New paracyclophane phosphine for highly enantioselective ruthenium-catalyzed hydrogenation of prochiral ketones

Article abstract of DOI:10.1055/s-2007-990917

The synthesis of a new paracyclophane phosphine is described. This ligand was highly efficient in the ruthenium-catalyzed asymmetric hydrogenation of various aromatic and heteroaromatic ketones. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-990917

PAPER
3877
New Paracyclophane Phosphine for Highly Enantioselective
Ruthenium-Catalyzed Hydrogenation of Prochiral Ketones
New
Paracyclophane
P
u
hosphine for
r
Ruthen
t
h
talyzedHyd
y
a
b
c
Department of Chemistry, Ludwig-Maximilians-Universität München, Butenandtstraße 5–13, 81377 München, Germany
Chemical Research Laboratory, 12 Mansfield Rd, Oxford, OX1 3TA, UK
Sanofi-Aventis, G 838, Industriepark Höchst, 65926 Frankfurt am Main, Germany
Fax +49(89)218077680; E-mail: paul.knochel@cup.uni-muenchen.de
Received 21 August 2007; revised 18 September 2007
PR2
PR2
PXyl2
PPh2
Abstract: The synthesis of a new paracyclophane phosphine is de-
scribed. This ligand was highly efficient in the ruthenium-catalyzed
asymmetric hydrogenation of various aromatic and heteroaromatic
ketones.
Key words: paracyclophane, hydrogenation, ruthenium, ketones,
P,P-ligands
1a: R = Ph
1b: R = Xyl
2
(R)-Phanephos
Figure 1 Phanephos 1 and new non-C2-symmetrical paracyclopha-
ne phosphine 2
The design of new chiral ligands for asymmetric catalysis
is a highly active field of research.1 Many chiral diphos-
phine ligands have been prepared and successfully ap-
plied in asymmetric catalysis with excellent
enantioselectivities.2 The [2,2]paracyclophane backbone
serves as a powerful tool to develop new and efficient
ligands for asymmetric catalysis.3 The Phanephos (1)
ligands (Figure 1; Xyl = 3,5-dimethylphenyl), C2-sym-
metrical diphosphines with a rigid paracyclophane back-
bone, belong to the most successful chiral ligands.4 They
have been efficiently used in rhodium-catalyzed hydroge-
nations of dehydroamino acids4 and allylic acids,5 ruthe-
nium-catalyzed hydrogenation of b-keto esters6 and
aromatic ketones,7 and palladium-catalyzed amination re-
actions.8 The chiral C2-symmetrical phosphinites based
on the paracyclophane backbone also proved to be very
efficient catalysts for rhodium-catalyzed hydrogenation
of N-acetyldehydroamino acids and esters.9 Hems et al.
prepared various non-C2-symmetrical paracyclophane
diphosphines by introducing substituents on one of the ar-
omatic rings of Phanephos (1). The performance of these
ligands was indistinguishable from that of the original
Phanephos (1) ligands in rhodium-catalyzed hydrogena-
tion of dehydroamino acids and ruthenium-catalyzed hy-
drogenation of acetophenone.10 However, apart from this
fascinating work, non-C2-symmetrical paracyclophane
diphosphines bearing two different kinds of aryl phos-
phines have not been synthesized until now. Herein, we
wish to report the synthesis of new ligand 2 (Figure 1) and
its applications in ruthenium-catalyzed asymmetric hy-
drogenation of ketones with high activity and excellent
enantioselectivities.
The monometalation of dibromide 311 by n-butyllithium,
followed by the addition of chlorodiphenylphosphine led
to an air-sensitive diphenylphosphine derivative, which
was protected in situ with sulfur to give the air-stable
phosphine sulfide 4 in 85% yield (Scheme 1). Butyllithi-
um effected bromine–lithium exchange on 4, and
subsequent quenching with chlorobis(3,5-dimethylphen-
yl)phosphine followed by in situ protection with sulfur
provided bis(phosphine sulfide)
5 in 87% yield
(Scheme 1). The deprotection of 5 was accomplished
smoothly when Raney nickel12 in methanol was used, and
this gave diphosphine 2 in 92% yield (Scheme 1).
Owing to the inherent atom-economical nature of hydro-
genation reactions, hydrogenation of prochiral ketones is
a most facile route for generating enantiomerically pure
alcohols. A significant breakthrough in ketone hydroge-
nation was achieved by Noyori and co-workers using
diphosphine–ruthenium(II)–diamine complexes.13 Signif-
icantly, this method allowed the development of very ef-
ficient catalysts for highly enantioselective hydrogenation
of a wide range of prochiral ketones.14 We found that the
ruthenium complex of ligand 2 serves as an excellent cat-
alyst for the asymmetric hydrogenation of various aromat-
ic ketones. Ruthenium catalysts 6a and 6b were prepared
by reaction of ligand 2 with [RuCl2(benzene)]2 in N,N-
dimethylformamide–toluene at 115 °C for 4 h, followed
by the addition of one equivalent of 1,2-diphenylethylene-
diamine (DPEN) and reaction at 115 °C for 2 h
(Scheme 2).15
Next, we examined ketone hydrogenation using rutheni-
um complexes 6a and 6b and acetophenone (7a) as the
model substrate under standard reaction conditions
(i-PrOH, 10 bar H2, t-BuOK/Ru 25:1, 1.0–2.0 M solutions)
(Table 1). Preliminary results indicated that the efficiency
of ruthenium complex 6b was high compared to that of 6a
SYNTHESIS 2007, No. 24, pp 3877–3885
Advanced online publication: 28.11.2007
DOI: 10.1055/s-2007-990917; Art ID: T13507SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
0
7

3878
M. N. Cheemala et al.
PAPER
Br
Br
1. BuLi, THF, –78 °C, 2 h
1. BuLi, THF, –78 °C, 1 h
2. ClPXyl2, –78 °C, 1 h;
r.t., 1.5 h
2. ClPPh2, –78 °C, 1 h;
r.t., 1.5 h
Br
PPh2
S
3. S8, r.t., 12 h
3. S8, r.t., 12 h
(R)-3
(R)-4: 85%
S
PXyl2
PXyl2
PPh2
Raney Ni, MeOH
r.t., 12 h
PPh2
S
(R)-2: 92%
(R)-5: 87%
Scheme 1 Synthesis of the new paracyclophane phosphine 2
H2
N
R1
R4
Xyl2
P
Cl
Ru
Cl
1. [RuCl2(C6H6)]2, toluene–DMF,
PXyl2
PPh2
R2
R3
115 °C, 4 h
2. DPEN, 115 °C, 2 h
N
P
H2
Ph2
>99%
(R)-2
6a: R1 = R4 = H; R2 = R3 = Ph
6b: R1 = R4 = Ph; R2 = R3 = H
Scheme 2 Preparation of ruthenium complexes 6a and 6b
(Table 1, entries 1 and 2). This indicates that the stereo-
chemistry of the diamine plays a major role in achieving
high reaction rates and enantioselectivities in ketone hy-
drogenation.5 Furthermore, when the substrate/catalyst
(S/C) ratio was increased to 10000:1 in the reduction of
acetophenone with catalyst 6b, the desired alcohol 8a was
obtained in quantitative yield, but the enantioselectivity
reduced from 97 to 95% ee (Table 1, entries 5 and 6).
Table 1 Hydrogenation of Acetophenone (7a) Catalyzed by Ruthe-
nium Complexes 6a and 6ba
O
OH
Me
6a or 6b, t-BuOK, 25 °C
*
Me
H2 (10 bar)
7a
8a
Entry
Catalyst
6a
S/Cb
500
Time (h)
eec (%)
In addition, we investigated the scope of the ketone sub-
strates for the asymmetric hydrogenation using 6b
(Table 2). Various types of substituted acetophenone de-
rivatives 7a–l were reduced in high conversions, thus pro-
viding the corresponding chiral alcohols 8a–l in high
enantioselectivities (Table 2).
