A stereochemical study of optically active thiazolidines

Article abstract of DOI:10.1016/S0957-4166(01)00117-3

We report a stereochemical study of a series of free N-H and N-methylated 1,3-thiazolidines bearing H or CH₃ at C-(2). These compounds were readily prepared from ephedrine and pseudoephedrines. The stereochemistry of the compounds under study was deduced using ¹H and ¹³C NMR spectroscopy. Two isomers were found for compounds having a methyl group at C-(2) (i.e. C-(2)HCH₃); interconversion of these isomers, presumably via a non-cyclic zwitterionic intermediate, was observed.

Full text of DOI:10.1016/S0957-4166(01)00117-3

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 12 (2001) 711–717
A stereochemical study of optically active thiazolidines
Alejandro Cruz,a,* Aurora Va´squez-Badillo,b Iris Ramos-Garc´ıab and Rosalinda Contrerasb,*
aDepartamento de Qu´ımica, Unidad Profesional Interdisciplinaria de Biotecnolog´ıa del IPN,
Av. Acueducto de Guadalupe s/n Col. Barrio la Laguna Ticoman, Mexico
bDepartamento de Qu´ımica, Centro de Investigacio´n y de Estudios Avanzados del IPN, A.P. 14-740, CP 07000, Mexico
Received 1 December 2000; accepted 19 February 2001
Abstract—We report a stereochemical study of a series of free N-H and N-methylated 1,3-thiazolidines bearing H or CH3 at C-(2).
These compounds were readily prepared from ephedrine and pseudoephedrines. The stereochemistry of the compounds under
study was deduced using 1H and 13C NMR spectroscopy. Two isomers were found for compounds having a methyl group at C-(2)
(i.e. C-(2)HCH3); interconversion of these isomers, presumably via a non-cyclic zwitterionic intermediate, was observed. © 2001
Elsevier Science Ltd. All rights reserved.
1. Introduction
the C-(4) methyl groups in anti-positions to each
other. This, in turn, influences the configuration at
C-(2).
Optically
active
heterocycles
derived
from
aminoalcohols1 and aminothiols2 are used as chiral
inductors in asymmetric syntheses and, therefore, the
study of their stereochemistry is of relevance. We are
interested in the stereochemistry of ephedrine-derived
heterocycles,3 such as 1,3-oxazolidines and especially
in the structures of their N-borane adducts, which we
have been studying mainly by NMR spectroscopy.
1,3-Oxazolidines, bearing a substituent in the C-(2)
position3a–c (C-(2)HR), exist as two isomers which dif-
fer in their C-(2) configuration and are in equilibrium
with each other, as detailed in Scheme 1. Isomerisa-
tion may take place via a non-cyclic, short-lived,
zwitterionic species. In the case of 2,3-dimethyl-1,3-
oxazolidines (X=O), derived from ephedrine or pseu-
doephedrine, we have found that the C-(4)-methyl
group determines the preferred configuration at the
neighbouring nitrogen atom, with the N-methyl and
In the preferred isomer (A in Scheme 1), the N-
methyl group is oriented anti to the two C-methyl
groups. Isomers B can have two conformers by inver-
sion of the N atom. In 1,3-oxazolidines, isomers B
are present only in very minor amounts and their
structures cannot be easily studied. Furthermore, the
corresponding N-H 1,3-oxazolidines are insufficiently
stable in order to be used in conformational studies.
To further advance this work, we decided to analyse
the behaviour of 1,3-thiazolidines in comparison with
1,3-oxazolidines and to revisit the stereochemistry of
these heterocycles in general. The main aim was to
compare N-methyl and N-H compounds (N.B. free
N-H oxazolidines are unstable), and to investigate
isomers of the type B (X=S).
Scheme 1. Proposed isomerisation pathway for C-(2) isomers in heteroazolidines; X=O or S atoms.
