Stereoselective preparation of trifluoromethyl containing 1,4-oxathiolane derivatives through ring expansion reaction of 1,3-oxathiolanes

Article abstract of DOI:10.1016/j.tet.2005.10.050

Trifluoromethyl containing 1,4-oxathiolanes are synthesized in excellent yields and high stereoselectivities from the expansion reactions of sulfur ylide intermediates, which were prepared from the reaction of 2-diazo-3,3,3- trifluoro-propionic acid methy

Full text of DOI:10.1016/j.tet.2005.10.050

Tetrahedron 62 (2006) 829–832
Stereoselective preparation of trifluoromethyl containing
1,4-oxathiolane derivatives through ring expansion
reaction of 1,3-oxathiolanes
*
Shifa Zhu, Chunhui Xing and Shizheng Zhu
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Fenglin Lu, Shanghai 20032, China
Received 25 August 2005; revised 19 October 2005; accepted 21 October 2005
Available online 8 November 2005
Abstract—Trifluoromethyl containing 1,4-oxathiolanes are synthesized in excellent yields and high stereoselectivities from the expansion
reactions of sulfur ylide intermediates, which were prepared from the reaction of 2-diazo-3,3,3-trifluoro-propionic acid methyl ester and
1,3-oxathiolanes in the presence of Rh2(OAc)4.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
Porter et al. reported 1,4-oxathiolanes could be synthesized
from the reaction of 1,3-oxathiolanes and a silylated diazo-
acetate in the presence of a copper catalyst in moderate yield
and low diastereomeric ratio.5 In this paper, we will report the
stereoselective synthesis trifluoromethyl containing 1,4-
oxathiolane from the reaction of 2-diazo-3,3,3-trifluoro-
propionic acid methyl ester and 1,3-oxathiolanes (Scheme 1).
Considerable attention has been given to trifluoromethyl
containing organic compounds as agrochemical and phar-
maceutical agents due to their unique properties arising from
altered electron density, acidity, and lipophilicity.1 Accord-
ingly, the development of new methods for the synthesis
of the trifluoromethyl containing organic compounds is
continuous to be a an important area of research
in agricultural, medicinal, and organic chemistry.2 1,4-
Oxathiolanes are important heterocycles occurring in natural
and medicinal molecules,3 for example, RNA polymerase
inhibitor tagetitoxin.4 Although the preparation of nonfluoro-
1,4-oxathiolane are well documented, however, the stereo-
selective ratio of the products mostly is still low, in particular
to those containing quaternary carbons.5 Furthermore, it is
difficult to introduce fluorine atoms into 1,4-oxathiolanes.6
O
SH
OH
CF3
CO2Me
S
R1
R2
+
+
N2
R2
R1
O
MeO2C
MeO2C
CO2Me
CF3
CF3
R1
CF3
S
S
S
R1
R2
R1
R2
O
R2
O
O
2. Results and discussion
Scheme 1.
As part of a project on synthesis of fluorine-containing
molecules using fluorinated diazocompounds, we wish to
develop a method to synthesize trifluoromethyl containing
1,4-oxathiolane through ring expansion of 1,3-oxathiolane
started from 2-diazo-3,3,3-trifluoro-propionic acid
methyl ester.
1,3-Oxathiolane 2 can be readily obtained from the reaction
of 2-mercapto ethanol and carbonyl compounds in the
presence of CAN in excellent yields. Initial studies were
focus on the reaction of 1,3-oxathiolanes 2 derived from
aromatic aldehydes and diazocompounds 1. To a refluxing
benzene solution of 1,3-oxathilane 2 and catalyst was added
a benzene solution of diazocompound 1 in 2 h. The stirring
continues for an additional 2 h. Rh2(OAc)4 is a superior
catalyst than the copper catalysts, for example, Cu(acac)2,
which is contradict to the results reported by Porter.5
Keywords: Stereoselective synthesis; Diastereomeric ratio; Lipophilicity;
Sulfur ylide; Diazo; Trifluoromethyl; 1,4-Oxathiolane.