1d
2
12
1
25 (S)
97 (S)
97 (S)
97 (S)
97 (S)
95 (S)
6b
500
3
6b
1000
2000
5000
10000
1
4
6b
1
To explore the substrate scope further, we investigated the
asymmetric hydrogenation of ketones 9a–e, 11a,b, 13, 15,
and 17 bearing various types of side chains R and Ar at the
a-position (Table 3). Elongation of the ketone side chain
R from methyl to ethyl, n-butyl, n-pentyl, or phenethyl did
not affect the reactivity or enantioselectivity (Table 3, en-
tries 1–4). Introducing branching at the a-position of the
ketone leads to long reaction times and poor selectivities
(Table 3, entry 5). We also examined the chemoselective
hydrogenation of a,b-unsaturated ketones 11a and 11b
(Table 3, entries 6 and 7). Ketone 11a was smoothly re-
duced to afford the allylic alcohol 12a in 94% ee, whereas
ketone 11b furnished alcohol 12b in 37% ee. We also ex-
tended this hydrogenation of ketones to heteroaromatic
ketones 13, 15, and 17, providing the corresponding alco-
5
6b
1.5
2.5
6e
6b
a Reagents and conditions: 1 M 7a, cat. 6a or 6b, t-BuOK (t-BuOK/
cat. = 25:1), i-PrOH, H2 (10 bar).
b S/C = ratio of substrate to catalyst.
c The ee was determined by chiral GC or chiral HPLC.
d Only 55% conversion was achieved.
e t-BuOK/cat. = 100:1.
hols 14, 16, and 18 in 96%, 93%, and 92% ee, respectively
(Table 3, entries 8–10).
Synthesis 2007, No. 24, 3877–3885 © Thieme Stuttgart · New York

PAPER
New Paracyclophane Phosphine for Ruthenium-Catalyzed Hydrogenation
3879
Table 2 Asymmetric Hydrogenation of Substituted Acetophenones
7 Catalyzed by Ruthenium Complex 6ba
Table 2 Asymmetric Hydrogenation of Substituted Acetophenones
7 Catalyzed by Ruthenium Complex 6ba (continued)
O
OH
O
OH
6b, t-BuOK, 25 °C
6b, t-BuOK, 25 °C
Me
Me
Me
Me
R
R
R
R
H
2 (10 bar), S/C = 2000
H
2 (10 bar), S/C = 2000
7a–l
8a–l
7a–l
8a–l
Entry Substrate
Time (h) Productb eec (%)
Entry Substrate
11
Time (h) Productb eec (%)
1
1
8a
97
O
2
8k
97
O
Me
Me
7a
7k
2
1.5
8b
96
O
12
2
8l
94
O
Me
Me
MeO
Ph
7b
7l
3
4
5
6
7
1
8c
8d
8e
8f
97
94
97
97
96
O
a
Reagents and conditions: 1 M 7, 6b (7/6b = 2000:1), t-BuOK
(t-BuOK/6b = 25:1), i-PrOH, H2 (10 bar).
Me
Me
b Full conversion was achieved in each case.
c The ee was determined by chiral GC or chiral HPLC.
7c
2
Me
O
Table 3 Asymmetric Hydrogenation of Aryl and Hetaryl Ketones
Catalyzed by Ruthenium Complex 6ba
Me
O
OH
6b, t-BuOK, 25 °C
Ar
R
7d
Ar
H
2 (10 bar), S/C = 2000
1.5
1.5
1
O
9a–e, 11a–b
13, 15 and 17
10a–e, 12a–b
14, 16 and 18
MeO
Me
Entry Substrate
Time (h) Productb eec (%)
7e
1
2
3
4
5
1.5
1.5
1.5
2
10a
10b
10c
10d
10e
97
97
94
90
38
O
O
O
O
O
O
Cl
Me
9a
9b
9c
9d
9e
7f
8g
O
n-Bu
Me
Cl
7g
8
1
8h
94
O
n-Pent
Me
F3C
7h
9
1
2
8i
8j
96
96
O
Ph
F
Me
7i
5
10
O
Me
7j
Synthesis 2007, No. 24, 3877–3885 © Thieme Stuttgart · New York

3880
M. N. Cheemala et al.
PAPER
Table 3 Asymmetric Hydrogenation of Aryl and Hetaryl Ketones
Catalyzed by Ruthenium Complex 6ba (continued)
OH
Me
O
R
R
R
R
Me
6b, t-BuOK, 25 °C
O
OH
H2 (10 bar), 2–4 h
6b, t-BuOK, 25 °C
S/C = 2000
> 96% yield
Ar
R
Ar
H
2 (10 bar), S/C = 2000
19a–d
20a–d
9a–e, 11a–b
13, 15 and 17
10a–e, 12a–b
14, 16 and 18
OH
Me
OH
Time (h) Productb eec (%)
Cl
Cl
O
O
Entry Substrate
6
Me
1
2
3
12a
12b
14
94
37
96
O
O
Me
Ph
20a: 96% ee
20b: 90% ee
11a
OH
Me
OH
Me
7
Me
Me
MeO
MeO
11b
20c: 97% ee
20d: 94% ee
8
O
Scheme 3 Asymmetric hydrogenation of disubstituted acetophe-
nones 20 in the presence of catalyst 6b
Me
N
13
15
All reactions were carried out under an argon atmosphere in dried
glassware. Melting points were uncorrected and measured on a Dr.
Tottoli (Büchi B-540) apparatus. NMR spectra were recorded on
Bruker ARX 200, AC 300, WH 400, and 600 instruments. IR spec-
tra were recorded on a Nicolet 510 or a Perkin-Elmer 281 spectro-
meter. Mass spectra were recorded on a Varian CH 7A, and high-
resolution mass spectra on a Varian MAT 711 spectrometer. Optical
rotation values were measured on a Perkin-Elmer 241 polarimeter.
All ketone substrates for the catalytic hydrogenation were commer-
cially available and used without further purification.
9
2.5
4
16
18
93
92
O
O
Me
Me
S
10
Fe
(R)-4-Bromo-12-diphenylphosphinothioyl[2.2]paracyclophane
(4)
17
a Reagents and conditions: 1 M ketone, 6b (ketone/6b = 2000:1),
t-BuOK (t-BuOK/6b = 25:1), i-PrOH, H2 (10 bar).
b Full conversion was achieved in each case.
Dibromide 3 (1.83 g, 5.0 mmol) and THF (15 mL) were added to a
50-mL Schlenk flask under an argon atmosphere. A soln of 1.5 M
n-BuLi in pentane (3.7 mL, 5.5 mmol) was added slowly to the
above soln at –78 °C, and the mixture was stirred for 1 h. ClPPh2
(1.33 g, 6.0 mmol, 1.2 equiv) was added, and the mixture was stirred
for 1 h at –78 °C, then warmed to r.t. and stirred for 1.5 h. Sulfur
(1.60 g, 50.0 mmol, 10 equiv) was added, and the mixture was
stirred overnight at r.t. The mixture was quenched with sat. aq
NH4Cl (20 mL) and the aqueous layer was extracted with CH2Cl2
(4 × 30 mL). The combined organic layers were washed with H2O
(50 mL) and brine (50 mL), dried (MgSO4), and concentrated in
vacuo. The crude product was purified by flash chromatography
(silica gel, n-pentane–Et2O, 10:1).
c The ee was determined by chiral GC or chiral HPLC.
To broaden the application of this ruthenium-catalyzed
hydrogenation, we attempted the hydrogenation of disub-
stituted acetophenones 19a–c using catalyst 6b, and ob-
tained alcohols 20a–c in 90–97% ee (Scheme 3). The
reduction of ketone 19d bearing two methoxy groups in
meta and para positions of the aromatic ring was accom-
plished smoothly, leading to the corresponding alcohol
White solid; yield: 2.14 g (85%); mp 148.1–148.9 °C; [a]D20 –22.9
(c 0.4, CH2Cl2).
