Chiral ruthenabicyclic complexes: Precatalysts for rapid, enantioselective, and wide-scope hydrogenation of ketones

Article abstract of DOI:10.1021/ja202296w

A novel ruthenabicyclic complex with base shows excellent catalytic activity in the asymmetric hydrogenation of ketones. The turnover frequency of the hydrogenation of acetophenone reaches about 35 000 min^-1 in the best case, affording 1-phenylethanol in >99% ee. Several aliphatic and base-labile ketones are smoothly converted to the corresponding alcohols in high enantioselectivity. The catalytic cycle for this hydrogenation, in which the ruthenabicyclic structure of the catalyst is maintained, is proposed on the basis of the deuteration experiment and spectroscopic analysis data.

Full text of DOI:10.1021/ja202296w

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pubs.acs.org/JACS
Chiral Ruthenabicyclic Complexes: Precatalysts for Rapid,
Enantioselective, and Wide-Scope Hydrogenation of Ketones
Kazuhiko Matsumura,†,‡ Noriyoshi Arai,† Kiyoto Hori,‡ Takao Saito,‡ Noboru Sayo,‡ and Takeshi Ohkuma*,†
†Division of Chemical Process Engineering, Faculty of Engineering, Hokkaido University, Sapporo, Hokkaido 060-8628, Japan
‡Corporate Research and Development Division, Takasago International Corporation, 1-4-11 Nishi-Yawata, Hiratsuka,
Kanagawa 254-0073, Japan
S Supporting Information
b
ABSTRACT: A novel ruthenabicyclic complex with base
shows excellent catalytic activity in the asymmetric hydro-
genation of ketones. The turnover frequency of the hydro-
genation of acetophenone reaches about 35 000 minꢀ1 in
the best case, affording 1-phenylethanol in >99% ee. Several
aliphatic and base-labile ketones are smoothly converted to
the corresponding alcohols in high enantioselectivity. The
catalytic cycle for this hydrogenation, in which the ruthe-
nabicyclic structure of the catalyst is maintained, is proposed
on the basis of the deuteration experiment and spectro-
scopic analysis data.
symmetric hydrogenation of ketones is a key technology for
small- to industrial-scale production of optically active
Figure 1. Structures and preparation of chiral Ru(II) complexes.
Conditions: (a) DAIPEN (1.1 equiv), (C2H5)2NH (1.0 equiv),
CH3OH, reflux, 3 h; (b) DAIPEN (1.0 equiv), DMF (rt., 6 h) or
toluene (80 °C, 2 h); (c) NaOTf (1.1 equiv), toluene, rt, 3 h.
A
compounds, including medicines, agrochemicals, and perfumes.1
Development of new efficient catalysts for this reaction is a
challenging subject from both a scientific and practical viewpoint.
Since 1995 we have reported enantioselective hydrogenation of
ketones catalyzed by Ru complexes bearing chiral diphosphine
and diamine ligands.1,2 A series of alkyl aryl ketones, heteroaro-
matic ketones, unsymmetrical benzophenones, and R,β-unsatu-
rated ketones is converted to the chiral alcohols with an excellent
enantiomeric excess (ee) of >99% in the best cases, when the
catalyst precursors RuXY(xylbinap)(daipen) (X, Y = Cl, Cl or H,
η1-BH4)3 with or without an alkaline base are employed for this
reaction.4 We herein report asymmetric hydrogenation of ke-
tones by using novel ruthenabicyclic complexes as precatalysts.
The catalyst efficiency, enantioselectivity, and scope of substrates
are all superior to those of our previous systems.
quantitatively gave the triflate complex 1b, leaving the
ruthenabicyclic structure intact. RuCl(daipena)(dm-segphos)
(1c)11 was prepared by the same procedure from the corre-
sponding cationic complex.8 When DPEN was used instead of
DAIPEN, the corresponding RuCl2 complex was obtained
exclusively.3
Figure 2 shows an ORTEP diagram of the single-crystal X-ray
analysis of (SN,SP)-1c.8 The unique ruthenabicyclo[2.2.1] ske-
leton causes the significantly distorted octahedral structure
(C(1)ꢀRuꢀCl(1) angle: 153°). The Cl(1)ꢀRu bond length
of 2.64 Å is longer than that of the related trans-RuCl2-
(diphosphine)(diamine) complexes.12 The very small Cl(1)ꢀ
RuꢀN(1)ꢀH(1) torsion angle of about 1.5° means the Cl(1)ꢀ
Ru and N(1)ꢀH(1) bonds are arranged almost in parallel.12 The
Cl(1)ꢀH(1) distance of 2.65 Å is much shorter than the
expected van der Waals separation length of 3.0 Å.
