Novel perfluoroacyl olefinations of aldehydes using β-thio-substituted perfluoroalkyl enol ethers

Article abstract of DOI:10.1021/jo990282p

α-(Methylthio)- or α-(phenylthio)-substituted perfluoroacylolefinations of nonenolizable aldehydes using the β-lithio-β- thio-perfluoroalkyl enol ethers 1-4 stereoselectively proceeded to give (Z)- α,β-unsaturated perfluoroalkyl ketones 9a-e, 10a-c, 11a-c, and 12a. The α- (thio)-α,β-unsaturated trifluoromethyl ketones were easily converted to 3- (thio)-2-(trifluoromethyl)-1,3-butadienes 21a-c and 22a,b in moderate to high yields (41-85%).

Full text of DOI:10.1021/jo990282p

5162
J . Org. Chem. 1999, 64, 5162-5165
Novel P er flu or oa cyl Olefin a tion s of Ald eh yd es Usin g
â-Th io-Su bstitu ted P er flu or oa lk yl En ol Eth er s
Mitsuhiro Yoshimatsu,* Tomomi Sugimoto, Naoyuki Okada, and Sayaka Kinoshita
Department of Chemistry, Faculty of Education, Gifu University, Yanagido 1-1, Gifu 501-1193, J apan
Received February 16, 1999
R-(Methylthio)- or R-(phenylthio)-substituted perfluoroacylolefinations of nonenolizable aldehydes
using the â-lithio-â-thio-perfluoroalkyl enol ethers 1-4 stereoselectively proceeded to give (Z)-R,â-
unsaturated perfluoroalkyl ketones 9a -e, 10a -c, 11a -c, and 12a . The R-(thio)-R,â-unsaturated
trifluoromethyl ketones were easily converted to 3-(thio)-2-(trifluoromethyl)-1,3-butadienes 21a -c
and 22a ,b in moderate to high yields (41-85%).
Sch em e 1
Alkenyl trifluoromethyl ketones have been used as
novel intermediates for the synthesis of biologically active
fluorinated compounds.1 Some methods for the prepara-
tion of the alkenyl ketones have been reported using the
aldol condensation of the trifluoroacetone,2 the Horner-
Emmons reactions of the iminophosphonate,3 the reac-
tions of the boronate ester,4 and the oxidation of the
corresponding alcohols.5 Especially, the iminophosphon-
ate route is convenient from the viewpoint of its direct
preparation from aldehydes. We have recently reported
the tandem formyl olefinations of aldehydes and ketones
using the R-lithio 2-ethoxyvinyl sulfide or selenide.6
Lithium enol ethers are good candidates for the olefina-
tions of carbonyl compounds;7 however, it is difficult to
generate the lithiated perfluoroalkyl enol ethers because
the addition-elimination reaction of the fluorides easily
occurs.8 The transmetalation of the â-bromo perfluoro-
alkyl enol ethers is available as an alternative route.9
On the other hand, the vinyl sulfides are easily
lithiated by treatment with strong base; therefore, the
R-lithio vinyl sulfides easily react with electrophiles to
give the adducts.10 If the â-sulfur-substituted perfluoro-
alkyl enol ether could be prepared, â-lithio perfluoroalkyl
enol ethers could easily be generated. Their lithium
agents would react with aldehydes or ketones to gives
allylic alcohols, whose isomerization afford the R,â-
unsaturated perfluoroalkyl ketones (Scheme 1). We now
report the novel perfluoroacylolefination of the aldehydes
using â-lithio-â-thio-substituted perfluoroalkyl enol ethers.