*
Corresponding author. Tel.: C86 21 54925184; fax: C86 21 64166128;
e-mail: zhusz@mail.sioc.ac.cn
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.10.050

830
S. Zhu et al. / Tetrahedron 62 (2006) 829–832
The reaction gives 1,4-oxathiolanes 3 in high yields with
excellent diastereomeric ratio. 1,3-Oxathiolanes derived
from the aromatic aldehydes substituted with electron-
withdrawing groups lead to the products in relatively higher
yields than those electron-donating ones, but with lower
diastereometric ratio (Table 1, entries 6–8). Chemical shift
data from the NMR spectrum of the products suggests that
the major isomer is the one in which the carbmethoxy and
phenyl groups are trans-oriented. Those electron-rich
substrates give 1,4-oxathiolanes in higher trans/cis ratio
than those electron-poor ones. For example, it gives to
almost exclusively trans diastereoselective products when
the aromatic ring was substituted with methoxy group
(Table 1, entry 8). The nitro-substituted substrate, however,
it gives only 3:2 trans/cis diastereoselective ratio (Table 1,
entry 8).
Scheme 2. The molecular structure of 3a.
Spiro structures existed in many medicinally or biologically
important molecules.7 How to efficiently synthesize such
compounds is still a challenge subject. It is in particular
difficult to introduce fluorine atom into spiro-molecules.
Spiro 1,3-oxathiolanes can be easily available from cyclic
ketone with 2-mercapto ethanol. Based on the above
experiments, the [1,2]-rearrangement of the intermediate
sulfur ylides of spiro 1,3-oxathiolanes should give the
trifluoromethyl containing spiro 1,4-oxatiolane. Under the
same reaction conditions, the spiro compound 6 was indeed
obtained in 59% yield, which was in line with our initial
speculations (Scheme 3).
Table 1.
N2
Ar
Ar
O
S
H
Rh2(OAc)4
O
+
S
Benzene, reflux
F3C
MeO2C
CO2Me
CF3
1
2
3
Entry
1,3-Oxathiolanes
Product
Yield (%)a trans/cisb
1
2
3
4
5
6
7
8
ArZPh (2a)
3a
3b
3c
3d
3e
3f
93
65
75
75
96:4
97:3
98:2
97:3
92:8
2:1
92:8
O99:1
ArZo-F–C6H4–(2b)
ArZo-Cl–C6H4–(2c)
ArZo-Br–C6H4–(2d)
ArZp-Br–C6H4–(2e)
ArZp-NO2–C6H4–(2f)
ArZp-CH3–C6H4–(2g)
ArZp-MeO–C6H4–(2h)
92
100
88
3g
3h
83
N2
a All products were fully characterized by spectroscopic methods. The
yields were isolated yields.
O
Rh2(OAc)4
+
O
b Determined by 1H NMR integration of the reaction mixture.
Benzene, reflux
CF3
S
F3C
S
CO2Me
CO2Me
1
4
The relative stereochemistry of 3 was further confirmed by a
X-ray crystal diffraction analysis of compound 3a
(Scheme 2). The structural analysis clearly shows the 1,4-
oxathiolane ring of 3a keeps in a thermodynamic stable
chair conformation. The large groups, methoxyl carbonyl
and phenyl ring, lie in the equatorial position of six-member
ring. Trifluoromethyl group, smaller than methoxyl carbonyl
group, situates in the axial position. What resulted in the
low diastereomeric ratio (2:1) with regard to the reaction of
2-(4-nitro-phenyl)-1,3-oxathiolane with 1,4-oxathiolane?
We know that the trifluoromethyl and aromatic ring are
in cis position according to the crystallographic study.
The electrostatic repulsion between the trifluoromethyl
and nitrophenyl, an electron-deficient group, makes the
relatively bulky methoxyl carbonyl group tend to be axial
set, in order to reduce such repulsion.
