Synthesis of chiral sultams and their application as chiral auxiliaries in an asymmetric Diels-Alder reaction

Article abstract of DOI:10.1016/j.tetasy.2004.12.026

A number of bicyclic chiral sultams were synthesized based on 1,3-dipolar cycloaddition reactions of nitrile oxides and nitrones with prop-1-ene-1,3- sultone. The corresponding N-enoyl sultams were prepared by acylation. Their relative effectiveness as new chiral auxiliaries in asymmetric synthesis was evaluated for the asymmetric Diels-Alder reactions with cyclopentadiene. Good chemical yield and excellent endo selectivity were observed. The relationship between the structure and their effectiveness in promoting asymmetric induction of the synthetic chiral sultams was investigated.

Full text of DOI:10.1016/j.tetasy.2004.12.026

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 16 (2005) 761–771
Synthesis of chiral sultams and their application as chiral
auxiliaries in an asymmetric Diels–Alder reaction
Hong-Kui Zhang,a Wing-Hong Chan,b,* Albert W. M. Lee,b
Wai-Yeung Wongb and Ping-Fang Xiab
aDepartment of Chemistry, Xiamen University, Xiamen, China
bDepartment of Chemistry and Central Laboratory of the Institute of Molecular Technology for Drug Discovery and Synthesis,
Hong Kong Baptist University, Kowloon Tong, Kowloon, Hong Kong
Received 1 September 2004; revised 13 December 2004; accepted 17 December 2004
Abstract—A number of bicyclic chiral sultams were synthesized based on 1,3-dipolar cycloaddition reactions of nitrile oxides and
nitrones with prop-1-ene-1,3-sultone. The corresponding N-enoyl sultams were prepared by acylation. Their relative effectiveness as
new chiral auxiliaries in asymmetric synthesis was evaluated for the asymmetric Diels–Alder reactions with cyclopentadiene. Good
chemical yield and excellent endo selectivity were observed. The relationship between the structure and their effectiveness in pro-
moting asymmetric induction of the synthetic chiral sultams was investigated.
ꢀ 2005 Elsevier Ltd. All rights reserved.
1. Introduction
between the structures of synthetic chiral auxiliaries
and their effectiveness in asymmetric synthesis, we have
synthesized a number of bicyclic structurally demanding
chiral sultams. Subsequently, their relative effectiveness
in asymmetric synthesis was evaluated for the asymmet-
ric Diels–Alder reaction with cyclopentadiene.
The introduction of chirality through the use of chiral
auxiliaries has been demonstrated as an effectual means
for preparing homochiral materials.1,2 Most chiral auxi-
liaries reported in the literature have been derived from
naturally occurring compounds such as alkaloids,3,4
a-amino acids,5 terpenes6,7 and carbohydrates.8,9 In par-
ticular, the importance of Evanꢀs et al. 1,3-oxazolidin-2-
ones and Oppolzer chiral sultams for asymmetric
carbon–carbon bond formation has been well docu-
mented.10,11 On the other hand, chiral auxiliaries
prepared by rational synthetic design have received in-
tense attention from numerous research groups.12 Dia-
stereofacial discrimination exhibited by the substrates
as the result of incorporating a chiral auxiliary is the
key feature in such approaches, which has been widely
exploited in asymmetric synthesis. Conceivably, minor
variations in the structure of an auxiliary may exert
great influence on the effectiveness of the asymmetric
induction in a chemical transformation. In this regard,
chiral auxiliaries derived from rational chemical design
in contrast to those from natural products may provide
greater flexibility for improvement through structural
variations. To investigate extensively the relationship
2. Results and discussion
As revealed from numerous examples in the litera-
ture,12,13 sterically demanded chiral auxiliaries could
be built on bicyclic or polycyclic ring systems. In our
previous findings, tricyclic chiral sultams assembled
from prop-1-ene-1,3-sultone 1 and cyclopentadiene has
demonstrated to be effective chiral auxiliaries.14
Furthermore, based on the 1,3-dipolar cycloaddition of
1 with nitrile oxides or nitrones, a series of structurally
related bicyclic sultams comprising an isoxazoline or
isoxazolidine moiety were synthesized under an expedi-
tious synthetic route described in Scheme 1. Via a five-
step protocol developed in our laboratory,14c chiral sul-
tams 10–13 were obtained in optically active form. Spe-
cifically, nucleophilic ring opening of racemic sultone
adducts 4a,b obtained from 1,3-dipolar cycloaddition
of 1 and nitrile oxides 2a,b by (S)-(ꢀ)-a-methylbenzyl-
amine in ethanol at 70 ꢁC for about 10 h afforded a
*
Corresponding author. Tel.: +852 2339 7063; fax: +852 2339 7348;
e-mail: whchan@hkbu.edu.hk
0957-4166/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2004.12.026

762
H.-K. Zhang et al. / Tetrahedron: Asymmetry 16 (2005) 761–771
H
O
toluene
O
N
R1
C
N O
S
r.t.
O2
H
R1
(S)-(-)-
α−
Methylbenzylamine
THF, reflux
1)
2 a-b
O
+
4 a-b
S
O2
2) POCl3 / reflux
H
PhH2C
O
O
N
C
toluene
reflux
1
O
PhH2C N
S
H
R2
O2
H
R2
3 a-b
5 a-b
H
O
H
O
H
H
H
O
O
Me
H
Ph
Me
H
Ph
NH
N
NH
N
N
N
C
C
N
N
+
S
S
+
S
S
O2
H
R1
O2
R1
O2
O2
H
H
R1
R1
1) HCO2H
10 a-b
11 a-b
6 a-b
7 a-b
2) KOH,
ethanol
H
H
O
H
H
O
O
O
Me
H
Ph
Me
H
Ph
NH
NH
Bn N
Bn N
+
N
N
C
C
Bn N
Bn N
+
S
S
O2
O2
S
S
H
H
R2
R2
O2
O2
H
H
R2
R2
12 a-b
13 a-b
9 a-b
8 a-b
H
H
O
H
O
O
O
O
N
R3
N
R3
N
N
S
S
O2
O2
H
R1
R1
+
1) n-BuLi/THF
15 a, d
15 b, c
O
2)
R3
Cl
H
H
O
O
O
R3
R3
14
(R3 = H, CH3)
N
N
BnN
BnN
+
S
S
O2
O2
H
H
R2
R2
15 e, g, h
15 f
15f
15a
15c 15d 15e
15g
15b
Ph
15h
2a-13a 2b-13b
R1
Ph
Ph
t-Bu
R1
R2
Ph
Ph
t-Bu
t-Bu
R2
R3
Ph
CH3 CH3
Ph
Ph
H
CH3 CH3
H
CH3
CH3
Scheme 1. Preparation of bicyclic chiral sultams.
diastereomeric mixture of internal ammonium sulfonate
salts. POCl3 mediated cyclization of the internal salts
furnished a 1:1 diastereomeric mixture of 6 and 7. The
mixture can be easily separated by column chromato-
graphy to give homochiral materials 6a, 7a and 6b, 7b.
The structure of 6a was established unambiguously by
X-ray crystallographic analysis. Treatment of 6 and 7
with concentrated formic acid at 70–80 ꢁC for 5 h fol-
lowed by base hydrolysis afforded 10 and 11, respec-
tively. In a representative trial, starting from 1, the
total yield of 10a, 11a and 10b, 11b over the five-step
reaction sequence can reach 52% and 35%, respectively.
Using a similar approach, column chromatographically
separable homochiral diastereomeric 8a, 9a and 8b, 9b
were obtained. Debenzylation of 8 and 9 gave chiral sul-
tams 12 and 13 in a total yield about 25% over five steps.
Again, the structures of the adducts were established
firmly by NMR spectroscopic methods and X-ray crys-
tallographic analysis as exemplified by 8b (Fig. 1).
Apparently, due to the higher reactivity of nitrile oxides
in contrast to nitrones towards 1 in the corresponding
dipolar cycloaddition reaction, the yield of the corre-
sponding sultam isoxazolines is higher than those of
the isoxazolidines. On the other hand, as outlined in
Scheme 2, a more convergent synthesis of 10 and 11
can be achieved by using the chiral sultam 14 as the
starting material.15 For instance, overall yields of 52%
and 35% over a three-step sequence were obtained for
the preparation of 10a and 11a, 10b and 11b, respec-
tively. It is noteworthy that structurally demanded t-but-
yl and pyrenyl group were introduced in 10b, 11b and
12b, 13b, respectively. With this chiral set of synthetic

H.-K. Zhang et al. / Tetrahedron: Asymmetry 16 (2005) 761–771
763
sultams at our disposal, we could embark on an investi-
gation to assess their suitability as chiral auxiliaries
in promoting asymmetric reactions. The Diels–Alder
reaction, allowing the formation of two sigma bonds
in a stereo- and regioselective manner, has been often
utilized by synthetic chemists as an indispensable syn-
thetic tool for building up complex molecules. To look
for a versatile chiral auxiliary in asymmetric synthesis
from the chiral pool of synthetic sultams, Diels–Alder
reaction was thus chosen as the ꢁtest reactionꢀ for fishing
out the best candidate among all structural related chiral
sultams. Accordingly, dienophiles incorporating the var-
ious chiral auxiliary were prepared by making the corre-
sponding N-enoyl sultams. Thus, N-acylation of chiral
sultams by successive treatment with n-butyllithium
and acid chlorides afforded the corresponding N-acryl-
oyl sultams 15c,g and N-crotonyl sultams 15a,b,d,e,f,h
as shown in Table 1. The results revealed that crotonoyl-
ation proceeded well and gave high yields of products
while a much lower yield of about 35% of N-acryloyl
sultams resulted. Modification of the reaction condi-
tions and the adoption of Thomꢀs procedure16 did not
alleviate the problem of low yield. Nevertheless, with
the array of chiral dienophiles in hand, we have set the
stage for conducting asymmetric Diels–Alder reactions
Figure 1. X-ray structure of 8b.