The ruthenabicyclic complex (SN,SP)-1a exhibited excellent
catalytic activity and enantioselectivity in the hydrogenation of
acetophenone (3a) in a t-C4H9OK containing alcoholic solvent
(Scheme 1 and Table 1). The order of solvents in the reaction
rate was ethanol g 2-propanol . methanol (entries 1ꢀ3).
Interestingly, a 1:1 ethanol/2-propanol mixed solvent gave the
highest reactivity. Thus, the hydrogenation with a substrate-to-
catalyst molar ratio (S/C) of 10 000 under 50 atm of H2 at
The novel ruthenabicyclic complex RuCl[(S)-daipena][(S)-
xylbinap] [(SN,SP)-1a] (DAIPENA = anion of DAIPEN at the
2-position of an anisyl group) was readily prepared from the
cationic complex [RuCl(p-cymene){(S)-xylbinap}]Cl5 and (S)-
DAIPEN (1.1 equiv) with (C2H5)2NH (1.0 equiv) in refluxed
methanol (98% isolated yield; see Figure 1, conditions (a)).6ꢀ8
Interestingly, the known RuCl2[(S)-xylbinap][(S)-daipen] [(SP,
SN)-2a]4a was exclusively obtained under the same reaction
conditions (a) or the aprotic conditions (b), when the neutral
complex RuCl2[(S)-xylbinap](dmf)n9 or the dinuclear complex
[(CH3)2NH2][{RuCl[(S)-xylbinap]}2(μ-Cl)3]10 was used in-
stead of [RuCl(p-cymene){(S)-xylbinap}]Cl. The RuCl2 com-
plex 2a is not an actual intermediate to 1a, so that only a trace
amount of 1a was formed from 2a under the reaction conditions
(a). Treatment of 1a with NaOTf in toluene [conditions (c)]
Received: March 14, 2011
Published: June 16, 2011
r
2011 American Chemical Society
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|

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Table 1. Hydrogenation of 3a catalyzed by Ru complexesa
entry Rub S/Cc
base solvent H2, atm time, h % yieldd % eed
1
2
3
4
5
6
7
8
9
1a 10000 tBuOK MeOH
50
50
50
50
50
7
0.75
0.22
0.42
>99
>99
>99
99
>99
>99
>99
>99
>99
>99
>99
>99
>99
ndf
1a 100000 tBuOK EtOH
1a 100000 tBuOK iPrOH
1a 10000 tBuOK Ae
1a 100000 tBuOK Ae
1a 100000 tBuOK Ae
1a 10000 tBuOK Ae
0.017 >99
0.10
0.25
>99
>99
>99
>99
>99
>99
1
24
Figure 2. ORTEP drawing of (SN,SP)-1c. All protons except those on
the diamine ring and some substitutents are omitted for clarity.8
1a
1a
2000 tBuOK toluene
2000 tBuOK CH2Cl2
10
10
10
10
10
10
10
10
1
2.5
2.5
0.13
5
10 1a 10000 DBU
Ae
Scheme 1. Asymmetric Hydrogenation of Ketones
11 1a
12 1a
1000 DBU toluene
1000 DBU CH2Cl2
1.2
5
8
96
13 1b 10000 DBU
Ae
0.083 >99
>99
>99
>99
98
14 1b
4000 DBU toluene
4000 DBU CH2Cl2
2
3
>99
>99
98
15 1b
16 1c 10000 tBuOK Ae
17 2a 10000 tBuOK MeOH
18 2a 100000 tBuOK iPrOH
24
9
50
50
10
89
94
4
>99
9
98
19 2a
1000 DBU iPrOH
5
98
a Unless otherwise stated, reactions were conducted at 11ꢀ35 °C using a
1.0ꢀ3.3 M solution of 3a containing (SN,SP)-1 or (SP,SN)-2a, and a base
(1.7ꢀ33 mM). b Ru complexes. c Substrate-to-catalyst molar ratio.
d Determined by chiral GC analysis. (R)-4a was obtained. e A = EtOH/
iPrOH (1:1). f Not determined.
