4-substituted-phenyl(bisoxazoline)-rhodium complexes: Efficiency in the catalytic asymmetric reductive aldol reaction

Article abstract of DOI:10.1002/ejoc.200600722

Electronic effects of the substituents on the phenyl ring of the phenyl(bisoxazoline) ligand skeleton of rhodium catalysts was examined in the asymmetric reductive aldol reactions of acrylates and aldehydes. The electron-withdrawing NO₂ group o

Full text of DOI:10.1002/ejoc.200600722

FULL PAPER
DOI: 10.1002/ejoc.200600722
4-Substituted-Phenyl(bisoxazoline)-Rhodium Complexes: Efficiency in the
Catalytic Asymmetric Reductive Aldol Reaction
Takushi Shiomi,[a] Jun-ichi Ito,[a] Yoshihiko Yamamoto,[a] and Hisao Nishiyama*[a]
Keywords: Asymmetric catalysis / Aldol reactions / Oxazolines / Hydrosilanes / Rhodium
Electronic effects of the substituents on the phenyl ring of
the phenyl(bisoxazoline) ligand skeleton of rhodium catalysts
was examined in the asymmetric reductive aldol reactions
of acrylates and aldehydes. The electron-withdrawing NO2
group of Rh(4-NO2-Phebox-R)(OAc)2 showed an increase in
the enantioselectivity of the products in the reductive reac-
tion of methyl acrylate but not in the reactions of tert-butyl-
and trimethylsilyl acrylates. Theoretical calculations of the
corresponding model rhodium-Phebox complexes indicate
that the remote electron-withdrawing substituent slightly
shortens the Rh–Cphebox bond. Also, the Rh–C bonds of Rh(4-
NO2-Phebox-iPr)(OAc)2 and the corresponding Rh(4-H-Phe-
box-iPr)(OAc)2 were compared on the basis of X-ray analysis.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2006)
Introduction
In asymmetric catalysis, chiral ligands are inevitable
counterparts to metal atoms and aid to control the catalytic
activity and stereochemical interaction between substrates
and reagents. We have demonstrated remote electronic con-
trol in asymmetric catalysis and shown that the substituents
on the ligands that are situated far from the active metal
center can significantly influence the enantioselectivity and
the rate of the reaction.[1,2] We have shown that electron-
withdrawing groups enhance the reaction rate and induce
higher levels of enantioselectivity in the asymmetric hydro-
silylation of simple ketones catalyzed by Rh–Pyridine(bis-
oxazoline) (abbreviated Pybox) and the asymmetric cyclo-
propanation of olefins with Ru–Pybox. Similar remote elec-
tronic effects of ligand–substituents has been observed in
both asymmetric and nonasymmetric catalysis.[3–8]
Recently, we reported that chiral Rh–Phebox complexes
exhibited high performance in the asymmetric reductive al-
dol reaction of acrylates and aldehydes with hydrosilanes to
give high anti-selectivity and high enantioselectivity.[9] The
complexes also act as efficient catalysts for the asymmetric
conjugate reduction of unsaturated ketones and esters.[10,11]
We report here a remote substituent effect in the asymmet-
ric reductive aldol reaction with chiral Rh–Phebox catalysts
by using 4-substituted-phenyl(bisoxazoline) ligands.[12–14]
Results and Discussion
Synthesis of Ligands and Complexes
4-Substituted (X)-Phebox–iPr/H ligands 1a (X = NO2),
1c (X = Me), and 1d (X = MeO) were readily synthesized
in three steps by acid chloride formation of the correspond-
ing 4-substituted isophthalic acids in thionyl chloride, con-
densation with the appropriate β-amino alcohol, and oxaz-
oline formation with methanesulfonyl chloride and triethyl-
amine, according to the same procedure used for the prepa-
ration of prototype 1b (X = H) (Scheme 1). Heating of a
mixture of ligand 1 and RhCl3(H2O)3 in a methanol solu-
tion gave corresponding chloro complexes 3. The chloro
complexes could in turn be converted into acetato com-
plexes 5 in high yields by treatment with an excess amount
of silver acetate. 4-NO2-Phebox benzyl complex 6 was pre-
pared in the same sequence from ligand 2 and chloro com-
plex 4.
Structure Analysis
[a] Department of Applied Chemistry, Graduate School of Engi-
neering,
The molecular structure of 5a was analyzed by X-ray
crystallography and showed the C2 symmetric form (Fig-
ure 1). The 4-NO2-Phebox skeleton meridionally binds to
Nagoya University, Chikusa, Nagoya 464-8603, Japan
Fax: +81-52-789-3209
E-mail: hnishi@apchem.nagoya-u.ac.jp
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Rh(4-X-Phebox-R) Complexes in Asymmetric Reductive Aldol Reactions
FULL PAPER
Figure 1. Molecular structure of complex 5a. Selected bond lengths
[Å] and angles [°]: Rh1–C1 1.914(3), Rh1–N1 2.055(3), Rh1–N2
2.057(3), Rh1–O9 2.195(2); C1–Rh1–O9 174.38(12), N1–Rh1–N2
159.00(10), C1–Rh1–N1 79.72(12), C1–Rh1–N2 79.29(12).