20d,
a precursor of (–)-salsolidine, in 94% ee
(Scheme 3).16
IR (neat): 3440 (br, w), 2912 (w), 1629 (s), 1425 (m), 1325 (m),
1102 (m), 789 (s), 656 (s) cm–1.
1H NMR (600 MHz, CDCl3): d = 7.83–7.71 (m, 5 H), 7.48–7.35 (m,
6 H), 6.65–6.53 (m, 5 H), 3.60–3.49 (m, 2 H), 3.39–3.35 (m, 1 H),
3.01–2.97 (m, 1 H), 2.90–2.71 (m, 4 H).
13C NMR (150 MHz, CDCl3): d = 145.0 (d, J = 8.6 Hz), 141.6,
138.6 (d, J = 13.0 Hz), 138.5, 136.9 (d, J = 3.1 Hz), 136.3, 135.5 (d,
J = 11.8 Hz), 134.6 (d, J = 86.2 Hz), 133.4, 132.9 (d, J = 10.6 Hz),
132.8 (d, J = 11.8 Hz), 132.2 (d, J = 84.6 Hz), 131.9 (d, J = 10.2
Hz), 131.3 (d, J = 3.1 Hz), 131.2 (d, J = 3.0 Hz), 131.1, 128.1 (d,
In summary, we have described the synthesis of a new
non-C2-symmetrical paracyclophane diphosphine 2. Its
ruthenium(II) complex 6b prepared from the (S,S)-di-
amine is highly effective for the asymmetric hydrogena-
tion of various aromatic ketones, quite comparable to the
C2-symmetrical dixylylphosphine 1b.7 The study of new
analogues of 2 and their applications is currently under-
way in our laboratory.
Synthesis 2007, No. 24, 3877–3885 © Thieme Stuttgart · New York

PAPER
New Paracyclophane Phosphine for Ruthenium-Catalyzed Hydrogenation
3881
J = 12.4 Hz), 128.0, (d, J = 12.4 Hz), 127.8 (d, J = 87.2 Hz), 127.2,
35.4, 34.7 (d, J = 4.9 Hz), 33.7 (d, J = 1.1 Hz), 31.92.
IR (neat): 3444 (br, w), 2019 (w), 1655 (s), 1450 (s), 1210 (s), 876
(s), 765 (m), 667 (m), 586 (m) cm–1.
31P NMR (81 MHz, CDCl3): d = 40.44.
MS (EI, 70 eV): m/z (%) = 504 (37), 502 [M+] (34), 321 (18), 320
(100), 319 (16), 209 (10), 183 (11).
HRMS (EI): m/z calcd for C28H2479BrP32S: 502.0520; found:
1H NMR (600 MHz, CDCl3): d = 7.47–7.44 (m, 2 H), 7.41–7.36 (m,
5 H), 7.24–7.20 (m, 5 H), 7.04–7.02 (m, 3 H), 6.65–6.63 (m, 1 H),
6.57–6.48 (m, 6 H), 3.02–2.89 (m, 6 H), 2.63–2.54 (m, 2 H), 2.35
(s, 6 H), 2.18 (s, 6 H).
13C NMR (150 MHz, CDCl3): d = 143.3 (d, J = 14.7 Hz), 143.1 (d,
J = 15.1 Hz), 139.5 (d, J = 12.1 Hz), 139.4 (d, J = 13.9 Hz), 139.3
(d, J = 6.1 Hz), 138.9 (d, J = 7.1 Hz), 138.2 (d, J = 12.2 Hz), 138.1
(d, J = 12.6 Hz), 137.5 (d, J = 17.5 Hz), 137.4 (d, J = 16.9 Hz),
137.3 (d, J = 7.9 Hz), 137.2 (d, J = 8.7 Hz), 135.9 (d, J = 0.9 Hz),
135.7 (d, J = 0.9 Hz), 134.2 (d, J = 6.8 Hz), 134.1 (d, J = 6.1 Hz),
133.4 (d, J = 22.8 Hz), 133.3 (d, J = 22.8 Hz), 133.0 (d, J = 20.4
Hz), 132.7 (d, J = 8.7 Hz), 132.3 (d, J = 6.8 Hz), 131.3 (d, J = 1.1
Hz), 130.6 (d, J = 20.9 Hz), 130.3 (d, J = 0.9 Hz), 129.3 (d, J = 0.8
Hz), 128.5 (d, J = 0.8 Hz), 128.3 (d, J = 22.7 Hz), 128.2 (d, J = 22.0
Hz), 35.8 (d, J = 18.7 Hz), 35.7 (d, J = 19.0 Hz), 33.2 (d, J = 2.6
Hz), 33.0 (d, J = 2.5 Hz), 21.4, 21.2.
502.0512.
(R)-4-Bis(3,5-ditolyl)phosphinothioyl[2.2]paracyclophane (5)
Phosphine sulfide 4 (755 mg, 1.5 mmol) and THF (5 mL) were add-
ed to a 25-mL Schlenk flask under an argon atmosphere. A soln of
1.5 M n-BuLi in pentane (1.2 mL, 1.7 mmol) was added slowly to
the above soln at –78 °C, and the mixture was stirred for 2 h. (3,5-
Me2C6H3)2PCl (500 mg, 1.8 mmol, 1.2 equiv) was added, and the
mixture was stirred for 1 h at –78 °C, then warmed to r.t. and stirred
for 1.5 h. Sulfur (482 mg, 15.0 mmol, 10 equiv) was added, and the
mixture was stirred overnight at r.t. The mixture was quenched with
sat. aq NH4Cl (10 mL), and the aqueous layer was extracted with
CH2Cl2 (4 × 15 mL). The combined organic layers were washed
with H2O (50 mL) and brine (50 mL), dried (MgSO4), and concen-
trated in vacuo. The crude product was purified by flash chromatog-
raphy (silica gel, n-pentane–Et2O, 5:1).
31P NMR (81 MHz, CDCl3): d = 0.69, 0.03.
MS (EI, 70 eV): m/z (%) = 632 [M+] (14), 428 (32), 320 (100), 309
(11).
HRMS (EI): m/z calcd for C44H42P2: 632.2762; found: 632.2777.
White solid; yield: 910 mg (87%); mp 291 °C; [a]D20 –20.9 (c 0.4,
CH2Cl2).
Ruthenium–Diamine Complexes 6a and 6b
IR (neat): 3441 (br, w), 2785 (w), 1594 (m), 1447 (m), 1389 (m),
1101 (m), 874 (s), 725 (s), 696 (s) cm–1.
A 25-mL Schlenk flask under an argon atmosphere was charged
with bisphosphine 2 (50 mg, 0.07 mmol, 1.0 equiv) and [RuCl2(ben-
zene)]2 (16 mg, 0.035 mmol) in anhyd toluene (2.0 mL) and DMF
(1.5 mL). The mixture was heated to 115 °C for 4 h, and then 1,2-
diphenylethylenediamine (DPEN; 15 mg, 0.07 mmol, 1.0 equiv)
was added. After stirring for 2 h at 115 °C, the mixture was allowed
to reach r.t. while stirring overnight. The solvent was evaporated
under high vacuum and Et2O (2 mL) and CH2Cl2 (2 mL) were added
to the crude mixture. After evaporation of the solvent, the desired
complexes were obtained as purple compounds in quantitative
yields. The residue was used for hydrogenations without any further
purification.
