An efficient direct asymmetric synthesis of 3-substituted phthalides

Article abstract of DOI:10.1055/s-0030-1260222

A facile, two-step, asymmetric synthesis of 3-substituted phthalides has been developed. The enantiopure amide, obtained through coupling of 2-iodobenzoic acid with (S)-1-(pyrrolidin-2-ylmethyl)-1H-imidazole, was magnesiated using isopropylmagnesium chloride. Corresponding reactions with a range of aldehydes were carried out in situ by either direct addition or transmetallation using zinc(II) chloride. Intramolecular esterification of the adduct allowed the versatile asymmetric synthesis of phthalides in up to 88% enantiomeric excess. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0030-1260222

PAPER
3435
An Efficient Direct Asymmetric Synthesis of 3-Substituted Phthalides
A
Z
symmetric Sy
h
a
ubstituted
nP hthalides -Bin Zhang, Yong-Qin Lu, Xin-Fang Duan*
Department of Chemistry, Beijing Normal University, Beijing 100875, P. R. of China
Fax +86(10)58802075; E-mail: xinfangduan@vip.163.com
Received 22 July 2011; revised 10 August 2011
corresponding organozinc reagent. Subsequent addition
to an aldehyde was carried out diastereoselectively, which
led to the synthesis of a variety of enantioenriched 3-sub-
stituted phthalides (Scheme 1). This asymmetric synthesis
Abstract: A facile, two-step, asymmetric synthesis of 3-substituted
phthalides has been developed. The enantiopure amide, obtained
through coupling of 2-iodobenzoic acid with (S)-1-(pyrrolidin-2-yl-
methyl)-1H-imidazole, was magnesiated using isopropylmagne-
sium chloride. Corresponding reactions with a range of aldehydes of 3-substituted phthalides was straightforward and oper-
were carried out in situ by either direct addition or transmetallation ationally easy to apply. The chiral auxiliary 1 could be
using zinc(II) chloride. Intramolecular esterification of the adduct
conveniently recovered after the phthalide was generated.
allowed the versatile asymmetric synthesis of phthalides in up to
More importantly, this method provided potential access
to a range of substituents at C-3 of the phthalides starting
from compound 2.
8
8% enantiomeric excess.
Key words: phthalide, magnesiation, chiral auxiliary, diastereose-
lective addition, asymmetric synthesis
O
N
The 3-substituted phthalide moiety, especially in enan-
tiopure form, is found widely in natural products, includ-
i
ii
1
N
N
I
2
3
spirolaxine,4
N
ing
fuscinarin,
3-butylphthalide,
H
2
N
5
6
1b,7
1
cytosporone E, typhaphalide, isopestacin, cryphonec-
8
9
O
tric acid, and rubiginone H. These compounds possess a
broad range of biological activities and significant phar-
macological potentials. For instance, (S)-(–)-3-bu-
tylphthalide, which is an active ingredient in the Chinese
folk medicine of celery seed oil extract, has been reported
to exhibit antitumor activity, as well as mosquitocidal, ne-
maticidal, and antifungal activities.11 These facts have
generated extensive and enduring efforts toward the syn-
N
O
O
iii
N
OH
iv
N
O
1
0
M
*
R
N
R
4
N
3
N
N
Scheme 1 Enantioselective synthesis of 3-substituted phthalides.
thesis of related compounds. Methodologies leading to Reagents and conditions: (i) 2-IC H COCl, Et N, CH Cl , 0 °C;
6
4
3
2
2
+
optically active 3-alkyl-substituted phthalides are highly (ii) i-PrMgCl (or i-PrMgCl then ZnCl ); (iii) RCHO, then H O ;
2
3
(
iv) p-TsOH, toluene, reflux.
desirable. Currently, most reported synthetic methods in-
1
2
volve asymmetric hydrogenation, asymmetric hydro-
acylation, enantioselective additions of organozinc (S)-1-(Pyrrolidin-2-ylmethyl)-1H-imidazole (1)17 was
reagents, asymmetric reductions of ketoesters, or the prepared as previously described and acylated with 2-io-
1
3
1
4
15
1
6
use of chiral auxiliaries.
