Development of a new chiral spiro oxazolinylpyridine ligand (spymox) for asymmetric catalysis

Article abstract of DOI:10.1055/s-0028-1087675

A novel optically active 2-(oxazolinyl)pyridine ligand (Spymox) having a spiro binaphthyl backbone was synthesized from an a,a-disubstituted a-amino acid (H-Bin-OH), and successfully used in palladium-catalyzed asymmetric allylic alkylations to afford the

Full text of DOI:10.1055/s-0028-1087675

LETTER
241
Development of a New Chiral Spiro Oxazolinylpyridine Ligand (Spymox)
for Asymmetric Catalysis
Development of
a
a
Ne
w
Chiral
z
S
piro Oxa
u
zolinylpyridi
t
ne
L
iga
a
nd ka Shibatomi,* Tsubasa Muto, Yusuke Sumikawa, Akira Narayama, Seiji Iwasa*
Department of Materials Science, Toyohashi University of Technology, 1-1 Hibarigaoka, Tempaku-cho, Toyohashi 441-8580, Japan
Fax +81(532)48 5833; E-mail: shiba@tutms.tut.ac.jp; E-mail: iwasa@tutms.tut.ac.jp
Received 5 October 2008
The synthesis of Spymox (1) is shown in Scheme 2. H-
[(R)-Bin]-OEt (3) was synthesized from (R)-2,2¢-bis(bro-
momethyl)-1,1¢-binaphthyl (2) and ethyl isocyanoacetate
using a phase-transfer catalyst in 84% yield. This proce-
dure is much more concise than the previous report using
glycine tert-butyl ester Schiff base.5 The amido alcohol 4
was obtained by the condensation of 3 with 2-picolinoyl
chloride, followed by reduction of the ethyl ester with
LiBH4. After chlorination of the primary alcohol with
SOCl2, the oxazoline ring was formed under basic condi-
tions to afford (R)-1 with 45% yield (25% overall yield).
Abstract: A novel optically active 2-(oxazolinyl)pyridine ligand
(Spymox) having a spiro binaphthyl backbone was synthesized
from an a,a-disubstituted a-amino acid (H-Bin-OH), and success-
fully used in palladium-catalyzed asymmetric allylic alkylations to
afford the corresponding alkylated products with 99% ee.
Key words: ligand design, a-amino acid, spiro compounds, asym-
metric catalysis, allylic substitution
Development of new chiral ligands for asymmetric syn-
thesis is an important research subject in synthetic organic
chemistry. Recently, optically active spiro compounds
have attracted significant attention as a new class of chiral
ligands because their rigid spiro structure can result in a
fairly rigid transition-state geometry during the course of
asymmetric metal catalysis.1 However, there are few re-
ports on the successful development of spiro chiral
ligands, especially which have spiro structure on their side
arm, because of the difficulty involved in the preparation
of these ligands in optically pure form.2,3 Herein, we have
designed chiral spiro 2-(oxazolinyl)pyridine (Spymox) as
a novel N,N-bidentate ligand.4 Spymox was efficiently
synthesized from 2-picolinic acid and H-Bin-OR,5 which
is an a,a-disubstituted a-amino acid with an axial chiral
binaphthyl backbone (Scheme 1). Surprisingly, no report
have been appeared on the application of this unique arti-
ficial amino acid to asymmetric catalysis, though chiral a-
amino acids have been frequently used as synthons for nu-
merous chiral ligands6 and organocatalysts.7 In this paper,
we discuss the concise synthesis of spymox and its suc-
cessful application to palladium-catalyzed asymmetric al-
lylic alkylations.8
O
H2N
OEt
Br
a,b
84% (2 steps)
Br
2
H-(R)-Bin-OEt (3)
O
N
OH
HN
c,d
67% (2 steps)
e,f
45% (2 steps)
(R)-Spymox (1)
4
Scheme 2 Reagents and conditions: (a) CNCH2CO2Et (1.2 equiv),
n-Bu4N+HSO4 (20 mol%), K2CO3 (10 equiv), MeCN, reflux, 18 h;
–
(b) concd HCl, EtOH, r.t., 6 h; (c) 2-picolinoyl chloride·HCl (1.1
equiv), Et3N (4 equiv), CH2Cl2, r.t., 4 h; (d) LiBH4 (5 equiv), THF,
r.t., 12 h; (e) SOCl2 (10 equiv), CHCl3, reflux, 6 h; (f) 2.5 N aq NaOH
(10 equiv), 1,4-dioxane, 60 °C, 20 h.
