Double Asymmetric Hydrogenation of Linear β,β-Disubstituted α,β-Unsaturated Ketones into γ-Substituted Secondary Alcohols using a Dual Catalytic System

Article abstract of DOI:10.1002/chem.201701527

Double asymmetric hydrogenation of linear β,β-disubstituted α,β-unsaturated ketones catalyzed by the DM-SEGPHOS/DMAPEN/Ru^II complex with t-C₄H₉OK afforded the γ-substituted secondary alcohols in high diastereo- and enantioselectivities. Some mechanistic experiments suggested that two different reactive species, type (I) and (II), were reversibly formed in this catalytic system: Type (I) with the diamine ligand DMAPEN enantioselectively hydrogenated the enones into the chiral allylic alcohols, and type (II) without the diamine ligand diastereoselectively hydrogenated the allylic alcohols into the γ-substituted secondary alcohols. This dual catalysis protocol was successfully applied to the reaction of a variety of aliphatic- and aromatic-substituted enone substrates.

Full text of DOI:10.1002/chem.201701527

A Journal of
Accepted Article
Title: Double Asymmetric Hydrogenation of Linear β,β-Disubstituted
α,β-Unsaturated Ketones into γ-Substituted Secondary Alcohols
with Dual Catalytic Systems
Authors: Noriyoshi Arai, Hironori Satoh, Ryo Komatsu, and Takeshi
Ohkuma
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To be cited as: Chem. Eur. J. 10.1002/chem.201701527
Link to VoR: http://dx.doi.org/10.1002/chem.201701527
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10.1002/chem.201701527
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COMMUNICATION
Double Asymmetric Hydrogenation of Linear β,β-Disubstituted
α,β-Unsaturated Ketones into γ-Substituted Secondary Alcohols
with Dual Catalytic Systems
Noriyoshi Arai, Hironori Satoh, Ryo Komatsu, and Takeshi Ohkuma*
a) Equilibration between two catalytic species
Abstract: Double asymmetric hydrogenation of linear β,β-
H2
N
H
H
disubstituted α,β-unsaturated ketones catalyzed by the DM-
SEGPHOS/DMAPEN/Ru(II) complex with t-C4H9OK afforded the γ-
substituted secondary alcohols in high diastereo- and
enantioselectivities. Some mechanistic experiments suggested that
two different reactive species, type (I) and (II), were reversibly
formed in this catalytic system: Type (I) with the diamine ligand
DMAPEN enantioselectively hydrogenated the enones into the chiral
allylic alcohols, and type (II) without the diamine ligand
diastereoselectively hydrogenated the allylic alcohols into the γ-
substituted secondary alcohols. This dual catalysis protocol was
successfully applied to the reaction of a variety of aliphatic- and
aromatic-substituted enone substrates.
H2N
R2N
Sol
Sol
solvent
+
(ligands)
(ligands)
Ru
Ru
N
R2
catalyst type (II)
for hydrogenation
of alkenes
catalyst type (I)
for hydrogenation
of ketones
δ–
δ+
δ+
C
O
H
H
δ–
(ligands)
Ru
δ–
H
H
N
X
δ+
(ligands)
Ru
catalytic intermediate
of the hydrogenation
N
R2
of alkenes with functionality (X)
with catalyst (II)
transition structure of
hydrogenation of
ketones with catalyst (I)
Asymmetric hydrogenation of unsaturated compounds into the
optically active saturated products has contributed greatly to a
range of research fields, including organic synthesis, medicinal
science, and functional materials.[1] Generally, chiral catalysts
for this transformation are appropriately designed according to
b) Double asymmetric hydrogenation of α,β-unsaturated ketones
asymmetric hydrogenation
R2
O
R2 OH
with dual catalysis
R3
R3
*
R1
R1
*
H2
catalyst type (I)
H2
catalyst type (II)
the chemical features of substrates.
We have reported
R2 OH
asymmetric hydrogenation of ketones catalyzed by chiral Ru
complexes.[2,3] The catalytic species (type (I)) is a Ru hydride
coordinated by a diamine derivative which has at least one NH2
R3
R1
*
Scheme 1. Primary concept for the double asymmetric hydrogenation of α,β-
unsaturated ketones using a dual catalytic system.
group (Scheme 1-a)).