Herein, we report a versatile enantioselective synthesis of
-substituted phthalides involving chiral intermediate 2,
dobenzoyl chloride to afford amide 2. Subsequent magne-
siation was carried out with isopropylmagnesium chloride
via iodine exchange, followed by diastereoselective ad-
dition to the aldehyde in situ. In our hands, attempts to pu-
1
8
3
which is an amide derived from coupling of 2-iodoben-
zoyl chloride and (S)-1-(pyrrolidin-2-ylmethyl)-1H-imi-
dazole (Scheme 1). The scaffold 1 has been successfully
used in chiral ionic liquid as a highly efficient asymmetric
rify the adduct
3 by recrystallization or flash
chromatography on silica gel were unsuccessful. Com-
pound 3 was therefore used directly without purification
for the intramolecular esterification promoted by p-tolu-
enesulfonic acid. The corresponding enantioenriched 3-
substituted phthalide 4 was generated after recovering the
starting chiral template 1; the results are summarized in
Table 1.
1
7
organocatalyst in Michael addition reactions. Consider-
+
ing that the imidazole moiety has strong affinity to Li ,
2
+
2+
Mg , and Zn , we also expected it to display efficient
asymmetric induction when used as a chiral inductor in
diastereoselective additions to a carbonyl group. To this
end, amide 2 was either magnesiated with isopropylmag- It can be seen that the diastereoselectivity of addition was
nesium chloride or subsequently transmetallated into the sensitive to the reaction temperature, and the best results
were achieved at –70 °C (Table 1, entries 1–9). In addi-
tion, the solvent also had a slight impact on the diastereo-
selectivity (Table 1, entries 9–11). Addition of lithium
chloride significantly reduced the enantiomeric excess
SYNTHESIS 2011, No. 21, pp 3435–3438
x
x.
x
x
.
2
0
1
1
Advanced online publication: 13.09.2011
DOI: 10.1055/s-0030-1260222; Art ID: F72111SS
Georg Thieme Verlag Stuttgart · New York
©

3
436
Z.-B. Zhang et al.
PAPER
Table 1 Enantioselective Synthesis of 3-Substituted Phthalides 4 through Magnesiation as Illustrated in Scheme 1a
Entry
RCHO
Reagent
Solvent
THF
Temp (°C)
–20
–40
–70
–20
–40
–70
–20
–40
–70
–70
–70
–70
–70
–70
–70
–70
–70
–70
–70
Yield (%)b [a]D
% eec
43 (R)
68 (R)
88 (R)
48
1
2
3
4
5
6
7
8
9
PhCHO
i-PrMgCl
i-PrMgCl
i-PrMgCl
i-PrMgCl
i-PrMgCl
i-PrMgCl
i-PrMgCl
i-PrMgCl
i-PrMgCl
i-PrMgCl
i-PrMgCl
i-PrMgCl·LiCl
i-PrMgCl
i-PrMgCl
i-PrMgCl
i-PrMgCl
i-PrMgCl
i-PrMgCl
i-PrMgCl
THF
THF
70
67
67
–41.7 (c 0.31, CHCl3)
2-ClC H CHO
THF
6
4
THF
70
THF
–139.1 (c 0.30, CHCl3)
+26.5 (c 0.22, CHCl3)
82
4-BrC H CHO
THF
56
6
4
THF
63
THF
88
10
11
12
13
14
15
16
17
18
19
toluene
74
Et O
80
2
THF
THF
THF
THF
THF
THF
THF
THF
43
2-MeC H CHO
63
64
65
74
65
62
60
+48.7 (c 0.12, CHCl3)
–17.5 (c 0.11, CHCl3)
–32.6 (c 0.35, CHCl3)
+220.9 (c 0.43, CHCl3)
+49.7 (c 0.23, CHCl3)
+51.8 (c 0.18, CHCl3)
+11.8 (c 0.10, CHCl3)
86
6
4
4-MeC H CHO
88 (R)
88 (R)
82
6
4
4-ClC H CHO
6
4
2-BrC H CHO
6
4
n-PrCHO
i-PrCHO
t-BuCHO
80 (R)
77 (R)
66 (R)
a
b
c
The magnesiation was conducted at –70 °C; the molar ratio of 2/i-PrMgCl/RCHO was 1:1.2:1.2.
Two-step overall isolated yield.
Determined by HPLC analysis using a Chiralcel OD-H column. The chromatograms were compared against a racemic mixture.
(
ee) of the final product (Table 1, entry 12). It was shown sponding chiral template was easily prepared, incorporat-
that, for aromatic aldehydes, over 80% ee can be achieved ed, and recovered after the products were formed. This
under the optimized conditions. On the other hand, the synthesis allows the enantioselective preparation of vari-
best ee obtained with aliphatic aldehydes was 80%; in this ous 3-substituted phthalides and the related procedures
case the side chains of the aldehyde might adversely affect
the reaction diastereoselectivity (Table 1, entries 17–19).
