same Ru catalyst with S/C = 2960 afforded
S)-11 in 91% ee with 99% conversion. The observed
ee's were much higher than the simple averages of
ee's obtained with the R/R,R and R/S,S diastereo-
meric catalysts: 53% ee for (S)-5, and 87% ee for (S)-
8
1
[
a]
Reactions were conducted at 8 atm of H
2
and at 25 °C
using a 1.0 M solution of the ketone (2.5 mmol) in a 1 : 1 2-
propanol±DMF mixture containing t-C OK and the poly-
mer-bound complex (R,SS)-3a. Substrate:catalyst:t-
OK = 3125 : 1 : 65.
(
4
H
9
C
4
H
9
[
[
b]
[b]
See footnote of Table 1.
Conversion and ee were determined by chiral GC analy-
[
17,18]
c]
11.
sis. No conjugate reduction products were observed. Abso-
lute configuration was determined by the sign of rotation.
Conclusion
[
13]
(
S)-b-ionol [(S)-9] in 84% ee.
The high chemo- and
This polymer-anchored catalyst system demonstrates
excellent performance. The asymmetric hydrogena-
tion is usable for certain practical synthesis of chiral
alcohols, because: (1) the extent of enantioselection
is very similar to that of homogeneous hydrogenation;
enantioselectivity were sustained over ten repeated
runs, affording a total TON of 29,260 (Table 3). The
product solution was separated from the catalyst by
transfer with a cannula, concentrated under reduced
pressure, and distilled to give the chiral alcohol. This
procedure is operationally beneficial in the prepara-
tion of certain allylic alcohols including 9. In homoge-
neous hydrogenation, because of the general instabil-
(2) the repeated use of the recovered catalyst leads to
a relatively high total TON, up to 33,000; (3) the hy-
drogenation rate is comparable to that of the corre-
sponding homogeneous reaction under similar con-
ditions. This method will be useful for combinatorial
synthesis of chiral alcohols.
[
13a]
ity of allylic alcohols,
removal of the Ru residue by
filtration through a short silica-gel column, prior to
distillation, is recommended.
When 2,4,4-trimethyl-2-cyclohexenone (10), a cyc-
lic enone, was hydrogenated with (R,SS)-3a in a 1 : 1
2
-propanol±DMA mixture with S/C = 3125 at 8 atm
Experimental Section
and 25 °C for 21 h, the cyclic allylic alcohol (S)-11
was produced in 93% ee and in 99% yield. The S and
R alcohols are very important as synthetic intermedi-
General Remarks
[
14]
ates of bioactive terpenes and odorants.
The de-
Gas chromatographic (GC) analysis was conducted on a Shi-
mazu GC-17A instrument with a Chirasildex CB column (b-
cyclodextrin, df = 0.25 mm, 0.32 mm i. d. ´ 25 m, CHROM-
PAC) using helium carrier gas (40±50 kPa) with a split ratio
of 20 : 1. High-performance liquid chromatographic (HPLC)
analysis was conducted on a Shimazu SCL10A instrument
with a CHIRALPAK AS column (4.6 mm i. d. ´ 250 mm, Daicel
Chemical Ind.) eluted with a 1 : 200 2-propanol±hexane mix-
gree and sense of the enantioselection were compar-
able with those obtained with RuCl [(R)-binap][(S,S)-
2
[8,15]
dpen].
The catalyst was reused seven times with-
out problems, after which the rate was to some extent
lowered. The reaction gave a total TON of 27,250,
while the product ee was consistently in the range of
9
3±95% (Table 4). The diastereomeric catalyst
1
31
(
R,RR)-3a hydrogenated the enone 10, giving (S)-11
ture (0.5 mL/min). H and
P NMR spectra (400 and
[16]
in 81% ee.
162 MHz, respectively) were recorded on a JEOL a 400 FT-
1
NMR. The chemical shifts of H NMR resonances are re-
ported in parts-per-million (d) relative to tetramethylsilane.