The catalyst type (I) smoothly
hydrogenates C=O groups through a six-membered transition
–
+
–
+
structure in which the Hδ –Ruδ –Nδ –Hδ quadrupole fits with the
+
–
Cδ =Oδ dipole.[2–5] The less polar C=C groups are hardly
reduced by this catalytic system. On the other hand, catalyst
type (II) with vacant coordination sites (solvents occupy them in
this scheme) is appropriate for the hydrogenation of C=C
moieties through coordination with the π-orbital. The presence
of another coordinative functionality (X) in the molecule
promotes the alkene hydrogenation with formation of a stable
chelate intermediate.[6] In general, the σ-coordinative C=O
groups are much more slowly reduced with the catalyst (II).[2]
We expected that when these two species, type (I) and (II), were
reversibly formed as shown in Scheme 1-a), both polar C=O and
less polar C=C groups would be smoothly hydrogenated via the
dual catalysis. According to this protocol, we designed double
asymmetric hydrogenation of linear β,β-disubstituted α,β-
unsaturated ketones into the γ-substituted secondary alcohols in
high diastereo- and enantioselectivities (Scheme 1-b)). The
carbonyl hydrogenation of the enone into the allylic alcohol is
catalyzed by the species (I),[7,8] and then the alkene
hydrogenation into the saturated alcohol is promoted by the
catalyst type (II).[9]
asymmetric hydrogenation has been reported to our knowledge.
We selected (E)-4-phenyl-3-penten-2-one (1a) as a standard
substrate to investigate the catalyst structure and reaction
No efficient catalyst for this double
conditions (Table 1).
[RuCl2{(S)-tolbinap}{(R)-dmapen}]
((SP,RN)-4a) with t-C4H9OK was the first choice for a catalyst
system showing excellent catalytic performance in the
asymmetric hydrogenation of alkenyl aryl ketones into the
secondary allylic alcohols.[7b,10] When enone 1a (0.77 mmol)
was hydrogenated in 2-propanol (4.5 mL) with (SP,RN)-4a and t-
C4H9OK in a substrate/catalyst/base molar ratio (S/C/B) of
500:1:5 under 50 atm of H2 at 0°C (ice bath) in 6 h and then
25°C (ambient temperature) in 34 h, anti-(2R,4S)-4-phenyl-2-
pentanol (anti-(2R,4S)-2a) (4% yield, 46% ee), syn-(2S,4S)-2a
(6% yield, 82% ee), and (R)-4-phenyl-3-penten-2-ol ((R)-3a)
(90% yield, 30% ee) were obtained (Table 1, entry 1). The
saturated ketone, 4-phenyl-2-pentanone, was not detected. The
hydrogenation of allylic alcohol 3a was slow, but this result
suggested that our dual catalysis concept was reasonable. The
increase in bulkiness close to the Ru center of catalysts 4b and
4c resulted in a higher conversion of 3a into 2a (entries 2 and 3).
The bulkiness seems to assist in full or partial elimination of the
diamine ligand, increasing the amount of the type(II) species
[*]
Prof. Dr. N. Arai, H. Satoh, R. Komatsu, Prof. Dr. T. Ohkuma
Division of Applied Chemistry and Frontier Chemistry Center,
Faculty of Engineering, Hokkaido University
Sapporo, Hokkaido 060-8628 (Japan)
(see Scheme 1-a)).
Use of the (S)-DM-SEGPHOS/(R)-
E-mail: ohkuma@eng.hokudai.ac.jp
DEAPEN/Ru(II) complex (SP,RN)-5 increased the yield of 2a
(anti/syn = 2.5:1) to 99% (entry 4).[10] To our delight, anti-2a
Supporting information for this article is given via a link at the end of
the document.
