An efficient diphosphine/hybrid-amine combination for ruthenium(II)- catalyzed asymmetric hydrogenation of aryl ketones

Article abstract of DOI:10.1002/adsc.201000577

Readily available and modular hybrid amine/benzimidazole-based 1H-benzimidazole-2-methanamine (BIMA) ligands in combination with 2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane (DIOP) afford efficient catalytic systems for the ruthenium(II)-catalyzed asymmetric hydrogenation (AH) of a number of aryl ketones. The AH proceeds smoothly with substrate-to-catalyst (S/C) molar ratios of up to 100,000 (TOF of 6500ah ^-1, 8aatm) giving chiral alcohols in up to 99% ee.

Full text of DOI:10.1002/adsc.201000577

UPDATES
DOI: 10.1002/adsc.201000577
An Efficient Diphosphine/Hybrid-Amine Combination for
Ruthenium(II)-Catalyzed Asymmetric Hydrogenation of Aryl
Ketones
Yuehui Li,a Yougui Zhou,b Qixun Shi,a Kuiling Ding,a Ryoji Noyori,c
and Christian A. Sandovala,*
a
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences, 345 Lingling Rd, Shanghai 200032, Peopleꢀs Republic of China
Fax : (+86)-21-5492-5312; e-mail: sandoval@sioc.ac.cn
Enantiotech Corp., Ltd., Zhongshan Torch Hi-Tech Industrial Development Zone, Guangdong Province, Peopleꢀs
b
Republic of China
c
Department of Chemistry and Research Center for Materials Science, Nagoya University, Nagoya, Japan
Received: July 22, 2010; Revised: November 16, 2010
Dedicated to Professor Henri B. Kagan for his contribution to asymmetric catalysis.
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201000577.
Abstract: Readily available and modular hybrid
amine/benzimidazole-based 1H-benzimidazole-2-
methanamine (BIMA) ligands in combination with
2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis(diphen-
ACHTUNGTRENNUNGylphosphino)butane (DIOP) afford efficient catalyt-
ic systems for the ruthenium(II)-catalyzed asym-
metric hydrogenation (AH) of a number of aryl ke-
tones. The AH proceeds smoothly with substrate-
to-catalyst (S/C) molar ratios of up to 100,000 (TOF
of 6500 hÀ1, 8 atm) giving chiral alcohols in up to
99% ee.
symmetrical hybrid amino-ligands consisting of the
ubiquitous amine (NH2) functionality and a second
chelating moiety.[6] Among these, highly efficient sys-
tems have resulted from the NH2/pyridine combina-
tion, which have interestingly been capable of gener-
ating alcohols via AH[3d,7] and ATH[8] in high enantio-
purity. We recently reported that the related NH2/
benzimidazole hybrid BIMA (a-1H-benzimidazole-2-
methanamine) ligands further allow for the hydroge-
nation to proceed uncharacteristically in non-protic
solvents.[9]
Herein, we report the subsequent finding that
DIOP/BIMA[10] combinations generate highly effec-
tive catalysts for the Ru-catalyzed AH of simple and
cyclic aryl ketones. Thus, hydrogenation of acetophe-
none (1) proceeded smoothly under 20 atm of H2 with
a substrate-to-catalyst (S/C) molar ratio of 100,000
giving (S)-1-phenylethanol [(S)-2] quantitatively in
Keywords: alcohols; asymmetric catalysis; hydroge-
nation; N ligands; ruthenium
The catalytic generation of chiral alcohols can be con- 98% ee when catalyzed by RuCl2ACTHNUTRGNEUNG[(S,S)-diop][(S)-Me-
veniently achieved by asymmetric hydrogenation bimaH] [(SS,S)-4] under basic conditions in toluene/t-
(AH) and asymmetric transfer hydrogenation (ATH) BuOH (9:1, v/v) solvent (Scheme 1).
