Enantioselective reaction of α-lithiated thiazolidines as new chiral formyl anion equivalents

Article abstract of DOI:10.1016/j.tetasy.2004.08.010

The reaction of lithiated N-Boc-thiazolidine and N-Boc-benzothiazolidine with benzophenone in the presence of (-)-sparteine afforded the products with up to 97% ee and 93% ee, respectively. The reaction with various aromatic and aliphatic aldehydes also afforded the products with high enantioselectivity and moderate diastereoselectivity. Each diastereomer could be converted to optically active diols. Consequently, lithiated N-Boc-thiazolidine and N-Boc-benzothiazolidine serve as chiral formyl anion equivalents. The reaction was confirmed to proceed through a dynamic thermodynamic resolution pathway.

Full text of DOI:10.1016/j.tetasy.2004.08.010

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 15 (2004) 3059–3072
Enantioselective reaction of a-lithiated thiazolidines as
new chiral formyl anion equivalents
Libo Wang, Shuichi Nakamura, Yuji Ito and Takeshi Toru*
Department of Applied Chemistry, Graduate School of Engineering, Nagoya Institute of Technology,
Gokiso, Showa-ku, Nagoya 466-8555, Japan
Received 13 June 2004; accepted 9 August 2004
Abstract—The reaction of lithiated N-Boc-thiazolidine and N-Boc-benzothiazolidine with benzophenone in the presence of (ꢀ)-
sparteine afforded the products with up to 97% ee and 93% ee, respectively. The reaction with various aromatic and aliphatic
aldehydes also afforded the products with high enantioselectivity and moderate diastereoselectivity. Each diastereomer could be con-
verted to optically active diols. Consequently, lithiated N-Boc-thiazolidine and N-Boc-benzothiazolidine serve as chiral formyl anion
equivalents. The reaction was confirmed to proceed through a dynamic thermodynamic resolution pathway.
ꢀ 2004 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Chiral formyl anion equivalents are useful tools for
asymmetric synthesis. There are many examples of chi-
ral formyl anion equivalents using various chiral auxilia-
ries. Diastereoselective reactions of carbanions derived
from dithioacetals,1 N,S-acetals,2 hemithioacetals,3 1,3-
dioxolanes4 and 1,3-oxazolidines,5 have been reported.
On the other hand, there are only a few enantioselective
reactions reported and reactions of carbanions derived
from dithioacetals6 and oxazolidines7 have been
reported. We have previously reported highly enantio-
selective lithiation–substitution reactions of a-thio
carbanion of various sulfides in the presence of bis-
(oxazoline)s,8,9 and an enantioselective reaction using
unsymmetrical dithioacetals as chiral formyl anion
equivalents.10 We recently reported the first highly
enantioselective reaction of the thiazolidine.11 Herein
we report in detail an enantioselective reaction of lithi-
ated N-Boc-thiazolidine and N-Boc-benzothiazolidine
with benzophenone and various aromatic and aliphatic
aldehydes and the subsequent transformation of the
products to chiral 1,2-ethanediols.
2.1. Reaction of Li-1 and Li-2 with benzophenone
We first examined the reaction of lithiated N-Boc-thiaz-
olidine Li-1 and N-Boc-benzothiazolidine Li-2 with ben-
zophenone using either (ꢀ)-sparteine 5, 2,2-bis{2-[(4S)-
alkyl-1,3-dioxazolinyl]}propane 6a–c [bis(oxazoline)–
R], or (1R,2R)-N,N,N0N0-tetramethylcyclohexane-1,2-
diamine 7, as a chiral ligand (Scheme 1). N-Boc-thiazol-
idine 1 and N-Boc-benzothiazolidine 2 were treated
with 1.2equiv of n-BuLi for 15min at an appropriate
temperature and subsequently with 1.2equiv of a chiral
ligand for 1h. To the resultant solution was added
1.3equiv of benzophenone with the corresponding
enantiomeric products 3 and 4 obtained. The results
are shown in Table 1. The reaction in THF in the pres-
ence of (ꢀ)-sparteine at ꢀ78ꢁC gave product 3 in good
yield but with low enantioselectivity (entry 1), while
when the reaction was performed in Et2O and hexane,
good enantioselectivity was obtained (entries 2 and 3).
On the other hand, the reaction in cumene showed high
enantioselectivity (entries 4 and 5). The reaction in tolu-
ene at ꢀ78ꢁC also showed excellent enantioselectivity
(entry 6), while at ꢀ95ꢁC the enantioselectivity (entry
7) was slightly lowered. The enantioselectivity also
decreased when performed at higher temperatures
(entries 8 and 9). The reaction using s-BuLi or t-BuLi
did not improve the yield (entries 10 and 11). Bis(oxazo-
line)-iPr 6a and bis(oxazoline)-tBu 6b showed rather low
*
Corresponding author. Tel./fax: +81 52 735 5217; e-mail: toru@
nitech.ac.jp
0957-4166/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2004.08.010

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L. Wang et al. / Tetrahedron: Asymmetry 15 (2004) 3059–3072
Table 2). Treatment of N-Boc-thiazolidine 1 with
1) RLi (1.2 eq.)
Boc
N
Boc
N
OH
2) chiral ligand (1.2 eq.)
3) benzophenone (1.3 eq.)
1.2equiv of n-BuLi and 1.2equiv of (ꢀ)-sparteine in tolu-
ene at ꢀ78ꢁC for 1h, followed by the addition of vari-
ous aldehydes, gave the corresponding alcohols 8a–17a
in good yields. Since each diastereomer derived from
the reaction with aromatic aldehydes could not be sepa-
rated by column chromatography, the obtained alcohols
8a–13a were converted to the corresponding acetates
8b–13b, which could be easily separated by column
chromatography. When benzaldehyde was used, prod-
uct 8a was obtained in 74% yield and in a 42:58 dia-
stereomer ratio. The enantiomeric excess of the syn-
and anti-isomers were determined to be 93% and 88%
ee, respectively, by the HPLC analysis after conversion
to the corresponding acetate (entry 1). The reaction of
lithiated N-Boc-thiazolidine Li-1 with other aromatic
aldehydes such as p-tolualdehyde, p-anisaldehyde, p-
chlorobenzaldehyde, 1-naphthaldehyde, and 2-naphtha-
ldehyde gave the corresponding products 9a–13a, each
syn- and anti-isomer of which had high enantiomeric
purity (entries 2–6). Although the reaction with prop-
anal afforded product 14a with moderate enantioselec-
tivity (entry 7), the reaction with other aliphatic
aldehydes, such as 3-methylbutanal, cyclohexanecarbal-
dehyde and 2,2-dimethylpropanal, afforded products
15a–17a with high enantioselectivities (entries 8–10).
The syn- and anti-isomers of 14a–17a could be separated
by column chromatography. The reaction of lithiated N-
Boc-benzothiazolidine Li-2 with various aldehydes gave
the corresponding alcohols 18–23 in high yields. Both
the syn- and anti-isomers were formed with high enan-
tioselectivity. In the reaction of 2, the syn- and anti-iso-
mers of alcohols 18–23 were easily separable by column
chromatography. When benzaldehyde was used, alcohol
18 was obtained in 93% yield in a 60:40 diastereomer
ratio, with the enantiomeric excesses of the syn- and
anti-isomers were determined to be 93% and 88% ee,
respectively, (entry 11). The reaction with various
aromatic aldehydes afforded the corresponding products
Ph
Ph
solvent, temp.
S
1
S
3
Boc
N
OH
1) RLi (1.2 eq.)
Boc
2) chiral ligand (1.2 eq.)
3) benzophenone (1.3 eq.)
N
Ph
Ph
S
solvent, temp.
S
2
4
NMe2
NMe2
O
O
N
N
N
N
R
R
6a: R =iPr
b: R =tBu
c: R = Ph
7
5
Scheme 1.
enantioselectivity12 (entries 12 and 13), whereas with
bis(oxazoline)-Ph 6c, 3 was obtained with good enantio-
selectivity but with the opposite stereochemistry of that
obtained above (entry 14). Cyclohexanediamine 7 did
not afford a satisfactory result (entry 15). The reaction
of lithiated N-Boc-benzothiazolidine 2 with benzophen-
one using (ꢀ)-sparteine 5 in toluene or cumene both at
ꢀ78ꢁC and at ꢀ95ꢁC gave good enantiomeric purity
of product 4 in good yield (entries 16–19).
2.2. Reaction of Li-1 and Li-2 with aldehydes
The enantioselective reaction of lithiated N-Boc-thiazol-
idine Li-1 and lithiated N-Boc-benzothiazolidine Li-2
with various aldehydes was next examined (Scheme 2,
Table 1. Enantioselective reaction of lithiated N-Boc-thiazolidine 1 and N-Boc-benzothiazolidine 2 with benzophenone
Entry
Substrate
RLi
Solvent
Chiral ligand
Reaction temperature (ꢁC)
Product
Yield (%)
Ee (%)a
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
2
2
2
2
n-BuLi
n-BuLi
n-BuLi
n-BuLi
n-BuLi
n-BuLi
n-BuLi
n-BuLi
n-BuLi
s-BuLi
t-BuLi
n-BuLi
n-BuLi
n-BuLi
n-BuLi
n-BuLi
n-BuLi
n-BuLi
n-BuLi
THF
Et2O
5
ꢀ78
ꢀ78
ꢀ78
ꢀ78
ꢀ95
ꢀ78
ꢀ95
ꢀ50
ꢀ30
ꢀ78
ꢀ78
ꢀ78
ꢀ78
ꢀ78
ꢀ78
ꢀ78
ꢀ78
ꢀ95
ꢀ95
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
4
4
4
4
76
43
44
54
36
65
32
69
35
31
36
53
57
17
21
74
70
60
53
19
60
2
5
3
Hexane
Cumene
Cumene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Cumene
Toluene
Cumene
5
84
92
4
5
5
5
97
97
6
5
7
5
92
64
8
5
9
5
ꢀ13
53
10
11
12
13
14
15
16
17
18
19
5
5
35
6a
6b
6c
7
ꢀ13
ꢀ68
82
ꢀ19
93b
94b
92b
93b
5
5
5
5
a Determined by the HPLC analysis using chiralcel OD-H.
b Determined by the HPLC analysis using chiralpak AD-H.

