Preparation of (2,3-dihydrobenzofuran-3-yl)acetic acid via Rh-catalyzed asymmetric hydrogenation

Article abstract of DOI:10.1246/bcsj.20130324

A preparation via Rh-catalyzed asymmetric hydrogenation has been developed for (2,3-dihydrobenzofuran-3-yl)-acetic acid derivatives, a key intermediate in the synthesis of the active pharmaceutical ingredient for GPR40 agonist, fasiglifam. Use of a cationic rhodium-Et-FerroTANE complex yielded the desired product in high enantiomeric excess (91%) and quantitative yield, and was thus recommended for further process development.

Full text of DOI:10.1246/bcsj.20130324

© 2014 The Chemical Society of Japan
Bull. Chem. Soc. Jpn. Vol. 87, No. 4, 539-543 (2014)
539
Preparation of (2,3-Dihydrobenzofuran-3-yl)acetic Acid
via Rh-Catalyzed Asymmetric Hydrogenation
Masayuki Yamashita,*1 Nobuyuki Negoro,2 Tsuneo Yasuma,1 and Toru Yamano3
1Chemical Development Laboratories, CMC Center, Takeda Pharmaceutical Company Limited,
2-17-85 Juso-honmachi, Yodogawa-ku, Osaka 532-8686
2Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited,
26-1 Muraoka-Higashi 2-chome, Fujisawa, Kanagawa 251-8555
3Environment and Safety Department, Takeda Pharmaceutical Company Limited,
2-17-85 Juso-honmachi, Yodogawa-ku, Osaka 532-8686
Received November 21, 2013; E-mail: masayuki.yamashita@takeda.com
A preparation via Rh-catalyzed asymmetric hydrogenation has been developed for (2,3-dihydrobenzofuran-3-yl)-
acetic acid derivatives, a key intermediate in the synthesis of the active pharmaceutical ingredient for GPR40 agonist,
fasiglifam. Use of a cationic rhodium-Et-FerroTANE complex yielded the desired product in high enantiomeric excess
(91%) and quantitative yield, and was thus recommended for further process development.
Optically active 2,3-dihydrobenzofuran derivatives are key
scaffolds for a variety of active pharmaceutical ingredients such
as selective kappa opioid receptor agonists,1a subtype selective
PPARα agonists,1b selective cannabinoid receptor 2 agonists,1c
as well as natural products such as (+)-myrtopsine,1d and endo-
phytic fungus Xylaria sp.1e GPR40 agonist fasiglifam, [(3S)-
6-({2¤,6¤-dimethyl-4¤-[3-(methylsulfonyl)propoxy]biphenyl-
3-yl}methoxy)-2,3-dihydrobenzofuran-3-yl]acetic acid hemi-
hydrate (Figure 1), a candidate as a novel antidiabetic agent,2
was also built around this scaffold.
Various synthetic methods, such as asymmetric epoxidation,
asymmetric dihydroxylation, chiral pool synthesis, and optical
resolution, have been developed to obtain optically active 2,3-
dihydrobenzofuran derivatives.1,2 Although asymmetric hydro-
genation is a straightforward approach to obtain optically active
hydrogenated heterocycles, including 2,3-dihydrobenzofuran
derivatives, the harsh reaction conditions required make suc-
cessful reactions rare.3 We envisioned that recent advancements
in ligand designs might enable us to overcome the issues of
reactivity and enantioselectivity.
A great deal of effort has been devoted to developing effi-
cient and potent chiral ligands for use in asymmetric hydro-
genation.4 We previously reported asymmetric hydrogenation
of allylamines with complexes prepared from rhodium and
ferrocene-based diphosphines, demonstrating that selection of a
suitable catalyst can pave the way for achieving high reactivity
and enantioselectivity.5 The lesson has encouraged us to inves-
tigate the asymmetric hydrogenation of benzofuran derivatives
1a and 1b, considered to be challenging.3 In general, olefins
carrying an ester moiety are considered advantageous in asym-
metric hydrogenation due to the anchoring ability, solubility,
and stability provided by the ester functionality; this led us to
choose compound 1a as a promising candidate substrate.4i
We evaluated various chiral rhodium precatalysts, which
were prepared in situ from 1 mol % each of [Rh(cod)2]OTf and
ferrocene-based phosphine ligands in MeOH at room temper-
ature. In preliminary trials using ligands 3a-3c and 3k-3q,6,7
hydrogenation of compound 1a gave poor to moderate
enantioselectivities and/or chemical yields (Table 1).