of the corresponding ketone using transition metal-
Screening of representative C2-chiral bisphosphines
based catalysts comprised of well designed chiral li- in combination with several hybrid NH2/imidazole-
gand(s).[1] For AH of simple aryl ketones, trans- based ligands using [RuCl2(h6-benzene)]2 to generate
RuCl2(diphosphine)(1,2-diamine) catalysts in i-PrOH the catalyst in situ revealed that the DIOP/3 combina-
solvent under basic conditions have yielded the most tion gave optimum catalytic performance both in
efficient and general systems.[2] Here, the highly che- terms of activity and enantioselectivity.[11] Further-
moselective reduction stems from the synergistic more, catalysts using the NH2/benzimidazole combi-
À
action of the (re)generated RuH NH2 component nation were significantly more efficient compared to
which functions through a metal-ligand bifunctional the simple NH2/imidazole counterparts. Table 1 de-
mechanism.[3–5] More recently, this functional motif tails the subsequent evaluation of 3 using similar in
has been further expanded by the development of un- situ generated catalyst [S/C=1000, P(H2)=8 atm, t=
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Yuehui Li et al.
UPDATES
with (S)-2 being obtained in 92% and 83% ee when
3d or 3e were used, respectively.
Isolated RuCl
2ACHTUNGTRNE[NUNG (S,S)-DIOP][(S)-3b] [(SS,S)-4] and
RuCl2A[(S,S)-DIOP][(S)-3c] [(SS,S)-5] complexes were
CTHUNGTRENNUNG
obtained as a mixture of stereo- and regioisomers in
75–76% yield by heating DMF mixtures of [RuCl2(h6-
benzene)]2 and (S,S)-DIOP at 1008C (2 h), followed
by addition of (S)-3b or (S)-3c in CH2Cl2.
For the latter, increasing the temperature (> 708C)
resulted in a non-reversible shift towards the tenta-
tively assigned trans-isomer,[12] which was obtained as
a mixture of regioisomers in a ca 3:1 ratio. The
31P NMR spectrum of (SS,S)-4 displayed predomi-
nantly one pair of resonances at d=40.0, 27.9 (JP, P
=
42.7 Hz, >95%) ppm, while (SS,S)-5 showed signals
centred at d=40.1 and 28.2 (JP, P =42.5 Hz, ca 95%)
ppm. Both complexes are stable and can be handled
and stored in air. Importantly, the AH of 1 catalyzed
by isolated (SS,S)-4 and (SS,S)-5 (regardless of the
isomer ratio obtained) gave (S)-2 in the same ee
(96%) and as for the corresponding in situ generated
catalyst systems {conditions: [1]=0.33M, S/C=1000,
P(H2)=8 atm, toluene/t-BuOH (9:1) solvent}.
Scheme 1. Asymmetric hydrogenation of acetophenone (1)
to (S)-phenylethanol [(S)-2] catalyzed by RuCl
[(S)-Me-bima] [(SS,S)-(4)].
2ACHTUNGTRENUN[NG (S,S)-diop]
Table 2 contrasts the outcome for AH of 1 cata-
lyzed by (SS,S)-5 under various reaction conditions.
In terms of selectivity, the catalysis was highly influ-
enced by the solvent used. Non-protic solvents and t-
BuOH generally yielded (S)-2 in higher ee (90–92%)
while hydrogenation was considerable less selective in
other protic solvents (31–59% ee). Interestingly, the
enantioselectivity was greatly enhanced by using sol-
vent mixtures. Thus, toluene/EtOH and toluene/i-
PrOH 19:1 (v/v) mixtures gave (S)-2 in 97% ee which
is dramatically higher than the corresponding 39 and
59% ee obtained in EtOH and i-PrOH alone. Similar-
ly, AH using a toluene/t-BuOH mixture gave (S)-2 in
96% ee. In contrast, the ee for (S)-2 was not influ-
enced by the base type (MOH or t-BuOM, M=K,
Na) or base concentration ([base]=5–20 mM) gener-
ally yielding (S)-2 in 96–97% ee. No reaction was ob-
served with K2CO3 and t-BuOLi. Similarly, no ee %
effects were observed over a 4–60 atm H2 pressure
range although, as expected, the turnover frequency
(TOF)[13] increased considerably with increasing pres-
sure. Increasing the temperature to 508C yielded (S)-
Table 1. Asymmetric hydrogenation of acetophenone (1)
catalyzed by in situ generated catalyst comprised of
[RuCl2(h6-benzene)]2, (S,S)-DIOP and (S)-3.[a]
Entry
Ligand
Yield[b] [%]
ee[b] [%] (config.)[c]
1
2
3
4
5
6
7
8
9
3a
100
100
100
99
99
100
99
89 (S)
96 (S)
96 (S)
92 (S)
83 (S)
95 (S)
96 (S)
96 (S)
97 (S)
(S)-3b
(S)-3c
(S)-3d
(S)-3e
(S)-3f
(S)-3g
(S)-3h
(S)-3i
100
81
[a]
Reaction conditions: [1]=0.33M (S/C=1000); [(S,S)-
DIOP and [3]=0.33 mM; [[RuCl2(h6-benzene)]2]=
0.15(2) mM, [t-BuOK]=20 mM; P(H2)=8 atm; t=1 h;
T=258C; toluene/t-BuOH (9:1 v/v).
