Catalytic asymmetric conjugate reduction with ethanol: A more reactive system Pd(II)-iPr-DUPHOS complex with molecular sieves 4A

Article abstract of DOI:10.1016/j.jorganchem.2007.10.005

We describe herein the catalytic asymmetric conjugate reduction of α,β-unsaturated carbonyl compounds using a novel cationic Pd-ⁱPr-DUPHOS complex. In this reaction, EtOH worked well as a solvent and a reducing agent, and the reaction was compl

Full text of DOI:10.1016/j.jorganchem.2007.10.005

Available online at www.sciencedirect.com
Journal of Organometallic Chemistry 693 (2008) 867–873
www.elsevier.com/locate/jorganchem
Catalytic asymmetric conjugate reduction with ethanol: A more
reactive system Pd(II)–iPr-DUPHOS complex with molecular sieves 4A
a
a
b
Daiki Monguchi , Christine Beemelmanns , Daisuke Hashizume ,
a
a,
*
Yoshitaka Hamashima , Mikiko Sodeoka
a
Synthetic Organic Chemistry Laboratory, RIKEN, 2-1 Hirosawa, Wako 351-0198, Japan
b
Molecular Characterization Team, RIKEN, 2-1 Hirosawa, Wako 351-0198, Japan
Received 21 August 2007; received in revised form 2 October 2007; accepted 2 October 2007
Available online 9 October 2007
Abstract
We describe herein the catalytic asymmetric conjugate reduction of a,b-unsaturated carbonyl compounds using a novel cationic
Pd–iPr-DUPHOS complex. In this reaction, EtOH worked well as a solvent and a reducing agent, and the reaction was completed
within several hours in most cases to afford the reduced compounds almost quantitatively with modest to good enantioselectivity (up
to 72% ee). It was found that the Pd–iPr-DUPHOS complex was more reactive than the previously reported Pd–BINAP complex when
molecular sieves 4A was added as an additive. Based on an X-ray structural analysis of [Pd{(S,S)-iPr-duphos}](OTf)2 complex, a working
hypothesis of the reaction mechanism is also described.
ꢀ 2007 Elsevier B.V. All rights reserved.
Keywords: Palladium; Asymmetric catalysis; Conjugate reduction; Ethanol; DUPHOS; Molecular sieves 4A
1. Introduction
hydrides and dihydropyridine derivatives by more environ-
mentally benign and atom-economical reducing agents is in
high demand.
Catalytic asymmetric conjugate reduction of b,b-disub-
stituted electron-deficient olefins is an efficient method for
the construction of tertiary stereogenic carbon centers.
Great efforts have been devoted to the development of
practical asymmetric reactions, and excellent enantioselec-
tivity was achieved with the development of Cu-bisphos-
phine and Rh-Phebox complexes [1–3]. In addition, chiral
secondary amines were reported to be excellent catalysts
for asymmetric conjugate reduction of a,b-unsaturated
aldehydes and ketones [4]. These reactions normally
require a more-than-stoichiometric amount of reducing
agents such as hydrosilane, NaBH4, and Hantzsch ester,
and thus a large amount of co-products are formed, which
should be removed as a waste. In terms of atom economy
and environmental concerns, replacement of metal
We recently reported an efficient catalytic asymmetric
conjugate reduction of enones using cationic Pd complexes
1a and 2a (Fig. 1 and Scheme 1) [5,6]. This reaction can
be carried out in EtOH at room temperature to give the
corresponding reduced products in high chemical yield
with good to excellent enantioselectivity. Importantly, safe
and clean EtOH is used not only as a solvent but also as a
hydride source. In addition, the only co-product in this
reaction is acetaldehyde diethylacetal, which can be readily
removed under reduced pressure. Regardless of these
advantages, the scope of the Pd–BINAP system is limited:
(1) reduction of specific enones was sluggish as discussed
later in Table 1 and (2) additionally, less reactive a,b-unsat-
urated esters could not be used in the Pd–BINAP-catalyzed
conjugate reduction. Therefore, the development of a more
highly reactive Pd catalyst is extremely desirable. In this
article, we have developed a novel cationic Pd–iPr-
DUPHOS complex as a promising catalyst for catalytic
*
Corresponding author. Tel.: +81 048 467 9373; fax: +81 048 462 4666.