3
1
The chemical shifts of P NMR resonances are reported in
parts-per-million (d) relative to external phosphoric acid.
Signal patterns are indicated as s, singlet; d, doublet; t, tri-
plet; q, quartet; m, multiplet; br, broad peak. Optical rotation
measurements of chiral products were performed on a JAS-
CO P-1010-GT polarimater using a sodium lamp in the indi-
cated solvent in a 5 mm i. d. ´ 5 cm cell.
Reaction with Catalysts Formed from
the Racemic DPEN Ligand
Hydrogenation of the aromatic ketone 4 is known to
proceed with a higher rate and better enantioselectiv-
ity with RuCl [(R)-binap][(R,R)-dpen] than with the
2
372
Adv. Synth. Catal. 2001, 343, 369±375

FULL PAPERS
Materials
Asymmetric Hydrogenation of 1'-Acetonaphthone
(4)
Polymer-bound BINAPs, (R)-1a and (R)-1b, were furnished
by Oxford Asymmetry International. The loading amounts
The Ru complex (R,RR)-3a (29.3 mg, catalyst content 9.48
mmol) was placed in a 500-mL glass autoclave equipped with
a Teflon-coated magnetic stirring bar, and the air in the auto-
clave was replaced with argon. A solution of ketone 4 (20.1 g,
118 mmol, S/C = 12,300) in a 1 : 1 mixture of 2-propanol and
DMF (120 mL), and a 1.0 M t-C H OK solution in t-C H OH
of the BINAPs on the polymer were 0.40 mmol/g and
6
0
.59 mmol/g, respectively. [RuCl
2
(h -benzene)]
2
was pur-
chased from Aldrich Chemical Co. and used without further
purification. (R,R)-DPEN [(R,R)-2] was purchased from Kan-
kyo Kagaku Co. and used without further purification. The
cyclic enone 10 was purchased from Aldrich, and the other
ketone substrates for hydrogenation were purchased from
Tokyo Chemical Industry Co. All substrates were washed
with a 0.1 M KOH solution and purified by distillation or re-
crystallization. Guaranteed-reagent grade 2-propanol was
4
9
4
9
(2.3 mL, 2.3 mmol), which had been degassed by bubbling ar-
gon, were added to the autoclave. The mixture was degassed
by five vacuum±filling with argon cycles. Hydrogen was initi-
ally introduced into the autoclave at a pressure of 5 atm, then
reduced to 2 atm by careful release of the stop valve. After this
procedure had been repeated seven times, the vessel was
pressurized to 8 atm. The mixture was stirred by a magnetic
freshly distilled over CaH
grade DMA and DMF were distilled over CaH
2
before use. Guaranteed-reagent
and stored in
2
[
7]
Schlenk tubes. Hydrogen of 99.99999% purity (Nippon Sana-
so) was used. Argon gas (99.998%) was further purified by
passage through a BASF catalyst R3±11 column at 80 °C.
stirrer at ca. 500 rpm at 25 °C for 97 h. The yield was deter-
mined by GC to be 96%. GC: column temp, 150 °C; injection
temp, 200 °C; He, 50 kPa; retention time (t ) of (R)-5,
R
R R
41.5 min (1.5%); t of (S)-5, 35.3 min (94.5%); t of 4,
16.7 min (4.0%). The solution phase was moved into a separa-
tion funnel, diluted with ether (100 mL), washed three times
with brine (30 mL), and dried with anhydrous Na SO . After
removal of Na SO , the residue was purified by bulb-to-bulb
distillation to give (S)-5 (18.7 g, 92% yield, 96% purity, 97%
Preparation of Polymer-Bound BINAP/Diamine
Ru complex (R,RR)-3a
2
4
2
4
6
[RuCl
2
(h -benzene)]
2
(102.9 mg, 0.206 mmol) and (R)-1a
24
[8,19]
1
ee). [a]
d = 1.68 (d, 3 H, J = 6.8 Hz, CH
D
:
±81.9 (c = 1.01, ether).