â-Sulfur-substituted fluoroalkyl enol ethers (E)-1-4
were conveniently prepared under Wittig reaction condi-
tions using phenylthio- or methylthiomethyltriphenylphos-
phorane and CF3CO2Et or CF3CF2CO2Et.11 We first
examined the lithiation of (E)-2-ethoxy-1,1,1-trifluoro-3-
(phenylthio)prop-2-ene (1) using n-BuLi at -78 °C, and
the successive treatment with benzaldehyde afforded the
allylic alcohol 5a in 86% yield. The structure of 5a was
1
determined by the IR and H, 13C, and 19F NMR spectra,
MS, and elemental analysis. We also examined the
reactions of 1 with other nonenolizable aldehydes, and
these results are shown in Table 1 (entries 1-5). We then
examined the isomerization of 5a using various acids
such as trimethylsilyl trifluoromethanesulfonate (TM-
SOTf), polyphosphoric acid trimethylsilyl ester (PPSE),6
BF3‚Et2O, and other protic acids. p-Toluenesulfonic acid
(TsOH) was suitable for the dehydration or the isomer-
ization. The reaction of 5a with 1 equiv of p-TsOH in
ClCH2CH2Cl gave 1,1,1-trifluoro-4-phenyl-3-(phenylthio)-
but-3-en-2-one (9a ) in 91% yield. tert-Butylaldehyde
afforded the R,â-unsaturated trifluoromethyl ketone 9b
(entry 2). The structure of the product 9b was mainly
determined on the basis of the spectral data, showing the
carbonyl absorption at ν 1730 cm-1 in the IR spectrum,
revealing the olefinic absorption at δ 7.39 (s) ppm in the
1H NMR, and exhibiting three quartets at δ 116.21 (J )
292 Hz) due to CF3, 166.30 (J ) 2 Hz) due to the 4-C,
and 179.75 (J ) 34 Hz) due to the carbonyl group in the
13C NMR spectrum. The 19F NMR spectrum also showed
one singlet at δ -7.62 ppm. The other stereoisomers were
not detected in the spectral data. Cinnamaldehyde ste-
reoselectively gave (3Z,5E)-1,1,1-trifluoro-6-phenyl-3-
(phenylthio)hexa-3,5-diene (9c) (entry 3). The trifluoro-
methyl enynyl ketone 9d and the furyl derivative 9e were
also obtained; however, the reaction of â-lithio enol ether
1 with ketones such as acetone or cyclohexanone or
enolizable aldehydes did not give the adduct and the enol
ether 1 was recovered. 1,1,1,2,2-Pentafluoroethyl enol
(1) Koyanagi, T.; Yoneda, T.; Kanamori, F.; Kanbayashi, S.; Tan-
imura, T.; Horiuchi, N. Eur. Pat. Appl. EP 744400 A2 27, 1996, 27 pp.
Yamaguchi, M.; Ito, Y.; Shibayama, A.; Yamaji, Y.; Hanai, R.; Uotsu,
S.; Sadohara, H. PCT Int. Appl. WO 9728127 A17, 1997, 203 pp.
(2) Mead, D.; Loh, R.; Asato, A. E.; Lin, R. S. H. Tetrahedron Lett.
1985, 26, 2873.
(3) Ishihara, T.; Maekawa, T.; Ando, T. Tetrahedron Lett. 1983, 24,
4229.
(4) Takada, E.; Hara, S.; Suzuki, A. Heteroatom Chem. 1992, 3, 483.
(5) Linderman, R. J .; Graves, D. M. Tetrahedron Lett. 1987, 28, 4259.
(6) Yoshimatsu, M.; Oguri, K.; Ikeda, K.; Gotoh, S. J . Org. Chem.
1998, 63, 4475.
(7) Vlattas, I.; Vecchia, L. D.; Lee, A. O. J . Am. Chem. Soc. 1976,
98, 2008.
(8) Begue, J . P.; Bonnet-Delpon, D.; Rock, M. H. Tetrahedron Lett.
1996, 37, 257. Begue, J . P.; Bonnet-Delpon, D.; Bouvet, D.; Rock, M.
H. J . Org. Chem. 1996, 61, 9111.
(9) Bonnet-Delpon, D.; Bouvet, D.; Ourevitch, M.; Rock, M. H.
Synthesis 1998, 288.
(10) Cookson, R.; Parsons, P. J . Chem. Soc., Chem. Commun. 1976,
990. Braum, M. Chem. Ber. 1979, 112, 1495. Oshima, K.; Takahashi,
H.; Yamamoto, H.; Nozaki, H. J . Am. Chem. Soc. 1973, 95, 2694.
(11) Begue, J . P.; Bonnet-Delpon, D.; Nee, G.; Wu, S. W. J . Org.
Chem. 1992, 57, 807.
10.1021/jo990282p CCC: $18.00 © 1999 American Chemical Society
Published on Web 06/17/1999

Novel Perfluoroacyl Olefinations of Aldehydes
J . Org. Chem., Vol. 64, No. 14, 1999 5163
Ta ble 1. r-Th iotr iflu or oa cetylolefin a tion s of Ald eh yd es
Sch em e 2
a n d Keton es
5b which proceeded to give octa-2,5-dien-4-ol 13 in 66%
yield; however, the treatment of 13 with p-toluenesulfonic
acid gave the dihydrobenzo[b]thiophene (15) via the
intramolecular cyclization of 14a and not 1,1,1-trifluoro-
7,7-dimethyl-3,5-bis(phenylthio)-4-(trifluoromethyl)octa-
3,5-dien-2-one (16) via the hydrolysis of 14b (Scheme 2).