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COMMUNICATION
Table 1. Double asymmetric hydrogenation of enone 1a into the saturated
alcohol 2a with chiral Ru catalysts.[a]
was obtained in an excellent ee of 98% with high
diastereoselectivity (anti/syn = 15:1) by using a [RuCl2{(S)-dm-
segphos}][(S)-dmapen] ((SP,SN)-6a)/t-C4H9OK system, although
the mono-hydrogenation product 3a remained (entry 5). The
diastereo- and enantioselectivity were somewhat decreased in
the reaction with the (S)-DM-SEGPHOS/(S)-DEAPEN/Ru(II)
complex (SP,SN)-6b (entry 6). The mono-hydrogenation product
3a was obtained quantitatively with the complex (SP,SN)-7
bearing the strongly binding diamine DPEN (entry 7).[2,10]
Double hydrogenation of 1a was observed in tert-butyl alcohol,
but the yield and stereoselectivity of 2a were lower than those in
2-propanol (entry 8). Interestingly, higher conversion of the 3a
hydrogenation was achieved in a 3:1 mixture of 2-propanol and
tert-butyl alcohol (entry 9). Allylic alcohol 3a was almost
completely reduced with an S/C/B of 300:1:5 to afford anti-2a
(anti/syn = 11:1) in 98% ee (entry 10).[11] The reaction was
retarded with excess amount of (S)-DMAPEN (entry 11).
Ru cat.
O
t-C4H9OK
H2
+
+
solvent
0 to 25°C, 40 h
OH
50 atm
1a
OH
OH
+
anti-(2R,4S)-2a
syn-(2S,4S)-2a
(R)-3a
(C2H5)2
O
Ar2
P
R2
N
Ar2
P
Cl
Cl
Ru
Cl
N
O
O
Ru
Cl
P
Ar2
N
H2
P
Ar2
N
H2
O
(SP,RN)-4
(SP,RN)-5: Ar = 3,5-(CH3)2C6H3
a: Ar = 4-CH3C6H4, R = CH3
b: Ar = 4-CH3C6H4, R = C2H5
c: Ar = 3,5-(CH3)2C6H3, R = C2H5
A variety of linear β,β-disubstituted enones 1 were converted
to the γ-substituted secondary alcohols 2 in high diastereo- and
enantioselectivities in the double hydrogenation with the (SP,SN)-
6a/t-C4H9OK catalyst system (Table 2). The reactions of 4-
phenyl-3-penten-2-ones (R1 = C6H5, R3 = CH3) with a methyl-
and an ethyl-β-substituent, 1a (R2 = CH3) and 1b (R2 = C2H5),
gave similar results (entries 1 and 2). The anti-γ-isopropyl
alcohol, anti-2c, was also obtained in an excellent ee of 99%,
although the diastereoselectivity was lowered (entry 3). The
enone substrates with the para-substituents on the β-phenyl ring,
1d–1g, were hydrogenated to afford the desired γ-aryl alcohols,
2d–2g, in 95–98% ee (anti/syn = 8:1–14:1) (entries 4–6, and 8).
The reaction of 1f was carried out with an S/C of 1000 for 50 h
to afford 2f in 83% yield (entry 7). The ethyl ketone 1h (R3 =
C2H5) was converted to the alcohol 2h in 98% ee with a
remarkably high anti/syn selectivity of 23:1 (entry 9). The
reaction rate was slowed in the reaction of the bulky isopropyl
ketone 1i, but the anti-product 2i was obtained with high
stereoselectivity (entry 10). The alkenyl phenyl ketone 1j was
converted to a 1:1 mixture of anti (84% ee) and syn (83% ee)
isomers (entry 11). The anti-2j in 96% ee (anti/syn = 3:1) was
obtained when the diastereomeric complex (SP,RN)-6a was used
instead of (SP,SN)-6a (entry 12). The β,β-dialkyl enones, 1k (R1
= n-C4H9, R2 = CH3) and 1l (R1 = cyclo-C6H11, R2 = CH3), were
quantitatively converted to the γ-branched saturated alcohols, 2k
and 2l, in 92% ee (anti/syn = 2:1) and 94% ee (anti/syn = 3:1),
respectively, under the regular conditions (entries 13 and 14).
