Stereoselective synthesis of kurzilactone and determination of its absolute configuration

Article abstract of DOI:10.1016/S0957-4166(01)00506-7

Both (5S,7S)- and (5R,7S)-isomers of kurzilactone were synthesized from a 'chiral epoxy-aldehyde synthon' through the coupling of an acyl anion equivalent and the dianion of acetoacetate, followed by formation of the Kawa-type lactone by cyclization and elimination. Comparing the spectral data of the synthesized and naturally occurring kurzilactone, the C(5)- and C(7)-stereogenic centers of the natural kurzilactone was assigned a corrected anti-relationship with (5R,7S)-absolute configuration.

Full text of DOI:10.1016/S0957-4166(01)00506-7

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 12 (2001) 2835–2843
Stereoselective synthesis of kurzilactone and determination of its
absolute configuration
Biao Jiang* and Zili Chen
Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Fenglin Road, Shanghai 200032, PR China
Received 12 October 2001; accepted 8 November 2001
Abstract—Both (5S,7S)- and (5R,7S)-isomers of kurzilactone were synthesized from a ‘chiral epoxy-aldehyde synthon’ through
the coupling of an acyl anion equivalent and the dianion of acetoacetate, followed by formation of the Kawa-type lactone by
cyclization and elimination. Comparing the spectral data of the synthesized and naturally occurring kurzilactone, the C(5)- and
C(7)-stereogenic centers of the natural kurzilactone was assigned a corrected anti-relationship with (5R,7S)-absolute configura-
tion. © 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
the (7S)-stereochemistry by coupling an acyl anion
equivalent 4 with an appropriate ‘chiral epoxy aldehyde
synthon’ 3, forming the C(5)-stereogenic center by con-
densation of the aldehyde function in the chiral synthon
3 with the acetoacetate dianion 5. The a,b-unsaturated-
d-lactone was formed by reduction and elimination of
the b-carbonyl group.
We disclose herein a strategy for the synthesis of kurzi-
lactone, a new Kawa-type lactone.1 Our interest in this
class of compounds stems from their close structural
relationship to the pharmacologically important statin
family which are highly potent inhibitors of 3-hydroxy-
3-methylglutaryl agent coenzyme A reductase.2 Kurzi-
lactone was isolated from leaves of Cryptocarya kurzii,
a plant which is indigenous to Malaysia. A preliminary
report included a tentative stereochemical assignment
established through an NMR experiment; both stereo-
genic centers bearing hydroxyl groups in the side chain
were assigned a syn-relationship. Kurzilactone shows
remarkable cytotoxicity against KB cells (IC50=1 mg/
mL).1a Because the absolute configuration of kurzilac-
tone has not been assigned, our synthetic strategy was
to develop an enantioselective synthetic method for
kurzilactone with hydroxyl groups in both syn- or
trans-relationship and to determine the absolute
configuration of the natural product.
2. Results and discussion
A convergent route toward kurzilactone was devised
through a simple disconnection of the two bonds, as
illustrated in Fig. 1. We envisaged the introduction of
* Corresponding author. E-mail: jiangb@pub.sioc.ac.cn
Figure 1. Retrosynthesis of kurzilactone.
0957-4166/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(01)00506-7

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B. Jiang, Z. Chen / Tetrahedron: Asymmetry 12 (2001) 2835–2843
The desired epoxy aldehyde synthon 3 was prepared
from ethyl (S)-4-chloro-3-hydroxy butanoate 7, which
was obtained from the commercial 4-chloroacetoacetate
63 in 94% yield (97% e.e.) by hydrogenation over cata-
lytic ruthenium-optically active phosphine complex
Ru(OAc)2[(R)-(−)-BINAP] (0.1% mol) at a pressure of
40 kg/cm2 at 100°C for 1.5 h. The chlorohydrin 7 was
protected as the tert-butyldimethylsilyl ether 8 ([h]2D0=
−21.7, c 1.03, CHCl3), which was reduced with LiAlH4
at 0°C,4 and oxidized the resulting alcohol 9 under
Swern conditions5 to give aldehyde 10 in 92%. The
aldehyde 10 was converted to diethyl acetal 11 in 74%
yield by treatment with triethyl orthoformate with
Amberlyst-15 as catalyst.6 Subsequent cleavage of the
silyl ether with tetrabutylammonium fluoride in THF7
directly gave the desired ‘chiral epoxy aldehyde syn-
thon’ equivalent 128 (Scheme 1).
gave a 76% yield of the 5,7-cis-dihydroxy ketone 19a
along with its trans-isomer 19b in a ratio of 1.7:1. These
isomers were separable by flash column chromatogra-
phy (Scheme 2).
To identify the stereochemistry of the two stereogenic
centers in 19a, the silyl group was removed by treat-
ment with pyridinium hydrofluoride. Treatment of the
resulting diol with dimethoxypropane gave the fixed
six-membered ring 1,3-dioxane 20. The relative stereo-
chemistry of C(5) and C(7) was assigned as syn with
(5R,7S)-configuration based on the NOE correlation
between the protons on C(5) and C(7) at chemical shift
4.10 and 4.25 ppm (Fig. 2), which was confirmed by
X-ray structural analysis of the final product. Thus, the
5,7-dihydroxy system in 19b had a trans-relationship
with (5S,7S)-configuration.
The aryl fragment was prepared from trans-cin-
namaldehyde 13, the aldehyde of which was trans-
formed into the thioacetal 14 in 70% with
1,3-propanedithiol and ceric ammonium nitrate as the
catalyst in chloroform.9 The epoxide 12 was coupled
with the acyl anion equivalent 14 (1.0 equiv.), prepared
by metallation at −78°C with 1.0 equiv. of n-butyl-
lithium in the presence of BF3·Et2O at −78°C to obtain
15 in 58% yield. After masking the resulting hydroxyl
group with tert-butyldimethylsilyl chloride, the diethyl
acetal 16 was treated with 50% aqueous CF3CO2H in
chloroform10 at 0°C over 2 h to give aldehyde 17 in
95% yield.
Compound 19 has the fully elaborated backbone of
kurzilactone. The syn-dihydroxyl group of natural
kurzilactone was tentatively deduced on the basis of
NOE correlation between C(5)H and C(7)H. To the
best of our knowledge, it is difficult to assign the
relationship between the 1,3-dihydroxyl system and the
methylene group in the open chain.12 To determine the
correct absolute configuration of natural kurzilactone,
both isomers of kurzilactone were synthesized by the
following steps. The ketone function in 19 was reduced
with NaBH4 in THF at −40°C to yield the hydroxy
ester 21, which was cyclized by treatment with catalytic
p-TsOH in CH2Cl2 at room temperature to form b-
hydroxy-d-lactone 22.13 Elimination of the b-hydroxyl
group in 22 was effected via mesylate displacement by
treatment with methanesulfonyl chloride and triethy-
lamine in dichloromethane,14 which afforded the a,b-
unsaturated-d-lactone 23. After cleavage of the
thioketal with HgClO4/CaCO3 in THF/H2O (5:1)15 and
removal of the silyl protecting group,16 (5S,7S)-kurzi-
lactone 25a and (5R,7S)-kurzilactone 25b were
obtained in 58 and 79% yields, respectively (Scheme 3,
Fig. 3).