11ꢀ35 °C was completed in 1 min to afford (R)-1-phenylethanol
[(R)-4a] in >99% ee (entry 4).13 The timeꢀconversion relation-
ship of this reaction with an S/C of 100 000 was measured as
2 min, 39.7%; 3 min, 74.3%; and 6 min, 100% (entry 5). No
distinct incubation period like that seen in the reaction with the
2a/t-C4H9OK catalyst system was observed. The turnover
in high yield and 95% ee (entries 3 and 4).15 The reaction with 2a
resulted in a much less satisfactory result (entry 5). For hydrogenation
of 1-tetralone (3e),16 a cyclic aromatic ketone, RuCl[(S)-daipena]-
[(R)-dm-segphos] [(SN,RP)-1c] with t-C4H9OK acted as an
excellent catalyst (entry 6). The corresponding RuCl2[(R)-dm-
segphos][(S)-daipen] [(RP,SN)-2b] gave only medium yield with
lower stereoselectivity (entry 7). 6-Methoxy-1-tetralone (3f) was
quantitatively converted to 4f in 98% ee by using (SN,RP)-1c
(entry 8).16 Hydrogenation of 2-hydroxyacetophenone (3g)
and the 40-methoxy ketone 3h was catalyzed by the (SN,SP)-
1a/DBU system to give (S)-4g and 4h in high ees (entries 9 and
10).17 The reaction of 3g with the 2a/t-C4H9OK system gave
only trace amounts of 4g with many unidentified compounds due
to the significant instability of 3g to base. Acetol (3i), an aliphatic
hydroxy ketone, was reduced with (SN,SP)-1a to afford (R)-4i in
95% ee (entry 11). The finding that the enantiomeric sense was
opposite that of the reaction of 3g with the same catalyst suggests
that the priority order of groups in the enantioface-recognition is
C6H5 > CH2OH > CH3.
ESI mass-spectroscopic (MS) analysis of (SN,SP)-1a in
CH2Cl2 and methanol showed prominent signals centered at
m/z 1184.4 ([M]+) and 1149 ([M ꢀ Cl]+), respectively. The
31P{1H} NMR spectrum in benzene-d6 and methanol-d4/
CD2Cl2 (2:1) showed AB quartet signals at δ 53.3, 61.1
(Jpꢀp = 38.2 Hz) and δ 19.7, 36.7 (Jpꢀp = 32.9 Hz), respectively.
The [M ꢀ Cl]+ signals remained pronounced in the MS analysis
of a reaction mixture of hydrogenation of 3a in methanol. The 1H
NMR measurement of 1a in the methanol-d4/CD2Cl2 mixture
under 1 atm of H2 at ꢀ50 °C showed a broad signal at δ ꢀ0.35,
which suggested the formation of the Ru(η2-H2) species.18
The 31P{1H} NMR signals of (SN,SP)-1a in benzene-d6 (δ
53.3 and 61.1) were converted to the peaks at δ 55.9 and 59.9
frequency (TOF) between 2ꢀ3 min reached about 35 000 minꢀ1
.
Complete conversion of the hydrogenation under lower pressure
of H2 was achieved without loss of enantioselectivity (entries 6
and 7). Aprotic toluene and CH2Cl2 were also usable solvents,
although the reactivity was lower than that in the alcoholic
solvents (entries 8 and 9). Addition of a base for activation of
the precatalyst 1a was required in this reaction system. DBU, an
organic base, was useful for the hydrogenation in the ethanol/2-
propanol mixture instead of t-C4H9OK (entry 10), but it was not
sufficiently basic for the reaction in the aprotic solvents (entries
11 and 12). It was noteworthy that the corresponding triflate
complex 1b showed high reactivity in toluene and CH2Cl2 as well
as in the alcoholic solvent by using DBU as a base (entries
13ꢀ15). The 1c/t-C4H9OK system also achieved a high level of
reactivity and enantioselectivity, although these were slightly
lower than those of the 1a/t-C4H9OK catalyst (entry 16 vs 7). In
contrast to the ruthenabicyclic precatalysts 1, the ordinary RuCl2
complex 2a showed relatively low activity and enantioselectivity
in methanol (entry 17 vs 1). The most appropriate solvent was
2-propanol, but the reaction rate (TOF = 950 minꢀ1; entry 18)
was slower than that using 1a (TOF = 6000 minꢀ1; entry 3).