E-mail address: sodeoka@riken.jp (M. Sodeoka).
0022-328X/$ - see front matter ꢀ 2007 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2007.10.005

868
D. Monguchi et al. / Journal of Organometallic Chemistry 693 (2008) 867–873
Pri
iPr
H
O
P
P
PPh2
PPh2
P 2+ OH2
Pd
P
P
P
P
2TfO-
Pd Pd
*
*
*
O
P
OH2
Pri
iPr
H
2TfO-
1
2
a: (
R
)-BINAP
b: (S,S
)-iPr-Duphos
Fig. 1. Chiral Pd complexes used in this work.
substituted bisphosphine ligand DUPHOS was next exam-
ined [7]. As we expected, a better chemical yield (29%) was
observed when 1b was used as a catalyst (entry 3). To
improve the reaction rate, we planned to examine the use
of Pd l-hydroxo complex 2b, expected to facilitate the
formation of a Pd-ethoxide intermediate as a result of
hydroxide and alkoxide exchange reaction (vide infra).
Unfortunately, however, all attempts to obtain pure 2b
were unsuccessful. According to our previous observation
that molecular sieves 4A acts as a weak base and dehydrat-
ing agent to facilitate the formation of 2a from 1a [6a], we
next examined the in situ formation of the Pd l-hydroxo
complex 2b or its equivalent from the aqua-type complex
1b. To our delight, the reaction proceeded very smoothly
when 1b was used in combination with molecular sieves
4A, and complete consumption of 3a was observed after
20 h. The corresponding product 4a was isolated in 95%
yield with 21% ee (entry 4). In contrast, the reaction with
1a under identical reaction conditions yielded 4a in only
35% yield after even 60 h (entry 5). These results clearly
indicate that 1b is superior to 1a in terms of the reaction
rate, when they were used in combination with molecular
sieves 4A. Even though improvement of the enantioselec-
tivity is necessary, this higher reactivity achieved with an
alkyl-substituted electron-rich bisphosphine prompted us
to examine the scope and limitations of this catalytic
system.
With the more reactive catalytic system in hand, we first
applied this system to other enone substrates (Table 2). All
reactions conducted in Table 2 were complete within
several hours. In the case of substrates having a less bulky
alkyl-substituent at the b-position (3b, 3c), the enantiose-
lectivity was poor (entries 1 and 2). Interestingly, as the
bulkiness of the b-substituent was increased (3d and 3e),
the enantioselectivity was improved (entries 3 and 4). In
particular, the substrate bearing iPr group at the b-position
was converted to 4e in 98% yield with 70% ee. In addition,
enones with a substituent at the ortho position of the aro-
matic ring were also good substrates. The reactions of 3f
and 3g having an electron-donating group gave the prod-
ucts in good yield with high enantioselectivity (56% ee
and 72% ee, respectively) (entries 5 and 6). Finally, Br-
substituted substrate 3h also underwent the conjugate
reduction without difficulty to afford 4h in 83% yield with
64% ee (entry 7). In this reaction, the Br group was com-
pletely intact, and no debrominated compounds were
formed. It should be noted that all products obtained in
this work have the absolute configuration opposite to those
R
O
R
O
Pd cat. 1 or 2 (5 mol % Pd)
74~96% ee
Ar
Me
Ar
Me
EtOH, rt
3
4
Scheme 1.
Table 1
Optimization of the reaction conditions
Pd cat.
(5 mol % Pd)
additive
Me
O
Me
O
*
Me
Me
EtOH (0.25 M), rt
3a
4a
Entry
Pd cat.
Additive
Time (h)
Yielda (%)
eeb (%)
1
2
3
4
5
a
1a
2a
1b
1b
1a
–
–
–
20
20
20
20
60
9
21
29
95
35
82
80
15c
21c
69
MS4A
MS4A
Isolated yield.
b
c
Determined by chiral HPLC.