O
Ar2
P
R2
N
Ar2
P
H2
N
Cl
Ru
Cl
Cl
Ru
Cl
O
O
P
Ar2
N
H2
P
Ar2
N
H2
O
(SP,SN)-6
(SP,SN)-7: Ar = C6H5
a: Ar = 3,5-(CH3)2C6H3, R = CH3
b: Ar = 3,5-(CH3)2C6H3, R = C2H5
Yield [%],[b] ee [%][c]
Ent
ry
Conv
[%][b]
Ru cat.
Solvent
anti-2a
syn-2a
3a
1
(SP,RN)-4a
(SP,RN)-4b
(SP,RN)-4c
(SP,RN)-5
2-PrOH
2-PrOH
2-PrOH
2-PrOH
2-PrOH
2-PrOH
2-PrOH
t-BuOH
IP/TB[g]
IP/TB[g]
IP/TB[g]
100
93[d]
100
100
100
99
4, 46
6, 26
56, 85
71, 89
74, 98
73, 95
0
6, 82
12, 83
37, 90
28, 79
5, 40
19, 86
0
90, 30
73, 40
7, 93
2
3
4
1, nd
5
(SP,SN)-6a
(SP,SN)-6b
(SP,SN)-7
20,[e] 58
7, 28
6
7
100
100[f]
100
100
23[j]
100, 86
57,[e] 77
4,[e] 42
<1, nd
17, 69
8
(SP,SN)-6a
(SP,SN)-6a
(SP,SN)-6a[h]
(SP,SN)-6a[h,i]
23, 94
87, 98
87, 98
0
4, 61
8, 52
8, 45
0
9
Allylic alcohol (R)-3a in 91% ee was the major product with a
small amount of anti-2a at the early stage of the hydrogenation
of 1a with the Ru complex (SP,SN)-6a (Scheme 2, equation (1)).
The isolated (R)-3a in 86% ee was hydrogenated by the (SP,SN)-
6a/t-C4H9OK catalyst system to afford anti-(2R,4S)-2a in high
diastereo- and enantioselectivities comparable to those in the
double hydrogenation of 1a (equation (2)). The reaction using
[RuCl2{(S)-dm-segphos}(dmf)n] ((S)-8) without a diamine ligand
gave almost the same result. These data suggest that the
double hydrogenation proceeds through enone 1a → allylic
alcohol 3a → saturated alcohol 2a, as shown in Scheme 1-b).
The diamine ligand DMAPEN is not necessary in the second
hydrogenation of 3a into 2a. Either of two reaction pathways
may account for the transformation of 3a to 2a: 1) hydrogenation
10
11
[a] Unless otherwise stated, reactions were conducted at 0°C (6 h) and then
25°C (34 h) under 50 atm of H2 using 0.63–1.06 mmol of enone 1a (0.13–0.21
M) in solvent containing a Ru complex and t-C4H9OK. 1a/Ru/t-C4H9OK =
500:1:5. [b] Determined by 1H NMR analysis. 100% conversion means enone
1a was not detected. 0% yield means the corresponding peaks were not
observed. [c] Determined by HPLC analysis on a chiral stationary phase. [d]
4-Phenyl-2-pentanone in 2% was detected. [e] The Z isomer in 1% was
detected. [f] Unidentified compounds were observed. [g] IP/TB = 2-PrOH/t-
BuOH (3:1). [h] 1a/Ru = 300:1. [i] (S)-DMAPEN (7 equiv. to 6a) was added.
[j] The Z isomer of 1a in 6% was detected.