DBU was useless even in the alcoholic solvent (entry 19 vs 10).
The ruthenabicycle-catalyst system was applied to the asym-
metric hydrogenation of ketones, which are difficult substrates to
reduce with high reactivity and enantioselectivity by using the
precatalysts 2 (Scheme 1, Table 2). Hydrogenation of aliphatic
ketones 3b and 3c with 1a gave the chiral alcohols in 90% ee and 77%
ee, respectively (entries 1 and 2).14 The enantioselectivity of 85% in
the reaction of 3b with 2a was reported.2 A rigid bicyclic ketone
3-quinuclidinone (3d) was hydrogenated by using 1a with an S/C of
50 000ꢀ100 000 under 30 atm of H2 affording 3-quinuclidinol (4d)
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Table 2. Hydrogenation of Ketones 3 Catalyzed by Ru
Complexesa
Scheme 2. Proposed Catalytic Cycle for Asymmetric Hy-
drogenation of Ketones Catalyzed by the Chiral Ruthenabi-
cyclic Complexesa
entry 3
Rub
S/Cc
base solventd time, h % yielde % eef
1
b (SN,SP)-1a
4000 tBuOK
P
5
5
96 90 (R)
2
c
(SN,SP)-1a 10000 tBuOK
P
>99 77 (R)
3g
4g
5g
6
d (SN,SP)-1a 50000 tBuOK
d (SN,SP)-1a 100000 tBuOK
d (SP,SN)-2a 20000 tBuOK
P
6
>99
92
95 (S)
95 (S)
86 (S)
97 (S)
90 (S)
98 (S)
95 (S)
97 (S)
P
6
P
6
50
e
e
f
(SN,RP)-1c
(RP,SN)-2b
(SN,RP)-1c
2000 tBuOK
1000 tBuOK
1000 tBuOK
2000 DBU
2000 DBU
1500 DBU
A
P
14
15
21
5
>99
42
7
8
A
M
E
>99
>99
>99
9
g (SN,SP)-1a
10 h (SN,SP)-1a
11h
(SN,SP)-1a
5
i
M
5
95 95 (R)
a Unless otherwise stated, reactions were conducted under 10 atm of H2
at 5ꢀ30 °C using 3 (0.5ꢀ2.0 M) in solvent containing a Ru complex and
a base (5ꢀ100 mM). b Ru complexes. c Substrate-to-catalyst molar ratio.
d A = EtOH/iPrOH (1:1). E = ethanol. M = methanol. P = 2-propanol.
f
e Determined by GC or HPLC analysis. Determined by chiral GC or
HPLC analysis.8 Absolute configurations of 4 are indicated in the
parentheses. g Under 30 atm of H2. h Under 15 atm of H2.
when 2 equiv of t-C4H9OK were added. The observed 1H NMR
signals of the t-C4H9O moiety (δ 1.24) and presence of the
four amino-protons suggested formation of the RuO-t-C4H9
complex.8 This complex was reacted with methanol (6 equiv)
to afford the RuOCH3 complex, which showed the NMR signal
of the CH3O moiety (δ 3.16).8 This signal was broadened with
the addition of a large excess amount of methanol. The MS
analysis of this mixture revealed formation of the Ru cationic
species (m/z 1149). When the RuO-t-C4H9 complex was mixed
with H2 (1 atm) or 4a (3 equiv), two RuH species showing
hydride peaks at δ ꢀ6.50 and ꢀ13. 55 were afforded.8 The latter
species did not show signals of the coordinated benzylic amino
protons. This mixture acted as the catalyst for hydrogenation of
3a to give (R)-4a in >99% ee under the regular conditions. The
NMR peaks at δ ꢀ6.50 disappeared by the addition of 3a, but the
other peaks at δ ꢀ13.55 remained.
a X = Cl or OTf. R = alkyl, aryl, H. R0 = CH3, H. P—P = XylBINAP.
NH2—NH2 = DAIPENA.
alcohol, A is the most preferable species. The amide complex D
reacts with hydrogen (partly with a primary or secondary
alcohol) to furnish the RuH species C.
