Efficient preparation of new rhodium- and iridium-[bis(oxazolinyl)-3,5- dimethylphenyl] complexes by C-H bond activation: Applications in asymmetric synthesis

Article abstract of DOI:10.1002/adsc.200606049

The bis(oxazolinyl)-3,5-dimethylphenylrhodium and -iridium complexes were synthesized in high yields by an efficient C-H bond activation method with 4,6-dimethyl-1,3-bis(oxazolinyl)benzene derivatives. The catalytic activity of the complexes was examined

Full text of DOI:10.1002/adsc.200606049

FULL PAPERS
DOI: 10.1002/adsc.200606049
Efficient Preparation of New Rhodium- and Iridium-[Bis(oxazo-
À
linyl)-3,5-dimethylphenyl] Complexes by C H Bond Activation:
Applications in Asymmetric Synthesis
a
a
a,
Jun-ichi Ito, Takushi Shiomi, and Hisao Nishiyama *
a
Department of Applied Chemistry, Graduate School of Engineering, Nagoya University, Chikusa, Nagoya 464-8603, Japan
Fax : (+81)-52-789-3209; e-mail: hnishi@apchem.nagoya-u.ac.jp
Received: February 10, 2006; Accepted: May 8, 2006
Abstract: The bis(oxazolinyl)-3,5-dimethylphenylrho- and benzaldehyde. It was found that the rhodium
dium and -iridium complexes were synthesized in complex of 3,5-dmPhebox showed the higher catalyt-
high yields by an efficient CÀH bond activation ic activity, whereas the corresponding iridium com-
method with 4,6-dimethyl-1,3-bis(oxazolinyl)benzene plexes proved to be less active.
derivatives. The catalytic activity of the complexes
was examined for the asymmetric conjugate reduc-
tion of (E)-ethyl 3-phenylbut-2-enoate and the asym- Keywords: asymmetric catalysis; bisoxazoline; CÀH
metric reductive aldol reaction of tert-butyl acrylate bond activation; iridium; rhodium
Introduction
We have reported that bis(oxazolinylphenyl)rhodium
complexes, (Phebox)Rh, show highly efficient catalyt-
ic activity in the asymmetric conjugate reduction of
a,b-unsaturated carbonyl compounds and the asym-
metric reductive aldol reaction of acrylates and alde-
[
1,2]
hydes.
As a catalyst precursor (R-Phebox)RhCl2
A
C
H
T
R
E
U
N
G
(H O) was conveniently prepared by a CÀH bond ac-
2
tivation method with 1,3-bis(oxazolinyl)benzene, (R-
Phebox)H, and rhodium trichloride in methanol solu-
tion (Scheme 1). However, the yields of the desired
complexes turned out to be relatively low or around
middle range up to ca. 50%.[ In spite of efforts to
improve the efficiency by employing several modifica-
tions, such as addition of appropriate bases, choice of
solvents, and reaction temperature, etc., we could not
find any better solution. Although we also attempted
several transmetallation routes with (R-Phe-
1a]
Scheme 1.
[
3]
box)SnMe , the yields have not been improved. Hy-
3
pothetically, we thought that CÀH bond activation at lustrate the catalytic activity of the obtained 3,5-di-
the undesired 4- or 6-position of (R-Phebox)H might methyl-Phebox complexes.
decrease the yields. In this context, Richards et al. ob-
served a similar phenomenon of CÀH bond activation
at position 4 in the reaction of (Phebox)H and Pd- Results and Discussion
[
4]
A
C
H
T
R
E
U
N
G
(OAc) . Finally, we decided that two methyl groups
2
should be introduced into the benzene skeleton of Preparation of Ligands
Phebox, starting from the corresponding isophthalic
acid. This modification has been shown in some cases 3,5-Dimethyl-R-Phebox ligands 1a and 1b were readi-
in preparation of pincer complexes.[ In addition, we ly synthesized in three steps by chlorination of 4,6-di-
disclose here two asymmetric catalyses in order to il- methylisophthalic acid in thionyl chloride, condensa-
5]
Adv. Synth. Catal. 2006, 348, 1235 – 1240
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1235

Jun-ichi Ito et al.
FULL PAPERS
groups at the neighboring positions of the oxazoline
substitutents. The chloride complexes could, in turn,
be converted to the acetate complexes 4 and 5 by
treatment with an excess of silver acetate in high
yields (77–96%).