thesized compounds 8 and 10, respectively (Tables 1 and
2).[15–19] Isocyanide complex 8 previously reported by us has
a Rh–Cphebox bond length of 1.941 Å, whereas the calcula-
tion gave a little longer length of 1.97 Å for that of model
7b.[11d,11f] However, the Rh–C2
(2.10 Å) and the C2–
isonitrile
N2 (1.150–1.168 Å) bond lengths of 7 are in good accord-
ance with those of real complex 8 (2.106 and 1.145 Å,
respectively). The NO2 electron-withdrawing group slightly
shortens the Rh–Cphebox bond (1.963 Å for 7a) so that the
bite angle N–Rh–N becomes wider when compared with
those of 7b and 7c (1.970 and 1.971 Å, respectively). This
inclination was also found for formaldehyde model com-
plexes 9a–c, 1.923 Å for 9a versus 1.932 Å for 9c compared
with 1.93 Å for acetone complex 10 previously reported by
us.[11d]
Scheme 1.
the rhodium atom with a Rh–C bond length of 1.914(3) Å
compared with 1.923 Å for that of 5b, whose structure was
previously reported.[10a] Thus, 4-NO2-Phebox rhodium
complex 5a has a slightly shorter Rh–C bond length, and
it has a wider N,N bite angle [159.00(10)°] compared with
that of 5b [158.36(7)°].
As for the natural charges, the electron-withdrawing
Theoretical Calculations
group influences the charges on C1 and N2 for the isocya-
Calculations were performed for model isocyanides 7a–c nide complexes and the charges on C1 and C2 for the form-
and model aldehyde complexes 9a–c to compare bond aldehyde complexes. As a consequence, the NO2 group de-
lengths, bond angles, and natural charges to those of syn- creases the electron density on the nitrogen atom of the iso-
Table 1. Selected bond lengths, bond angle, and natural charges for complexes 7a–c.
Complex
X
Bond length [Å]
Rh–Cl
Bond angle [°]
N–Rh–N
Natural charge
Rh–C1
Rh–N1
Rh–C2
C2–N2
Rh
C1
C2
N2
7a
7b
7c
NO2
H
OMe
1.963
1.970
1.971
2.100
2.090
2.100
2.410
2.420
2.420
2.100
2.110
2.100
1.150
1.168
1.150
156.5
156.3
155.9
0.615
0.615 0.023
0.616 –0.001
0.032
0.333
0.332
0.333
–0.417
–0.424
–0.425
Table 2. Selected bond lengths, bond angle, and natural charges for complexes 9a–c.
Complex
X
Bond length [Å]
Rh–C1 Rh–N1 Rh–Cl1 Rh–Cl2 Rh–O1
Bond angle [°]
N–Rh–N
Natural charge
C2–O1
Rh
C1
C2
O1
9a
9b
9c
NO2
H
OMe
1.923
1.931
1.932
2.090
2.090
2.090
2.390
2.390
2.390
2.410
2.420
2.420
2.350
2.370
2.370
1.210
1.210
1.210
158.7
158.5
158.0
0.721
0.719
0.719
0.098
0.090
0.066
0.269 –0.528
0.265 –0.526
0.264 –0.525
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T. Shiomi, J.-i. Ito, Y. Yamamoto, H. Nishiyama
FULL PAPER
cyanide skeleton and the carbon atom of the formaldehyde lyst 6. Therefore, the differences among the substituents at
functionality. In conclusion, it can be thought that the re- the 4-position is diminished.
mote substituents on the Phebox skeleton control the elec-
Table 3. Reductive aldol reaction of methyl acrylate and benzalde-
tronic state of the equatorial ligand through the rhodium
atom to influence the catalytic reactions to some extent.
hyde with Rh(Phebox) catalysts 5 and 6.[a]
Entry
Catalyst Yield of 11 [%] anti/syn % ee anti % ee syn
1
2
3
4
5
5a
5b
5c
5d
6
93
97
95
95
95
88:12
87:13
85:15
85:15
87:13
87
83
77
77
86
1
1
32
28
1
[a] Aldehyde (1.0 mmol), catalyst (0.01 mmol), methyl acrylate
(1.5 mmol), silane (1.6 mmol), toluene (2 mL), 50 °C, 0.5 h. Abso-
lute configuration, (2R,3S) for anti and (2S,3S) for syn.
Asymmetric Reductive Aldol Reactions
The asymmetric reductive coupling reaction of benzalde-
hyde and methyl acrylate was first examined with 4-substi-
tuted/isopropyl catalysts 5a–d, 4-nitro/benzyl catalyst 6
(1 mol-%), and (EtO)2MeSiH (1.6 equiv.) in a toluene solu-
tion heated at 50 °C (Scheme 2; Table 3). The reactions were
complete within 0.5 h in all cases to give the aldol products
in high yields (93–97%) with not much variance in the anti/
syn product ratios of 11. 4-Nitro/isopropyl catalyst 5a and
benzyl catalyst 6 gave higher ee’s, 87% and 86%, respec-
tively, compared with an ee of 77% for both 4-methyl cata-
lyst 5c and 4-methoxy catalyst 5d. Thus, a weak electronic
effect of the substituent at the 4-position of the phenyl ring
was observed.