When the hydrogenation is carried out in a less polar aprotic
solvent, such as toluene and CH2Cl2, 1a (X = Cl) does not ionize
and requires strong base t-C4H9OK to remove Clꢀ in the manner
of Dcb, providing the amide complex D (see Table 1, entries 8, 9,
11, and 12). Hydrogen reacts with D to give C and less reactive
C0, and then C reduces ketone to return to D. 1b (X = OTf)
reversibly loses ꢀOTf to form A under the aprotic conditions and
transforms to the amide complex D through B and C. DBU is
sufficiently basic for this process (see Table 1, entries 14 and 15).
Then D returns to C by reaction with hydrogen in the aprotic
media. The alcoholic products formed in this reaction may
promote the same pathway that occurs in the alcohol.
Treatment of the RuO-t-C4H9 complex with 2-propanol-d8
afforded the two kinds of RuD species and the RuO-i-C3D7
complex, in which the most reactive one benzylic amino proton
was deuterated in >95%. Three other amino protons were
deuterated in <50%. No ortho aryl deuterium incorporation
was detected in the recovered 1a after deuteration (10 atm) of
acetone in methanol quenched with HCl (methanol solution),
suggesting the Ruꢀaryl bond of 1a was maintained through the
reaction.8
Scheme 2 illustrates a plausible mechanism for the hydro-
genation of ketones with ruthenabicyclic complexes 1 based on
the spectroscopic analysis. The Xꢀ (X = Cl or OTf) readily
liberates from 1 to give the cationic species A in an alcoholic
medium. Hydrogen reversibly interacts with A to form the
molecular hydrogen species B. The base (t-C4H9OK or DBU)-
induced heterolysis of hydrogen forms the active RuH complex
C, which is the rate-determining step. The monoamino RuH
complex C0, which shows feeble activity, is formed as a minor
compound. The ketonic substrate is smoothly reduced by C to
form an alcoholic product and the amideꢀRu complex D. The
complex D is in rapid equilibrium with A and the alkoxide
complexes E. In the presence of excess amounts of the polar
The benzylic amino axial-proton (Hax) of the RuH complex C
is the most reactive among the four amino protons, because the
HꢀRuꢀNꢀHax torsion angle is expected to be the smallest based
on the structure of 1c (Figure 2).2,18 The ketonic substrate is
reduced by C through the six-membered pericyclic transition
state (TS) F (metalꢀligand cooperative TS), in which the
H
δꢀꢀRuδ+ꢀNδꢀꢀHaxδ+ quadrupole of the catalyst fits with the
Cδ+dOδꢀ dipole of the substrate.2,12 The key issue is that C has
a ruthenabicyclic structure, in contrast to the previous RuCl2-
(diphosphine)(1,2-diamine)/t-C4H9OK catalyst systems in
which the corresponding trans-RuH2 complexes are the expected
active species.18,19 The difference of the trans influence between
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Journal of the American Chemical Society
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arene-carbon and H to the RuꢀH could be a primary reason for
the marked difference in reactivity between the two catalyst
systems.
Sirlin, C.; Pfeffer, M. Organometallics 2008, 27, 5852–5859. (c) Baratta,
W.; Chelucci, G.; Magnolia, S.; Siega, K.; Rigo, P. Chem.—Eur. J. 2009,
15, 726–732.
(7) Related works; see: (a) Koike, T.; Ikariya, T. Organometallics
2005, 24, 724–730. (b) Sortais, J.-B.; Pannetier, N.; Holuigue, A.; Barloy,
L.; Sirlin, C.; Pfeffer, M.; Kyritsakas, N. Organometallics 2007,
26, 1856–1867.
(8) See the Supporting Information for details.
(9) Kitamura, M.; Tokunaga, M.; Ohkuma, T.; Noyori, R. Org. Synth.
1993, 71, 1–13.
(10) (a) Ikariya, T.; Ishii, Y.; Kawano, H.; Arai, T.; Saburi, M.;
Yoshikawa, S.; Akutagawa, S. J. Chem. Soc. Chem. Commun. 1985,
922–924. (b) King, S. A.; DiMichele, L. In Catalysis of Organic Reactions;
Scaros, M. G., Prunier, M. L., Eds.; Marcel Dekker: New York, 1994; pp
157ꢀ166. (c) Ohta, T.; Tonomura, Y.; Nozaki, K.; Takaya, H. Organo-
metallics 1996, 15, 1521–1523. (d) Mashima, K.; Nakamura, T.; Matsuo,
Y.; Tani, K. J. Organomet. Chem. 2000, 607, 51–56.