The absolute stereochemistry of the product was opposite to that from
Pd–BINAP complexes.
asymmetric conjugate reduction. This complex in combina-
tion with molecular sieves 4A showed much higher reactiv-
ity than the Pd–BINAP systems, being applicable to the
efficient reduction of even a,b-unsaturated esters. The reac-
tion mechanism is also discussed based on an X-ray struc-
tural analysis of an anhydrous Pd-DUPHOS complex.
2. Results and discussion
We chose 3a as a model compound, because the
Pd–BINAP complexes were less effective for this substrate.
The reaction of 3a was carried out in the presence of
5 mol% of Pd in ethanol at room temperature (Table 1).
When 1a was used as a catalyst, the reaction was slow.
The reduced product 4a was obtained in only 9% yield after
20 h, although the ee was high (entry 1). The Pd l-hydroxo
complex 2a slightly improve the chemical yield to give 4a in
16% yield (entry 2). It is likely that the poor chemical yield
in these reactions might be due to insufficient nucleophilic-
ity of a putative palladium hydride (Pd-H) intermediate.
Therefore, we envisaged that the reactivity of the Pd-H
species would be enhanced if a more electron-donating
bisphosphine ligand was used. Thus, the use of alkyl-

D. Monguchi et al. / Journal of Organometallic Chemistry 693 (2008) 867–873
869
Table 2
Catalytic asymmetric conjugate reduction of enones
Table 3
Catalytic asymmetric conjugate reduction of an ester
R1
O
R1
O
Pd cat. 1b (5 mol %)
R2
Ar
R2
CO2Et
CO2Et
Pd cat. 1 (5 mol %)
Ar
MS4A, EtOH (1 M), rt
3
4
MS4A, EtOH (1 M), rt
Entry Ar
R1 R2 Substrate Product Time Yielda eeb
5
6
(h)
(%)
(%)
Entry
Pd cat.
Time (h)
Yielda (%)
eeb (%)
1
2
3
4
5
6
7
Ph
Ph
Ph
Ph
2-
Me Me 3b
Me Ph 3c
Et Me 3d
iPr Me 3e
Me Me 3f
Me Me 3g
4b
4c
4d
4e
4f
2
96
16
1
2
a
1b
1a
4
40
95
69
35 (R)c
49 (R)c
(S)c
26
14
2
95
84
98
91
85
83
(S)d
32
Isolated yield.
Determined by chiral HPLC.
See Ref. [2b].
b
c
(S)c
70
5
(R)c
56e
2
MeOC6H4
2-
MeC6H4
MS4A
4g
4h
2
72e
1
2
MS4A
EtOH
H2O
2-BrC6H4 Me Me 3h
7
64
(S)f
CH3CHO
CH3CH(OEt)2
MS4A
H2O
P
P
H
CH3
a
b
c
d
e
f
P
P
O
H
Isolated yield.
Determined by chiral HPLC.
See Ref. [5].
Pd
Pd
CH
*
*
O
R
H
See Ref. [2b].
R
O
The absolute configuration of the product has not been determined.
See Section 4.
Ar
Me
Ar
Me
EtOH
P
4
3
Ar
Ar
R
P
P
P
Ar
R
R
H
Pd
*
Pd
O
Pd
P
O
H
H
*
*
observed when the Pd-(R)-BINAP complex 2a was used,
even though both catalysts constitute a similar chiral envi-
ronment around Pd with Pr groups and Ph groups at the
upper-left and lower-right corners, respectively (vide infra)
[5].
P
O
Me
Me
Me
i
Scheme 2. Proposed catalytic cycle.
Considering the higher reactivity of 1b with molecular
sieves 4A, the catalytic asymmetric conjugate reduction
of a,b-unsaturated ester was examined under identical con-
ditions. (E)-Ethyl 4-methyl-3-phenylpent-2-enoate 5 was
chosen as a substrate, and two Pd complexes derived from
removing water molecules produced in these steps. In addi-
tion, the electron-rich phosphine ligand might enhance the
nucleophilicity of the Pd-H intermediate, thereby the less
reactive substrates, in particular, enoate 5 could undergo
the conjugate reduction smoothly. Additionally, DUPHOS
may also increase the reactivity of the resulting Pd enolate,
and the final protonation is accelerated. These factors can
explain the higher reactivity of the present catalytic system.