L. Wang et al. / Tetrahedron: Asymmetry 15 (2004) 3059–3072
3061
Boc
N
Boc
N
OH
Boc
N
1) n-BuLi (1.2 eq).
OH
2) (-)-sparteine (1.2 eq.)
3) RCHO (1.3 eq.)
R
+
R
S
toluene, -78oC
S
S
anti-8a-17a
syn-8a-17a
1
Boc
Boc
N
OH
OH
1) n-BuLi (1.2 eq).
Boc
N
N
2) (-)-sparteine (1.2 eq.)
3) RCHO (1.3 eq.)
R
R
S
S
toluene, -78oC
S
syn-18-23
2
anti-18-23
Scheme 2.
Table 2. Enantioselective reaction of Li-1 and Li-2 with various aldehydes
Entry
Substrate
R
Product
Yield (%)
syn/antia
syn Ee (%)b
anti Ee (%)b
c
1
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
Ph
8a
9a
74
65
58
65
55
72
67
54
69
63
93
92
92
96
89
97
42:58
46:54
43:57
42:58
22:78
42:58
59:41
53:47
61:39
51:49
60:40
53:47
55:45
51:49
57:43
58:42
93c
69c
66c
60c
64c
65c
46
88
2
p-MeC6H4
p-MeOC6H4
p-ClC6H4
1-Naphthyl
2-Naphthyl
Et
89c
90c
88c
88c
90c
3
10a
11a
12a
13a
14a
15a
16a
17a
18
4
5
6
d
7
—
87
89
87
88
93
88
89
86
86
8
i-Pr
c-Hex
77
73
9
10
11
12
13
14
15
16
tert-Bu
Ph
72
93
p-MeC6H4
p-MeOC6H4
p-ClC6H4
1-Naphthyl
2-Naphthyl
19
20
75
72
21
22
78
71
23
73
a Determined by the 1H NMR analysis.
b Determined by the HPLC analysis using chiralcel OD-H, OJ-H, or chiralpak AD-H.
c Determined by the HPLC analysis after conversion to the acetate.
d The enantiomeric purity could not be determined by various chiral columns.
19–23, the syn- and anti-isomers of which were formed
with high enantioselectivity (entries 12–16).13 Generally,
the anti-isomers had higher enantiomeric purity than the
syn-isomers except for 18 (entry 11). The syn-isomers
formed from N-Boc-benzothiazolidine 2 had higher
enantioselectivities than those from N-Boc-thiazolidine
1, whereas the anti-isomers obtained from N-Boc-thiaz-
olidine 1 and N-Boc-benzothiazolidine 2 had the same
range of enantiomeric excess.
shifts for the Hb protons in comparison with those of the
corresponding syn-isomers. On the other hand, the Ja,b
values of syn-18–23 were not clearly defined because
both protons of Ha and Hb appeared as broad singlets.
The Ha and Hb protons of syn-18–23 appeared at higher
and lower field, respectively, than those of the corres-
ponding anti-isomers. Thus, the relative stereochemistry
of 9b–13b, that is, 9a–13a, and 19–23 was tentatively
assigned by comparison of the Ja,b values and the chem-
ical shifts for the Ha and Hb protons with those for 8b
and 18.
2.3. Configuration of the stereochemistry of 8b–13b and
18–23
2.4. Conversion to optically active 1,2-ethanediols
The relative stereochemistry of syn-8b and syn-18 was
confirmed by X-ray crystallographic analysis (Fig. 1),
and the absolute configuration was determined by trans-
formation to the known chiral 1-phenyl-1,2-ethanediol
(vide infra).
In order to define the absolute configuration, the syn-
and anti-isomers of 8b–13b and 18–23 were separately
converted to the chiral 1,2-ethanediols. Thus, syn- and
anti-8b–13b were treated with mercury(II) chloride in
aqueous CH3CN at room temperature for 6–12h to give
The chemical shifts of the Ha and Hb protons and their
coupling constants in the H NMR spectra of 8a–13a
and 18–23 are shown in Table 3. Generally, the anti-iso-
mers of 8b–13b showed larger Ja,b values and downfield
the
corresponding
2-acetoxy-2-arylacetaldehydes,
1
which, without isolation, were subjected to reduction
with LiAlH4 in THF at 0ꢁC. Optically active 1-aryl-
1,2-ethanediols 24–29 were obtained in good yields

3062
L. Wang et al. / Tetrahedron: Asymmetry 15 (2004) 3059–3072
Figure 1. The Chem 3D structures derived from the X-ray crystallography of syn-8b and syn-18.
Table 3. The 1H NMR analysis for the products 8b–13b and 18–23
ols 25–29 were also obtained from 9b–13b. Under simi-
lar reaction conditions, products 15b and 16b formed in
the reaction of 1 and aliphatic aldehydes could be con-
verted to the corresponding 1,2-ethanediols 30 and 31
with moderate yields without loss of the enantiomeric
purity (entries 13–16). Since the deprotection of 18 using
mercury(II) chloride afforded product 24 in rather low
yield, 18–23 were treated with mercury(II) acetate in
aqueous acetic acid for 6 h at 50ꢁC to give the corre-
sponding 2-hydroxy-2-arylacetaldehydes, which were
subjected to reduction with NaBH4 in MeOH at room
temperature to give the corresponding chiral 1,2-ethan-
ediols 24–29 in good yields (entries 13–24). Similarly,
the absolute configurations of syn-18–23 and anti-18–
23 were determined to be (10S,2R) and (10R,2R), respec-
tively. Therefore, the major isomers of 3 and 4 obtained
in the reaction of Li-1 and Li-2 with benzophenone were
tentatively assigned to be the R-isomer.
Compounda
Ja,b (Hz)
d Ha (ppm)
d Hb (ppm)
syn-8b
anti-8b
syn-9b
4.2
6.6
4.2
6.8
4.2
6.8
4.2
6.8
4.2
6.2
3.8
6.4
5.96
5.98
5.94
5.90
5.91
5.93
5.92
5.94
6.80
6.63
6.13
6.11
5.83
5.95
5.81
5.92
5.80
5.91
5.76
5.90
6.11
6.31
5.90
6.04
5.34
5.45
5.29
5.44
5.30
5.43
5.25
5.39
5.59
5.84
5.43
5.58
4.80
4.74
4.80
4.67
4.78
4.68
4.75
4.73
5.55
5.54
4.98
4.87
anti-9b
syn-10b
anti-10b
syn-11b
anti-11b
syn-12b
anti-12b
syn-13b
anti-13b
syn-18
b
Recrystallization of the products was attempted to in-
crease the enantiopurity. For example, a single recrystal-
lization of anti-8b (88% ee) from hexane was found to
increase the enantiomeric purity to 99% ee. It was con-
verted to the corresponding optically active 1,2-ethane-
diol (R)-24 with 99% ee (Scheme 4). The enantiomeric
purity of other crystalline products could also be im-
proved by recrystallization. Thus, the present enantiose-
lective reaction of lithiated N,S-acetals provides an
efficient method for the synthesis of enantiomerically
pure 1,2-ethanediols.
—
7.8
anti-18
syn-19
b
—
7.8
anti-19
syn-20
b
—
7.8
anti-20
syn-21
b
—
7.0
anti-21
syn-22
b
—
6.2
anti-22
syn-23
anti-23
b
—
7.6
a The relative stereochemistry is the one tentatively assigned except for
8b and 18.
b Each Ha and Hb proton appeared as a broad signal.
2.5. Reaction mechanism
It is important to determine whether the reaction pro-
ceeds through asymmetric deprotonation15 or asymmet-
ric substitution.16 We examined the reaction of Li-1 and
racemic tert-butyl 2-(tributylstannyl)thiazolidine-3-
carboxylate 32 that was prepared from lithiated 1 with
tributylstannyl chloride with benzophenone in the pres-
ence of (ꢀ)-sparteine.17 Treatment of 32 with a mixture
of 1.2equiv of n-BuLi and (ꢀ)-sparteine at ꢀ78ꢁC for
15min in toluene followed by the addition of 1.3equiv
of benzophenone gave the product (R)-3 with 60% ee
(Scheme 5). The enantiomeric purity of (R)-3 was
slightly diminished, reduced from that (76% ee) obtained
(Scheme 3, Table 4). The reaction of syn-8b and anti-8b
gave optically active 1-phenyl-1,2-ethanediol 24 in 66%
and 57% yields, respectively, without loss of the enantio-
meric purity. The absolute configurations of the 1,2-
ethanediols 24 derived from syn-8b and anti-8b were
assigned to be S and R, respectively, by comparison of
the values of the specific rotation with those reported
(entries 1 and 2).14 Therefore, the absolute configura-
tions of syn-8b and anti-8b were determined to be
(10S,2R) and (10R,2R), respectively. Chiral 1,2-ethanedi-

L. Wang et al. / Tetrahedron: Asymmetry 15 (2004) 3059–3072
Boc
3063
OAc
OAc
OH
N
HgCl2
CH3CN/H2O
LiAl H4
THF, rt
R
HO
OHC
R
R
*
*
S
8b-13b, 15b-16b
24-31
Boc
OH
OH
N
OAc
Ar
Hg(OAc)2, CaCO3
AcOH/H2O
NaBH4
THF, rt
Ar
HO
Ar
OHC
S
*
*
24-29
18-23
Scheme 3.
Table 4. Conversion of 8b–13b and 18–23 to chiral 1,2-ethanediols 24–31
Entry
Substrate
1,2-Ethanediolsa
R
Ee (%)
Yield (%)
Eeb (%)
1
syn-8b
anti-8b
syn-9b
Ph
Ph
93
88
69
89
66
90
60
88
64
88
65
90
77
87
73
89
93
88
75
93
72
88
78
89
71
86
73
86
(S)-24
66
57
68
75
55
58
73
62
60
62
52
54
44
49
69
57
74
59
54
67
61
55
62
71
57
61
58
49
92
87
67
88
66
90
60
88
63
87
64
88
77
85
70
89
93
88
74
89
69
88
78
87
69
82
73
85
2
(R)-24
(S)-25
(R)-25
(S)-26
(R)-26
(S)-27
(R)-27
(S)-28
(R)-28
(S)-29
(R)-29
(S)-30
(R)-30
(S)-31
(R)-31
(S)-24
(R)-24
(S)-25
(R)-25
(S)-26
(R)-26
(S)-27
(R)-27
(S)-28
(R)-28
(S)-29
(R)-29
3
p-MeC6H4
p-MeC6H4
p-MeOC6H4
p-MeOC6H4
p-ClC6H4
p-ClC6H4
1-Naphthyl
1-Naphthyl
2-Naphthyl
2-Naphthyl
i-Pr
4
anti-9b
syn-10b
anti-10b
syn-11b
anti-11b
syn-12b
anti-12b
syn-13b
anti-13b
syn-15b
anti-15b
syn-16b
anti-16b
syn-18
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
i-Pr
c-Hex
c-Hex
Ph
Ph
anti-18
syn-19
p-MeC6H4
p-MeC6H4
p-MeOC6H4
p-MeOC6H4
p-ClC6H4
p-ClC6H4
1-Naphthyl
1-Naphthyl
2-Naphthyl
2-Naphthyl
anti-19
syn-20
anti-20
syn-21
anti-21
syn-22
anti-22
syn-23
anti-23
a The absolute configuration was determined by comparison of the value of the specific rotation with those reported.
b Calculated by comparison of the value of the specific rotation with those reported.
in the reaction of N-Boc-thiazolidine 1 under similar
conditions, which are different from those performed
in the reaction described earlier in Scheme 1, but 60%
ee of the product is enough to rule out the asymmetric
deprotonation, because the reaction through asymmet-
ric deprotonation should afford the racemic product.
Thus, the reaction proceeds through asymmetric
substitution.
1.3equiv of benzophenone (entry 6, Table 1). These
results indicate that the reaction of lithiated N-Boc-
thiazolidine with benzophenone, and hence possibly
with aromatic and aliphatic aldehydes, should proceed
through a dynamic thermodynamic resolution pathway.
3. Conclusion
The Beak test using a deficient amount of the electro-
phile16f,18 was examined. After treatment of 1 with n-
BuLi and (ꢀ)-sparteine in toluene at ꢀ78ꢁC, 0.1equiv
of benzophenone was added (Scheme 6). The enantio-
meric purity of the product 3 was 79% ee, which was
lower than that (97% ee) obtained in the reaction with
In summary, the enantioselective reaction of lithiated N-
Boc-thiazolidine and N-Boc-benzothiazolidine with var-
ious carbonyl compounds in the presence of (ꢀ)-sparte-
ine proceeded with high enantioselectivity and moderate
diastereoselectivity. The reaction was found to proceed
through a dynamic thermodynamic resolution pathway.