The acetoacetate dianion provides a four-carbon chain
to homologate simpler molecules. The utility of this
homologation is that all four carbons can subsequently
be reacted regioselectively. Thus, the acetoacetate unit
is one of the most versatile starting materials available
in the synthesis of complex natural products. Despite
the simplicity of the idea, only a few reactions of
1,3-dianions and 1,3-dianion equivalents with 1,2-
dielectrophiles have been reported.11 Ethyl acetoacetate
18 was treated with sodium hydride in THF at 0°C.
The mixture was stirred for 10 min before cooling to
−10°C; then a solution of n-butyllithium in hexane was
added and the mixture was cooled to −50°C. Coupling
the aldehyde 17 with the dianion of ethyl acetoacetate 5
The structure of 25a was confirmed by determination of
the X-ray crystal structure, which demonstrated the
C(5) and C(7) hydroxyl groups had syn-relationship. In
comparing the spectral data of the synthesized and
O
OH
OTBDMS
CO2Et
a
b
c
Cl
CO2Et
Cl
CO2Et
Cl
6
7
8
OTBDMS
CH2OH
OTBDMS
CH(OEt)2
OTBDMS
CHO
d
e
f
O
CH(OEt)2
12
Cl
Cl
Cl
11
9
10
Scheme 1. Reagents: (a) H2/Ru(OAc)2[(R)-BINAP]/EtOH, 40 kg/cm2, 100°C, 1.5 h, 94%; (b) TBDMSCl/imidazole/DMAP/
CH2Cl2, 24 h, 98%; (c) LiAlH4/Et2O, 0°C, 2 h, 91%; (d) (COCl)2/DMSO/Et3N/CH2Cl2, −60°C, 92%; (e) HC(OEt)3/Amberlyst-15/
CH2Cl2, rt, 48 h, 74%; (f) n-Bu4NF/THF, 24 h, 60%.

B. Jiang, Z. Chen / Tetrahedron: Asymmetry 12 (2001) 2835–2843
2837
CAN
S
O
CH(OEt)2
HS(CH ) SH
CHO
2 3
+
S
70%
12
n-BuLi
14
13
58%
BF3.Et2O
TBDMSCl
Imidazole
OH
OTBDMS
S
S
S
S
CH(OEt)2
CH(OEt)2
81%
16
15
95%
50% CF3COOH
OTBDMS
CHO
O
O
S
S
+
O
17
18
1, NaH, 0 oC
2, n-BuLi, -10 oC
then -50 oC
76%
OR OH
O
OR OH
O
S
S
S
S
+
CO2Et
CO2Et
19a R=TBDMS,
19b R=TBDMS
Scheme 2.
4.25ppm
H7
S
S
H5
O
O
O
O
S
S
CO2Et
O
7
5
4.10 ppm
O
20
EtO2C
Figure 2. NOEs of C(5)H and C(7)H.
natural kurzilactone, the synthesized kurzilactone 25b
has the same spectral data [1H NMR in CDCl3, 1H
NMR in benzene-d6, 13C NMR, NOESY and a posi-
tive specific rotation: [h]2D0=+84 (c 0.23, CHCl3) com-
parable with the reported specific rotation:
[h]2D0=+100, c 2.4, CHCl3)].1a Isomer 25a has different
C(5)H and C(7)H chemical shifts (lH: 4.40 and 4.20
ppm 1H NMR in benzene-d6), whereas the chemical
shifts of C(5)H and C(7)H in the natural product are
equivalent at lH: 4.48 ppm (Table 1). Compound 25a
also shows negative optical rotation ([h]2D0=−60.8, c
0.68, CHCl3). By comparison of the spectral data for
the synthesized and naturally isolated kurzilactones,
the correct stereochemistry of the C(5) and C(7)
stereogenic centers of naturally occurring Kurzilactone
is anti-(5R,7S).

2838
B. Jiang, Z. Chen / Tetrahedron: Asymmetry 12 (2001) 2835–2843
OR OH
O
OR OH OH
NaBH4
S
S
S
S
CO2Et
CO2Et
(93%)
21 a
19 a (5R,7S)
19 b (5S,7S)
R=TBDMS
21 b (92%)
R=TBDMS
p-TsOH
O
O
O
OR
O
OR
S
S
S
S
MsCl, Et3N
OH
(54%)
(53%)
(91%)
23 a
23 b
22 a
22 b
(91%)
R = TBDMS
R = TBDMS
O
HgClO4
CaCO3
O
OH O
O
O
OR
O
HF, CH3CN
25 a
(58%)
(5S,7S)-Kurzilactone
O
O
OH O
R = TBDMS
(74%)
(76%)
24 a
24 b
25 b (5R,7S)-Kurzilactone (79%)
Scheme 3.
4. Experimental
4.1. Ethyl (S)-4-chloro-3-hydroxybutanonate 7
An autoclave was charged with a solution of ethyl
4-chloro-3-oxobutanonate 6 (20 g, 121.5 mmol) in
methanol (300 mL) and was hydrogenated over
Ru(OAc)2[(R)-(−)-BINAP] (200 mg) at a pressure of 40
kg/cm3 at 100°C for 1.5 h. The reaction mixture was
concentrated under reduced pressure. The residue was
distilled under reduced pressure to afford 7 (19 g, 94%)
as a colorless oil, bp 95–97°C/3 mmHg. The enan-
tiomeric excess of 7 was determined to be 97% e.e. by
HPLC analysis of the corresponding (R)-MTPA ester.
[h]2D0=−20.5 (c 5.5, CHCl3) [lit.3a for (S)-7 in 96% e.e.,
[h]2D4=−19.1 (c 7.71, CHCl3)].
Figure 3. The X-ray crystal structure of compound 25a.
3. Conclusions
In conclusion, a practical convergent pathway has been
developed for the synthesis of both (5S,7S)- and
(5R,7S)-isomers of kurzilactone by the coupling of an
acyl anion equivalent with the dianion of acetoacetate
and a ‘chiral epoxy aldehyde synthon,’ followed by
formation of the Kawa type-lactone by cyclization and
elimination. By comparison of the spectral data of the
synthesized and naturally occurring kurzilactone, the
two stereogenic carbons in natural kurzilactone were
assigned a corrected (5R,7S)-configuration.