* Corresponding authors. E-mail: rcontrer@mail.cinvestav.mx
0957-4166/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(01)00117-3

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A. Cruz et al. / Tetrahedron: Asymmetry 12 (2001) 711–717
2. Results and discussion
as was observed by NMR analyses. However, the same
reaction for the chlorodeoxy-norpseudoephedrine
hydrochloride 2a in refluxing water afforded mainly
erythro-isomers 3a and 4a in a 15:85 ratio, whereas the
chlorodeoxy-pseudoephedrine hydrochloride 2b gave
isomers 3b and 4b in a 64:36 ratio (Scheme 3). Previ-
ously we reported that, in the course of the substitution
reaction of chlorodeoxy-pseudoephedrines, retention of
the C-(1) configuration results from double inversion
via an aziridine intermediate.3h Presumably 4 arises
from the reaction in water as the result of a competing
SN2 reaction where, because an aziridine intermediate is
probably less solvated, the double inversion pathway is
less favoured.
Herein, we describe the synthesis and stereochemistry
of a series of 1,3-thiazolidines derived from ephedrines
bearing different C-(2) substituents. In addition, we
have found a stereoselective preparation of the threo-3
and erythro-4 isomers of the thiosulfonic deoxy-
ephedrine derivatives. A synthetic route to 1,3-thiazo-
lidines, starting from the respective aminothiols and
formaldehyde, can be found in the literature4 (Scheme
2). However, aminothiols oxidise readily to give the
corresponding disulfides; thus, the reactions must be
carried out under an inert atmosphere. Even under
these conditions the yields of the disulfide products are
poor.
Acidic hydrolysis of the sulfonic acid group of com-
pounds 3 and 4 in 30% aqueous HCl3 afforded the
corresponding aminothiol hydrochlorides (Table 1). In
order to avoid their oxidation after neutralisation with
30% aqueous NaOH, the carbonyl compound (dis-
solved in CHCl3) was added before the base and, under
these conditions, cyclisation occurred without the for-
mation of unwanted disulfides (Scheme 4).
We report here a simple method for the synthesis of
1,3-thiazolidines by the in situ reaction of thioephed-
rines with carbonyl compounds. The thiosulfonic
amines 3a and 3b are available by treatment of the
corresponding threo-isomers of the chlorodeoxy-
ephedrine hydrochlorides 2a and 2b with anhydrous
sodium thiosulfate in refluxing ethanol. In both reac-
tions the configuration at C-(1) is retained completely,
Scheme 2. Syntheses of thiazolidines.4
Scheme 3. Stereochemistry in the synthesis of amino thiosulfonic compounds.
Table 1. 1H and 13C NMR data of compounds 3 and 4, l ppm (J Hz)
H1 (d)
H2
CH3 (d)
N-CH3
H-N
C6H5
C1
C2
C3
C4
3a
4a
3b
4b
4.38 (8.6)
4.66 (3.3)
4.45 (8.8)
4.84 (3.2)
3.84
3.77
3.84, m
3.64, m
1.06 (6.5)
1.12 (6.6)
1.08, d (6.6)
1.07, d (6.4)
7.99
7.88
8.63
8.41
7.2–7.4
7.2–7.5
7.2–7.4
7.2–7.4
56.1
55.7
59.3
59.5
52.3
51.5
54.9
54.3
17.0
15.3
14.1
12.8
2.64
2.68
31.3
32.0

A. Cruz et al. / Tetrahedron: Asymmetry 12 (2001) 711–717
713
Scheme 4. Preparation of thiazolidines 7–17.
The condensation of acetaldehyde with the respective
aminothiols leads to two C-(2) isomers a and b in each
case (compounds 8, 9, 14, and 15). Attempts to separate
these isomeric mixtures by chromatography, recrystalli-
sation and differential solubility failed and, since the
ratio of both isomers remained constant in all experi-
ments, the existence of an equilibrium is proposed,
similar to that suggested previously for the analogous
1,3-oxazolidines3a–c (Scheme 1). Fortunately, in the case
of the 1,3-thiazolidines, the second isomer b was present
in an appreciable amount, thus allowing its solution-
state structure to be elucidated (Schemes 5 and 6). In
addition, the preparation of N-H compounds (N-H
compounds 6, 7, 12, and 13 have been previously
reported by Kone and Gelbcke4) enabled direct com-
parison with the N-CH3 analogues prepared in this
study.
Structural assignments were based on the comparison
with 1,3-oxazolidines using the steric effects exerted by
1
Scheme 5. Isomeric and conformational equilibrium for 2-methylthiazolidines 8a and 8b, with selected H and [13C] NMR data;
analogous oxazolidine 183a–c is shown for comparison.