These findings showed that compound 1a is not a promising
substrate for asymmetric hydrogenation under these conditions.
Thus, we concentrated our efforts on developing an asym-
metric hydrogenation of the corresponding carboxylic acid 1b.
In the asymmetric hydrogenation of compound 1b, the same
reaction conditions were employed, but with the addition of
a base such as sodium methoxide (Table 2), referring to the
literature.8
We describe herein an efficient asymmetric hydrogenation of
(6-hydroxybenzofuran-3-yl)acetic acid, according to a strategy
comprising substrate, chiral ligand, and additive selection. The
strategy is expected to be utilized for the synthesis of other
substituted 2,3-dihydrobenzofuran derivatives.
Me
As shown in Table 2, most ligands gave good to excellent
chemical yields. Josiphos ligands carrying electron-rich and
bulky substituents (R2 = t-Bu) yielded good overall outcomes
for compound 1b (Table 2, Entries 4 and 10). The effect of
the electronic properties of the R1 groups on the resulting
enantioselectivities seems to be limited (Table 2, Entries 4 vs.
O
O
Me
S
O
Me
O
O
0.5 H2O
CO2H
Figure 1. Structure of fasiglifam.
Published on the web February 4, 2014; doi:10.1246/bcsj.20130324

540
Bull. Chem. Soc. Jpn. Vol. 87, No. 4 (2014)
Rh-Catalyzed Asymmetric Hydrogenation
Table 1. Asymmetric Hydrogenation of Compound 1a with
Josiphos, Et-FerroTANE, BoPhoz, DUPHOS, and BPEa)
Table 2. Asymmetric Hydrogenation of Compound 1b with
Josiphos, Et-FerroTANE, BoPhoz, DUPHOS, and BPEa)
HO
HO
HO
HO
O
O
O
O
*
[Rh(cod)2]OTf, ligand 3 (s/c=100)
[Rh(cod)2]OTf, ligand 3 (s/c=100)
H2(0.7 MPa), methanol, rt, 2h
*
H2(0.7 MPa), NaOMe, methanol, rt, 2h
CO2Me
CO2Me
CO2H
CO2H
1b
2b
1a
2a
ee/%b)
Yield/%b)
Entry
Ligand
ee/%b)
Yield/%b)
Entry
Ligand
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
6
8
2
95
92
81
90
27
93
23
66
95
91
88
65
95
95
99
98
98
1
2
3
4
5
6
7
8
9
3a
3b
3c
3k
3l
3m
3n
3o
3p
3q
0
27
6
4
19
0
30
0
48
43
68
90
50
68
66
75
31
46
42
52
79
36
27
58
41
35
81
91
15
75
67
62
59
46
10
a) Structure of ligands are shown in Table 2. Reaction con-
ducted on 0.25 mmol scale at room temperature under 0.7 MPa
of H2. b) Determined by HPLC analysis using CHIRALPAK
AS-H column.
10); however, their steric properties may have a considerable
influence (Table 2, Entries 4 vs. 8).
a) Reaction conducted on 0.25 mmol scale at room temperature
under 0.7 MPa of H2, using NaOMe (0.5 equiv to 1b). b) Deter-
mined by HPLC analysis using CHIRALPAK AD-H column.
Et-FerroTANE, ligand 3k, gave the best combination of
good enantioselectivity and chemical yield (Table 2, Entry 11).