O
N
H2N
CO2R
N
The asymmetric induction of Spymox was evaluated by
using it in the palladium-catalyzed asymmetric alkylation
of racemic 1,3-diphenyl-2-propenyl acetate (5a).9 Fortu-
nately, the palladium complex of (R)-1 catalyzed the alky-
lation of 5a with dimethyl malonate to afford the desired
product 6a with 99% ee. As sumarized in Table 1, excel-
lent enantioselectivities were observed in a variety of sol-
vents, including highly polar solvents and protic solvents.
Notably, the use of tert-butyl methyl ether (TBME) as the
solvent resulted in a dramatic enhancement of the catalyt-
ic activity to afford 6a in a high yield, even at ambient
+
N
CO2H
(R)-Spymox (1)
H-(R)-Bin-OR
Scheme 1 Design of novel chiral spiro oxazolinylpyridine ligand
SYNLETT 2009, No. 2, pp 0241–0244
Advanced online publication: 15.01.2009
DOI: 10.1055/s-0028-1087675; Art ID: U10808ST
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x.
2
0
0
9

242
K. Shibatomi et al.
LETTER
temperature (entry 7). Moderate enantioselectivities were
observed when monosubstituted 2-(oxazolinyl)pyridine
ligands (pymox) were used in the same reaction (entries 8
and 9).10 These results clearly show that our ligand with a
spiro bicyclic oxazoline backbone is very advantageous
for asymmetric induction.
Table 2 Asymmetric Allylic Alkylation of Various 1,3-Diaryl-2-
propenyl Acetatesa
CH2(CO2Me)2 (2 equiv)
(R)-1 (12 mol%)
[Pd(η3-C3H5)Cl]2 (5 mol%)
O
O
OAc
K2CO3 (1 equiv)
MeO
Ar
OMe
Ar
Ar
rac-5a–e
TBME, 14 h
Ar
Table 1 Asymmetric Allylic Alkylation of 5a with Dimethyl Mal-
6a–e
onate Catalyzed by Pd-Spymox Complexa
a: Ar = Ph
d: Ar = 4-MeC6H4
b: Ar = 4-O2NC6H4 e: Ar = 3-MeC6H4
c: Ar = 4-ClC6H4
CH2(CO2Me)2 (2 equiv)
O
O
ligand (12 mol%)
[Pd(η3-C3H5)Cl]2 (5 mol%)
K2CO3 (1 equiv)
Yield (%)b
ee (%)c
99 (R)
n.d.
n.d.
99
OAc
Ph
MeO
Ph
OMe
Entry
Substrate
5a
Temp (°C)
Ph
Ph
1
2
3
4d
5
6
7
8
9
r.t.
r.t.
55
55
r.t.
55
r.t.
55
55
90
<5
<5
84
27
92
30
73
94
solvent, r.t., 14 h
rac-5a
6a
5b
5b
O
N
(S)-pymox-Ph: R = Ph
(S)-pymox-Bn: R = Bn
5b
N
R
5c
99
5c
99
Entry
Solvent
CH2Cl2
THF
Ligand
(R)-1
(R)-1
(R)-1
(R)-1
(R)-1
(R)-1
(R)-1
Yield (%)b
ee (%)c
99 (R)
99 (R)
99 (R)
99 (R)
99 (R)
99 (R)
99 (R)
14 (S)
45 (S)
5d
97
1
29
29
26
15
23
91
90
5d
97
2
5e
98
3
i-PrOH
DMF
a All reactions were carried out with 2 equiv of dimethyl malonate and
1 equiv of K2CO3 in the presence of palladium complex prepared
from (R)-1 (12 mol%) and [Pd(h3-C3H5)Cl]2 (5 mol%) unless other-
wise noted.
4
5
toluene
toluene
TBME
TBME
TBME
6d
7
b Isolated yield.
c Determined by HPLC analysis.
d NaH (1 equiv) was used instead of K2CO3.