Me
H
Ph
Toluene
r.t.
N
C
6 a-b
+
+
7 a-b
R
C
N O
2 a-b
1) HCOOH
2) KOH, ethanol
S
O2
10 a-b
+
11 a-b
Scheme 2. Alternative route in making chiral sultams.
Table 1. Acylation of chiral bicyclic sultams
Entry
Sultam
N-Enoyl sultam AuxH
Yield (%)
O
R
Cl
R=
H
O
O
1
10a
CH3
85
N
N
S
O2
H
H
Ph
15a
O
O
O
N
N
2
3
4
11a
11a
10b
CH3
82
37
80
S
O2
H
H
Ph
15b
O
N
N
H
S
O2
H
Ph
15c
H
O
O
N
N
CH3
S
O2
H
t-Bu
15d
H
O
O
N
BnN
5
12a
CH3
85
S
O2
H
Ph
15e
(continued on next page)

764
H.-K. Zhang et al. / Tetrahedron: Asymmetry 16 (2005) 761–771
Table 1 (continued)
Entry
Sultam
N-Enoyl sultam AuxH
Yield (%)
O
R
Cl
R=
H
O
O
O
N
BnN
6
7
13a
12a
CH3
80
33
S
O2
H
H
Ph
15f
O
N
BnN
H
S
O2
H
Ph
15g
H
O
O
N
BnN
S
8
12b
CH3
85
O2
H
15h
Table 2. Asymmetric Diels–Alder reaction of 15 with cyclopentadiene
22
½aꢁD of the acid
Entry
N-Enoyl sultam
Temp, ꢁC (time, h)
Diastereomeric
products: drb
De
40
Yield (%)
80
Carboxylic acid
(from adduct, %)
16a 70
¼
1
15a
ꢀ50 (6)
18a (16a, 78)
ꢀ138
17a 30
16a 90
¼
16a 91
2
15a
15aa
15b
15c
15d
15e
15e
15f
ꢀ78 (12)
ꢀ78 (12)
ꢀ78 (12)
ꢀ78 (5)
ꢀ78 (12)
ꢀ50 (6)
ꢀ78 (12)
ꢀ78 (12)
ꢀ78 (6)
ꢀ78 (8)
ꢀ78 (1)
80
82
74
44
60
80
92
92
56
98
98
78
80
86
86
72
90
87
92
83
80
98
17a 10
3
¼
17a
9
16b 13
¼
4
19a (17b, 72)
19b (17c, 75)
18a (16d, 83)
18a (16e, 80)
+141
+135
ꢀ139
ꢀ138
17b 87
16c 28
¼
5
17c 72
16d 80
¼
6
17d 20
16e 90
¼
16e 96
7
17e 10
8
¼
17e
16f
4
4
9
¼
19a (17f, 78)
18b (16g, 73)
18a (16h, 72)
+140
ꢀ136
ꢀ139
17f 96
16g 78
¼
16h 99
10
11
12
15g
15h
17g 22
¼
17h
16a 96
1
O
c
¼
17a
4
Ax
a 0.5 equiv of SnCl4 was used while TiCl4 was used in other entries.
b Ratios determined by 1H NMR.
c Aux = oxazolidinone, also see Ref. 10.
to find the best auxiliary within the synthetic chiral pool.
In the presence of TiCl4, chiral dienophiles 15a–h bear-
ing structurally related sultam moieties were allowed to
react with excess cyclopentadiene at low temperature.
The results of the cycloaddition are summarized in
Table 2. In general, the reactions proceeded smoothly
to afford cycloadducts with excellent chemical yield
and very high endo selectivity. The diastereoselectivities
of the cycloaddition were established by 1H NMR meth-
ods. The stereochemistry of the major products was
determined from the stereochemical correlations of their
hydrolyzed carboxylic acids 18a,b and 19a,b with known

H.-K. Zhang et al. / Tetrahedron: Asymmetry 16 (2005) 761–771
765
R3
R3
AxH
+
COOH
O
Aux
O
16 a-h
/ THF
Lewis acid
18 a-b
LiOH
Ax
15a - 15h
R3
R3
THF/H2O
R3
AxH
+
COOH
19 a-b
O
Aux
17 a-h
e
a
b
c
d
f
g
h
CH3 CH3
CH3 CH3
H
H
CH3 CH3 CH3
CH3 CH3 CH3
H
H
CH3
CH3
16
17
18
19
CH3
CH3
H
H
Scheme 3. Characterization of cycloadducts and regeneration of the auxiliaries.
compounds17 (Scheme 3). Non-destructive removal of
the chiral auxiliary was readily accomplished by saponi-
fication under standard conditions.17a Up to 80% yield
of the chiral sultam auxiliaries was recovered, which
can be repeatedly used after purification by column
chromatography. The stereochemical structure of the
cycloadducts was also unambiguously confirmed by
the X-ray crystallographic analysis as exemplified by
the adduct 17c (Fig. 2).
A closer examination of the experimental results in
Table 2 revealed that minor variation in the structure
of an auxiliary may have great influence on the effective-
ness of the asymmetric induction in a chemical transfor-
mation. Comparing results in entries 2 and 7; 5 and 10 in
Table 2, it is evident that chiral auxiliaries containing
the isoxazolidine moiety are superior to those of the
isoxazoline derivatives in terms of chiral induction.
For instance, cyclopentadiene, in reaction with 15e
could achieve the same level of dr as that of 15a, but
at a higher temperature. Conceivably, the more planar
nature of the bicyclic isoxazolidine moiety in 15a renders
the attack of cyclopentadiene from both sides of the
dienophile equally accessible. The diastereoselectivity
of the substrate can be improved by introducing a more
sterically demanding tert-butyl group in replacing the
phenyl group. Thus, higher diastereoselectivity was
observed for 15d (Table 2, entry 6). To substantiate fur-
ther our strategy to develop an auxiliary with improved
performance via rational design, a pyrenyl group was
incorporated into the synthetic chiral sultam 12b. Pre-
sumably, the bulky pyrenyl substituent may completely
shield one face of the dienophile 15h, according to the
HPLC chromatogram of the crude products, the major
diastereomer was formed in 99%. Apparently, the effec-
tiveness of 15h in promoting asymmetric Diels–
Alder reaction is as good as Evanꢀs oxazolidinone but
not better in terms of chemical yield (Table 2, entries
11 vs 12).
Figure 2. X-ray structure of 17c.
Most of the reactions were conducted at ꢀ78 ꢁC and
0.5 equiv of TiCl4 was chosen as the catalyst for promot-
ing the asymmetric reaction. By increasing the reaction
temperature from ꢀ78 to ꢀ50 ꢁC, both N-enoyl sultams
15a and 15e reacted in a faster rate with cyclopentadiene
but at the expense of the diastereoselectivity (Table 2,
entries 1 vs 2 and 7 vs 8). On the other hand, one of
the key issues to be addressed in this study is the effect
of chiral auxiliaries on the extent of asymmetric induc-
tion of the Diels–Alder reaction as exemplified by the
reaction of cyclopentadiene to N-enoyl sultams 15a–h.
From the product distribution of the cycloadducts, it
was apparent that the fine structure of a chiral auxiliary
exerts a significant effect on the asymmetric induction of
the Diels–Alder reaction under comparable conditions.
The stereochemical outcome of the products we ob-
tained in the cycloaddition may be rationalized by
inspection of proposed transition state model in Scheme
4.14b Under the influence of a Lewis acid, the major
product may arise from the top-endo transition state in
a preferred conformation of 15e in cycloaddition of
15e with cyclopentadiene. This transition state is stabi-
lized by the secondary molecular orbital interactions be-
tween the carbonyl carbon of N-crotonoyl sultam and
cyclopentadiene, and the top-endo attack alleviates a ste-

766
H.-K. Zhang et al. / Tetrahedron: Asymmetry 16 (2005) 761–771
information may be obtained free of charge from
The Director, CCDC, 12 Union Road, Cambridge,
CB2 1EZ, UK (Fax: +44-1223-336-033; e-mail: depos-
it@ccdc.cam.ac.uk or www: http://www.ccdc.cam.ac.
uk).
CH
Ax
3
top-endo
H
CH
H
3
H
H
(favored)
N
H
O
O
O
N
S
M
O
(major)
16e
Bn
O
3.2. Preparation of 2-isoxazolines 4a/4b
H
H
H C
3
bottom-endo
To a solution of chlorosuccinimide (NCS) (3.0 mmol)
and 0.08 mL of pyridine in 5 mL dry dichloromethane
was added aldoximes (3.0 mmol) in one portion with
stirring. The mixture was stirred under nitrogen at
40 ꢁC for 20 min, and then continued stirring at room
temperature for 0.5 h until the NCS was completely dis-
solved. The solution then turned to a green-blue colour.
A solution of 1-propene-1,3-sultone (1.0 mmol) in
10 mL of dry toluene was added. Then, Et3N (5.0 mmol)
in 5 mL of dry toluene was added over 3 h by a syringe
pump at room temperature. The mixture was stirred at
room temperature for 24 h. The reaction was quenched
by adding 10 mL of saturated ammonium chloride solu-
tion. Organic phase was separated. The aqueous layer
was extracted with dichloromethane (3 · 10 mL). The
combined organic phase was dried over magnesium sul-
fate, and evaporated under reduced pressure to yield the
crude product, which was purified by column chroma-
tography on silica gel (ethyl acetate/petroleum ether,
1:3, v/v) to give products 4a and 4b.