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Table 2. Double asymmetric hydrogenation of enones 1 into the saturated
alcohols 2.[a]
H2 (50 atm)
(SP,SN)-6a, t-C4H9OK
(1)
(2)
1a
anti-2a
+
3a
(SP,SN)-6a
i-C3H7OH/t-C4H9OH (3:1)
0 to 25°C, 10 h
R2
O
R2 OH
R3
R1
6%, 99% ee 41%, 91% ee
t-C4H9OK
H2
+
R3
S/C = 300
R1
1
2
H2 (50 atm)
a: R1 = C6H5, R2 = R3 = CH3
g: R1 = 4-ClC6H4, R2 = R3 = CH3
Ru cat., t-C4H9OK
b: R1 = C6H5, R2 = C2H5, R3 = CH3 h: R1 = C6H5, R2 = CH3, R3 = C2H5
c: R1 = C6H5, R2 = i-C3H7, R3 = CH3 i: R1 = C6H5, R2 = CH3, R3 = i-C3H7
d: R1 = 4-CH3C6H4, R2 = R3 = CH3 j: R1 = C6H5, R2 = CH3, R3 = C6H5
e: R1 = 4-C6H5C6H4, R2 = R3 = CH3 k: R1 = n-C4H9, R2 = R3 = CH3
f: R1 = 4-CH3OC6H4, R2 = R3 = CH3 l: R1 = c-C6H11, R2 = R3 = CH3
(R)-3a
anti-(2R,4S)-2a
i-C3H7OH
O
86% ee
0 to 25°C, 40 h
S/C = 200
Ar2
P
Cl
O
O
Ru(dmf)n
Ru cat. Yield [%] anti/syn ee (anti-2a) [%]
P
Ar2
Cl
82
84
15:1
13:1
98
98
(SP,SN)-6a
(S)-8
2
O
(S)-8: Ar = 3,5-(CH3)2C6H3
Entry
1
1
S/C[b]
300
300
300
300
300
300
1000
300
300
300
300
300
300
300
Conv [%][c]
100
100
100
100
100
100
100
100
100
86
Yield [%][c]
95 (95)
98 (81)
91 (87)
90 (80)
91 (77)
96 (85)
83 (78)[f]
98 (93)
92 (89)
70 (63)
92
anti/syn[c]
11:1
12:1
4:1
ee [%][d]
98
H2 (50 atm)
D OH
(SP,SN)-6a, t-C4H9OK
1a
1b
1c
1d
1e
1f
i-C3H7OH
2
99
0 to 25°C, 40 h
rac-3ad1
S/C = 200
3
99
D
D
D
D
(4%)(95%)
H D OH
(2%) (69%)
4
11:1
8:1
97
H
D OH
D OH
5
95
(3)
+
+
6
14:1[e]
13:1[e]
12:1
23:1
22:1
1:1
98
anti-2ad1: 50%, 93% ee syn-2ad1: 28%, 98% ee
(S)-3ad1: 22%, 54% ee
7
1f
98
Scheme 2. Experiments for mechanistic consideration.
8
1g
1h
1i
98
9
98
hydrogenation conditions.
hydrogenation of 3a occurred via formation of ruthenium
alkoxide of the allylic alcohol.
This suggested that the
10
11
12[h]
13
14
94
1j
96
84[g]
96
A plausible mechanism for the double hydrogenation of α,β-
unsaturated ketone 1a with the (SP,SN)-6a/t-C4H9OK catalyst
system consisting of dual catalytic cycles (I) and (II) is shown in
Scheme 3. The catalytic cycle (I) hydrogenates α,β-unsaturated
ketone 1a to the allylic alcohol (R)-3a,[2,7] and the cycle (II)
converts (R)-3a into the saturated alcohol (2R,4S)-2a. Catalytic
cycle (I): (SP,SN)-6a is converted to the catalytic cycle species
with the hydride source, H2, in a base containing alcoholic
solvent. The (RuH) amide complex A is reversibly converted to
the cationic species B in the alcoholic media. The species B
and H2 form C, followed by deprotonation with the base to afford
1j
100
100
100
>99 (85)
98 (93)
99 (95)
3:1
1k
1l
2:1[i]
3:1[e]
92[i]
94[i]
[a] Unless otherwise stated, reactions were conducted at 0°C (6 h) and then
25°C (34–42 h) under 50 atm of H2 using 0.50–1.60 mmol of enone 1 (0.10–
0.31 M) in a 3:1 mixture of 2-propanol and tert-butyl alcohol containing Ru
complex (SP,SN)-6a and t-C4H9OK. Ru/t-C4H9OK = 1:5. [b] Substrate/catalyst
molar ratio. [c] Determined by 1H NMR analysis. 100% conversion means
enone 1 was not detected. The yield of the isolated product is given in
parenthesis. The unreacted allylic alcohols were obtained as byproducts. [d]
Data for anti-2 determined by GC or HPLC analysis on a chiral stationary
phase. [e] Determined by GC analysis. [f] Reaction at 0°C (6 h) and then
25°C (44 h). [g] The ee value of syn-2j was 83%. [h] (SP,RN)-6a was used
instead of (SP,SN)-6a. [i] Determined after conversion to the phenylcarbamate.