4.2. Ethyl (S)-4-chloro-3-(tert-butyldimethylsilyloxyl)-
butanoate 8
A solution of compound 7 (1.66 g, 10 mmol) in CH2Cl2
(30 mL) was stirred with tert-butyldimethysilylchloride
(2 g, 13.2 mmol), imidazole (3.4 g, 50 mmol) and a
catalytic amount of DMAP (10 mg) overnight at rt
under N2. The reaction mixture was poured into water
(20 mL) and was then neutralized by dropwise addition

B. Jiang, Z. Chen / Tetrahedron: Asymmetry 12 (2001) 2835–2843
2839
Table 1. 1H NMR in CCl3D and C6D6 data for naturally isolated kurzilactone and synthesized (5S,7S)-kurzilactone 25a and
(5R,7S)-kurzilactone 25b
C
Naturally isolated kurzilactone 1a
lH (J Hz) CDCl3 lH (J Hz) C6D6
(5R,7S)-Kurzilactone 25b
(5S,7S)-Kurzilactone 25a
lH (J Hz) C6D6
6.04 dd, 1H (10, 2) 5.80 dd, 1H (9.8, 2)
lH (J Hz) CDCl3 lH (J Hz) C6D6 lH (J Hz) CDCl3
2
3
4
5
6
6.00 dd, 1H (10, 2)
5.77 dd, 1H (10, 2) 6.00 dd, 1H (10, 2)
5.77 m, 1H
5.97 m, 1H
1.59 m, 2H
4.48 m, 1H
1.59 m, 2H
6.90 ddd, 1H (10, 5.5, 3) 5.97 m, 1H
6.90 m, 1H
2.39 m, 2H
4.77 m, 1H
1.88 m, 2H
6.90 m, 1H
2.47 m, 2H
4.78 m, 1H
2.10 m, 1H
1.90 m, 1H
4.40 m, 1H
2.95 m, 2H
5.97 m, 1H
1.50 m, 2H
4.40 m, 1H
2.50 m, 1H
2.30 m, 1H
4.20 m, 1H
1.50 m, 2H
2.39 m, 2H
4.77 m, 1H
1.88 m, 2H
1.59 m, 1H
4.48 m, 1H
1.59 m, 2H
7
8
4.50 m, 1H
2.81 dd, 1H (17, 8)
2.93 dd, 1H (17, 3.5)
4.48 m, 1H
2.53 m, 2H
4.50 m, 1H
4.48 m, 1H
2.81 dd, 1H (17.4, 8.8) 2.53 m, 2H
2.93 dd, 1H (17.4, 2.8)
10 6.73 d, 1H (16)
11 7.58 d, 1H (16)
6.58 d, 1H (16)
7.50 d, 1H (16)
6.73 d, 1H (16)
7.58 d, 1H (16)
6.58 d, 1H (16) 6.74 d, 1H (16)
7.50 d, 1H (16) 7.60 d, 1H (16)
6.50 d, 1H (16)
7.45 d, 1H (16)
2%
3% 7.39–7.54, 5H
7.00–7.30, 5H
7.39–7.54, 5H
7.00–7.30, 5H
7.26–7.57, 5H
7.00–7.20, 5H
4%
5%
6%
4.4. (S)-4-Chloro-3-(tert-butyldimethylsilyloxyl)butanal
of cold aqueous HCl (0.5 M). The aqueous phase was
extracted with CH2Cl2 (2×10 mL). The combined organic
phase was washed with saturated aqueous Na2CO3 and
brine, dried with anhydrous Na2SO4. After removal of
solvent, the residue was purified by flash column chro-
matography on silica gel (eluted with petroleum ether/
CH2Cl2=3:1) to give 8 as a colorless oil (2.75 g, 98%):
[h]2D0=−21.7 (c 1.03, CHCl3); IR (neat) 2958, 2932, 2859,
1739, 1473, 1378, 1311 cm−1; 1H NMR (CDCl3) l 4.3 (m,
1H), 4.15 (q, J=7.2 Hz, 2H), 3.5 (m, 2H), 2.7 (dd,
J=15.2 Hz, 4.8 Hz, 1H), 2.5 (dd, J=15.2 Hz, 7.2 Hz,
1H), 1.25 (t, J=7.2 Hz, 3H), 0.85 (s, 9H), 0.15 (s, 3H),
0.10 (s, 3H) ppm; 13C NMR (CDCl3) l 171.0, 69.6, 60.7,
48.2, 40.5, 25.7, 18.0, 14.3, −4.6, −4.9 ppm; Ms m/e
(relative intensity) 281 (M++1, 85), 245 (59), 223 (100),
195 (46), 171 (17), 115 (26), 85 (41), 75 (36); HRMS calcd
for C12H26O3SiCl: 281.1339; found: 281.1336.
10
To a solution of oxalyl chloride (1.1 mL) in dry CH2Cl2
(30 mL) was added DMSO (1.8 mL) and the mixture
heated at −60°C under N2 for 25 min. A solution of
compound 9 (2.14 g, 9 mmol) in dry CH2Cl2 (5 mL) was
added dropwise. The reaction mixture was stirred for a
further 2 h, Et3N (7 mL) was added and the mixture
stirred for 0.5 h. The mixture was allowed to warm to
rt and then poured into ice-water (50 mL). The aqueous
phase was extracted with CH2Cl2 (3×15 mL). The com-
bined organic phase was washed with brine, dried
(Na2SO4) and filtered. Concentration of the filtrate
followed by flash column chromatography on silica gel
(eluted with petroleum ether/CH2Cl2=3:1) yielded alde-
hyde 10 as a colorless oil (1.95 g, 92%): [h]2D0=−17.6 (c
1.650, CHCl3); IR (neat) 2958, 2932, 2898, 2860, 1728,
1435, 1312 cm−1; 1H NMR (CDCl3) l 9.8 (t, J=1.84 Hz,
1H), 4.35 (m, 1H), 3.55 (dd, J=11 Hz, 4.8 Hz, 1H), 3.45
(dd, J=11 Hz, 6.4 Hz, 1H), 2.75 (m, 2H), 0.9 (s, 9H),
0.15 (s, 3H), 0.1 (s, 3H) ppm; 13C NMR (CDCl3) l 200.4,
67.9, 48.8, 48.0, 25.6, 18, −4.6, −4.9 ppm; Ms m/e (relative
intensity) 237 (M++1, 4), 217 (M+−29, 3), 179 (M+−57,
26), 149 (47), 117 (100), 101 (96), 75 (83); HRMS calcd
for C10H21O2SiCl: 236.0999; found: 236.0955.