3064
L. Wang et al. / Tetrahedron: Asymmetry 15 (2004) 3059–3072
OH
HgCl2
CH3CN/H2O
LiAl H4
THF, rt
recrystallization
hexane
HO
anti-8b
anti-8b
Ph
R
(R)-24
88% ee
79%, 99% ee
58%, 99% ee, [α]D22= -38.8(c 0.63, EtOH)
22
lit. 14[α]D = +38.9(c 0.70, EtOH) for (S)
Scheme 4.
rile (20mL) was added 4-dimethylaminopyridine
(150mg, 1.23mmol). The reaction mixture was stirred
for 24h at room temperature. Saturated aqueous NH4Cl
was added and the mixture extracted with ethyl acetate.
The organic extracts were dried over Na2SO4 and con-
centrated under reduced pressure. The residue was puri-
fied by column chromatography (silica gel 100g,
Boc
N
Boc
N
OH
1) n-BuLi / (-)-sparteine
2) benzophenone
Ph
Ph
X
toluene, -78oC
S
S
(R)-3
1: X = H
32: X = SnBu3
64%, 76% ee (from 1)
53%, 60% ee (from 32)
1
hexane/ethyl acetate = 99:1) to give 2 (1.54g, 53%); H
Scheme 5.
NMR (CDCl3): d 1.56 (9H, s), 5.19 (2H, s), 6.88–7.12
(3H, m), 7.51–7.78 (1H, m); 13C NMR (CDCl3): d 28.5,
51.2, 81.2, 116.5, 122.0, 123.3, 125.0, 151.8; IR (neat):
2978, 2929, 1714, 1580, 1474, 1367, 1274, 1158, 1014,
854, 746cmꢀ1; MS (FAB) m/z (%): 237 (M+, 11), 180
(10), 136 (51), 57 (100). Anal. Calcd for C12H15NO2S:
C, 60.73; H, 6.37; N, 5.90. Found: C, 60.69; H, 6.39;
N, 5.77.
1) n-BuLi
Boc
OH
Boc
N
2) (-)-sparteine
N
3) benzophenone (X eq.)
Ph
Ph
S
3
toluene, -78oC
S
1
X = 0.1: 6%, 79% ee
X = 1.3: 65%, 97% ee
4.2. Typical procedure for the reaction of 1 and 2 with
benzophenone
Scheme 6.
4.2.1. tert-Butyl 2-(1-hydroxy-1,1-diphenylmethyl)thiazo-
lidine-3-carboxylate 3. To a solution of 1 (24mg,
0.127mmol) in toluene (0.6mL) was added n-BuLi
(0.10mL, 1.49molLꢀ1 solution in hexane, 0.152mmol)
dropwise over a period of 5min at ꢀ78ꢁC, and the reac-
tion mixture stirred for 15min. Then a solution of (ꢀ)-
sparteine (36mg, 0.152mmol) in toluene (0.3mL) was
added. After the reaction mixture was stirred for 1h, a
solution of benzophenone (30mg, 0.165mmol) in tolu-
ene (0.3mL) was added and the mixture stirred for an
additional 20min. Saturated aqueous NH4Cl was added
and the mixture extracted with CH2Cl2. The combined
organic extracts were washed with brine, dried over
Na2SO4 and concentrated under reduced pressure to
leave a residue, which was purified by column chroma-
tography (silica gel 10g, hexane/EtOAc = 95:5) to give
Each diastereomer was converted to optically active 1,2-
ethanediols without substantial racemization during the
reaction. The present new chiral formyl anionequiva-
lents provide a convenient method for the preparation
of optically active 1,2-ethanediols.
4. Experimental section
4.1. Synthesis of tert-Butyl thiazolidine-3-carboxylate 1
and tert-butyl benzothiazolidine-3-carboxylate 2
4.1.1. tert-Butyl thiazolidine-3-carboxylate 1.19 A solu-
tion of thiazolidine (1.42g, 15.9mmol) and di-tert-butyl
dicarbonate (3.47g, 15.9mmol) in THF (30mL) and
water (30mL) was stirred for 20h at room temperature.
The reaction mixture was extracted with ethyl acetate.
The organic extracts were dried over Na2SO4 and con-
centrated under reduced pressure. The residue was puri-
fied by column chromatography (silica gel 100g, hexane/
ethyl acetate = 96:4) to give 1 (3.0g, 100%); 1H
NMR (200MHz, CDCl3): d 1.47 (9H, s), 2.97 (2H, t,
J = 6.2Hz), 3.67 (2H, t, J = 6.2Hz), 4.42 (2H, s);
13C NMR (50MHz, CDCl3): d 29.7, 32.2, 48.7, 51.5,
80.3, 153.2; IR (neat): 2975, 2880, 1698, 1476, 1455,
1391, 1260, 1161, 874, 768cmꢀ1; MS (FAB) m/z (%):
190 (M++1, 13), 132 (19), 88 (8), 57 (100). Anal. Calcd
for C8H15NO2S: C, 50.76; H, 7.99; N, 7.40. Found: C,
50.77; H, 8.20; N, 7.17.
1
3 (31mg, 65%). Mp 148–149ꢁC; H NMR (CDCl3): d
1.17 (9H, s), 2.79–2.97 (2H, m), 3.42–3.76 (2H, m),
4.51 (1H, br), 6.29 (1H, s), 7.17–7.54 (10H, m); 13C
NMR (CDCl3): d 27.9, 31.8, 49.6, 70.6, 80.8, 81.4,
126.6, 126.8, 127.3, 128.0, 142.6, 144.8, 153.3; IR
(KBr): 3404, 3054, 2973, 1692, 1493, 1450, 1403, 1272,
1151, 1095, 1063, 982, 887, 740, 697cmꢀ1; MS (FAB)
m/z (%): 372 (M++1, 6), 354 (4), 298 (80), 254 (44),
188 (47), 154 (22), 132 (76), 105 (27), 88 (40), 57 (100).
Anal. Calcd for C21H25NO3S: C, 67.89; H, 6.78; N,
3.77. Found: C, 67.90; H, 6.88; N, 3.65; HPLC (Daicel
Chiralcel OD-H, hexane/i-PrOH = 95:5, 0.5mL/min) tR
10.8 (S) and 12.8 (R) min.
4.1.2. tert-Butyl benzothiazolidine-3-carboxylate 2.20 To
a solution of benzothiazolidine (1.68g, 12.2mmol) and
di-tert-butyl dicarbonate (2.67g, 12.2mmol) in acetonit-
4.2.2. tert-Butyl 2-(1-hydroxy-1,1-diphenylmethyl)benzo-
thiazolidine-3-carboxylate 4. The reaction was carried
out as described above except for using 2 (27mg,

L. Wang et al. / Tetrahedron: Asymmetry 15 (2004) 3059–3072
3065
0.110mmol), n-BuLi (0.10mL, 1.32molLꢀ1 solution in
hexane, 0.132mmol), (ꢀ)-sparteine (32mg, 0.138mmol),
and benzophenone (26mg, 0.144mmol). Usual work-up
gave the crude product, which was purified by column
chromatography (silica gel 10g, hexane/EtOAc = 98:2)
to afford 4 (34mg, 74%). Mp 165–166ꢁC; 1H NMR
(CDCl3): d 1.22 (9H, s), 3.15 (1H, br), 6.76 (1H, s),
6.95–7.52 (14H, m); 13C NMR (CDCl3): d 27.9, 72.2,
82.3, 82.5, 118.7, 121.3, 124.0, 125.1, 126.7, 127.2,
127.5, 128.2, 141.3, 143.6, 151.8; IR (KBr): 3437, 3056,
2977, 1691, 1467, 1367, 1336, 1161, 1060, 859, 755,
732cmꢀ1; MS (FAB) m/z (%): 420 (M++1, 4), 402 (6),
346 (51), 302 (33), 236 (49), 180 (37), 154 (58), 136
(100), 105 (32), 57 (100). Anal. Calcd for C25H25NO3S:
C, 71.57; H, 6.01; N, 3.34. Found: C, 71.38; H, 6.20;
N, 3.33; HPLC (Daicel Chiralpak AD-H, hexane/
i-PrOH = 98:2, 0.5mL/min) tR 32.8 (R) and 42.4 (S) min.
137.1, 137.4, 154.6; IR (neat): 3442, 2977, 2936, 1694,
1514, 1475, 1392, 1265, 1163, 1111, 1061, 895, 853,
765, 737, 703cmꢀ1; MS (FAB) m/z (%): 310 (M++1,
5), 236 (100), 188 (47), 132 (65), 88 (38), 57 (82). Anal.
Calcd for C16H23NO3S: C, 62.11; H, 7.49; N, 4.53.
Found: C, 62.12; H, 7.55; N, 4.46.
4.3.3. (10S,2R)- and (10R,2R)-tert-Butyl 2-[1-hydroxy-1-
(4-methoxyphenyl)methyl]thiazolidine-3-carboxylate syn-
10a and anti-10a. 1H NMR (CDCl3): d 1.48 (9H, s),
2.51–2.80 (2H, m), 3.23–3.38 (2H, m), 3.80 (3H, s),
3.88–4.07 (1H, m), 4.76 (0.6H, d, J = 6.6Hz, anti), 4.82
(0.4H, br, syn), 5.30 (0.4H, br, syn), 5.33 (0.6H, d,
J = 6.6Hz, anti), 6.86 (2H, d, J = 8.6Hz), 7.29 (2H, d,
J = 8.6Hz); 13C NMR (CDCl3): d 28.5, 30.2, 49.5,
53.5, 55.3, 68.2, 81.4, 113.3, 128.3, 132.2, 158.7, 159.1;
IR (neat): 3447, 2976, 2836, 1693, 1513, 1457, 1392,
1249, 1171, 1111, 1034, 894, 828, 768, 737, 703cmꢀ1
;
4.3. General procedure for the reaction of 1 and 2 with
aldehydes.
MS (FAB) m/z (%): 326 (M++1, 4), 252 (100), 208
(57), 188 (62), 132 (87), 88 (51), 57 (100). Anal. Calcd
for C16H23NO4S: C, 59.05; H, 7.12; N, 4.30. Found:
C, 59.21; H, 7.11; N, 4.24.
To a solution of 1 or 2 in toluene was added n-BuLi
(1.2equiv) dropwise over a period of 5min at ꢀ78ꢁC.
The mixture was stirred for an additional 15min at the
same temperature and then a solution of (ꢀ)-sparteine
(1.2equiv) in toluene added. After the reaction mixture
was stirred for 1h, a solution of an aldehyde (1.3equiv)
in toluene was added, and then the reaction mixture stir-
red for an appropriate time. Saturated aqueous NH4Cl
was added and the aqueous layer extracted with
CH2Cl2. The combined organic extracts were washed
with brine, dried over Na2SO4 and concentrated under
reduced pressure to leave a residue, which was purified
by column chromatography to give the corresponding
alcohol.
4.3.4. (10S,2R)- and (10R,2R)-tert-Butyl 2-[1-hydroxy-1-
(4-chlorophenyl)-methyl]thiazolidine-3-carboxylate syn-
11a and anti-11a. 1H NMR (CDCl3): d 1.46 (9H, s),
2.60–2.80 (2H, m), 3.10–3.25 (2H, m), 3.92–4.15 (1H,
m), 4.77 (0.6H, d, 6.6Hz, anti), 4.85 (0.4H, br, syn),
5.27 (0.4H, d, J = 4.0Hz, syn), 5.29 (0.6H, d,
J = 6.6Hz, anti), 7.24–7.36 (4H, m); 13C NMR (CDCl3):
d 28.3, 30.2, 49.6, 53.5, 67.9, 81.4, 127.8, 128.5, 133.5,
138.6, 155.0; IR (neat): 3441, 2977, 1693, 1475, 1454,
1392, 1257, 1163, 909, 850, 733, 700cmꢀ1; MS (FAB)
m/z (%): 330 (M++1, 28), 256 (100), 212 (38), 188
(100), 132 (100), 88 (75), 57 (100). Anal. Calcd for
C15H20 ClNO3S: C, 54.62; H, 6.11; N, 4.25. Found: C,
54.73; H, 6.02; N, 4.18.
Since the diastereomers of alcohol 8a–13a were not sep-
arated, spectral and analytical data of the mixture of the
diastereomers are shown below. These alcohols were
converted into the acetates (vide infra).
4.3.5. (10S,2R)- and (10R,2R)-tert-Butyl 2-[1-hydroxy-1-
(1-naphthyl)methyl]thiazolidine-3-carboxylate
syn-12a
and anti-12a. 1H NMR (CDCl3): d 1.42 (9H, s), 2.62–
2.91 (2H, m), 3.09–3.38 (2H, m), 3.95–4.17 (1H, m),
5.22 (0.8H, d, J = 5.2Hz, anti), 5.28 (0.2H, br, syn),
5.57 (0.2H, d, J = 3.2Hz, syn), 5.70 (0.8H, d,
J = 5.2Hz, anti), 7.34–8.06 (7H, m); 13C NMR (CDCl3):
d 27.9, 30.8, 49.2, 53.4, 68.0, 80.8, 125.0, 125.2, 125.4,
125.7, 128.1, 128.4, 130.1, 133.2, 153.7; IR (KBr):
3426, 3051, 2975, 2931, 1686, 1475, 1392, 1257, 1161,
1099, 892, 858, 774cmꢀ1; MS (FAB) m/z (%): 346
(M++1, 12), 272 (100), 228 (29), 188 (31), 132 (51), 88
(31), 57 (69). Anal. Calcd for C19H23NO3S: C, 66.06;
H, 6.71; N, 4.05. Found: C, 66.05; H, 6.85; N, 3.87.
4.3.1. (10S,2R)- and (10R,2R)-tert-Butyl 2-(1-hydroxy-1-
phenylmethyl)thiazolidine-3-carboxylate syn-8a and anti-
8a. 1H NMR (CDCl3): d 1.45 (9H, s), 2.40–2.75 (2H,
m), 3.15–3.41 (2H, m), 3.87–4.05 (1H, m), 4.83 (0.6H,
d, J = 6.2Hz, anti), 4.89 (0.4H, br, syn), 5.31 (0.4H,
br, syn), 5.36 (0.6H, d, J = 6.2Hz, anti), 7.20–7.35 (5H,
m); 13C NMR (CDCl3): d 28.4, 30.2, 49.6, 53.5,
68.0, 81.3, 127.1, 127.5, 127.8, 140.0, 153.8; IR (neat):
3441, 2977, 1693, 1475, 1454, 1392, 1257, 1163, 909,
850, 733, 700cmꢀ1; MS (FAB) m/z (%): 296 (M++1,
16), 222 (89), 188 (34), 132 (58), 88 (38), 57 (100). Anal.
Calcd for C15H21NO3S: C, 60.99; H, 7.17; N, 4.74.
Found: C, 60.86; H, 7.42; N, 4.62.
4.3.6. (10S,2R)- and (10R,2R)-tert-Butyl 2-[1-hydroxy-1-
(2-naphthyl)methyl]thiazolidine-3-carboxylate
syn-13a
4.3.2. (10S,2R)- and (10R,2R)-tert-Butyl 2-[1-hydroxy-1-
(4-tolyl)methyl]thiazolidine-3-carboxylate syn-9a and
anti-9a. 1H NMR (CDCl3): d 1.46 (9H, s), 2.33 (3H,
s), 2.55–2.77 (2H, m), 3.21–3.46 (2H, m), 4.16–4.30
(1H, m), 4.75 (0.5H, d, J = 6.6Hz, anti), 4.84 (0.5H, d,
J = 4.2Hz, syn), 5.31 (0.5H, br, syn), 5.34 (0.5H, d,
J = 6.6Hz, anti), 7.09–7.27 (4H, m); 13C NMR (CDCl3):
d 21.3, 28.4, 30.2, 49.5, 53.5, 68.0, 81.2, 127.0, 128.5,
and anti-13a. 1H NMR (CDCl3): d 1.44 (9H, s), 2.56–
2.78 (2H, m), 3.23–3.41 (2H, m), 3.93–4.18 (1H, m),
4.92 (0.6H, d, J = 6.6Hz, anti), 4.97 (0.4H, d,
J = 4.6Hz, syn), 5.43 (0.4H, br, syn), 5.45 (0.6H, d,
J = 6.6Hz, anti), 7.44–7.53 (3H, m), 7.79–7.84 (4H, m);
13C NMR (CDCl3): d 28.4, 30.3, 49.7, 53.5, 68.2, 81.5,
124.9, 125.9, 127.4, 127.6, 127.8, 132.8, 133.0, 137.6,
154.9; IR (KBr): 3439, 3055, 2977, 2936, 1693, 1475,