6
59%
Scheme 3.
For comparison, 1,3-oxathiolane 5 was treated with
trifluoromethyl diazoacetate 1 under similar reaction
conditions, no [1,2]-rearrangement of intermediate sulfur
ylides was not observed. The elimination product 7 was
dominant (48%) (Scheme 4). The reaction might be
preceded through a five-membered ring intermediate.
In summary, we have developed an efficient method for the
stereoselective synthesis of trifluoromenthyl 1,4-oxathio-
lane through ring expansion of 1,3-oxathiolane ylide using
H
H
N2
Ph
O
H
Ph
O
S
Rh2(OAc)4
O
+
CF3
CO2Me
S
Ph
Benzene, reflux
S
F3C
CO2Me
F3C
CO2Me
1
5
7
48%
Scheme 4.

S. Zhu et al. / Tetrahedron 62 (2006) 829–832
831
trifluoromethyl diazoactetate in the presence of Rh2(OAc)4.
This catalytic, stereoselective and mild reaction will be the
method of choice in many instances.
independent reflection were measured in range 2.36!q!
27.08. The structure was solved by directed methods and
expanded using Fourier techniques. The nonhydrogen atoms
were refined anisotropically, hydrogen atoms were included
but not refined. The final cycle of fullmatrix least-square
refinement was base on F2. The final R and wR value were
0.0490 and 0.1128, respectively. All calculations were
performed using the SHELX-97 program.
3. Experimental
Melting points were measured on a Temp-Melt apparatus
1
and are uncorrected. Solvents were dried before use. H,
19F, and 13C NMR spectra were recorded on a Varian-360L
instrument or Bruker DRX-400 spectrometer with TMS and
TFA (dCFCl3ZdTFAC76.8) as the internal and external
standards and the upfield as negative. IR spectra were
obtained with an IR-440 Shimadzu spectrophotometer.
Low-resolution mass spectra and high-resolution mass
spectra (HRMS) were obtained on a Finnigan GC–MS
4021 and Finnigan MAT-8430 instrument, respectively.
The X-ray structural analysis was performed with a
Rigaku/AFC 7R Diffractometer. Elemental analyses were
performed by this Institute.
3.1.2. 2-(2-Fluoro-phenyl)-3-trifluoromethyl-1,4-oxa-
thiinane-3-carboxylic acid methyl ester (3b). Colorless
crystal with mp: 71–73 8C, yield: 65%, IR (KBr): 3001,
2955, 2923, 1750, 1491, 1458, 1434, 1258, 1164 cmK1. 1H
NMR (300 MHz, CDCl3): d 2.48 (d, 1H, JZ13.2 Hz), 3.43
(t, 1H, JZ15.0 Hz), 3.77 (s, 3H), 4.06 (t, 1H, JZ12.0 Hz),
4.49 (d, 1H, JZ11.7 Hz), 5.48 (s, 1H), 6.94–7.59 (m,
4H) ppm. 13C NMR (75 MHz, CDCl3): d 25.1, 53.6, 57.2 (d,
JF–CZ26.5 Hz), 70.0, 82.3, 114.4, 114.7, 123.9, 129.1 (q,
JF–CZ283.4 Hz), 129.5, 130.8, 130.9, 165.0 ppm. 19F NMR
(282 MHz, CDCl3): d K60.3 (s, 3F) K116.8 (s, 1F) ppm.
EI-MS (m/z, %): 324 (MC, 6), 200 (100), 172 (23), 123 (46),
113 (12), 59 (45). Anal. Calcd for C13H12F4O3S: C; 48.15,
H; 3.73%. Found: C; 47.97, H; 3.84%.