Scheme 3.
Table 4. Reductive aldol reaction of tert-butyl acrylate, benzalde-
hyde, and 1-naphthaldehyde with Rh(Phebox) catalysts 5 and 6.[a]
Entry Catalyst
Aldehyde
Yield of 12,13 anti/syn % ee
% ee
syn
[%]
ratio
anti
1
2
3
4
5
5a
5b
5c
5d
6
PhCHO
PhCHO
PhCHO
PhCHO
PhCHO
1-NpCHO
1-NpCHO
1-NpCHO
1-NpCHO
1-NpCHO
82
93
94
90
90
92
97
99
94
99
96:4
95:5
95:5
94:6
94:6
98:2
97:3
97:3
96:4
98:2
93
92
92
92
94
95
95
95
95
98
10
10
12
17
17
31
20
24
14
8
6
7
8
9
5a
5b
5c
5d
6
10
[a] Aldehyde (1.0 mmol), catalyst (0.01 mmol), tert-butyl acrylate
(1.5 mmol), silane (1.6 mmol), toluene (2 mL), 50 °C, 0.5 h. Abso-
lute configuration for 12 (2R,3S) for anti and (2R,3R) for syn; for
13 not determined.
Trimethylsilyl acrylate was in turn employed because it
may be synthetically important to directly produce the cor-
responding aldol-carboxylic acid after facile hydrolysis un-
der acidic conditions. The reaction with benzaldehyde in the
presence of 4-nitro catalyst 5a afforded 14 with a slightly
Scheme 2.
Next, when the reaction of tert-butyl acrylate as a sub- lower anti/syn ratio of 82:18 and 81% ee (Scheme 4; Table 5,
strate and benzaldehyde as an acceptor was employed, all Entry 1) compared with an anti/syn ratio of 86:14 and 86%
of the catalysts exhibited high efficiency and the catalysis ee with catalyst 5b (Entry 2). However, the reaction of
proceeded at 50 °C within 0.5 h to again give almost the 1-naphthaldehyde with 5a afforded 15 with good stereose-
same anti/syn ratio of 94:6–96:4 and 92–94% ee for aldol lectivity: anti/syn ratio 87:13 and 96% ee (Entry 4). The
products 12 (Scheme 3; Table 4). In the case of 1-naph- electronic effect of the nitro group is not clear from these
thaldehyde, not significant, but a slight increase in the ratio examples, and it is probably slightly dependent on the sub-
and ee, 98:2 and 98%, respectively, for aldol product 13 strates. Benzyl catalyst 6 also gave higher anti/syn ratios
were observed as the highest limit with 4-nitro/benzyl cata- (Entries 3, 6).
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Rh(4-X-Phebox-R) Complexes in Asymmetric Reductive Aldol Reactions
FULL PAPER
isophthalic acid were purchased from Aldrich. For preparation of
1b, 3b, and 5b, see ref.[10a]
Synthesis of [(S,S)-4-NO2-Phebox-iPr]H (1a): A mixture of 5-nitro-
isophthalic acid (1.05 g, 5.00 mmol) and thionyl chloride (11 mL)
was heated at reflux for 48 h, and the excess thionyl chloride was
then removed under reduced pressure to give 5-nitroisophthaloyl
chloride, which was used in the next step without further purifica-
tion. A solution of the acid chloride in CH2Cl2 (20 mL) was slowly
added to a solution of -valinol (1.03 g, 10.0 mmol) and triethyl-
amine (10.5 mL) in CH2Cl2 (20 mL) at 0 °C. The mixture was
stirred at room temp. for 1 h. Methanesulfonyl chloride (0.85 mL,
11 mmol) was added at 0 °C, and the mixture was then stirred at
room temp. for 5 h. Formation of product 1a was monitored by
TLC examination. At 0 °C, aqueous potassium carbonate (1 , ca
30 mL) was added, and the mixture was extracted with ethyl ace-
tate. The organic layer was washed with saturated brine, dried with
magnesium sulfate, and concentrated. The crude product was puri-
fied by column chromatography on silica gel (ethyl acetate/hexane,
1:3) to give 1a as a colorless solid. Yield: 1.05 g (3.05 mmol), 61%.
Rf = 0.7 (ethyl acetate/hexane, 2:1. M.p. 66–68 °C. [α]2D8 = –97.9 (c
1.0, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 0.95 (d, J = 6.6 Hz,
6 H), 1.04 (d, J = 6.9 Hz, 6 H), 1.87 (m, 2 H), 4.17 (m, 4 H), 4.48
(m, 2 H), 8.82 (t, J = 1.5 Hz, 1 H), 8.86 (d, J = 1.5 Hz, 2 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 18.29, 18.91, 32.88, 70.83, 72.98,
Scheme 4.