Structure Analysis
The molecular structures of 2b and 3b could be ana-
lyzed by X-ray crystallography to show their C2v sym-
metrical forms (Figure 1). Phebox skeletons meridia-
nally bind to the rhodium atom and the iridium atom
with an RhÀC bond length of 1.91 Š and an IrÀC
Scheme 2.
tion with b-amino alcohol, and oxazoline formation bond length of 1.93 Š, respectively. The bond angles
with methanesulfonyl chloride and triethylamine of NÀRhÀN and NÀIrÀN are 159.798 and 158.52, re-
(
Scheme 2).
spectively. The rhodium complex has thus slightly
shorter metalÀC bond and wider N,N bite angle com-
pared to the iridium complex.
Preparation of Complexes
Heating of a mixture of chiral ligand 1a or non-chiral Application to Asymmetric Catalysis
1
b, RhCl3
corresponding
ipPhebox)RhCl2
dmPhebox)RhCl2
Scheme 3). The yields were greatly improved, com- (E)-Ethyl 3-phenylbut-2-enoate (6) was selected as a
A
C
H
T
R
E
U
N
G
(H O) , and NaHCO in methanol gave the
2
3
3
chloride
complexes
(3,5-dm- Asymmetric Conjugate Reduction of a,b-Unsaturated
A
C
H
T
R
E
U
N
G
(H O) 2a (81%) and (3,5-dm- Ester
2
ACHTREUNG
(H O) 2b (84%), respectively
2
(
paring to that (56%) for (ipPhebox)RhCl (H O) pre- probe substrate (Scheme 4). The catalytic reduction
A
H
R
U
2 2
viously reported by us.[ In addition, although we of the ester 6 was carried out with 1 mol% of the
could not synthesize so far the corresponding iridium chiral acetate complexes 4a and 5a in combination
complex by the CÀH bond activation reaction with with diethoxymethylsilane (1.5 equivs.) in toluene so-
1]
(
ipPhebox)H and H IrCl (H O) , the iridium com- lution at 508C, respectively. The reaction with the
A
H
R
U
G
2
6 2 6
plexes 3a and 3b were fortunately obtained albeit in a rhodium complex 4a was complete within half an
middle range of 61% and 65%, respectively. Thus, hour. After hydrolysis, the reduction product 7 was
the CÀH bond activation at the desired position was obtained in 90% yield with 96% ee (R) (Table 1, run
realized efficiently by introduction of the two methyl 1). Thus, the rhodium catalyst 4a proved to be an
active catalyst and kept the enantioselectivity, com-
pared to that previously reported for the non-3,5-di-
[
1a]
methyl-substituted one; 96%, 96% ee (R).
On the
other hand, the iridium complex 5a was first exam-
ined but proved to show a slightly lower catalytic ac-
tivity compared to the rhodium one. The reaction
took a longer time at 508C to give the product 7 in
63–64% yield with 56–72% ee (runs 2 and 4).
Asymmetric Reductive Aldol Reaction
The asymmetric coupling reaction of benzaldehyde
and tert-butyl acrylate was then examined with 4a and
5
a (Scheme 5). The catalytic reaction was carried out
with 1 mol% of the chiral acetate complexes 4a and
a in combination with diethoxymethylsilane (1.6
5
equivs.) in toluene solution at 508C, respectively. The
rhodium complex 4a exhibited a high activity to give
the reductive aldol product 8 in 98% yield, 95:5 of
anti:syn, and 92% ee for 8anti (Table 2, run 1). Ethyl
Scheme 3.
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Adv. Synth. Catal. 2006, 348, 1235 – 1240

New Rhodium- and Iridium-[bis(oxazolinyl)-3,5-dimethyphenyl] Complexes
FULL PAPERS
Figure 1. X-ray analysis of the complex 2b and 3b. Selected bond lengths [Š] and angles [8]: 2b, RhÀC 1.913, RhÀO 2.234,
NÀRhÀN 159.79; 3b, IrÀC 1.930, IrÀO 2.243, NÀIrÀN 158.52.
Table 1. Asymmetric conjugate reduction of (E)-ethyl 3-phe-
[a]
nylbut-2-enoate with Rh- and Ir-(Phebox) catalysts.