Determined by GC analysis.
Determined by [a]D measurement.
[b]
[c]
1 h, T=258C]. For most combinations, AH proceeded 2 in slightly lower ee (93%).
smoothly giving (S)-2 quantitatively within the 1 h
To compare the solvent influence on catalytic effi-
period. The notable exception was for 3i which only ciency further, reaction profiles were obtained under
managed 81% conversion. Hydrogenation using achi- analogous conditions using toluene, t-BuOH and a
ral 3a, gave the product alcohol in 89% ee. This value toluene/t-BuOH (9:1, v/v) mixture as solvent {condi-
was increased upon a-methyl substitution, although tions: [(SS,S)-4]=0.2 mM, S/C=2000, [t-BuOK]=
the enantioselectivity was not influenced to any great 30 mM, P(H2)=8 atm, 258C} (Figure 1).[14] Hydroge-
extent by the steric bulk of R1. Accordingly, (S)-2 was nation proceeded smoothly and quantitatively in all
obtained consistently in 96Æ1% ee for all combina- cases with calculated maximum TOF values (8 atm,
tions except where the R2 substituent on the benzimi- 50% conversion) of 6500, 3800 and 5200 hÀ1, respec-
dazole moiety contained an electron-withdrawing tively. The relatively high TOF observed in toluene
group (3d, e). Here, the enantioselectivity was lower, solvent alone is particularly noteworthy[15] since, typi-
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An Efficient Diphosphine/Hybrid-Amine Combination for Ruthenium(II)-Catalyzed Asymmetric Hydrogenation
Table 2. Asymmetric hydrogenation of acetophenone (1) catalyzed by RuCl2ACHTUNGTRENNUNG
[(S,S)-DIOP][(S)-3c] [(SS,S)-5].[a]
t [h] T [8C] Yield[d] [%] ee[d] [%] (config.)[e]
Entry Solvent[b]
Base
Base conc. [mM] P [atm] S/C[c]
1
2
3
4
5
6
7
8
toluene
CH2Cl2
Et2O
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
20
20
20
20
20
20
20
20
20
20
20
8
8
8
8
8
8
8
8
8
60
8
8
8
1000
1000
1000
1000
1000
1000
1000
1000
1000
10,000
1000
1000
1000
1
1
2
1
1
1
1
1
1
1
1
1
1
25
25
25
25
25
25
25
25
25
25
50
25
25
100
97
100
31
100
100
28
92 (S)
92 (S)
91 (S)
39 (R)
59 (S)
90 (S)
97 (S)
97 (S)
96 (S)
97 (S)
93 (S)
96 (S)
97 (S)
EtOH
i-PrOH
t-BuOH
toluene/EtOH[f]
toluene/i-PrOH[f] t-BuOK
toluene/t-BuOH t-BuOK
toluene/t-BuOH t-BuOK
toluene/t-BuOH t-BuOK
55
9
100
100
100
100
100
10
11
12
13
toluene/t-BuOH t-BuONa 20
toluene/t-BuOH KOH
5
[a]
[b]
[c]
[d]
[e]
[f]
Reaction conditions: [1]=0.33–0.82M; [(SS,S)-5]=0.16–0.33 mM.
Toluene/t-BuOH 9:1 (v/v) ratio used.
S/C=substrate-to-catalyst molar ratio.
Determined by GC analysis.
Determined by [a]D measurement.