To obtain more insight into the reaction mechanism,
structural determination of the Pd–iPr-DUPHOS complex
was examined. Unfortunately, all attempts to obtain a sin-
gle crystal of 1b under usual vapor diffusion method were
unsuccessful. But concentration of a hexane–CH2Cl2
(1: 1) solution of 1b under reduced pressure afforded an
anhydrous complex 1b0. This yellow crystalline was apt
to absorb water molecules and change to the original 1b
as yellow oil when it was left in the solvent at room temper-
ature for several hours. To our delight, however, we suc-
ceeded in determining the structure of 1b0 unequivocally
by X-ray analysis (Fig. 2). The molecular structure displays
a square-planar coordination for palladium (II) ligated
with two phosphorous atoms of DUPHOS and two oxygen
atoms of trifluormethanesulfonyl group. Two trif-
luoromethansulfonyl groups are positioned in the open
i
BINAP and Pr-DUPHOS, 1a and 1b, were compared
(Table 3). The reaction catalyzed by 1b was complete after
4 h in the presence of molecular sieves 4A, affording 6 in
95% yield with 35% ee (entry 1). In contrast, the reaction
with 1a was slow and did not reach completion even after
40 h (entry 2). Interestingly, in contrast to the reactions of
enones, the same sense of enantioselection was observed in
these reactions.
A proposed catalytic cycle is outlined in Scheme 2. First,
the Pd aqua complex 1b may be transformed to 2b or a sim-
ilar hydroxo complex with the aid of molecular sieves 4A,
and the generated Pd-OH acts as a Brønsted base to form a
Pd-ethoxide complex. Subsequent b-hydride elimination
affords a Pd-H intermediate. The enones 3 coordinating
to the Pd complex would undergo hydride transfer, and
the resulting Pd enolate is protonated by ethanol to com-
plete the catalytic cycle. Acetaldehyde formed during the
oxidation step is converted to diethylacetal. It is likely that
molecular sieves 4A promotes acetal formation and the
generation of the Pd-ethoxide intermediate from 2b by

870
D. Monguchi et al. / Journal of Organometallic Chemistry 693 (2008) 867–873
space (upper-left and lower-right corners), avoiding unfa-
vorable interaction with the Pr group on the ligand (side-
view).
case of Pd-DUPHOS system, the putative Pd enolate hav-
ing an electron-rich phosphine ligand would undergo the
final protonation smoothly, since the nucleophilicity of
the enolate is increased. Consequently, reversible reactions
going back to 8 would be retarded, making the insertion
step a major enantio-determining step. Such a reverse of
the stereochemistry was not observed in the case of 5
(Table 3). This is probably because the smooth protonation
occurred, since the corresponding enolate of esters should
be more reactive. Therefore, it seems that the absolute ste-
reochemistry was determined in the insertion step even in
the case of the Pd–BINAP system, which is in accord with
the prediction. The models of the complex of 3 and 8 were
constructed with a parallel alignment between the C@C
bond and the Pd–H bond. Other skewed coordination
modes should be considered to understand the b-substitu-
ent effect of the enones. Although the story is not so simple,
the working hypothesis discussed here would be useful for
further improvement.
i
A simplified model of the putative Pd-H intermediate 8
i
is shown in Scheme 3. As viewed side-on, the Pr group of
the (S,S)-DUPHOS occupies the upper-left side of the open
space around the coordination site for the enone. There-
fore, a favorable complex between 3 and 8 would be the
model A shown in Scheme 4. In contrast, the model B
would suffer from steric repulsion between the methyl
i
ketone moiety of the substrate and the Pr group of the
ligand. Even though the ee depends on the nature of the
substrate, the sense of enantioselection can be explained
by using the model A on the assumption that enantioselec-
tion is mainly determined in the hydride transfer step. In
contrast, this idea was not applicable to the Pd-(R)-BIN-
AP-catalyzed conjugate reduction of the enones, where
the observed stereochemistry was opposite to the predic-
tion based on similar models depicted in Scheme 4 [8].