1
Scheme 6. Isomers 9a and 9b, and selected H and [13C] NMR data; analogous oxazolidine 193a–c is shown for comparison.

714
A. Cruz et al. / Tetrahedron: Asymmetry 12 (2001) 711–717
Table 2. 1H NMR data of compounds 6–17, l (ppm) [J, Hz]
H4
H5
R6
R7
CH3
N-R
C6H5
6
7
3.17
2.85
2.80
3.58
2.70
3.33
3.32
3.00
3.37
3.10
3.46
3.71
3.20
3.40
3.84
3.45
4.72 [6.2]
4.10 [9.9]
4.24 [6.2]
4.99 [5.7]
4.10 [9.4]
4.16 [9.4]
4.19 [5.7]
4.05 [9.5]
4.49 [5.8]
3.92 [8.4]
4.53 [5.8]
4.59 [5.5]
4.08 [8.9]
4.10 [6.8]
4.60 [5.9]
4.12 [9.2]
3.79 [8.3]
4.15 [8.7]
3.68
1.52 [6.2]
4.30
1.64 [6.7]
1.42
1.54
4.26 [9.1]
4.37 [9.5]
4.73
1.54 [6.6]
4.99
4.45 [8.3]
4.40 [8.7]
1.55 [5.8]
4.86
1.50 [5.9]
4.48
0.74 [6.7]
1.24 [6.4]
0.75 [6.6]
0.75 [6.6]
1.09 [6.9]
1.08 [7.9]
0.73 [6.6]
1.01 [5.2]
0.86 [6.4]
1.23 [6.3]
0.79 [6.6]
0.81 [7.3]
1.22 [6.4]
1.20 [7.1]
0.82 [6.7]
1.19 [6.2]
2.47
2.40
2.24
2.40
2.28
2.39
2.21
2.20
2.10
2.25
1.88
1.88
1.95
1.95
2.12
2.11
7.15–7.50
7.10–7.50
7.15–7.50
7.15–7.50
7.00–7.50
7.00–7.50
7.00–7.50
7.10–7.40
7.20–7.50
7.20–7.50
7.15–7.35
7.15–7.40
7.15–7.40
7.15–7.40
7.15–7.35
7.14–7.44
8a
8b
9a
9b
10
11
12
13
14a
14b
15a
15b
16
17
1.69
1.54
4.53 [9.1]
4.50 [8.5]
1.72 [6.2]
4.99
1.60 [6.2]
4.83 [6.4]
1.86
1.68
1.66
1.78
1.70
methyl groups shielding the vicinal 13C nuclei and the
deshielding effect of the N-lone pair on vicinal 1H
nuclei.3a–c
groups are on opposite sides of the ring and one of the
methyl groups is more strongly affected by the N-lone
pair than the other (l 4.45 and 3.79 ppm; Scheme 7).
Comparison of 6 with the analogous N-H compound
12 shows that the nitrogen atom in 12 undergoes fast
inversion, and that all three vicinal C–1H nuclei are
deshielded. On the other hand, the mutual steric shield-
ing effects of the C-(2) and N-methyl groups are appar-
ent in comparison of the 13C NMR data of compounds
6 and 10, and 10 and 16.
1
Analysis of H and 13C NMR data for isomers 8a and
8b indicated that 8a is the favoured isomer, its three
methyl groups being in mutual anti-positions (Tables 2
and 3). This assumption is based on analogy with the
corresponding 1,3-oxazolidine and the deshielding
effect of the nitrogen lone pair (Scheme 5). Isomer 8b
exerts a deshielding effect on both the C-(2) and C-(4)
protons, which can be attributed to a similar popula-
tion of both N-methyl conformers. Steric effects exerted
by the N-methyl group are reflected in the positions of
the 13C NMR signals of both the C-(2) and C-(4)
methyl groups of 8b. The same analysis can be applied
to isomers 9a and 9b derived from pseudoephedrine.
The N-H heterocycles 14 and 15 bearing a C-(2) methyl
group (Scheme 8) have an isomeric ratio comparable to
that of the N-methyl analogues. The signals for the
C-(2) and C-(4) protons of 14a and 15a are shifted to
higher frequencies with respect to those of 8a and 9a,
respectively, indicating that N-lone pair inversion is
rapid, and that both N-H conformers are present in
similar concentrations.