The structure of the product 15 was elucidated by
showing the existence of an ethoxy group at δ 1.09 (3H,
t, J ) 7 Hz, Me) and 3.39 (2H, q, J ) 7 Hz, OCH2) in the
1H NMR spectrum, by exhibiting two singlets at δ 8.23
and 18.71 due to the CF3 groups in the 19F NMR
spectrum, and by showing the ion peak assigned to the
benzothiophene at m/z 518 (M+), 449 (M+ - CF3), and
202 (M+ - (CF3 + PhSCdCH(OEt)CF3)) in the MS
spectrum.
2-Sulfur- or 2-selenium-stabilized allylic cations have
been reported to react with the soft nucleophiles to
regioselectively afford the allylated compounds.12 Tri-
fluoromethyl-substituted allylic cations bearing the 2-sul-
fur atom are expected to be good electrophiles. Therefore,
we examined the reactions of the R-trifluoromethyl-
substituted allylic cations stabilized by the sulfur atom
at the 2-position. The allylic alcohols 5a and 7a were
converted to the acetals 17 and 18 by treatment with
p-toluenesulfonic acid/CH(OEt)3 at 78 °C. The reaction
of 17 with allyltrimethylsilane in the presence of SnCl4
was examined; however, it did not undergo the intermo-
lecular allylation but exclusively formed 2-(benzylidene)-
3-ethoxy-3-(trifluoromethyl)benzothiophene (19) via the
intramolecular cyclization. The 3-(methylthio)-substitut-
ed 18 also gave the cyclized product 20 in good yield
(Scheme 3).
ether 2 was also lithiated at -78 °C, and the treatments
with almost the same aldehydes afforded (Z)-1,1,1,2,2-
pentafluoro-4-(phenylthio)pent-4-en-3-ones (10a -c) in
good yields (entries 6-8).
We next examined the lithiation and reaction of the
MeS-substituted enol ether 3. The reaction with benz-
aldehyde stereoselectively proceeded to give the allylic
alcohol 7a , and successive treatment with p-TsOH af-
forded the MeS-substituted trifluoromethyl ketone 11a
in high yield (entry 9). Other MeS-substituted ketones,
11b-c and 12a , were also obtained (entries 10-12);
however, the dehydration of 8b gave a complex mixture.
Recently, we reported that the tandem R-(phenylthio)-
or R-(phenylseleno)-substituted formylolefinations of al-
dehydes and ketones stereoselectively proceeded to give
the 2,4-bis(phenylthio)- or (phenylseleno)penta-2,4-di-
enals and 2,4,6-tris(phenylthio)hepta-2,4,6-trienal de-
rivatives in good yields.6 To examine the tandem R-(phen-
ylthio)trifluoroacetylolefination of the aldehydes, we
examined the second addition reaction of PhSCLid
C(OEt)CF3 to the R,â-unsaturated trifluoromethyl ketone
We next investigated how to utilize the R,â-unsatu-
rated trifluoromethyl ketones in the synthesis of other
fluorinated compounds. Trifluoromethyl 1,3-dienes13 or
enynes14 can be employed as useful intermediates for the
synthesis of biologically active compounds. Most synthetic
(12) For general experimental procedures, see: Yoshimatsu, M.;
Gotoh, S.; Ikeda, K.; Komori, M. J . Org. Chem. 1998, 63, 6619.
(13) Shen, Y.; Qiu, W. Tetrahedron Lett. 1987, 28, 4283. Shen, Y.;
Xiang, Y. J . Chem. Soc., Perkin Trans. 1 1991, 2493. Shen, Y.; Xiang,
Y. Tetrahedron Lett. 1990, 31, 2305. Begue, J .-P.; Bonnet-Delpon, D.;
M’Bida, A. Tetrahedron Lett. 1993, 34, 7753. Shen, Y. Acc. Chem. Res.
1998, 31, 584. Begue, J .-P.; Bonnet-Delpon, D.; Bouvet, D.; Rock, M.
H. J . Org. Chem. 1996, 61, 9111.
(14) Shen, Y.; Qiu, W. J . Chem. Soc, Chem. Commun. 1987, 703.
Shen, Y.; Xiang, Y.; Qiu, W. J . Chem. Soc., Perkin Trans. 1 1991, 2965.

5164 J . Org. Chem., Vol. 64, No. 14, 1999
Yoshimatsu et al.
water (150 mL). The organic layer was separated, and the
aqueous layer was extracted with ether. The combined organic
layer was dried over MgSO4. The solvent was removed under
reduced pressure. The residue was crystalized from pentane
and filtered to remove Ph3PO. The filtrate was evaporated,
and the residue was purified by column chromatography on
silica gel eluting with hexane to give the title compound (4.39
g, 88%) as a colorless oil.