We speculate that enantio-determining step in these two
reactions may be different: the hydride transfer step in
the reaction catalyzed by 2a would be reversible because
the final protonation step is not fast enough [9], and pro-
tonation of the Pd enolate intermediate might determine
the final absolute stereochemistry of the product. In the
3. Conclusions
We have developed a catalytic asymmetric conjugate
reduction with EtOH using a novel Pd–iPr-DUPHOS com-
plex combined with molecular sieves 4A. This catalyst sys-
Fig. 2. X-ray structure of 1b0.
Scheme 3.

D. Monguchi et al. / Journal of Organometallic Chemistry 693 (2008) 867–873
871
Model A
Model B
iPr
iPr
iPr
iPr
P
R
O
P
R
O
O
P
Pd H
P
Pd H
Me
R
Ar
Me
4 (minor)
Ar
Me
4 (major)
Ar
iPr
Ar
Me
R
O
Scheme 4. A possible mechanism for asymmetric induction.
tem shows greater reactivity than the previous Pd–BINAP
system, and the reduction of enones and enoates proceeded
smoothly. Even though the enantioselectivity observed in
the present work varied depending on the substrate, we
believe that the present results would provide a guide for
a better understanding of the reaction. Systematic tuning
of the catalyst using various known alkyl-substituted bis-
phosphine ligands based on our hypothesis will lead to
great improvement of the reaction efficiency. Further inves-
tigations into the improvement of the reaction efficiency
and to confirm our proposed reaction mechanism are
underway in our laboratory.
(10 lL) at room temperature. The mixture was stirred at
room temperature for 2 h. The precipitated AgCl was
filtered off through Celite, and the filtrate was evaporated
under reduced pressure to afford 1b (113 mg, 0.13 mmol)
in 90% yield.
1b: 1H NMR (400 MHz, CDCl3, TMS) d = 0.81 (d, 6H,
J = 6.6 Hz), 0.86 (d, 6H, J = 6.6 Hz), 1.15 (d, 6H,
J = 6.8 Hz), 1.26 (d, 6H, J = 6.8 Hz), 1.66–1.69 (m, 2H),
1.78–1.82 (m, 2H), 1.99–2.03 (m, 2H), 2.30–2.49 (m, 4H),
2.51–2.54 (m, 4H), 3.10–3.30 (m, 2H), 4.49 (br-s, 4H,
H2O), 7.79 (br-s, 2H), 7.87 (br-s, 2H); 31P NMR (160
MHz, CDCl3, 85% H3PO4) d = ꢀ71.4: [a]D = ꢀ16.5
(29 ꢂC, c = 1.3, CHCl3).
4. Experimental
4.2. X-ray crystal structure analysis of 1b0
All asymmetric reactions were carried out without pre-
caution to exclude air and moisture. NMR spectra were
recorded on a JEOL-LA 300 or 400 spectrometer, operat-
Crystal
data:
C28H44F6O6P2PdS2 Æ CH2Cl2 Æ H2O,
˚
FW = 926.03, hexagonal P61, a = 17.3064(4) A, c =
1
3
26.4722(6) A, V = 6866.5(3) A ; DX = 1.344 Mg mꢀ3
;
˚ ˚
ing at 300 or 400 MHz for H NMR, 75.0 or 100 MHz
for 13C NMR. Chemical shifts were reported downfield
Z = 6; l(Mo Ka) = 0.743 mmꢀ1, T = 100 K. Block shaped
colorless crystals were grown under reduced pressure from
a hexane–CH2Cl2 solution of 1b. A single crystal with the
dimensions of 0.48 · 0.25 · 0.19 mm was mounted on a
glass capillary and set on a Rigaku RAXIS-RAPID
diffractometer. The diffraction data were collected using
graphite-monochromated Mo Ka radiation. The unit cell
dimensions were determined using 70265 reflections with
6ꢂ 6 2h 6 60ꢂ. The diffraction data of 76918 within
6ꢂ 6 2h 6 60ꢂ were collected and merged to give 13002
unique reflections with Rint of 0.0628. The structure was
solved by a direct method and refined on F2 by a least-
squares method by the programs SIR2004 and SHELXL97,
respectively. The crystal showed twinning by merohedry.