Run Catalyst Temperature/Time [8C/ Yield of 7
%
ee
h]
[%]
1
2
3
4
4a
5a
5a
5a
50/0.5
50/6.0
reflux/6.0
50/10
90
64
33
63
96
56[
14
72
Scheme 4.
b]
[
c]
[
a]
Ester 6 (1.0 mmol), cat. (0.01 mmol), silane (1.5 mmol),
toluene (2.0 mL).
[
[
b]
c]
(
S).
Ester (1.0 mmol), cat. (0.02 mmol), silane (3.0 mmol), tol-
uene (2.0 mL).
acetate can also be used as a solvent rather than THF
(
runs 2 and 3). On the other hand, the iridium com-
plex 5a can also catalyze the reaction but gives a low
yield of 19% with a slightly lower stereoselectivity
(
run 5). An increase of the catalyst loading (2.5
mol%) and a higher temperature did not improved
the yield and selectivity (runs 6 and 7). It is worthy of Scheme 5.
[a]
Table 2. Asymmetric reductive aldol reaction of tert-butyl acrylate and benzaldehyde with (Phebox)-Rh and Ir catalysts.
Run
Catalyst
Temperature/Time [8C/h]
Yield of 8 [%]
ratio of anti:syn
% ee
anti
syn
1
4a
4a
4a
4b
5a
5a
5a
5b
50/0.5
50/0.5
50/0.5
50/0.5
50/6.0
50/2.0
90/1.0
50/2.0
98
74
99
94
19
23
48
56
95:5
89:11
95:5
96:4
93:7
93:7
91:9
96:4
92
88
91
-
89
90
89
-
7
9
8
-
16
8
4
-
[
[
b]
c]
2
3
4
5
6
7
8
[
d]
[
[
[
[
a]
b]
c]
d]
Benzaldehyde (1.0 mmol), cat. (0.01 mmol), tert-butyl acrylate (1.5 mmol), silane (1.6 mmol), toluene (3.0 mL).
THF (3.0 mL) as a solvent.
EtOAc (3.0 mL) as a solvent.
Benzaldehyde (0.2 mmol), cat. (0.01 mmol), tert-butyl acrylate (0.6 mmol), silane (0.62 mmol), toluene (2.0 mL).
Adv. Synth. Catal. 2006, 348, 1235 – 1240
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www.asc.wiley-vch.de
1237

Jun-ichi Ito et al.
FULL PAPERS
note that the non-chiral complexes 4b and 5b were
also employed as catalysts and showed a similar anti-
selectivity of 96:4, respectively.
JH,H =6.9 Hz, 6H), 1.02 (d, JH,H =6.6 Hz, 6H), 1.83 (m,
2
7
H), 2.59 (s, 6H), 4.03–4.15 (m, 4H), 4.26–4.38 (m, 2H),
13
1
.11 (s, 1H), 8.20 (s, 1H); C{ H} NMR (75 MHz, CDCl ):
3
d=18.3, 18.9, 21.7, 32.9, 69.2, 73.2, 124.7, 131.0, 134.0, 140.9,
1
1
8
62.8; IR (KBr): n=2961, 892, 1647, 1558, 1468, 1366,
À1
067 cm ; anal. calcd. for C H N O : C 73.14, H 8.59, N
2
0
28
2
2
Conclusions
.51; found: C 73.11, H 8.75, N 8.53.
4,6-dm-dmPhebox)H (1b): The preparation procedure of
b is similar to that of 1a. Yield: 1.23 g (4.11 mmol, 82%);
(
We have synthesized 3,5-dimethyl-substituted Phebox
derivatives and their rhodium and iridium complexes.
The structures were clarified by X-ray analysis. The
1
1
colorless solid; mp: 143–1448C. H NMR (300 MHz,
CDCl ): d=1.35 (s, 12H), 2.54 (s, 6H), 4.03 (s, 6H), 7.03 (s,
3
13
1
rhodium complexes were examined as catalysts for 1H), 8.13 (s, 1H); C{ H} NMR (75 MHz, CDCl ): d=
3
the asymmetric conjugate reduction and the asymmet- 21.36, 28.55, 67.94, 78.41, 125.0, 131.1, 133.8, 140.6, 161.8; IR
ric reductive aldol reaction and revealed high efficien- (KBr): n=2967, 2890, 1640, 1441, 1351, 1310, 1188, 1051,
À1
1
9
011 cm ; anal. calcd. for C H N O : C 71.97, H 8.05, N
cy and selectivity. In addition, the corresponding iridi-
um complexes were obtained, but the reactions result-
ed in a lower efficiency than the rhodium ones.