3.1. General procedure for ring expansion
A mixture of 1,3-oxathiolane (2) (1 mmol) and Rh2(OAc)4
(5 mg, 0.01 mmol) in dry benzene (2 mL) was heated to
reflux under a nitrogen atmosphere. A solution of 2-diazo-
3,3,3-trifluoro-propionic acid methyl ester (1) (201 mg,
1.2 mmol) in benzene (2 mL) was added dropwise over 2 h
through syringe. Reflux was continued for 2 h, and then the
mixture was allowed to cool to rt. The solvent was removed
under reduced pressure and the residue was purified by a
flash chromatography on silica gel (petroleum–ethyl
acetate) to give the ring expansion product 1,4-oxathiolane
(3). The procedure for the preparation of products 6 and 7
are similar to that of 3.
3.1.3. 2-(2-Chloro-phenyl)-3-trifluoromethyl-1,4-oxa-
thiinane-3-carboxylic acid methyl ester (3c). Colorless
crystal, mp: 69–71 8C, yield: 75%, IR (KBr): 3011, 2958,
2967, 1934, 1740, 1478, 1437, 1258, 1160 cmK1. 1H NMR
(300 MHz, CDCl3): d 2.49 (d, 1H, JZ12.6 Hz), 3.47 (t, 1H,
JZ13.5 Hz), 3.75 (s, 3H), 4.06 (t, 1H, JZ11.7 Hz), 4.49 (d,
1H, JZ11.7 Hz), 5.59 (s, 1H), 7.25–7.65 (m, 4H) ppm. 13C
NMR (75 MHz, CDCl3): d 25.7, 54.0, 58.1, 70.2, 79.8,
125.4 (q, JF–CZ282.9 Hz), 126.4, 128.5, 129.8, 130.5,
132.8, 135.3, 164.7 ppm. 19F NMR (282 MHz, CDCl3): d
K59.7 (s, 3F) ppm. EI-MS (m/z, %): 340 (MC, 2), 200
(100), 172 (20), 139 (27), 113 (11), 59 (34). Anal. Calcd for
C13H12ClF3O3S: C; 45.82, H; 3.55%. Found: C; 45.85, H;
3.62%.
3.1.1. 2-Phenyl-3-trifluoromethyl-1,4-oxathiinane-3-carboxy-
lic acid methyl ester (3a). Colorless crystal with mp:
59–61 8C, yield: 93%, IR (KBr): 2987, 2957, 2924, 1747,
1
1498, 1455, 1432, 1253, 1164 cmK1. H NMR (300 MHz,
3.1.4. 2-(2-Bromo-phenyl)-3-trifluoromethyl-1,4-oxa-
thiinane-3-carboxylic acid methyl ester (3d). Colorless
crystal, mp: 97–99 8C, yield: 75%, IR (KBr): 3062, 2995,
CDCl3): d 2.44 (d, 1H, JZ13.5 Hz), 3.41 (t, 1H,
JZ12.3 Hz), 3.80 (s, 3H), 4.07 (t, 1H, JZ11.7 Hz), 4.49
(d, 1H, JZ11.4 Hz), 5.49 (s, 1H), 7.32–7.46 (m, 5H) ppm.
2920, 1745, 1474, 1431, 1262, 1225, 1170, 1153, 1095 cmK1
.
1H NMR (300 MHz, CDCl3): d 2.48 (d, 1H, JZ13.8 Hz),
3.46 (t, 1H, JZ12.0 Hz), 3.75 (s, 3H), 4.05 (t, 1H, JZ
12.0 Hz), 4.49 (d, 1H, JZ11.7 Hz), 5.59 (s, 1H), 7.15–7.56
(m, 4H) ppm. 13C NMR (75 MHz, CDCl3): d 25.7, 54.1,
58.0, 70.2, 82.4, 123.6, 125.5 (q, JF–CZ285.1 Hz), 126.9,
130.1, 130.9, 131.8, 136.9, 164.6 ppm. 19F NMR (282 MHz,
CDCl3): d K59.5 (s) ppm. EI-MS (m/z, %): 340/342 (MC,
1/1), 200 (100), 185 (15), 183 (16), 172 (19), 113 (8), 59
(29). Anal. Calcd for C13H12BrF3O3S: C; 40.54, H; 3.14%.