To the best of our knowledge, this is the first asymmetric
hydrogenation of substituted (benzofuran-3-yl)acetic acid 1b
using Rh-Et-FerroTANE catalyst under low hydrogen pressure
(less than 1 MPa).9 The proximity of a chirogenic center to
phosphorus in Et-FerroTANE could be beneficial to the
achievement of high enantioselectivitiy. DUPHOS and BPE
gave moderate enantioselectivities, as shown in Table 2 (Entries
13-17). This finding clearly indicates a particular utility for
Et-FerroTANE yielding a favorable outcome for this reaction.
It has been reported that a phenolic hydroxy group of a sub-
strate was essential to obtain a good enantioselectivity in some
asymmetric hydrogenations.10 To clarify the role of the hydroxy
group in this case, the 6-hydroxy group in compound 1a and 1b
was replaced with a 6-methoxy group (Table 3 and Table 4).
Hydrogenation of compound 1c, the analogue of com-
pound 1a, gave the same enantioselectivity compared with 1a
(Table 1, Entries 5, 8, 9 vs. Table 3). Furthermore, the same
tendency was obtained by the asymmetric hydrogenation of
compound 1d, the analogue of compound 1b (Table 2 vs.
Table 4). The replacement of the 6-hydroxy group by the 6-
methoxy group did not affect the nature of the reaction. This
finding suggests that the 6-hydroxy group may be situated
outside the coordination sphere of the Rh-Et-FerroTANE 1b
complex and not affect the asymmetric hydrogenation.
3a R1 = Ph, R2 = c-hexyl
3b R1 = c-hexyl, R2 = c-hexyl
3c R1 = Ph, R2 = 3,5-xylyl
P(R2
P(R1)2
)
3d
3e
3f
R
R
R
1 = Ph, R2 = t-Bu
2
1 = 3,5-xylyl, R2 = c-hexyl
1 = 4-MeO-3,5-xylyl, R2 = 3,5-xylyl
Fe
Josiphos
3g R1 = 3,5-(CF3)2C6H3, R2 = 3,5-xylyl
3h R1 = c-hexyl, R2 = t-Bu
R1 = t-Bu, R2 = 3,5-xylyl
3i
3j
R1 = 4-CF3C6H4, R2 = t-Bu
P
PPh2
N
Fe
3l BoPhoz
3k Et-FerroTANE
PPh2
Fe
P
R3
R4
R4
P
3p Me-BPE R4=Me
3q Et-BPE R4=Et
3m Me-DuPHOS R3=Me
3n Et-DuPHOS R3=Et
3o iPr-DuPHOS R3=iPr
P
P
R3
R3
P
R4
R4
R3
sodium methoxide (0.1 to 0.5 equiv) (Table 5, Entries 1, 2, and
3). Additional investigation may be needed to clarify the role of
base in this reaction.
The robustness of this reaction was successfully confirmed
by the preparation of 2b on an approximately 25 g-scale reac-
tion (Table 5, Entry 3, see Experimental).
Further investigation has revealed that the asymmetric
hydrogenation of (benzofuran-3-yl)acetic acid 1b using Rh-
Et-FerroTANE is a suitable method to synthesize fasiglifam in
a large scale (Scheme 1).2
In conclusion, we have accomplished the asymmetric hydro-
genation of (6-hydroxybenzofuran-3-yl)acetic acid 1b using
Rh-Et-FerroTANE in quantitative yield and good enantio-
It has been reported that sodium carboxylate is superior to
carboxylic acid as a substrate for Rh-catalyzed asymmetric
hydrogenations.8 In our study, the corresponding sodium car-
boxylate enhances reactivity as expected.
The tolerance toward base may indicate that both the counter
cation and the nucleophilicity of the carboxylate group have
little effect on reactivity and selectivity (Table 5). The reaction
proceeded smoothly, even in the presence of substoichiometric

M. Yamashita et al.
Bull. Chem. Soc. Jpn. Vol. 87, No. 4 (2014)
Experimental
541
selectivity. The reaction is capable of considerably further
scale-up. Our success in realizing the highly enantioselective
hydrogenation of compound 1b indicates that recent advance-
ment in asymmetric catalysis, coupled with an optimization
strategy for additives and alternative substrates, has enabled us
to expand the applicability of asymmetric hydrogenation.