Table 2 Enantioselective Synthesis of 3-Substituted Phthalides 4
Using Organozinc as Illustrated in Scheme 1a
The enantioselective synthesis of 3-substituted phthalides
using organozinc reagent was then examined. The zinc re-
agent was prepared by transmetallation with zinc chloride
after initial magnesiation. The results are shown in
Table 2. Overall, the addition of organozinc to aromatic
aldehydes was rather sluggish and could be carried out at
room temperature. The corresponding addition reactions
to aliphatic aldehydes were unsuccessful. The results re-
vealed that the ee values of final products were compara-
ble to those obtained with Grignard reagents, however, in
the present case, the facile reaction could be conducted at
room temperature. Similarly, addition of lithium chloride
significantly lowered the final ee values (Table 2, entry
Entry RCHO
Conditions
Yield ee
(%) (%)c
b
1
2
3
4
2-ClC H CHO
i-PrMgCl, then ZnCl2
i-PrMgCl, then ZnCl2
i-PrMgCl, then ZnCl2
73
70
73
71 (–)
6
4
4-ClC H CHO
84 (R)
86 (–)
62 (–)
84 (+)
6
4
4-BrC H CHO
6
4
4-BrC H CHO
i-PrMgCl·LiCl, then ZnCl2 71
i-PrMgCl, then ZnCl2 64
6
4
5
2-BrC H CHO
6 4
a
The magnesiation was conducted at –70 °C, then transmetallated
and reacted with the aldehyde at room temperature; the molar ratio of
2
/i-PrMgCl/ZnCl /RCHO was 1:1.2:1.2:1.2.
Two-step overall isolated yield.
4
).
2
b
In conclusion, a facile, two-step asymmetric synthesis of
c
Determined by HPLC analysis using a Chiralcel OD-H column. The
3
-substituted phthalides has been developed. The corre- chromatograms were compared against a racemic mixture.
Synthesis 2011, No. 21, 3435–3438 © Thieme Stuttgart · New York

PAPER
Asymmetric Synthesis of 3-Substituted Phthalides
3437
are very straightforward. It is rationalized that this effi- organic layer was washed to neutral and dried over anhydrous
Na CO . After removal of the solvent, the residue was purified by
cient asymmetrical induction results from the strong affin-
ity of Mg or Zn to the imidazole moiety.
2
3
2
+
2+
flash column chromatography to give the title phthalide.
2
0
Yield: 150 mg (70%); white solid; mp 100–102 °C; [a] D –41.7 (c
.31, CHCl ); 88% ee.
0
3
All NMR spectra were recorded with a 400 MHz (100 MHz for 13C)
–
1
IR (KBr): 1745, 1465, 1456, 1286, 1070, 746 cm .
Bruker NMR spectrometer and all spectra recorded in CDCl with
3
1
tetramethylsilane as an internal standard. Infrared data were ac-
quired with an AVATAR 360 FT-IR spectrophotometer. Optical ro-
tation data were recorded with a Perkin–Elmer 241 MC polarimeter
operating at 589 nm. HPLC were conducted with a P-3800 Varian
instrument with a UV/Vis detector operating at 254 nm. Melting
points were recorded with a TECH X-4 microscopic instrument and
are uncorrected. i-PrMgCl and i-PrMgCl·LiCl were prepared and ti-
trated according to Knochel’s procedures.1 (S)-1-(Pyrrolidin-2-yl-
H NMR (400 MHz, CDCl ): d = 7.96 (d, J = 7.6 Hz, 1 H), 7.65 (t,
J = 7.5 Hz, 1 H), 7.55 (t, J = 7.5 Hz, 1 H), 7.23–7.28 (m, 4 H),
7.26–7.29 (m, 2 H), 6.40 (s, 1 H).
+)-3-(2-Methylphenyl)isobenzofuran-1(3H)-one20
3
(
(Table 1,
Entry 13)
2
0
Yield: 63%; white solid; mp 110–113 °C; [a]
CHCl ); 86% ee.
+48.7 (c 0.12,
D
9
3
1
7
methyl)-1H-imidazole was synthesized by established procdures.
IR (KBr): 1757, 1464, 1286, 1067, 761 cm–1.