4.3. (S)-4-Chloro-3-(tert-butyldimethylsilyloxyl)butanol
9
A solution of 8 (560 mg, 2 mmol) in Et2O (5 mL) was
added slowly to a solution of LiAlH4 (76 mg) in Et2O
(20 mL) at 0°C. The reaction mixture was allowed to
warm to room temperature slowly. After stirring for 2
h at rt, a few drops of ethyl acetate was added to quench
the reaction. The reaction mixture was filtered through
Celite and washed with ether (3×20 mL). Concentration
of the filtrate followed by flash column chromatography
(eluted with petroleum ether/EtOAc=3:1) gave 9 as a
colorless oil (435 mg, 91%): [h]2D0=−15.3 (c 1.75, CHCl3);
IR (neat) 3359, 2957, 2859, 1473 cm−1; 1H NMR (CDCl3)
l 4.15 (m, 1H), 3.75 (m, 2H), 3.5 (d, J=5.77 Hz, 2H),
2.2 (br, 1H), 1.8 (m, 2H), 0.85 (s, 9H), 0.15 (s, 6H) ppm;
13C NMR (CDCl3) l 71.0, 59.4, 48.0, 36.6, 25.9, 18.1,
−4.5, −4.8 ppm; Ms m/e (relative intensity) 238 (M+, 0.2),
223 (100), 221 (2), 181 (4), 167 (12), 149 (44), 107 (50),
71 (20), 43 (100); HRMS calcd for C6H14O2SiCl:
181.0451; found: 181.0453.
4.5. (S)-4-Chloro-1,1-diethoxy-(tert-butyldimethylsilyl-
oxyl)butane 11
A mixture of orthoformic acid triethyl ester (8 mL) and
compound 10 (2.36 g, 10 mmol) in CH2Cl2 (20 mL) was
stirred with Amberlyst-15 (1 g) under N2 for 48 h at rt.
The catalyst was filtered and washed with CH2Cl2 (2×10
mL). After removal of the solvent, the crude product was
purified by flash column chromatography on silica gel
(eluted with petroleum ether/CH2Cl2=4:1) to give 11 as
a colorless oil (2.28 g, 74%). [h]2D0=−10.8 (c, 0.481,
CHCl3); IR (neat) 2931, 1473, 1377, 1257, 1125, 1091,
1
1065 cm−1; H NMR (CD3COCD3) l 4.70 (m, 1H), 4.1

2840
B. Jiang, Z. Chen / Tetrahedron: Asymmetry 12 (2001) 2835–2843
(m, 1H), 3.7 (m, 4H), 3.5 (m, 2H), 1.9 (m, 1H), 1.8 (m,
1H), 1.15 (m, 6H), 0.9 (s, 9H), 0.15 (s, 3H), 0.13 (s, 3H)
ppm; 13C NMR (CD3COCD3) l 101.3, 70.8, 62.4, 62.0,
50.9, 40.6, 26.8, 19.0, 16.3, −3.6, −3.9 ppm; Ms m/e
(relative intensity) 310 (M+, 0.4), 265 (42), 229 (19), 193
(100), 143 (40), 103 (72); HRMS calcd for
C12H26O2SiCl: 265.1390; found: 265.1385.
with brine, dried (Na2SO4) and filtered. Concentration
of the filtrate followed by flash column chromatogra-
phy on silica gel (eluted with petroleum ether/
EtOAc=5:1) yielded 15 as a colorless oil (220 mg,
58%): [h]2D0=−4.2 (c 0.502, CH3COCH3); IR (neat)
3487, 2974, 2929, 1447, 1423, 1375, 1124 cm−1; 1H
NMR (CD3COCD3) l 7.5 (m, 2H), 7.3 (m, 2H), 7.25
(m, 1H), 6.9 (d, J=15.9 Hz, 1H), 6.4 (d, J=15.9 Hz,
1H), 4.7 (m, 1H), 4.1 (m, 1H), 3.65 (m, 2H), 3.45 (m,
2H), 2.9 (m, 2H), 2.75 (m, 2H), 2.2 (m, 2H), 2.0 (m,
2H), 1.8 (m, 1H), 1.7 (m, 1H), 1.1 (m, 6H) ppm; Ms
m/e (relative intensity) 382 (M+, 3), 336 (M+−46, 79),
290 (51), 237 (57), 221 (100), 185 (36), 161 (37), 129
(90), 103 (48); anal. calcd for C20H30O3S2: C, 62.79; H,
7.90. Found: C, 63.16; H, 8.13%.
4.6. (S)-(1,1-Diethoxy)-3-epoxybutane 12
To a solution of 11 (1.18 g, 3.8 mmol) in dry CH2Cl2
(20 mL) was added a solution of n-Bu4NF in THF
(1.0 M, 10 mL, 10 mmol) for 24 h at rt under N2. The
reaction mixture was then poured into water (20 mL)
and extracted with CH2Cl2 (3×5 mL). The combined
organic extracts were washed with brine, dried
(Na2SO4) and filtered. The solvent was removed under
reduced pressure keeping the heating bath below 15°C.
The residue was subjected to flash chromatography
(eluted with petroleum ether (30–60)/CH2Cl2=5:1) to
yield epoxide 12 as a colorless oil (367 mg, 60%):
[h]2D0=−7 (c 0.502, CHCl3); IR (neat) 2962, 1368, 1260,
4.9. 2-((4,4-Diethoxy-(2S)-(tert-butyldimethyl-
siloxyl))butyl)-2-(2-phenyl-1-ethenyl)-1,3-dithiane 16
A solution of 15 (200 mg, 0.52 mmol) in CH2Cl2 (10
mL) was treated with tert-butyldimethylsilylchloride
(150 mg, 1 mmol) and imidazole (200 mg, 2.94 mmol)
under N2 overnight at rt. The mixture was diluted
with CH2Cl2 (20 mL), and the resulting solution was
washed with cold aqueous HCl (0.5 M, 2×10 mL),
saturated Na2CO3, and brine. The organic phase was
dried over anhydrous Na2SO4. After removal of sol-
vent in vacuo, the residue was purified by flash chro-
matography on silica gel (eluted with petroleum
ether/EtOAc=20:1) to give 16 as a colorless oil (210
mg, 81%): [h]2D0=+17.3 (c, 1.32, CH3COCH3); IR
(neat) 2956, 2930, 2857, 1472, 1447, 1377, 1255, 1118,
1
1142, 1058, 981, 960, 882 cm−1; H NMR (CDCl3) l
4.7 (dd, J=6.7 Hz, 4.7 Hz, 1H), 3.65 (m, 4H), 3.1 (m,
1H), 2.75 (t, J=4.5 Hz, 1H), 2.5 (dd, J=5 Hz, 2.7 Hz,
1H), 1.8 (m, 2H), 1.25 (m, 6H) ppm; 13C NMR
(CDCl3) l 101.5, 62.2, 61.7, 49.1, 46.8, 38.1, 15.6 ppm;
Ms m/e (relative intensity) 160 (M+, 10), 149 (100),
133 (5), 105 (11), 103 (15).