1
The effect of the lone pair on the H nuclear shielding
of vicinal hydrogen atoms can be observed in com-
pound 6. In its favoured conformer, the two methyl
These optically active thiazolidines 7–17 are suitable
bases for the synthesis of stable N-BH3 adducts, of
which the synthesis and stereochemistry will be
reported in due course.
Table 3. 13C NMR data of compounds 6–17, l (ppm)
C2
C4
C5
R6
R7
C-CH3
N-CH3
3. Conclusions
6
7
59.8
62.3
67.4
66.7
68.8
68.5
72.0
74.2
54.6
54.8
69.1
72.6
68.5
70.2
73.3
72.5
63.8
69.1
65.2
69.6
64.8
62.3
69.9
66.8
62.6
67.5
54.7
57.4
53.5
55.5
57.3
58.5
53.4
57.7
57.6
62.8
59.7
60.1
65.8
64.7
61.4
66.5
15.8
14.9
17.0
14.3
16.0
14.2
17.6
16.6
16.6
17.0
16.7
16.0
17.0
17.8
16.8
17.1
41.7
36.9
37.5
36.4
34.7
36.9
32.4
32.3
Substitution of oxygen in 1,3-oxazolidines by sulfur, to
give 1,3-thiazolidines derived from ephedrines, allowed
the effect of sulfur on the stereochemistry of the five-
membered ring to be assessed. Structural analogies in
heterocycles can be established, such as in 1,3-oxazo-
lidines 18 and 19 versus 1,3-thiazolidines 8a and 9a
according to the pronounced similarity of their NMR
spectral data.
8a
8b
9a
9b
10
11
12
13
20.7
19.7
18.4
25.5
24.2
27.7
29.8
29.6
14a 65.4
14b 64.4
15a 65.8
15b 64.7
16
17
21.3
21.4
25.4
In contrast to 1,3-oxazolidines, 1,3-thiazolidines (with
C-(2)-HR) exist as two stable isomers in a ratio that
enabled the stereochemistry to be deduced from NMR
data. Also, the series of N-H derivatives for the 1,3-thi-
azolidines, not available for the oxygen counterparts,
25.4
32.3
33.8
75.0
74.9
31.1
31.8

A. Cruz et al. / Tetrahedron: Asymmetry 12 (2001) 711–717
715
1
Scheme 7. Selected H and [13C] NMR data for compounds 6, 10, 12, and 16.
1
Scheme 8. Isomers of N-H thiazolidines (14a,b and 15a,b), and selected H and [13C] NMR data.
made it possible to determine the effect of the N-sub-
stituent on the stereochemistry and conformational
behaviour. The similar isomeric ratio of C-(2)-CH3
compounds bearing N-H or N-methyl groups demon-
strates that it is not the N-substituent that determines
the formation of these isomers but the presence of
oxygen or sulfur in the ring. It was also found that
the more stable isomers for C-(2)-CH3 compounds
have a cis-arrangement of the C-(4)-CH3 and C-
(2)-CH3 groups and an anti-arrangement of the N-
CH3 group.
apparatus and are uncorrected. 1H and 13C NMR
spectra of 1,3-thiazolidines and thiosulfonic acids
were recorded in CDCl3 and DMSO-d6, respectively,
on Jeol GSX-270 and Jeol Eclipse 400 spectrometers.
The EI mass spectra (20 eV) were obtained with an
HP 5958 spectrometer. Compounds 2a and 2b were
prepared as reported.5
4.1. (1R,2R)-Thiosulfonic deoxy-norpseudoephedrine
acid 3a
To
a solution of chlorodeoxy-norpseudoephedrine
hydrochloride 2a (14.6 g, 79.9 mmol) in dry ethanol
(100 mL) was added sodium thiosulfate (15.15 g, 95.9
mmol) and the mixture was heated under reflux for 3
h. The reaction mixture was cooled to 0°C, and the
precipitated sulfonic acid derivative was collected by
filtration, washed with cold water and dried com-
pletely. A white solid was obtained (7.10 g, 63.6%);
4. Experimental
All reagents were of commercial quality and used
without further purification. Solvents were freshly dis-
tilled before use following established procedures.
