t-Bu-QuinoxP* ligand: Applications in asymmetric Pd-catalyzed allylic substitution and Ru-catalyzed hydrogenation

Article abstract of DOI:10.1021/jo071192k

(Chemical Equation Presented) The potential of the t-Bu-QuinoxP* ligand (1) as a chiral ligand in asymmetric synthesis was examined. The ligand exhibited good to excellent asymmetric induction in Pd-catalyzed asymmetric allylic substitution of 1,3-diphenyl-2-propenyl acetate (up to 98.7% ee) and in Ru-catalyzed asymmetric hydrogenation of ketones (up to 99.9% ee).

Full text of DOI:10.1021/jo071192k

high to almost perfect enantioselectivity in Rh-catalyzed asym-
metric hydrogenation.3-5 However, the sensitivity to air of these
ligands, which is derived from the high electron density of the
phosphorus atom, has hampered their widespread application
in various asymmetric catalyses. In order to overcome this
difficulty, we recently developed an air-stable P-chiral phosphine
ligand, t-Bu-QuinoxP* (1), as an alternative.6,7 This ligand
exhibited excellent asymmetric induction not only in Rh-
catalyzed hydrogenation6 but also in Rh-catalyzed 1,4-addition,6
Pd-catalyzed ring-opening reaction,6 and Rh-catalyzed hydro-
silylation.8 Herein we report the results of further investigation
of 1, where ligand 1 was successfully applied to asymmetric
Pd-catalyzed allylic substitution9 and Ru-catalyzed hydrogena-
tion.10
t-Bu-QuinoxP* Ligand: Applications in
Asymmetric Pd-Catalyzed Allylic Substitution
and Ru-Catalyzed Hydrogenation
Tsuneo Imamoto,* Miwako Nishimura, Aya Koide, and
Kazuhiro Yoshida
Department of Chemistry, Graduate School of Science, Chiba
UniVersity, Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
imamoto@faculty.chiba-u.jp
ReceiVed June 8, 2007
The potential of the t-Bu-QuinoxP* ligand (1) as a chiral
ligand in asymmetric synthesis was examined. The ligand
exhibited good to excellent asymmetric induction in Pd-
catalyzed asymmetric allylic substitution of 1,3-diphenyl-2-
propenyl acetate (up to 98.7% ee) and in Ru-catalyzed
asymmetric hydrogenation of ketones (up to 99.9% ee).
In order to determine the crystal structure of a transition-
metal catalyst coordinated with 1, we first prepared PdCl2[(R,R)-
1] (2) by mixing 1 with PdCl2(cod) in dichloromethane (eq 1).
A pure crystal for X-ray diffraction study was obtained by slow
diffusion of pentane into the concentrated dichloromethane
solution of 2 at room temperature.
The design and synthesis of new and efficient chiral ligands
have played a central role in the development of highly
enantioselective transition-metal-catalyzed asymmetric reac-
tions.1,2 In the past decade, we have focused our attention on
the development of a series of C2-symmetric P-chiral phosphine
ligands. 1,2-Bis(alkylmethylphosphino)ethanes (BisP*) and 1,2-
bis(alkylmethylphosphino)methanes (MiniPHOS), representa-
tives of C2-symmetric P-chiral phosphine ligands, exhibit very
The crystal structure and the selected bond distances and
angles of 2 are shown in Figure 1 and Table 1, respectively.11
Pd-P distances (2.2327(9) and 2.2326(8) Å) and Pd-Cl
distances (2.3656(8) and 2.3671(9) Å) are within the typical
range for dichloropalladium complexes bearing diphosphine
* To whom correspondence should be addressed. Tel: +81-43-290-2791.
Fax: +81-43-290-2791. E-mail: imamoto@faculty.chiba-u.jp.
(1) For representative reviews, see: (a) Tang, W.; Zhang, X. Chem. ReV.
2003, 103, 3029-3069. (b) Cre´py, K. V. L.; Imamoto, T. Top. Curr. Chem.
