CsF-Catalyzed Trifluoromethylation
J . Org. Chem., Vol. 64, No. 8, 1999 2875
relative to the standard: CFCl3 for 19F, and trimethylsilane/
CHCl3 for 1H and 13C NMR spectra. IR spectra were recorded
using NaCl plates. Mass spectra were measured at 70 ev.
Ma ter ia ls. (Trifluoromethyl)trimethylsilane (TMS-CF3)
was prepared by the literature procedure.25 Cesium fluoride
was purchased from Aldrich and was finely powdered and used
directly from the oven, where it was stored at 200 °C.
Benzonitrile and ethylene glycol dimethyl ether were pur-
chased from Aldrich and used as received. All of the substrates
(esters, aldehydes, and ketones) were purified by distillation/
recrystallization before use.
Ta ble 2. Cesiu m F lu or id e Ca ta lyzed
Tr iflu or om eth yla tion a of Ald eh yd es a n d Keton es a t
Room Tem p er a tu r e
Gen er a l Tr iflu or om eth yla tion P r oced u r e for Ester s.
At room temperature, CsF (0.1 mM) was added to a mixture
of ester (10 mM) and TMS-CF3 (10.25 mM). The reaction was
monitored by 19F NMR. After complete disappearance of the
TMS-CF3 resonance (-67.4 ppm) hydrolysis was carried out
over 3 h by using 4 N HCl (4 mL). The resulting product was
extracted with ether (30 mL). After removing the ether the
trifluoromethylated ketones were found in good to excellent
yields (Table 1).
1,1,1-Tr iflu or o-4-p h en yl-2-bu ta n on e (9c): Colorless liq-
1
uid; IR (film) 1760 (s, CdO) cm1; H NMR (CDCl3) δ 3.10 (m,
4H), 7.21 (m, 5H); 19F NMR (CDCl3) δ -80.2 (s); MS (EI) m/z
(species, rel int) 202 (M+, 85), 133 (M+ - CF3, 100), 105
(PhCH2CH2+, 30), 91 (PhCH2+, 60); HRMS calcd for C10H9F3O
(M+) 202.0605, found 202.0603.
tr a n s-1,1,1-Tr iflu or o-4-p h en yl-3-bu ten -2-on e (9e): Col-
1
orless liquid; IR (neat) 1608 (s, CdO) cm-1; H NMR (CDCl3)
δ 7.39 (d, 1H, J ) 16 Hz)), 7.65 (m, 5H); 8.10 (d, 1H, J ) 16
Hz); 19F NMR (CDCl3) δ -85.0 (s); MS (EI) m/z (species, rel
int) 200 (M+, 80), 131 (M+ - CF3, 100), 103 (PhCHdCH+, 60),
77 (C6H5+, 22).
1,1,1-Tr iflu or o-4-p h en yl-3-bu tyn -2-eth oxy-2-tr im eth yl-
silyl eth er (8f): Yellow liquid; 95% yield; 1H NMR (CDCl3) δ
0.31 (s, 9H), 1.30 (t, J ) 7 Hz), 3.85 (q, J ) 3.5 Hz), 7.40 (m,
5H); 13C NMR (CDCl3) δ 1.08, 15.01, 60.60, 81.10, 87.02, 91.00
(q, J C-C-F ) 28.5 Ηz), 122.50 (q, J C-F ) 286), 128.48, 129.62,
131.84; 19F NMR (CDCl3) δ -84.42 (s); MS (EI) m/z (species,
rel int) 297 (M+ - F, 10), 271 (M+ - OEt, 47), 247 (M+ - CF3,
100), 129 (PhCdCCO+, 9), 73 (SiMe3+, 3).
other products were isolated. Known compounds were
identified by comparing spectral data with the spectral
data reported in the literature.