Sch em e 3
(E)-2-Eth oxy-1,1,1-tr iflu or o-3-(p h en ylth io)p r op -2-en e
(1): 1H NMR (400 MHz, CDCl3) δ 1.37 (3H, t, J ) 7 Hz), 4.11
(2H, q, J ) 7 Hz), 6.48 (1H, d, J ) 1 Hz), 7.27-7.36 (3H, m),
7.40-7.42 (2H, m); 13C NMR (100 MHz, CDCl3) δ 15.36 (q),
69.00 (t, J C-F ) 3 Hz, OCH2), 117.75 (d, J C-F ) 5 Hz, 3-C),
120.41 (s, J C-F ) 275 Hz, CF3), 127.83 (d), 129.40 (d × 2),
130.45 (d × 2), 133.61 (s), 139.95 (s, J C-F ) 34 Hz, 2-C); 19F
NMR (376.4 MHz, CDCl3) δ -8.94 (3F, s, CF3); MS m/z 171
(M+ - Ph). Anal. Calcd for C11H11F3OS: C, 53.22; H, 4.47.
Found: C, 53.24; H, 4.50.
Ta ble 2. Syn th esis of
3-Tr iflu or om eth yl-2-(th io)-1,3-bu ta d ien es
P r ep a r a tion of P er flu or oa lk yl Allylic Alcoh ols 5a -e,
6a -c, 7a -c, a n d 8a ,b. Typ ica l P r oced u r e. BuLi (1.60 mL,
2.40 mmol) was added dropwise to a THF (6 mL) solution of
2-ethoxy-1,1,1-trifluoro-3-(phenylthio)-2-propene (0.50 g, 2.00
mmol) at -78 °C under an Ar atmosphere. A THF (2.0 mL)
solution of benzaldehyde (0.26 g, 0.24 mmol) was added to the
mixture. The reaction mixture was poured into water (100 mL),
and the organic layer was separated. The aqueous layer was
extracted with ether. The organic layer and the extracts were
combined and dried over MgSO4. The solvent was removed
under reduced pressure. The residue was purified by a
preparative TLC on silica gel eluting with AcOEt-hexane (1:
40) to give (E)-2-ethoxy-1,1,1-trifluoro-4-phenyl-3-(phenylthio)-
but-2-en-4-ol (5a ) (0.65 g, 86%) as a pale yellow oil.
(2E,5E)-2-E t h oxy-1,1,1-t r iflu or o-6-p h en yl-3-(p h en yl-
th io)h exa -2,5-d ien -4-ol (5c): H NMR (400 MHz, CDCl3) δ
methods for these compounds involve the well-known
Wittig type reaction of trifluoromethyl ketones. We first
examined the reaction of the enones 11a with methyl-
enetriphenylphosphorane at -78 °C, and 3-(methylthio)-
2-(trifluoromethyl)buta-1,3-diene (21a ) was obtained in
44% yield (Table 2, entry 1). The structure of 21a was
determined by its NMR spectrum. The 1H NMR spectrum
exhibited three olefinic absorptions at δ 5.83, 6.05, and
6.84 ppm. The 13C NMR spectrum shows three carbons
at δ 123.36 (t, J C-F ) 5 Hz) due to the CH2 and at δ 137.97
(s, J C-F ) 30 Hz) due to the 2-C. The 19F NMR also
exhibited one singlet at δ -12.78 (CF3). The reaction of
cinnamaldehyde gave the triene 21b in high yield (entry
2). Fluoroenyne 21c was stereoselectively obtained (entry
3). The phenylthio derivatives 9a ,b also gave the dienes
22a ,b (entries 4 and 5).
In conclusion, we have reported a convenient method
for the R-(thio)-substituted perfluoroacylolefination of
nonenolizable aldehydes using the â-(thio)-perfluoroalkyl
enol ethers. The tandem perfluoroacylolefination did not
proceed; however, the R-(thio)-R,â-unsaturated trifluoro-
methyl ketones were steroselectively converted to the
3-(thio)-2-(trifluoromethyl)buta-1,3-dienes.