18 24
2
2
.33; found: C 71.93, H 8.14, N 9.34.
Synthesis of Rh and Ir Complexes
Experimental Section
(
3,5-dm-ipPhebox)RhCl2
1.10 mmol), 1a (328 mg, 1.00 mmol) and sodium bicarbonate
84 mg, 1.1 mmol) were placed in a 100 mL flask. After ad-
A
H
R
U
G
General Remarks
(
1H and C NMR spectra were obtained at 258C on a
13
dition of methanol (20 mL) and H2O (2 mL), the mixture
was stirred at 608C for 1 h. The concentrated residue was
passed through a silica gel column with ethyl acetate/hexane
(2:1) as eluent to give 2a as a brown solid; yield: 422 mg
(0.81 mmol, 81%); mp 3208C (dec). H NMR (300 MHz,
CDCl3): d =0.93 (d, JH,H =6.9 Hz, 6H), 0.95 (d, JH,H =
1
Varian Mercury 300 spectrometer. H NMR chemical shifts
are reported in d units, in ppm relative to the singlet at
1
3
7
.26 ppm for chloroform. C NMR spectra are reported in
terms of chemical shift (d, ppm) relative to the triplet at d=
7.0 ppm for CDCl as an internal standard. Infrared spectra
1
7
3
were recorded on a JASCO FT/IR-230 spectrometer. Abso-
lute toluene and hydrosilane were purchased from TCI.
Column chromatography was performed with a silica gel
column (Merck silica gel 60). 4,6-Dimethylisophthalic acid
was prepared by the reported method.[
6.9 Hz, 6H), 2.42 (m, 2H), 2.58 (s, 6H), 2.83 (br, 2H), 4.23
(m, 2H), 4.63–4.73 (m, 4H), 6.78 (s, 1H); C{ H} NMR
13
1
(75 MHz, CDCl ): d=15.26, 19.20, 19.58, 29.27, 66.50, 70.83,
3
127.5, 128.4, 141.2, 127.9, 128.1, 140.8, 171.4 (d, JRh,C
=
6]
3.5 Hz), 181.4 (d, JRh,C =24.5 Hz); IR (KBr): n=3455, 2954,
À1
1
614,
1485,
1385,
944 cm
;
anal.
calcd.
for
C H Cl N O Rh: C 46.26, H 5.63, N 5.39; found: C 46.08,
20
29
2
2
3
H 5.63, N 5.14.
3,5-dm-dmPhebox)RhCl2(H O) (2b): The preparation
2
Synthesis of Ligands
(
A
H
R
U
G
procedure of 2b was similar to that of 2a but a different
eluent (ethyl acetate/chloroform=2:1) was used for column
(
4,6-dm-ipPhebox)H (1a): To a suspension of 4,6-dimethyli-
sophthalic acid (971 mg, 5.0 mmol) in toluene (5 mL) was
slowly added thionyl chloride (3.0 mL). The mixture was re-
fluxed for 5 h and then excess thionyl chloride was removed
under reduced pressure to give 4,6-dimethylisophthaloyl
chloride, which was used in next step without further purifi-
cation.
chromatography. Yield: 413 mg, (0.84 mmol, 84%); brown
1
solid; mp 3398C (dec). H NMR (300 MHz, CDCl ): d=
3
1
6
2
3
1
.54 (s, 12H), 2.58 (s, 6H), 3.59 (br, 2H, H O), 4.48 (s, 4H),
2
1
3
1
.74 (s, 1H); C{ H} NMR (75 MHz, CDCl ): d=19.17,
3
7.64, 65.17, 82.05, 127.9, 128.1, 140.8, 169.9 (d, JRh,C
=
.4 Hz), 181.8 (d, JRh,C =23.9 Hz); IR (KBr): n=3408, 2977,
A solution of 4,6-dimethylisophthaloyl chloride in THF
10 mL) was slowly added to a solution of l-valinol (1.03 g,
0.0 mmol) and triethylamine (20 mL) in THF (30 mL) at
8C. The mixture was stirred at room temperature for 2 h.
À1
602, 1487, 1455, 1381, 954 cm
;
anal. calcd. for
(
1
0
C H Cl N O Rh·(H O): C 42.45, H 5.34, N 5.50; found: C
A
H
R
U
G
18 25
2
2
3
2
4
2.76, H 5.04, N 5.21.