1H NMR (600 MHz, CDCl3): d = 7.96–7.93 (m, 2 H), 7.73–7.69 (m,
2 H), 7.51–7.47 (m, 5 H), 7.33–7.31 (m, 4 H), 7.26–7.23 (m, 2 H),
7.10–7.08 (m, 2 H), 7.02 (br s, 1 H), 6.72–6.69 (m, 2 H), 6.66–6.63
(m, 2 H), 3.42–3.47 (m, 2 H), 3.33–3.26 (m, 2 H), 2.86–2.80 (m, 2
H), 2.71–2.66 (m, 2 H), 2.31 (s, 6 H), 2.23 (s, 6 H).
13C NMR (150 MHz, CDCl3): d = 144.93 (d, J = 9.6 Hz), 144.9 (d,
J = 9.6 Hz), 139.6 (d, J = 13.3 Hz), 139.4 (d, J = 13.2 Hz), 137.5 (d,
J = 12.9 Hz), 137.3 (d, J = 13.2 Hz), 136.6 (d, J = 3.6 Hz), 136.5 (d,
J = 3.7 Hz), 136.1 (d, J = 11.7 Hz), 135.9 (d, J = 12.3 Hz), 135.7 (d,
J = 83.3 Hz), 135.0 (d, J = 83.8 Hz), 134.7 (d, J = 11.8 Hz), 134.4
(d, J = 12.0 Hz), 133.2 (d, J = 10.5 Hz), 133.0 (d, J = 3.1 Hz), 132.7
(d, J = 3.5 Hz), 131.6 (d, J = 10.3 Hz), 131.5 (d, J = 84.8 Hz), 131.2
(d, J = 84.8 Hz), 131.1 (d, J = 3.1 Hz), 130.9 (d, J = 10.1 Hz), 130.9
(d, J = 2.8 Hz), 129.3 (d, J = 10.1 Hz), 127.9 (d, J = 12.5 Hz), 127.8
(d, J = 87.7 Hz), 127.8 (d, J = 12.5 Hz), 127.7 (d, J = 88.7 Hz), 35.4
(t, J = 5.2 Hz), 33.8 (d, J = 16.0 Hz), 21.8 (d, J = 0.9 Hz), 21.5 (d,
J = 0.9 Hz).
Ruthenium–Diamine Complex 6a [{(R)-2}RuCl2{(R,R)-DPEN}]
Complex 6a was prepared with (R,R)-DPEN.
1H NMR (200 MHz, CDCl3): d = 8.46–8.20 (m, 3 H), 8.01–7.45 (m,
3 H), 7.40–7.25 (m, 4 H), 7.20–7.11 (m, 7 H), 7.00–6.85 (m, 7 H),
6.70–6.68 (m, 1 H), 6.60–6.58 (m, 1 H), 6.50–6.39 (m, 6 H), 4.50–
4.48 (m, 1 H), 4.11–4.10 (m, 1 H), 2.76–2.69 (m, 2 H), 2.62–2.50
(m, 2 H), 2.29 (s, 6 H), 2.12 (s, 6 H), 1.94–1.87 (m, 2 H), 1.71–1.66
(m, 2 H).
31P NMR (81 MHz, CDCl3): d = 38.71, 38.39.
MS (EI, 70 eV): m/z (%) = 696 [M+] (45), 521 (28), 320 (100), 309
31P NMR (81 MHz, CDCl3): d = 48.16 (d, J = 28.9 Hz), 44.79 (d,
J = 27.0 Hz).
(12), 183 (21).
HRMS (EI): m/z calcd for C44H42P232S2: 696.2203; found:
696.2211.
Ruthenium–Diamine Complex 6b [{(R)-2}RuCl2{(S,S)-DPEN}]
Complex 6b was prepared with (S,S)-DPEN.
1H NMR (200 MHz, CDCl3): d = 8.36–8.34 (m, 2 H), 8.30–8.26 (m,
1 H), 8.10–8.05 (m, 1 H), 8.00–7.92 (m, 1 H), 7.40–7.25 (m, 4 H),
7.20–7.10 (m, 8 H), 7.05–6.90 (m, 7 H), 6.76 (s, 1 H), 6.60–6.54 (m,
2 H), 6.47–6.36 (m, 5 H), 4.50–4.48 (m, 1 H), 4.19–4.12 (m, 1 H),
2.86–2.70 (m, 2 H), 2.60–2.55 (m, 2 H), 2.23 (s, 6 H), 2.02 (s, 6 H),
1.95–1.86 (m, 2 H), 1.71–1.66 (m, 2 H).
(R)-4-Bis(3,5-ditolyl)phosphino-12-diphenylphosphino[2.2]-
paracyclophane (2)
A 100-mL Schlenk flask was charged with a slurry of Raney-Ni in
H2O (1.8 g) under an argon atmosphere. The Raney-Ni was washed
with MeOH (4 × 15 mL). A soln of phosphine sulfide 4 (698 mg,
1.0 mmol) in THF (5 mL) was then transferred to this flask, MeOH
(30 mL) was added, and the mixture was stirred at r.t. under an ar-
gon atmosphere for 12 h (conversion was monitored by 31P NMR).
The mixture was filtered under argon, and the Raney Ni residue was
washed with THF (4 × 15 mL). Concentration of the combined fil-
trate under reduced pressure afforded 2.
31P NMR (81 MHz, CDCl3): d = 47.46 (d, J = 28.1 Hz), 44.19 (d,
J = 27.1 Hz).
Hydrogenation of Ketones Catalyzed by Ruthenium Complex
6b; General Procedure
A 10-mL Schlenk flask under an argon atmosphere was charged
with catalyst 6b (2.1 mg, 0.002 mmol) and the appropriate ketone
(4 mmol, ketone/catalyst = 2000) in i-PrOH (4 mL). A 1.0 M soln
White solid; yield: 583 mg (92%); mp 211.0–212.2 °C; [a]D20 –22.4
(c 0.4, CH2Cl2).
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of t-BuOK in i-PrOH (0.05 mL, 0.05 mmol) was added. The mix-
ture was stirred at r.t. for 15 min, and then transferred under an ar-
gon atmosphere to an autoclave equipped with a glass tube and a
stirring bar. The autoclave was then purged with H2 (3 × 5 bar) and
finally pressurized to 10 bar. The mixture was stirred for the appro-
priate time (see Tables 2 and 3) until full conversion was achieved.
The H2 gas was released, the solvent was evaporated, and the resi-
due was filtered through a short pad of silica gel and washed with
Et2O. Conversion was checked by 1H NMR spectroscopy or GC and
enantioselectivity was determined by chiral GC or chiral HPLC.
(R)-1-(3-Methoxyphenyl)ethanol (8e)
Alcohol 8e was prepared from 7e (601 mg, 0.55 mL, 4.0 mmol) by
the general procedure described above for the hydrogenation of ke-
tones catalyzed by ruthenium complex 6b (2.1 mg, 0.002 mmol).
Colorless oil; yield: 584 mg (96%); [a]D20 +54.8 (c 1.0, CHCl3).
The ee was determined by chiral GC (DEX-CB column, 100 °C, 60
min, constant): 29.8 min (R), 34.7 (S); 97% ee.
1H NMR (300 MHz, CDCl3): d = 7.29 (d, J = 8.2 Hz, 1 H), 6.97–
6.95 (m, 2 H), 6.83 (ddd, J = 1.0, 2.6, 8.2 Hz, 1 H), 4.88 (q, J = 6.5
Hz, 1 H), 3.83 (s, 3 H), 2.00 (br s, 1 H), 1.50 (d, J = 6.5 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 159.7, 147.6, 129.5, 117.6, 112.8,
110.1, 70.3, 55.2, 25.1.
(R)-1-Phenylethanol (8a)
Alcohol 8a was prepared from 7a (480 mg, 0.49 mL, 4.0 mmol) by
the general procedure described above for the hydrogenation of ke-
tones catalyzed by ruthenium complex 6b (2.1 mg, 0.002 mmol).