the (RuH2) complex D.
The active complex D readily
hydrogenates 1a to (R)-3a with regeneration of the amide
complex A in equilibrium with B. Catalytic cycle (II): The allylic
alcohol (R)-3a reversibly reacts with the cationic species B to
form the allylic alkoxide complex E under a basic condition in
which the diamine ligand DMAPEN is fully or partly removed
from the Ru center to provide coordination sites for the alkene
moiety of 3a. The N(CH3)2 group confers the diamine ligand
with the appropriate binding ability. Hydride migration from the
Ru center to the β- or γ-position of the alkoxide affords the
ruthenacyclic complex F or F’. Hydrogenolysis of the Ru–C
bond of F or F’ to convert these complexes to G followed by
release of (2R,4S)-2a reproduces the cationic species B.
of the C=C bond of 3a, or 2) isomerization of 3a into 4-phenyl-2-
pentanone through 1,3-hydrogen migration from the C2-position
to the C4-position followed by carbonyl hydrogenation of this
ketone. Next, therefore, we examined the hydrogenation of
racemic 2-deuterated allylic alcohol rac-3ad1 with the (SP,SN)-
6a/t-C4H9OK catalyst system to determine the reaction pathway
(equation (3)). The deuterium content at the C4-position of the
saturated alcohols, anti- and syn-2ad1, was very low, revealing
that 3a was exclusively converted to 2a by the alkene
hydrogenation.[12] Interestingly, no reaction of the methyl ether
of the allylic alcohol 3a was observed under the standard
In summary, we report herein the first successful example of
the double asymmetric hydrogenation of linear β,β-disubstituted
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10.1002/chem.201701527
Chemistry - A European Journal
COMMUNICATION
Me2
H
Science of Synthesis: Stereoselective Synthesis, Vols. 1 and 2 (Eds.; J.
G. de Vries, G. A. Molander), Thieme, Stuttgart, 2011; c)
Comprehensive Chirality, Vol. 5 (Eds.: E. M. Carreira, H. Yamamoto, K.
Maruoka), Elsevier, Amsterdam, 2012.
P
P
N
H+
1a
Ru
N
H2
H
(R)-3a
[2]
[3]
Review: T. Ohkuma, N. Arai, Chem. Rec. 2016, 16, 2801–2819.
For recent study, see: K. Matsumura, N. Arai, K. Hori, T. Saito, N. Sayo,
T. Ohkuma, J. Am. Chem. Soc. 2011, 133, 10696–10699.
D
H2
+
Me
N
Me2
N
Me2
N
[H]
–2HCl
H
H
2
Cl
Ru
Cl
P
P
P
P
P
P
[4]
[5]
Many transition-state models have been proposed in recent years.
Here we use a simple model to clearly show the dual catalysis concept.
For selected mechanistic studies, see: a) K. Abdur-Rashid, S. E.
Clapham, A. Hadzovic, J. N. Harvey, A. J. Lough, R. H. Morris, J. Am.
Chem. Soc. 2002, 124, 15104–15118; b) C. A. Sandoval, T. Ohkuma, K.
Muñiz, R. Noyori, J. Am. Chem. Soc. 2003, 125, 13490–13503; c) R. J.
Hamilton, S. H. Bergens, J. Am. Chem. Soc. 2006, 128, 13700–13701;
d) S. A. French, D. Di Tommaso, A. Zanotti-Gerosa, F. Hancock, C. R.