(
3,5-dm-ipPhebox)IrCl2
A
H
R
U
G
(3a):
IrCl H ·6H O
6 2 2
Methanesulfonyl chloride (2.0 mL, 26 mmol) was added at
8C, and then the mixture was stirred at room temperature
2
0
(570 mg, 1.11 mmol), 1a (328 mg, 1.0 mmol) and sodium bi-
carbonate (277 mg, 3.30 mmol) were placed in a 100 mL
flask. After addition of 2-propanol (40 mL), the mixture was
refluxed for 10 h. The concentrated residue was purified by
column chromatography on silica gel with ethyl acetate/
hexane (2:1) as eluent to give 3a as a yellow solid; in yield:
for 14 h. Formation of the product 1a was monitored by
TLC examination; R =0.7 (ethyl acetate/hexane=3:1). At
0
added and the mixture was extracted with ethyl acetate. The
organic layer was washed with saturated brine, was dried
over magnesium sulfate, and was concentrated. The crude
product was purified by column chromatography on silica
gel (ethyl acetate/hexane 1:3) to give 1a as a colorless solid;
f
8C, aqueous potassium carbonate (1 N, ca. 50 mL) was
1
371 mg (0.61 mmol, 61%); mp 2048C (dec). H NMR
(300 MHz, CDCl3): d=0.95 (d, JH,H =6.6 Hz, 6H), 0.98 (d,
JH,H =6.9 Hz, 6H), 2.43 (m, 2H), 2.62 (s, 6H), 4.19 (m, 2H),
2
3
13
1
yield: 1.29 g (3.91 mmol, 78%); mp 38–398C; [a] : À155.1
4.73–4.86 (m, 4H), 6.63 (s, 1H); C{ H} NMR (75 MHz,
D
1
(
c 1.00, CHCl ). H NMR (300 MHz, CDCl ): d=0.93 (d,
CDCl ): d=15.34, 18.85, 19.58, 29.02, 67.10, 70.85, 125.8,
3
3
3
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New Rhodium- and Iridium-[bis(oxazolinyl)-3,5-dimethyphenyl] Complexes
FULL PAPERS
1
1
26.6, 140.9, 162.8, 176.9; IR (KBr): n=3361, 2921, 1603,
(3,5-dm-dmPhebox)Ir
(0.39 mmol, 77%); yellow solid; mp 2698C (dec). H NMR
A
H
T
E
U
(OAc)
ACHTREUNG
2
2
À1
1
485,
1384,
1332,
1218 cm
;
anal.
calcd.
for
C H Cl IrN O ·0.5
found: C 40.64, H 5.07, N 4.24.
(H O) (3b): The preparation pro-
A
H
R
U
G
(300 MHz, CDCl ): d=1.47 (s, 12H), 1.67 (s, 6 h), 2.67 (s,
20
29
2
2
3
4
8
2
3
1
3
1
6
H), 4.57 (s, 4H), 6.62 (s, 1H), 7.93 (br, 2H); C{ H} NMR
(
3,5-dm-dmPhebox)IrCl2
ACHTREUNG
2
(75 MHz, CDCl ): d=18.70, 23.51, 26.92, 65.20, 81.95, 126.1,
3
cedure of 3b was similar to that of 3a; Yield: 375 mg
0.65 mmol, 65%). Complex 3b was also obtained by the re-
action of IrCl ·3 H O (389 mg, 1.10 mmol) with 1b (300 mg,
1
1
26.8, 140.2, 170.3, 177.2, 182.9; IR (KBr): n=3372, 2929,
645, 1600, 1464, 1380, 1327, 1212, 1050, 954 cm ; anal.
(
À1
3
2
calcd. for C H IrN O : C 42.10, H 4.98, N 4.46; found: C
2
2
31
2
7
1
.00 mmol) in the presence of NaHCO (92 mg, 1.1 mmol);
3
4
1.85, H 4.79, N 4.12.