1
H NMR (400 MHz, CDCl ): d = 7.91 (d, J = 7.6 Hz, 1 H), 2.43 (s,
3
(
S)-{2-[(1H-Imidazol-1-yl)methyl]pyrrolidin-1-yl}(2-iodophe-
3
H), 7.60 (t, J = 7.4 Hz, 1 H), 7.51 (t, J = 7.4 Hz, 1 H), 7.28 (d,
nyl)methanone (2)
J = 7.6 Hz, 1 H), 7.19 (m, 2 H), 7.07 (m, 1 H), 6.85 (d, J = 7.6 Hz,
H), 6.62 (s, 1 H), 2.43 (s, 3 H).
(R)-3-(4-Methylphenyl)isobenzofuran-1(3H)-one13
Entry 14)
To an excess of thionyl chloride (10 mL) was added 2-iodobenzoic
acid (2.5 g, 10 mmol) and the solution was heated at reflux for 3 h.
Benzene (50 mL) was added, and the resulting azeotrope was dis-
tilled off. The remaining acid chloride was dissolved in CH C1 (30
1
(Table 1,
2
2
mL) and gradually added to a solution of (S)-1-(pyrrolidin-2-yl-
20
Yield: 64%; white solid; mp 113–117 °C; [a]
–17.5 (c 0.11,
D
methyl)-1H-imidazole (1.4 g, 9 mmol) and Et N (3.0 g, 30 mmol)
3
CHCl ); 88% ee.
3
in CH C1 (50 mL) at 0 °C. After stirring at that temperature for 2 h,
2
2
–
1
IR (KBr): 1751, 1514, 1464, 1286, 1056, 736 cm .
the mixture was brought to r.t. and stirred overnight. The mixture
was quenched with 10% aqueous NaHCO (50 mL) and the organic
1
3
H NMR (400 MHz, CDCl ): d = 7.89 (d, J = 7.6 Hz, 1 H), 7.57 (t,
J = 7.5 Hz, 1 H), 7.48 (t, J = 7.6 Hz, 1 H), 7.25 (d, J = 7.6 Hz, 1 H),
3
phase was dried over Na CO . After evaporation under reduced
2
3
pressure, the resulting residue was purified by flash column chro-
matography over silica gel to give the title product (69% yield) as a
thick oil. The compound was characterized as its hydrogen chloride
salt (prepared in ethereal solution).
7
.10 (m, 4 H), 6.31 (s, 1 H), 2.28 (s, 3 H).
(
+)-3-(2-Bromophenyl)isobenzofuran-1(3H)-one21 (Table 1, En-
try 16)
2
0
2
0
Yield: 74%; white solid; mp 124–126 °C; [a]
CHCl ); 82% ee.
D
+220.9 (c 0.43,
White crystals; [a]D –20.4 (c 0.43, CHCl3).
3
–
1
IR (KBr): 3408, 2961, 1627, 1581, 1411, 1290, 1016, 771 cm .
–
1
IR (KBr): 1767, 1465, 1433, 1284, 1210, 1064, 745 cm .
1
H NMR (400 MHz, CDCl ): d = 10.12 (s, 1 H), 7.80 (d, J = 7.9 Hz,
3
1
H NMR (400 MHz, CDCl ): d = 7.89 (d, J = 7.4 Hz, 1 H), 7.58–
3
1
7
1
H), 7.51 (s, 1 H), 7.37–7.40 (m, 2 H), 7.21 (d, J = 7.3 Hz, 1 H),
.07 (t, J = 7.6 Hz, 1 H), 4.75 (br, 2 H), 4.52 (br, 1 H), 3.27 (br,
H), 3.11–3.16 (m, 1 H), 2.07 (br, 3 H), 1.90 (br, 1 H).
7
.60 (m, 2 H), 7.48–7.50 (m, 2 H), 7.19–7.15 (m, 2 H), 6.98 (d,
J = 7.4 Hz, 1 H), 6.88 (s, 1 H).
(–)-3-(4-Bromophenyl)isobenzofuran-1(3H)-one21 (Table 1, En-
try 9)
1
3
C NMR (100 MHz, CDCl ): d = 24.1, 28.4, 49.1, 50.5, 57.3, 91.9,
3
1
19.7, 121.5, 126.8, 128.6, 130.5, 136.5, 139.2, 142.5, 170.1.
2
0
+
Yield: 67%; white solid; mp 127–129 °C; [a]
CHCl ); 88% ee.
D
–26.5 (c 0.22,
HRMS: m/z [M + H] calcd for C H N OI: 382.0416; found:
1
5
17
3
3
3
82.0417.
–
1
IR (KBr): 1761, 14871463, 1285, 1065, 742 cm .