A. Catlow, Chem. Commun. 2007, 2381–2383; e) S. Takebayashi, N.
Dabral, M. Miskolzie, S. H. Bergens, J. Am. Chem. Soc. 2011, 133,
9666–9669; f) P. A. Dub, N. J. Henson, R. L. Martin, J. C. Gordon, J.
Am. Chem. Soc. 2014, 136, 3505–3521.
catalytic
cycle (I)
Ru
Ru
N
H2
N
H
N
H2
H
H
C
A
(SP,SN)-6a
+
H+
Me2
N
P
P
H2
(2R,4S)-2a
Ru
(R)-3a
N
H2
H
H+
H+
B
H
O
O
H
P
P
L
L
[6]
[7]
See for example: J. M. Brown in Comprehensive Asymmetric Catalysis,
Vol. 1 (Eds.; E. N. Jacobsen, A. Pfaltz, H. Yamamoto), Springer, Berlin,
Heidelberg, 1999, pp. 121–182.
catalytic
cycle (II)
Ru
Ru
P
L
P
H
H
E
For asymmetric hydrogenation of α,β-unsaturated ketones into the
chiral allylic alcohols catalyzed by BINAP/1,2-diamine/Ru(II)-type
complexes, see: a) T. Ohkuma, M. Koizumi, H. Doucet, T. Pham, M.
Kozawa, K. Murata, E. Katayama, T. Yokozawa, T. Ikariya, R. Noyori, J.
Am. Chem. Soc. 1998, 120, 13529–13530; b) N. Arai, K. Azuma, N. Nii,
T. Ohkuma, Angew. Chem. 2008, 120, 7567–7570; Angew. Chem. Int.
Ed. 2008, 47, 7457–7460.
G
H
O
P
P
hydride
migration
O
P
Ru
H
L
Ru
H2
H
P
L
L
F'
F
[8]
For selected efficient catalysts for asymmetric hydrogenation of α,β-
unsaturated ketones into the allylic alcohols, see the following. For Ru
catalysts: a) M. J. Burk, W. Hems, D. Herzberg, C. Malan, A. Zanotti-
Gerosa, Org. Lett. 2000, 2, 4173–4176; b) R. Patchett, I. Magpantay, L.
Saudan, C. Schotes, A. Mezzetti, F. Santoro, Angew. Chem. 2013, 125,
10542–10545; Angew. Chem. Int. Ed. 2013, 52, 10352–10355; c) S.-M.
Lu, Q. Gao, J. Li, Y. Liu, C. Li, Tetrahedron Lett. 2013, 54, 7013–7016;
d) X. Chen, H. Zhou, K. Zhang, J. Li, H. Huang, Org. Lett. 2014, 16,
3912–3915. For Ir catalysts: e) K. Mashima, T. Akutagawa, X. Zhang, H.
Takaya, J. Organomet. Chem. 1992, 428, 213–222; f) Q.-Q. Zhang, J.-
H. Xie, X.-H. Yang, J.-B. Xie, Q.-L. Zhou, Org. Lett. 2012, 14, 6158–
6161.
Scheme 3. Plausible mechanism of the double hydrogenation of enone 1a
through a dual catalytic system. P—P = (S)-DM-SEGPHOS; NMe2—NH2
(S)-DMAPEN; L = DMAPEN or a weakly bonding compound.
=
α,β-unsaturated ketones, which we achieved by using a novel
dual catalytic system of the DM-SEGPHOS/DMAPEN/Ru(II)
complex with t-C4H9OK. This system is designed to reversibly
form two hydrogenation catalysts, a catalyst type (I) and (II),
where type (I) bears a diamine ligand DMAPEN and selectively
hydrogenates the enone substrates to the chiral allylic alcohols,
and type (II) lacks the diamine ligand and preferentially reduces
the alkenyl groups of the allylic alcohols. Using this system, the
γ-substituted secondary alcohols are obtained with high
diastereo- and enantioselectivities in a one-pot reaction.
[9]
For hydrogenation of optically active or racemic secondary allylic
alcohols with chiral catalysts, see the following. For Ru catalysts: a) M.