1
1.15 (3H, t, J ) 7 Hz), 2.59 (1H, d, J ) 9 Hz), 3.83-4.00 (2H,
m), 5.50 (1H, brt, J ) 7 Hz), 6.18 (1H, dd, J ) 5 and 15 Hz),
6.65 (1H, dd, J ) 1 and 15 Hz), 7.17-7.32 (8H, m), 7.35-7.37
(2H, m); 13C NMR (100 MHz, CDCl3) δ 15.03 (q, J C-F ) 4 Hz,
Me), 69.50 (t, J C-F ) 4 Hz, OCH2), 69.62 (d, J C-F ) 3 Hz, 4-C),
121.02 (s, J C-F ) 279 Hz, CF3), 126.67 (d × 2), 126.91 (d),
128.00 (d), 128.29 (s), 128.43 (d), 128.52 (d × 2), 129.01 (d ×
2), 129.38 (d × 2), 131.95 (d), 132.76 (s), 136.17 (s), 145.99 (s,
J C-F ) 34 Hz, 2-C); 19F NMR (376.4 MHz, CDCl3) δ -16.90
(3F, s, CF3); MS m/z 380 (M+). Anal. Calcd for C20H19F3O2S:
C, 63.15; H, 5.03. Found: C, 63.26; H, 5.03.
(E)-2-Eth oxy-1,1,1-tr iflu or o-3-(m eth ylth io)-4-ph en ylbu t-
1
2-en -4-ol (7a ): H NMR (400 MHz, CDCl3) δ 1.38 (3H, t, J )
7 Hz), 2.23 (3H, s), 2.82 (1H, brd, J ) 9 Hz), 4.01-4.14 (2H,
m), 5.92 (1H, d, J ) 9 Hz), 7.25-7.43 (5H, m); 13C NMR (100
MHz, CDCl3) δ 15.59 (q), 16.92 (q), 69.23 (t), 69.60 (d), 121.34
(s, J C-F ) 278 Hz, CF3), 125.80 (d × 2), 127.87 (d), 128.53 (d ×
2), 137.03 (s), 140.51 (s), 144.43 (s, J C-F ) 34 Hz, 2-C); 19F NMR
(376.4 MHz, CDCl3) δ -17.48 (3F, s, CF3); MS m/z 292 (M+).
Anal. Calcd for C13H15F3O2S: C, 53.42; H, 5.17. Found: C,
53.91; H, 5.21.
(E)-3-Ethoxy-1,1,1,2,2-pentafluoro-4-(methylthio)-5-phen-
ylp en t-3-en -5-ol (8a ): 1H NMR (400 MHz, CDCl3) δ 1.35 (3H,
t, J ) 7 Hz), 2.22 (3H, s), 2.97 (1H, d, J ) 9 Hz), 3.97-4.05
(1H, m), 4.19-4.26 (1H, m), 5.93 (1H, d, J ) 9 Hz), 7.23-7.39
(5H, m); 13C NMR (100 MHz, CDCl3) δ 15.30 (q), 16.61 (q),
68.80 (d), 69.25 (t, J C-F ) 4 Hz, OCH2), 112.98 (s, J C-F ) 38
and 259 Hz, CF2), 118.73 (s, J C-F ) 38 and 287 Hz, CF3), 125.65
(d × 2), 127.65 (d), 128.32 (d × 2), 139.61 (s), 140.37 (s), 143.14
(s, J C-F ) 24 Hz, 3-C); 19F NMR (376.4 MHz, CDCl3) δ -32.52
(1F, d, J ) 277 Hz, CF2), -30.74 (1F, d, J ) 2 and 277 Hz,
CF2), -5.35 (3F, t, J ) 2 Hz, CF3); MS m/z 342 (M+). Anal.
Calcd for C14H15F5O2S: C, 49.12; H, 4.42. Found: C, 49.18;
H, 4.49.
Exp er im en ta l Section 12
Gen er a l. 1H (400 MHz) and 13C (100 MHz) NMR spectra
were recorded in CDCl3 with TMS as the internal standard.
The 19F NMR (376.4 MHz) spectra were obtained in CDCl3
with trifluoroacetic acid as the external standard. The stereo-
chemistries of the products were determined by NOE experi-
ments.
P r ep a r a tion of (E)-2-Eth oxy-1,1,1-tr iflu or o-3-(p h en yl-
th io)-2-p r op en e (1). Typ ica l P r oced u r e. BuLi was added
dropwise to a THF (70 mL) solution of phenylthiomethyltri-
phenylphosphonium chloride15 (8.40 g, 20.0 mmol) at -38 °C,
and the reaction mixture was stirred for 30 min. Ethyl
trifluoroacetate (5.60 g, 40.0 mmol) was added to it. The whole
was stirred at room temperature for 3 days and poured into
(2E,5Z)-2-E t h oxy-1,1,1-t r iflu or o-7,7-d im et h yl-3,5-b is-
(p h en ylt h io)-4-(t r iflu or om et h yl)oct a -2,5-d ien -4-ol (13):
(15) Mukaiyama, T.; Fukuyama, S.; Kumamoto, T. Tetrahedron Lett.