Table 5. Reductive aldol reaction of trimethylsilyl acrylate, benzal-
dehyde, and 1-naphthaldehyde with Rh(Phebox) catalysts 5 and
6.[a]
Entry Catalyst Aldehyde Yield of 14,15 anti/syn
% ee
anti
% ee
syn
[%]
1
2
3
4
5
6
5a
5b
6
5a
5b
6
PhCHO
PhCHO
PhCHO
1-NpCHO
1-NpCHO
1-NpCHO
87
98
93
85
92
94
82:18
86:14
91:9
87:13
88:12
91:9
81
86
88
96
91
92
2
3
37
23
59
55
125.1, 129.9, 133.1, 148.0, 160.7 ppm. IR (KBr disk): ν = 1653,
˜
1348, 975 cm–1. C18H23N3O4 (345.39): calcd. C 62.59, H 6.71, N
12.17; found C 62.61, H 6.67, N 12.18.
[a] Aldehyde (1.0 mmol), catalyst (0.01 mmol), trimethylsilyl acry-
late (1.5 mmol), silane (1.6 mmol), toluene (3 mL), 50 °C, 0.5 h.
Absolute configuration for 14 (2R,3S) for anti and (2R,3R) for syn;
for 15 not determined.
[(S,S)-4-Me-Phebox-iPr]H (1c): Starting from 5-methylisophthalic
acid (900 mg, 5.00 mmol). Colorless oil. Yield: 1.28 g, 81%. [α]2D5
1
= –98.5 (c 1.0, CHCl3). H NMR (300 MHz, CDCl3): δ = 0.93 (d,
J = 6.6 Hz, 6 H), 1.03 (d, J = 6.9 Hz, 6 H), 1.86 (m, 2 H), 2.41 (s,
3 H), 4.12 (m, 4 H), 4.41 (m, 2 H), 7.90 (d, J = 0.9 Hz, 2 H), 8.27
(s, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 18.13, 19.02, 21.15,
70.11, 72.63, 125.2, 127.9, 131.4, 138.2, 162.8 ppm. IR (KBr disk):
Conclusions
We have demonstrated the synthesis of 4-substituted-
phenyl(bisoxazoline) ligands and their rhodium complexes
and have examined the catalytic asymmetric reductive aldol
reactions with acrylates and aldehydes. We have found that
4-nitro-substituted catalysts show a slight increase in the
anti/syn selectivity and enantioselectivity of the reaction
and they also provide the highest limits compared with
those of the prototype catalyst. These catalysts also clearly
gave higher efficiencies compared with those of the elec-
tron-donating group catalysts. Although we cannot clarify
whether the electron-withdrawing group enhances the aldol
reaction of the rhodium-enolate or the coordination of the
aldehyde, we think that the slightly shorter Rh–Cphebox
bond length, at least in some cases, may influence the tran-
sition state of the enantio-determining step of the reaction
to cause the increase in the enantioselectivity.
ν = 1652, 1234, 978 cm–1. C H N O (314.42): calcd. C 72.58, H
˜
19 26
2
2
8.33, N 8.91; found C 72.54, H 8.48, N 8.81.
[(S,S)-4-MeO-Phebox-iPr]H (1d): Starting from 5-methoxyiso-
phthalic acid (785 mg, 4.00 mmol). Colorless solid. Yield: 1.08 g,
81%. M.p. 75–76 °C. [α]2D7 = –105.7 (c 1.0, CHCl3). 1H NMR
(300 MHz, CDCl3): δ = 0.92 (d, J = 6.6 Hz, 6 H), 1.03 (d, J =
6.9 Hz, 6 H), 1.86 (m, 2 H), 3.87 (s, 3 H), 4.12 (m, 4 H), 4.40 (m,
2 H), 7.60 (d, J = 1.2 Hz, 2 H), 8.10 (t, J = 1.2 Hz, 1 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 18.15, 19.01, 55.74, 70.19, 72.68,
116.3, 120.5, 129.3, 159.2, 162.5 ppm. IR (KBr disk): ν = 1650,
˜
1595, 1375, 978 cm–1. C19H26N2O3 (330.42): calcd. C 69.06, H 7.93,
N 8.48; found C 68.98, H 8.06, N 8.43.
[(S,S)-4-NO2-Phebox-Bn]H (2): Starting from 5-nitroisophthalic
acid (1.05 g, 5.00 mmol) and -phenylalaninol (1.51 g, 10.0 mmol).