General. All experiments were carried out under argon
atmosphere by standard Schlenk techniques. Reagents and
solvents were obtained from commercial sources and used
without further purification.
Compounds 1a and 1b were synthesized by the reported
method.2 Compound 1c was synthesized from compound 1a
using MeI and K2CO3 in DMF at 70 °C. Compound 1d was
synthesized from compound 1c using 1 M NaOH aqueous solu-
tion in MeOH at 60 °C.
Table 3. Asymmetric Hydrogenation of Compound 1c with
BoPhoz, DUPHOS, and BPEa)
MeO
MeO
O
O
*
[Rh(cod)2]OTf, ligand 3 (s/c=10)
H2(0.7 MPa), methanol, 70°C, 3h
CO2Me
CO2Me
The purity of compounds was assessed by elemental analysis
or analytical HPLC (>95%).
1c
2c
(S)-Methyl (6-Hydroxy-2,3-dihydrobenzofuran-3-yl)ace-
tate (2a). To methyl (6-hydroxybenzofuran-3-yl)acetate (1a)
(51 mg, 0.25 mmol) in a glass autoclave was added a solution
of (R,R)-BPE (3p, 6.5 mg, 0.025 mmol) and [Rh(cod)2]OTf (12
mg, 0.025 mmol, s/c = 10) in methanol (2.5 mL) by cannula.
Hydrogen (0.7 MPa) was introduced, and the reaction mixture
was stirred at room temperature. After 2 h, enantiomeric excess
(48%) and chemical yield (42%) were determined by HPLC
analysis using racemic compound of 2a as the external stand-
ard. (CHIRALPAK AS-H, eluted with n-hexane/2-propanol =
85/15 (v/v); flow rate, 0.75 mL min¹1; detection, 220 nm;
room temperature).
Entry
Ligand
ee/%b)
Yield/%b)
1
2
3
3l
3o
3p
14
4
53
90
74
24
a) Reaction conducted on 0.25 mmol scale at room temperature
under 0.7 MPa of H2. b) Determined by HPLC analysis using
CHIRALPAK AD-RH column.
Table 4. Asymmetric Hydrogenation of Compound 1d with
Josiphos, Et-FerroTANE, BoPhoz, DUPHOS, and BPEa)
MeO
MeO
O
O
*
[Rh(cod)2]OTf, ligand 3 (s/c=20)
H2(0.7 MPa), NaOMe, methanol, rt, 5h
CO2H
CO2H
1d
2d
Table 5. Asymmetric Hydrogenation of Compound 1b with
Various Basesa)
Entry
Ligand
ee/%b)
Yield/%b)
HO
HO
O
O
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
3a
3b
3c
3d
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
7
7
8
85
93
91
96
38
75
96
88
88
79
88
86
95
90
88
[Rh(cod)2]OTf, (S, S)-Et-FerroTane (s/c=100)
H2(0.7 MPa), base, methanol, rt, 2h
CO2H
CO2H
1b
2b
82
63
40
27
80
86
7
71
39
56
47
66
Entry
Base (equiv to 1b)
ee/%b)
Yield/%b)
1
2
3c)
4
5
6
7
8
NaOMe (0.1 equiv)
NaOMe (0.5 equiv)
NaOMe (0.5 equiv)
NaOMe (1.0 equiv)
t-BuOK (0.5 equiv)
K2CO3 (0.5 equiv)
Cs2CO3 (0.5 equiv)
Li2CO3 (0.5 equiv)
90
91
90
91
90
90
91
91
95
98
100
65
100
100
100
100
a) Reaction conducted on 0.25 mmol scale at room temper-
ature under 0.7 MPa of H2. b) Determined by HPLC analysis
(CHIRALPAK AD-H column). (S,S)-Et-FerroTANE affords
(S)-configuration of compound 2b. c) Reaction conducted on
25 g scale.
a) Reaction conducted on 0.25 mmol scale at room temperature
under 0.7 MPa of H2, using NaOMe (0.5 equiv to 1d). b) Deter-
mined by HPLC analysis using CHIRALPAK AS-H column.