8
(S)-pymox-Bn
(S)-pymox-Ph
65
15
9e
Table 3 Asymmetric Allylic Alkylation of 5a with Various Mal-
a All reactions were carried out with 2 equiv of dimethyl malonate and
1 equiv of K2CO3 in the presence of palladium complex prepared
from ligand (12 mol%) and [Pd(h3-C3H5)Cl]2 (5 mol%).
b Isolated yield.
onatesa
(R)-1 (12 mol%)
[Pd(η3-C3H5)Cl]2 (5 mol%)
K2CO3 (2 equiv)
O
O
R1O
Ph
OR1
c Determined by HPLC analyses.
rac-5a +
R2
Ph
HCR2(CO2R1)2
d The reaction run at 80 °C.
TBME
7a–d (2 equiv)
e The reaction run for 48 h.
a: R1 = Et, R2 = H c: R1 = Me, R2 = Me
8a–d
b: R1 = Bn, R2 = H
d: R1 = Me, R2 = F
Next, the scope of the substrate was expanded to various
substituted 1,3-diphenyl-2-propenyl acetates. As shown
in Table 2, excellent enantioselectivities (97–99% ee)
were observed in all the examples, though substrates pos-
sessing electron-withdrawing or electron-donating groups
required high temperatures or the use of NaH as a base to
facilitate a high rate of conversion.
Entry
Nucleo- Temp (°C) Time (h) Yield (%)b ee (%)c
phile
1
2
3
4
7a
7b
7c
7d
55
55
55
rt
24
14
14
48
82
90
94
58
>99 (R)
>99
99 (S)
>99
Finally, we tested several malonates (7a–e) as nucleo-
philes (Table 3). The reactions of 5a with dialkyl mal-
onates 7a,b proceeded smoothly to afford the desired
products 8a,b with 98–99% ee (entries 1 and 2). The use
of a-substituted malonates, including the a-fluorinated
malonate 7d,11 also afforded the corresponding allylated
products 8c,d with excellent enantioselectivities (entries 3
and 4).
a All reactions were carried out with 2 equiv of dimethyl malonate and
2 equiv of K2CO3 in the presence of palladium complex prepared
from (R)-1 (12 mol%) and [Pd(h3-C3H5)Cl]2 (5 mol%).
b Isolated yield.
c Determined by HPLC analysis.
Synlett 2009, No. 2, 241–244 © Thieme Stuttgart · New York

LETTER
Development of a New Chiral Spiro Oxazolinylpyridine Ligand
243
A plausible transition-state model is proposed in Figure 1.
One of naphthyl rings on the ligand shields the upper
right-hand side of the p-allyl palladium complex; thus, the
position of nucleophilic attack as well as the formation of
the p-allyl complex (two phenyl groups would be located
below) are properly controlled.
References and Notes
(1) A recent review for chiral phosphine ligands on a spiro
scaffold: Xie, J.-H.; Zhou, Q.-L. Acc. Chem. Res. 2008, 41,
581.
(2) Most of the reported efficient spiro chiral ligands have a 1,1¢-
spirobiindane backbone. For examples, see: (a) Birman,
V. B.; Rheingold, A. L.; Lam, K.-C. Tetrahedron:
Asymmetry 1999, 10, 125. (b) Hu, A.-G.; Fu, Y.; Xie, J.-H.;
Zhou, H.; Wang, L.-X.; Zhou, Q.-L. Angew. Chem. Int. Ed.
2002, 41, 2348. (c) Xie, J.-H.; Wang, L.-X.; Fu, Y.; Zhu,
S.-F.; Fan, B.-M.; Duan, H.-F.; Zhou, Q.-L. J. Am. Chem.
Soc. 2003, 125, 4404. (d) Xie, J.-H.; Duan, H.-F.; Fan, B.-
M.; Cheng, X.; Wang, L.-X.; Zhou, Q.-L. Adv. Synth. Catal.
2004, 346, 625. (e) Zhu, S.-F.; Yang, Y.; Wang, L.-X.; Liu,
B.; Zhou, Q.-L. Org. Lett. 2005, 7, 2333. (f) Cheng, X.;
Zhang, Q.; Xie, J.-H.; Wang, L.-X.; Zhou, Q.-L. Angew.
Chem. Int. Ed. 2005, 44, 1118. (g) Zhu, S.-F.; Xie, J.-B.;
Zhang, Y.-Z.; Li, S.; Zhou, Q.-L. J. Am. Chem. Soc. 2006,
128, 12886. (h) Chen, C.; Zhu, S.-F.; Liu, B.; Wang, L.-X.;
Zhou, Q.-L. J. Am. Chem. Soc. 2007, 129, 12616.