Colorless oil. Yield: 1.25 g, 56%. [α]2D8 = +6.1 (c 1.0, CHCl3). 1H
NMR (300 MHz, CDCl3): δ = 2.80 (dd, J = 5.7, 13.8 Hz, 2 H),
3.24 (dd, J = 5.1, 13.8 Hz, 2 H), 4.21 (dd, J = 7.8, 8.7 Hz, 2 H),
4.44 (dd, J = 8.7, 9.3 Hz, 2 H), 4.66 (m, 2 H), 7.22–7.35 (m, 10 H),
8.82 (t, J = 1.5 Hz, 1 H), 8.87 (d, J = 1.5 Hz, 2 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 41.60, 68.15, 72.46, 125.3, 126.6, 128.5,
Experimental Section
1
General: H- and 13C NMR spectra were obtained at 25 °C with a
129.1, 129.8, 133.2, 137.3, 148.1, 161.3 ppm. IR (KBr disk): ν =
˜
Varian Mercury 300 spectrometer. 1H NMR chemical shifts are
1654, 1539, 1346, 974 cm–1. C26H23N3O4 (441.48): calcd. C 70.73,
H 5.25, N 9.52; found C 70.67, H 5.28, N 9.55.
reported relative to the singlet at δ = 7.26 ppm for chloroform. 13
C
NMR spectra are reported relative to the triplet at δ = 77.0 ppm
for CDCl3 as an internal standard. Infrared spectra were recorded
with a JASCO FTIR-230 spectrometer. Absolute toluene and
(EtO)2MeSiH were purchased from TCI. Column chromatography
was performed with a silica gel column (Merck Silica gel 60). 5-
Nitroisophthalic acid, 5-methylisophthalic acid, and 5-methoxy-
Synthesis of [Rh{(S,S)-4-NO2-Phebox-iPr}(OAc)2]·H2O (5a):
RhCl3·3H2O (579 mg, 2.20 mmol), 1a (691 mg, 2.00 mmol), and so-
dium hydrogencarbonate (168 mg, 2.00 mmol) were placed in a 50-
mL flask. After addition of methanol (20 mL) and H2O (1 mL),
the mixture was stirred at 60 °C for 5 h. The concentrated residue
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T. Shiomi, J.-i. Ito, Y. Yamamoto, H. Nishiyama
FULL PAPER
was passed through a silica gel column with ethyl acetate/hexane
13C NMR (CDCl3): δ = 23.81, 39.81, 64.29, 75.85, 122.1, 127.0,
(2:1) as eluent to give 3a as a brown solid. Yield: 326 mg
128.8, 129.2, 132.3, 136.1, 145.1, 171.5, 182.4, 200.8 (d, JRh–C =
(0.61 mmol), 30%. M.p. 208 °C (dec). 1H NMR (300 MHz, 24.5 Hz) ppm. C30H30N3O9Rh (586.04): calcd. C 53.03, H 4.45, N
CDCl3): δ = 0.94 (d, J = 6.6 Hz, 6 H), 0.99 (d, J = 7.2 Hz, 6 H),
2.41 (m, 2 H), 4.22 (m, 2 H), 4.74–4.88 (m, 4 H), 8.47 (s, 2 H)
ppm. Complex 3a (268 mg, 0.50 mmol) and silver acetate (334 mg,
2.00 mmol) were placed in a 50-mL flask. After addition of CH2Cl2
(15 mL), the mixture was stirred at room temp. for 12 h. After fil-
tration and removal of the solvent under reduced pressure, the resi-
due was purified by column chromatography on silica gel with ethyl
acetate/methanol (10:1) to give 5a as a yellow solid. Yield: 220 mg
(0.38 mmol), 76%. M.p. 135 °C (dec). 1H NMR (300 MHz,
CDCl3): δ = 0.71 (d, J = 6.6 Hz, 6 H), 0.98 (d, J = 6.9 Hz, 6 H),
1.66 (s, 6 H), 2.27 (br., 2 H), 2.52 (m, 2 H), 4.45 (m, 2 H), 4.73–
4.86 (m, 4 H), 8.48 (s, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ
= 14.35, 19.15, 23.78, 29.30, 68.09, 71.65, 121.9, 132.1, 145.0, 171.0,
182.2, 200.8 (d, JRh–C = 24.5 Hz) ppm. C22H30N3O9Rh·(0.5EtOAc)
(627.45): calcd. C 45.94, H 5.46, N 6.70; found C 45.80, H 5.29, N
6.63.
6.18; found C 53.03, H 4.27, N 6.36.
X-ray Crystallographic Determination: Single-crystals suitable for
X-ray analysis were obtained by recrystallization from hexane/
dichloromethane/ethyl acetate at room temp.
mounted on a CryoLoop with Paratone-N, and diffraction data
were collected in θ ranges with graphite-monochromated Mo-Kα
radiation (λ = 0.71073 Å). An empirical absorption correction was
applied by using SADABS. The structure was solved by direct
methods and refined by full-matrix least-squares on F2 by using
SHELXTL. All non-hydrogen atoms except ethyl acetate were re-
fined with anisotropic displacement parameters. Refinement de-
A crystal was
tails: Empirical formula. C22H30N3O9Rh·0.3(C4H8O2); Mr
=
612.77; crystal system: hexagonal; space group: P61 (#169); a =
17.291(3), b = 17.291, c = 17.575(7) Å; V = 4551(2) Å3; Z = 6;
ρcalcd. = 1.342 Mgm–3; µ = 0.613 mm–1; F(000) = 1896; crystal size
= 0.50ϫ0.50ϫ0.20 mm; θ range = 2.69–27.60°; index ranges: –22
[Rh{(S,S)-4-Me-Phebox-iPr}(OAc)2]·H2O (5c): The preparation Յ h Յ 15, –21 Յ k Յ 22, –22 Յ l Յ 18; reflections collected: 31924;
procedure of 3c was similar to that of 3a with 1c (628 mg, independent reflections: 6540 [Rint = 0.0627]; completeness to θ
2.00 mmol). Brown solid. Yield: 760 mg (1.50 mmol), 75%. M.p.