Melting points were measured using a Gallenkamp

716
A. Cruz et al. / Tetrahedron: Asymmetry 12 (2001) 711–717
mp 220–223°C; [h]D=−197.92 (c=19.3 mg/10 mL,
DMSO); 13C NMR (DMSO-d6) data for the phenyl
group, l (ppm): Ci 139.0, Co 128.6, Cm 129.3, Cp
128.3.
(CDCl3) data for the phenyl group, l (ppm): Ci
139.41, Co 129.1, Cm 128.1, Cp 127.0.
4.7. (4R,5R)-2,2-Dihydro-3,4-dimethyl-5-phenyl-1,3-
thiazolidine 7
4.2. (1R,2R)-Thiosulfonic deoxy-pseudoephedrine acid
Yellow liquid, 65% yield; [h]D=−7.4 (c=17.5 mg/10
mL, CHCl3); MS m/z (%): 193 (18) [M+]; 13C NMR
(CDCl3) data for the phenyl group, l (ppm): Ci 140.7,
Co 128.4, Cm 128.5, Cp 127.4.
3b
Compound 3b was prepared from 2b analogously to 3a.
White solid; 90% yield; mp 160°C (dec.); [h]D=
−146.3 (c=15.0 mg/10 mL, H2O); 13C NMR (DMSO-
d6) data for the phenyl group, l (ppm): Ci 138.6, Co
129.0, Cm 128.3, Cp 128.3.
4.8. (2R,4R,5S)-2-Hydro-2,3,4-trimethyl-5-phenyl-1,3-
thiazolidine 8a and (2S,4R,5S)-2-hydro-2,3,4-trimethyl-
5-phenyl-1,3-thiazolidine 8b
Yellow liquid, 80% yield. The product was a mixture
(4:1) of C-(2) isomers 8a and 8b; MS m/z (%): 207
(10) [M+]; 13C NMR (CDCl3) data for the phenyl
group, l (ppm): 8a: Ci 142.1, Co 129.7, Cm 127.8, Cp
127.0; 8b: Ci 138.6, Co 128.7, Cm 128.1, Cp 127.0.
4.3. (1S,2R)-Thiosulfonic deoxy-norephedrine acid 4a
To
a solution of chlorodeoxy-norpseudoephedrine
hydrochloride 2a (7.77 g, 37.74 mmol) in water (100
mL) was added sodium thiosulfate (7.16 g, 45.3
mmol) and the reaction mixture was heated under
reflux for 4 h. A slightly yellow precipitate was
obtained, which was filtered off and washed with cold
water (6.3 g, 67.6%); mp 219°C (dec.); [h]D=+138.95
(c=17.2 mg/10 mL, DMSO); 13C NMR (DMSO-d6)
data for the phenyl group, l (ppm): Ci 138.7, Co
129.2, Cm 128.8, Cp 128.2.
4.9. (2R,4R,5R)-2-Hydro-2,3,4-trimethyl-5-phenyl-1,3-
thiazolidine 9a and (2S,4R,5R)-2-hydro-2,3,4-trimethyl-
5-phenyl-1,3-thiazolidine 9b
Brown liquid, 90% yield, which is a mixture of C-(2)
isomers 9a/9b in a 7:3 ratio. 13C NMR (CDCl3) data
for the phenyl group l (ppm), 9a: Ci 140.5, Co 128.6,
Cm 128.5, Cp 128.5. 9b: Ci 139.6, Co 128.4, Cm 128.5,
Cp 127.2.
4.4. (1S,2R)-Thiosulfonic deoxy-ephedrine acid 4b
Compound 4b was prepared from 2b analogously to
4a. A sticky solid was obtained, identified as a mix-
ture (36:64) of the isomers 4b and 3b, respectively.
The isomers were separated by selectively dissolving
the threo-isomer 3b in hot ethanol. The undissolved
white solid was identified as the erythro-isomer 4b;
yield 30%; mp 140°C (dec.); [h]D=+81.6 (c=14.7 mg/
10 mL, DMSO); 13C NMR (DMSO-d6) data for the
phenyl group, l (ppm): Ci 139.2, Co 129.6, Cm 129.0,
Cp 128.6.