H
(disfavored)
Ax
17e
O
H
O
(minor)
N
2
BnN
Ax =
S
O
H
Ph
Scheme 4. Preferred conformation of 15e in endo transition state.
ric encumbrance between the incoming diene and aro-
matic ring of the dienophile.
In conclusion, we have demonstrated the possibility to
improve the effectiveness of synthetic chiral auxiliaries
by minor variations on their structures.
3. Experimental
3.1. General information
3.2.1. 3-Phenyl-4,5-oxathiain-4,4-dioxide[3,4-d]-2-isoxazo-
line 4a. Yield 82%; mp 151–153 ꢁC; 1H NMR
(270 MHz, CDCl3): d 4.64 (dd, J = 3.6, 10.8 Hz, 1H),
4.81 (d, J = 10.8 Hz, 1H), 5.19 (dd, J = 8.8 Hz, 1H),
5.78 (dd, J = 3.6, 8.8 Hz, 1H), 7.48 (m, 3H), 7.75 (m,
2H); 13C NMR (67.8 MHz, CDCl3): d 66.7, 71.0, 85.0,
126.4, 127.3, 129.1, 131.3, 150.9; IR (KBr): 3069, 2976,
1447,1376, 1349, 1208, 1158, 1014, 952, 863 cmꢀ1; MS
(EI) m/z: 239 (M+), 144, 117, 77; C10H9NO4S requires
239. Anal. Calcd for C10H9NO4S: C, 50.19; H, 3.80;
N, 5.86; S, 13.40. Found: C, 50.14; H, 3.85; N, 6.01; S,
13.36.
Unless otherwise noted, solvents and starting materials
were obtained from commercial suppliers. All chemicals
were reagent grade and used without further purifica-
tion. Melting points were taken on a MEL-TEMP melt-
ing point apparatus, and were reported uncorrected in
ꢁC. 1H NMR and 13C NMR spectra were recorded
on a Varian INOVA Unity (400 MHz for 1H, and
100.6 MHz for 13C) or on a JOEL JNM-EX 270
1
(270 MHz for H, and 67.8 MHz for 13C) in CDCl3.
Chemical shifts were recorded in ppm (d) relative to
TMS. Optical rotations were taken on a JASCO DIP-
1000 digital polarimeter. IR was recorded on a Nicolet
Magna 550 spectrometer. Electron impact (EI, 70 eV,
positive mode) or fast atomic bombardment (FAB, po-
sitive mode) mass spectra were recorded on a Finnigan
MAT SSQ-710 spectrometer. High resolution mass
spectra (HRMS m/z) were recorded on a QSTAR
Pulsar/LC/MS/MS System, ESI-QTOF instrument
(Applied Biosystem, Canada). Elemental analyses were
preformed on a Perkin Elmer 240B microanalyzer in
Chengdu Institute of Organic Chemistry, Sichuan, Chi-
na. All glass equipment were dried in an oven at 120 ꢁC
prior to use.
3.2.2. 3-t-Butyl-4,5-oxathiain-4,4-dioxide[3,4-d]-2-isoxazo-
line 4b. Yield 60%; mp 113–115 ꢁC; 1H NMR
(270 MHz, CDCl3): d 1.35 (s, 9H), 4.59 (dd, J = 3.6,
4.0 Hz, 1H), 4.70 (d, J = 8.8 Hz, 1H), 4.72 (d,
J = 10.8 Hz, 1H), 5.56 (dd, J = 3.6, 8.8 Hz, 1H); 13C
NMR (67.8 MHz, CDCl3): d 29.2, 33.8, 67.9, 70.5,
85.1, 160.5; IR (KBr): 2983, 1478, 1346, 1250, 1238,
1018, 948 cmꢀ1; MS (EI) m/z: 219 (M+), 173, 117, 57;
C8H13NO4S requires 219; HRMS (ESI) m/z C8H13NO4S
(M+). Calcd: 219.0566. Found: 219.0560.
3.3. Preparation of isoxazolidines 5a/5b
Single-crystal X-ray diffraction experiments were carried
out at room temperature on a Bruker Axs SMART 1000
CCD area-detector diffractometer using graphite-mono-
chromated Mo-Ka radiation (k = 0.71073 A). Crystallo-
graphic data (comprising hydrogen atom coordinates,
thermal parameters and full tables of bond lengths and
angles) for the structural analysis has been deposited
with the Cambridge Crystallographic Centre (CCDC-
261644 for 8b and CCDC-261645 for 17c). Copies of this
A mixture of nitrone (3.0 mmol) and 1-propene-1,3-sul-
tone (1.0 mmol) in 15 mL of dry toluene was stirred
under nitrogen at 120 ꢁC for 24 h.18 The reaction mixture
was cooled to room temperature and added saturated
ammonium chloride (15 mL). Organic layer was sepa-
rated, and aqueous layer was extracted with ethyl ace-
tate (3 · 15 mL). The combined organic phase was
dried over anhydrous magnesium sulfate. After removal

H.-K. Zhang et al. / Tetrahedron: Asymmetry 16 (2005) 761–771
767
of solvent, the crude products were purified by flash col-
umn chromatography on silica gel (ethyl acetate/petro-
leum ether = 1:2) to give pure adducts 5a and 5b.
3.4.1.1. (3aR,6aR)-3-Phenyl-5-(S)-a-phenylethyl-4,5-
thiazolidine-4,4-dioxide[3,4-d]-2-isoxazoline 6a. Yield
21
48%; mp 164–166 ꢁC; ½aꢁ ¼ þ126:2 (c 0.9, CHCl3);
D
1H NMR (270 MHz, CDCl3): d 1.60 (d, J = 6.8 Hz,
3H), 3.26 (dd, J = 4.0, 12.4 Hz, 1H), 3.49 (d,
J = 12 Hz, 1H), 4.74 (q, J = 7.2 Hz, 1H), 5.04 (d,
J = 9.6, 1H), 5.38 (dd, J = 3.2, 10.0 Hz, 1H), 7.27–7.38
(m, 5H), 7.77–7.89 (m, 4H), 8.17 (d, J = 7.6 Hz, 1H);
13C NMR (67.8 MHz, CDCl3): d 19.1, 47.8, 54.6, 69.5,
81.1, 127.2, 127.4, 127.5, 128.2, 128.7, 128.8, 128.9,
130.0, 130.9, 132.8, 134.3, 139.7, 151.5; IR (KBr):
2919, 2857, 1497, 1460, 1446, 1320, 1212, 1140, 1106,
953, 922, 841 cmꢀ1. Anal. Calcd for C18H18N2O3S: C,
63.14; H, 5.30; N, 8.18. Found: C, 63.00; H, 5.50; N,
7.90. MS (FAB): m/z 343 (M+1)+; C18H18N2O3S re-
quires 342.
3.3.1. 2-Benzyl-4,5-oxathiain-4,4-dioxide-3-phenyl[3,4-d]-
isoxazolidine 5a. Yield 86%; mp 165–167 ꢁC; 1H NMR
(400 MHz, CDCl3): d 3.77 (d, J = 14.8 Hz, 1H), 3.96 (d,
J = 14.4 Hz, 1H), 4.06 (dd, J = 7.2, 14.4 Hz, 1H), 4.22
(d, J = 7.2 Hz, 1H), 4.33 (dd, J = 3.5, 11.2 Hz, 1H),
4.46 (d, J = 11.2 Hz, 1H), 5.14 (dd, J = 3.2, 7.2 Hz,
1H), 7.30–7.51 (m, 10H); 13C NMR (67.8 MHz, CDCl3):
d 59.3, 69.2, 69.8, 73.8, 79.6, 127.5, 127.9, 128.2, 128.4,
129.1, 129.2, 134.8, 136.5; IR (KBr): 3038, 2883, 1648,
1499, 1456, 1369, 1355, 1156, 948, 849, 701 cmꢀ1; MS
(EI) m/z: 331 (M+), 254, 236, 181, 115, 91, 77;
C17H17NO4S requires 331. Anal. Calcd for
C17H17NO4S: C, 61.60; H, 5.18; N, 4.23; S, 9.68. Found:
C, 61.36; H, 5.11; N, 4.13; S, 9.48.
3.4.1.2. (3aS,6aS)-3-Phenyl-5-(S)-a-phenylethyl-4,5-
thiazolidine-4,4-dioxide[3,4-d]-2-isoxazoline 7a. Yield
3.3.2. 2-Benzyl-4,5-oxathiain-4,4-dioxide-3-10-pyrenyl-
[3,4-d]isoxazolidine 5b. Yield 86%; mp 240–242 ꢁC;
1H NMR (270 MHz, CDCl3): d 3.91 (s, 2H), 4.44 (dd,
J = 3.6, 11.2 Hz, 1H), 4.46 (s, 1H), 4.59 (d,
J = 10.8 Hz, 1H), 5.42 (dd, J = 3.6, 4.8 Hz, 1H), 7.22–
7.27 (m, 5H), 8.05–8.32 (m, 8H), 8.75 (d, J = 9.5 Hz,
1H); 13C NMR (100.6 MHz, CDCl3): d 59.5, 69.1,
70.0, 70.1, 80.4, 122.6, 124.6, 125.2, 125.3, 125.7,
125.8, 126.3, 127.2, 127.6, 128.3, 128.4, 128.7, 129.6,
130.6, 131.3, 132.0, 136.5; IR (KBr): 2948, 2876, 1602,
21
36%; mp 164–166 ꢁC; ½aꢁ ¼ ꢀ148:0 (c 0.5, CHCl3);
D
1H NMR (400 MHz, CDCl3): d 1.70 (d, J = 6.4 Hz,
3H), 3.37 (d, J = 11.6 Hz, 1H), 3.53 (dd, J = 4.0,
11.6 Hz, 1H), 4.97 (q, J = 6.4 Hz, 1H), 5.07 (d,
J = 9.2 Hz, 1H), 5.49 (dd, J = 3.6, 9.2 Hz, 1H), 7.26–
7.39 (m, 5H), 7.46–7.49 (m, 3H), 7.80–7.82 (m, 2H);
13C NMR (100.6 MHz, CDCl3): d 17.4, 45.1, 51.3,
68.9, 80.8, 127.0, 127.2, 127.7, 128.2, 128.3, 128.6,
128.9, 129.2, 130.6, 130.8, 131.1, 139.0, 151.4; IR
(KBr): 2923, 2855, 1736, 1446, 1358, 1306, 1218, 1135,
1056, 996, 928, 837, 773 cmꢀ1; HRMS (ESI) m/z
C18H18N2O3NaS (M+Na)+. Calcd: 365.0936. Found:
365.0941.