Figure 1 A plausible transition-state model
(3) Examples of spiro chiral ligands other than those listed in
ref. 2: (a) Jiang, Y.; Mi, A.; Yan, M.; Sun, J.; Lou, R.; Deng,
J. J. Am. Chem. Soc. 1997, 119, 9570. (b) Arai, M. A.; Arai,
T.; Sasai, H. Org. Lett. 1999, 1, 1795. (c) Arai, M. A.;
Kuraishi, M.; Arai, T.; Sasai, H. J. Am. Chem. Soc. 2001,
123, 2907. (d) Wu, S.-L.; Zhang, W.-C.; Zhang, Z.-G.;
Zhang, X.-M. Org. Lett. 2004, 6, 3565. (e) Lin, C. W.; Lin,
C.-C.; Lam, L. F.-L.; Au-Yeung, T. T.-L.; Chan, A. S. C.
Tetrahedron Lett. 2004, 45, 7379. (f) Lait, S. M.; Parvez,
M.; Keay, B. A. Tetrahedron: Asymmetry 2004, 15, 155.
(g) Guo, Z.; Guan, X.; Chen, Z. Tetrahedron: Asymmetry
2006, 17, 468. (h) Koranne, P. S.; Tsujihara, T.; Arai, M. A.;
Bajracharya, G. B.; Suzuki, T.; Onitsuka, K.; Sasai, H.
Tetrahedron: Asymmetry 2007, 18, 919.
In conclusion, we have synthesized a novel optically ac-
tive spiro ligand from H-Bin-OH; this has been success-
fully applied to palladium-catalyzed asymmetric allylic
alkylations. To the best of our knowledge, this is the first
example of the use of H-Bin-OH derivatives for asym-
metric catalysis. Further study on the application of H-
Bin-OH and its derivatives to the preparation of novel
chiral catalysts are under way.
Typical Procedure for Asymmetric Allylic Alkylations
A flame-dried flask under argon was charged with (R)-1 (0.024
mmol) and [Pd(h3-C3H5)Cl]2 (0.01 mmol). Dichloromethane (1
mL) was added to this mixture. After the reaction mixture was
stirred for 1 h at r.t., CH2Cl2 was evaporated in vacuo. Residual Pd
complex was dissolved into TBME (5 mL). 1,3-Diphenyl-2-prope-
nyl acetate (5a, 0.2 mmol), dimethyl malonate (0.4 mmol), and
K2CO3 (0.4 mmol) were added to this solution. The reaction mixture
was stirred for 14 h at r.t. The reaction was quenched with sat. aq
NH4Cl, and the mixture was extracted by CH2Cl2. The organic layer
was dried over Na2SO4, concentrated, and chromatographed on
SiO2 to give 6a in 90%yield with 99% ee.
(4) Recent reviews on nitrogen-containing chiral ligands:
(a) Fache, F.; Schulz, E.; Tommasino, M. L.; Lemaire, M.
Chem. Rev. 2000, 100, 2159. (b) McManus, H. A.; Guiry,
P. J. Chem. Rev. 2004, 104, 4151.
(5) Synthesis of H-Bin-OR and their application to peptide
chemistry: (a) Mazaleyrat, J.-P.; Gaucher, A.; Wakselman,
M.; Tchertanov, L.; Guilhem, J. Tetrahedron Lett. 1996, 37,
2971. (b) Mazaleyrat, J.-P.; avrda, J.; Wakselman, M.
Tetrahedron: Asymmetry 1997, 8, 619. (c) Mazaleyrat,
J.-P.; Boutboul, A.; Lebars, Y.; Gaucher, A.; Wakselman,
M. Tetrahedron: Asymmetry 1998, 9, 2701. (d) Mazaleyrat,
J.-P.; Wright, K.; Gaucher, A.; Wakselman, M.; Oancea, S.;
Formaggio, F.; Toniolo, C.; Setnika, V.; Kapitán, J.;
Keiderling, T. A. Tetrahedron: Asymmetry 2003, 14, 1879.
(6) (a) Catalytic Asymmetric Synthesis, 2nd ed.; Ojima, I., Ed.;
Wiley-VCH: New York, 2000. (b) Comprehensive
Asymmetric Catalysis, Vol. 1-3; Jacobsen, E. N.; Pfaltz, A.;
Yamamoto, H., Eds.; Springer: New York, 1999.