4.10. (4R,5S)-2,2,3,4-Tetramethyl-5-phenyl-1,3-thiazo-
lidine 10
The product was contaminated with the correspond-
ing disulfide (30%), and so was only studied by
NMR. 13C NMR (CDCl3) data for the phenyl group,
l (ppm): Ci 142.0, Co 128.4, Cm 127.5, Cp 127.0.
4.11. (4R,5R)-2,2,3,4-Tetramethyl-5-phenyl-1,3-thiazo-
lidine 11
Yellow liquid, 60% yield; [h]D=+23.7 (c=29.5 mg/10
mL, CHCl3); MS m/z (%): 221 (3) [M+]; 13C NMR
(CDCl3) data for the phenyl group, l (ppm): Ci
140.2, Co 128.8, Cm 128.6, Cp 127.5.
4.5. General procedure for the synthesis of 1,3-thiazo-
lidines 6–17
The thiosulfonic compounds 3a,b and 4a,b were
hydrolysed over 3 h at reflux with 30% aqueous HCl.
The carbonyl compound (ketone or aldehyde), dis-
solved in CHCl3, was added at rt, and the reaction
mixture was stirred for 1 h (the reaction was per-
formed at 0°C for aldehydes and at rt for ketones).
CHCl3 (140 mL) was added, followed by 30%
aqueous NaOH, to give a pH of 8. The mixture was
extracted with CHCl3 and the organic extract washed
with water, dried and evaporated. The crude com-
pounds were purified by chromatography (column
with silica gel 60) using CHCl3 as the eluent.
4.12. (4R,5S)-2,2,3-Trihydro-4-methyl-5-phenyl-1,3-
thiazolidine 12
Yellow liquid, 81% yield; [h]D=+55 (c=13.10 mg/10
mL, CHCl3); MS m/z (%): 179 (27) [M+]; 13C NMR
(CDCl3) data for the phenyl group, l (ppm): Ci
141.2, Co 129.1, Cm 128.5, Cp 127.6.
4.13. (4R,5R)-2,2,3-Trihydro-4-methyl-5-phenyl-1,3-
thiazolidine 13
Dark yellow solid, 68% yield; mp 46–50°C; [h]D=
−125.9 (c=17.0 mg/10 mL, CHCl3); MS m/z (%): 179
(79) [M+]; 13C NMR (CDCl3) data for the phenyl
group, l (ppm): Ci 140.7, Co 128.6, Cm 128.1, Cp
127.3. Anal. calcd for C10H13NS: C, 66.94; H, 7.25;
N, 7.81. Found: C, 66.54; H, 7.57; N, 7.30%.
4.6. (4R,5S)-2,2-Dihydro-3,4-dimethyl-5-phenyl-1,3-
thiazolidine 6
Yellow liquid, 50% yield; [h]D=−7.2 (c=12.5 mg/10
mL, CHCl3); MS m/z (%): 193 (27) [M+]; 13C NMR

A. Cruz et al. / Tetrahedron: Asymmetry 12 (2001) 711–717
717
4.14. (2R,4R,5S)-2,3-Dihydro-2,4-dimethyl-5-phenyl-1,3-
Acknowledgements
thiazolidine 14a and (2S,4R,5S)-(−)-2,3-dihydro-2,4-
dimethyl-5-phenyl-1,3-thiazolidine 14b
A.C. is grateful for financial support from Conacyt
Mexico (Grant No. 32190-E). The authors would like
to thank Professor Bernd Wrackmeyer for the critical
reading.
Greenish yellow liquid (90% yield), a mixture of C-(2)
isomers 14a and 14b in a 3:1 ratio. MS m/z (%):
193.2 (10) [M+]; 13C NMR (CDCl3) data of phenyl
group, l (ppm): 14a: Ci 139.6, Co 128.5, Cm 128.1, Cp
127.1; 14b: Ci 141.2, Co 128.8, Cm 128.1, Cp 127.1. Anal.
calcd for C11H15NS·0.75H2O: C, 63.88; H, 8.04; N,
6.77. Found: C, 63.68; H, 7.54; N, 6.48%.
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dock, D. C.; Brown, J. M. Tetrahedron: Asymmetry 2000,
11, 3591; (d) Sto¨ver, M.; Lu¨tzen, A.; Ko¨ll, P. Tetrahedron:
Asymmetry 2000, 11, 371; (e) Corey, E. J.; Helal, C. J.