Toluene/EtOH or i-PrOH 19:1 (v/v) used as solvent.
with addition of an equivalent (relative to catalyst) of
PPh3. No such effect was observed for (SS,S)-5. For
example, in the AH of 6e using (SS,S)-4, the ee of
product (S)-7e was enhanced from 97 (entry 5) to
99% ee (entry 6) when PPh3 (1 equiv.) was added. In
contrast, (S)-7e was obtained in 96% ee with/without
PPh3 addition (entries 7 and 8) when (SS,S)-5 was
used. Also, while the latter displays high activity using
KOH or t-BuOK base, (SS,S)-4 requires t-BuOK for
optimum TOF and selectivity. Such characteristic var-
iations suggest that subtle differences arise from the
electronic properties of the BIMA ligand in concert
with, and influenced by, the particular reaction pa-
rameters used (see Table 1).
Figure 1. Reaction profiles for the asymmetric hydrogena-
tion of acetophenone (1) catalyzed by RuCl2ACTHNUTRGNEUNG[(S,S)-diop][(S)-
3b] [(SS,S)-(4)]. Reaction conditions: [1]=0.4M, [(SS,S)-4]=
0.2 mM, [t-BuOK]=30 mM, P(H2)=8 atm, 258C.
Ring-substituted 1-phenylethanols were generated
in high ee values (>96%) and showed relatively
minor electronic effects resulting from the para and
cally, a protic solvent (i-PrOH) is required for opti- meta substituents. The steric hindrance arising from
mum activity in NH2-mediated hydrogenation of ke- ortho-substitution in 6b resulted in a reduced TOF
tones.[2–4,6,7] Although a noticeable reduction in 1 con- (longer reaction time needed) although, similarly,
sumption beyond ca. 80% conversion was evident, im- little influence on enantioselectivity was evident (96%
portantly, addition of t-BuOH (10% v/v) completely ee). Hydrogenation proceeded smoothly for substitut-
circumvented such a behaviour while concomitantly ed 2’-Cl-benzophenone (10) and heteroaromatic 11
increasing the ee from 92 (toluene) to 97% (toluene/t- giving the corresponding alcohols in 99% ee. Similar-
BuOH).[16]
ly, the AH of highly electron-rich substituted 12 was
The DIOP/BIMA combination efficiently catalyzed readily achieved (ee=96–97%) even at an S/C ratio
the AH of a variety of aryl ketones in high enantiose- of 100,000 (12a, entry 14). Of special note is the high
lectivity (96–99% ee) as listed in Table 3 (Scheme 2). activity and enantioselectivity (96–98%) obtained for
Moreover, the system was rather robust with purifica- cyclic aryl ketones.[17] AH of 6-substituted 13b and
tion of substrate or solvent (typically by distillation) 13c gave products in 98 and 97% ee, respectively,
not being necessary. Overall, although catalysis by while the 7-OMe derivative 13d was hydrogenated in
both (SS,S)-4 and (SS,S)-5 complexes proceeded with 97% ee.
similar activity and selectivity, subtle differences were
In summary, the DIOP/BIMA combination yields
apparent. Most notably, for (SS,S)-4 the ee of ob- efficient, selective, cost-effective and robust Ru-based
tained alcohol was consistently increased by 2–5% catalysts for the AH of a variety of aryl ketones.
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Yuehui Li et al.
UPDATES
Table 3. Asymmetric hydrogenation of aryl ketones (6, 8–13) catalyzed by RuCl
G
ACHTUNGTRENNUNG
[(S,S)-DIOP][(S)-3c] [(SS,S)-5].[a]
Entry
Ketone
Catalyst
PPh3 [equiv.][b]
S/C[c]
P [atm]
t [h]
Yield[d] [%]
ee[d] [%] (config.)[e]
1
2
3
4
5
6
7
8
1
6b
6c
6d
6e
6e
6e
6e
6f
8
9
10
11
12a
12b
13a
13b
13b
13c
13d
U
1
1
1
–
–
1
–
1
1
1
1
1
1
–
–
1
1
–
–
1
100,000
1000
5000
5000
1000
1000
5000
5000
1000
1000
1000
1000
1000
100,000
1000
1000
1000
5000
1000
5000
30
12
8
8
8
8
8
8
8
8
8
8
8
30
8
8
8
12
8
20
10
4
9
5
5
6
6
10
5
2
5
3
20
10
5
5
10
5
100
100
100
100
100
100
100
100
100
100
100
100
100
>99
100
100
100
100
100
100
98 (S)
96 (S)
99 (S)
96 (S)
97 (S)
99 (S)
96 (S)
96 (S)
97 (S)
99 (S)
99 (S)
99 (R)
98 (S)
96 (S)
97 (S)
96 (S)
98 (S)
97 (S)
97 (S)
97 (S)
9
10
11
12
13
14
15
16
17
18
19
20
12
10
[a]
Conditions: [6, 8-13]=0.33–2.5M; [(SS,S)-4 or 5]=0.025–0.33 mM; [t-BuOK]=11–20 mM; T=258C; toluene/t-BuOH
(9:1 v/v).