1968, 3787. Van Leusen, A. M.; Reith, B. A.; Iedema, A. J . W.; Strating,
J . Recl. Trav. Chim. Pay-Bas, 1972, 91, 37. Wittig, G.; Schlosser, M.
Chem. Ber. 1961, 94, 1373.

Novel Perfluoroacyl Olefinations of Aldehydes
J . Org. Chem., Vol. 64, No. 14, 1999 5165
1H NMR (400 MHz, CDCl3) δ 1.08 (3H, s, J ) 7 Hz), 1.20 (9H,
s), 3.69-3.76 (2H, m), 4.31 (1H, brs), 6.95 (1H, brs), 7.16-
7.31 (10H, m); 13C NMR (100 MHz, CDCl3) δ 15.17 (q), 30.22
(q × 3), 35.99 (s), 68.90 (t), 81.55 (s, J C-F ) 27 Hz, 4-C), 120.65
(s, J C-F ) 278 Hz, CF3), 124.30 (s, J C-F ) 288 Hz, CF3), 124.50
(s), 126.58 (d), 126.66 (d), 127.39 (d × 2), 127.58 (d × 2), 129.13
(d × 2), 129.40 (d × 2), 130.22 (s, J C-F ) 3 Hz), 135.06 (s),
135.93 (s), 151.17 (s, J C-F ) 36 Hz, 2-C), 159.42 (d); 19F NMR
(376.4 MHz, CDCl3) δ 6.67 (3F, q, J ) 5 Hz, CF3), 19.15 (3F,
q, J ) 15 Hz, CF3); MS m/z 536 (M+). Anal. Calcd for
(Z)-2,2-Dieth oxy-1,1,1-tr iflu or o-3-(m eth ylth io)-4-p h en -
ylbu t-3-en e (18): 1H NMR (400 MHz, CDCl3) δ 1.30 (6H, t, J
) 7 Hz), 2.08 (3H, s), 3.63-3.77 (4H, m), 7.25-7.39 (4H, m),
7.75-7.77 (2H, m); 13C NMR (100 MHz, CDCl3) δ 15.29 (q ×
2), 18.55 (q), 59.33 (t × 2, J C-F ) 1 Hz), 100.16 (s, J C-F ) 30
Hz, 2-C), 120.49 (s, J C-F ) 292 Hz, CF3), 128.44 (d), 128.50 (d
× 2), 129.70 (d × 2), 132.40 (s), 135.90 (s), 138.97 (d, J C-F ) 1
Hz, 4-C); 19F NMR (376.4 MHz, CDCl3) δ -1.40 (3F, s, CF3);
MS m/z 320. Anal. Calcd for C15H19F3O2S: C, 56.24; H, 5.98.
Found: C, 56.43; H, 5.84.
C
25H26F6O2S2: C, 55.95; H, 4.88. Found: C, 56.17; H, 4.86.
(Z)-2-(Ben zylid en e)-3-et h oxy-3-(t r iflu or om et h yl)-3H -
ben zo[b]th iop h en e (19): 1H NMR (400 MHz, CDCl3) δ 1.23
(3H, t, J ) 7 Hz), 3.08-3.15 (1H, m), 3.42-3.49 (1H, m), 6.07
(1H, s), 6.95 (1H, brd, J ) 7 Hz), 7.10-7.19 (1H, m), 7.23-
7.27 (1H, m), 7.44-7.47 (4H, m), 7.61-7.62 (2H, m); 13C NMR
(100 MHz, CDCl3) δ 15.44 (q), 60.24 (t), 120.28 (d), 124.02 (s,
J C-F ) 285 Hz, CF3), 124.95 (d), 125.44 (d), 129.55 (d), 129.64
(d), 129.92 (d × 2), 130.61 (d), 131.01 (s), 135.10 (d × 2), 138.34
(s), 143.61 (s), 145.01 (s); 19F NMR (376.4 MHz, CDCl3) δ 0.78
(3F, s, CF3); MS m/z 336 (M+). Anal. Calcd for C18H15F3OS:
C, 64.27; H, 4.50. Found: C, 64.38; H, 4.58.
Isom er iza tion Rea ction s of Allylic Alcoh ols by p-
TsOH. Typ ica l P r oced u r e. A ClCH2CH2Cl (13 mL) solution
of (E)-2-ethoxy-1,1,1-trifluoro-4-phenyl-3-(phenylthio)but-2-en-
4-ol (5a ) (1.33 g, 3.98 mmol) and p-TsOH (0.98 g, 5.17 mmol)
was refluxed for 10 min. The reaction mixture was poured into
a saturated NaHCO3 (150 mL) solution, and the organic layer
was separated. The aqueous layer was extracted with CHCl3.