Products 6a–d and 8a–d were identical in all respects to the known
literature compounds.12–15
See the references section for analytical details of new compounds
1, 4, 5e, and 6e.16–19
CAS Registry Numbers
5a: 73930-97-9; 5b: 881397-70-2; 5c: 195192-51-9; 5d: 881397-
68-8; pymox-Ph: 153880-57-0; pymox-Bn: 108915-08-8; 7d: 344-
14-9.
(7) (a) Dalko, P. I.; Moisan, L. Angew. Chem. Int. Ed. 2004, 43,
5138. (b) Berkessel, A.; Gröger, H. Asymmetric
Organocatalysis; Wiley-VCH: Weinheim, 2005.
(c) Enantioselective Organocatalysis: Reactions and
Experimental Procedures; Dalko, P. I., Ed.; Wiley-VCH:
Weinheim, 2007.
Acknowledgment
(8) Reviews on the asymmetric allylic alkylation reaction:
(a) Paquin, J.-F.; Lautens, M. In Comprehensive Asymmetric
Catalysis, Suppl. 2; Jacobsen, E. N.; Pfaltz, A.; Yamamoto,
H., Eds.; Springer: Berlin, 2004, 73–95; and references
therein. (b) Pfaltz, A.; Lautens, M. In Comprehensive
Asymmetric Catalysis, Vol. 2; Jacobsen, E. N.; Pfaltz, A.;
Yamamoto, H., Eds.; Springer: New York, 1999, 833–884;
and references therein.
This study was supported by a Grant-in-Aid for Scientific Research
(C) (No. 20550137) from Japan Society for the Promotion of Sci-
ence. We thank The Nippon Synthetic Chemical Industry Co., Ltd.
for supplying ethyl isocyanoacetate used in this study.
Synlett 2009, No. 2, 241–244 © Thieme Stuttgart · New York

244
K. Shibatomi et al.
LETTER
751, 696, 615 cm–1. Anal. Calcd (%) for C30H22N2O: C,
(9) Palladium-catalyzed asymmetric allylic alkylation using a
spiro chiral ligand having a 1,1¢-spirobiindane backbone
84.48; H, 5.20; N, 6.57. Found: C, 84.67; H, 5.15; N, 6.36.
[a]D –72.4 (c 1.25, CHCl3).
(SDP) has been reported, see ref. 2d
.
(10) A previous report on asymmetric allylic alkylation using
pymox–Pd complex also shows moderate enantioselectivity
(50% ee): Nordström K., Macedo E., Moberg C.; J. Org.
Chem.; 1997, 62: 1604
(11) Palladium-catalyzed asymmetric allylic alkylations with
fluorinated carbanion: (a) Fukuzumi, T.; Shibata, N.;
Sugiura, M.; Yasui, H.; Nakamura, S.; Toru, T. Angew.
Chem. Int. Ed. 2006, 45, 4973. (b) Jiang, B.; Huang, Z.-G.;
Cheng, K.-J. Tetrahedron: Asymmetry 2006, 17, 942.
(c) Zhang, F.; Song, Z. J.; Tschaen, D.; Volante, R. P. Org.
Lett. 2004, 6, 3775. (d) Komatsu, Y.; Sakamoto, T.;
Kitazume, T. J. Org. Chem. 1999, 64, 8369.
(12) For compounds 6a, 8c, see: Imamoto, T.; Nishimura, M.;
Koide, A.; Yoshida, K. J. Org. Chem. 2007, 72, 7413.
(13) For compounds 6b–d, 8b, see: Kinoshita, N.; Kawabata, T.;
Tsubaki, K.; Bando, M.; Fuji, K. Tetrahedron 2006, 62,
1756.