1
yield: 63%; yellow solid; mp 3568C (dec). H NMR
(
2
300 MHz, CDCl ): d=1.58 (s, 12H), 2.63 (s, 6H), 3.22 (br,
H, H O), 4.59 (s, 4H), 6.59 (s, 1H); C{ H} NMR
2
3
13
1
(
75 MHz, CDCl ): d=18.84, 27.87, 65.90, 82.02, 126.31,
26.33, 140.7, 161.4, 175.6; IR (KBr): n=3567, 2976, 2918,
3
X-ray Crystallographic Determination
1
1
9
3
605, 1544, 1487, 1455, 1400, 1382, 1336, 1217, 1057, 1022,
À1
Single crystals suitable for X-ray analysis were obtained by
recrystallization from dichloromethane/hexane at room tem-
perature. A crystal was mounted on a quartz fiber, and dif-
fraction data were collected in q ranges at 173 K with a
Bruker SMART APEX CCD diffractometer with graphite-
monochromated MoKa radiation (l=0.71073 Š). An empiri-
cal absorption correction was applied by using SADABS.
The structure was solved by direct method and refined by
55, 845 cm ; anal. calcd. for C H Cl IrN O (580.53): C
18
25
2
2
3
7.24, H 4.34, N 4.83; found: C 36.92, H 4.38, N 4.57.
3,5-dm-ipPhebox)Rh(OAc) (H O) (4a): The complex 3a
260 mg, 0.50 mmol) and silver acetate (334 mg, 2.00 mmol)
were placed in a 50 mL flask. After addition of CH Cl
(
A
H
R
U
G
ACHTREUNG
2
2
(
2
2
(
5 mL), the mixture was stirred at room temperature for
2
4 h. After removal of the solvent under reduced pressure,
the residue was purified by column chromatography on
silica gel with ethyl acetate/methanol (5:1) to give 4a as a
yellow solid; yield: 224 mg (0.40 mmol, 80%); mp 2258C
2
full-matrix least-square on F by using SHELXTL. All non-
hydrogen atoms were refined with anisotropic displacement
parameters.
1
(
dec). H NMR (300 MHz, CDCl ): d=0.66 (d, JH,H
=
3
6
.9 Hz, 6H), 0.92 (d, JH,H =7.2 Hz, 6H), 1.65 (s, 6H), 2.48
Refinement
details:
2b:
empirical
formula;
(
(
m, 2H), 2.58 (s, 6H), 4.31 (m, 2H), 4.58–4.67 (m, 4H), 5,99
C H Cl N O Rh·(H O); M = 509.23; temperature 173(2)
18
25
2
2
3
2
r
br, 2H), 6.78 (s, 1H); 13C{ H} NMR (75 MHz, CDCl ): d=
1
3
K; crystal system: orthorhombic; space group: Ibca; a =
1
1
1
1
6
4.15, 19.02, 19.22, 23.97, 28.97, 66.88, 70.48, 127.7, 128.3,
40.4, 172.3 (d, JRh,H =4.0 Hz), 182.0 (d, JRh,H =1.7 Hz),
90.2 (d, JRh,H =24.5 Hz); IR (KBr): n=3411, 2956, 2874,
605, 1483, 1383, 1324, 1245, 1223, 1073, 1020, 936,
8
Š
.5867(5), b = 16.7843(10), c = 29.3837(18) Š, V = 4234.8(4)
, Z = 8, 1calcd. = 1.597 Mg/m , m = 1.084 mm , F(000) =
3
3
À1
3
2
080, crystal size = 0.25 ” 0.15 ” 0.10 mm , q range = 1.39–
À1
27.488; index ranges: À11ꢀhꢀ10, À13ꢀkꢀ21, À33ꢀlꢀ38;
92 cm ; anal. calcd. for C H N O Rh: C 50.89, H 6.23,
24
35
2
7
reflections collected 14252, independent reflections 2434
N 4.95; found: C 50.36, H 6.23, N 4.75.