1503, 1467, 1363, 1223, 1156, 954, 850, 772 cmꢀ1
;
HRMS (ESI) m/z C27H22NO4S (M+H)+. Calcd:
456.1269. Found: 456.1290; Anal. Calcd for
C27H21NO4S: C, 71.19; H, 4.65; N, 3.07. Found: C,
71.11; H, 4.58; N, 3.00.
3.4.1.3. (3aR,6aR)-3-t-Butyl-5-(S)-a-phenylethyl-4,5-
thiazolidine-4,4-dioxide[3,4-d]-2-isoxazoline 6b. Yield
3.4. General procedure for the preparation of chiral
bicyclic sultams
20
D
72%; ½aꢁ ¼ þ10:5 (c 1.4, CHCl3); 1H NMR
(400 MHz, CDCl3): d 1.36 (s, 9H), 1.63 (d, J = 7.2 Hz,
1H), 3.22 (dd, J = 4.8, 12.0 Hz, 1H), 3.46 (dd, J = 1.2,
12.0 Hz, 1H), 4.57 (d, J = 9.2 Hz, 1H), 4.83 (q,
J = 6.8 Hz, 1H), 5.17 (m, 1H), 7.30–7.38 (m, 5H);
13C NMR (100.6 MHz, CDCl3): d 18.41, 29.14, 33.47,
46.41, 53.84, 70.49, 80.96, 127.18, 128.05, 128.70,
139.51, 161.02; IR (KBr): 3461, 2979, 1479, 1457,
1379, 1293, 1159, 1131, 896, 776 cmꢀ1; MS (FAB) m/z
323 (M+1)+, 149, 105, 77, 57; C16H22N2O3S requires
322; HRMS (ESI) m/z C16H22N2NaO3S (M+Na)+.
Calcd: 345.1249. Found: 345.1243.
3.4.1. Preparation of N-alkyl bicyclic sultams. To a
solution of isoxazoline 4a or 4b (2.0 mmol) in dry
THF (20 mL) was added (S)-(a)-methyl-benzylamine
(3.6 mmol). The mixture was refluxed under nitrogen
for about 24 h. The course of the reaction was moni-
tored by TLC. When isoxazolidine was completely con-
sumed, the reaction mixture was cooled down to room
temperature. Phosphorus oxychloride (7.2 mmol) was
added, and the mixture was refluxed for 12 h. Dimeth-
ylamino pyridine (0.36 mmol) and triethylamine
(6 mL) was added at room temperature. The mixture
was then refluxed under nitrogen for 36 h. Water
(2 mL) was carefully added to destroy the excess phos-
phorus oxychloride. The mixture was concentrated
under reduced pressure. Water (15 mL) was added,
and extracted with dichloromethane (4 · 20 mL). The
combined organic phase was dried over anhydrous
MgSO4. After the removal of solvent, the residue was
subjected to column chromatography on silica gel (ethyl
acetate/petroleum ether = 1:5, v/v) to give pure 6a/7a
and 6b/7b.
3.4.1.4. (3R,3aR,6aR)-2-Benzyl-3-phenyl-5-(S)-a-phen-
ylethyl-4,5-thiazoline-4,4-dioxide[3,4-d]isoxazolidine
21
D
8a. Yield 43%; mp 115–117 ꢁC; ½aꢁ ¼ ꢀ32:2
1
(c 1.80, CHCl3); H NMR (270 MHz, CDCl3): d 1.65
(d, J = 5.4 Hz, 3H), 2.89 (dd, J = 5.4, 13.5 Hz, 1H),
3.11 (d, J = 13.5 Hz, 1H), 3.75 (d, J = 13.5 Hz, 1H),
3.91 (t, J = 8.1 Hz, 1H), 4.01 (d, J = 13.5 Hz, 1H), 4.22
(d, J = 5.4 Hz, 1H), 4.70 (q, J = 5.4 Hz, 1H), 4.81 (dd,
J = 2.7, 8.1 Hz, 1H), 7.27–7.44 (m, 13H), 7.55 (d,
J = 8.1 Hz, 2H); 13C NMR (67.8 MHz, CDCl3): d 19.5,
46.0, 54.0, 58.8, 72.1, 73.4, 74.5, 127.0, 127.3, 127.7,
127.9, 128.0, 128.4, 128.5, 128.6, 128.9, 135.5, 136.4,
139.8; IR (KBr): 1610, 1457, 1294, 1229, 1150,
737 cmꢀ1; MS (FAB) m/z: 435 (M+H)+, 419, 331, 236,
Following the above procedure, pure 8a/9a and 8b/9b
were obtained in 85% yield from isoxazolidines 5a and
5b.

768
H.-K. Zhang et al. / Tetrahedron: Asymmetry 16 (2005) 761–771
105, 91; C25H26N2O3S requires 434; HRMS (ESI) m/z
768 cmꢀ1; HRMS (ESI) m/z C10H11N2O3S (M+H)+.
Calcd: 239.0490. Found: 239.0488.
C25H26N2O3S (M)+. Calcd: 434.1664. Found: 434.1660.
3.4.1.5.
phenylethyl-4,5-thiazoline-4,4-dioxide[3,4-d]isoxazolidine
(3S,3aS,6aS)-2-Benzyl-3-phenyl-5-(S)-a-
3.4.2.2. (3aR,6aR)-3-t-Butyl-4,5-thiazolidine-4,4-diox-
21
D
ide[3,4-d]-2-isoxazoline 10b. Yield 74%; ½aꢁ ¼ ꢀ6:5 (c
20
1
9a. Yield 40%; mp 125–127 ꢁC; ½aꢁ ¼ ꢀ14:0 (c 1.50,
D
1.02, CHCl3); H NMR (270 MHz, CDCl3): d 1.34 (s,
9H), 3.52 (dqd, J = 2.4, 3.0, 3.0 Hz, 1H), 3.73 (dd,
J = 5.4, 14.3 Hz, 1H), 4.52 (d, J = 7.6 Hz, 1H), 4.10 (s,
br, 1H), 5.10 (m, 1H); 13C NMR (67.8 MHz, CDCl3):
d 29.44, 33.72, 45.95, 70.10, 88.67, 162.46; IR (KBr):
3224, 3167, 2997, 1481, 1412, 1340, 1186, 1150, 901,
752 cmꢀ1; MS (FAB) m/z 219 (M+1)+, 146, 162, 57;
C8H14N2O3S requires 218; HRMS (ESI) m/z
C8H15N2O3S (M+H)+. Calcd: 219.0803. Found:
219.0808.
CHCl3); 1H NMR (270 MHz, CDCl3): d 1.67 (d,
J = 8.1 Hz, 3H), 3.03 (d, J = 13.5 Hz, 1H), 3.25 (dd,
J = 5.4, 13.5 Hz, 1H), 3.63 (d, J = 13.5 Hz, 1H), 3.90–
3.98 (m, 2H), 4.18 (d, J = 8.1 Hz, 1H), 4.89 (q,
J = 2.7 Hz, 1H), 5.06 (dd, J = 8.1, 13.5 Hz, 1H), 7.22–
7.47 (m, 13H), 7.56 (d, J = 5.4 Hz, 2H); 13C NMR
(67.8 MHz, CDCl3): d 17.2, 44.5, 50.0, 58.9, 71.5,
74.6, 74.7, 126.8, 127.3, 127.5, 127.9, 128.0, 128.3,
128.4, 128.7, 128.9, 135.5, 136.6, 139.5; IR (KBr):
1612, 1493, 1296, 1151, 1000, 762 cmꢀ1; MS (FAB)
m/z: 435 (M+H)+, 419, 331, 236, 105, 91; C25H26N2O3S
requires 434; HRMS (ESI) m/z C25H26N2O3S
(M)+. Calcd: 434.1664. Found: 434.1661.
3.4.2.3. (3R,3aR,6aR)-2-Benzyl-3-phenyl-4,5-thiazo-
line-4,4-dioxide[3,4-d]isoxazolidine 12a. Yield 40%;
21
D
mp 121–124 ꢁC; ½aꢁ ¼ ꢀ55:3 (c 1.25, CHCl3); 1H
NMR (400 MHz, acetone-d6): d 2.89 (s, 1H), 3.24 (d,
J = 14.0 Hz, 1H), 3.38 (d, J = 14.4 Hz, 1H), 3.74 (d,
J = 14.8 Hz, 1H), 3.88 (d, J = 14.4 Hz, 1H), 3.98 (dd,
J = 6.8, 14.0 Hz, 1H), 4.14 (d, J = 6.8 Hz, 1H), 5.16
(dd, J = 2.8, 5.2 Hz, 1H), 7.20–7.32 (m, 5H), 7.35–7.46
(m, 3H), 7.57–7.59 (m, 2H); 13C NMR (100.6 MHz, ace-
tone-d6): d 44.6, 59.2, 72.1, 74.5, 83.3, 127.2, 128.2,
128.6, 128.7, 128.9, 129.2, 137.0, 138.0; IR (KBr):
3232, 2903, 1463, 1283, 1132 cmꢀ1; HRMS (ESI) m/z
C17H19N2O3S (M+H)+. Calcd: 331.1116. Found:
331.1114.