Relative to (SS,S)-4 or 5.
S/C=substrate-to-catalyst molar ratio.
Determined by GC or HPLC analysis.
Determined by [a]D measurement.
[KOH]=40 mM used as base.
[b]
[c]
[d]
[e]
[f]
Experimental Section
General
Moisture- and air-sensitive manipulations were conducted
using standard Schlenk techniques under an argon atmos-
phere. CH2Cl2 was distilled from CaH2 prior to use. Toluene
(AR grade, Aladin Reagent Co.) and t-BuOH (GR grade,
Tianjin Beilian Co.) were used as purchased. Acetophenone
(1, Sinopharm Chemical Co.) and tetralone (13a, Acros
Chemical Co.) were distilled from CaH2 prior to use. Unless
otherwise noted all other commercially available ketones
were purchased from Acros Chemical Co. and used without
purification. [RuCl2(h6-benzene)]2 and all phosphine ligands
were purchased from Strem Chemical Co. The syntheses of
a-R-1H-benzimidazole-2-methanamine ligands [R-BIMAH,
3a, b, f, h] have been previously reported.[9]
Gas chromatography (GC) analysis was conducted on a
Hewlett Packard 6890 or 7820 instrument equipped with a
BETA-DEXPTMP 120 fused silica capillary column (df=
0.25 mm, 0.25 mm i.d., 30 m, Supelco). P1PH- and P31PP NMR
data were collected on Varian Mercury vx 300 and 400 spec-
trometers. Chemical shifts are expressed in parts per million
(ppm) relative to tetramethylsilane and phosphoric acid so-
lution (85%) for 1H and 31P NMR, respectively. MS
Scheme 2. Asymmetric hydrogenation of aryl ketones (6, 8–
13) catalyzed by RuCl2A[(S,S)-diop][(S)-3b] [(SS,S)-4] and
[(S,S)-diop][(S)-3c] [(SS,S)-(5)].
(MALDI) were conducted on a Voyager-DE STR (Applied
Biosystems Co.).
CTHUNGTRENNUNG
RuCl2ACHTUNGTRENNUNG
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An Efficient Diphosphine/Hybrid-Amine Combination for Ruthenium(II)-Catalyzed Asymmetric Hydrogenation
C45H55Cl2N3P2FeRu·1/2C6H12: C 58.41, H 5.79, N 4.64;
Synthesis
found: C 58.68, H 5.68, N 4.63; IR (KCl pellet): v=
3052 cmÀ1 (N H).
The synthesis of (S)-1-(5-methoxy-1H-benzimidazol-2-yl)-
À
ACHTUNGTRENNUNG
ethanamine [(S)-3c] is given as a representative example.[18]
To a mixture of Z-Val-OH (1.9 g, 8.5 mmol), 4-methoxy-1,2-
phenylenediamine (1.2 g, 8.5 mmol) and EDC·HCl (1.7 g,
8.5 mmol) was added CH2Cl2 (20 mL) and the suspension
stirred at room temperature for 12 h. The resulting mixture
was further diluted with CH2Cl2 (20 mL), washed with water
(10 mL), saturated aqueous Na2CO3 (10 mL), 1M aqueous
HCl (10 mL) and brine. The combined organic layers were
dried over anhydrous Na2SO4, filtered and the solvent re-
moved under reduced pressure to yield a brown foam. To
this was added glacial acetic acid (15 mL). The solution was
stirred at 658C for 12 h, then 40% HBr in H2O (18 mL) was
added and the mixture stirred for a further 12 h at room
temperature. Solvent was removed under reduced pressure.