To merge the intensities of the equivalent reflections from
each of two components, the data were processed by the
TWIN 0 1 0 1 0 0 0 0 ꢀ1 command in the SHELXL97 pro-
gram on the refinements. The final R values against 6868
unique reflections (2hmax = 60ꢂ) with I > 2r(I) are 0.0472
and 0.1218 for R(F) and wR(F2), respectively. The absolute
structure of the crystal was determined by anomalous dis-
persion effects; the resulted configuration of the 1b0 agrees
1
from TMS (=0) for H NMR. For 13C NMR, chemical
shifts were reported in the scale relative to the solvent
used an internal reference. IR was measured on Thermo
Nicolet AVATAR 370 FT-IR equipped with Dura-
Scopeꢁ. Optical rotations were measured on a JASCO
DIP-370 polarimeter. Column chromatography was per-
formed with silica gel 60 (40–100 lm) purchased from
Kanto Chemical Co. The enantiomeric excesses (ees) were
determined by HPLC analysis using JASCO Borwin
Ver.1.5 systems consisting of the following; pump, JAS-
CO PU-2080 plus; detector, JASCO CD-2095 plus mea-
sured at 254 nm or 280 nm; column, DAICEL
CHIRALPAK AS-H, and CHIRALCEL OJ-H; mobile
phase, hexane/2-propanol (IPA). Commercially available
dehydrated EtOH was used directly. Molecular sieves
4A 1/16 purchased from Wako Pure Chemical Industries,
Ltd. was used after drying at 150 ꢂC for 20 h under
reduced pressure.
4.1. Preparation of palladium aqua complex (1b)
[Pd{(S,S)-iPr-duphos}]Cl2 was prepared according to
with the (S,S) configuration of the Pr-DUPHOS ligand.
i
the reported procedure [7a]. To
a
solution of
Programs used: SIR2004: M.C. Burla, R. Caliandro, M.
Camalli, B. Carrozzini, G.L. Cascarano, L. De Caro, C.
Giacovazzo, G. Polidori, R. Spagna, J. Appl. Cryst. 38
[Pd{(S,S)-iPr-duphos}]Cl2 (87 mg, 0.15 mmol) in CH2Cl2
(4 mL) was added AgOTf (75.3 mg, 0.29 mmol), H2O

872
D. Monguchi et al. / Journal of Organometallic Chemistry 693 (2008) 867–873
1
(2005) 381–388; SHELXL97: G.M. Sheldrick, University of
Go¨ttingen, Germany, 1997.
4-(Naphthalen-3-yl)pentan-2-one (4a): Viscous oil. H
NMR (300 MHz, CDCl3) d = 1.35 (d, J = 7.0 Hz, 3H),
2.07 (s, 3H), 2.70–2.90 (m, 2H), 3.47 (tdd, J = 6.6, 6.6,
6.6 Hz, 1H), 7.34–7.48 (m, 3H), 7.63 (br-s, 1H), 7.78 (d,
J = 8.1 Hz, 3H); 13C NMR (75 MHz, CDCl3): d = 207.7,
143.6, 133.6, 132.3, 128.2, 127.6, 127.5, 126.0, 125.5,
125.4, 124.9, 51.9, 35.5, 30.6, 22.0; IR (neat) m 2962,
1712, 1600, 1506, 1357, 1271, 1161, 1128 cmꢀ1; HPLC
(DAICEL CHIRALCEL OJ-H, n-hexane/IPA = 99/1,
flow rate: 0.5 mL/min, UV: 254 nm, smajor 21.2 min, sminor
24.3 min for 4a from 1b); [a]D = +8.93 (28 ꢂC, c = 0.5, 21%
ee from 1b, CHCl3), [a]D = ꢀ31.3 (28 ꢂC, c = 0.14, 69% ee
from 1a, CHCl3).
