7034 J . Org. Chem., Vol. 66, No. 21, 2001
Dawood et al.
) 50.15, 7.92 Hz), 5.93 (ddd, 1H, J ) 43.22, 21.44, 1.89 Hz),
7.23-7.42 (m, 4H), 7.52-7.60 (m, 3H), 8.14 (d, 1H, J ) 7.91
Hz); 19F NMR δ -98.15 (dddd, 1F, J ) 50.56, 21.14, 10.11,
1.84 Hz), -109.10 (dt, 1F, J ) 43.20, 10.11 Hz), -111.94 (m,
1F); MS m/e 342 (M+), 322 (M+ - HF), 180, 136, 108. Anal.
Calcd for C16H10ClF3SO: C, 56.07; H, 2.94. Found: C, 55.96;
H, 2.82.
benzylidene-2-fluoro-2,3-dihydrothiochroman-4-ones 3.
This is the first report of successful stereoselective
electrochemical direct R-fluorination of fused type, sulfur-
containing heterocyclic compounds.
Exp er im en ta l Section
3-(4-Ch lor ob en zyl)-2,3-d iflu or o-2,3-d ih yd r ot h ioch r o-
m a n -4-on e (6). Mp 136-137 °C; H NMR δ 3.32 (d, 2H, J )
3-Benzylidene-2,3-dihydrothiochroman-4-one and 3-ben-
zylthiochromone derivatives 1a ,b and 2 were synthesized
according to procedures reported in the literature.21,22
An odic Flu or in ation of Th ioch r om an -4-on e an d 1-Th io-
ch r om on e Der iva tives. Electrolysis was conducted at a
platinum anode and cathode (2 × 2 cm2) in 0.3 M solution of
a fluoride salt in dimethoxyethane (30 mL) containing thio-
chromanone 1 or thiochromone 2 derivative (1 mmol) by using
an H-type divided cell with a glass diaphragm under a nitrogen
atmosphere at an ambient temperature. Constant current (6
mA cm-2) or controlled potential was applied until a complete
consumption of the starting substrate was achieved (monitored
by TLC and GC-MS). After the electrolysis, the resulting
electrolytic solution was passed through a short column of
silica gel using ethyl acetate as eluent. The collected solution
was evaporated under vacuum. Then, the yield of the fluori-
nated product was calculated by means of 19F NMR by using
a known amount of monofluorobenzene as an internal stan-
dard. The yield was calculated on the basis of the integral
ratios between the monofluorobenzene and the fluorinated
product. After that, the product was isolated by column
chromatography on silica gel using a hexane/ethyl acetate
eluent (5:1).
1
21.76 Hz), 5.63 (dd, 1H, J ) 49.79, 6.59 Hz), 7.25-7.38 (m,
6H), 7.57 (ddd, 1H, J ) 8.90, 7.91, 1.48 Hz), 8.15 (dd, 1H, J )
7.91, 1.48 Hz); 19F NMR δ -94.62 (m, 1F), -100.24 (dd, 1F, J
) 49.94, 20.34 Hz); MS (FAB+) (m/e) 325 (M+ + H), 304, 289,
197, 154, 126. HRMS (FAB+): Calcd for C16H12ClF2OS:
325.0265. Found: 325.0320. Anal. Calcd for C16H11ClF2SO: C,
59.17; H, 3.41; S, 9.87. Found: C, 58.93; H, 3.46; S, 9.87.
3-(4-Ch lor oben zyliden e)-2-(1-piper idyl)-2,3-dih ydr oth io-
ch r om a n -4-on e (8). To a solution of 2-fluorothiochroman-4-
one derivative 3b (0.152 g, 0.5 mmol) in acetonitrile (10 mL)
was added piperidine (0.1 mL, 1 mmol). The reaction mixture
was stirred at room temperature for 12 h. The solvent was
evaporated under vacuum, and the residue was chromato-
graphed using hexane/ethyl acetate (3:1) as eluent to afford
1
0.147 g (80%) of pure 8. Mp 46-47 °C; H NMR δ 1.44-1.58
(m, 6H), 2.32-2.43 (m, 4H), 4.87 (s, 1H), 7.23 (d, 2H, J ) 8.24
Hz), 7.37 (d, 2H, J ) 8.24 Hz), 7.47-7.58 (m, 3H), 8.31 (s, 1H),
8.49 (d, 1H, J ) 7.58 Hz); 13C NMR (DEPT) δ 24.65, 26.33,
53.03 (CH2), 67.84, 126.31, 127.40, 128.25, 128.84, 129.72,
130.88, 134.54 (CH), 131.79, 132.42, 136.75, 139.41, 161.57,
178.03 (C); MS m/e 369 (M+), 326, 312, 286, 250, 221, 149, 108,
84. Anal. Calcd for C21H20ClNSO: C, 68.19; H, 5.45; N, 3.79;
S, 8.67. Found: C, 67.98; H, 5.65; N, 3.60; S, 8.49.