Colorless oil; yield: 469 mg (96%); [a]D20 +40.4 (c 1.0, CHCl3).
(R)-1-(3-Chlorophenyl)ethanol (8f)
Alcohol 8f was prepared from 7f (618 mg, 0.52 mL, 4.0 mmol) by
the general procedure described above for the hydrogenation of ke-
tones catalyzed by ruthenium complex 6b (2.1 mg, 0.002 mmol).
Colorless oil; yield: 601 mg (96%); [a]D20 +42.4 (c 1.0, CHCl3).
The ee was determined by chiral GC (DEX-CB column, 110 °C, 60
min, constant): 8.5 min (R), 8.9 (S); 97% ee.
1H NMR (300 MHz, CDCl3): d = 7.20–7.29 (m, 5 H), 4.66 (q,
J = 6.5 Hz, 1 H), 2.80 (br s, 1 H), 1.30 (d, J = 6.4 Hz, 1 H).
The ee was determined by chiral GC (DEX-CB column, 110 °C, 10
13C NMR (75 MHz, CDCl3): d = 146.4, 128.8, 127.7, 125.9, 70.6,
min, 50 °C/min, 160 °C, 30 min): 12.9 min (R), 13.2 (S); 97% ee.
1H NMR (300 MHz, CDCl3): d = 7.37–7.36 (m, 1 H), 7.26–7.21 (m,
3 H), 4.89–4.82 (m, 1 H), 1.98 (d, J = 3.5 Hz, 1 H), 1.47 (d, J = 6.5
Hz, 3 H).
25.6.
(R)-1-(4-Methoxyphenyl)ethanol (8b)
Alcohol 8b was prepared from 7b (600 mg, 4.0 mmol) by the gen-
eral procedure described above for the hydrogenation of ketones
catalyzed by ruthenium complex 6b (2.1 mg, 0.002 mmol).
13C NMR (75 MHz, CDCl3): d = 147.8, 134.3, 129.7, 127.5, 125.6,
123.5, 69.8, 25.2.
Colorless oil; yield: 584 mg (96%); [a]D20 +43.6 (c 1.0, CHCl3).
(R)-1-(4-Chlorophenyl)ethanol (8g)
Alcohol 8g was prepared from 7g (618 mg, 0.52 mL, 4.0 mmol) by
the general procedure described above for the hydrogenation of ke-
tones catalyzed by ruthenium complex 6b (2.1 mg, 0.002 mmol).
Colorless oil; yield: 614 mg (98%); [a]D20 +26.8 (c 1.0, CHCl3).
The ee was determined by chiral GC (DEX-CB column, 110 °C, 60
min, constant): 26.0 min (R), 30.0 (S); 96% ee.
1H NMR (300 MHz, CDCl3): d = 7.31–7.26 (m, 2 H), 6.89–6.86 (m,
2 H), 4.84 (q, J = 6.4 Hz, 1 H), 3.79 (s, 3 H), 1.47 (d, J = 6.4 Hz, 3
H), 1.83 (br s, 1 H).
The ee was determined by chiral GC (DEX-CB column, 130 °C, 60
13C NMR (75 MHz, CDCl3): d = 159.0, 138.0, 126.6, 113.8, 69.9,
min, constant): 9.2 min (R), 10.7 (S); 96% ee.
1H NMR (300 MHz, CDCl3): d = 7.30–7.28 (m, 2 H), 6.90–6.87 (m,
2 H), 4.82 (q, J = 6.7 Hz, 1 H), 1.24 (br s, 1 H), 1.30 (d, J = 6.8 Hz,
3 H).
55.3, 25.0.
(R)-1-(3-Tolyl)ethanol (8c)
Alcohol 8c was prepared from 7c (537 mg, 0.54 mL, 4.0 mmol) by
the general procedure described above for the hydrogenation of ke-
tones catalyzed by ruthenium complex 6b (2.1 mg, 0.002 mmol).
13C NMR (75 MHz, CDCl3): d = 158.2, 136.5, 124.8, 112.1, 68.2,
24.5.
Colorless oil; yield: 523 mg (96%); [a]D20 +64.2 (c 1.0, CHCl3).
(R)-1-[4-(Trifluoromethyl)phenyl]ethanol (8h)
Alcohol 8h was prepared from 7h (753 mg, 4.0 mmol) by the gen-
eral procedure described above for the hydrogenation of ketones
catalyzed by ruthenium complex 6b (2.1 mg, 0.002 mmol).
Colorless oil; yield: 715 mg (94%); [a]D20 +34.9 (c 1.0, CHCl3).
The ee was determined by chiral GC (DEX-CB column, 110 °C, 60
min, constant): 9.5 min (R), 9.7 (S); 97% ee.
1H NMR (300 MHz, CDCl3): d = 7.27–7.22 (m, 1 H), 7.19–7.15 (m,
2 H), 7.08 (d, J = 7.5 Hz, 1 H), 4.85 (q, J = 6.5 Hz, 1 H), 2.36 (s, 3
H), 1.88 (s, 1 H), 1.48 (d, J = 6.5 Hz, 3 H).
The ee was determined by chiral GC (DEX-CB column, 110 °C, 60
13C NMR (75 MHz, CDCl3): d = 145.8, 138.1, 128.4, 128.2, 126.1,
min, constant): 9.3 min (R), 9.7 (S); 94% ee.
1H NMR (300 MHz, CDCl3): d = 7.61–7.59 (m, 2 H), 7.49–7.46 (m,
2 H), 4.98–4.91 (m, 1 H), 1.98 (d, J = 3.3 Hz, 1 H), 1.49 (d, J = 6.3
Hz, 3 H).
122.4, 70.4, 25.1, 21.4.
(R)-1-(2-Tolyl)ethanol (8d)
Alcohol 8d was prepared from 7d (537 mg, 0.52 mL, 4.0 mmol) by
the general procedure described above for the hydrogenation of ke-
tones catalyzed by ruthenium complex 6b (2.1 mg, 0.002 mmol).
Colorless oil; yield: 534 mg (98%); [a]D20 +48.2 (c 1.0, CHCl3).
13C NMR (75 MHz, CDCl3): d = 149.7 (q, J = 1.4 Hz), 129.6 (q,
J = 32.3 Hz), 125.6, 125.4 (q, J = 3.9 Hz), 124.1 (q, J = 271.6 Hz),
69.8, 25.4.
(R)-1-(3-Fluorophenyl)ethanol (8i)
The ee was determined by chiral GC (DEX-CB column, 100 °C, 15
Alcohol 8i was prepared from 7i (552 mg, 0.49 mL, 4.0 mmol) by
the general procedure described above for the hydrogenation of ke-
tones catalyzed by ruthenium complex 6b (2.1 mg, 0.002 mmol).
Colorless oil; yield: 532 mg (95%); [a]D20 +42.4 (c 1.0, CHCl3).
min, 5 °C/min, 160 °C, 30 min): 20.1 min (R), 22.1 (S); 94% ee.
1H NMR (300 MHz, CDCl3): d = 7.52–7.49 (m, 1 H), 7.26–7.21 (m,
1 H), 7.19–7.13 (m, 2 H), 5.12 (q, J = 6.4 Hz, 1 H), 2.34 (s, 3 H),
1.82 (s, 1 H), 1.46 (d, J = 6.4 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 143.8, 134.2, 130.3, 127.1, 126.3,
124.4, 66.8, 23.9, 18.9.
The ee was determined by chiral GC (DEX-CB column, 110 °C, 10
min, 50 °C/min, 160 °C, 20 min): 8.5 min (R), 10.1 (S); 96% ee.