˚
Selected distances (A) and angles (ꢂ) are as follows:
Pd(1)–O(4) 2.165(3), Pd(1)–O(1) 2.171(4), Pd(1)–P(2)
2.2181(13), Pd(1)–P(1) 2.2293(12), O(4)–Pd(1)–O(1)
89.56(13), O(4)–Pd(1)–P(2) 174.83(11), O(1)–Pd(1)–P(2)
90.86(10), O(4)–Pd(1)–P(1) 93.37(10), O(1)–Pd(1)–P(1)
175.88(11), P(2)–Pd(1)–P(1) 86.47(4), C(1)–P(1)–Pd(1)
109.47(16), C(7)–P(1)–Pd(1) 115.55(17), C(10)–P(1)–Pd(1)
114.76(15), C(2)–P(2)–Pd(1) 109.51(16), C(20)–P(2)–Pd(1)
113.92(17), C(17)–P(2)–Pd(1) 116.7(2), S(1)–O(1)–Pd(1)
118.9(2), S(2)–O(4)–Pd(1) 119.7(2), P(1)–C(10)–H(10)
107.6, P(2)–C(17)–H(17) 107.3.
1
4-(2-Methoxyphenyl)pentan-2-one (4f): Viscous oil. H
4.3. Preparation of starting materials
NMR (300 MHz, CDCl3) d = 1.25 (d, J = 6.7 Hz, 3H),
2.08 (s, 3H), 2.61 (dd, J = 8.3, 15.8 Hz, 1H), 2.78 (dd,
J = 5.6, 15.1 Hz, 1H), 3.66–3.70 (m, 1H), 3.73 (s, 3H),
6.85–6.94 (m, 2H), 7.15–7.22 (m, 2H); 13C NMR
(75 MHz, CDCl3) d = 20.1, 29.0, 30.1, 50.8, 55.3, 110.5,
120.6, 126.8, 127.2, 134.1, 156.7, 208.5; IR (neat) m 2962,
1711, 1599, 1491, 1461, 1355, 1239, 1161, 1123,
1025 cmꢀ1; HPLC (DAICEL CHIRALPAK AS-H, n-hex-
ane/IPA = 99/1, flow rate: 1.0 mL/min, UV: 254 nm, sminor
12.1 min, smajor 14.1 min); [a]D = +8.46 (26 ꢂC, c = 0.2,
56% ee, CHCl3).
Starting materials 3a, 3f, and 3g were synthesized
according to the procedure described in Supporting Infor-
mation of our previous paper [5]. Other compounds are
known in the literature [2b,5].
(E)-4-(naphthalen-3-yl)-3-penten-2-one (3a): Amor-
phous solid. 1H NMR (300 MHz, CDCl3) d = 2.33 (s,
3H), 2.65 (d, J = 1.1 Hz, 3H), 6.66 (br-s, 1H), 7.48–7.53
(m, 2H), 7.60 (dd, J = 1.8, 8.3 Hz, 1H), 7.82–7.88 (m,
3H), 7.96 (br-s, 1H); 13C NMR (75 MHz, CDCl3)
d = 198.9, 153.6, 139.6, 133.5, 133.1, 128.5, 128.2, 127.6,
126.7, 126.5, 126.2, 124.8, 124.0, 32.3, 18.3; IR (solid) m
4-(2-Methylphenyl)pentan-2-one (4g): Viscous oil. 1H
NMR (400 MHz, CDCl3) d = 1.23 (d, J = 6.8 Hz, 3H),
2.09 (s, 3H), 2.37 (s, 3H), 2.63–2.79 (m, 2H), 3.56 (tdd,
J = 6.8, 6.8, 6.8 Hz, 1H), 7.07–7.18 (m, 4H); 13C NMR
(100 MHz, CDCl3) d = 207.6, 144.2, 135.1, 130.4, 126.2,
125.9, 124.9, 51.3, 30.6, 30.4, 21.5, 19.5; IR (neat) m 2964,
2926, 2873, 1712, 1490, 1456, 1354, 1292, 1260, 1161,
1029 cmꢀ1; HPLC (DAICEL CHIRALCEL OJ-H, n-hex-
ane/IPA = 200/1, flow rate: 0.5 mL/min, UV: 254 nm,
smajor 23.5 min, sminor 29.4 min); [a]D = +21.43 (26 ꢂC,
c = 0.6, 72% ee, CHCl3).