(E)-3-Ben zylid en e-2,3-d ih yd r o-2-flu or oth ioch r om a n -4-
on e (3a ). Mp 64-65 °C; 1H NMR δ 6.80 (d, 1H, J ) 45.86
Hz), 7.30-7.49 (m, 8H), 8.02 (s, 1H), 8.43 (dd, 1H, J ) 7.58, 1
Hz); 13C NMR (DEPT) δ 90.26 (d, CH, J ) 173.30 Hz), 126.38,
126.56, 126.65, 127.67, 128.18, 128.32, 128.55, 128.61, 131.32,
131.46 (CH), 134.43, 134.74, 136.64, 137.79, 177.26 (C); 19F
NMR δ -98.30 (d, J ) 45.96 Hz); MS m/e 270 (M+), 249, 238,
221, 108. Anal. Calcd for C16H11FSO: C, 71.09; H, 4.10.
Found: C, 71.09; 4.37.
2,3-Diflu or o-3-(R-flu or o-4-ch lor oben zyl)-2,3-dih ydr oth io-
ch r om a n -4-on e-1,1-d ioxid e (9). A mixture of the trifluo-
rothiochroman-4-one derivative 3b (0.171 g, 0.5 mmol) and
m-chloroperbenzoic acid (0.207 g, 1.2 mmol) in dichlo-
romethane (20 mL) was stirred at room temperature for 24 h.
The reaction mixture was diluted with water, and the product
was extracted with dichloromethane. The organic phase was
collected, washed with aqueous Na2CO3 solution, then dried
over anhydrous Na2SO4, and filtered. The filtrate was evapo-
rated under reduced pressure, and the solid product was
recrystallized from ethanol to give 0.167 g (89% yield) of pure
trifluorosulfone 9. Mp 173-175 °C; 1H NMR δ 5.22 (dd, 1H, J
) 48.30, 6.60 Hz), 6.30 (dd, 1H, J ) 43.03, 24.24 Hz), 7.46 (d,
2H, J ) 8.58 Hz), 7.63 (d, 2H, J ) 8.58 Hz), 7.90-8.12 (m,
3H), 8.34 (d, 1H, J ) 7.92 Hz); 19F NMR δ -101.69 (m, 1F),
-107.71 (dt, 1F, J ) 43.20, 8.27 Hz), -109.42 (ddd, 1F, J )
47.80, 8.27, 2.76 Hz); MS (FAB+) m/e 375 (M+ + H), 359, 307,
289, 273, 242, 187, 154, 136, 107. Anal. Calcd for C16H10ClF3-
SO3: C, 51.28; H, 2.69. Found: C, 51.36; H, 2.96.
(E)-3-(4-Ch lor oben zylid en e)-2,3-d ih yd r o-2-flu or oth io-
1
ch r om a n -4-on e (3b). Mp 81-82 °C; H NMR δ 6.76 (d, 1H,
J ) 45.53 Hz), 7.32 (d, 2H, J ) 8.25 Hz), 7.42 (d, 2H, J ) 8.25
Hz), 7.50-7.62 (m, 3H), 8.10 (s, 1H), 8.49 (d, 1H, J ) 7.59
Hz); 19F NMR δ -99.39 (d, J ) 45.97 Hz); MS m/e 304 (M+),
285, 249, 221, 167, 149, 108. Anal. Calcd for C16H10ClFSO: C,
63.06; H, 3.31. Found: C, 63.07; 3.56.
2,3-Diflu or o-3-(R-flu or ob en zyl)-2,3-d ih yd r ot h ioch r o-
m a n -4-on e (4a ). Yellow oil; 1H NMR δ 5.38 (dd, 1H, J ) 50.15,
7.92 Hz), 6.07 (ddd, 1H, J ) 43.38, 22.10, 1.89 Hz), 7.24-7.61
(m, 8H), 8.16 (dd, 1H, J ) 7.92, 1.32 Hz); 19F NMR δ -98.14
(dddd, 1F, J ) 50.56, 21.14, 10.11, 1.84 Hz), -109.24 (dt, 1F,
J ) 43.20, 10.11 Hz), -112.15 (m, 1F); MS m/e 308 (M+), 288
(M+ - HF), 180, 136, 109. Anal. Calcd for C16H11F3SO: C,
62.33; H, 3.60. Found: C, 62.30; H, 3.64.
Ack n ow led gm en t. We are grateful to the J apan
Society for the Promotion of Science (J SPS) for the
financial support (Grant-in-Aid for Scientific Research
No. 1299307). K.M.D. is greatly indebted to the J SPS
for a postdoctoral fellowship (1999-2001).
2,3-Diflu or o-3-(R-flu or o-4-ch lor oben zyl)-2,3-dih ydr oth io-
1
ch r om a n -4-on e (4b). Yellow oil; H NMR δ 5.39 (dd, 1H, J
(21) Levai, A.; Schag, J . B. Pharmazie 1979, 34, 11.
(22) Levai, A.; Szabo, Z. Bull. Soc. Chim. Fr. 1991, 128, 976.
J O0104936