The crude salt was dissolved in water (5 mL) and Na2CO3
was added until the pH was 8. Following extraction with
ethyl acetate (3ꢂ250 mL), the organic fraction was dried
over anhydrous Na2SO4, filtered and the solvent removed
under reduced pressure. The resulting crude mixture was pu-
rified by flash chromatography (ethyl acetate/methanol: 10/
1) giving (S)-3c as a pale yellow hydroscopic powder; yield:
1.1 g (67%); [a]2D5: +50.38 (c, 1.0; MeOH); 1H NMR
(400 MHz, DMSO-d6, 248C): d=7.38 (d, J=8.8 Hz, 1H),
7.02 (s, 1H), 6.76 (d, J=8.8 Hz, 1H), 4.83 and 4.21 (m, 1H,
CH), 7.38 (s, 3H), 1.44 (d, J=6.4 Hz, 3H); 13C NMR
(75 MHz, CDCl3, 248C): d=167.4, 159.3, 155.2, 138.7, 115.6,
110.4, 97.4, 55.4, 45.9, 23.1 ppm; MS (ESI): m/z=192 [M+
H]+; HRMS (ESI) m/z:192.1135, for calcd. C10H14N3O [M+
H]+: 192.1131; IR (KCl pellet): v=2968, 1629, 1451, 1197,
1152, 1027, 804, 629 cmÀ1.
Hydrogenation
Description of a typical in situ hydrogenation: Accurately
weighed amounts of [RuCl2(h6-benzene)]2 (16.3 mg, 16 mM)
and (S,S)-DIOP (32.5 mg, 32 mM) were stirred at 1008C in
DMF (2 mL) for 30 min. Following removal of the solvent
under high vacuum, a dark red solid was obtained. This was
used in all subsequent in situ hydrogenations. An accurately
weighed sample of this red solid (0.8 mg, 0.33 mM) and (S)-
3 (0.2–0.3 mg) were placed in a Schlenk tube and CH2Cl2
(2 mL) was added. The mixture was degassed by running
argon through the solution (3 min), stirred at room tempera-
ture (5 min), and then the solvent was removed under
vacuum. Degassed toluene (3 mL) and acetophenone (1,
0.12 mL, S/C=1000) were added. The mixture was then
added under argon to a pre-oven-dried (1208C) 100-mL
glass autoclave containing solid t-BuOK (6.7 mg, 20 mM),
and a magnetic stirring bar. H2 was introduced under 4 atm
pressure with several quick release-fill cycles before being
set to the desired pressure. The solution was vigorously
stirred at 258C and H2 consumption monitored. Following
the designated reaction time, the H2 was released, and a
small aliquot of the crude product mixture was analyzed by
chiral GC to determine conversion and ee of (S)-2: BETA-
DEXTM 120 fused silica capillary column (df=0.25 mm,
0.25 mm i.d., 30 m, Supelco; P=100.3 kPa; T=1258C): tR of
(R)-2=12.3 min; tR of (S)-2=12.9 min.
Hydrogenation with RuCl2ACTHNUTRGENUGN[(S,S)-DIOP][(S)-3b or 3c]
[(SS,S)-4 or 5]: A typical hydrogenation procedure is given
for 3,4-dimethoxyacetophenone (12a) using (SS,S)-5 (iso-
meric mixture). Accurately weighed amounts of (SS,S)-5
(2.3 mg, 0.025 mM) and solid t-BuOK (60 mg, 11 mM) were
added to a 350-mL autoclave containing a magnetic stirring
bar and placed under high vacuum for at least 10 min before
purging with argon. A mixture of toluene (90 mL), t-BuOH
(10 mL) and 12a (45.0 g, 2.5M, S/C=100,000) were placed
into a Schlenk tube, degassed by running argon though the
solution (10 min) and then added to the autoclave under an
argon atmosphere. H2 was introduced and set at 30 atm. The
solution was vigorously stirred at 258C and H2 consumption
monitored. The H2 was carefully released after 20 h, the so-
lution passed through a short pad of silica gel and solvent
removed under reduced pressure. The crude product mix-
ture was analyzed by NMR and HPLC to determine conver-
sion and ee of (S)-1-(3,4-dimethoxyphenyl)ethanol [(S)-14];
[a]2D5: À34.18 (c 1.10, CHCl3), lit.[19] [a]2D5: À38.38 (c 2.85,
CHCl3) for (S)-enantiomer; 1H NMR (300 MHz, CDCl3):
d=6.90 (s, 1H), 6.85–6.77 (m, 2H), 4.76 (q, J=6.3 Hz, 1H),
3.84 (s, 3H), 3.83 (s, 3H), 1.43 (d, J=6.3 Hz, 3H); 13C NMR
(75 MHz, CDCl3): d=148.4, 147.6, 138.2, 117.0, 110.4, 108.1,
69.3, 55.4, 55.3, 24.6; HPLC (column, Chiracel OD-H;
eluent, hexane/i-propyl alcohol=95/5; temperature 258C;
flow rate, 0.7 mLminÀ1; l=214 nm): tR of (S)-14 (major),
55.9 min; tR of (R)-14, 61.4 min. Conversion >99%, ee=
96%.