Found: C; 40.69, H; 3.27%.
13C NMR (75 MHz, CDCl3): d 24.7, 53.4, 55.8 (d, JF–C
Z
24.8 Hz), 69.5, 82.4, 125.1 (q, JF–CZ283.3 Hz), 127.2,
128.0, 128.5, 137.5, 166.1 ppm. 19F NMR (282 MHz,
CDCl3): d K59.89 (s) ppm. EI-MS (m/z, %): 306 (MC,
6), 200 (100), 172 (21), 105 (42), 77 (15), 59 (21). Anal.
Calcd for C13H13F3O3S: C; 50.98, H; 4.28%. Found: C;
51.10, H; 4.25%.
X-ray data of 3a
C13H13F3O3S: MwZ306.29, CCDC no. 284941, ortho-
˚
rhombic, space group: P2(1)2(1)2(1), aZ6.755(10) A bZ
3.1.5. 2-(4-Bromo-phenyl)-3-trifluoromethyl-1,4-oxa-
thiinane-3-carboxylic acid methyl ester (3e). Colorless
crystal, mp: 62–64 8C, yield: 92%, IR (KBr): 2996, 2957,
1749, 1489, 1338, 1249, 1173, 1162, 1099 cmK1. 1H NMR
(300 MHz, CDCl3): d 2.44 (d, 1H, JZ13.5 Hz), 3.37 (t, 1H,
JZ12.3 Hz), 3.78 (s, 3H), 4.02 (t, 1H, JZ11.7 Hz), 4.46
(d, 1H, JZ11.7 Hz), 5.41 (s, 1H), 7.24–7.26 (m, 2H),
7.41–7.44 (m, 2H) ppm. 13C NMR (75 MHz, CDCl3): d
21.0, 53.7, 55.3, 69.4, 85.8, 125.0 (q, JF–CZ283.4 Hz),
˚
˚
7.867(11) A, cZ12.937(18) A; aZ91.464(3)8, bZ92.651(3)8,
gZ108.662(2)8; VZ650.06(16) A , ZZ1, DcZ1.794 g/cm ,
F(000)Z348. Radiation, Mo Ka (lZ0.71073 A). Crystal
dimension, 0.58!0.44!0.34 mm.
3
3
˚
˚
Intensity data were collected at 293(2) K with a Bruker P4
four-circle diffractometer with graphite monochromator and
Mo Ka radiation (lZ0.71073 A). A total of 8147
˚

832
S. Zhu et al. / Tetrahedron 62 (2006) 829–832
129.1, 131.0, 131.4, 136.6, 166.0 ppm. 19F NMR (282 MHz,
CDCl3): d K59.8 (s) ppm. EI-MS (m/z, %): 340/342 (MC,
4/4), 200 (100), 185 (26), 183 (24), 172 (21), 113 (17), 77
(7), 59 (35). HR-EI-MS calcd for C13H12BrF3O3S (MC):
383.9643; found: 383.9657.
JZ5.7 Hz), 4.18 (t, 1H, JZ8.1 Hz) ppm. 13C NMR (75 MHz,
CDCl3): d 22.6, 22.6, 27.6, 32.9, 53.2, 60.0, 77.1, 124.0 (q,
JF–CZ277.7 Hz), 165.7 ppm. 19F NMR (282 MHz, CDCl3): d
K52.1 (dd, J1Z10.1 Hz, J2Z36.7 Hz) ppm. EI-MS (m/z, %):
298(MC,3),200(100),188(20),159(18),142(71),91(29),59
(53),45(64).HR-MALDI-MScalcdforC12H17F3O3SNa(MC
NaC): 321.0748; found: 321.0759.