Angew. Chem., Int. Ed. Engl. 1998, 37, 1986; (f) Gawley,
L. E.; Zhang, P. J. Org. Chem. 1996, 61, 8103.
4.15. (2R,4R,5R)-2,3-Dihydro-2,4-dimethyl-5-phenyl-
1,3-thiazolidine 15a and (2S,4R,5R)-(−)-2,3-dihydro-
2,4-dimethyl-5-phenyl-1,3-thiazolidine 15b
Brown liquid (94% yield), composed of a mixture of the
C-(2) isomers 15a and 15b in a 3:1 ratio. 13C NMR
(CDCl3) data for the phenyl group, l (ppm) 15a: Ci
140.7, Co 128.5, Cm 128.1, Cp 127.3; 15b: Ci 140.8, Co
128.5, Cm 128.0, Cp 127.3.
2. Gawley, R. E.; Zhong, Q.; McPhail, A. T. Tetrahedron:
Asymmetry 2000, 11, 2093.
3. (a) Santiesteban, F.; Grimaldo, C.; Contreras, R.; Wrack-
meyer, B. J. Chem. Soc., Chem. Commun. 1983, 1486; (b)
Contreras, R.; Santiesteban, F.; Paz-Sandoval, A.; Wrack-
meyer, B. Tetrahedron 1984, 40, 3829; (c) Paz-Sandoval,
M. A.; Santiesteban, F.; Contreras, R. Magn. Reson.
Chem. 1985, 23, 428; (d) Tlahuext, H.; Contreras, R.
Tetrahedron: Asymmetry 1992, 3, 727; (e) Tlahuext, H.;
Contreras, R. Tetrahedron: Asymmetry 1992, 3, 1145; (f)
Cruz, A.; Flores-Parra, A.; Tlahuext, H.; Contreras, R.
Tetrahedron: Asymmetry 1995, 6, 1933; (g) Cruz, A.;
Mac´ıas Mendoza, D.; Barraga´n-Rodr´ıguez, E.; Tlahuext,
H.; Noth, H.; Contreras, R. Tetrahedron: Asymmetry 1997,
8, 3903; (h) Cruz, A.; Gen´ız, E.; Contreras, R. Tetra-
hedron: Asymmetry 1997, 9, 3991.
4.16. (4R,5S)-3-Hydro-2,2,4-trimethyl-5-phenyl-1,3-
thiazolidine 16
Pale yellow solid, 44% yield; mp 51–54°C; [h]D=−11.3
(c=17.7 mg/10 mL, CHCl3); MS m/z (%): 207 (11)
[M+]; 13C NMR (CDCl3) data for the phenyl group, l
(ppm): Ci 140.8, Co 128.8, Cm 128.2, Cp 127.1. Anal.
calcd for C12H17NS: C, 69.56; H, 8.26; N, 6.76. Found:
C, 68.43; H, 8.31; N, 6.38%.
4.17. (4R,5R)-3-Hydro-2,2,4-trimethyl-5-phenyl-1,3-
thiazolidine 17
4. (a) Kone, B.; Gelbcke, M. Spectrochim. Acta 1983, 39,
409; (b) Kone, B.; Gelbcke, M. Bull. Soc. Chim. Belg.
1983, 92, 139.
5. Flores-Parra, A.; Suarez-Moreno, P.; Sa´nchez Ru´ız, S. A.;
Tlahuextl, M.; Jaen-Gaspar, J.; Tlahuext, H.; Salas-Coro-
nado, R.; Cruz, A.; Noth, H.; Contreras, R. Tetrahedron:
Asymmetry 1988, 9, 1661.
Pale yellow liquid, 43% yield; [h]D=−146.15 (c=19.5
mg/10 mL, CHCl3); MS m/z (%): 207 [M+] (25); 13C
NMR (CDCl3) data for the phenyl group, l (ppm): Ci
139.8, Co 128.2, Cm 128.6, Cp 127.4. Anal. calcd for
C12H17NS: C, 69.56; H, 8.21; N, 6.76. Found: C, 68.75;
H, 8.13; N, 6.71%.
.
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