Kitamura, I. Kasahara, K. Manabe, R. Noyori, H. Takaya, J. Org. Chem.
1988, 53, 708–710; b) Q. Chen, F.-L. Qing, Tetrahedron 2007, 63,
11965–11972. For Rh catalysts: c) J. M. Brown, I. Cutting, J. Chem.
Soc. Chem. Commun. 1985, 578–579; d) J. M. Brown, Angew. Chem.
1987, 99, 169–182; Angew. Chem. Int. Ed. Engl. 1987, 26, 190–203; e)
J. Holz, B. Schäffner, O. Zayas, A. Spannenberg, A. Börner, Adv. Synth.
Catal. 2008, 350, 2533–2543. For Ir catalysts: f) Y. Zhu, K. Burgess, J.
Am. Chem. Soc. 2008, 130, 8894–8895.
Acknowledgements
[10] DEAPEN
=
2-diethylamino-1-phenylethylamine; DMAPEN
=
2-
(4,4’-bi-1,3-
1,2-
dimethylamino-1-phenylethylamine; DM-SEGPHOS
benzodioxole)-5,5’-diylbis[di(3,5-xylyl)phosphane];
=
This work was supported by a Grant-in-Aid from the Japan
Society for the Promotion of Science (JSPS) (No. 15H03802)
DPEN
=
diphenylethylenediamine; TolBINAP
=
2,2’-bis(di-4-tolylphosphanyl)-
and
a grant from the MEXT (Japan) program "Strategic
1,1’-binaphthyl; XylBINAP
binaphthyl.
=
2,2’-bis(di-3,5-xylylphosphanyl)-1,1’-
Molecular and Materials Chemistry through Innovative Coupling
Reactions" of Hokkaido University.
[11] Hydrogenation of enone 1a with Ir catalysts bearing chiral sulfoximine-
derived P,N-ligands (S/C = 100, 60 atm H2, rt) gave the saturated
ketone, 4-phenyl-2-pentanone, in 65–75% yield and in 79–81% ee
accompanied by the saturated alcohol 2a (diastereomeric structure was
not mentioned) in 57–66% ee as a byproduct. See: S.-M. Lu, C. Bolm,
Chem. Eur. J. 2008, 14, 7513–7516.
Keywords: asymmetric catalysis • chiral alcohols •
hydrogenation • ruthenium • unsaturated ketones
[1]
See for example: a) The Handbook of Homogeneous Hydrogenation
(Eds.: J. G. de Vries, C. J. Elsevier), Wiley-VCH, Weinheim, 2007; b)
[12] The reason for a low deuterium content of 69% at the C2-position of the
minor syn-2ad1 is not clear.
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10.1002/chem.201701527
Chemistry - A European Journal
COMMUNICATION
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COMMUNICATION
Dual Asymmetric Catalyst System
A dual asymmetric catalyst system
Noriyoshi Arai, Hironori Satoh, Ryo
realizes double hydrogenation of
linear β,β-disubstituted α,β-
unsaturated ketones into the γ-
Komatsu, and Takeshi Ohkuma*
O
OH
OH
Ph
Ph
+ H2
Ph
*
Page No. – Page No.
+ H2
substituted secondary alcohols with
Me2
chiral
diamine
X
Ru
H
X
Ru
H
Double Asymmetric Hydrogenation
of Linear β,β-Disubstituted α,β-
P
N
P
P
L
L
high
diastereo-
and
*
*
enantioselectivities. The Ru catalyst
with a diamine ligand hydrogenates
the enones to the allylic alcohols
exclusively, and then the reversibly
formed catalyst without diamine
Unsaturated
Ketones
into
γ-
P
N
H2
Substituted Secondary Alcohols with
Dual Catalytic Systems
catalyst for
C=O hydrogenation
catalyst for
C=C hydrogenation
P—P = ( S)-DM-SEGPHOS; NMe 2—NH2
chiral diamine = (S)-DMAPEN; X = H or OR;
=
selectively
reduces
the
allylic
alcohols to the saturated alcohols.
L = weakly bonding compound
This article is protected by copyright. All rights reserved.