2003, 229, 1-40. (c) Guiry, P. J.; Saunders, C. P. AdV. Synth. Catal. 2004,
346, 497-537.
(3) Imamoto, T.; Watanabe, J.; Wada, Y.; Masuda, H.; Yamada, H.;
Tsuruta, H.; Matsukawa, S.; Yamaguchi, K. J. Am. Chem. Soc. 1998, 120,
1635-1636.
(4) Yamanoi, Y.; Imamoto, T. J. Org. Chem. 1999, 64, 2988-2989.
(5) Gridnev, I. D.; Yamanoi, Y.; Higashi, N.; Tsuruta, H.; Yasutake,
M.; Imamoto, T. AdV. Synth. Catal. 2001, 343, 118-136.
(6) Imamoto, T.; Sugita, K.; Yoshida, K. J. Am. Chem. Soc. 2005, 127,
11934-11935.
(7) Both enantiomers of t-Bu-QuinoxP* are commercially available from
Aldrich Chemical Company. Imamoto, T.; Sugita, K.; Yoshida, K. U.S.
Patent 2007021610, 2007; Imamoto, T.; Sugita, K.; Yoshida, K. JP Patent,
2007056007, 2007.
(8) Imamoto, T.; Itoh, T.; Yamanoi, Y.; Narui, R.; Yoshida, K.
Tetrahedron: Asymmetry 2006, 17, 560-565.
(9) (a) Trost, B. M.; Van Vranken, D. L. Chem. ReV. 1996, 96, 395-
422. (b) Trost, B. M.; Crawley, M. L. Chem. ReV. 2003, 103, 2921-2944.
(10) Ohkuma, T.; Noyori, R. In Handbook of Homogeneous Hydrogena-
tion; de Vries, J. G., Elsevier, C. J., Eds.; Wiley-VCH: Weinheim, Germany,
2007; Vol. 3, pp 1105-1163.
(11) The unit cell contained two Pd complexes and two dichloromethane
molecules. One of the Pd complexes and the dichloromethane molecules
are omited in Figure 1 and Table 1; CCDC 649473 for the compounds
contains supplementary crystallographic data. The data can be obtained free
of charge via http://www.ccdc.cam.ac.uk/conts/retrieving.html (or from The
Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB2
IEZ, UK; fax: (+44) 1223-336-033; e-mail: deposit@ccdc.cam.ac.uk).
(2) For recent representative examples, see: (a) Tang, W.; Zhang, X.
Angew. Chem., Int. Ed. 2002, 41, 1612-1614. (b) Ostermeier, M.; Priess,
J.; Helmchen, G. Angew. Chem., Int. Ed. 2002, 41, 612-614. (c) Hu, A.-
G.; Fu, Y.; Xie, J. H.; Zhou, H.; Wang, L. X.; Zhou, Q. L. Angew. Chem.,
Int. Ed. 2002, 41, 2348-2350. (d) Tang, W.; Wang, W.; Zhang, X. Angew.
Chem., Int. Ed. 2003, 42, 943-946. (e) Hoge, G.; Wu, H.-P.; Kissel, W.
S.; Pflum, D. A.; Greene, D. J.; Bao, J. J. Am. Chem. Soc. 2004, 126, 5966-
5977. (f) Fu, Y.; Hou, G. H.; Xie, J. H.; Xing, L.; Wang, L. X.; Zhou, Q.
L. J. Org. Chem. 2004, 69, 8157-8160. (g) Wu, S.; Zhang, W.; Zhang, Z.;
Zhang, X. Org. Lett. 2004, 6, 3565-3567. (h) Hu, X. P.; Zheng, Z. Org.
Lett. 2004, 6, 3585-3588. (i) Imamoto, T.; Oohara, N.; Takahashi, H.
Synthesis 2004, 1353-1358. (j) Imamoto, T.; Cre´py, K. V. L.; Katagiri, K.