3.1.6. 2-(4-Nitro-phenyl)-3-trifluoromethyl-1,4-oxa-
thiinane-3-carboxylic acid methyl ester (3f). Colorless
crystal, mp: 77–79 8C, yield: 100%, IR (KBr): 3000, 2961,
2914, 1751, 1744, 1608, 1517, 1350, 1251, 1157, 1104,
1032 cmK1. 1H NMR (300 MHz, CDCl3): d 2.50 (d, 1H, JZ
13.8 Hz), 3.42 (t, 1H, JZ12.3 Hz), 3.83 (s, 3H), 4.06 (t, 1H,
JZ12.0 Hz), 4.52 (d, 1H, JZ11.7 Hz), 5.57 (s, 1H),
7.58–7.61 (m, 2H), 8.14–8.18 (m, 2H) ppm. 13C NMR
(75 MHz, CDCl3): d 24.7, 53.8, 55.2, 69.3, 80.9, 123.0,
126.8, 130.5, 144.6, 147.8, 165.9 ppm. 19F NMR (282 MHz,
CDCl3): d K59.7 (s) ppm. EI-MS (m/z, %): 351 (MC, 1),
200 (100), 172 (17), 113 (3), 77 (1), 59 (5). Anal. Calcd for
C13H12NF3O5S: C; 44.45, H; 3.44, N; 3.99%. Found: C;
44.36, H; 3.27, N; 3.89%.
3.1.10. 3,3,3-Trifluoro-2-[2-(1-phenyl-vinyloxy)-ethyl-
sulfanyl]-propionic acid methyl ester (7). Pale yellow
oil (152 mg, 48%), IR (KBr): 3467, 2959, 1751, 1713, 1686,
1
1439, 1361, 1269, 1147, 1111 cmK1. H NMR (300 MHz,
CDCl3): d 3.21 (q, 2H, JZ4.8 Hz), 3.80 (s, 3H), 3.82 (s,
1H), 4.10 (t, 2H, JZ6.0 Hz), 4.23 (d, 1H, JZ3.0 Hz), 4.72
(d, 1H, JZ3.3 Hz), 7.34–7.62 (m, 5H) ppm. 13C NMR
(75 MHz, CDCl3): d 31.4, 49.7, 53.2, 63.2, 83.2, 127.8 (q,
JF–CZ282.8 Hz), 125.0, 125.4, 128.2, 128.6, 159.6,
165.6 ppm. 19F NMR (282 MHz, CDCl3): d K52.5 ppm.
EI-MS (m/z, %): 321 (MC, 15), 201 (100), 179 (6), 141 (17),
77 (5), 59 (8). HR-MALDI-MS calcd for C14H15F3O3SNa:
343.0592; found: 343.0598.
3.1.7. 2-(4-Methyl-phenyl)-3-trifluoromethyl-1,4-oxa-
thiinane-3-carboxylic acid methyl ester (3g). Pale yellow
liquid, yield: 88%, IR (KBr): 3009, 2958, 2865, 2253, 1749,
Acknowledgements
1715, 1616, 1516, 1437, 1363, 1264, 1224, 1171, 1105 cmK1
.
1H NMR (300 MHz, CDCl3): d 2.35 (s, 3H), 2.44 (d, 1H,
JZ12.6 Hz), 3.42 (t, 1H, JZ11.2 Hz), 3.80 (s, 3H), 4.06
(t, 1H, JZ11.7 Hz), 4.49 (d, 1H, JZ12.0 Hz), 5.45 (s, 1H),
7.12–7.15 (m, 2H), 7.26–7.35 (m, 2H) ppm. 13C NMR
(75 MHz, CDCl3): d 21.2, 24.7, 53.5, 55.8, 69.6, 82.4,
123.3, 127.1, 128.6, 134.6, 138.2, 166.2 ppm. 19F NMR
(282 MHz, CDCl3): d K59.9 (s) ppm. EI-MS (m/z, %): 320
(MC, 8), 200 (100), 172 (15), 119 (50), 91 (17), 84 (19),
59 (27). HR-MALDI-MS calcd for C14H15F3O3SNa
(MCNaC): 343.0592; found: 343.0593.
This work was financially supported by the National Natural
Science Foundation of China (NNSFC) (Nos. 20372077 and
20472106).