157 °C (dec). 1H NMR (300 MHz, CDCl3): δ = 0.92 (d, J = 6.6 Hz, restraints/parameters: 6540/1/382; goodness-of-fit on F2: 1.065;
6 H), 0.97 (d, J = 7.2 Hz, 6 H), 2.40 (m, 2 H), 3.49 (s, 3 H), 4.26 Final R indices [IϾ2σ(I)]; R1 = 0.0315, wR2 = 0.0801; R indices
= 27.60°, 99.2%; max/min transmission: 1.000000/0.702050; data/
(m, 2 H), 4.65–4.79 (m, 4 H), 7.44 (s, 2 H) ppm. The preparation (all data): R1 = 0.0364, wR2 = 0.0838; absolute structure param-
procedure of 5c was similar to that of 5a with 3c (253 mg, eter –0.02(2); largest diff. peak/hole 0.724/–0.462 eÅ–3. CCDC-
0.5 mmol) and silver acetate (334 mg, 2 mmol). Yellow solid. Yield:
186 mg (0.34 mmol), 67%. M.p. 241 °C (dec). 1H NMR (300 MHz,
CDCl3): δ = 0.69 (d, J = 6.6 Hz, 6 H), 0.95 (d, J = 7.2 Hz, 6 H),
611476 contains the supplementary crystallographic data for this
paper. These data can be obtained free of charge from The Cam-
bridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
1.66 (s, 6 H), 2.51 (m, 2 H), 2.51 (s, 3 H), 3.54 (br., 2 H), 4.38 (m, data_request/cif.
2 H), 4.62–4.74 (m, 4 H), 7.44 (d, J = 3.0 Hz, 2 H) ppm. 13C NMR
Computational Methods: Geometry optimizations and atomic
(75 MHz, CDCl3): δ = 14.19, 19.23, 21.55, 24.00, 29.16, 67.65,
70.89, 128.2, 131.3, 133.0, 171.6, 182.1, 184.4 (d, JRh–C = 23.9 Hz)
ppm. C23H33N2O3Rh (552.42): calcd. C 50.01, H 6.02, N 5.07;
found C 49.85, H 5.82, N 4.84.
charge calculations for the optimized geometries were carried out
with the Gaussian 03 program package.[15] The geometries of com-
plexes 7a–c, 9a–c were fully optimized by means of the Becke’s
three-parameter hybrid density functional method (B3LYP)[16] with
the basis set, which uses a double-ζ basis set with the relativistic
[Rh{(S,S)-4-MeO-Phebox-iPr}(OAc)2]·H2O (5d): The preparation
procedure of 3d was similar to that of 3a with 1d (660 mg, effective core potential of Hay and Wadt (LanL2 ECP)[17] for Rh
2.00 mmol). Brown solid. Yield: 729 mg (1.40 mmol), 70%. M.p.
and the 6-31G(d)[18] basis sets for other elements. Natural charges
156 °C (dec). 1H NMR (300 MHz, CDCl3): δ = 0.93 (d, J = 6.9 Hz, were computed at the same level by using the natural population
6 H), 0.98 (d, J = 7.2 Hz, 6 H), 2.40 (m, 2 H), 3.87 (s, 3 H), 4.28
(m, 2 H), 4.65–4.80 (m, 4 H), 7.24 (s, 2 H) ppm. The preparation
procedure of 5d was similar to that of 5a with 3d (261 mg,
0.5 mmol) and silver acetate (334 mg, 2 mmol). Yellow solid. Yield:
analysis method as implemented in Gaussian 03.[19]
Typical Reactions, 11-anti/syn (Table 3, Entry 1): To a mixture of
rhodium complex 5a (5.8 mg, 0.010 mmol) and benzaldehyde
(106 mg, 1.00 mmol) in toluene (2.0 mL), methyl acrylate (129 mg,
135 µL, 1.50 mmol) was added at 50 °C. Diethoxymethylsilane
(215 mg, 1.60 mmol) was then slowly added by a syringe. The mix-
ture was stirred at 50 °C for 0.5 h. At 0 °C, ethanol (1 mL) was
added and the solvent was removed under reduced pressure. THF
(1 mL), MeOH (1 mL), and aq HCl (4 , 1 mL) were added and
the mixture was stirred for 30 min. A saturated aqueous solution
of sodium hydrogencarbonate (15 mL) was added and the mixture
was extracted with ethyl acetate (3ϫ5 mL). The combined organic
1
212 mg (0.37 mmol), 75%. M.p. 85 °C (dec). H NMR (300 MHz,
CDCl3): δ = 0.69 (d, J = 6.6 Hz, 6 H), 0.95 (d, J = 7.2 Hz, 6 H),
1.66 (s, 6 H), 2.51 (m, 2 H), 3.90 (s, 3 H), 4.39 (m, 2 H), 4.62–4.75
(m, 4 H), 7.25 (s, 2 H) ppm. 13C NMR (CDCl3): δ = 14.49, 19.20,
23.78, 29.34, 56.24, 71.11, 114.4, 131.3, 157.0, 171.5, 176.7 (d,
JRh–C = 24.3 Hz), 182.2 ppm. C23H33N2O8Rh·(0.2EtOAc) (586.04):
calcd. C 48.78, H 5.95, N 4.78; found C 48.66, H 6.01, N 4.71.