The combined organic layers were dried over MgSO4. The
solvent was removed under reduced pressure. The residue was
purified by a column chromatography on silica gel eluting with
AcOEt-hexane (1:40) to give (Z)-1,1,1-trifluoro-4-phenyl-3-
(phenylthio)but-3-en-2-one (9a ) (1.11 g, 91%) as a yellow oil.
(Z)-1,1,1-Tr iflu or o-4-p h en yl-3-(p h en ylth io)bu t-3-en -2-
on e (9a ): 1H NMR (400 MHz, CDCl3) δ 7.18-7.27 (5H, m),
7.37-7.48 (3H, m), 7.94-7.97 (2H, m), 8.09 (1H, s); 13C NMR
(100 MHz, CDCl3) δ 116.69 (s, J C-F ) 292 Hz, CF3), 127.02 (d
× 2), 128.69 (d × 2), 129.31 (d × 2), 131.76 (d × 2), 131.77 (d
× 2), 133.35 (s), 133.67 (s), 134.87 (s), 150.92 (d), 180.02 (s);
19F NMR (376.4 MHz, CDCl3) δ -7.07 (3F, s, CF3); MS m/z
308 (M+). Anal. Calcd for C16H11F3OS: C, 62.13; H, 3.91.
Found: C, 62.83; H, 3.75.
1-Eth oxy-2-(m eth ylth io)-1-(tr iflu or om eth yl)in den e (20):
1H NMR (400 MHz, CDCl3) δ 1.19 (3H, t, J ) 7 Hz), 2.48 (3H,
s), 3.03-3.10 (1H, m), 3.27-3.35 (1H, m), 6.41 (1H, s), 7.11-
7.16 (2H, m), 7.30-7.34 (1H, m), 7.46 (1H, brd, J ) 7 Hz); 13
C
NMR (100 MHz, CDCl3) δ -11.12 (q), 15.09 (q), 59.87 (t), 89.74
(s, J C-F ) 30 Hz), 119.72 (d), 123.74 (s, J C-F ) 285 Hz, CF3),
124.68 (d), 124.92 (d), 126.22 (d), 130.43 (d), 137.90 (s), 143.73
(s), 144.95 (s); 19F NMR (376.4 MHz, CDCl3) δ -1.37 (3F, s,
CF3); MS m/z 227 (M+ - OEt). Anal. Calcd for C13H13F3OS:
C, 56.92; H, 4.78. Found: C, 56.80; H, 4.85.
(Z)-1,1,1-Tr iflu or o-3-(m eth ylth io)-4-p h en ylbu t-3-en -2-
Syn th eses of 3-(Meth ylth io)- or 3-(P h en ylth io)-2-(tr i-
flu or om eth yl)-1,3-bu ta d ien es 21a -c a n d 22a -b. Typ ica l
P r oced u r e. Under an Ar atmosphere, BuLi (1.30 mL, 2.00
mmol) was added to a THF (5 mL) solution of methyltri-
phenylphosphonium bromide (0.71 g, 2.00 mmol) at -30 °C.
The mixture was stirred for 30 min and then cooled to -78
°C. A THF (1 mL) solution of (Z)-1,1,1-trifluoro-3-(methylthio)-
4-phenylbut-3-en-2-one (11a ) (0.25 g, 1.00 mmol) was added
dropwise to the mixture. The whole was stirred overnight at
room temperature. The workup procedure afforded (Z)-3-
(methylthio)-4-phenyl-2-(trifluoromethyl)buta-1,3-diene (21a )
(0.11 g, 44%) as a yellow oil.
1
on e (11a ): H NMR (400 MHz, CDCl3) δ 2.28 (3H, s), 7.46-
7.51 (3H, m), 7.87 (1H, s), 7.89-7.92 (2H, m); 13C NMR (100
MHz, CDCl3) δ 17.22 (q), 116.73 (s, J C-F ) 293 Hz, CF3), 128.80
(d × 2), 131.40 (d), 131.48 (s), 131.88 (d × 2), 133.86 (s), 148.22
(d), 179.53 (s, J C-F ) 34 Hz, CO); 19F NMR (376.4 MHz, CDCl3)
δ -7.97 (3F, s, CF3); MS m/z 246 (M+). Anal. Calcd for C11H9F3-
OS: C, 53.65; H, 3.68. Found: C, 53.72; H, 3.70.