In conclusion, the newly devised ruthenabicyclic complexes
RuX(daipena)(xylbinap) (X = Cl, OTf) with base (t-C4H9OK,
DBU) exhibit remarkably high catalytic activity in the hydro-
genation of ketones. A turnover frequency of about 35 000 minꢀ1
is achieved in the best case. The enantioselectivity and scope for
the substrates are even superior to those of the previous RuCl2-
(xylbinap)(daipen)/t-C4H9OK system, which is one of the most
efficient catalysts. The catalytic cycle for this hydrogenation, in
which the ruthenabicyclic structure of the catalyst is maintained,
is proposed on the basis of the deuteration experiment and
spectroscopic analysis data.
’ ASSOCIATED CONTENT
(11) DM-SEGPHOS = (4,40-bi-1,3-benzodioxole)-5,50-diylbis(di-
(3,5-xylyl)phosphine), see: (a) Saito, T.; Yokozawa, T.; Ishizaki, T.;
Moroi, T.; Sayo, N.; Miura, T.; Kumobayashi, H. Adv. Synth. Catal. 2001,
343, 264–267. (b) Shimizu, H.; Nagasaki, I.; Matsumura, K.; Sayo, N.;
Saito, T. Acc. Chem. Res. 2007, 40, 1385–1393.
(12) The RuCl2(diphosphine)(diamine) complexes have the short-
er ClꢀRu bond length and the larger ClꢀRuꢀNꢀHax torsion angles;
for example: RuCl2[(R)-tolbinap][(R,R)-dpen] (2.41ꢀ2.43 Å; 20°),
RuCl2[(S)-tolbinap][(R)-dmapen] (2.41 Å; 15°), RuCl2[(S)-binap]-
[(R)-iphan] (2.42ꢀ2.43 Å; 6°). See: (a) 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, 1703–1707.
(b) Ooka, H.; Arai, N.; Azuma, K.; Kurono, N.; Ohkuma, T. J. Org. Chem.
2008, 73, 9084–9093. (c) Arai, N.; Akashi, M.; Sugizaki, S.; Ooka, H.;
Inoue, T.; Ohkuma, T. Org. Lett. 2010, 12, 3380–3383.
S
Supporting Information. Preparative methods and
b
properties of chiral ruthenabicyclic complexes 1, procedures
for asymmetric hydrogenation of ketones 3, NMR, GC, and
HPLC behavior, [R]D values of products, and the X-ray structure
of (SN,SP)-1c (CIF). This material is available free of charge via
the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
ohkuma@eng.hokudai.ac.jp
(13) The reaction temperature was immediately increased from 11
to 35 °C by the heat of reaction.
’ ACKNOWLEDGMENT
This work was supported by a Grant-in-Aid from the Japan
Society for the Promotion of Science (JSPS) (No. 21350048).
We thank Dr. Kimiko Hasegawa at the Rigaku Corporation
for her help in analyzing the X-ray diffraction data. We thank
also Messrs. Yoshihiro Yaguchi and Akihiro Kawaraya, Mrs.
Kyoko Zaizen, and the ruthenabicyclic catalysts (RUCY)
research members at the Takasago International Corporation
for measurement of NMR and mass spectra, and experimental
assistance.
(14) (a) Jiang, Q.; Jiang, Y.; Xiao, D.; Cao, P.; Zhang, X. Angew.
Chem., Int. Ed. 1998, 37, 1100–1103. (b) Li, W.; Hou, G.; Wang, C.;
Jiang, Y.; Zhang, X. Chem. Commun. 2010, 46, 3979–3981.
(15) Asymmetric hydrogenation of 3d with the diphosphine/diamineꢀ
RuCl2 complexes; see: Tsutsumi, K.; Katayama, T.; Utsumi, N.;
Murata, K.; Arai, N.; Ohkuma, T. Org. Process Res. Dev. 2009, 13, 625–628
and ref 12c.