3
H NMR (CDCl ):
(333.0 mg, BINAP content 0.133 mmol) were placed in a 20-
3
), 5.69 (q, 1 H, J = 6.8 Hz,
mL Schlenk flask. After the air in the flask had been replaced
with argon, degassed DMA (7.5 mL) was added. The mixture
CHOH), 7.47±7.55 (m, 3 H, aromatics), 7.68 (d, 1 H, J = 7.2 Hz,
aromatic), 7.78 (d, 1 H, J = 8.4 Hz, aromatic), 7.89 (d, 1 H,
J = 7.2 Hz, aromatic), 8.13 (d, 1 H, J = 8.4 Hz, aromatic).
[7]
was degassed and heated at 80 °C without stirring for 24 h.
After the mixture had cooled to 25 °C, the solution phase was
removed with a cannula fitted with filter paper, and the beads
were rinsed five times with DMA (5.0 mL). Then (R,R)-2
(
141.6 mg, 0.667 mmol) and DMA (7.5 mL) were added, and
Sequential Asymmetric Hydrogenation of
Aromatic Ketones, 4 and 6a±c
the mixture was degassed and heated at 80 °C without stir-
[
7]
ring for 24 h. After the mixture had cooled to 25 °C, the se-
parated beads were rinsed seven times with DMA (5.0 mL),
seven times with ether (5.0 mL), and dried under reduced
pressure (1 torr) at 40 °C for 24 h to give (R,RR)-3a (yield:
(R,RR)-3a (3.1 mg, catalyst content 1.00 mmol) was placed in
a 100-mL glass autoclave. A solution of 4 (419.4 mg,
2.46 mmol, S/C = 2470/batch) in a 1 : 1 2-propanol±DMF
3
41 mg). The purity of (R,RR)-3a estimated by gel-phase
mixture (2.5 mL) and a 1.0 M t-C
OH (50 mL, 50 mmol) were added to the autoclave, and
hydrogen was introduced to a pressure of 8 atm. The mix-
4 9
H OK solution in t-
3
1
31
P NMR analysis was 81%. P NMR (DMA with a portion of
4 9
C H
DMSO-d
7.5 (br s, cis isomer). The trans : cis ratio was 7 : 1.
R,SS)-3a: The complex was prepared by the same proce-
6
): d = 47.5 (s, trans isomer), 50.0 (br s, cis isomer),
[7]
5
ture was stirred at ca. 500 rpm at 25 °C. The solution phase
was removed by cannula and the remaining catalyst beads
were washed five times with a 1 : 1 2-propanol±DMF mixture
(2.5 mL). (S)-5 was purified using the same procedure as
that described in the former section. To this glass autoclave,
6a (334.4 mg, 2.49 mmol) dissolved in a 1 : 1 2-propanol±
(
6
dure as described above: [RuCl
.0996 mmol), (R)-1a (154.4 mg, 0.0618 mmol), (S,S)-2
62.2 mg, 0.293 mmol). (R,SS)-3a (yield: 155.8 mg). The pur-
2
(h -benzene)]
2
(49.8 mg,
0
(
31
6
ity was 80%. P NMR (DMA with a portion of DMSO-d ):
d = 46.9 (s, trans isomer), 50.7 (br s, cis isomer), 57.1 (br s,
cis isomer). The trans:cis ratio was 21 : 1.
DMF mixture (2.5 mL) and a 1.0 M t-C
4 9
H OK solution in t-
4 9
C H OH (50 mL, 50 mmol) were added, and hydrogenation
(
R,RR/SS)-3a: The complex was prepared by the same
was conducted using the same procedure as that outlined
above. The four different chiral alcohols, (S)-5a and (S)-7a±
c, were obtained by repeating the hydrogenation procedure
with use of the same catalyst. The data of each product is de-
scribed below.
6
procedure as described above: [RuCl
2
(h -benzene)]
11.0 mg, 0.022 mmol), (R)-1a (72.6 mg, 0.029 mmol), (±)-2
29.1 mg, 0.137 mmol). (R,SS)-3a (yield: 72.6 mg). The pur-
2
(
(
ity was 68%. The (R,RR)-3a and (R,SS)-3a were mixed at a
ratio of 1 : 1.