3066
L. Wang et al. / Tetrahedron: Asymmetry 15 (2004) 3059–3072
1392, 1267, 1162, 1109, 890, 858, 819, 741, 703cmꢀ1; MS
(FAB) m/z (%): 346 (M++1, 3), 272 (100), 228 (44), 188
(27), 132 (56), 88 (36), 57 (100). Anal. Calcd for
C19H23NO3S: C, 66.06; H, 6.71; N, 4.05. Found: C,
66.10; H, 6.83; N, 3.89.
4.3.9. (10S,2R)- and (10R,2R)-tert-Butyl 2-(1-hydroxy-1-
cyclohexyl)thiazolidine-3-carboxylate syn-16a and anti-
20
16a. syn-16a: ½aꢁ ¼ þ55:9 (c 0.583, CHCl3, 73% ee);
D
1H NMR (CDCl3): d 1.47 (9H, s), 1.01–1.73 (11H, m),
2.22 (1H, d, J = 8.2Hz), 2.82–3.08 (2H, m), 3.40–3.54
(2H, m), 4.11 (1H, br), 5.30 (1H, br); 13C NMR
(CDCl3): d 26.0, 26.1, 26.3, 28.4, 29.8, 41.6, 49.1, 53.4,
66.0, 77.2, 80.6, 152.9; IR (KBr): 3468, 2976, 2926,
2852, 1695, 1475, 1392, 1258, 1164, 1105, 903,
737cmꢀ1; MS (FAB) m/z (%): 302 (M++1, 34), 246
(58), 228 (60), 202 (42), 188 (52), 132 (82), 88 (39), 57
(100). Anal. Calcd for C15H27NO3S: C, 59.77; H, 9.03;
N, 4.65. Found: C, 59.96; H, 8.83; N, 4.65; HPLC (Dai-
cel Chiralcel OD-H, hexane/i-PrOH = 95:5, 0.5 mL/min)
tR 23.2 (10R,2R) and 28.4 (10S,2S) min (73% ee). anti-
4.3.7. (10S,2R)- and (10R,2R)-tert-Butyl 2-(1-hydroxyprop-
yl)thiazolidine-3-carboxylate syn-14a and anti-14a. syn-
1
14a: H NMR (CDCl3): d 1.00 (3H, t, J = 7.4Hz), 1.47
(9H, s), 1.40–1.60 (2H, m), 2.31 (1H, br), 2.84–3.10
(2H, m), 3.48–3.69 (2H, m), 4.10 (1H, br), 5.10 (1H,
br); 13C NMR (CDCl3): d 10.4, 22.8, 28.5, 30.5, 49.4,
68.0, 75.0, 80.8, 153.6; IR (neat): 3458, 2974, 2936,
2884, 1694, 1457, 1392, 1256, 1167, 1108, 1051, 972,
880, 770, 737cmꢀ1; MS (FAB) m/z (%): 248 (M++1,
44), 230 (2), 192 (89), 188 (49), 174 (80), 132 (56), 88
(36), 57 (100); Anal. Calcd for C11H21NO3S: C, 53.41;
H, 8.56; N, 5.66. Found: C, 53.25; H, 8.68; N, 5.83;
HPLC (Daicel Chiralcel OJ-H, hexane/i-PrOH = 95:5,
0.5mL/min) tR 10.1 (10S,2S) and 13.9 (10R,2R) min
20
D
1
16a: ½aꢁ ¼ þ58:0 (c 0.470, CHCl3, 89% ee); H NMR
(CDCl3): d 1.47 (9H, s), 1.20–1.75 (11H, m), 2.63 (1H,
br), 2.83–3.05 (2H, m), 3.24–3.43 (2H, m), 4.10 (1H,
br), 5.26 (1H, d, J = 8.8Hz); 13C NMR (CDCl3): 25.5,
26.2, 26.6, 28.4, 30.7, 40.1, 49.0, 53.5, 64.4, 79.8, 81.5,
155.1; IR (neat): 3453, 2977, 2926, 2853, 1694, 1392,
1258, 1163, 1104, 910, 734cmꢀ1; MS (FAB) m/z (%):
302 (M++1, 30), 246 (69), 228 (76), 202 (30), 188 (44),
132 (89), 88 (41), 57 (100). Anal. Calcd for C15H27NO3S:
C, 59.77; H, 9.03; N, 4.65. Found: C, 59.96; H, 9.08; N,
4.67; HPLC (Daicel Chiralpak AD-H, hexane/i-
PrOH = 98:2, 0.5mL/min) tR 19.6 (10R,2S) and 24.5
(10S,2R) min (89% ee).
1
(46% ee). anti-14a: H NMR (CDCl3): d 1.02 (3H, t,
J = 7.2Hz), 1.48 (9H, s), 1.40–1.60 (2H, m), 2.24 (1H,
br), 2.90–3.00 (2H, m), 3.35–3.48 (2H, m), 4.16 (1H, d,
J = 6.8Hz), 5.13 (1H, d, J = 6.8Hz); 13C NMR (CDCl3):
d 10.0, 21.2, 28.4, 31.2, 48.2, 64.1, 76.5, 80.7, 154.0; IR
(neat): 3455, 2974, 2935, 2881, 1693, 1392, 1256, 1167,
1109, 1051, 971, 880, 770, 733cmꢀ1; MS (FAB) m/z
(%): 248 (M++1, 51), 230 (3), 192 (100), 188 (50), 174
(80), 132 (59), 88 (34), 57 (96). Anal. Calcd for
C11H21NO3S: C, 53.41; H, 8.56; N, 5.66. Found: C,
53.44; H, 8.68; N 5.51. The enantiomeric purity could
not be determined by the HPLC analysis using various
chiral columns.
4.3.10. (10S,2R)- and (10R,2R)-tert-Butyl 2-(1-hydroxy-
2,2-dimethylpropyl)thiazolidine-3-carboxylate
syn-17a
20
D
and anti-17a. syn-17a: ½aꢁ ¼ þ54:8 (c 0.386, CHCl3,
1
72% ee); H NMR (CDCl3): d 0.94 (9H, s), 1.48 (9H,
s), 2.56 (1H, d, J = 10.4Hz), 2.77–3.00 (2H, m), 3.35–
3.56 (2H, m), 4.26 (1H, br), 5.42 (1H, br); 13C NMR
(CDCl3): d 26.5, 28.5, 30.8, 35.1, 48.5, 53.4, 64.8, 80.5,
152.5; IR (neat): 3474, 2960, 2877, 1697, 1476, 1393,
4.3.8. (10S,2R)- and (10R,2R)-tert-Butyl 2-(1-hydroxy-2-
methylpropyl)thiazolidine-3-carboxylate syn-15a and
20
D
anti-15a. syn-15a: ½aꢁ ¼ þ66:0 (c 1.54, CHCl3, 77%
1
ee); H NMR (CDCl3): d 0.91 (3H, d, J = 6.6Hz), 1.06
(3H, d, J = 8.6Hz), 1.48 (9H, s), 1.79–1.99 (1H, m),
2.16 (1H, d, J = 7.0Hz), 2.83–3.03 (2H, m), 3.40–3.56
(2H, m), 4.15 (1H, br), 5.30 (1H, br); 13C NMR (CDCl3):
d 18.4, 19.6, 28.5, 30.6, 32.3, 49.2, 66.4, 78.2, 80.7, 153.0;
IR (neat): 3473, 2965, 2877, 1694, 1472, 1391, 1256, 1166,
1106, 1064, 995, 907, 884, 766, 736cmꢀ1; MS (FAB) m/z
(%): 262 (M++1, 38), 244 (4), 206 (82), 188 (100), 132
(44), 88 (31), 57 (68). Anal. Calcd for C12H23NO3S: C,
55.14; H, 8.87; N, 5.36. Found: C, 54.94; H, 8.99; N,
5.17; HPLC (Daicel Chiralcel OD-H, hexane/i-
1367, 1263, 1162, 1098, 1016, 982, 893, 765, 734cmꢀ1
;
MS (FAB) m/z (%): 276 (M++1, 25), 258 (3), 220 (40),
202 (11), 188 (47), 132 (59), 88 (31), 57 (100). Anal.
Calcd for C13H25NO3S: C, 56.69; H, 9.15; N, 5.09.
Found: C, 56.84; H, 9.15; N 4.94. HPLC (Daicel Chir-
alpak AD-H, hexane/i-PrOH = 98:2, 0.5mL/min) tR
17.7 (10R,2R) and 21.0 (10S,2S) min (72% ee). anti-17a:
20
D
½aꢁ ¼ þ36:4 (c 0.566, CHCl3, 87% ee); 1H NMR
(CDCl3): d 1.01 (9H, s), 1.48 (9H, s), 2.63 (1H, br),
2.80–3.09 (2H, m), 3.22–3.47 (2H, m), 4.25 (1H, br),
5.37 (1H, d, J = 6.2Hz); 13C NMR (CDCl3): d 26.7,
28.5, 30.3, 34.1, 49.2, 53.5, 60.2, 80.5, 82.3, 154.8; IR
(neat): 3489, 2977, 2871, 1698, 1478, 1392, 1367, 1268,
1162, 1094, 1077, 1012, 902, 786, 734cmꢀ1; MS (FAB)
m/z (%): 276 (M++1, 41), 258 (3), 220 (74), 202 (21),
188 (56), 132 (67), 88 (36), 57 (100). Anal. Calcd for
C13H25NO3S: C, 56.69; H, 9.15; N, 5.09. Found: C,
56.60; H, 9.39; N, 5.08. HPLC (Daicel Chiralpak AD-
H, hexane/i-PrOH = 99:1, 0.5mL/min) tR 23.1 (10R,2S)
and 27.5 (10S,2R) min (87% ee).
PrOH = 95:5, 0.5mL/min) tR 16.4 (10S,2S) and 19.3
20
D
(10R,2R) min (77% ee). anti-15a: ½aꢁ ¼ þ51:3 (c 0.427,
CHCl3, 87% ee); 1H NMR (CDCl3): d 0.91 (3H, d,
J = 6.6Hz), 1.06 (3H, d, J = 8.6Hz), 1.48 (9H, s), 1.79–
1.99 (1H, m), 2.28 (1H, br), 2.82–3.06 (2H, m), 3.32–
3.48 (2H, m), 4.13 (1H, br), 5.18 (1H, d, J = 8.4Hz);
13C NMR (CDCl3):d 14.8, 20.0, 28.4, 30.1, 30.8, 48.9,
64.9, 79.8, 81.5, 155.2; IR (neat): 3462, 2967, 2875,
1702, 1469, 1392, 1270, 1162, 1109, 1053, 1005, 911,
876, 771, 734cmꢀ1; MS (FAB) m/z (%): 262 (M++1,
27), 244 (6), 206 (48), 188 (100), 132 (51), 88 (36), 57
(74). Anal. Calcd for C12H23NO3S: C, 55.14; H, 8.87;
N, 5.36. Found: C, 55.34; H, 8.92; N 5.11. HPLC (Daicel
Chiralpak AD-H, hexane/i-PrOH = 98:2, 0.5mL/min) tR
24.0 (10R,2S) and 28.2 (10S,2R) min (87% ee).
4.3.11. (10S,2R)- and (10R,2R)-tert-Butyl 2-(1-hydroxy-1-
phenylmethyl)benzothiazolidine-3-carboxylate syn-18 and
20
D
anti-18. syn-18: Mp 115–117ꢁC; ½aꢁ ¼ þ75:5 (c 1.84,
CHCl3, 93% ee); 1H NMR (CDCl3): d 1.36 (9H, s),
2.88 (1H, d, J = 5.2Hz), 4.80 (1H, br), 5.83 (1H, br),