Tetrahedron: Asymmetry 2004, 15, 2213-2218. (k) Cheng, X.; Zhang, Q.;
Xie, J.-H.; Wang, L. X.; Zhou, Q. L. Angew. Chem., Int. Ed. 2005, 44,
1118-1121. (l) Pa`mies, O.; Die´guez, M.; Claver, C. J. Am. Chem. Soc.
2005, 127, 3646-3647. (m) Takahashi, Y.; Yamamoto, Y.; Katagiri, K.;
Danjo, H.; Yamaguchi, K.; Imamoto, T. J. Org. Chem. 2005, 70, 9009-
9012. (n) Yan, Y.; Zhang, X. J. Am. Chem. Soc. 2006, 128, 7198-7202.
(o) Zhu, S. F.; Xie, J. B.; Zhang, Y. Z.; Li, S.; Zhou, Q. L. J. Am. Chem.
Soc. 2006, 128, 12886-12891. (p) Imamoto, T.; Yashio, K.; Cre´py, K. V.
L.; Katagiri, K.; Takahashi, H.; Kouchi, M.; Gridnev, I. D. Organometallics
2006, 25, 908-914.
10.1021/jo071192k CCC: $37.00 © 2007 American Chemical Society
Published on Web 08/10/2007
J. Org. Chem. 2007, 72, 7413-7416
7413

selectivity to 89% ee (Table 2, entry 10).14 Similar enantio-
selectivity (90% ee) was observed in the reaction of pyrrolidine
with BSA (Table 2, entry 11). Butylamine gave lower enantio-
selectivity (73% ee), while cyclohexylamine as a primary amine
gave high enantioselectivity (89% ee; Table 2, entries 12 and
13).
The potential of t-Bu-QuinoxP* (1) as a chiral ligand was
next explored for the Ru-catalyzed asymmetric hydrogenation
of ketones. It was found that a premixed Ru complex generated
from [RuCl2(η6-C6H6)]2 and 1 was an excellent catalyst for the
reaction. When a solution of 3-oxo-3-phenylpropionic acid ethyl
ester in EtOH/CH2Cl2 containing the (R,R)-t-Bu-QuinoxP*-
Ru complex was stirred under 20 atm H2 in a stainless steel
autoclave at 50 °C for 24 h, corresponding alcohol 6a was
obtained in 89% isolated yield with 99.3% ee (Table 3, entry
1). The enantioselectivity was not strongly affected by substit-
uents (electron-donating or electron-withdrawing) on the aro-
matic ring, and a series of 3-oxo-3-arylpropionic acid ethyl esters
were hydrogenated with almost perfect enantioselectivities
(Table 3, entries 2-7).16 High enantioselectivities were also
achieved in the reactions of 3-oxobutyric acid methyl ester and
4-chloro-3-oxobutyric acid ethyl ester, having an alkyl group
at the R1 position (Table 3, entries 8 and 9).17 When the reaction
was carried out with â-keto amide instead of â-keto ester,
product 6j having slightly lower enantioselectivity (97% ee) was
obtained (Table 3, entry 10). On the other hand, the hydrogena-
tion of diketone, 5,5-dimethyl-2,4-hexanedione, gave product
6k with excellent enantioselectivity (99.0% ee; Table 3, entry
11). It should be noted that the enantioselectivities described
here are among the best results reported so far.
Finally, the activity of the catalyst was examined. When the
reaction of 3-oxo-3-phenylpropionic acid ethyl ester was carried
out under 100 atm at 100 °C in the presence of 0.02 mol % of
Ru catalyst, TON of 2500 (50% isolated yield) was realized
albeit with decreased enantioselectivity to 95% ee (Table 3, entry
12).
In conclusion, we have examined the catalytic potential of
the t-Bu-QuinoxP* ligand (1) in Pd-catalyzed asymmetric allylic
substitution and Ru-catalyzed asymmetric hydrogenation and
obtained corresponding nonracemic compounds in high yields
with good to excellent enantioselectivities. Further modifications
of the ligand and studies of its applications in asymmetric
catalysis are in progress in our laboratory.