Although the effect of solvent has been examined,2 we
have found that no solvent was required for the reaction
of low boiling liquid substrates. When necessary we used
ethylene glycol dimethyl ether as the solvent (with solids
and some high boiling liquids) and benzonitrile for low
boiling substrates. The use of these solvents allowed ease
of separation of the desired products from the reaction
mixture.
1,1,1-Tr iflu or o-4-p h en yl-3-bu tyn -2-on e (9f): Yellow liq-
uid; 87% yield; IR (film) 2250 (s, CdC), 1760 (s, CdO) cm-1
;
1H NMR (CDCl3) δ 7.52 (m, 5H); 13C NMR (CDCl3) δ 83.34,
100.48, 114.86 (q, J C-F ) 286.5 Ηz), 118.07, 128.7, 132.48,
133.90, 168.00 (q, J C-F ) 28.0 Hz); 19F NMR δ -80.17 (s); MS
(EI) m/z (species, rel int) 198 (M+, 4), 129 (M+ - CF3, 100),
101 (M+ - COCF3, 10).
Gen er a l Tr iflu or om eth yla tion P r oced u r e for Su lfon ic,
Su lfin ic, a n d Selen ic Ester s. Ester (10.0 mM) and TMS-
CF3 (10.25 mM) were taken in a Schlenk flask, and powdered
CsF (0.1 mM) was added at room temperature. The reaction
mixture was heated until the 19F NMR spectrum of the mixture
showed the complete disappearance of TMS-CF3 resonance
(67.4). The product was distilled from the reaction mixture and
identified by comparing the spectral data reported in the
literature.
Con clu sion
A general, efficient, CsF-catalyzed process for trifluo-
romethylation of carboxylic, sulfonic, sulfinic, and selenic
esters was developed. At room temperature (25 °C), with
catalytic amounts of cesium fluoride, carboxylic esters
were found to react to give the silyl ether intermediates,
which afforded the trifluoromethyl ketones after hydroly-
sis. Sulfonic, sulfinic, and selenic esters also show good
reactivity giving trifluoromethylated compounds. The
trifluoromethylation method was also applied to alde-
hydes and ketones, which were transformed to trifluo-
romethyl silyl ether intermediates and afforded trifluo-
romethylated alcohols in excellent yields after acid
hydrolysis. We have successfully reacted TMS-CF3 with
esters and other substrates that have been reported to
be unreactive in the literature.
P h en yl tr iflu or om eth yl su lfoxid e: Colorless liquid; 1H
NMR (CDCl3) δ 8.33-7.56 (m, 5H), 19F NMR (CDCl3) δ -78.5
(q, J ) 12 Hz).
Meth yl tr iflu or om eth yl su lfoxid e: 1H NMR (CDCl3) δ
3.10 (q, J H-F ) 1), 19F NMR (CDCl3) δ -79.6 (q, J ) 13).
Gen er a l Tr iflu or om eth yla tion P r oced u r e for Ald e-
h yd es a n d Keton es. In a typical reaction, the aldehyde or
ketone (10 mM) and (trifluoromethyl)trimethylsilane (10.25
mM) were placed in a flask, and CsF (0.0015 g, 0.1 mM) was
added as solid. The reaction was exothermic, and the solution
changed from colorless to yellowish. It was stirred at 25 °C
for 3 h and was hydrolyzed with 4 N HCl solution (6 mL) for
2 h at room temperature. The reaction mixture was diluted
with water (20 mL), and the products were extracted with
ether (25 mL). The ether extract was dried over anhydrous
MgSO4 and filtered. Removal of ether at reduced pressure gave
the products in good yield.
Exp er im en ta l Section
1
Gen er a l Com m en ts. H, 13C, and 19F NMR spectra were
recorded in CDCl3 on a spectrometer operating at 200, 50, and
188 MHz, respectively. Chemical shifts are reported in ppm
tr a n s-1,1,1-Tr iflu or o-4-p h en yl-3-bu ten -2-ol: Colorless
solid; IR (neat) 3350 (broad, OH), 1600 (s, CdC) cm-1; 1H NMR