RuCl2ACHTUNGTRENNUNG[(S,S)-DIOP][(S)-3a or 3c] [(SS,S)-4 or 5]
The procedure for [(SS,S)-5] is given: [RuCl2(h6-benzene)]2
(18.2 mg, 0.036 mmol) and (S,S)-DIOP (36.3 mg,
0.073 mmol) were dissolved in DMF (3 mL) and placed in a
20-mL Schlenk tube under an argon atmosphere. Argon was
bubbled through the solution for 5 min and the solution was
stirred at 1008C for 2 h. Following solvent removal under
vacuum, (S)-Me-BIMAM [(S)-3c] (13.9 mg, 0.073 mmol)
was added together with degassed CH2Cl2 (3 mL). The solu-
tion was then stirred at room temperature for 6 h. Following
reduction of the volume to ca. 0.5 mL (under vacuum), addi-
tion of hexane (5 mL) yielded a yellow precipitate. The su-
pernatant was removed by filtration and the resulting
powder was dried under vacuum to give (SS,S)-5 as a mix-
ture of isomers; yield: 45.5 mg (75%); mp 2158C (dec.);
31P NMR (161 MHz, CDCl3): major isomer (75%): d=40.2
(d, JP, P =42.4 Hz), 28.0 (d, JP, P =42.4 Hz); minor isomer
(25%): d=40.0 (d, JP,P =42.4 Hz), 29.5 (d, JP, P =42.4 Hz);
after heating at 908C in toluene for 2 h: d=48.6 (d, JP, P
=
36.5 Hz), 29.3 (d,
J
P, P =36.5 Hz); 1H NMR (400 MHz,
DMSO-d6, 218C): d=12.3 (br, 1H, imidazole-NH), 8.21 (m,
2H), 7.91 (m, 2H), 7.62–7.16 (m, 18H), 4.35 (dd, J=10.8,
8.8 Hz, 1H, CH), 4.06 (m, 1H), 3.76 (m, 1H, CH), 3.74 (s,
3H, OCH3), 1.37–1.23 (m, 3H, CH3), 1.03 (s, 6H, CH3);
13C NMR (100 MHz, CDCl3, 218C): d=155.5, 154.4, 142.3,
136.1, 131.6, 129.3–128.0 (m, aromatic carbons), 126.5, 80.1,
72.7, 55.5, 52.0, 35.0, 29.0, 26.8, 20.9; MS (MALDI): m/z=
790.2 [MÀCl2H]+; elemental analysis, calcd. (%) for
Adv. Synth. Catal. 2011, 353, 495 – 500
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
499

Yuehui Li et al.
UPDATES
lenzuela, A. M. Z. Slawin, Organometallics 2007, 26,
16–19; h) M. Ito, A. Sakaguchi, C. Kobayashi, T. Ikar-
iya, J. Am. Chem. Soc. 2007, 129, 290–291; i) L. Dah-
lenburg, C. Kꢃhnlein, Inorg. Chim. Acta, 2008, 361,
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Angew. Chem. 2008, 120, 7567–7570; Angew. Chem.
Int. Ed. 2008, 47, 7457–7460.
Acknowledgements
This work was supported by the Chinese Academy of Scien-
ces (No. O7210122R0) and the National Natural Science
Foundation of China (No. 20620140429). Enantiotech Corp.,
Ltd. is also acknowledged for financial support.
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ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2011, 353, 495 – 500