FIGURE 1. Crystal structure of PdCl2[(R,R)-1] (2); hydrogen atoms
are omitted for clarity.
TABLE 1. Selected Bond Distances and Angles of PdCl2[(R,R)-1]
(2)
Bond Distance (Å)
Pd(1)-Cl(1)
Pd(1)-P(1)
2.3656(8)
2.2327(9)
Pd(1)-Cl(2)
Pd(1)-P(2)
2.3671(9)
2.2326(8)
Bond Angle (deg)
Cl(1)-Pd(1)-Cl(2)
Cl(2)-Pd(1)-P(2)
93.50(3)
90.01(3)
Cl(1)-Pd(1)-P(1)
P(1)-Pd(1)-P(2)
90.59(3)
87.57(3)
ligands.12 The sum of the four angles at palladium involving
P(1), P(2), Cl(1), and Cl(2) is 361.7°. The bite angle of the
ligand is 87.57(3)°, and the small distortion is balanced by the
Cl-Pd-Cl angle of 93.50(3)°. The geometry around the Pd
center is described as skewed square planar, which can be
ascribed to steric repulsion between the chlorine atom and the
bulky tert-butyl group: the dihedral angle between the coor-
dination planes of P(1)-Pd-P(2) and Cl(1)-Pd-Cl(2) is 13.8°.
The enantioinduction ability of ligand 1 was examined in Pd-
catalyzed asymmetric allylic substitution (Table 2).13 When the
reaction of 1,3-diphenyl-2-propenyl acetate (3) with dimethyl
malonate was carried out in the presence of 0.5 mol % of [PdCl-
(η3-C3H5)]2 (1.0 mol % of Pd), 1.1 mol % of 1, and base [KOAc
and N,O-bis(trimethylsilyl)acetamide (BSA)] at room temper-
ature, the alkylation product was obtained with high enantio-
selectivity (92% ee) (Table 2, entry 1). The substituted malonates
and acetyl acetone as nucleophiles gave comparable enantio-
selectivities (Table 2, entries 2-7). Lowering the reaction
temperature improved enantioselectivity: the highest enantio-
selectivity (98.7% ee) was observed when the reaction of methyl
malonate was performed at a low temperature of -50 °C (Table
2, entry 8).
Experimental Section
Synthesis of [(R,R)-2,3-Bis((tert-butyl)methylphosphino)quinox-
aline]dichloropalladium (2). A mixture of PdCl2(cod) (29 mg, 0.1
mmol) and (R,R)-t-Bu-QuinoxP* (1) (33 mg, 0.1 mmol) in CH2Cl2
(14) Nemoto, T.; Masuda, T.; Akimoto, Y.; Fukuyama, T.; Hamada, Y.
Org. Lett. 2005, 7, 4447-4450.
Asymmetric allylic amination using (R,R)-t-Bu-QuinoxP*-
Pd catalyst was also applicable, affording optically active allylic
amines. When the reaction was carried out with morpholine as
nucleophile, N-(1,3-diphenyl-2-propenyl)morpholine (4h) was
obtained in 69% yield with 78% ee (Table 2, entry 9). Addition
of BSA significantly enhanced the reaction rate and the
(15) Byproducts were observed only in the reaction of 3-oxo-3-
arylpropionic acid ethyl esters having an electron-donating group on the
aromatic ring. We found that the byproducts were formed by the reaction
of produced alcohol 6 with EtOH in the presence of the t-Bu-QuinoxP*-
Ru complex under the same conditions as those for the hydrogenation.
Further, 6c also reacted with MeOH to give the 3-methoxy-3-(4′-methoxy-
phenyl)propionic acid ethyl ester. In the absence of hydrogen or Ru complex,
no reaction occurred between 6c and alcohol.