(Z)-1,1,1,2,2-P en ta flu or o-4-(m eth ylth io)-5-p h en ylp en t-
1
4-en -3-on e (12a ): H NMR (400 MHz, CDCl3) δ 2.25 (3H, s),
7.43-7.50 (3H, m), 7.84 (1H, s), 7.84-7.90 (2H, m); 13C NMR
(100 MHz, CDCl3) δ 16.88 (q), 108.43 (s, J C-F ) 36 and 271
Hz, CF2), 118.06 (s, J C-F ) 34 and 288 Hz, CF3), 128.60 (d ×
2), 131.07 (d), 131.60 (d × 2), 132.35 (s), 133.69 (s), 146.98 (d,
J C-F ) 5 Hz, 5-C), 181.90 (s, J C-F ) 34 Hz, CO); 19F NMR (376.4
MHz, CDCl3) δ -35.73 (2F, s, CF2), -3.50 (3F, s, CF3); MS
m/z 296 (M+). Anal. Calcd for C12H9F5OS: C, 48.65; H, 3.06.
Found: C, 48.66; H, 3.09.
(Z)-5,5-Dim et h yl-3-(p h en ylt h io)-2-(t r iflu or om et h yl)-
h exa -1,3-d ien e (22a ): 1H NMR (400 MHz, CDCl3) δ 1.33 (9H,
s), 5.65 (1H, s), 5.73 (1H, d, J ) 2 Hz), 6.45 (1H, s), 7.12-7.26
(5H, m); 13C NMR (100 MHz, CDCl3) δ 30.60 (q × 3), 30.76 (s),
122.54 (t, J C-F ) 5 Hz, 1-C), 123.19 (s, J C-F ) 275 Hz, CF3),
125.97 (s), 126.48 (d), 129.12 (d × 2), 129.37 (d × 2), 135.15
(s), 137.87 (s, J C-F ) 29 Hz, 2-C), 152.90 (d); 19F NMR (376.4
MHz, CDCl3) δ -14.37 (3F, s, CF3); MS m/z 286 (M+). Anal.
Calcd for C15H17F3S: C, 62.92; H, 5.98. Found: C, 62.74; H,
6.04.
P r ep a r a tion s of 1,1,1-Tr iflu or o-3-bu ten -2-on e Dieth yl
Aceta ls 17 a n d 18. Typ ica l P r oced u r e. A dry EtOH (10.0
mL) solution of (E)-2-ethoxy-1,1,1-trifluoro-4-phenyl-3-(phen-
ylthio)but-2-en-4-ol (1.33 g, 3.75 mmol), ethyl orthoformate
(2.78 g, 18.8 mmol), and p-TsOH (0.14 g, 0.75 mmol) was
refluxed for 10 min. Et3N (3 drops) was added to a reaction
mixture. The workup procedure afforded the title compound
(1.03 g, 71%) as a pale yellow oil.
Ack n ow led gm en t. The support of a part of this
work by the Ministry of Education, Science and Culture,
J apan, is gratefully acknowledged.
(Z)-2,2-Die t h oxy-1,1,1-t r iflu or o-4-p h e n yl-3-(p h e n yl-
1
th io)bu t-3-en e (17): H NMR (400 MHz, CDCl3) δ 1.20 (6H,
t, J ) 7 Hz), 3.59-3.61 (2H, m), 3.62-3.74 (2H, m), 6.98-
7.02 (1H, m), 7.06-7.16 (2H, m), 7.17-7.23 (5H, m), 7.56 (1H,
s), 7.65-7.67 (2H, m); 13C NMR (100 MHz, CDCl3) δ 15.15
Su p p or tin g In for m a tion Ava ila ble: Characterization
data for the products 2-4, 5a -c, 5e, 6a -c, 7b-c, 8b, 9b-e,
10a -c, 11b-c, 15, 21a -c, and 22b and 1H NMR spectra,
complete with peak assignments of other products and full lists
of the IR spectral data. This material is available free of charge
via the Internet at http://pubs.acs.org.
(qx2), 59.29 (tx2), 100.02 (s, J C-F ) 30 Hz, 2-C), 122.78 (s, J C
-F
) 292 Hz, CF3), 125.66 (d), 127.34 (s), 128.17 (d × 4), 128.64
(d × 2), 128.89 (d), 130.03 (d × 2), 135.04 (s), 135.69 (s), 142.37
(d); 19F NMR (376.4 MHz, CDCl3) δ -2.59 (3F, s, CF3); MS
m/z 382. Anal. Calcd for C20H21F3O2S: C, 62.81; H, 5.53.
Found: C, 62.83; H, 5.49.
J O990282P