Me
HO
HO
O
O
OH
esterification
+
Me
S
O
Me
CO2H
CO2Me
O
O
O
2b
4
5
Me
O
1. Mitsunobu reaction
2. Hydrolysis
Me
S
O
O
Me
O
0.5 H2O
CO2H
Scheme 1. Preparation of fasiglifam.

542
Bull. Chem. Soc. Jpn. Vol. 87, No. 4 (2014)
Rh-Catalyzed Asymmetric Hydrogenation
1H NMR spectrum and Elemental analysis data were
obtained after purification.
References
a) G.-H. Chu, M. Gu, J. A. Cassel, S. Belanger, T. M.
1
1H NMR (CDCl3): ¤ 2.50-2.61 (m, 1H), 2.69-2.79 (m, 1H),
3.72 (s, 3H), 3.73-3.85 (m, 1H), 4.26 (dd, J = 9.0 and 6.0 Hz,
1H), 4.75 (t, J = 9.0 Hz, 1H), 4.86 (s, 1H), 6.30-6.35 (m, 2H),
6.95-7.00 (m, 1H). MS m/z 209 (M + H)+. Anal. Calcd for
C11H12O4: C, 63.45; H, 5.81%. Found: C, 63.49; H, 5.81%.
(S)-(6-Hydroxy-2,3-dihydrobenzofuran-3-yl)acetic Acid
(2b). To a solution of (6-hydroxy-1-benzofuran-3-yl)acetic
acid (1b) (1.92 g, 10 mmol), NaOMe (0.27 g, 5 mmol) in meth-
anol (35 mL) in a glass autoclave was added a solution of 1,1¤-
bis((2S,4S)-2,4-diethylphosphotano)ferrocene (3k, 44 mg, 0.1
mmol) and [Rh(cod)2]OTf (47 mg, 0.1 mmol, s/c = 100) in
methanol (15 mL) by cannula. Hydrogen (0.7 MPa) was intro-
duced, and the reaction mixture was stirred at room temper-
ature. After 2 h, enantiomeric excess (90%) and chemical yield
(quantitative) were determined by HPLC analysis using racemic
compound of 2b as the external standard. (CHIRALPAK AD-H,
eluted with n-hexane/ethanol/trifluoroacetic acid = 900/100/1
(v/v/v); flow rate, 1.0 mL min¹1; detection, 220 nm; room tem-
perature). The reaction mixture was concentrated. The residue
was diluted with water and 1 M aqueous HCl solution and
extracted with AcOEt. The extract was washed with brine,
dried over anhydrous Na2SO4, and concentrated. The residue
was purified by silica gel column chromatography (AcOEt:
hexane = 35:65 and then 100:0) to afford 2b (1.76 g, 91%) as a
slightly yellow solid.
Graczyk, R. N. DeHaven, N. Conway-James, M. Koblish, P. J.
Little, D. L. DeHaven-Hudkins, R. E. Dolle, Bioorg. Med. Chem.
Lett. 2005, 15, 5114. b) G. Q. Shi, J. F. Dropinski, Y. Zhang, C.
Santini, S. P. Sahoo, J. P. Berger, K. L. MacNaul, G. Zhou, A.
Agrawal, R. Alvaro, T.-a. Cai, M. Hernandez, S. D. Wright, D. E.
Moller, J. V. Heck, P. T. Meinke, J. Med. Chem. 2005, 48, 5589.
c) P. Diaz, S. S. Phatak, J. Xu, F. R. Fronczek, F. Astruc-Diaz,
C. M. Thompson, C. N. Cavasotto, M. Naguib, ChemMedChem
2009, 4, 1615. d) B. B. Snider, X. Wu, Heterocycles 2006, 70, 279.
e) F. Xu, Y. Zhang, J. Wang, J. Pang, C. Huang, X. Wu, Z. She,
L. L. P. Vrijmoed, E. B. G. Jones, Y. Lin, J. Nat. Prod. 2008, 71,
1251. f) S. K. Dinda, S. K. Das, G. Panda, Synthesis 2009, 1886.
g) Y. Wang, A. Zhang, Tetrahedron 2009, 65, 6986. h) R. P.