(12) (a) Steffen, W. L.; Palenik, G. J. Inorg. Chem. 1976, 15, 2432-
2439. (b) Ozawa, F.; Kubo, A.; Matsumoto, Y.; Hayashi, T. Organometallics
1993, 12, 4188-4196.
(13) It is known that C2-symmetric ligands are not so effective for Pd-
catalyzed asymmetric allylic substitution as expected from their wide range
of success in other catalytic asymmetric reactions; see ref 9.
(16) It is noted that hydrogenation product 6g (99.8% ee) is the key
intermediate for epinephrine. See: Singer, R. A.; Carreira, E. M. Tetra-
hedron Lett. 1997, 38, 927-930.
(17) It is noted that hydrogenation product 6i (99.2% ee) is the key
intermediate for carnitine. See: Kitamura, M.; Ohkuma, T.; Takaya, H.;
Noyori, R. Tetrahedron Lett. 1988, 29, 1555-1556.
7414 J. Org. Chem., Vol. 72, No. 19, 2007

TABLE 2. Asymmetric Allylic Alkylation and Amination of Racemic 1,3-Diphenyl-2-propenyl Acetate Catalyzed by (R,R)-t-Bu-QuinoxP*-Pd
Complexa
catalyst
loading
time
(h)
yieldb
(%)
eec (%)
entry
Nu-H
additive
temp
rt
rt
rt
rt
rt
rt
rt
(configd)
1
2
3
4
5
H2C(COOMe)2
HCCH3(COOMe)2
HC(n-Bu)(COOEt)2
HC(CH2Ph)(COOEt)2
HC(NHCHO)(COOEt)2
HC(NHAc)(COOEt)2
H2C(COMe)2
HCCH3(COOMe)2
morpholine
morpholine
KOAc + BSA
KOAc + BSA
KOAc + BSA
KOAc + BSA
KOAc + BSA
KOAc + BSA
KOAc + BSA
KOAc + BSA
-
BSA
BSA
BSA
BSA
1 mol % Pd
1 mol % Pd
1 mol % Pd
1 mol % Pd
1 mol % Pd
1 mol % Pd
1 mol % Pd
3 mol % Pd
2 mol % Pd
2 mol % Pd
2 mol % Pd
2 mol % Pd
4 mol % Pd
1
1
1
85 (4a)
97 (4b)
87 (4c)
93 (4d)
94 (4e)
83 (4f)
88 (4g)
92 (4b)
69 (4h)
94 (4h)
81 (4i)
92 (S)
95 (R)
92
90
91
91 (R)
95 (S)
98.7 (R)
78
89
90 (R)
73
48
26
27
1
20
13
13
20
63
48
6
7
8e
9
10
11
12
13f
-50 ˚C
rt
rt
rt
rt
rt
pyrrolidine
butylamine
cyclohexylamine
>99 (4j)
96 (4k)
89
a Reaction conditions: (allylic alkylation) 1,3-diphenyl-2-propenyl acetate (3)/malonate or acetylacetone/BSA/t-Bu-QuinoxP* (1)/[PdCl(η3-C3H5)]2/CH2Cl2
) 0.50 mmol/1.5 mmol/1.5 mmol/0.0055 mmol/0.0025 mmol/2.0 mL; 1 mol % of Pd; (allylic amination) 1,3-diphenyl-2-propenyl acetate (3)/amine/BSA/
t-Bu-QuinoxP* (1)/[PdCl(η3-C3H5)]2/CH2Cl2 ) 0.50 mmol/1.5 mmol/1.5 mmol/0.011 mmol/0.0050 mmol/2.0 mL; 2 mol % of Pd, unless otherwise stated.
b Isolated yield. c Chiral HPLC analysis. d Absolute configuration was determined by comparing chiral HPLC retention times with data in the literature.
e Reaction conditions: 1,3-diphenyl-2-propenyl acetate (3)/methyl malonate/BSA/t-Bu-QuinoxP* (1)/[PdCl(η3-C3H5)]2/CH2Cl2 ) 0.50 mmol/1.5 mmol/1.5
mmol/0.016 mmol/0.0075 mmol/2.0 mL; 3 mol % of Pd. f Reaction conditions: 1,3-diphenyl-2-propenyl acetate (3)/cyclohexylamine/BSA/t-Bu-QuinoxP*
(1)/[PdCl(η3-C3H5)]2/CH2Cl2 ) 0.50 mmol/1.5 mmol/1.5 mmol/0.021 mmol/0.010 mmol/1.0 mL; 4 mol % of Pd.