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New Paracyclophane Phosphine for Ruthenium-Catalyzed Hydrogenation
3883
1H NMR (300 MHz, CDCl3): d = 7.23–7.19 (m, 1 H), 7.05–7.00 (m,
2 H), 6.90–6.85 (m, 1 H), 4.81 (q, J = 6.5 Hz, 1 H), 1.96 (br s, 1 H),
1.40 (d, J = 6.5 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 163.0 (d, J = 246.1 Hz), 148.5 (d,
J = 6.4 Hz), 129.9 (d, J = 7.7 Hz), 120.9 (d, J = 2.6 Hz), 114.2 (d,
J = 21.2 Hz), 112.3 (d, J = 21.2 Hz), 69.7 (d, J = 2.1 Hz), 25.2.
(R)-1-Phenylpentan-1-ol (10b)
Alcohol 10b was prepared from 9b (649 mg, 0.66 mL, 4.0 mmol)
by the general procedure described above for the hydrogenation of
ketones catalyzed by ruthenium complex 6b (2.1 mg, 0.002 mmol).
Colorless oil; yield: 624 mg (95%); [a]D20 +28.9 (c 1.0, CHCl3).
The ee was determined by chiral GC (DEX-CB column, 100 °C, 15
min, 5 °C/min, 160 °C, 45 min): 24.3 min (S), 24.4 (R); 97% ee.
(R)-1-(1-Naphthyl)ethanol (8j)
1H NMR (300 MHz, CDCl3): d = 7.31–7.29 (m, 4 H), 7.25–7.21 (m,
1 H), 4.61 (t, J = 7.2 Hz, 1 H), 1.84 (br s, 1 H), 1.78–1.62 (m, 2 H),
1.38–1.16 (m, 4 H), 0.85 (t, J = 7.1 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 144.9, 128.4, 127.4, 125.9, 74.7,
38.8, 28.0, 22.6, 14.0.
Alcohol 8j was prepared from 7j (681 mg, 0.61 mL, 4.0 mmol) by
the general procedure described above for the hydrogenation of ke-
tones catalyzed by ruthenium complex 6b (2.1 mg, 0.002 mmol).
Colorless oil; yield: 661 mg (96%); [a]D20 +68.8 (c 1.0, CHCl3).
The ee was determined by chiral GC (DEX-CB column, 115 °C, 15
min, 15 °C/min, 160 °C, 60 min): 26.8 min (S), 27.4 (R); 96% ee.
(R)-1-Phenylhexan-1-ol (10c)
1H NMR (300 MHz, CDCl3): d = 8.13–8.12 (m, 1 H), 7.89–7.86 (m,
1 H), 7.77 (d, J = 8.2 Hz, 1 H), 7.67 (d, J = 7.2 Hz, 1 H), 7.55–7.45
(m, 3 H), 5.70–5.62 (m, 1 H), 2.02 (d, J = 2.8 Hz, 1 H), 1.67 (d,
J = 6.57 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 141.3, 133.8, 130.2, 128.9, 127.9,
126.0, 125.6, 125.5, 123.1, 122.0, 67.1, 24.3.
Alcohol 10c was prepared from 9c (713 mg, 4.0 mmol) by the gen-
eral procedure described above for the hydrogenation of ketones
catalyzed by ruthenium complex 6b (2.1 mg, 0.002 mmol).
Colorless oil; yield: 714 mg (96%); [a]D20 +36.0 (c 1.0, CHCl3).
The ee was determined by chiral GC (DEX-CB column, 100 °C, 15
min, 5 °C/min, 160 °C, 45 min): 26.6 min (S), 26.7 (R); 94% ee.
1H NMR (300 MHz, CDCl3): d = 7.34–7.24 (m, 5 H), 4.63–4.62 (m,
1 H), 1.86 (d, J = 3.1 Hz, 1 H), 1.79–1.60 (m, 2 H), 1.45–1.27 (m, 6
H), 0.89–0.84 (m, 3 H).
13C NMR (75 MHz, CDCl3): d = 145.0, 128.4, 127.4, 125.9, 74.5,
39.1, 31.7, 25.5, 22.5, 14.0.
(R)-1-(2-Naphthyl)ethanol (8k)
Alcohol 8k was prepared from 7k (681 mg, 0.52 mL, 4.0 mmol) by
the general procedure described above for the hydrogenation of ke-
tones catalyzed by ruthenium complex 6b (2.1 mg, 0.002 mmol).
Colorless oil; yield: 675 mg (98%); [a]D20 +60.4 (c 1.0, CHCl3).
The ee was determined by chiral GC (DEX-CB column, 115 °C, 15
min, 15 °C/min, 160 °C, 60 min): 25.5 min (R), 26.3 (S); 97% ee.
1H NMR (300 MHz, CDCl3): d = 7.84–7.80 (m, 4 H), 7.51–7.44 (m,
3 H), 5.05 (q, J = 6.5 Hz, 1 H), 1.98 (br s, 1 H), 1.58 (d, J = 6.2 Hz,
3 H).
13C NMR (75 MHz, CDCl3): d = 143.2, 133.3, 132.9, 128.3, 127.9,
127.6, 126.1, 125.8, 123.8, 123.7, 70.5, 25.1.
(R)-1,3-Diphenylpropan-1-ol (10d)
Alcohol 10d was prepared from 9d (841 mg, 4.0 mmol) by the gen-
eral procedure described above for the hydrogenation of ketones
catalyzed by ruthenium complex 6b (2.1 mg, 0.002 mmol).
Colorless oil; yield: 815 mg (96%); [a]D20 +41.2 (c 1.0, CHCl3).
The ee was determined by chiral HPLC (Chiracel OD-H column,
flow rate 0.5 mL/min, heptane–i-PrOH, 90:10, l = 215 nm, 25 °C):
tR = 22.7 min (minor), tR = 25.5 min (major); 90% ee.
1H NMR (300 MHz, CDCl3): d = 7.36–7.19 (m, 10 H), 4.72–4.66
(m, 1 H), 2.76–2.67 (m, 2 H), 2.20–1.98 (m, 2 H), 1.90 (d, J = 3.6
Hz, 1 H).
(R)-1-Biphenyl-4-ylethanol (8l)
Alcohol 8l was prepared from 7l (785 mg, 4.0 mmol) by the general
procedure described above for the hydrogenation of ketones cata-
lyzed by ruthenium complex 6b (2.1 mg, 0.002 mmol).
Colorless oil; yield: 769 mg (97%); [a]D20 +51.0 (c 1.0, CHCl3).
13C NMR (75 MHz, CDCl3): d = 144.5, 141.7, 128.5, 128.4, 128.3,
127.6, 125.9, 125.8, 73.9, 40.4, 32.0.
The ee was determined by chiral GC (DEX-CB column, 100 °C, 7
min, 5 °C/min, 160 °C, 60 min): 40.6 min (R), 42.7 (S); 94% ee.
(R)-2-Methyl-1-phenylpropan-1-ol (10e)
1H NMR (300 MHz, CDCl3): d = 7.60–7.57 (m, 4 H), 7.46–7.41 (m,
4 H), 7.37–7.32 (m, 1 H), 4.95 (q, J = 6.5 Hz, 1 H), 1.87 (br s, 1 H),
1.54 (d, J = 6.5 Hz, 3 H).
Alcohol 10e was prepared from 9e (593 mg, 0.60 mL, 4.0 mmol) by
the general procedure described above for the hydrogenation of ke-
tones catalyzed by ruthenium complex 6b (2.1 mg, 0.002 mmol).
13C NMR (75 MHz, CDCl3): d = 144.8, 140.8, 140.4, 128.7, 127.2,
127.1, 125.8, 70.1, 25.1.
Colorless oil; yield: 541 mg (90%); [a]D20 +12.8 (c 1.0, CHCl3).
The ee was determined by chiral GC (DEX-CB column, 110 °C, 30
min, 5 °C/min, 160 °C, 45 min): 17.9 min (R), 18.6 (S); 38% ee.