2
4
(S)-5: 84% yield (358.2 mg), 97% ee. [a]
D
: ±82.4 (c = 1.00,
[
8,19]
1
(
R,RR)-3b: This complex was prepared by the same pro-
ether).
section.
(S)-7a: 77% yield (261.5 mg), 95% ee. [a]
GC and H NMR data are described in the former
6
cedure as that used for 3a: [RuCl
.135 mmol), (R)-1b (153.5 mg, 0.0910 mmol), (S,S)-2
95.9 mg, 0.452 mmol). (R,RR)-3b (yield: 160.2 mg). The
2
2
(h -benzene)] (67.7 mg,
3
1
0
(
D
: ±70.3 (c = 1.01,
of (R)-7a, 14.3 min
of (S)-7a, 16.3 min (97.5%); t of 6a, 5.5 min
[8,20]
CHCl
3
).
GC: column temp, 125 °C; t
R
31
purity was 84%. P NMR (DMA with a portion of DMSO-
(2.3%); t
(0.2%).
R
R
d ): d = 47.6 (s, trans isomer), 49.9 (br s, cis isomer), 57.5 (br
6
3
2
s, cis isomer). The trans:cis ratio could not be determined
because the peaks were not completely separated.
(S)-7b: 83% yield (312.6 mg), 84% ee. [a]
D
:
±42.3
[8,21]
(c = 1.05, CHCl
3
).
GC: column temp, 110 °C; t
R
of (R)-
Adv. Synth. Catal. 2001, 343, 369±375
373

asc.wiley-vch.de
7
2
b, 35.4 min (7.8%); t
1.3 min (0.3%).
R
of (S)-7b, 38.6 min (91.9%); t
R
of 6b,
lated from eight experiment sets, and values were first-or-
der-plotted to be 508 (moles/mole of Ru ´ h). Correlations
between period, conversion, and % ee of (S)-7d, are as fol-
lows: (10, 3, ±), (20, 3, ±), (40, 5, ±), (80, 29, ±), (120, 46, 79),
(160, 63, 79), (250, 96, 79), (300, 99, 79).
3
2
(
S)-7c: 85% yield (353.2 mg), 84% ee. [a]
D
: ±29.3 (c = 1.14,
GC: column temp, 140 °C; t of (R)-7c,
of (S)-7c, 19.1 min (91.5%); t of 6c,
[
8,22]
benzene).
1
1
R
8.7 min (7.7%); t
3.9 min (0.8%).
R
R
Hydrogenation with trans-RuCl
dpen] (homogeneous system): Conditions [trans-
RuCl [(R)-binap][(R,R)-dpen] (2.5 mg, 2.48 mmol), 6d
599.2 mg, 4.99 mmol), 1.0 M t-C OK in t-C OH (0.10
mL, 0.10 mmol), 2-propanol (2.5 mL), DMF (2.5 mL), 8 atm
, 25 °C]. Conversions and ee's were determined by GC
analysis, the conditions and t of compounds of which are
2
[(R)-binap][(R,R)-
2
Asymmetric Hydrogenation of b-Ionone (8)
(
4
H
9
4 9
H
Conditions [(R,RR)-3a (3.1 mg, catalyst content 1.00 mmol), 8
477.0 mg, 2.48 mmol, S/C = 2470), 1.0 M t-C OK in t-
OH (50 mL, 50 mmol), 2-propanol (1.25 mL), DMF (1.25
mL), 8 atm H , 25 °C, 15 h]. (S)-9 (400.0 mg, 83% yield). No
conjugate reduction products were observed by H NMR
analysis. HPLC [t of (R)-9, 24.8 min (8.1%); t of (S)-9,
9.8 min (91.9%)]. [a] 84% ee.