Enantioselective Synthesis of 3-Substituted Phthalides; Typical
Procedure
(
1
H NMR (400 MHz, CDCl ): d = 7.90 (d, J = 7.6 Hz, 1 H), 7.60 (t,
3
J = 7.5 Hz, 1 H), 7.51 (t, J = 7.5 Hz, 1 H), 7.45 (d, J = 7.8 Hz, 2 H),
7
R)-3-Phenylisobenzofuran-1(3H)-one16b (Table 1, Entry 3)
.24 (d, J = 7.6 Hz, 1 H), 7.09 (d, J = 7.8 Hz, 2 H), 6.29 (s, 1 H).
Under an Ar atmosphere, a four-necked flask equipped with a mag-
netic stirrer was charged with amide 2 (380 mg, 1.0 mmol) and THF
–)-3-(2-Chlorophenyl)isobenzofuran-1(3H)-one21 (Table 1, En-
try 6)
(
(
1
40 mL). The mixture was cooled to –70 °C, and i-PrMgCl (1.0 mL,
.2 mmol) was slowly added by a syringe. The mixture was stirred
2
0
Yield: 67%; white solid; mp 120–124 °C; [a]
–139.1 (c 0.30,
D
CHCl ); 82% ee.
at –70 °C for 3 h, then a solution of benzaldehyde (127 mg, 1.2
mmol) in THF (40 mL) was added slowly during 1 h. After addi-
tion, the mixture was stirred at –70 °C for 3 h [for reactions with
3
–
1
IR (KBr): 1766, 1466, 1443, 1285, 1063, 760 cm .
1
H NMR (400 MHz, CDCl ): d = 7.90 (d, J = 7.6 Hz, 1 H), 7.58 (t,
3
zinc reagents, ZnCl (1.6 g, 1.2 mmol) was added before the addi-
2
J = 7.5 Hz, 1 H), 7.45–7.51 (m, 2 H), 7.41 (d, J = 7.9 Hz, 1 H), 7.24
tion of an aldehyde and the temperature was allowed to come to r.t.
slowly; the aldehyde solution was added and stirred overnight]. The
(
t, J = 7.7 Hz, 1 H), 7.16 (t, J = 7.4 Hz, 1 H), 7.03 (t, J = 7.4 Hz,
H), 6.89 (s, 1 H).
1
reaction was quenched with 10% aqueous NaHCO (90 mL) and ex-
3
(R)-3-(4-Chlorophenyl)isobenzofuran-1(3H)-one14a
(Table 1,
tracted with CH Cl (3 × 70 mL). The organic layers were com-
2
2
bined and dried over anhydrous Na CO . After removal of the
Entry 15)
2
3
solvent, the residue was dissolved in toluene (60 mL) and p-TsOH
1.8 g, 1.0 mmol) was added. The mixture was heated at reflux for
h, then a solution of 2% aq H SO (50 mL) was added and the
20
Yield: 65%; white solid; mp 126–128 °C; [a]D –32.6 (c 0.35,
(
5
CHCl ); 88% ee.
3
2
4
–
1
IR (KBr): 1757, 1487, 1457, 1284, 1066, 1004, 746 cm .
aqueous layer was separated to recover the chiral template 1. The
Synthesis 2011, No. 21, 3435–3438 © Thieme Stuttgart · New York

3
438
Z.-B. Zhang et al.
PAPER
1
H NMR (400 MHz, CDCl ): d = 7.98 (d, J = 7.6 Hz, 1 H), 7.67 (t,
(8) Arnone, A.; Assante, G.; Nasini, G.; Strada, S.; Vercesi, A.
J. Nat. Prod. 2002, 65, 48.
3
J = 7.5 Hz, 1 H), 7.58 (t, J = 7.5 Hz, 1 H), 7.37 (d, J = 7.8 Hz, 1 H),
7
.32 (d, J = 7.8 Hz, 1 H), 7.23 (d, J = 7.8 Hz, 2 H), 6.39 (s, 1 H).
(9) Puder, C.; Zeeck, A.; Beil, W. J. Antibiot. 2000, 53, 329.
(10) Kosaka, M.; Sekiguchi, S.; Naito, J.; Uemura, M.;
Kuwahara, S.; Watanabe, M.; Harada, N.; Hiroi, K. Chirality
2005, 17, 218.
R)-3-(n-Propyl)isobenzofuran-1(3H)-one16b (Table 1, Entry 17)
(
2
0
Yield: 65%; colorless oil; [a]D +49.7 (c 0.23, CHCl ); 80% ee.