TABLE 3. Asymmetric Hydrogenation of Ketones Catalyzed by
CDCl3) δ 1.25 (d, J ) 16.8 Hz, 18H), 2.26 (d, J ) 11.9 Hz, 6H),
8.09 (dd, J ) 6.6, 3.6 Hz, 2H), 8.34 (dd, J ) 6.4, 3.7 Hz, 2H);
13C{1H} NMR (99.45 MHz, CDCl3) δ 6.23-6.55 (m), 27.89,
36.68-37.04 (m), 130.17, 133.58, 142.54 (t, J ) 4.1 Hz), 154.06
(t, J ) 56.6 Hz); 31P{1H} NMR (202.35 MHz, CDCl3) δ 56.27 (s);
(R,R)-t-Bu-QuinoxP*-Ru Complexa
[R]20 ) +24.8 (c 1.04, CHCl3); HRMS (FAB) calcd for C18H28-
D
ClN2P2Pd (M+ - Cl) 475.0455, found 475.0431.
H2 temp
(atm) (˚C)
yieldb
(%)
eec (%),
Typical Procedure for Pd-Catalyzed Asymmetric Allylic
Alkylation (Table 2, entry 1). A solution of [PdCl(η3-C3H5)]2 (0.9
mg, 2.5 µmol) and (R,R)-t-Bu-QuinoxP* (1) (1.8 mg, 5.5 µmol) in
CH2Cl2 (0.5 mL) was stirred for 10-30 min at room temperature.
Subsequently, to the solution was added a solution of 1,3-diphenyl-
2-propenyl acetate (126 mg, 0.50 mmol) in CH2Cl2 (1.5 mL),
dimethyl malonate (171 µL, 1.50 mmol), N,O-bis(trimethylsilyl)-
acetamide (367 µL, 1.50 mmol), and a pinch of AcOK. After being
stirred for 1 h at room temperature, the reaction mixture was diluted
with Et2O and quenched by addition of saturated NH4Cl solution.
The mixture was extracted with Et2O and washed with brine. The
organic phase was dried over Na2SO4 and concentrated under
vacuum. The obtained residue was purified by silica gel column
chromatography.
entry
R1
R2
(configd)
1
2
3
4
5
6
Ph
OEt
OEt
OEt
OEt
OEt
OEt
20
20
50
20
20
50
100
20
20
20
20
50
70
70
70
70
70
70
89 (6a) 99.3 (S)
94 (6b) 98.9 (S)
73 (6c)e 99.3 (S)
87 (6d) 99.5 (S)
4-MeC6H4
4-MeOC6H4
4-BrC6H4
4-ClC6H4
4-FC6H4
88 (6e)
93 (6f)
99.9 (S)
99.8
7f 3,4-dimethoxyphenyl OEt
82 (6g)e 99.8
8
9
Me
ClCH2
OMe
OEt
NMe2
t-Bu
OEt
50 >99 (6h)g 99.7 (R)
50
50
50
96 (6i)
99.2
10 Me
11 Me
12i Ph
94 (6j)h 97
93 (6k)h 99.0
50 (6a) 95 (S)
100 100
a Reaction conditions: ketone/t-Bu-QuinoxP* (1)/[RuCl2(η6-C6H6)]2/
EtOH/CH2Cl2 ) 0.67 mmol/0.015 mmol/0.0067 mmol/3.0 mL/1.0 mL; 2
mol % of Ru, unless otherwise stated. b Isolated yield. c Chiral HPLC or
GC analysis. d Absolute configuration was determined by comparing chiral
HPLC or GC retention times with data in the literature. e Racemic 3-ethoxy-
3-arylpropionic acid ethyl ester was produced as a byproduct. The low yield
can be attributed to the byproduct.15 f 16 h. g Conversion yield determined
by 1H NMR analysis. h NMR yield determined by using 1,4-bis(trimethyl-
silyl)benzene as an internal standard. i Reaction conditions: 3-oxo-3-
phenylpropionic acid ethyl ester/t-Bu-QuinoxP* (1)/[RuCl2 (η6-C6H6)]2/
EtOH/CH2Cl2 ) 6.0 mmol/0.00132 mmol/0.00060 mmol/3.0 mL/1.0 mL;
0.02 mol % of Ru, 48 h.