4.7. 2-(1-Styryl)-1,3-dithian 14
1
A mixture of trans-cinnamaldehyde (13.2 g, 12.6 mL,
100 mmol), 1,3-propanedithiol (12 mL, 120 mmol) and
ceric amonium nitrate (5.48 g, 10 mmol) in dry CHCl3
(250 mL) was stirred overnight at rt. The reaction
mixture was diluted with CHCl3 (1 L), then washed
with 5% aqueous NaOH solution (3×100 mL) and
dried. The solvent was removed under reduced pres-
sure and the brown residue was purified through flash
chromatography over silica gel (eluted with petroleum
ether/EtOAc=5:1) to afford 14 as needles (15.4 g,
70%): mp 57–58°C; IR (KBr) 3027, 2898, 1496, 1448,
1066 cm−1; H NMR (CD3COCD3) l 7.5 (m, 2H), 7.3
(m, 3H), 6.8 (d, J=15.9 Hz, 1H), 6.25 (d, J=15.9 Hz,
1H), 4.8 (m, 1H), 4.15 (m, 1H), 3.55 (m, 2H), 3.3 (m,
2H), 2.9 (m, 2H), 2.7 (m, 2H), 2.15 (m, 2H), 2.05 (m,
2H), 1.8 (m, 1H), 1.6 (m, 1H), 1.05 (m, 6H), 0.9 (s,
9H), 0.15 (s, 3H), 0.12 (s, 3H) ppm; Ms m/e (relative
intensity) 450 (M+−46, 10), 439 (M+−57, 2), 379 (4),
221 (92), 189 (45), 129 (56), 103 (100), 75 (71); anal.
calcd for C26H44O3S2Si: C, 62.85; H, 8.93. Found: C,
63.03; H, 8.90%.
1
1422, 1275, 1169 cm−1; H NMR (CDCl3) l 7.30 (m,
4.10. (3S)-(tert-Butyldimethylsilyloxyl)-4-(2-styryl-
[1,3]dithian-2-yl)-butyraldehyde 17
5H), 6.75 (d, J=16 Hz, 1H), 6.25 (dd, J=16 Hz, 7
Hz, 1H), 4.75 (d, J=7 Hz, 1H), 2.9 (m, 4H), 2.15 (m,
1H), 1.85 (m, 1H) ppm; Ms m/e (relative intensity) 222
(M+, 100), 189 (13), 147 (89), 129 (4), 115 (23), 103
(3). Anal. calcd for C12H14S2: C, 64.81; H, 6.35.
Found: C, 64.54; H, 6.34.
To a solution of 16 (218 mg, 0.44 mmol) in chloro-
form (4 mL) was added 50% aqueous CF3COOH (2
mL) in dropwise at 0°C. After 2 h the mixture was
poured into saturated aqueous Na2CO3 (20 mL). The
aqueous phase was extracted with CH2Cl2 (3×10 mL).
The combined organic phase was washed with brine
and dried (Na2SO4). After removal of solvent in
vacuo, the residue was purified by flash chromatogra-
phy on silica gel (eluted with petroleum ether/
EtOAc=10:1) to give 17 as a white solid (176 mg,
4.8. (S)-4,4-Diethoxy-1-(2-styryl-[1,3]dithian-2-yl)butan-
2-ol 15
To a solution of 14 (444 mg, 2 mmol) and 12 (160 mg,
1 mmol) in dry THF (25 mL) was added a solution of
n-BuLi in hexane (1.0 M, 2 mL, 2 mmol) at −78°C
under N2 for 25 min. Then a solution of BF3·Et2O
(0.07 mL) in dry THF (2 mL) was added dropwise.
After 1 h, the reaction was quenched by the slow
addition of MeOH (0.2 mL) followed by saturated
aqueous NH4Cl (2 mL). The mixture was extracted
with CH2Cl2 (3×10 mL). The extracts were washed
95%):
mp
56–58°C;
[h]2D0=+10.5
(c
0.605,
CH3COCH3); IR (KBr) 2957, 2911, 2851, 2726, 1720,
1472, 1253, 1127, 1086, 1072 cm−1; H NMR (CDCl3)
1
l 9.8 (s, 1H), 7.45 (m, 2H), 7.35 (m, 3H), 6.82 (d,
J=15.8 Hz, 1H), 6.25 (d, J=15.9 Hz, 1H), 4.5 (m,
1H), 2.95 (m, 2H), 2.8 (m, 1H), 2.7 (m, 2H), 2.6 (m,
1H), 2.25 (d, J=5.8 Hz, 2H), 2.0 (m, 2H), 0.85 (s,

B. Jiang, Z. Chen / Tetrahedron: Asymmetry 12 (2001) 2835–2843
2841
9H), 0.15 (s, 3H), 0.12 (s, 3H) ppm; Ms m/e (relative
intensity) 422 (M+, 1), 365 (M+−57, 0.7), 291 (2), 247
(4), 221 (15), 129 (100), 73 (34); anal. calcd for
C22H34O2S2Si: C, 62.51; H, 8.11. Found: C, 62.64; H,
8.09%.
treated with 2,2-dimethoxylpropane (2 mL), DMF (0.1
mL) and p-TsOH (10 mg) at 0°C overnight. The reac-
tion mixture was diluted with CH2Cl2 (10 mL) and
washed with saturated aqueous Na2CO3 (20 mL),
brine and distilled water, dried (Na2SO4) and filtered.
Concentration of the filtrate followed by flash column
chromatography on silica gel (eluted with petroleum
ether/EtOAc=10:1) yielded 20 as a colorless oil (10
mg, 29%). [h]2D0=+3.7 (c 0.301, CH3COCH3); IR (neat)
2935, 2846, 1739, 1709, 1472, 1379, 1285 cm−1. 1H
NMR (CDCl3) l 7.35–7.0 (m, 5H), 6.95 (d, J=15.8
Hz, 1H), 6.35 (d, J=15.8 Hz, 1H), 4.25 (m, 1H), 4.10
(m, 1H), 3.9 (m, 2H), 3.1 (s, 2H), 2.7 (m, 2H), 2.4–2.2
(m, 6H), 2.05 (m, 2H), 1.65 (m, 2H), 1.25–1.5 (m, 6H),
0.95 (m, 3H) ppm; FAB Ms m/e (relative intensity)
479 (M++1, 100). Ms m/e: anal. calcd for C25H34O5S2:
C, 62.73; H, 7.16. Found C, 62.80; H, 7.45%.