(14) For compound 8a, see: Braga, A. L.; Vargas, F.; Sehnem,
J. A.; Braga, R. C. J. Org. Chem. 2005, 70, 9021.
(17) Compound 4: 1H NMR (300 MHz, CDCl3): d = 8.45 (m,
1 H), 8.23 (m, 2 H), 7.96–7.86 (m, 5 H), 7.55 (m, 1 H), 7.48–
7.37 (m, 6 H), 7.29–7.23 (m, 2 H), 5.19 (dd, J = 5.2, 8.0 Hz,
1 H), 4.01 (dd, J = 8.0, 11.5 Hz, 1 H), 3.83 (dd, J = 5.2, 11.5
Hz, 1 H), 3.23 (d, J = 13.7 Hz, 1 H), 3.11 (d, J = 12.4 Hz, 1
H), 2.54 (d, J = 13.7 Hz, 1 H), 2.45 (d, J = 12.4 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 165.0, 149.6, 148.2, 137.8,
135.4, 135.4, 134.8, 134.6, 134.4, 133.2, 133.2, 133.1,
132.0, 132.0, 128.6, 128.4, 128.4, 128.1, 128.1, 127.4,
126.6, 126.1, 126.0, 125.6, 125.4, 122.3, 70.2, 66.9, 41.0,
38.9. IR (neat): 3846, 3343, 3053, 2928, 1667, 1525, 1457,
1324, 1245, 1058, 817, 752, 697, 621, 436 cm–1. Anal. Calcd
(%) for C30H24N2O2: C, 80.06; H, 5.44; N, 6.30. Found: C,
81.34; H, 5.74; N, 6.03. [a]D –90.5 (c 1.0, CHCl3).
(18) Compound 5e: 1H NMR (300 MHz, CDCl3): d = 7.29–7.05
(m, 8 H), 6.60 (d, J = 15.3 Hz, 1 H), 6.41–6.28 (m, 2 H), 2.36
(s, 3 H), 2.32 (s, 3 H), 2.13 (s, 3 H). 13C NMR (75 MHz,
CDCl3): d = 170.2, 139.3, 138.4, 138.2, 136.2, 132.6, 129.0,
128.9, 128.63, 128.57, 127.8, 127.5, 124.2, 124.0, 76.4,
21.6, 21.49, 21.45. Anal. Calcd (%) for C19H20O2: C, 81.40;
H, 7.19; O, 11.41. Found: C, 81.06; H, 6.62.
(15) For compound 8d, see: Jiang, B.; Huang, Z.-G.; Cheng,
K.-J. Tetrahedron: Asymmetry 2006, 17, 942.
(16) Compound 1: 1H NMR (300 MHz, CDCl3): d = 8.71 (m,
1 H), 8.08 (m, 1 H), 7.95 (m, 4 H), 7.77 (m, 1 H), 7.65 (d,
J = 8.0 Hz, 1 H), 7.50 (d, J = 8.4 Hz, 1 H), 7.46–7.38 (m,
4 H), 7.33 (d, J = 8.8 Hz, 1 H), 7.27–7.20 (m, 2 H), 4.65 (d,
J = 8.8 Hz, 1 H), 3.95 (d, J = 8.8 Hz, 1 H), 2.94 (d, J = 13.1
Hz, 1 H), 2.88 (d, J = 13.3 Hz, 1 H), 2.72 (d, J = 13.3 Hz,
1 H), 2.65 (d, J = 13.1 Hz, 1 H). 13C NMR (75 MHz, CDCl3):
d = 162.1, 149.8, 147.0, 136.7, 135.4, 134.7, 134.5, 133.7,
133.1, 133.0, 132.1, 131.9, 128.7, 128.5, 128.4, 128.4,
128.3, 127.5, 127.4, 127.2, 126.0, 125.7, 125.4, 125.1,
124.4, 82.5, 77.3, 44.4, 43.5. IR (neat): 3847, 3741, 3475,
3053, 2938, 1635, 1577, 1469, 1361, 1302, 1092, 968, 813,
(19) Compound 6e: 1H NMR (300 MHz, CDCl3): d = 7.26–7.00
(m, 8 H), 6.44 (d, J = 15.6 Hz, 1 H), 6.29 (dd, J = 15.6 Hz,
1 H), 4.21 (dd, J = 10.8, 8.4 Hz, 1 H), 3.94 (d, J = 10.8 Hz,
1 H), 3.70 (s, 3 H), 3.53 (s, 3 H), 2.33 (s, 3 H), 2.31 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 168.4, 168.0, 140.3, 138.4,
138.1, 136.9, 131.9, 129.1, 128.7, 128.5, 128.0, 127.2,
124.8, 123.7, 57.7, 52.76, 52.74, 52.60, 52.57, 49.3. Anal.
Calcd (%) for C22H24O4: C, 74.98; H, 6.86; O, 18.16. Found:
C, 74.69; H, 6.86. [a]D +24.1 (c 0.63, CHCl3). The er was
determined by HPLC [hexane–2-PrOH (96:4), 0.5 mL/min]
using a CHIRALPAK AD column (0.46 cm × 25 cm): tR
(major isomer) = 23.0 min; tR (minor isomer) = 26.5 min.
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