(R)-1-Phenylpropan-1-ol (10a)
1H NMR (300 MHz, CDCl3): d = 7.35–7.23 (m, 5 H), 4.34 (d,
J = 7.1 Hz, 1 H), 1.98–1.89 (m, 2 H), 0.99 (d, J = 7.0 Hz, 3 H), 0.79
(d, J = 7.0 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 143.6, 128.1, 127.3, 126.5, 80.0,
35.2, 19.0, 18.2.
Alcohol 10a was prepared from 9a (537 mg, 0.54 mL, 4.0 mmol) by
the general procedure described above for the hydrogenation of ke-
tones catalyzed by ruthenium complex 6b (2.1 mg, 0.002 mmol).
Colorless oil; yield: 523 mg (96%); [a]D20 +32.4 (c 1.0, CHCl3).
The ee was determined by chiral GC (DEX-CB column, 110 °C, 60
min, constant): 11.9 min (R), 13.2 (S); 97% ee.
(R,E)-4-Phenylbut-3-en-2-ol (12a)
1H NMR (300 MHz, CDCl3): d = 7.36–7.26 (m, 5 H), 4.60 (t,
J = 6.5 Hz, 1 H), 1.94 (br s, 1 H), 1.84–1.76 (m, 2 H), 0.93 (t, J = 6.5
Hz, 3 H).
Alcohol 12a was prepared from 11a (585 mg, 4.0 mmol) by the gen-
eral procedure described above for the hydrogenation of ketones
catalyzed by ruthenium complex 6b (2.1 mg, 0.002 mmol).
13C NMR (75 MHz, CDCl3): d = 144.6, 128.4, 127.4, 125.9, 76.0,
31.9, 10.1.
Colorless oil; yield: 563 mg (90%); [a]D20 +36.8 (c 1.0, CHCl3).
The ee was determined by chiral GC (DEX-CB column, 115 °C, 20
min, 5 °C/min, 160 °C, 30 min): 18.8 min (R), 19.7 (S); 94% ee.
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M. N. Cheemala et al.
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1H NMR (300 MHz, CDCl3): d = 7.41–7.30 (m, 4 H), 7.28–7.22 (m,
1 H), 6.58 (dd, J = 0.9, 15.9 Hz, 1 H), 6.27 (dd, J = 6.4, 15.8 Hz, 1
H), 4.55–4.46 (m, 1 H), 1.71 (br s, 1 H), 1.39 (d, J = 6.4 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 136.7, 133.5, 129.4, 128.5, 127.6,
126.4, 68.9, 23.4.
1-(3,4-Dichlorophenyl)ethanol (20a)
Alcohol 20a was prepared from 19a (756 mg, 4.0 mmol) by the gen-
eral procedure described above for the hydrogenation of ketones
catalyzed by ruthenium complex 6b (2.1 mg, 0.002 mmol).
Colorless oil; yield: 745 mg (98%); [a]D20 +35.8 (c 1.0, CHCl3).
The ee was determined by chiral GC (DEX-CB column, 160 °C, 60
min, constant): 6.6 min (R), 7.1 (S); 97% ee.
1H NMR (300 MHz, CDCl3): d = 7.45 (d, J = 2.1 Hz, 1 H), 7.39 (d,
J = 8.3 Hz, 1 H), 7.18 (ddd, J = 0.6, 2.1, 8.3 Hz, 1 H), 4.84 (q,
J = 6.5 Hz, 1 H), 1.91 (br s, 1 H), 1.45 (d, J = 6.6 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 146.0, 132.5, 131.2, 130.4, 127.5,
124.7, 69.2, 25.3.
MS (EI, 70 eV): m/z (%) = 190 [M+] (35), 175 (100), 147 (47), 111
(70).
(R,E)-1,3-Diphenylprop-2-en-1-ol (12b)
Alcohol 12b was prepared from 11b (833 mg, 0.52 mL, 4.0 mmol)
by the general procedure described above for the hydrogenation of
ketones catalyzed by ruthenium complex 6b (2.1 mg, 0.002 mmol).
Colorless oil; yield: 816 mg (98%); [a]D20 +2.0 (c 1.0, CHCl3).
The ee was determined by chiral HPLC (Chiracel OD-H column,
flow rate 0.5 mL/min, heptane–i-PrOH, 90:10, l = 215 nm, 25 °C):
tR = 14.8 min (minor), tR = 19.1 min (major); 37% ee.
1H NMR (300 MHz, CDCl3): d = 7.46–7.21 (m, 10 H), 6.69 (d,
J = 0.9, 15.8 Hz, 1 H), 6.38 (d, J = 6.4, 15.8 Hz, 1 H), 5.38 (d,
J = 6.4 Hz, 1 H), 2.12 (br s, 1 H).
HRMS (EI): m/z calcd for C8H8Cl2O: 189.9952; found: 189.9953.
1-(1,3-Benzodioxol-5-yl)ethanol (20b)
13C NMR (75 MHz, CDCl3): d = 142.7, 136.5, 131.5, 130.5, 128.6,
128.5, 127.8, 127.7, 126.6, 126.3, 75.1.
Alcohol 20b was prepared from 19b (657 mg, 4.0 mmol) by the
general procedure described above for the hydrogenation of ketones
catalyzed by ruthenium complex 6b (2.1 mg, 0.002 mmol).
Colorless oil; yield: 625 mg (94%); [a]D20 +42.6 (c 1.0, CHCl3).
(R)-1-(3-Pyridyl)ethanol (14)
Alcohol 14 was prepared from 13 (484 mg, 0.44 mL, 4.0 mmol) by
the general procedure described above for the hydrogenation of ke-
tones catalyzed by ruthenium complex 6b (2.1 mg, 0.002 mmol).
The ee was determined by chiral GC (DEX-CB column, 100 °C, 7
min, 5 °C/min, 160 °C, 60 min): 19.7 min (R), 20.1 (S); 90% ee.
Colorless oil; yield: 483 mg (98%); [a]D20 +21.8 (c 1.0, CHCl3).
1H NMR (300 MHz, CDCl3): d = 6.87 (d, J = 1.8 Hz, 1 H), 6.80
(ddd, J = 0.5, 1.8, 8.0 Hz, 1 H), 6.75 (d, J = 8.0 Hz, 1 H), 5.92 (s, 2
H), 6.80 (q, J = 6.4 Hz, 1 H), 1.90 (br s, 1 H), 1.44 (d, J = 6.40 Hz,
3 H).
13C NMR (75 MHz, CDCl3): d = 147.7, 146.8, 139.9, 118.6, 108.0,
106.0, 100.9, 70.2, 25.1.
The ee was determined by chiral GC (DEX-CB column, 40 °C, 15
min, 3 °C/min, 160 °C, 60 min): 45.8 min (R), 46.8 (S); 96% ee.
1H NMR (300 MHz, CDCl3): d = 8.50–8.42 (m, 2 H), 7.71 (tt,
J = 7.9, 1.7 Hz, 1 H), 7.27–7.23 (m, 1 H), 4.91 (q, J = 6.6 Hz, 1 H),
2.98 (br s, 1 H), 1.49 (d, J = 6.5 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 148.4, 147.2, 141.3, 133.3, 123.5,
67.8, 25.2.
MS (EI, 70 eV): m/z (%) = 166 [M+] (71), 151 (97), 148 (12), 123
(27), 93 (100).
HRMS (EI): m/z calcd for C9H10O3: 166.0630; found: 166.0623.
(R)-1-(2-Thienyl)ethanol (16)
Alcohol 16 was prepared from 15 (505 mg, 0.43 mL, 4.0 mmol) by
the general procedure described above for the hydrogenation of ke-
tones catalyzed by ruthenium complex 6b (2.1 mg, 0.002 mmol).
Colorless oil; yield: 502 mg (98%); [a]D20 +16.4 (c 1.0, CHCl3).