4.11. Preparation of compounds 19a and 19b
To a suspension of NaH (60%, 48 mg) in dry THF (20
mL) under N2 was added dropwise ethyl acetoacetate
(130 mg) in dry THF (5 mL) at 0°C over 1 h. The
mixture was stirred for 10 min before cooling to −
10°C; then a solution of n-BuLi in hexane (2.0 M, 0.5
mL, 1 mmol) was added dropwise and cooled to −
50°C. The mixture was stirred for a further 25 min
and then a solution of aldehyde 17 (400 mg, 0.95
mmol) in dry THF (5 mL) was added and the mixture
stirred for 1 h, followed by addition of MeOH (0.3
mL) and saturated NH4Cl (5 mL). The aqueous phase
was extracted with CH2Cl2 (10 mL). The combined
organic phase was washed with brine, dried (Na2SO4)
and filtered. Concentration of the filtrate followed by
flash column chromatography on silica gel (eluted with
petroleum ether/EtOAc=4:1) yielded 19a (250 mg)
and 19b (148 mg) in 76% of yield. Data for 19a:
[h]2D0=+16 (c 0.104, CH3COCH3); IR (neat) 3528,
2955, 2930, 2857, 1743, 1714, 1472, 1412, 1368, 1316
4.13. Preparation of compounds 21a and 21b
A solution of 19a (400 mg, 0.72 mmol) in dry THF
(20 mL) under N2 was treated with NaBH4 (10 mg) in
one portion for 1 h at −40°C, then 0.2 M aqueous
HCl (10 mL) was added to end the reaction. The
aqueous phase was extracted with CH2Cl2 (2×10 mL)
and the combined organic phase was washed with
saturated aqueous Na2CO3, brine, dried (Na2SO4) and
filtered. After removal of solvent in vacuo, the residue
was purified by flash column chromatography on silica
gel (eluted with petroleum ether/EtOAc=2:1) to yield
21a as a colorless oil (373 mg, 93%). IR (neat) 3467,
2955, 2929, 2857, 1734, 1472, 1447, 1375, 1256, 1190
cm−1; Ms m/e (relative intensity) 552 (M+−2, 1), 447
(34), 315 (24), 221 (38), 169 (100), 129 (57), 81 (58).
1
cm−1; H NMR (C6D6) l 7.5 (m, 2H), 7.3 (m, 3H), 7.1
(d, J=15.8 Hz, 1H), 6.5 (d, J=15.8 Hz, 1H), 4.65 (m,
1H), 4.5 (m, 1H), 4.08 (q, J=7.1 Hz, 2H), 3.2 (s, 2H),
2.8 (m, 2H), 2.6 (d, J=6.1 Hz, 2H), 2.5 (m, 2H), 2.42
(m, 2H), 1.9 (m, 2H), 1.75 (m, 1H), 1.5 (m, 1H), 1.15
(s, 9H), 1.05 (t, J=7.1 Hz, 3H), 0.4 (s, 3H), 0.35 (s,
3H) ppm. Ms m/e (relative intensity) 552 (M+, 1), 506
(M+−46, 4), 495 (3), 445 (7), 357 (7), 313 (8), 221 (42),
167 (58), 129 (100), 115 (22), 73 (43); anal. calcd for
C28H44O5S2Si: C, 60.83; H, 8.02. Found: C, 61.01; H,
8.20%.
21b was prepared same procedure as 21a in 92% yield:
IR 3490, 2954, 2931, 2857, 1735, 1472, 1373, 1333,
1257 cm−1; Ms m/e (relative intensity) 554 (M+, 5),
5.08 (M+−46, 13), 169 (88), 129 (100), 81 (46).
19b: [h]2D0=−15.0 (c, 0.254, CH3COCH3); IR (neat)
3499, 2955, 2931, 2857, 1744, 1715, 1472, 1412, 1314
1
cm−1. H NMR (C6D6) l 7.5 (m, 2H), 7.3 (m, 3H), 7.1
(d, J=15.8 Hz, 1H), 6.5 (d, J=15.8 Hz, 1H), 4.78 (m,
1H), 4.6 (m, 1H), 4.08 (q, J=7.1 Hz, 2H), 3.2 (s, 2H),
2.8 (m, 2H), 2.65 (d, J=6.1 Hz, 2H), 2.42 (m, 2H),
2.38 (d, J=3.6 Hz, 2H), 2.1 (m, 1H), 1.75 (m, 2H),
1.55 (m, 1H), 1.1 (s, 9H), 1.05 (t, J=7.1 Hz, 3H), 0.4
(s, 3H), 0.35 (s, 3H) ppm. Ms m/e (relative intensity)
552 (M+, 1), 506 (M+−46, 3), 449 (8), 357 (7), 313 (11),
221 (43), 167 (38), 129 (100), 115 (26), 73 (53); anal.
calcd for C28H44O5S2Si: C, 60.83; H, 8.02. Found C,
61.04; H, 8.06%.
4.14. Preparation of compounds 22a and 22b
To a solution of 21a (370 mg, 0.67 mmol) in CH2Cl2
(10 mL) was added p-toluenesulfonic acid (1 mg) and
the mixture stirred at rt for 2 h. The mixture was
poured into saturated NaHCO3 (10 mL) and extracted
with CH2Cl2 (3×5 mL). The combined organic phase
was washed with brine, dried (Na2SO4) and filtered.
Concentration of the filtrate followed by flash column
chromatography on silica gel (eluted with petroleum
ether/EtOAc=1:1) yielded 22a as a colorless oil (184
mg, 54%). IR (neat) 3443, 2955, 2929, 2856, 1756,
1735, 1472, 1389, 1361 cm−1; Ms m/e (relative inten-
sity) 508 (M+, 8), 451 (M+−57, 11), 433 (M+−57–18,
16), 377 (15), 273 (96), 221 (60), 129 (100), 73 (63).
4.12. Preparation of compound 20
A solution of 19a (40 mg, 0.072 mmol) in dry THF (2
mL) was treated with pyridinium hydrofluoride (0.1
mL, 65–70% in THF) under N2 for 10 h at 0°C. Then
a saturated aqueous NaHCO3 (20 mL) was added.
The mixture was extracted with CH2Cl2 (3×10 mL),
and the combined organic phase was washed with
brine and distilled water, dried (Na2SO4) and filtered.
After removal of the solvent in vacuo, the residue was
22b was prepared same procedure as 22a in 53% yield.