1673, 1583, 1385, 1359, 1280, 1232, 1174, 1009, 957 cmꢀ1
.
(E)-4-(2-methoxyphenyl)-3-penten-2-one (3f): Viscous
oil. 1H NMR (400 MHz, CDCl3) d = 2.25 (s, 3H), 2.45
(s, 3H), 3.83 (s, 3H), 6.27 (s, 1H), 6.89–6.96 (m, 2H),
7.13 (d, J = 8.0 Hz, 1H), 7.28–7.32 (m, 1H); 13C NMR
(100 MHz, CDCl3) d = 198.7, 156.3, 154.8, 133.1, 129.4,
128.6, 126.5, 120.4, 111.0, 55.5, 32.2, 20.4; IR (neat) m
1680, 1596, 1487, 1434, 1353, 1259, 1231, 1178,
1025 cmꢀ1
.
(E)-4-(2-methylphenyl)-3-pentene-2-one (3g): Viscous
oil. 1H NMR (400 MHz, CDCl3) d = 2.25 (s, 3H), 2.28
(s, 3H), 2.41 (d, J = 1.6 Hz, 3H), 6.15 (br-s, 1H), 7.06
(d, J = 6.8 Hz, 1H), 7.14–7.26 (m, 3H); 13C NMR
(100 MHz, CDCl3) d = 198.7, 156.4, 143.9, 133.8, 130.3,
127.6, 126.9, 126.5, 125.6, 32.1, 21.3, 19.8; IR (neat) m
1684, 1610, 1598, 1485, 1425, 1353, 1259, 1174,
4.5. Determination of absolute configuration of 4h
A solution of 4h (11 mg, 0.046 mmol, 64% ee) and 10%
Pd/C (2 mg) in ethanol (0.1 mL) was stirred at ambient
temperature under hydrogen atmosphere (1 atm) for 2 h.
Evaporation of the solvent, following by silica gel chro-
matography hexane/AcOEt (3/1, Rf = 0.3) gave 4b in
83% yield (6.2 mg, 0.038 mmol) with 57% ee. The absolute
configuration were determined by comparing retention
times of each isomer on chiral HPLC: DAICEL CHIR-
ALPAK AS-H, n-hexane/IPA = 98/2, flow rate: 0.5 mL/
min, UV = 254 nm, smajor = 14.9 min (S), sminor = 17.6
min (R).
961 cmꢀ1
.
4.4. General procedure for the catalytic asymmetric
conjugate reduction (Table 2)
A solution of 1b (4.4 mg, 0.005 mmol), 3 g (17 mg,
0.1 mmol), and molecular sieves 4A (20 mg) in ethanol
(0.1 mL) was stirred at ambient temperature for 2 h.
Evaporation of the solvent, following by silica gel column
chromatography hexane/AcOEt (9/1, Rf = 0.3) gave 4g in
85% yield (14.9 mg, 0.085 mmol) with 72% ee. The ee was
determined by chiral HPLC analysis. For compounds 4b,
4d, 4e, and 4h, see Ref. [5]. For compounds 4c and 6, see
[2b].
5. Supplementary material
CCDC 657104 contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free
of charge from The Cambridge Crystallographic Data Cen-
tre via www.ccdc.cam.ac.uk/data_request/cif.

D. Monguchi et al. / Journal of Organometallic Chemistry 693 (2008) 867–873
873
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Acknowledgement
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This work was supported by a Grant-in-Aid for Young
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