[
R(int) = 0.0478], completeness to q = 27.488,100.0%; max/
(
3,5-dm-dmPhebox)Rh(OAc) (H O) (4b): Yield: 221 mg
A
H
R
U
G
ACHTREUNG
2
2
1
min transmission 1.000000/0.754755; data/restraints/parame-
(
(
6
0.41 mmol, 82%); yellow solid; mp 2908C (dec). H NMR
300 MHz, CDCl ): d=1.45 (s, 12H), 1.68 (s, 6H), 2.61 (s,
2
ters 2434/0/136; goodness-of-fit on F 0.983; final R indices
3
1
3
1
[I>2s(I)]: R1 = 0.0284, wR2 = 0.0688; R indices (all data): R1
H), 4.48 (s, 4H), 4.97 (br, 2H, H2O), 6.77 (s, 1H); C{ H}
NMR (75 MHz, CDCl ): d=19.12, 23.73, 27.07, 64.69, 82.13,
= 0.0379, wR2 = 0.0738; largest diff. peak/hole 0.953/À0.722
3
À3
1
2
1
27.9, 128.2, 140.5, 171.1 (JRh,C =4.0 Hz), 189.7 (JRh,C
=
e·Š ; 3b: empirical formula; C18H25Cl2IrN2O3·(H2O); Mr =
5.1 Hz); IR (KBr): n=3395, 2971, 2925, 1599, 1483, 1456,
598.52; temperature 173(2) K; crystal system: monoclinic;
À1
380, 1324, 1252, 1213, 1051, 1016, 950 cm ; anal. calcd. for
space group: P2 /n; a = 8.8453(5), b = 8.4164(4), c =
1
3
C H N O Rh: C 49.08, H 5.80, N 5.20; found: C 49.13, H
27.7472(14) Š, b = 90.8520(10)8, V = 2065.43(18) Š , Z = 4,
22
31
2
7
3
À1
5
.72, N 5.23.
3,5-dm-ipPhebox)Ir
304 mg, 0.50 mmol) and silver acetate (501 mg, 3.00 mmol)
were placed in a 50 mL flask. After addition of THF
10 mL), the mixture was stirred at 608C for 12 h. After re-
1
calcd.
= 1.925 Mg/m , m = 6.749 mm , F(000) = 1168, crystal
3
(
A
H
R
U
G
A
H
R
U
size = 0.40 ” 0.30 ” 0.20 mm , q range = 1.47À27.528; Index
ranges: À9ꢀhꢀ11, À9ꢀkꢀ10, À36ꢀlꢀ36; reflections collect-
ed 14172, independent reflections 4750 [R(int) = 0.0911],
(
(
o
completeness to q = 27.52 , 99.9%; max/min transmission
moval of the solvent under reduced pressure, the residue
was purified by column chromatography on silica gel with
ethyl acetate/methanol (10:1) to give 5a as a yellow solid;
1
.000000/0.613727; data/restraints/parameters 4750/1/258;
2
goodness-of-fit on F 1.068; final R indices [I>2s(I)]: R1 =
1
0.0286, wR2 = 0.0693; R indices (all data): R1 = 0.0308,
yield: 315 mg (0.48 mmol, 96%); mp: 2168C (dec). H NMR
À3
wR2 = 0.0723; largest diff. peak/hole 1.805/À1.548 e·Š
.
(
300 MHz, CDCl ): d=0.71 (d, J
=6.6 Hz, 6H), 0.95 (d,
3
H,H
Crystallographic data (excluding structure factors) for the
structures reported in this paper have been deposited with
the Cambridge Crystallographic Data Centre as supplemen-
tary publication no. CCDC-297744 for 2b and CCDC-
JH,H =7.2 Hz, 6H), 1.68 (s, 6H), 2.52 (m, 2H), 2.65 (s, 6H),
4
.28 (m, 2H), 4.68–4.79 (m, 4H), 6.63 (s, 1H), 6.72 (br, 2H);
1
3
1
C{ H} NMR (75 MHz, CDCl ): d=14.20, 18.68, 19.30,
3
2
1
1
3.20, 28.89, 67.60, 70.54, 126.1, 126.5, 140.3, 171.3, 178.3,
2
97745 for 3b. Copies of the data can be obtained free of
83.1; IR (KBr): n=3435, 2958, 2931, 2874, 1605, 1483,
À1
384, 1325, 1244, 1223, 1074, 1019, 934, 691 cm ; anal.
charge on application to CCDC, 12 Union Road, Cambridge
CB2 1EZ, UK [fax.: (internat.) +44–1223/336–033; e-mail:
deposit@ccdc.cam.ac.uk].
calcd. for C H IrN O : C 43.96, H 5.38, N 4.27; found: C
24
35
2
7
43.85, H 5.32, N 4.10.
Adv. Synth. Catal. 2006, 348, 1235 – 1240
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.asc.wiley-vch.de
1239

Jun-ichi Ito et al.
FULL PAPERS
Conjugate Reduction of a,b-Unsaturated esters
2S,3R), 13.4 min (syn, 2S,3S), 15.1 min (anti, 2R,3S). The
NMR spectra were consistent with previously reported data;
see Supporting Information of ref.[
(
Table 1, run 1)
2]
To a mixture of the ester 6 (190 mg, 1.0 mmol) and the cata-
lyst 4a (5.4 mg, 0.01 mmol) in 2.0 mL of toluene was slowly
added diethoxymethylsilane (201 mg, 1.5 mmol) at 508C.