IR (neat) 3441, 2955, 2929, 2856, 1729, 1389, 1255
cm−1; Ms m/e (relative intensity) 508 (M+, 9), 451
(M+−57, 11), 433 (M+−57–18, 17), 401 (7), 377 (12),
273 (39), 221 (51), 129 (100), 73 (65).

2842
B. Jiang, Z. Chen / Tetrahedron: Asymmetry 12 (2001) 2835–2843
4.15. Preparation of compounds 23a and 23b
5.0 Hz, 1H), 2.8 (dd, J=15 Hz, 6.5 Hz, 1H), 2.3 (m,
2H), 2.05 (m, 1H), 1.75 (m, 1H), 0.85 (s, 9H), 0.15 (s,
6H) ppm; Ms m/e (relative intensity) 401 (M++1, 7),
343 (M+−57, 100), 325 (M+−57–18, 19), 255 (17), 231
(25), 131 (70); anal. calcd for C23H32O4Si: C, 68.96; H,
8.05; found: C, 68.47; H, 8.09%.
To a solution of 22a (180 mg, 0.35 mmol) and dry Et3N
(0.05 mL) in CH2Cl2 (20 mL) was added CH3SO2Cl
(0.08 mL, 1 mmol) at −40°C for 30 min. The mixture
was warmed to room temperature and was poured into
water (20 mL) and then extracted with CH2Cl2 (3×10
mL). The combined organic phase was washed with
brine, dried (Na2SO4) and filtered. Concentration of the
filtrate followed by flash chromatography on silica gel
(eluted with petroleum ether/EtOAc=2:1) yielded 23a
as a colorless oil (158 mg, 91%): [h]2D0=−28.1 (c 0.906,
CH3COCH3); IR (neat) 2954, 2929, 2856, 1727, 1472,
4.17. (5S,7S)-Kurzilactone 25a
To a solution of 24a (60 mg, 0.15 mmol) in CH3CN (15
mL) was added dropwise 70% aqueous HF (2 mL) and
the mixture stirred for 50 min at rt. The reaction
mixture was poured into saturated NaHCO3 (20 mL)
and extracted with CH2Cl2 (3×10 mL). The combined
organic phase was washed with brine, dried (Na2SO4)
and filtered. Concentration of the filtrate followed by
flash column chromatography on silica gel (eluted with
petroleum ether/EtOAc=1:1) yielded 25a as a white
solid (25 mg, 58%): mp 122–123°C; [h]2D0=−60.8 (c
0.683, CHCl3); IR (KBr) 3402, 2933, 1714, 1656, 1629,
1
1388, 1251, 1075, 1033, 1005 cm−1; H NMR (CDCl3) l
7.45 (d, J=7 Hz, 2H), 7.3 (3H, m), 6.82 (d, J=15.9 Hz,
1H), 6.8 (m, 1H), 6.2 (d, J=15.9 Hz, 1H), 5.95 (d,
J=9.7 Hz, 1H), 4.6 (m, 1H), 4.15 (m, 1H), 2.95 (m,
2H), 2.7 (m, 2H), 2.4–2.2 (m, 8H), 0.9 (s, 9H), 0.15 (s,
3H), 0.1 (s, 3H) ppm; Ms m/e (relative intensity) 490
(M+, 12), 433 (M+−57, 42), 293 (29), 255 (92), 221 (31),
169 (29), 129 (100), 75 (65); HRMS calcd for
C26H38O3S2Si: 490.2031; found: 490.2025.
1
1
1398, 1379, 1260, 1188 cm−1; H NMR (CDCl3) and H
NMR (C6D6) are listed in Table 1; 13C NMR (CDCl3)
l 200.4, 164.2, 145.3, 144.0, 130.9, 129.0, 128.5, 134.1,
126.0, 121.3, 75.5, 64.6, 46.6, 40.6, 30.0 ppm; Ms m/e
(relative intensity) 287 (M++1, 2), 269 (M++1–18, 3),
201 (7), 173 (13), 145 (20), 131 (100), 103 (33), 77 (13).
23b was obtained in 91% yield as a colorless oil using
the same procedure as that described for 23a: [h]2D0=
+21.3 (c 0.402, CH3COCH3); IR (KBr) 2954, 2929,
1
2856, 1720, 1389, 1251 cm−1; H NMR (CDCl3) l 7.5
X-Ray crystallation a=9.239(5), b=31.292(4), c=
3
,
,
(d, J=7.1 Hz, 2H), 7.4 (m, 2H), 7.3 (m, 1H), 6.9 (d,
J=15.9 Hz, 1H), 6.8 (m, 1H), 6.25 (d, J=15.9 Hz, 1H),
5.95 (d, J=9.8 Hz, 1H), 4.6 (m, 1H), 4.4 (m, 1H), 3.0
(m, 2H), 2.7 (m, 2H), 2.3 (m, 4H), 2.1 (m, 2H), 1.75 (m,
2H), 0.9 (s, 9H), 0.15 (s, 3H), 0.12 (s, 3H) ppm; Ms m/e
(relative intensity) 490 (M+, 9), 433 (M+−57, 27), 415
(M+−57–18, 9), 358 (37), 255 (54), 199 (52), 129 (100),
73 (44); HRMS calcd for C26H38O3S2Si: 490.2031;
found: 490.2029.
5.160(7) A, V=1491(2) A ; for Z=4 and Fw=286.33,
the calcd forted density is 1.27 g/cm3. The systematic
absences of: h00: h·2n 0k0: k·2n 00l: l·2n. Uniquely
determine the space group to be: P212121 (c19).
4.18. (5R,7S)-Kurzilactone 25b
Following the same procedure described as above, 25b
was obtained in 79% yield as a white solid. Mp 77–
79°C; [h]2D0=+84 (c 0.231, CHCl3); IR (KBr) 3476,
1710, 1637, 1426, 1386, 1266, 1254, 1184, 1058 cm−1; 1H
4.16. Preparation of compounds 24a and 24b
1
NMR (CDCl3) and H NMR (C6D6) are listed in Table
A solution of 23a (140 mg, 0.29 mmol), CaCO3 (150
mg) in THF/H2O (5:1, 10 mL) was treated with 4 M
aqueous HgClO4 (0.5 mL) for 5 min at 0°C. The
mixture was diluted with Et2O (50 mL) and then
filtered with Celite. Concentration of the filtrate fol-
lowed by flash chromatography on silica gel (eluted
with petroleum ether/EtOAc=5:1) yielded 24a as a pale
yellow solid (84 mg, 74%): mp 47–49°C; [h]2D0=−17.3 (c
0.365, CH3COCH3); IR (KBr) 2955, 2931, 2857, 1715,
1; 13C NMR (CDCl3) l 200.4, 164.2, 145.1, 144.0,
134.1, 130.9, 129.0, 128.5, 126.1, 121.5, 75.0, 64.2, 46.9,
41.7, 30.0 ppm; Ms m/e (relative intensity) 287 (M++1,
6), 269 (M++1–18, 6), 201 (7), 173 (12), 145 (17), 131
(100), 103 (29); HRMS calcd for C17H18O4: 286.1204;
found: 286.1202.