3.4.1.6. (3R,3aR,6aR)-2-Benzyl-3-pyrenyl-5-(S)-a-
phenylethyl-4,5-thiazoline-4,4-dioxide[3,4-d]isoxazolidine
20
D
8b. Yield 38%; ½aꢁ ¼ ꢀ36:7 (c 2.0, CHCl3); 1H NMR
(400 MHz, CDCl3): d 1.74 (d, J = 7.2 Hz, 1H), 2.99 (dd,
J = 4.4, 12.0 Hz, 1H), 3.23 (d, J = 11.6 Hz, 1H), 3.85 (d,
J = 14.4 Hz, 1H), 3.96 (d, J = 14.4 Hz, 1H), 4.34 (s, 1H),
4.76 (dd, J = 6.4, 13.2 Hz, 1H), 5.06 (dd, J = 4.0, 6.8 Hz,
1H), 5.23 (br m, 1H), 7.20–7.41 (m, 10H), 8.00–8.11 (m,
3H), 8.19–8.22 (m, 4H), 8.31 (d, J = 7.6 Hz, 1H), 8.79
(d, J = 9.2 Hz, 1H); 13C NMR (100.6 MHz, CDCl3): d
19.6, 46.1, 54.2, 59.2, 60.3, 72.5, 75.4, 123.0, 124.6,
125.2, 125.4, 125.6, 126.1, 127.2, 127.3, 127.4, 128.0,
128.1, 128.2, 128.3, 128.4, 128.7, 128.8, 129.6, 130.6,
131.2, 131.7, 136.6, 140.1; IR (KBr): 3042, 2938, 2871,
1643, 1503, 1467, 1312, 1141, 851, 706 cmꢀ1; HRMS
(ESI) m/z C35H30N2NaO3S (M+Na)+. Calcd:
581.1875. Found: 581.1878.
3.4.2.4. (3R,3aR,6aR)-2-Benzyl-3-pyrenyl-4,5-thiazo-
line-4,4-dioxide[3,4-d]isoxazolidine 12b. Yield 38%;
21
D
mp 125 ꢁC (dec); ½aꢁ ¼ ꢀ42:1 (c 1.70, CHCl3); 1H
NMR (270 MHz, CDCl3): d 3.43 (ddd, J = 2.8, 11.6,
14.0 Hz, 1H), 3.57 (dd, J = 6.0, 14.4 Hz, 1H), 3.85 (d,
J = 14.6 Hz, 1H), 3.95 (d, J = 14.6 Hz, 1H), 4.28 (m,
1H), 4.80 (dd, J = 6.0, 11.2 Hz, 1H), 5.36 (m, 1H),
7.26 (m, 5H), 8.04–8.15 (m, 3H), 8.22–8.26 (m, 4H),
8.34 (m, 1H), 8.78 (m, 1H); 13C NMR (67.8 MHz,
CDCl3): d 22.7, 31.6, 44.6, 59.5, 83.6, 122.7, 124.6,
125.2, 125.6, 125.7, 126.3, 126.8, 126.9, 127.3, 127.6,
127.7, 128.3, 128.4, 128.6, 129.5, 130.6, 131.3, 131.8,
136.5; IR (KBr): 3238, 2904, 1472, 1298, 1143,
3.4.2. Debenzylation of N-alkyl bicyclic sultams. A mix-
ture of N-alkyl bicyclic sultams (1.0 mmol) and freshly
distilled formic acid (20 mL) was stirred under nitrogen
for 12 h. Then, the mixture was heated to 70 ꢁC, and
stirred for 8 h. Formic acid was removed under reduced
pressure to give the crude product. To the crude product
was added 10% KOH in ethanol (30 mL). The mixture
was stirred at room temperature for 12 h, and acidified
with 6 N HCl (pH 3). The mixture was concentrated
under reduced pressure. The residue was extracted with
dichloromethane (5 · 15 mL). Removal of solvent gave
crude product, which was purified by column chroma-
tography on silica gel (ethyl acetate/petroleum
ether = 1:3, v/v) to afford pure products.
787 cmꢀ1
;
HRMS (ESI) m/z C27H22N2NaO3S
(M+Na)+. Calcd: 477.1248. Found: 477.1232.
3.5. General procedure for the N-acylation of bicyclic
sultams
To a solution of bicyclic sultam (1.0 mmol) in dry THF
(15 mL) was added n-butyl lithium (1.2 mmol, 1.6 M
solution in hexane) under nitrogen at ꢀ78 ꢁC. The mix-
ture was stirred at ꢀ78 ꢁC for 15 min. Cooling bath was
removed, and allowed the reaction temperature to warm
to room temperature. After stirring at room temperature
for 1 h, the reaction mixture again cooled down to
ꢀ78 ꢁC. A solution of freshly distilled acid chloride
(1.2 mmol) in 3 mL of dry THF was added. Stirring
the reaction mixture at ꢀ78 ꢁC for 15 min, the reaction
temperature was brought up to room temperature and
stirred for 2 h.
3.4.2.1. (3aR,6aR)-3-Phenyl-4,5-thiazolidine-4,4-diox-
ide-[3,4-d]-2-isoxazoline 10a. Yield 85%; mp 157–
21
D
159 ꢁC; ½aꢁ ¼ ꢀ141:5 (c 0.43, CHCl3); 1H NMR
(400 MHz, CDCl3): d 3.60 (dtd, J = 2.8, 3.2, 5.6 Hz,
1H), 3.81 (dd, J = 6.0, 14.4 Hz, 1H), 4.62 (dd, J = 6.0,
11.6 Hz, 1H), 5.01 (d, J = 8.0 Hz, 1H), 5.73 (dd,
J = 2.8, 8.4 Hz, 1H), 7.45 (m, 3H), 7.76 (m, 2H); 13C
NMR (100.6 MHz, CDCl3): d 46.6, 69.0, 88.6, 126.9,
127.4, 129.0, 131.2, 152.4; IR (KBr): 3248, 3000, 2966,
1446, 1394, 1352, 1324, 1184, 1144, 928, 840,

H.-K. Zhang et al. / Tetrahedron: Asymmetry 16 (2005) 761–771
769
Water (1 mL) was added to quench the reaction. After
the removal of solvent, the residue was treated with
water (10 mL) and ethyl acetate (15 mL). Organic phase
was separated, and aqueous was extracted with ethyl
acetate (3 · 10 mL). The combined organic phase was
dried over anhydrous MgSO4. Solvent was removed,
and the residue was subjected to column chromatogra-
phy on silica gel (ethyl acetate/petroleum ether = 1:3,
v/v) to give pure N-enoyl sultam.
128.6, 129.1, 129.2, 135.3, 136.4, 147.1, 163.5; IR
(KBr): 3031, 2964, 2881, 1683, 1644, 1462, 1340, 1247,
1195, 1141, 699 cmꢀ1; HRMS (ESI) m/z C21H22N2O4S
(M)+. Calcd: 398.4767. Found: 398.4765.
3.5.5. (3R,3aR,6aR)-5-Acryloyl-2-benzyl-3-phenyl-4,5-
thiazoline-4,4-dioxide[3,4-d]isoxazolidine
15g. Yield
21
D
1
33%; mp 120–122 ꢁC; ½aꢁ ¼ ꢀ6:4 (c 1.02, CHCl3); H
NMR (270 MHz, CDCl3): d 3.66 (dd, J = 4.0, 13.6 Hz,
1H), 3.77 (d, J = 14.4 Hz, 1H), 3.95 (d, J = 14.4 Hz,
1H), 4.17 (t, J = 6.8 Hz, 1H), 4.32 (d, J = 6.0 Hz, 1H),
4.42 (d, J = 14.4 Hz, 1H), 4.98 (dd, J = 4.4, 6.8 Hz,
1H), 5.96 (dd, J = 1.2, 10.4 Hz, 1H), 6.59 (dd, J = 1.2,
16.4 Hz, 1H), 7.02 (dd, J = 10.4, 16.4 Hz, 1H), 7.29–
7.33 (m, 5H), 7.39–7.45 (m, 3H), 7.51–7.53 (m, 2H);
13C NMR (67.8 MHz, CDCl3): d 44.8, 59.2, 73.8, 74.9,
74.6, 127.0, 127.6, 128.0, 128.3, 128.7, 129.2, 129.3,
132.4, 135.2, 136.4, 163.4; IR (KBr): 3032, 2961, 2881,
3.5.1. (3aR,6aR)-3-Phenyl-5-trans-crotonyl-4,5-thiazo-
line-4,4-dioxide[3,4-d]-2-isoxazoline 15a. Yield 85%;
21
mp 174–176 ꢁC; ½aꢁ ¼ þ151:8 (c 0.90, CHCl3);
D
1H NMR (270 MHz, CDCl3): d 1.90 (dd, J = 1.6, 6.8 Hz,
3H), 4.01 (dd, J = 4.3, 13.5 Hz, 1H), 4.72 (d, J = 13.8 Hz,
1H), 5.27 (d, J = 9.2 Hz, 1H), 5.55 (dd, J = 3.2, 9.2 Hz,
1H), 6.55 (qq, J = 1.6, 15.1 Hz, 1H), 7.15 (dq, J = 7.0,
14.9 Hz, 1H), 7.48 (m, 3H), 7.74 (m, 2H); 13C
NMR (67.8 MHz, CDCl3): d 18.5, 46.7, 71.4, 79.8, 121.1,
126.7, 127.1, 129.0, 131.2, 147.9, 151.5, 162.6; IR (KBr):
1685, 1648, 1463, 1342, 1242, 1196, 1142, 672 cmꢀ1
;
HRMS (ESI) m/z C20H20N2O4NaS (M+Na)+. Calcd:
407.1041. Found: 407.1045.
300, 2948, 1690, 1446, 1338, 1074, 923, 773, 685 cmꢀ1
;
MS (FAB) m/z: 307 (M+H)+, 239, 77, 69; C14H14N2O4S
requires 306; HRMS (ESI) m/z C14H15N2O4S (M+H)+.