Tripathi, A. K. Yadav, A. Ajay, S. S. Bisht, V. Chaturvedi, S. K.
Sinha, Eur. J. Med. Chem. 2010, 45, 142.
2
a) N. Negoro, S. Sasaki, S. Mikami, M. Ito, M. Suzuki, Y.
Tsujihata, R. Ito, A. Harada, K. Takeuchi, N. Suzuki, J. Miyazaki,
T. Santou, T. Odani, N. Kanzaki, M. Funami, T. Tanaka, A.
Kogame, S. Matsunaga, T. Yasuma, Y. Momose, ACS Med. Chem.
Lett. 2010, 1, 290. b) N. Negoro, S. Sasaki, M. Ito, S. Kitamura, Y.
Tsujihata, R. Ito, M. Suzuki, K. Takeuchi, N. Suzuki, J. Miyazaki,
T. Santou, T. Odani, N. Kanzaki, M. Funami, T. Tanaka, T.
Yasuma, Y. Momose, J. Med. Chem. 2012, 55, 1538. c) N. Negoro,
S. Sasaki, S. Mikami, M. Ito, Y. Tsujihata, R. Ito, M. Suzuki, K.
Takeuchi, N. Suzuki, J. Miyazaki, T. Santou, T. Odani, N. Kanzaki,
M. Funami, A. Morohashi, M. Nonaka, S. Matsunaga, T. Yasuma,
Y. Momose, J. Med. Chem. 2012, 55, 3960.
1H NMR (DMSO-d6): ¤ 2.39-2.49 (m, 1H), 2.61-2.71 (m,
1H), 3.56-3.68 (m, 1H), 4.14 (dd, J = 9.0, 6.8 Hz, 1H), 4.64
(t, J = 9.0 Hz, 1H), 6.15 (d, J = 2.2 Hz, 1H), 6.23 (dd, J = 8.0,
2.2 Hz, 1H), 6.98 (dd, J = 8.0, 0.7 Hz, 1H), 9.27 (br s, 1H),
12.33 (br s, 1H).
3
a) T. Ohta, T. Miyake, N. Seido, H. Kumobayashi, H.
Takaya, J. Org. Chem. 1995, 60, 357. b) M. Maris, W.-R. Huck, T.
Mallat, A. Baiker, J. Catal. 2003, 219, 52. c) P. Feiertag, M.
Albert, U. Nettekoven, F. Spindler, Org. Lett. 2006, 8, 4133. d) S.
Kaiser, S. P. Smidt, A. Pfaltz, Angew. Chem., Int. Ed. 2006, 45,
5194. e) N. Ortega, S. Urban, B. Beiring, F. Glorius, Angew.
Chem., Int. Ed. 2012, 51, 1710. f) N. Ortega, B. Beiring, S. Urban,
F. Glorius, Tetrahedron 2012, 68, 5185.
Anal. Calcd for C10H10O4¢0.2H2O: C, 60.73; H, 5.30%.
Found: C, 60.84; H, 5.35%.
Gram-Scale Synthesis of (S)-(6-Hydroxy-2,3-dihydroben-
zofuran-3-yl)acetic Acid (2b). To a solution of (6-hydroxy-1-
benzofuran-3-yl) acetic acid (1b) (26.9 g, 140 mmol), NaOMe
(3.8 g, 70 mmol) in methanol (500 mL) in a glass autoclave was
added a solution of 1,1¤-bis((2S,4S)-2,4-diethylphosphotano)-
ferrocene (3k, 620 mg, 1.4 mmol) and [Rh(cod)2]OTf (656 mg,
1.4 mmol, s/c = 100) in methanol (200 mL) by cannula.
Hydrogen (0.7 MPa) was introduced, and the reaction mixture
was stirred at room temperature. After 2 h, enantiomeric excess
(90%) and chemical yield (quantitative) were determined by
HPLC analysis using racemic 2b as the external standard.