The mixture was stirred for 0.5 h and then treated with hy-
drochloric acid (1 N, 1 mL). After extraction with ethyl ace-
tate and concentration, the residue was purified by silica gel
column chromatography with ethyl acetate/hexane to give
the product, ethyl (R)-3-phenylbutanoate (7) as a colorless
oil; yield: 173 mg (0.90 mmol, 90%). The ee was determined
Acknowledgements
H.N. gratefully acknowledges financial supports from the
Ministry of Education, Culture, Sports, Science and Technol-
ogy, Japan (Reaction Control of Dynamic Complexes, No.
4
20) and DAIKO Foundation.
by chiral HPLC analysis [DAICEL CHRALCEL OB
À1
column, 0.5 mLmin , i-PrOH/hexane (1:99), R =14.1 min
t
References
(
major), 16.8 min (minor)], 96% ee for R. The NMR spectra
were consistent with previously reported data; see ref.
[1a]
[
1] a) Y. Kanazawa, Y. Tsuchiya, K. Kobayashi, T. Shiomi, J.
Itoh, M. Kikuchi, Y. Yamamoto, H. Nishiyama, Chem.
Eur. J. 2006, 12, 63; b) Y. Tsuchiya, Y. Kanazawa, T.
Shiomi, K. Kobayashi, H. Nishiyama, Synlett 2004, 2493.
2] H. Nishiyama, T. Shiomi, Y. Tsuchiya, I. Matsuda, J.
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[3] Y. Motoyama, M. Okano, H. Narusawa, N. Makihara, K.
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[4] a) J. S. Fossey, C. J. Richards, Organometallics 2004, 23,
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21, 5259; c) D. J. Cµrdenas, A. M. Echavarren, M. C. R.
de Arellano, Organometallics 1999, 18, 3337.
[5] For NCN pincer, see: M. Gerisch, J. R. Krumper, R. G.
Bergman, T. D. Tilley, J. Am. Chem. Soc. 2001, 123,
5818; for PCP pincer, see: B. Rybtchinski, D. Milstein, J.
Am. Chem. Soc. 1999, 121, 4528; for reviews, see: M. E.
van der Boom, D. Milstein, Chem. Rev. 2003, 103, 1759;
M. Albrecht, G. van Koten, Angew. Chem. Int. Ed. 2001,
40, 3750.
[6] a) A. Schrçder, D. Karbach, R. Gꢁther, F. Vçgtle,
Chem. Ber. 1992, 125, 1881; b) A. W. van der Made,
R. H. van der Made, J. Org. Chem. 1993, 58, 1262; c) M.
Gerisch, J. R. Krumper, R. G. Bergman, T. D. Tilley, Or-
ganometallics 2003, 22, 47.
Reductive Aldol Reaction (Table 2, run 1)
[
To
.01 mmol) and benzaldehyde (106 mg, 1.0 mmol) in toluene
3.0 mL), tert-butyl acrylate (192 mg, 1.5 mmol) was added
a mixture of the rhodium complex 4a (5.7 mg,
0
(
at 508C. Then, diethoxymethylsilane (215 mg, 1.6 mmol) was
slowly added by a syringe. The mixture was stirred at 508C
for 0.5 h. At 08C, the reaction was quenched by addition of
aqueous HCl (4 N, 1 mL), MeOH (1 mL), and THF (1 mL).
After stirring for 30 min, the mixture was extracted with
ethyl acetate (3”5 mL). The combined organic layer was
washed with aqueous NaHCO (2”10 mL), and was dried
3
over MgSO . After concentration, the residue was purified
4
by silica gel column chromatography with hexane-ethyl ace-
tate (20:1) as an eluent to give a mixture of the desired
products 8anti and 8syn; yield: 231 mg (0.98 mmol, 98%).
1
The anti:syn ratio was determined by H NMR to be 95:5.
The optical purity wad determined by HPLC analysis with
DAICEL-CHIRALPAK AS-H (eluent: hexane/i-PrOH=
À1
9
9:1, flow rate: 1.0 mLmin ) to be 92% ee (2R,3S) for
anti; retention time: 8.9 min (syn, 2R,3R), 11.4 min (anti,
1240
www.asc.wiley-vch.de
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2006, 348, 1235 – 1240