Calcd: 307.0751. Found: 307.0748.
3.5.6. (3R,3aR,6aR)-2-Benzyl-3-pyrenyl-5-trans-croton-
yl-4,5-thiazoline-4,4-dioxide[3,4-d]isoxazolidine 15h. Yield
21
D
1
85%; ½aꢁ ¼ þ26:2 (c 1.4, CHCl3); H NMR (400 MHz,
3.5.2. (3aS,6aS)-5-Acryloyl-3-phenyl-4,5-thiazoline-4,4-
dioxide[3,4-d]-2-isoxazoline 15c. Yield 37%; mp 174–
CDCl3): d 2.01 (dd, J = 1.6, 2.8 Hz, 3H), 3.74 (dd,
J = 4.8, 13.6 Hz, 1H), 3.92 (s, 2H), 4.48 (d, J = 9.6 Hz,
2H), 5.19 (m, 1H), 6.82 (m, 1H), 7.21 (m, 1H), 7.24
(m, 5H), 8.03–8.14 (m, 3H), 8.22–8.24 (m, 4H), 8.33
(m, br, 1H), 8.69 (m, br, 1H); 13C NMR (100.6 MHz,
CDCl3): d 18.53, 44.87, 59.67, 60.37, 74.36, 75.13,
121.52, 124.57, 125.12, 125.25, 125.63, 125.81, 126.28,
127.21, 127.55, 127.69, 128.20, 128.30, 128.46, 128.50,
128.69, 128.77, 129.39, 130.52, 131.20, 131.83, 136.48,
147.42, 163.66; IR (KBr): 3031, 1688, 1642, 1452, 1343,
1295, 1249, 1195, 1140, 847, 756 cmꢀ1; HRMS (ESI) m/z
C31H26N2NaO4S (M+Na)+. Calcd: 545.1511. Found:
545.1516.
21
D
176 ꢁC; ½aꢁ ¼ ꢀ257:0 (c 0.90, CHCl3); 1H NMR
(270 MHz, CDCl3): d 4.03 (dd, J = 4.3, 14.0 Hz, 1H),
4.72 (d, J = 13.5 Hz, 1H), 5.28 (d, J = 6.8 Hz, 1H),
5.56 (dd, J = 4.0, 9.7 Hz, 1H), 5.89 (dd, J = 1.6,
10.3 Hz, 1H), 6.59 (dd, J = 1.6, 16.7 Hz, 1H), 6.82 (m,
1H), 7.46–7.75 (m, 5H); 13C NMR (67.8 MHz, CDCl3):
d 46.6, 71.4, 79.9, 126.6, 126.7, 127.2, 129.1, 131.2,
132.8, 151.5, 162.6; IR (KBr): 2998, 2950, 1686, 1642,
1443, 1328, 1068, 920, 772 cmꢀ1; HRMS (ESI) m/z
C13H12N2O4S (M)+. Calcd: 292.0518. Found: 292.0516.
3.5.3. (3aR,6aR)-3-t-Butyl-5-trans-crotonyl-4,5-thiazo-
line-4,4-dioxide[3,4-d]-2-isoxazoline 15d. Yield 85%;
3.6. General procedure for the asymmetric Diels–Alder
reaction
21
D
½aꢁ ¼ þ52:5 (c 2.00, CHCl3); 1H NMR (270 MHz,
CDCl3): d 1.35 (s, 9H), 1.95 (dd, J = 1.6, 7.0 Hz, 3H),
4.05 (dd, J = 4.9, 13.8 Hz, 1H), 4.54 (d, J = 13.5 Hz,
1H), 4.83 (d, J = 7.8 Hz, 1H), 5.32 (dd, J = 3.8, 8.1 Hz,
1H), 6.57 (dd, J = 1.6, 14.8 Hz, 1H), 7.16 (m, 1H); 13C
NMR (67.8 MHz, CDCl3): d 18.54, 28.70, 33.76,
46.07, 71.78, 79.80, 121.06, 147.54, 161.84, 162.53; IR
(KBr): 2936 1684, 1442, 1321, 1068, 768 cmꢀ1; MS
(FAB) m/z 287 (M+1)+, 218, 57; C12H18N2O4S requires
286; HRMS (ESI) m/z C12H18N2NaO4S (M+Na)+.
Calcd: 309.0885. Found: 309.0895.
To a solution of N-enoyl bicyclic sultam (1.0 mmol) in
dry dichloromethane (10 mL) was added titanium(IV)
chloride (0.6 mmol, 1 M solution in dichloromethane)
under nitrogen at room temperature. After stirring for
0.5 h, the reaction mixture was cooled down to ꢀ78 ꢁC.
A solution of cyclopentadiene (15 mmol) in 2 mL of
dry dichloromethane was added. The mixture was stirred
under nitrogen at ꢀ78 ꢁC for 12 h. The course of the
reaction was monitored by TLC. When N-enoyl sultam
was consumed, water (2 mL) was added. The mixture
was filtered through a short column packed with Celite,
washed with dichloromethane. The combined organic
phase was dried over anhydrous MgSO4. After the re-
moval of solvent, the residue was subjected to column
chromatography on silica gel (ether acetate/petroleum
ether = 1:4, v/v) to give pure cycloadducts.
3.5.4. (3R,3aR,6aR)-2-Benzyl-3-phenyl-5-trans-crotonyl-
4,5-thiazoline-4,4-dioxide[3,4-d]isoxazolidine 15e. Yield
21
D
1
85%; mp 132–134 ꢁC; ½aꢁ ¼ ꢀ14:9 (c 1.67, CHCl3); H
NMR (270 MHz, CDCl3): d 1.97 (dd, J = 1.6, 7.0 Hz,
3H), 3.64 (dd, J = 4.6, 13.8 Hz, 1H), 3.77 (d,
J = 14.0 Hz, 1H), 3.95 (d, J = 14.3 Hz, 1H), 4.15 (dd,
J = 7.3, 14.0 Hz, 1H), 4.34 (d, J = 10.3 Hz, 1H), 4.37
(d, J = 17.3 Hz, 1H), 4.96 (dd, J = 4.3, 7.3 Hz, 1H),
6.74 (qq, J = 1.6, 14.8 Hz, 1H), 7.17 (m, 1H), 7.25–
7.53 (m, 10H); 13C NMR (67.8 MHz, CDCl3): d 18.6,
45.0, 59.3, 73.8, 74.0, 74.8, 121.5, 127.5, 128.0, 128.2,
3.6.1. (3aR,6aR)-5-N-{(1R*,2S*,3R*,4S*)-3-Methyl-
bicyclo[2,2,1]hept-5-en-2-formyl}-3-phenyl-4,5-thiazolidine-
4,4-dioxide[3,4-d]-2-isoxazoline 16a. Yield 73%; mp
18
216–218 ꢁC; ½aꢁ ¼ þ294 (c 0.81, CHCl3); 1H
D

770
H.-K. Zhang et al. / Tetrahedron: Asymmetry 16 (2005) 761–771
NMR (270 MHz, CDCl3): d 1.14 (d, J = 7.0 Hz, 3H),
1.39 (dd, J = 1.6, 8.9 Hz, 1H), 1.54 (br s, 1H), 1.99 (m,
1H), 2.50 (br s, 1H), 2.92 (t, J = 4.1 Hz, 1H), 3.19 (br
s, 1H), 4.00 (dd, J = 4.3, 13.8 Hz, 1H), 4.55 (d,
J = 13.8 Hz, 1H), 5.29 (d, J = 9.2 Hz, 1H), 5.53 (dd,
J = 3.5, 9.2 Hz, 1H), 5.84 (dd, J = 2.7, 5.7 Hz, 1H),
6.34 (dd, J = 3.2, 5.7 Hz, 1H), 7.50 (m, 3H), 7.76 (m,
2H); 13C NMR (67.8 MHz, CDCl3): d 20.4, 38.5, 47.1,
47.4, 48.5, 49.6, 53.2, 71.6, 79.5, 126.8, 127.2, 129.1,
131.2, 139.1, 151.7, 172.4; IR (KBr): 2927, 1718, 1651,
129.1, 131.0, 135.2, 135.9, 139.1, 172.9; IR (KBr):
;
2923, 2876, 1705, 1457, 1394, 1016, 918, 706 cmꢀ1
HRMS (ESI) m/z C20H29N2O4S (M+H)+. Calcd:
465.1848. Found: 465.1852.
3.6.5. (3R,3aR,6aR)-5-N-{(1S*,2R*,3S*,4R*)-3-Methyl-
bicyclo[2,2,1]hept-5-en-2-formyl}-3-phenyl-4,5-thiazolidine-
4,4-dioxide[3,4-d]isoxazolidine
17e. Yield
9%;
18
D
½aꢁ ¼ ꢀ22 (c 0.38, CHCl3); 1H NMR (270 MHz,
CDCl3): d 1.14 (d, J = 7.0 Hz, 3H), 1.51 (d, J = 8.6 Hz,
1H), 1.62 (d, J = 8.8 Hz, 1H), 2.01 (m, 1H), 2.62 (br s,
1H), 3.00 (t, J = 3.5 Hz, 1H), 3.37 (br s, 1H), 3.63 (dd,
J = 4.2, 13.6 Hz, 1H), 3.76 (d, J = 13.6 Hz, 1H), 4.06
(d, J = 13.6 Hz, 1H), 4.10 (d, J = 6.8 Hz, 1H), 4.15 (d,
J = 13.6 Hz, 1H), 4.35 (d, J = 6.8 Hz, 1H), 4.94 (dd,
J = 4.3, 7.2 Hz, 1H), 5.88 (dd, J = 2.7, 5.7 Hz, 1H),
6.38 (dd, J = 2.7, 5.7 Hz, 1H), 7.29 (m, 5H), 7.43 (m,
3H), 7.53 (m, 2H); HRMS (ESI) m/z C20H29N2O4S
(M+H)+. Calcd: 465.1848. Found: 465.1856.