L. Wang et al. / Tetrahedron: Asymmetry 15 (2004) 3059–3072
3067
20
D
6.93–7.64 (9H, m); 13C NMR (CDCl3): d 28.4, 72.1,
75.2, 82.3, 117.9, 122.2, 124.0, 125.2, 125.6, 126.2,
127.2, 127.8, 128.1, 138.8, 151.1; IR (KBr): 3407, 2975,
1716, 1468, 1368, 1313, 1252, 1150, 1065, 1013, 748,
700cmꢀ1; MS (FAB) m/z (%): 344 (M++1, 9), 270
(21), 236 (14), 180 (9), 136 (35), 57 (100). Anal. Calcd
for C19H21NO3S: C, 66.45; H, 6.16; N, 4.08. Found:
C, 66.34; H, 6.27; N, 4.07; HPLC (Daicel Chiralpak
AD-H, hexane/i-PrOH = 95:5, 0.5mL/min) tR 27.1
(10S,2R) and 32.4 (10R,2S) min (93% ee). Crystal data
for syn-18: C19H21NO3S, M = 343.44, (0.48 · 0.47 ·
0.30mm), triclinic, P-1 (#2), a = 11.483(6), b =
½aꢁ ¼ þ51:2 (c 0.707, CHCl3, 72% ee); 1H NMR
(CDCl3): 1.39 (9H, s), 2.73 (1H, d, J = 4.2Hz), 3.79
(3H, s), 4.78 (1H, br), 5.80 (1H, br), 6.86–7.64 (8H,
m); 13C NMR (CDCl3): d 28.0, 55.2, 72.0, 74.8, 82.1,
113.4, 117.7, 122.1, 123.9, 125.0, 127.3, 128.1, 131.0,
138.3, 151.1, 158.9; IR (KBr): 3460, 2975, 1679, 1607,
1581, 1511, 1471, 1252, 1146, 1093, 1069, 1017, 832,
752cmꢀ1; MS (FAB) m/z (%): 374 (M++1, 6), 356
(11), 300 (71), 236 (53), 180 (30), 136 (100), 57 (100).
Anal. Calcd for C20H23NO4S: C, 64.32; H, 6.21; N,
3.75. Found: C, 64.36; H, 6.28; N, 3.62; HPLC (Daicel
Chiralpak AD-H, hexane/i-PrOH = 95:5, 1.0mL/min)
tR 24.1 (10S,2R) and 27.4 (10R,2S) min (72% ee). anti-
˚
12.896(6), c = 12.942(4)A, a = 69.80(3), b = 75.50(3),
20
D
3
˚
c = 77.14(3), V = 1721(1)A , l = 1.807mm, Z = 4,
18311 reflections measured. 5920 unique (Rint = 0.071).
20: mp 142.5–143.5ꢁC; ½aꢁ ¼ þ120:1 (c 0.460, CHCl3,
88% ee); 1H NMR (CDCl3): 1.56 (9H, s), 3.08 (1H,
br), 3.78 (3H, s), 4.68 (1H, dd, J = 3.8, 7.8Hz), 5.91
(1H, d, J = 7.8Hz), 6.81–7.52 (8H, m); 13C NMR
(CDCl3): d 28.4, 53.5, 55.3, 70.0, 83.0, 113.4, 118.3,
121.9, 124.0, 124.8, 128.6, 128.8, 131.1, 137.4, 153.0,
159.3; IR (KBr): 3456, 2967, 1699, 1514, 1470, 1368,
1251, 1160, 1036, 832, 746cmꢀ1; MS (FAB) m/z (%):
374 (M++1, 3), 356 (4), 300 (84), 236 (44), 180 (40),
136 (100), 57 (100). Anal. Calcd for C20H23NO4S: C,
64.32; H, 6.21; N, 3.75. Found: C, 64.30; H, 6.39; N,
3.59; HPLC (Daicel Chiralpak AD-H, hexane/i-
PrOH = 95:5, 1.0mL/min) tR 26.9 (10S,2S) and 31.0
(10R,2R) min (88% ee).
Final R indices [I > 3r(I)]: R = 0.066, Rw = 0.068.
CCDC reference number 244746. anti-18: mp 109–
20
D
110ꢁC; ½aꢁ ¼ þ117:2 (c 0.812, CHCl3, 88% ee); 1H
NMR (CDCl3): d 1.55 (9H, s), 3.08 (1H, br), 4.74 (1H,
d, J = 7.8Hz), 5.95 (1H, d, J = 7.8Hz), 6.88–7.51 (9H,
m); 13C NMR (CDCl3): d 28.3, 53.5, 69.9, 83.0, 118.2,
121.9, 124.0, 124.8, 127.4, 127.9, 128.1, 128.7, 137.6,
138.8, 151.2; IR (KBr): 3456, 3031, 2979, 1694, 1581,
1469, 1368, 1254, 1159, 1018, 910, 745, 699cmꢀ1; MS
(FAB) m/z (%): 344 (M++1, 3), 270 (42), 236 (23), 180
(20), 136 (78), 57 (100). Anal. Calcd for C19H21NO3S:
C, 66.45; H, 6.16; N, 4.08. Found: C, 66.54; H, 6.17;
N, 4.08; HPLC (Daicel Chiralcel OD-H, hexane/i-
PrOH = 95:5, 0.5mL/min) tR 16.9 (10S,2S) and 23.2
(10R,2R) min (88% ee).
4.3.14. (10S,2R)- and (10R,2R)-tert-Butyl 2-[1-hydroxy-
1-(4-chlorophenyl)methyl]benzothiazolidine-3-carboxylate
syn-21 and anti-21. syn-21: mp 145–147ꢁC;
20
4.3.12. (10S,2R)- and (10R,2R)-tert-Butyl 2-[1-hydroxy-1-
½aꢁ ¼ þ71:5 (c 1.20, CHCl3, 78% ee); 1H NMR
D
(4-tolyl)methyl]benzothiazolidine-3-carboxylate
and anti-19. syn-19:
syn-19
(CDCl3): d 1.38 (9H, s), 2.96 (1H, d, J = 4.0Hz), 4.75
(1H, br), 5.76 (1H, br), 6.94–7.61 (8H, m); 13C NMR
(CDCl3): d 28.1, 71.8, 74.8, 82.6, 117.9, 122.3, 124.2,
125.3, 127.6, 127.8, 128.2, 133.6, 137.3, 138.2, 151.2;
IR (KBr): 3461, 2974, 1705, 1671, 1469, 1369, 1255,
1154, 1014, 732cmꢀ1; MS (FAB) m/z (%): 378 (M++1,
7), 304 (26), 236 (32), 180 (20), 136 (88), 57 (100). Anal.
Calcd for C19H20ClNO3S: C, 60.39; H, 5.33; N, 3.71.
Found: C, 60.24; H, 5.51; N, 3.58; HPLC (Daicel Chir-
alpak AD-H, hexane/i-PrOH = 95:5, 0.5mL/min) tR
20
D
½aꢁ ¼ þ76:7 (c 0.830, CHCl3,
1
75% ee); H NMR (CDCl3): d 1.38 (9H, s), 2.34 (3H,
s), 2.78 (1H, d, J = 5.6Hz), 4.80 (1H, br), 5.81 (1H,
br), 6.93–7.65 (8H, m); 13C NMR (CDCl3): d 21.3,
28.1, 72.2, 75.1, 82.3, 117.8, 122.2, 124.0, 125.2, 125.6,
126.0, 128.8, 135.8, 137.5, 138.5, 151.1; IR (neat):
3456, 2978, 1714, 1581, 1469, 1367, 1254, 1161, 1016,
909, 819, 744cmꢀ1; MS (FAB) m/z (%): 358 (M++1,
7), 340 (6), 284 (98), 236 (78), 180 (47), 136 (100), 57
(100). Anal. Calcd for C20H23NO3S: C, 67.20; H, 6.49;
N, 3.92. Found: C, 67.10; H, 6.58; N, 3.93; HPLC (Dai-
cel Chiralpak AD-H, hexane/i-PrOH = 95:5, 0.5mL/
25.8 (10S, 2R) and 33.8 (10R,2S) min (78% ee). anti-21:
20
mp 152–153ꢁC; ½aꢁ ¼ þ107:3 (c 0.833, CHCl3, 89%
D
ee); 1H NMR (CDCl3): 1.55 (9H, s), 3.28 (1H, br),
4.73 (1H, dd, J = 4.0, 7.0Hz), 5.90 (1H, d, J = 7.0Hz),
6.89–7.53 (8H, m); 13C NMR (CDCl3): d 28.4, 53.5,
69.8, 83.2, 118.2, 121.9, 124.1, 125.0, 128.0, 128.5,
128.8, 133.9, 137.2, 137.6, 151.2; IR (KBr): 3442, 2976,
2929, 1713, 1580, 1469, 1368, 1254, 1158, 1069, 1015,
830, 742cmꢀ1; MS (FAB) m/z (%): 378 (M++1, 3), 304
(16), 236 (40), 180 (26), 136 (95), 57 (100). Anal. Calcd
for C19H20ClNO3S: C, 60.39; H, 5.33; N, 3.71. Found:
C, 60.21; H, 5.37; N, 3.74; HPLC (Daicel Chiralcel
OD-H, hexane/i-PrOH = 95:5, 0.5mL/min) tR 16.9
(10S,2S) and 27.1 (10R,2R) min (89% ee).
min) tR 29.6 (10S,2R) and 34.4 (10R,2S) min (75% ee).
20
D
anti-19: ½aꢁ ¼ þ110:6 (c 0.550, CHCl3, 93% ee); 1H
NMR (CDCl3): d 1.55 (9H, s), 2.31 (3H, s), 3.13 (1H,
br), 4.67 (1H, dd, J = 4.0, 7.8Hz), 5.92 (1H, d,
J = 7.8Hz), 6.88–7.52 (8H, m); 13C NMR (CDCl3): d
21.3, 28.3, 52.6, 69.9, 82.9, 118.3, 121.9, 124.0, 124.8,
127.3, 128.6, 128.8, 136.0, 137.5, 137.8, 151.2; IR (neat):
3453, 2975, 2929, 1713, 1580, 1469, 1368, 1254, 1160,
1017, 818, 745cmꢀ1; MS (FAB) m/z (%): 358 (M++1,
5), 340 (9), 284 (100), 236 (89), 180 (66), 136 (100), 57
(100). Anal. Calcd for C20H23NO3S: C, 67.20; H, 6.49;
N, 3.92. Found: C, 67.06; H, 6.62; N, 3.96; HPLC (Dai-
cel Chiralpak AD-H, hexane/i-PrOH = 95:5, 0.5mL/
min) tR 31.9 (10S, 2S) and 36.1 (10R,2R) min (93% ee).
4.3.15. (10S,2R)- and (10R,2R)-tert-Butyl 2-[1-hydroxy-1-
(1-naphthyl)methyl]benzothiazolidine-3-carboxylate syn-
20
22 and anti-22. syn-22: Mp 133–134ꢁC; ½aꢁ ¼ þ30:1 (c
D
4.3.13. (10S,2R)- and (10R,2R)-tert-Butyl 2-[1-hydroxy-
1-(4-methoxyphenyl)methyl]benzothiazolidine-3-carboxy-
late syn-20 and anti-20. syn-20: Mp 131–132ꢁC;
0.308, CHCl3, 71% ee); 1H NMR (CDCl3): d 1.20
(9H, s), 2.85 (1H, d, J = 5.2Hz), 5.55 (1H, br), 6.11
(1H, br), 6.94–7.61 (11H, m); 13C NMR (CDCl3): d