H
2
(
4 9
H
R
4 9
C H
described above. TOF was calculated from eight experiment
sets, and values were first-order-plotted to be 604. Correla-
tions between period, conversion, and % ee of (S)-7d, were
as follows: (5, 1, ±), (10, 2, ±), (20, 7, 77), (40, 20, 78), (80, 36,
2
1
R
R
2
5
[23]
1
D 3
: ±5.1 (c = 2.77, CHCl ),
7
8), (120, 53, 78), (160, 76, 79), (240, 100, 79).
Asymmetric Hydrogenation of 2,4,4-Trimethyl-2-
cyclohexenone (10)
Acknowledgements
Conditions [(R,SS)-3a (3.1 mg, catalyst content 0.79 mmol),
We are grateful to Oxford Asymmetry International for sup-
plying samples of the polymer-bound BINAPs (R)-1a and
1
0 (348 mg, 2.52 mmol, S/C = 3125), 1.0 M t-C
OH (50 mL, 50 mmol), 2-propanol (1.25 mL), DMA (1.25
mL), 8 atm H , 25 °C, 22 h]. (S)-11 (256.0 mg, 73% yield). No
,4-reduction products were observed by H NMR and GC
analyses. GC [column temp, 90 °C; t of (R)-11, 38.5 min
of (S)-11, 40.2 min (95.4%); t of 10, 23.0 min
93% ee.
4 9
H OK in t-
4 9
C H
(R)-1b. This work was financially supported by grants-in-
2
1
aid from the Ministry of Education, Culture, Sports, Science
and Technology of Japan (Nos. 07CE2004 and 11440188).
1
R
(
(
3.5%); t
1.1%)]. [a]
R
R
3
0
[13,14]
D
: ±83.8 (c = 1.10, ether),
References and Notes
Asymmetric Hydrogenation of Ketones with
R,RR/SS)-3a: Hydrogenation of 4
[
1] (a) R. Noyori, Asymmetric Catalysis in Organic Synth-
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(
Conditions [(R,RR/SS)-3a (3.1 mg, catalyst content 0.84
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H
1
999; (c) Catalytic Asymmetric Synthesis, 2nd Ed. (Ed.:
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H
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(
8
2
1
[2] Recent reviews: (a) D. Pini, A. Petri, A. Mastantuono,
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Hydrogenation of 10
Conditions [(R,RR/SS)-3a (3.1 mg, catalyst content 0.84
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C
4
H
9
OK in t-C
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262.6 mg, 75% yield, 91% ee). GC data are described above.
4
H
9
OH (50 mL, 50 mmol), 2-propanol (1.25
2
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(
(
1
Eds.: D. Obrecht, J. M. Villalgordo), Elsevier, Oxford,
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The kinetic experiments were conducted in a 100-mL glass
autoclave equipped with a sampling needle connected to a
stop valve. A small portion of the reaction mixture was col-
lected through this system at regular intervals and analyzed
by chiral GC.
Hydrogenation with (R,RR)-3a: Conditions [(R,RR)-3a
(
7.9 mg, catalyst content 2.50 mmol), 6d (597.9 mg,
4
0
2
.98 mmol), 1.0 M t-C
.10 mmol), 2-propanol (2.5 mL), DMF (2.5 mL), 8 atm H
5 °C]. Conversions and ee's were determined by GC analy-
of (R)-7d, 15.0 min; t of (S)-
of 6d, 6.7 min]. Initial rate (TOF) was calcu-
4 9 4 9
H OK in t-C H OH (0.10 mL,
2
,
sis. GC [column temp, 110 °C; t
d 16.2 min; t
R
R
7
R
374
Adv. Synth. Catal. 2001, 343, 369±375

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1
[
[
10] RuH signals were not observed by H NMR.
11] An ee of 99% was achieved by the use of XylBINAP/
[
4]
DAIPEN Ru complex. XylBINAP = 2,2'-bis(di-3,5-xy-
lylphosphino)-1,1'-binaphthyl. DAIPEN = 1,1-di(4-ani-
syl)-2-isopropyl-1,2-ethylenediamine.
Adv. Synth. Catal. 2001, 343, 369±375
375