References and notes
1. (a) Biomedical Frontiers of Fluorine Chemistry; Ojima, I.,
McCarthy, J. R., Welch, J. T., Eds.; ACS Symposium Series
639; American Chemical Society: Washington, DC, 1996. (b)
Welch, J. T. Tetrahedron 1987, 43, 3123–3197. (c) Synthesis
and Chemistry of Agrochemical III; Baker, D. R., Fenyes, J. G.,
Steffens, J. J., Eds.; ACS Symposium Series 504; American
Chemical Society: Washington, DC, 1992.
3.1.8. 2-(4-Methoxyl-phenyl)-3-trifluoromethyl-1,4-oxa-
thiinane-3-carboxylic acid methyl ester (3h). Pale yellow
solid with mp: 82–84 8C, yield: 83%, IR (KBr): 3021, 2982,
2841, 1743, 1616, 1515, 1436, 1293, 1261, 1171, 1156,
1103 cmK1. 1H NMR (300 MHz, CDCl3): d 2.45 (d, 1H, JZ
13.5 Hz), 3.41 (t, 1H, JZ12.0 Hz), 3.80 (s, 6H), 4.06 (t, 1H,
JZ11.7 Hz), 4.49 (d, 1H, JZ13.5 Hz), 5.41 (s, 1H),
6.82–6.85 (m, 2H), 7.27–7.31 (m, 2H) ppm. 13C NMR
(75 MHz, CDCl3): d 24.8, 53.4, 55.2, 55.7, 69.6, 82.1,
113.2, 125.2 (q, JF–CZ281.2 Hz), 128.5, 129.6, 159.6,
166.2 ppm. 19F NMR (282 MHz, CDCl3): d K59.8 (s) ppm.
EI-MS (m/z, %): 336 (MC, 18), 200 (100), 172 (16), 136
(98), 135 (82), 113 (10), 77 (9), 59 (21). Anal. Calcd for
C14H15F3O4S: C; 50.00, H; 4.50%. Found: C; 50.00, H;
4.47%.
2. (a) Asymmetric Fluoroorganic Chemistry; Ramachandran, P. V.,
Ed.; ACS Symposium Series 746; American Chemical Society:
Washington, DC, 1999. (b) Kitazume, T.; Yamazaki, T.
Experimental Methods in Organic Fluorine Chemistry; Gordon
and Breach Science: Amsterdam, 1998. (c) Burton, D. J.;
Yang, Z. Y.; Qiu, W. Chem. Rev. 1996, 96, 1641–1716.
3. Miyauchi, H.; Tanio, T.; Ohashi, N. Bioorg. Med. Chem. Lett.
1996, 6, 2377–2380.
4. (a) Mitchell, R. E.; Durbin, R. D. Physiol. Plant Pathol. 1981,
18, 157–168. (b) Mitchell, R. E.; Coddington, J. M.; Young, H.
Tetrahedron Lett. 1989, 30, 501–504.
3.1.9. 5-Trifluoromethyl-1-oxa-4-thia-spiro[5.5]undecane-
5-carboxylic acid methyl ester (6). Pale yellow liquid,
yield: 59%, IR (KBr): 3403, 2959, 2881, 1750, 1708,
5. Ioannou, M.; Porter, M. J.; Saez, F. Chem. Commun. 2002,
346–347.
6. Kawa, H.; Hamouda, H. A.; Ishikawa, N. Bull. Chem. Soc. Jpn.
1980, 53, 1694–1697.
1440, 1354, 1282, 1252, 1147, 1111 cmK1 1H NMR
.
(300 MHz, CDCl3): d 1.38–1.87 (m, 6H), 2.01–2.05 (m, 2H)
2.30–2.34(m,2H),2.86–3.04(m,2H),3.76(s,3H),3.86(t,1H,
7. Dandia, A.; Sachdeva, H.; Ahmed, N.; Joshi, K. C. Heterocycl.
Commun. 2000, 6, 181–188.