3068
L. Wang et al. / Tetrahedron: Asymmetry 15 (2004) 3059–3072
28.0, 71.6, 72.8, 82.4, 118.1, 122.1, 123.2, 124.1, 125.0,
125.2, 125.4, 125.9, 128.5, 128.6, 130.6, 133.4, 134.3,
138.6, 151.1; IR (KBr): 3453, 2977, 2932, 1713, 1580,
urated aqueous NH4Cl was then added and the aqueous
layer was extracted with CH2Cl2, The combined organic
extracts were washed with brine, dried over Na2SO4,
and concentrated under reduced pressure to leave a res-
idue, which was purified by column chromatography to
give acetates 8b–13b.
1469, 1393, 1367, 1253, 1161, 1015, 790, 774, 740cmꢀ1
;
MS (FAB) m/z (%): 394 (M++1, 3), 376 (3), 320 (49),
276 (59), 236 (53), 180 (50), 136 (100), 57 (100). Anal.
Calcd for C23H23NO3S: C, 70.20; H, 5.89; N, 3.56.
Found: C, 70.26; H, 6.06; N, 3.32; HPLC (Daicel Chir-
alpak AD-H, hexane/i-PrOH = 96:4, 0.5 mL/min) tR
4.4.1. (10S,2R)- and (10R,2R)-tert-Butyl 2-(1-acetoxy-1-
phenylmethyl)thiazolidine-3-carboxylate
syn-8b
and
20
D
38.6 (10S,2R) and 44.0 (10R,2S) min (71% ee). anti-22:
anti-8b. syn-8b: Mp 88–89ꢁC; ½aꢁ ¼ þ43:9 (c 0.544,
20
20
mp 50–51ꢁC; ½aꢁ ¼ þ56:4 (c 0.246, CHCl3, 86% ee);
CHCl3, 93% ee); ½aꢁ ¼ þ46:0 (c 0.390, CHCl3, 97%
D
D
1H NMR (CDCl3): d 1.32 (9H, s), 2.98 (1H, br), 5.54
(1H, d, J = 6.2Hz), 6.31 (1H, d, J = 6.2Hz), 6.90–8.16
(11H, m); 13C NMR (CDCl3): d 28.1, 53.1, 69.1, 83.5,
118.1, 121.7, 123.0, 124.0, 124.9, 125.3, 125.4, 125.9,
128.6, 128.8, 130.7, 133.4, 134.1, 138.5, 152.3; IR
(KBr): 3446, 3060, 2975, 1716, 1580, 1512, 1469, 1359,
1153, 1068, 856, 744cmꢀ1; MS (FAB) m/z (%): 394
(M++1, 2), 376 (4), 320 (40), 276 (38), 236 (40), 180
(32), 136 (100), 57 (100). Anal. Calcd for C23H23NO3S:
C, 70.20; H, 5.89; N, 3.56. Found: C, 70.24; H, 6.10;
N, 3.30; HPLC (Daicel Chiralcel OD-H, hexane/i-
PrOH = 96:4, 1.0 mL/min) tR 21.7 (10S,2S) and 27.6
(10R,2R) min (86% ee).
ee, after recrystallization from hexane); 1H NMR
(CDCl3): 1.36 (9H, s), 2.14 (3H, s), 2.83–3.05 (2H, m),
3.52 (2H, t, J = 6.2Hz), 5.34 (1H, d, J = 4.2Hz), 5.96
(1H, d, J = 4.2Hz), 7.40–7.30 (5H, m); 13C NMR
(CDCl3): d 21.4, 28.2, 30.5, 49.2, 66.6, 76.7, 80.9,
126.6, 128.0, 137.0, 152.9, 169.3; IR (KBr): 2973, 1749,
1700, 1455, 1369, 1229, 1162, 1106, 1027, 931, 893,
855, 748, 699cmꢀ1; MS (FAB) m/z (%): 338 (M++1,
3), 222 (100), 188 (41), 132 (47), 88 (27), 57 (60). Anal.
Calcd for C17H23NO4S: C, 60.51; H, 6.87; N, 4.15.
Found: C, 60.44; H, 7.10; N, 4.34; HPLC (Daicel Chir-
alpak AD-H, hexane/i-PrOH = 98:2, 0.5mL/min) 22.7
(10R,2S) and 25.2 (10S,2R) min (93% ee). Crystal data
for syn-8b: C17H23NO4S, M = 337.43, (0.31 · 0.18 ·
4.3.16. (10S,2R)- and (10R,2R)-tert-Butyl 2-[1-hydroxy-1-
(2-naphthyl)methyl]benzothiazolidine-3-carboxylate syn-
0.08mm), orthorhombic, P212121 (#19), a = 8.23(1),
3
˚
˚
b = 9.09(2), c = 22.54(4)A, b = 90, V = 1689(4)A , l =
1.871mm, Z = 4, 31284 reflections measured. 2909
20
D
23 and anti-23. syn-23: ½aꢁ ¼ þ30:4 (c 1.64, CHCl3,
1
73% ee); H NMR (CDCl3): d 1.23 (9H, s), 3.01 (1H,
d, J = 5.6Hz), 4.98 (1H, br), 5.90 (1H, br), 6.93–7.82
(11H, m); 13C NMR (CDCl3): d 27.9, 72.1, 75.3, 82.3,
117.8, 122.2, 123.9, 124.0, 125.2, 125.8, 126.0, 127.4,
127.8, 128.0, 132.8, 132.9, 136.3, 138.5, 151.1; IR (neat):
3423, 3058, 2956, 1714, 1581, 1508, 1468, 1367, 1253,
1161, 1069, 1016, 858, 744cmꢀ1; MS (FAB) m/z (%):
394 (M++1, 3), 376 (3), 320 (72), 276 (83), 236 (50),
180 (46), 136 (100), 57 (100). Anal. Calcd for
C23H23NO3S: C, 70.20; H, 5.89; N, 3.56. Found: C,
70.16; H, 5.96; N, 3.66; HPLC (Daicel Chiralcel OD-
unique (Rint = 0.058). Final R indices [I > 3r(I)]:
R = 0.066, Rw = 0.068. CCDC reference number
20
D
241322. anti-8b: mp 64–65ꢁC; ½aꢁ ¼ þ32:3 (c 0.362,
20
D
CHCl3, 88% ee); ½aꢁ ¼ þ36:6 (c 0.253, CHCl3, 99%
ee, after recrystallization from hexane); 1H NMR
(CDCl3): d 1.50 (9H, s), 2.09 (3H, s), 2.68–2.86 (2H,
m), 3.18 (2H, t, J = 6.2Hz), 5.45 (1H, d, J = 6.6Hz),
5.98 (1H, d, J = 6.6Hz), 7.37–7.30 (5H, m); 13C NMR
(CDCl3): 21.3, 28.5, 30.3, 48.9, 65.4, 75.8, 81.0, 127.8,
128.0, 135.9, 152.8, 169.3; IR (KBr): 2977, 1747, 1696,
1496, 1476, 1455, 1370, 1231, 1162, 1106, 1034, 969,
928, 857, 761, 701cmꢀ1; MS (FAB) m/z (%): 338
(M++1, 3), 222 (98), 188 (49), 132 (63), 88 (40), 57
(100). Anal. Calcd for C17H23NO4S: C, 60.51; H, 6.87;
N, 4.15. Found: C, 60.65; H, 6.84; N, 4.06; HPLC (Dai-
cel Chiralcel OD-H, hexane/i-PrOH = 99:1, 0.5mL/min)
16.2 (10S,2S) and 26.5 (10R,2R) min (88% ee).
H, hexane/i-PrOH = 95:5, 1.0mL/min) tR 17.2 (10S,2R)
20
D
and 23.1 (10R,2S) min (73% ee). anti-23a: ½aꢁ ¼ þ76:4
1
(c 0.513, CHCl3, 86% ee); H NMR (CDCl3): d 1.52
(9H, s), 3.36 (1H, br), 4.87(1H, dd, J = 4.0, 7.6Hz),
6.04 (1H, d, J = 7.6Hz), 6.89–7.80 (11H, m); 13C
NMR (CDCl3): d 28.3, 53.5, 69.9, 83.1, 118.3, 121.9,
124.1, 124.8, 124.9, 125.9, 127.0, 127.4, 127.8, 128.8,
132.7, 133.1, 136.3, 138.4, 153.0; IR (neat): 3423, 3060,
2976, 1712, 1581, 1508, 1469, 1369, 1255, 1160, 1017,
909, 858, 742cmꢀ1; MS (FAB) m/z (%): 394 (M++1,
2), 376 (2), 320 (36), 276 (49), 236 (23), 180 (27), 136
(91), 57 (100). Anal. Calcd for C23H23NO3S: C, 70.20;
H, 5.89; N, 3.56. Found: C, 69.92; H, 5.97; N, 3.64;
HPLC (Daicel Chiralpak AD-H, hexane/i-PrOH = 92:8,
0.5mL/min) tR 30.9 (10S,2S) and 38.1 (10R,2R) min
(86% ee).
4.4.2. (10S,2R)- and (10R,2R)-tert-Butyl 2-[1-acetoxy-1-
(4-tolyl)methyl]thiazolidine-3-carboxylate syn-9b and
20
D
anti-9b. syn-9b: Mp 127–128ꢁC; ½aꢁ ¼ þ45:4 (c
20
D
0.524, CHCl3, 69% ee); ½aꢁ ¼ þ64:6 (c 0.407, CHCl3,
1
98% ee, after recrystallization from hexane); H NMR
(CDCl3): d 1.37 (9H, s), 2.13 (3H, s), 2.32 (3H, s),
2.80–3.05 (2H, m), 3.40–3.52 (2H, m), 5.29 (1H, d,
J = 4.2Hz), 5.94 (1H, d, J = 4.2Hz), 7.10–7.25 (4H,
m); 13C NMR (CDCl3): d 21.9, 22.7, 29.4, 31.9, 49.2,
65.1, 75.3, 80.9, 125.1, 127.3, 133.9, 137.8, 152.9,
169.3; IR (KBr): 2977, 2929, 1747, 1701, 1371, 1231,
4.4. General procedure for the acetylation of alcohols 8a–
13a to acetates 8b–13b
1163, 1107, 1034, 962, 931, 857, 815, 738, 704cmꢀ1
;
MS (FAB) m/z (%): 352 (M++1, 3), 292 (9), 236 (100),
188 (51), 132 (53), 88 (27), 57 (68). Anal. Calcd for
C18H25NO4S: C, 61.51; H, 7.17; N, 3.99. Found: C,
61.61; H, 7.12; N, 3.87; HPLC (Daicel Chiralpak AD-
H, hexane/i-PrOH = 98.5:1.5, 0.8mL/min) tR 18.1
To a solution of alcohols 8a–13a in pyridine was added
a
catalytic amount of 4-dimethylaminopyridine
(0.1equiv) and acetic anhydride (5.0equiv) and then
the mixture was stirred for 3h at room temperature. Sat-