[Rh{(S,S)-4-NO2-Phebox-Bn}(OAc)2]·H2O (6): The preparation
procedure of 4 was similar to that of 3a with 2 (691 mg, layers were dried with MgSO4. After concentration, the residue was
2.00 mmol). Brown solid. Yield: 566 mg (0.90 mmol), 45%. M.p.
162 °C (dec). H NMR (300 MHz, CDCl3): δ = 2.82 (dd, J = 9.6,
purified by silica gel column chromatography with hexane/ethyl
acetate as an eluent to give the mixture of desired products 11-anti
and 11-syn in 93% (182 mg, 0.93 mmol). The anti/syn ratio was
determined by 1H NMR and found to be 88:12. The optical purity
was determined by HPLC analysis with DAICEL-CHIRALCEL
OD (eluent: hexane/iPrOH = 97:3, flow rate: 1.0 mL/min) and
found to be 87% ee (2R,3S) for anti; retention time: 13.1 (syn,
2R,3R), 15.8 (syn, 2S,3S), 20.2 (anti, 2R,3S), 37.1 min (anti, 2S,3R);
1
14.4 Hz, 2 H), 3.58 (dd, J = 4.80, 15.0 Hz, 2 H), 4.63 (m, 2 H),
4.67 (m, 2 H), 4.83 (m, 2 H), 7.22–7.38 (m, 10 H), 8.50 (s, 2 H)
ppm. The preparation procedure of 6 was similar to that of 5a with
4 (316 mg, 0.5 mmol) and silver acetate (334 mg, 2 mmol). Yellow
solid. Yield: 199 mg (0.29 mmol), 59%. M.p. 141 °C (dec). 1H
NMR (300 MHz, CDCl3): δ = 1.73 (s, 6 H), 2.66 (dd, J = 9.6,
14.1 Hz, 2 H), 3.68 (dd, J = 3.3, 13.8 Hz, 2 H), 4.68 (m, 2 H), 4.75 for HPLC analysis, see ref.[20] 11-anti: 1H NMR (300 MHz,
(m, 2 H), 4.79 (m, 2 H), 7.23–7.38 (m, 10 H), 8.51 (s, 2 H) ppm. CDCl3): δ = 1.02 (d, J = 7.2 Hz, 3 H), 2.82 (m, 1 H), 2.90 (d, J =
5598
www.eurjoc.org
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 5594–5600

Rh(4-X-Phebox-R) Complexes in Asymmetric Reductive Aldol Reactions
FULL PAPER
4.5 Hz, 1 H, OH), 3.73 (s, 3 H), 4.75 (dd, J = 8.4, 4.5 Hz, 1 H),
diazomethane for determination of the optical purity (HPLC)(elu-
7.26–7.41 (m, 5 H) ppm. 11-syn: 1H NMR (300 MHz, CDCl3): δ = ent: hexane/iPrOH, 97:3, flow rate: 1.0 mL/min): 96% ee for anti
1.13 (d, J = 6.9 Hz, 3 H), 3.68 (s, 3 H), 5.12 (d, J = 3.6 Hz, 1 H),
7.26–7.41 (m, 5 H) ppm. NMR spectra were consistent with the
authentic data previously reported in ref.[14a]
and 23% ee for syn. Retention time: 33.4 (syn, minor), 36.7 (syn,
major), 43.5 (anti, minor), 49.5 min. (anti, major). The absolute
configuration was not determined. 1H NMR (300 MHz, CDCl3):
15-anti: δ = 1.06 (d, J = 7.2 Hz, 3 H), 3.24 (dq, J = 7.2ϫ3 and
9.0 Hz, 1 H), 5.56 (d, J = 9.0 Hz, 1 H), 7.46–7.60 (m, 4 H), 7.84–
7.89 (m, 2 H), 8.27 (m, 1 H) ppm; 15-syn: δ = 1.11 (d, J = 7.2 Hz,
3 H, CH3), 6.10 (d, J = 2.1 Hz, 1 H, CHOH) ppm; Recrystallization
of the acid mixture from ether–hexane gave almost-pure acid 15-
12-anti/syn (Table 4, Entry 1): The reaction procedure was the same
as that of Entry 1, Table 1: tert-butyl acrylate (192 mg, 1.50 mmol).