1446, 1353, 1336, 1235, 1209, 1132, 917, 773 cmꢀ1
;
HRMS (ESI) m/z C19H20N2O4NaS (M+Na)+. Calcd:
395.1041. Found: 395.1043.
3.6.2. (3aR,6aR)-5-N-{(1S*,2R*,3S*,4R*)-3-Methyl-
bicyclo[2,2,1]hept-5-en-2-formyl}-3-phenyl-4,5-thiazolidine-
4,4-dioxide-[3,4-d]-2-isoxazoline
17a. Yield
7%;
18
D
½aꢁ ¼ ꢀ308 (c 0.42, CHCl3); 1H NMR (270 MHz,
CDCl3): d 1.08 (d, J = 7.0 Hz, 3H), 1.45 (dd, J = 1.6,
8.8 Hz, 1H), 1.57 (br m, 1H), 1.95 (m, 1H), 2.65 (br
m, 1H), 3.06 (t, J = 4.0 Hz, 1H), 3.28 (br m, 1H), 3.85
(dd, J = 4.3, 13.8 Hz, 1H), 4.63 (d, J = 14.0 Hz, 1H),
5.31 (d, J = 9.2 Hz, 1H), 5.51 (dd, J = 3.2, 9.2 Hz, 1H),
5.84 (dd, J = 2.7, 5.8 Hz, 1H), 6.32 (dd, J = 2.7,
5.8 Hz, 1H), 7.46 (m, 3H), 7.73 (m, 2H); 13C NMR
(100.6 MHz, CDCl3): d 20.0, 37.8, 46.8, 47.3, 47.8,
49.2, 52.3, 71.6, 80.0, 126.7, 127.2, 129.0, 131.1, 139.4,
151.8, 172.4; HRMS (ESI) m/z C19H20N2O4NaS
(M+Na)+. Calcd: 395.1041. Found: 395.1047.
3.6.6. (3R,3aR,6aR)-5-N-{(1R*,2S*,4S*)-Bicyclo[2,2,1]-
hept-5-en-2-formyl}-3-phenyl-4,5-thiazolidine-4,4-dioxide-
21
D
[3,4-d]isoxazolidine 16g. Yield 65%; ½aꢁ ¼ þ15:8 (c
1
0.60, CHCl3); H NMR (270 MHz, CDCl3): d 1.26 (br
s, 1H), 1.37–1.50 (m, 3H), 2.00–2.08 (m, 1H), 2.95 (br
m, 1H), 3.40 (br m, 1H), 3.51–3.59 (m, 1H), 3.71–3.79
(m, 1H), 3.99 (t, J = 14.3 Hz, 1H), 4.11–4.18 (m, 1H),
4.24–4.41 (m, 2H), 4.93 (dd, J = 4.1, 7.0 Hz, 1H), 5.93
(qq, J = 3.0, 7.0 Hz, 1H), 6.25 (dd, J = 3.0, 7.0 Hz,
1H), 7.27–7.54 (m, 10H); 13C NMR (67.8 MHz, CDCl3):
d 30.1, 30.8, 42.9, 43.9, 44.7, 47.0, 49.9, 59.1, 73.7, 74.8,
127.5, 128.0, 128.2, 128.7, 129.1, 129.2, 132.1, 135.2,
136.1, 137.7, 172.9; IR (KBr): 2971, 2876, 1701, 1456,
1348, 1331, 1247, 1190, 1027, 699 cmꢀ1; HRMS (ESI)
m/z C25H26N2NaO4S (M+Na)+. Calcd: 473.1511.
Found: 473.1515.
3.6.3. (3aS,6aS)-5-N-{(1S*,2R*,4R*)-Bicyclo[2,2,1]hept-
5-en-2-formyl}-3-phenyl-4,5-thiazolidine-4,4-dioxide-[3,4-
d]-2-isoxazoline 17c. Yield 62%; mp 218–220 ꢁC;
18
½aꢁ ¼ ꢀ239:2 (c 0.80, CHCl3); 1H NMR (400 MHz,
D
CDCl3): d 1.24–1.54 (m, 3H), 1.83–1.89 (m, 1H), 2.91
(br s, 1H), 3.39 (br s, 1H), 3.55 (m, 1H), 3.88 (dd,
J = 4.0, 14.0 Hz, 1H), 4.74 (d, J = 13.6 Hz, 1H), 5.30
(dd, J = 8.8, 17.2 Hz, 1H), 5.53 (m, 1H), 5.88 (dd,
J = 2.8, 5.6 Hz, 1H), 6.25 (dd, J = 2.8, 5.6 Hz, 1H),
7.50 (m, 3H), 7.76 (m, 2H); 13C NMR (67.8 MHz,
CDCl3): d 30.8, 42.8, 44.9, 47.0, 47.1, 49.9, 71.6, 79.8,
127.3, 129.1, 131.3, 132.1, 137.6, 138.1, 151.6, 171.8;
IR (KBr): 2977, 1711, 1565, 1447, 1350, 1241, 1178,
915, 772 cmꢀ1; HRMS (ESI) m/z C18H18N2O4NaS
(M+Na)+. Calcd: 381.0884. Found: 381.0910.
3.6.7. (3R,3aR,6aR)-5-N-{(1S*,2R*,4R*)-Bicyclo[2,2,1]-
hept-5-en-2-formyl}-3-phenyl-4,5-thiazolidine-4,4-dioxide-
18
D
[3,4-d]isoxazolidine 17g. Yield 18%; ½aꢁ ¼ ꢀ11 (c
1
0.35, CHCl3); H NMR (270 MHz, CDCl3): d 1.28 (m,
1H), 1.40–1.56 (m, 3H), 1.88–2.06 (m, 1H), 3.05 (m,
1H), 3.43 (m, 1H), 3.49–3.57 (m, 1H), 3.65–3.76 (m,
1H), 4.02 (t, J = 14.3 Hz, 1H), 4.12–4.17 (m, 1H),
4.26–4.38 (m, 2H), 4.95 (dd, J = 4.0, 7.2 Hz, 1H), 5.87
(dd, J = 3.0, 5.7 Hz, 1H), 6.18 (dd, J = 3.0, 5.7 Hz,
1H), 7.25–7.56 (m, 10H); 13C NMR (67.8 MHz, CDCl3):
3.6.4. (3R,3aR,6aR)-5-N-{(1R*,2S*,3R*,4S*)-3-Methyl-
bicyclo[2,2,1]hept-5-en-2-formyl}-3-phenyl-4,5-thiazolidine-
d
31.3, 32.0, 42.8, 43.9, 45.3, 47.1, 50.2, 59.1,
73.8, 74.0, 127.3, 127.8, 128.2, 128.7, 129.1, 129.2,
131.1, 135.4, 136.2, 137.9, 172.5; HRMS (ESI) m/z
C25H26N2NaO4S (M+Na)+. Calcd: 473.1511. Found:
473.1518.
4,4-dioxide[3,4-d]isoxazolidine
16e. Yield
81%;
18
D
½aꢁ ¼ þ42:4 (c 1.05, CHCl3); 1H NMR (270 MHz,
CDCl3): d 1.15 (d, J = 7.0 Hz, 3H), 1.50 (d, J = 8.6 Hz,
1H), 1.70 (d, J = 8.9 Hz, 1H), 2.03 (m, 1H), 2.55 (br
m, 1H), 3.01 (t, J = 3.5 Hz, 1H), 3.37 (s, 1H), 3.62 (dd,
J = 4.3, 13.5 Hz, 1H), 3.78 (d, J = 14.3 Hz, 1H), 4.03
(d, J = 14.3 Hz, 1H), 4.13 (d, J = 6.8 Hz, 1H), 4.20 (d,
J = 13.5 Hz, 1H), 4.35 (d, J = 6.8 Hz, 1H), 4.94 (dd,
J = 4.3, 7.0 Hz, 1H), 5.89 (dd, J = 2.7, 5.7 Hz, 1H),
6.39 (dd, J = 2.7, 5.7 Hz, 1H), 7.26 (m, 5H), 7.42 (m,
3H), 7.53 (d, J = 9.2 Hz, 2H); 13C NMR (67.8 MHz,
CDCl3): d 20.4, 38.1, 45.5, 47.1, 48.2, 49.5, 52.8, 59.0,
73.2, 73.7, 74.7, 127.4, 127.8, 128.1, 128.6, 129.0,
3.6.8. (3R,3aR,6aR)-5-N-{(1R*,2S*,3R*,4S*)-3-Methyl-
bicyclo[2,2,1]hept-5-en-2-formyl}-3-pyrenyl-4,5-thiazolidine-
4,4-dioxide[3,4-d]isoxazolidine
16h. Yield
80%;
21
D
½aꢁ ¼ þ83:3 (c 1.7, CHCl3); 1H NMR (400 MHz,
CDCl3): d 1.16 (d, J = 6.8 Hz, 3H), 1.55–1.60 (m, 2H),
1.75 (d, J = 8.4 Hz, 1H), 2.05 (m, 1H), 2.57 (s, 1H),
3.08 (t, J = 3.6 Hz, 1H), 3.51 (s, 1H), 3.74 (dd, J = 4.4,
13.6 Hz, 1H), 3.98 (q, J = 14.4 Hz, 2H), 4.30 (d,

H.-K. Zhang et al. / Tetrahedron: Asymmetry 16 (2005) 761–771
771
J = 13.2 Hz, 1H), 4.48 (m, 1H), 5.18 (t, J = 5.6 Hz, 1H),
References
5.98 (d d, J = 2.4, 5.2 Hz, 1H), 6.44 (dd, J = 3.2, 5.6 Hz,
1H), 7.22–7.27 (m, 5H), 8.03–8.15 (m, 3H), 8.25 (t,
J = 6.8 Hz, 1H), 8.36 (d, J = 6.4 Hz, 1H), 8.69 (d,
J = 6.8 Hz, 1H); 13C NMR (100.6 MHz, CDCl3): d
20.35, 38.26, 45.44, 47.23, 48.56, 49.60, 52.80, 59.54,
73.98, 75.23, 122.32, 124.59, 125.15, 125.25, 125.65,
125.82, 126.30, 127.22, 127.61, 128.22, 128.29, 128.47,
128.73, 128.89, 129.34, 130.53, 131.22, 131.31, 131.84,
136.18, 139.44, 173.26; IR (KBr): 2960, 1688, 1648,
1438, 1312, 1236, 1112, 1148, 708 cmꢀ1; HRMS (ESI)
m/z C36H32N2NaO4S (M+Na)+. Calcd: 611.1980.