L. Wang et al. / Tetrahedron: Asymmetry 15 (2004) 3059–3072
3069
(10R,2S) and 29.1 (10S,2R) min (69% ee). anti-9b:
(M++1, 6), 312 (8), 256 (100), 212 (38), 188 (53), 132
(58), 88 (31), 57 (89); Anal. Calcd for C17H22ClNO4S:
C, 54.91; H, 5.96; N, 3.77. Found: C, 54.96; H, 6.00;
N, 3.67; HPLC (Daicel Chiralcel OD-H, hexane/i-
PrOH = 99.5:0.5, 0.5mL/min) tR 23.6 (10S,2R) and
26.4 (10R,2S) min (60% ee). anti-11b: mp 84–85ꢁC;
20
D
½aꢁ ¼ þ22:9 (c 1.07, CHCl3, 89% ee); 1H NMR
(CDCl3): d 1.50 (9H, s), 2.08 (3H, s), 2.34 (3H, s),
2.62–2.80 (2H, m), 3.10–3.25 (2H, m), 5.44 (1H, d,
J = 6.8Hz), 5.90 (1H, d, J = 6.8Hz), 7.11–7.30 (4H,
m); 13C NMR (CDCl3): d 21.3, 21.4, 28.5, 30.4, 48.8,
65.4, 75.8, 80.9, 127.7, 128.7, 133.0, 138.2, 153.2,
169.4; IR (neat): 2976, 2929, 1745, 1702, 1516, 1453,
1368, 1232, 1164, 1107, 1036, 968, 864, 813, 767,
723cmꢀ1; MS (FAB) m/z (%): 352 (M++1, 3), 292
(13), 236 (100), 188 (52), 132 (56), 88 (30), 57 (70). Anal.
Calcd for C18H25NO4S: C, 61.51; H, 7.17; N, 3.99.
Found: C, 61.58; H, 7.23; N, 4.20; HPLC (Daicel Chir-
alpak AD-H, hexane/i-PrOH = 98:2, 0.5mL/min) tR
21.4 (10S,2S) and 24.6 (10R,2R) min (89% ee).
20
20
½aꢁ ¼ þ38:7 (c 0.426, CHCl3, 88% ee); ½aꢁ ¼ þ44:1
D
(c 0.520, CHCl3, >99% ee, after recrystallization from
D
1
hexane); H NMR (CDCl3): d 1.50 (9H, s), 2.09 (3H,
s), 2.40–2.80 (2H, m), 3.10–3.25 (2H, m), 5.39 (1H, d,
J = 6.8Hz), 5.94 (1H, d, J = 6.8Hz), 7.28–7.35 (4H,
m); 13C NMR (CDCl3): d 21.2, 28.5, 30.2, 49.0, 65.3,
75.1, 81.1, 128.2, 129.1, 134.3, 134.5, 153.2, 169.2; IR
(KBr): 2978, 2929, 1742, 1698, 1493, 1456, 1369, 1231,
1162, 1092, 1039, 1014, 906, 865, 819, 768, 737cmꢀ1
;
MS (FAB) m/z (%): 372 (M++1, 5), 312 (10), 256
(100), 212 (46), 188 (56), 132 (62), 88 (36), 57 (100).
Anal. Calcd for C17H22ClNO4S: C, 54.91; H, 5.96; N,
3.77. Found: C, 54.91; H, 5.99; N, 3.74; HPLC (Daicel
Chiralpak AD-H, hexane/i-PrOH = 98:2, 0.5mL/min)
tR 19.4 (10S,2S) and 21.9 (10R,2R) min (88% ee).
4.4.3. (10S,2R)- and (10R,2R)-tert-Butyl 2-[1-acetoxy-1-
(4-methoxyphenyl)methyl]thiazolidine-3-carboxylate syn-
20
D
10b and anti-10b. syn-10b: Mp 88–89ꢁC; ½aꢁ ¼ þ42:1 (c
20
D
0.587, CHCl3, 66% ee); ½aꢁ ¼ þ61:1 (c 0.183, CHCl3,
1
95% ee, after recrystallization from hexane); H NMR
(CDCl3): d 1.39 (9H, s), 2.12 (3H, s), 2.80–2.97 (2H,
m), 3.37–3.49 (2H, m), 3.78 (3H, s), 5.30 (1H, d,
J = 4.2Hz), 5.91 (1H, d, J = 4.2Hz), 6.82–6.89 (2H,
m), 7.24–7.29 (2H, m); 13C NMR (CDCl3): d 21.4,
28.3, 49.2, 53.5, 55.3, 66.5, 76.5, 80.9, 113.5, 128.0,
129.0, 153.1, 159.2, 169.3; IR (KBr): 2976, 2929,1747,
1698, 1515, 1458, 1369, 1232, 1174, 1114, 1034, 912,
733cmꢀ1; MS (FAB) m/z (%): 368 (M++1, 3), 308
(24), 252 (100), 208 (100), 188 (100), 132 (100), 88 (69),
57 (100). Anal. Calcd for C18H25NO3S: C, 58.83; H,
6.86; N, 3.81. Found: C, 58.92; H, 7.07; N, 3.70; HPLC
(Daicel Chiralcel OD-H, hexane/i-PrOH = 99.5:0.5,
4.4.5. (10S,2R)- and (10R,2R)-tert-Butyl 2-[1-acetoxy-1-
(1-naphthyl)methyl]thiazolidine-3-carboxylate
syn-12b
20
D
and anti-12b. syn-12b: ½aꢁ ¼ ꢀ16:0 (c 0.418, CHCl3,
1
64% ee); H NMR (CDCl3): d 1.36 (9H, s), 2.19 (3H,
s), 2.87–3.22 (2H, m), 3.47–3.73 (2H, m), 5.59 (1H, d,
J = 4.2Hz), 6.80 (1H, d, J = 4.2Hz), 7.35–8.26 (7H,
m); 13C NMR (CDCl3): d 21.9, 28.8, 30.3, 50.2, 60.2,
76.6, 82.0, 123.4, 125.3, 125.9, 126.4, 128.5, 129.0,
130.6, 133.2, 153.9, 169.6; IR (neat): 3053, 2978, 1747,
1695, 1598, 1512, 1476, 1368, 1228, 1161, 1106, 1068,
932, 898, 863, 775, 736, 704cmꢀ1; MS (FAB) m/z (%):
388 (M++1, 3), 272 (100), 228 (60), 188 (62), 132 (84),
88 (56), 57 (100); Anal. Calcd for C21H25NO4S: C,
65.09; H, 6.50; N, 3.61. Found: C, 64.92; H, 6.71; N.
3.55; HPLC (Daicel Chiralpak AD-H, Hexane/i-
0.5mL/min) tR 48.3 (10S,2R) and 53.4 (10R,2S) min
20
D
(66% ee). anti-10b: mp 71–72ꢁC; ½aꢁ ¼ þ18:8 (c
20
D
0.823, CHCl3, 90% ee); ½aꢁ ¼ þ20:7 (c 0.627, CHCl3,
>99% ee, after recrystallization from hexane); 1H
NMR (CDCl3): d 1.51 (9H, s), 2.08 (3H, s), 2.62–2.78
(2H, m), 3.11–3.24 (2H, m), 3.80 (3H, s), 5.43 (1H, d,
J = 6.8Hz), 5.93 (1H, d, J = 6.8Hz), 6.83–6.89 (2H,
m), 7.29–7.33 (2H, m); 13C NMR (CDCl3): d 21.3,
28.4, 48.7, 53.5, 55.2, 65.4, 75.4, 80.8, 113.4, 128.0,
129.0, 153.2, 159.4, 169.3; IR (KBr): 2977, 2936, 1745,
1697, 1515, 1457, 1369, 1232, 1174, 1034, 909,
733cmꢀ1; MS (FAB) m/z (%): 368 (M++1, 3), 308
(34), 252 (100), 208 (97), 188 (86), 132 (96), 88 (50), 57
(100). Anal. Calcd for C18H25NO5S: C, 58.83; H, 6.86;
N, 3.81. Found: C, 58.75; H, 7.05; N, 3.72; HPLC (Dai-
cel Chiralpak AD-H, hexane/i-PrOH = 95:5, 0.5mL/
min) tR 19.7 (10S,2S) and 22.1 (10R,2R) (90% ee).
PrOH = 98:2, 0.5mL/min) tR 24.2 (10R, 2S) and 30.6
20
D
(10S,2R) min (64% ee). anti-12b: ½aꢁ ¼ ꢀ11:3 (c
1
1.34, CHCl3, 88% ee); H NMR (CDCl3): d 1.39 (9H,
s), 2.11 (3H, s), 2.66–2.85 (2H, m), 3.16–3.37 (2H, m),
5.84 (1H, d, J = 6.2Hz), 6.63 (1H, d, J = 6.2Hz), 7.35–
8.26 (7H, m); 13C NMR (CDCl3): d 21.3, 28.4, 31.0,
48.5, 65.0, 76.1, 80.8, 123.3, 124.8, 125.5, 126.2, 128.6,
129.1, 131.9, 133.5, 153.6, 169.4; IR (neat): 2977, 1693,
1475, 1454, 1392, 1257, 1163, 909, 850, 733, 700cmꢀ1
;
MS (FAB) m/z (%): 388 (M++1, 3), 272 (100), 228
(62), 188 (31), 132 (52), 88 (33), 57 (66). Anal. Calcd
for C21H25NO4S: C, 65.09; H, 6.50; N, 3.61. Found:
C, 64.99; H, 6.66; N, 3.54; HPLC (Daicel Chiralcel
OJ-H, hexane/i-PrOH = 95:5, 0.5mL/min) tR 16.0
(10R,2R) and 20.1 (10S,2S) min (88% ee).
4.4.4. (10S,2R)- and (10R,2R)-tert-Butyl 2-[1-acetoxy-1-(4-
chlorophenyl)methyl]thiazolidine-3-carboxylate syn-11b
20
D
and anti-11b. syn-11b: Mp 122–123ꢁC; ½aꢁ ¼ þ44:9
4.4.6. (10S,2R)- and (10R,2R)-tert-Butyl 2-[1-acetoxy-1-
20
D
(c 0.670, CHCl3, 60% ee); ½aꢁ ¼ þ72:4 (c 0.387, CHCl3,
(2-naphthyl)methyl]thiazolidine-3-carboxylate
syn-13b
20
D
1
97% ee, after recrystallization from hexane); H NMR
(CDCl3): d 1.38 (9H, s), 2.14 (3H, s), 2.80–3.05 (2H,
m), 3.42–3.51 (2H, m), 5.25 (1H, d, J = 4.2Hz), 5.92
(1H, d, J = 4.2Hz), 7.25–7.33 (4H, br); 13C NMR
(CDCl3): d 21.3, 28.3, 30.5, 49.3, 66.4, 76.2, 81.1,
128.1, 128.3, 134.0, 135.5, 149.9, 169.2; IR (KBr):
2974, 2936, 1747, 1692, 1496, 1405, 1232, 1158, 1089,
1037, 932, 871, 785, 762cmꢀ1; MS (FAB) m/z (%): 372
and anti-13b. syn-13b: ½aꢁ ¼ þ42:5 (c 0.273, CHCl3,
1
65% ee); H NMR (CDCl3): d 1.27 (9H, s), 2.18 (3H,
s), 2.80–3.10 (2H, m), 3.45–3.57 (2H, m), 5.43 (1H, d,
J = 3.8Hz), 6.13 (1H, d, J = 3.8Hz), 7.43–7.48 (3H,
m), 7.79–7.83 (4H, m); 13C NMR (CDCl3): d 21.4,
28.2, 30.6, 49.2, 66.7, 77.2, 81.0, 124.2, 126.0, 127.4,
127.8, 128.0, 132.7, 133.0, 134.4, 153.2, 169.3; IR (neat):
3058, 2977, 2936, 1747, 1698, 1475, 1456, 1368, 1228,