1-(3,4-Dimethylphenyl)ethanol (20c)
Alcohol 20c was prepared from 19c (593 mg, 0.59 mL, 4.0 mmol)
by the general procedure described above for the hydrogenation of
ketones catalyzed by ruthenium complex 6b (2.1 mg, 0.002 mmol).
Colorless oil; yield: 583 mg (97%); [a]D20 +50.0 (c 1.0, CHCl3).
The ee was determined by chiral GC (DEX-CB column, 100 °C, 15
min, 5 °C/min, 160 °C, 60 min): 12.4 min (R), 14.5 (S); 92% ee.
The ee was determined by chiral GC (DEX-CB column, 100 °C, 7
1H NMR (300 MHz, CDCl3): d = 7.22 (dd, J = 1.6, 4.6 Hz, 1 H),
6.98–6.94 (m, 2 H), 5.16–5.08 (m, 1 H), 2.06 (br s, 1 H), 1.59 (d,
J = 6.4 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 149.8, 126.6, 124.4, 123.1, 66.2,
25.2.
min, 5 °C/min, 160 °C, 60 min): 15.4 min (R), 15.7 (S); 96% ee.
1H NMR (300 MHz, CDCl3): d = 7.15 (br s, 1 H), 7.12–7.09 (m, 2
H), 4.84 (q, J = 6.7 Hz, 1 H), 2.27 (s, 3 H), 2.26 (s, 3 H), 1.85 (br s,
1 H), 1.48 (d, J = 6.4 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 143.3, 136.6, 135.7, 129.7, 126.7,
122.7, 70.2, 25.0, 19.8, 19.4.
MS (EI, 70 eV): m/z (%) = 150 [M+] (43), 135 (82), 107 (100), 91
(49).
(R)-1-Ferrocenylethanol (18)
Alcohol 18 was prepared from 17 (912 mg, 4.0 mmol) by the gen-
eral procedure described above for the hydrogenation of ketones
catalyzed by ruthenium complex 6b (2.1 mg, 0.002 mmol).
HRMS (EI): m/z calcd for C10H14O: 150.1045; found: 150.1035.
Colorless oil; yield: 865 mg (94%); [a]D20 –30.2 (c 1.0, CHCl3).
1-(3,4-Dimethoxyphenyl)ethanol (20d)
The ee was determined by chiral HPLC (Chiracel OJ column, flow
rate 0.6 mL/min, heptane–i-PrOH, 95:5, l = 215 nm, 25 °C):
tR = 34.8 min (major), tR = 37.2 min (minor); 94% ee.
Alcohol 20d was prepared from 19d (721 mg, 4.0 mmol) by the
general procedure described above for the hydrogenation of ketones
catalyzed by ruthenium complex 6b (2.1 mg, 0.002 mmol).
1H NMR (300 MHz, CDCl3): d = 4.58–4.50 (m, 1 H), 4.22–4.20 (m,
2 H), 4.18 (s, 5 H), 4.15 (t, J = 1.9 Hz, 2 H), 1.85 (d, J = 4.7 Hz, 1
H), 1.43 (d, J = 6.3 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 94.5, 68.3, 67.9, 67.8, 66.1, 66.1,
65.6, 23.7.
Colorless oil; yield: 714 mg (98%); [a]D20 +49.6 (c 1.0, CDCl3).
The ee was determined by chiral GC (DEX-CB column, 120 °C,
120 min, constant): 46.5 min (R), 50.5 (S); 94% ee.
1H NMR (300 MHz, CDCl3): d = 6.92 (d, J = 2.0 Hz, 1 H), 6.87–
6.86 (m, 1 H), 6.83 (s, 1 H), 4.86–4.79 (m, 1 H), 3.88 (s, 3 H), 3.85
(s, 3 H), 1.86 (d, J = 2.2 Hz, 1 H), 1.47 (d, J = 6.7 Hz, 3 H).
Synthesis 2007, No. 24, 3877–3885 © Thieme Stuttgart · New York

PAPER
New Paracyclophane Phosphine for Ruthenium-Catalyzed Hydrogenation
3885
13C NMR (75 MHz, CDCl3): d = 149.0, 148.3, 138.5, 117.5, 111.0,
108.6, 70.2, 55.9, 55.8, 25.0.
(7) Burk, M. J.; Hems, W. P.; Herzburg, D.; Malan, C.; Zanotti-
Gerosa, A. Org. Lett. 2000, 2, 4173.
(8) Rossen, K.; Pye, P. J.; Maliakal, A.; Volante, R. P. J. Org.
Chem. 1997, 62, 6462.
(9) Zanotti-Gerosa, A.; Malan, C.; Herzburg, D. Org. Lett. 2001,
3, 3687.
MS (EI, 70 eV): m/z (%) = 182 [M+] (59), 167 (100), 139 (81), 124
(13).
HRMS (EI): m/z calcd for C10H14O3: 182.0943; found: 182.0923.
(10) Dominguez, B.; Zanotti-Gerosa, A.; Hems, W. Org. Lett.
2004, 6, 1927.
Acknowledgment
(11) For the preparation of the dibromide, see ref. 6, and for the
preparation of the racemic dibromide, see: Reich, H. J.;
Cram, D. J. J. Am. Chem. Soc. 1969, 91, 3527.
(12) (a) Korff, C.; Helmchen, G. Chem. Commun. 2004, 530.
(b) Liu, D.; Tang, W.; Zhang, X. Org. Lett. 2004, 6, 513.
(13) (a) Ohkuma, T.; Ooka, H.; Hashiguchi, S.; Ikariya, T.;
Noyori, R. J. Am. Chem. Soc. 1995, 117, 2675.
(b) Ohkuma, T.; Ooka, H.; Yamakawa, M.; Ikariya, T.;
Noyori, R. J. Am. Chem. Soc. 1995, 117, 10417.
(c) Doucet, H.; Ohkuma, T.; Murata, K.; Yokozawa, T.;
Kozawa, M.; Katayama, E.; England, A. F.; Ikariya, T.;
Noyori, R. Angew. Chem. Int. Ed. 1998, 37, 1703.
(14) (a) 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.
(b) Wu, J.; Chen, H.; Kwok, W.-H.; Guo, R.-W.; Zhou, Z.-
Y.; Yeung, C.-H.; Chan, A. S. C. J. Org. Chem. 2002, 67,
7908. (c) Cao, P.; Zhang, X. J. Org. Chem. 1999, 64, 2127.
(d) Ohkuma, T.; Koizumi, M.; Yoshida, M.; Noyori, R. Org.
Lett. 2000, 2, 1749. (e) Noyori, R.; Ohkuma, T. Pure Appl.
Chem. 1999, 71, 1493. (f) Mikami, K.; Korenaga, T.;
Terada, M.; Ohkuma, T.; Pham, T.; Noyori, R. Angew.
Chem. Int. Ed. 1999, 38, 495.
We thank the Fonds der Chemischen Industrie for the financial sup-
port and DAAD for financial support for M. Gayral. We also thank
Chirotech Technology Ltd. (Cambridge) for the generous gift of
(R)-4,12-dibromo[2.2]paracyclophane.
References
(1) (a) Noyori, R. Asymmetric Catalysis in Organic Synthesis;
Wiley: New York, 1994. (b) Ohkuma, T.; Kitamura, M.;
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Wiley-VCH: Weinheim, 2000, 1. (c) Spindler, F.; Blaser,
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(15) We used only the two diamines (R,R)-DPEN and (S,S)-
DPEN; DPEN = 1,2-diphenylethylenediamine. Complex 6a
was prepared by use of the (R,R)-amine, whereas the (S,S)-
diamine was used for complex 6b.
(16) Ponzo, V. L.; Kaufman, T. S. Tetrahedron Lett. 1995, 36,
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Synthesis 2007, No. 24, 3877–3885 © Thieme Stuttgart · New York