References
1
1652, 1626, 1392 cm−1; H NMR (CD3COCD3) l 7.7
(m, 3H), 7.4 (m, 3H), 7.05 (m, 1H), 6.9 (d, J=16.2 Hz,
1H), 5.95 (m, 1H), 4.7 (m, 1H), 4.55 (m, 1H), 2.95 (m,
2H), 2.45 (m, 2H), 1.9 (m, 2H), 0.85 (s, 9H), 0.10 (s,
3H), 0.05 (S, 3H) ppm; Ms m/e (relative intensity) 401
(M++1, 2), 343 (M+−57, 74), 325 (M+−57–18, 17), 255
(7), 231 (25), 131 (100), 103 (28), 75 (43); HRMS calcd
for C19H23O4Si: 343.1365; found: 343.1363.
1. (a) Fu, X.; Sevenet, T.; Hamid, A.; Hadi, A.; Remy, F.;
Pais, M. Phytochemistry 1993, 33, 1272; (b) Spencer, G.
F.; England, R. E.; Wolf, R. B. Phytochemistry 1984, 23,
2499; (c) Govindachari, T. R.; Parthasarathy, P. C. Tet-
rahedron Lett. 1971, 37, 3401; (d) Govindachari, T. R.;
Parthasarathy, P. C.; Modi, J. D. India J. Chem. 1972,
10, 149; (e) Hlubucek, J. R.; Robertson, A. V. Aust. J.
Chem. 1967, 20, 2199.
24b was obtained in 76% as a pale yellow solid using
the same procedure as 24a: mp 60–62°C; [h]2D0=+40.6 (c
0.715, CH3COCH3); IR (KBr) 2955, 2931, 2857, 1715,
2. For review, see: Graul, A.; Castaner, J. Drug Future 1997,
22, 956; (b) Roth, B. D.; Blankley, C. J.; Chucholowski,
A. W.; Ferguson, E.; Ho¨fle, M. L.; Ortwine, D. F.;
Newton, R. S.; Sekerke, C. S.; Sliskovic, D. R.; Stratton,
C. D.; Wilson, M. W. J. Med. Chem. 1991, 34, 357; (c)
Roth, B. D.; Ortwine, D. F.; Ho¨fle, M. L.; Stratton, C.
1
1652, 1626, 1392 cm−1; H NMR (CDCl3) l 7.60 (m,
3H), 7.4 (m, 3H), 6.9 (m, 1H), 6.8 (d, J=16.2 Hz, 1H),
6.0 (d, J=9.8 Hz, 1H), 4.6 (m, 2H), 2.9 (dd, J=15 Hz,

B. Jiang, Z. Chen / Tetrahedron: Asymmetry 12 (2001) 2835–2843
2843
D.; Sliskovic, D. R.; Wilson, M. W.; Newton, R. S. J.
Med. Chem. 1990, 33, 21; (d) Beck, G.; Jendralla, H.;
Kesseler, K. Synthesis 1995, 1014; (e) Hanamoto, T.;
Hiyama, T. Tetrahedron Lett. 1988, 29, 6467; (f) Slet-
zinger, M.; Verhoeven, T. R.; Volante, R. P.; Mcnamara,
J. M.; Corley, E. G.; Liu, T. M. H. Tetrahedron Lett.
1985, 26, 2951.
9. Mandal, P. K.; Roy, S. C. Tetrahedron 1995, 51, 7823.
10. Lorette, N. B.; Howard, W. L.; Brown, J. H., Jr. J. Org.
Chem. 1959, 24, 1731.
11. (a) Langer, P.; Eckardt, T. Angew. Chem., Int. Ed. Engl.
2000, 39, 4343; (b) Al-Tel, T. H.; Voelter, W. J. Chem.
Soc., Chem. Commun. 1995, 239; (c) Molander, G. A.;
Shubert, D. C. J. Am. Chem. Soc. 1986, 108, 4683.
12. Friebolin, H. Basic One- and Two-dimensional NMR
Spectroscopy; VCH: Weinheim, 1993.
13. Wolberg, M.; Hummel, W.; Wandrey, C.; Muller, M.
Angew. Chem., Int. Ed. Engl. 2000, 39, 4306.
14. Jiang, B.; Liu, Y.; Zhou, W. S. J. Org. Chem. 2000, 65,
6231.
3. (a) Ager, D. J.; Laneman, S. A. Tetrahedron: Asymmetry
1997, 8, 3327; (b) Davies, S. G.; Ichihara, O. Tetrahedron:
Asymmetry 1996, 7, 1919; (c) Yuasa, Y.; Tsuruta, H.
Liebiegs Ann. 1997, 1877.
4. (a) Ferdinandi, E. S.; Just, G. Can. J. Chem. 1971, 49,
1070; (b) Corey, E. J.; Cho, H.; Ru¨cker, C.; Hua, D. H.
A. Tetrahedron Lett. 1981, 22, 3455.
15. (a) Fujita, E.; Nagao, Y.; Kaneko, K. Chem. Pharm. Bull.
1978, 26, 3743; (b) Lipshutz, B. H.; Moretti, R.; Crow, R.
Tetrahedron Lett. 1989, 30, 15; (c) Balogh, M.; Cornelis,
A.; Laszlo, P. Tetrahedron Lett. 1984, 25, 3313; (d)
Smith, A. B., III; Dorsey, B. D.; Visnick, M.; Maeda, T.;
Malamas, M. S. J. Am. Chem. Soc. 1986, 108, 3110.
16. Newton, R. F.; Reynolds, D. P.; Finch, M. A. W.;
Kelly, D. R.; Roberts, S. M. Tetrahedron Lett. 1979, 20,
3981.
5. Mancuso, A. J.; Swern, D. Synthesis 1981, 165.
6. Patwardhan, S. A.; Dev, S. Synthesis 1974, 348.
7. Corey, E. J.; Venkateswarlu, A. J. Am. Chem. Soc. 1972,
94, 6190.
8. (a) Arand, M.; Archelas, A. R.; Barratti, J.; Furstoss, R.
PCT Int. Appl. WO 2000068394 A1, 2000; (b) Guerard,
C.; Alphand, V.; Archelas, A.; Demuynck, C.; Hecquet,
L.; Furstoss, R.; Bolte, J. Eur. J. Org. Chem. 1999, 12,
3399.