3070
L. Wang et al. / Tetrahedron: Asymmetry 15 (2004) 3059–3072
1161, 1107, 1035, 911, 858, 819, 733, 647cmꢀ1; MS
(FAB) m/z (%): 388 (M++1, 4), 272 (100), 228 (78),
188 (57), 132 (82), 88 (52), 57 (100). Anal. Calcd for
C21H25NO4S: C, 65.09; H, 6.50; N, 3.61. Found: C,
65.13; H, 6.73; N, 3.55; HPLC (Daicel Chiralcel OD-
H, hexane/i-PrOH = 99:1, 0.5mL/min) tR 28.2 (10R,2S)
m); 13C NMR (CDCl3): d 21.3, 68.1, 74.5, 125.8,129.0,
137.1, 137.5; IR (KBr): 3450–3250, 2925, 2886, 1401,
1093, 1069, 1037, 897, 821cmꢀ1
.
23
(R)-1-(4-Tolyl)-1,2-ethanediol (R)-25: ½aꢁ ¼ ꢀ60:8 (c
D
0.83, CHCl3, 88% ee).
and 34.3 (10S,2R) min (65% ee). anti-13b: mp 114–
20
D
115ꢁC; ½aꢁ ¼ þ13:5 (c 2.40, CHCl3, 90% ee);
4.5.3.
(S)-1-(p-Methoxyphenyl)-1,2-ethanediol
22
D
(S)-
20
D
½aꢁ ¼ þ15:0 (c 0.830, CHCl3, >99% ee, after recrystal-
26. ½aꢁ ¼ þ51:6 (c 0.49, CHCl3, 66% ee) lit.14
22
D
lization from hexane); 1H NMR (CDCl3): d 1.51 (9H, s),
2.12 (3H, s), 2.50–2.85 (2H, m), 3.10–3.30 (2H, m), 5.58
(1H, d, J = 6.4Hz), 6.11 (1H, d, J = 6.4Hz), 7.45–7.49
(3H, m), 7.79–7.86 (4H, m); 13C NMR (CDCl3): d
21.4, 28.5, 30.3, 48.9, 65.5, 76.1, 81.0, 125.2, 126.0,
127.5, 127.7, 128.0, 132.6, 133.1, 133.4, 153.1, 169.4;
IR (KBr): 3060, 2977, 2936, 1740, 1680, 1475, 1368,
½aꢁ ¼ þ74:1 (c 0.52, CHCl3 95% ee); mp 73–74ꢁC; H
1
NMR (CDCl3): d 2.14 (1H, br), 2.39 (1H, br), 3.60–
3.77 (2H, m), 3.80 (3H, s), 4.77 (1H, dd, J = 4.2,
7.8Hz), 6.86–6.91 (2H, m), 7.25–7.30 (2H, m); 13C
NMR (CDCl3): d 55.4, 68.1, 74.3, 113.8, 127.2, 132.1,
159.2; IR (KBr): 3400–3300, 2959, 2934, 1699, 1515,
1246, 1081, 1026, 834cmꢀ1
.
1238, 1167, 1098, 1047, 940, 865, 810, 749, 716cmꢀ1
;
22
D
MS (FAB) m/z (%): 388 (M++1, 3), 272 (100), 228
(37), 188 (36), 132 (43), 88 (24), 57 (66). Anal. Calcd
for C21H25NO4S: C, 65.09; H, 6.50; N, 3.61. Found:
C, 65.14; H, 6.48; N, 3.58; HPLC (Daicel Chiralpak
AD-H, hexane/i-PrOH = 98:2, 0.6mL/min) tR 23.9
(10S, 2S) and 30.2 (10R,2R) min (90% ee).
(R)-1-(p-Methoxyphenyl)-1,2-ethanediol (R)-26: ½aꢁ
ꢀ70:5 (c 0.53, CHCl3, 90% ee).
¼
4.5.4.
(S)-1-(4-Chlorophenyl)-1,2-ethanediol
(S)-27.
23
D
1
½aꢁ ¼ þ37:0 (c 0.82, CHCl3, 60% ee); mp 79–
81ꢁC; H NMR (CDCl3): d 2.56 (1H, br), 3.04 (1H,
br), 3.53–3.75 (2H, m), 4.77 (1H, dd, J = 3.6, 8.2Hz),
7.23–7.33 (4H, m); 13C NMR (CDCl3): d 67.9, 74.0,
127.2, 128.5, 133.5, 138.6; IR (KBr): 3400–3300, 2932,
4.5. Typical procedure for the preparation of optically
active 1,2-ethanediols 24–29 from 8b–16b
2895, 1493, 1088, 1037, 900, 831cmꢀ1
.
To a solution of syn-8b (121mg, 0.36mmol) in acetonit-
rile (2.4mL) and water (0.6mL) was added HgCl2
(293mg, 1.08mmol), and then the mixture stirred for
6h at room temperature. The reaction mixture was di-
luted with water and filtered, and the filtrate then ex-
tracted with CH2Cl2. The organic extracts were dried
over Na2SO4, filtered and concentrated under reduced
pressure to give an oil including 2-acetoxy-2-phenylacet-
aldehyde, which was dissolved in THF (0.5mL) and
added to a solution of LiAlH4 (68mg, 1.80mmol) in
THF (2mL) at 0ꢁC. The reaction mixture was stirred
for 3h at room temperature. 1mol/L HCl solution was
added slowly and the mixture extracted with diethyl
ether, dried over Na2SO4 and concentrated under re-
duced pressure to leave a residue that was purified by
column chromatography (hexane/EtOAc = 70:30) to
give (S)-24 (32mg, 66%).
23
D
(R)-1-(4-Chlorophenyl)-1,2-ethanediol (R)-27: ½aꢁ
¼
23
D
ꢀ53:7 (c 0.23, CHCl3, 88% ee) lit.21 ½aꢁ ¼ ꢀ60:0
(c 1.0, CHCl3, 98% ee).
24
D
4.5.5. (S)-1-(1-Naphthyl)-1,2-ethanediol (S)-28. ½aꢁ
¼
þ56:5 (c 0.38, CHCl3, 63% ee); mp 38–39ꢁC; 1H
NMR (CDCl3): d 1.85 (1H, br), 2.40 (1H, br), 3.70–
3.81 (2H, m), 5.62 (1H, dd, J = 2.8, 8.0Hz), 7.43–7.50
(3H, m), 7.80–7.85 (4H, m); 13C NMR (CDCl3): d
67.5, 71.6, 122.4, 123.3, 125.2, 125.5, 126.1, 128.2,
128.7, 130.6, 133.4, 136.0; IR (KBr): 3350–3150, 2929,
2876, 1459, 1374, 1334, 1107, 1079, 1033, 799,
779cmꢀ1
.
24
(R)-1-(1-Naphthyl)-1,2-ethanediol (R)-28: ½aꢁ ¼ ꢀ78:9
D
23
D
(c 0.38, CHCl3, 87% ee) lit.22 ½aꢁ ¼ ꢀ90:2 (c
1.0, CHCl3).
22
4.5.1. (S)-1-Phenyl-1,2-ethanediol (S)-24. ½aꢁ ¼ þ36:2
D
22
D
23
(c 0.30, EtOH, 92% ee) lit.14 ½aꢁ ¼ þ38:9 (c 3.60, Et-
4.5.6. (S)-1-(2-Naphthyl)-1,2-ethanediol (S)-29. ½aꢁ ¼
D
1
OH); mp 59–60ꢁC; H NMR (CDCl3): d 2.09 (1H, br),
2.55 (1H, br), 3.61–3.79 (2H, m), 4.82 (1H, dd, J = 3.6,
8.0Hz), 7.29–7.38 (5H, m); 13C NMR (CDCl3): d 68.0,
74.7, 125.8, 127.7, 128.3, 140.2; IR (KBr): 3300–
3200, 3031, 2933, 2871, 1448, 1100, 1072, 1052, 750,
698cmꢀ1. HPLC (Daicel Chiralpak OB-H, hexane/i-
PrOH = 90:10, 0.5mL/min) tR 15.2 (R) and 17.8 (S) min.
þ20:5 (c 0.70, EtOH, 64% ee); mp 104–106ꢁC; 1H
NMR (CDCl3): d 2.04 (1H, br), 2.58 (1H, br), 3.70–
3.90 (2H, m), 4.99 (1H, dd, J = 3.8, 8.0Hz), 7.43–7.50
(3H, m), 7.80–7.85 (4H, m); 13C NMR (CDCl3): d
68.1, 74.8, 123.7, 124.8, 125.9, 126.1, 127.5, 127.7,
128.1, 132.9, 133.0, 137.6; IR (KBr): 3400–3200, 2925,
2862, 1465, 1362, 1086, 824, 742cmꢀ1
.
22
(R)-1-Phenyl-1,2-ethanediol (R)-24: ½aꢁ ¼ ꢀ34:2 (c
23
(R)-1-(2-Naphthyl)-1,2-ethanediol (R)-29: ½aꢁ ¼ ꢀ28:6
D
D
23
D
0.43, EtOH, 88% ee).
(c 0.79, EtOH, 88% ee) lit.22 ½aꢁ ¼ ꢀ31:2 (c 1.0, EtOH).
20
22
D
4.5.2. (S)-1-(4-Tolyl)-1,2-ethanediol (S)-25. ½aꢁ
¼
4.5.7. (S)-3-Methyl-1,2-butanediol (S)-30. ½aꢁ ¼ þ7:9
D
22
D
20
þ46:2 (c 0.80, CHCl3, 67% ee) lit.14 ½aꢁ ¼ þ69:2
(c 0.26, CHCl3, 77% ee) lit.23 ½aꢁ ¼ þ10:3 (c
D
1
(c 1.10, CHCl3); mp: 64–66ꢁC; H NMR (CDCl3): d
2.04 (1H, br), 2.35 (3H, s), 2.46 (1H, br), 3.61–3.74
(2H, m), 4.80 (1H, dd, J = 3.6, 8.0Hz), 7.17–7.28 (4H,
1.15, CHCl3); 1H NMR (CDCl3): d 0.93 (3H, d,
J = 11.6), 0.97 (3H, d, J = 11.6), 1.63–1.79 (1H, m),
2.13 (2H, br), 3.38–3.56 (2H, m), 3.70 (1H, dd, J = 2.2,

L. Wang et al. / Tetrahedron: Asymmetry 15 (2004) 3059–3072
3071
10.2); 13C NMR (CDCl3): d 18.4, 18.9, 31.1, 65.0, 77.2;
IR (neat): 3500–3100, 2960, 2925, 2883, 1467, 1065,
14.0, 27.6, 28.6, 29.2, 33.1, 48.3, 49.4, 79.7, 153.7; IR
(neat): 2955, 1680, 1477, 1456, 1402, 1366, 1250, 1149,
1045, 874, 767, 673cmꢀ1; MS (EI) m/z (%): 422
1012, 876cmꢀ1
.
t
(M+ꢀ Bu). Anal. Calcd for C20H41NO2SSn: C, 50.22;
20
(R)-3-Methyl-1,2-butanediol (R)-30: ½aꢁ ¼ ꢀ8:8 (c
H, 8.64; N, 2.93. Found: C, 50.45; H, 8.64; N, 2.97.
D
0.31, CHCl3, 85% ee).
23
(S)-1-Cyclohexyl-1,2-ethanediol (S)-31: ½aꢁ ¼ þ3:7 (c
Acknowledgements
D
0.76, CHCl3, 70% ee).
This work was supported by a Grant-in-Aid for Scien-
tific Research (No. 11650890) from the Ministry of Edu-
cation, Science, Sports and Culture of Japan and an
NIT research promotion program. We thank Dr. Shinya
Kusuda, Ono Pharmaceutical Co., Ltd, for the X-ray
crystallographic analysis and the mass spectroscopy
measurement.
23
(R)-1-Cyclohexyl-1,2-ethanediol (R)-31: ½aꢁ ¼ ꢀ4:7 (c
D
23
D
0.73, CHCl3, 89% ee) lit.22 ½aꢁ ¼ ꢀ4:8 (c 0.92, CHCl3),
1
91% ee for R; H NMR (CDCl3): d 0.88–1.89 (11H, m),
2.68 (2H, br), 3.38–3.56 (2H, m), 3.69 (1H, dd, J = 2.2,
10.4Hz); 13C NMR (CDCl3): d 26.2, 26.5, 28.8, 29.1,
31.7, 40.8, 64.8, 76.5; IR (neat): 3500–3100, 2923,
2855, 1449, 1069, 892, 756cmꢀ1
.
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