Found: 611.1954.
1. Seyden-Penne, J. Chiral Auxiliaries and Ligands in Asym-
metric Synthesis; John Wiley & Sons: New York, 1995.
2. Handbook of Reagents for Organic Synthesis—Reagents,
Auxiliaries and Catalysts for C–C bonds; Coates, R. M.,
Denmark, S. E., Eds.; John Wiley & Sons: New York,
1999.
3. Myers, A. G.; Yang, B. H.; Chen, H.; Gleason, J. L.
J. Am. Chem. Soc. 1994, 116, 9361.
4. Vicario, J. L.; Badia, D.; Carrillo, L. J. Org. Chem. 2001,
66, 9030.
5. Davies, G. S.; Sanganee, H. J. Tetrahedron: Asymmetry
1995, 6, 671.
6. Boeckman, R. K.; Laci, M. A.; Johnson, A. T. Tetrahe-
dron: Asymmetry 2001, 12, 205.
3.7. General procedure for the saponification of
cycloadducts
7. Kawecki, R. Tetrahedron: Asymmetry 2003, 14, 2827–
2832.
8. Shing, T. K. M.; Chow, H. F.; Chung, I. H. F.
Tetrahedron Lett. 1996, 37, 3713–3716.
9. Nouguier, R.; Mignon, V.; Gras, J.-L. J. Org. Chem. 1999,
64, 1412.
10. Evans, D. A.; Chapman, K. T.; Bisaha, J. J. Am. Chem.
Soc. 1988, 110, 1238.
To a solution of LiOHÆH2O (8.0 mmol) in THF/H2O
(5:1, v/v) (5 mL/mmol) was added cycloadduct 15e
(1.0 mmol). The mixture was vigorously stirred at room
temperature for 24 h. When the reaction was completed
(monitored by TLC), solvents were removed. To the resi-
due was added water (20 mL/mmol) and adjusted to
pH 10 by adding saturated NaHCO3. The basic solution
was extracted with dichloromethane (3 · 15 mL). The
extracts were washed with brine, dried over anhydrous
MgSO4, concentrated under reduced pressure to recover
the chiral sultam auxiliary.
11. Oppolzer, W. Pure Appl. Chem. 1990, 62, 1241.
12. (a) Akkari, R.; Calmes, M.; Escale, F.; Iapichella, J.;
Rolland, M.; Martinez, J. Tetrahedron: Asymmetry 2004,
15(16), 2515; (b) Boeckman, R. K., Jr.; Reeder, L. M.
Synlett 2004, 8, 1399; (c) Kobayashi, T.; Tanaka, K.;
Miwa, J.; Katsumura, S. Tetrahedron: Asymmetry 2004,
15(2), 185; (d) Robiette, R.; Cheboub-Benchaba, K.;
Peeters, D.; Marchand-Brynaert, J. J. Org. Chem. 2003,
68(25), 9809; (e) Ding, X.; Ukaji, Y.; Fujinami, S.;
Inomata, K. Chem. Lett. 2003, 32(7), 582; (f) Lait, S.
M.; Parvez, M.; Keay, B. A. Tetrahedron: Asymmetry
2003, 14(6), 749; (g) Fernandez, F.; Garcia-Mera, X.;
Rodriguez-Borges, J. E.; Vale, M. L. C. Tetrahedron Lett.
2003, 44(3), 431; (h) Lakner, F. J.; Negrete, G. R. Synlett
2002(4), 643; (i) Boeckman, R. K., Jr.; Laci, M. A.;
Johnson, A. T. Tetrahedron: Asymmetry 2001, 12(2),
205; (j) Jiang, L.-S.; Chan, W.-H.; Li, W.-M. Zhongshan
Daxue Xuebao, Ziran Kexueban 2000, 39(4), 131; (k)
Carriere, A.; Virgili, A. Tetrahedron: Asymmetry 1996,
7(1), 227.
13. (a) Cipiciani, A.; Fringuelli, F.; Piermatti, O.; Pizzo, F.;
Ruzziconi, R. J. Org. Chem. 2002, 67, 2665; (b) Oppolzer,
W.; Blagg, J.; Rodriguez, I.; Walther, E. J. Am. Chem.
Soc. 1990, 112, 2767; (c) Evans, D. A.; Chapman, T.;
Bisaha, J. J. Am. Chem. Soc. 1984, 106, 4261; (d) Mayer,
S. C.; Pfizenmayer, A. J.; Cordova, R.; Li, W.-R.; Joullie,
M. M. Tetrahedron: Asymmetry 1994, 5, 519; (e) Chapuis,
C.; Rzepecki, P.; Bauer, T.; Jurczak, J. Helv. Chim. Acta
1994, 78, 145.
The aqueous layer was acidified by 6 N HCl to pH 1,
and then extracted with ethyl acetate (3 · 15 mL). The
combined organic phase was dried over anhy-
drous MgSO4, and concentrated to give carboxylic
acid.
3.7.1. (2-endo,3-exo)-3-Methyl-bicyclo[2,2,1]hept-5-en-2-
22
carboxylic acid 18a. Yield 82%; ½aꢁ ¼ ꢀ138 (c 0.96,
D
95% ethanol; lit.:17 ꢀ140); 1H NMR (270 MHz, CDCl3):
d 1.20 (d, J = 7.0 Hz, 1H), 1.46 (dd, J = 1.5, 8.6 Hz, 1H),
1.56 (d, J = 8.6 Hz, 1H), 1.83 (m, 1H), 2.41 (t,
J = 4.0 Hz, 1H), 2.48 (br s, 1H), 3.13 (br s, 1H), 6.04
(dd, J = 2.6, 5.6 Hz, 1H), 6.28 (dd, J = 3.3, 5.6 Hz,
1H); 13C NMR (67.8 MHz, CDCl3): d 21.0, 38.0, 45.9,
46.1, 48.9, 52.4, 133.2, 138.7, 180.2.
3.7.2. (2-endo)-Bicyclo[2,2,1]hept-5-en-2-carboxylic acid
22
18b. Yield 73%; ½aꢁ ¼ ꢀ136 (c 0.69, 95% ethanol;
D
lit.:17b ꢀ138); 1H NMR (270 MHz, CDCl3): d 1.21–
1.51 (m, 3H), 1.85–2.03 (m, 1H), 2.85–3.06 (m, 2H),
3.24 (br s, 1H), 6.01 (dd, J = 2.7, 5.6 Hz, 1H), 6.23
(dd, J = 2.7, 5.6 Hz, 1H); 13C NMR (67.8 MHz,
CDCl3): d 29.3, 42.8, 43.9, 45.8, 50.0, 132.7, 138.0,
181.5.
14. (a) Chan, W. H.; Lee, A. W. M.; Jiang, L. S.; Mak,
T. C. W. Tetrahedron: Asymmetry 1997, 8, 2501;
(b) Lin, J.; Chan, W. H.; Lee, A. W. M.; Wong,
W. Y. Tetrahedron 1999, 55, 13983; (c) Jiang, L. S.;
Chan, W. H.; Lee, A. W. M. Tetrahedron 1999, 55,
2245.
15. Zhang, H.; Chan, W. H.; Lee, A. W. M.; Xia, P.-F.;
Wong, W. Y. Lett. Org. Chem. 2004, 1, 63.
´
16. Thom, C.; Kocienski, P. Synthesis 1992, 582.
Acknowledgements
17. (a) Krotz, A.; Helmchen, G. Tetrahedron: Asymmetry
1990, 1(8), 537; (b) Akiyama, T.; Horiguchi, N.; Ida, T.;
Ozaki, S. Chem. Lett. 1995, 975; (c) Wrobleski, A.;
Saharabudhe, K.; Aube, J. J. Am. Chem. Soc. 2002, 124,
9974.
The work described in the paper was fully supported by
grants from the University Grants Committee of the
Hong Kong Special Administrative Region, China
(AOE/p-10/01 and HKBU 2024/OOP) and a grant from
the Hong Kong Baptist University (PRG/01-02/II-41).
18. Zhang, H.; Chan, W. H.; Lee, A. W. M.; Wong, W. Y.
Tetrahedron Lett. 2003, 44, 395.