Typical Procedure for Pd-Catalyzed Asymmetric Allylic
Amination (Table 2, entry 10). A solution of [PdCl(η3-C3H5)]2
(1.8 mg, 5.0 µmol) and (R,R)-t-Bu-QuinoxP* (1) (3.7 mg, 11 µmol)
in CH2Cl2 (0.5 mL) was stirred for 10-30 min at room temperature.
Subsequently, to the solution was added a solution of 1,3-diphenyl-
2-propenyl acetate (126 mg, 0.50 mmol) in CH2Cl2 (1.5 mL),
morpholine (131 µL, 1.50 mmol), and N,O-bis(trimethylsilyl)-
acetamide (367 µL, 1.50 mmol). After stirring for 13 h at room
temperature, the reaction mixture was concentrated under reduced
pressure, and the obtained residue was purified by silica gel column
chromatography.
Typical Procedure for Ru-Catalyzed Asymmetric Hydrogen-
ation (Table 3, entry 1). (R,R)-t-Bu-QuinoxP* (1) (4.9 mg, 15
µmol) and [RuCl2(η6-C6H6)]2 (3.4 mg, 6.7 µmol) were dissolved
in anhydrous and degassed DMF (0.5 mL) under nitrogen. The
mixture was heated to 100 °C for 10 min. After the mixture was
cooled to 50 °C, the solvent was removed under vacuum to give
the catalyst as a red-purple solid. The catalyst was taken into a
(3 mL) was stirred for 30 min at room temperature. All the volatiles
were removed under reduced pressure. The yellow residue was
dissolved in a minimum amount of CH2Cl2 and recrystallized by
slow diffusion of pentane into the concentrated dichloromethane
solution at room temperature to afford yellow cubic crystals for
single-crystal X-ray analysis (88% yield): 1H NMR (395.75 MHz,
J. Org. Chem, Vol. 72, No. 19, 2007 7415

glovebox and dissolved in degassed ethanol (3 mL). To the solution
was added 3-oxo-3-phenylpropionic acid ethyl ester (129 mg, 0.67
mmol) dissolved in CH2Cl2 (1 mL), and the mixture was transferred
to a stainless steel autoclave. The autoclave was purged with
hydrogen four times, and the hydrogen pressure was raised to 20
atm. After being stirred at 50 °C for 24 h, the reaction mixture
was cooled to room temperature and the hydrogen was released.
The solvents were removed, and the residue was dissolved in Et2O.
The solution was washed with water and brine and dried over
Na2SO4. After evaporation of all the volatiles, the residue was
purified by silica gel column chromatography.
Acknowledgment. We gratefully acknowledge financial
support from the Ministry of Education, Culture, Sports, Science
and Technology, Japan. We also thank Nippon Chemical Co.,
Ltd. for financial support.
Supporting Information Available: Characterization of all
compounds and X-ray crystal structure files (.cif) for 2. This
material is available free of charge via the Internet at
http://pubs.acs.org.
JO071192K
7416 J. Org. Chem., Vol. 72, No. 19, 2007