3
–
1
(11) (a) Momin, R. A.; Nair, M. G. J. Agric. Food Chem. 2001,
IR (neat): 1763, 1466, 1286, 1070, 746 cm .
49, 142. (b) Wang, X. W. Drugs Future 2000, 25, 16.
1
H NMR (400 MHz, CDCl ): d = 7.89 (d, J = 7.7 Hz, 1 H), 7.67 (td,
3
(c) Zheng, G. Q.; Kenny, P. M.; Zhang, J.; Lam, L. K. T.
J = 7.5, 1.0 Hz, 1 H), 7.52 (t, J = 7.5 Hz, 1 H), 7.43 (dd, J = 7.7,
Nutr. Cancer 1993, 19, 77. (d) Sato, H.; Yorozu, H.;
Yamaoka, S. Biomed. Res. 1993, 14, 385. (e) Yu, S.; You,
S.; Chen, H. Yaoxue Xuebao 1984, 101, 486; Chem. Abstr.
1984, 101, 222490c.
0
1
.7 Hz, 1 H), 5.48 (dd, J = 4.0, 8.1 Hz, 1 H), 1.97–2.03 (m, 1 H),
.72–1.78 (m, 1 H), 1.48–1.56 (m, 2 H), 0.99 (t, J = 7.4 Hz, 3 H).
(
1
R)-3-(Isopropyl)isobenzofuran-1(3H)-one16b (Table 1, Entry
8)
(12) For recent selected papers, see: (a) Zhang, B.; Xu, M.-H.;
Lin, G.-Q. Org. Lett. 2009, 11, 4712. (b) Everaere, K.;
Mortreux, A.; Carpentier, J.-F. Adv. Synth. Catal. 2003, 345,
2
0
Yield: 62%; white solid; mp 50–52 °C; [a]
CHCl ); 77% ee.
+51.8 (c 0.18,
D
3
67.
–
1
IR (KBr): 1759, 1465, 1456, 1285, 1071, 743 cm .
(13) Phan, D. H. T.; Kim, B.; Dong, V. M. J. Am. Chem. Soc.
1
H NMR (400 MHz, CDCl ): d = 7.83 (d, J = 7.6 Hz, 1 H), 7.60 (t,
2009, 131, 15608.
3
J = 7.4 Hz, 1 H), 7.46 (t, J = 7.4 HZ, 1 H), 7.38 (d, J = 7.6 Hz, 1 H),
(14) (a) Chang, H.-T.; Jeganmohan, M.; Cheng, C.-H. Chem.
Eur. J. 2007, 13, 4356. (b) Watanabe, M.; Hashimoto, N.;
Araki, S.; Butsugan, Y. J. Org. Chem. 1992, 57, 742.
5
.32 (s, 1 H), 2.21–2.24 (m, 1 H), 1.06 (d, J = 6.8 Hz, 3 H), 0.74 (d,
J = 6.8 Hz, 3 H).
(c) Soai, K.; Hori, H.; Kawahara, M. Tetrahedron:
(
R)-3-(tert-Butyl)isobenzofuran-1(3H)-one22 (Table 1, Entry 19)
Asymmetry 1991, 2, 253.
2
0
Yield: 60%; white solid; mp 60–62 °C; [a]D +11.8 (c 0.10,
CHCl ); 66% ee.
(15) (a) Xu, G.; Liu, Z.-Z.; Yang, J.-H.; Chen, S.-Z.; Yang, H.-Y.
Chin. Chem. Lett. 2007, 18, 653. (b) Ramachandran, P. V.;
Chen, G.-M.; Brown, H. C. Tetrahedron Lett. 1996, 37,
3
–
1
IR (KBr): 1757, 1461, 1291, 1218, 1076, 741 cm .
2205.
1
H NMR (400 MHz, CDCl ): d = 7.84 (d, J = 7.5 Hz, 1 H), 7.58 (t,
3
(16) (a) Min, Z.-L.; Zhang, Y.-H.; Lai, Y.-S.; Peng, S.-X. Chin.
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J = 7.5 Hz, 1 H), 7.44–7.47 (m, 2 H), 5.09 (s, 1 H), 0.96 (s, 9 H).
Acknowledgment
We gratefully acknowledge the National Nature Science Founda-
tion of China (Grant 20672014), the Beijing Key Subject Program,
Fundamental Research Funds for the Central Universities, and Dr.
Yao Ma for revising this manuscript.
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Synthesis 2011, No. 21, 3435–3438 © Thieme Stuttgart · New York