4
a) R. Noyori, Asymmetric Catalysis in Organic Synthesis,
John Wiley & Sons, New York, 1993. b) M. J. Burk, Acc. Chem.
Res. 2000, 33, 363. c) R. Noyori, Angew. Chem., Int. Ed. 2002, 41,
2008. d) W. Tang, X. Zhang, Chem. Rev. 2003, 103, 3029. e) H.-U.
Blaser, C. Malan, B. Pugin, F. Spindler, H. Steiner, M. Studer,
Adv. Synth. Catal. 2003, 345, 103. f) I. C. Lennon, P. H. Moran,
Curr. Opin. Drug Discovery Devel. 2003, 6, 855. g) X. Zhang,
Tetrahedron: Asymmetry 2004, 15, 2099. h) H. Shimizu, I.
Nagasaki, T. Saito, Tetrahedron 2005, 61, 5405. i) Handbook of
Homogeneous Hydrogenation, ed. by J. G. de Vries, C. J. Elsevier,
Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, 2007.
doi:10.1002/9783527619382.
(CHIRALPAK AD-H, eluted with n-hexane/ethanol/trifluoro-
¹1
acetic acid = 900/100/1 (v/v/v); flow rate, 1.0 mL min
detection, 220 nm; room temperature).
;
5
6
M. Yamashita, T. Yamano, Chem. Lett. 2009, 38, 100.
a) A. Togni, C. Breutel, A. Schnyder, F. Spindler, H.
The reaction mixture was concentrated. The residue was
diluted with water and 1 M HCl aqueous solution and extracted
with AcOEt. The extract was washed with brine, dried over
anhydrous Na2SO4, and concentrated to afford 2b as a brown
solid (28.0 g, purity 99%, quantitative). The residue was used
for the next step without further purification.
Landert, A. Tijani, J. Am. Chem. Soc. 1994, 116, 4062. b) H.-U.
Blaser, H.-P. Buser, H.-P. Jalett, B. Pugin, F. Spindler, Synlett
1999, 867. c) H.-U. Blaser, H.-P. Buser, R. Häusel, H.-P. Jalett, F.
Spindler, J. Organomet. Chem. 2001, 621, 34. d) H.-U. Blaser, W.
Brieden, B. Pugin, F. Spindler, M. Studer, A. Togni, Top. Catal.
2002, 19, 3. e) H.-U. Blaser, B. Pugin, F. Spindler, M. Thommen,
Acc. Chem. Res. 2007, 40, 1240.
Supporting Information
7
U. Berens, M. J. Burk, A. Gerlach, W. Hems, Angew.
Chem., Int. Ed. 2000, 39, 1981.
a) M. J. Burk, F. Bienewald, S. Challenger, A. Derrick,
1H NMR spectra of compound 2a, 2b, and HPLC charts of
racemic compound of 2a, 2b. This material is available free of
charge on the web at: http://www.csj.jp/journals/bcsj/.
8

M. Yamashita et al.
Bull. Chem. Soc. Jpn. Vol. 87, No. 4 (2014)
543
J. A. Ramsden, J. Org. Chem. 1999, 64, 3290. b) The asymmetric
hydrogenation of compound 1d using the [Rh(cod)2]OTf-3p
without sodium methoxide did not afford compound 2d (no
reaction), and the harsh reaction condition afforded only non-
hydrogenated methylester.
Yasuma, N. Negoro, M. Yamashita, M. Itou, WO 2008001931 A2,
2006. b) The same reaction was reported, See: T. Aotsuka, H.
Kanazawa, K. Kumazawa, WO 2012081570 A1, 2011.
10 a) S. Caille, R. Crockett, K. Ranganathan, X. Wang, J. C. S.
Woo, S. D. Walker, J. Org. Chem. 2011, 76, 5198. b) X. Wang, A.
Guram, S. Caille, J. Hu, J. P. Preston, M. Ronk, S. Walker, Org.
Lett. 2011, 13, 1881.
9
a) A preliminary result for the use of Rh-Et-FerroTANE in
hydrogenation of compound 1a and 1b was reported previously: T.