1
A mixture of products 12-anti and 12-syn (96:4, determined by H
NMR) was obtained as a colorless oil. Yield: 195 mg (0.82 mmol),
82%. The optical purity was determined by HPLC analysis with
DAICEL-CHIRALPAK AS-H (eluent: hexane/iPrOH = 99:1, flow
rate: 1.0 mL/min) to be 93% ee (2R,3S) for anti and 10% ee
(2R,3R) for syn. Retention time: 8.9 (syn, 2R,3R), 11.4 (anti,
2S,3R), 13.4 (syn, 2S,3S), 15.1 min. (anti, 2R,3S). 12-anti: 1H NMR
(300 MHz, CDCl3): δ = 1.02 (d, J = 6.9 Hz, 3 H), 1.44 (s, 9 H),
2.67 (m, 1 H), 3.11 (br., 1 H), 4.70 (dd, J = 8.1, 4.8 Hz, 1 H), 6.91–
anti. M.p. 109–110 °C. IR (KBr disk): ν = 3500–2600 (br), 1720,
˜
1402, 1265 cm–1. 13C NMR (75 MHz, CDCl3): δ = 14.95, 46.90,
73.52, 123.4, 124.8, 125.6, 126.2, 128.7, 128.8, 130.9, 133.8, 136.5,
181.1 ppm. [α]2D3 = –13.1 (c 1.56, EtOH). C14H14O3 (230.26): calcd.
C 73.03, H 6.13; found C 72.93, H 6.12.
1
7.38 (m, 5 H) ppm. 12-syn: H NMR (300 MHz, CDCl3): δ = 1.10
Acknowledgments
(d, J = 7.2 Hz, 3 H), 1.40 (s, 9 H), 2.67 (m, 1 H), 3.11 (br., 1 H),
5.03 (dd, J = 4.2, 3.0 Hz, 1 H), 6.91–7.38 (m, 5 H) ppm. NMR
spectra were consistent with the authentic data previously reported
in ref.[9]
This work was supported by the Grant-in-Aid for Scientific Re-
search for the Japan Society for the Promotion of Science. T. S. is
supported by the Research Fellowship of the Japan Society for the
Promotion of Science.
13-anti/syn (Table 4, Entry 6): The reaction procedure was the same
as that of Entry 1, Table 1: tert-butyl acrylate (192 mg, 1.50 mmol)
and 1-naphthaldehyde (156 mg, 1.00 mmol). A mixture of products
13-anti and 13-syn (98:2, determined by 1H NMR) was obtained
as a colorless oil. Yield: 263 mg (0.92 mmol), 92%. The optical
purity was determined by HPLC analysis with DAICEL-CHI-
RALPAK AD (eluent: hexane/iPrOH = 99:1, flow rate: 2.0 mL/
min) to be 95% ee (2R,3S) for anti and 31% ee for syn. Retention
time: 11.9 (syn, major), 15.1 (syn, minor), 17.6 (anti, 2R,3S),
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24.3 min. (anti, 2S,3R). 13-anti: H NMR (300 MHz, CDCl3): δ =
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1 H) ppm. 13-syn: H NMR (300 MHz, CDCl3): δ = 1.14 (d, J =
7.2 Hz, 3 H), 1.50 (s, 9 H), 2.99 (dq, J = 7.2ϫ3 and 3.0 Hz, 1 H),
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14-anti/syn (Table 5, Entry 3): The reaction procedure was the same
as that of Entry 1, Table 1: trimethylsilyl acrylate (216 mg,
1.50 mmol) and 6 (6.8 mg, 0.010 mmol). After work up, the crude
product was purified by chromatography with ethyl acetate as an
eluent to give a mixture of desired products 14-anti and 14-syn
1
(91:9, determined by H NMR) as a colorless solid. Yield: 168 mg
(0.93 mmol), 93%. Some of the product was converted into methyl
ester 11 with trimethylsilyl diazomethane for determination of the
optical purity (HPLC): 88% ee (2R,3S) for anti and 37% ee
(2R,3R) for syn. 1H NMR (300 MHz, CDCl3): 14-anti: δ = 1.03 (d,
J = 7.5 Hz, 3 H), 2.86 (dq, J = 7.5ϫ3 and 9.0 Hz, 1 H), 4.77 (d,
J = 9.0 Hz, 1 H), 7.30–7.40 (m, 5 H) ppm. 14-syn: δ = 1.15 (d, J =
7.2 Hz, 3 H, CH3), 5.19 (d, J = 3.9 Hz, 1 H, CHOH) ppm. Mixture
of 14: C10H12O3 (180.20): calcd. C 66.65, H 6.77; found C 66.43,
H 6.76.
15-anti/syn (Table 5, Entry 4): The reaction procedure was the same
as that of Entry 1, Table 1: trimethylsilyl acrylate (216 mg,
1.50 mmol) and 1-naphthaldehyde (156 mg, 1.00 mmol). After
work up, the crude product was purified by chromatography with
ethyl acetate as an eluent to give a mixture of desired products 15-
anti and 15-syn (91:9 determined by 1H NMR) as a colorless solid.
Yield: 196 mg (0.85 mmol), 85%. Some of the product was con-
verted into the corresponding methyl ester with trimethylsilyl
Eur. J. Org. Chem. 2006, 5594–5600
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5599

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