(16) Asymmetric hydrogenation of 3e and 3f by using the BINAP/
IPHANꢀRuCl2 complexes; see: (a) Ohkuma, T.; Hattori, T.; Ooka, H.;
Inoue, T.; Noyori, R. Org. Lett. 2004, 6, 2681–2683. See also: (b) Zhang,
H.; Taketomi, T.; Yoshizumi, T.; Kumobayashi, H.; Akutagawa, S.;
Mashima, K.; Takaya, H. J. Am. Chem. Soc. 1993, 115, 3318–3319.
(c) Huang, H.; Okuno, T.; Tsuda, K.; Yoshimura, M.; Kitamura, M.
J. Am. Chem. Soc. 2006, 128, 8716–8717. (d) Ito, M.; Endo, Y.; Ikariya,
T. Organometallics 2008, 27, 6053–6055. (e) Li, Y.; Zhou, Y.; Shi, Q.;
Ding, K.; Noyori, R.; Sandoval, C. A. Adv. Synth. Catal. 2011, 353,
495–500.
(17) The reaction of 3h did not proceed with Cp*Ir(OTf)-
(MsDPEN), which is known as an excellent catalyst for hydrogenation
of R-hydroxy ketones, see: Ohkuma, T.; Utsumi, N.; Watanabe, M.;
Tsutsumi, K.; Arai, N.; Murata, K. Org. Lett. 2007, 9, 2565–2567.
See also: Kadyrov, R.; Koenigs, R. M.; Brinkmann, C.; Voigtlaender,
D.; Rueping, M. Angew. Chem., Int. Ed. 2009, 48, 7556–7559.
(18) The η2-H2 signal of RuH(η2-H2)[(R)-binap][(R,R)-dpen] was
observed at δ ꢀ0.66. See: Hamilton, R. J.; Leong, C. G.; Bigam, G.;
Miskolzie, M.; Bergens, S. H. J. Am. Chem. Soc. 2005, 127, 4152–4153.
(19) (a) Sandoval, C. A.; Ohkuma, T.; Mu~niz, K.; Noyori, R. J. Am.
Chem. Soc. 2003, 125, 13490–13503. See also: (b) Abdur-Rashid, K.;
Clapham, S. E.; Hadzovic, A.; Harvey, J. N.; Lough, A. J.; Morris, R. H.
J. Am. Chem. Soc. 2002, 124, 15104–15118.
’ REFERENCES
(1) Recent reviews: (a) Ohkuma, T.; Noyori, R. In The Handbook of
Homogeneous Hydrogenation; de Vries, J. G., Elsevier, C. J., Eds.; Wiley-
VCH: Weinheim, 2007; Vol. 3, pp 1105ꢀ1163. (b) Arai, N.; Ohkuma,
T. In Science of Synthesis: Stereoselective Synthesis 2; Molander, G. A., Ed.;
Thieme: Stuttgart, 2010; pp 9ꢀ57.
(2) Reviews: (a) Ohkuma, T. Proc. Jpn. Acad. Ser. B 2010, 86,
202–219. (b) Noyori, R.; Ohkuma, T. Angew. Chem., Int. Ed. 2001, 40,
40–73.
(3) XylBINAP = 2,20-bis(di-3,5-xylylphosphino)-1,10-binaphthyl,
DAIPEN = 1,1-di(4-anisyl)-2-isopropyl-1,2-ethylenediamine. DPEN =
1,2-diphenylethylenediamine.
(4) (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, 13529–13530. (b) Ohkuma, T.; Koizumi,
M.; Mu~niz, K.; Hilt, G.; Kabuto, C.; Noyori, R. J. Am. Chem. Soc. 2002,
124, 6508–6509.
(5) Mashima, K.; Kusano, K.; Ohta, T.; Noyori, R.; Takaya, H.
J. Chem. Soc., Chem. Commun. 1989, 1208–1210.
(6) Asymmetric reduction of alkyl aryl ketones with ruthenacyclic
catalysts; see: (a) Baratta, W.; Ballico, M.; Baldino, S.; Chelucci, G.;
Herdtweck, E.; Siega, K.; Magnolia, S.; Rigo, P. Chem.—Eur. J. 2008,
14, 9148–9160. (b) Pannetier, N.; Sortais, J.-B.; Dieng, P. S.; Barloy, L.;
10699
dx.doi.org/10.1021/ja202296w |J. Am. Chem. Soc. 2011, 133, 10696–10699