1102
R. Mogi et al. / Journal of Fluorine Chemistry 128 (2007) 1098–1103
Table 6
The reaction between 4-fluorobenzaldehyde (19l) and TESCF2CH3 (15)
15
19l
Selectivity (%)a
20l
21l
1
2
1.2 equiv.
2.2 equiv.
1.0 equiv.
1.0 equiv.
60
40
0
100
The reactions were carried out using 19l 1.0 equiv. and 15 with CsF 0.1 equiv. in DMF at 110 8C for 18 h.
a
Selectivities were estimated from 1H NMR of reaction mixtures.
from Solvent Technologies. NMR spectra were obtained on a
Varian AS-400 spectrometer using CDCl3 as a solvent, TMS as
argon was added 26 mg (0.17 mmol) of 2-naphthaldehyde
19a. To the reaction mixture under stirring was added,
36 mg (0.2 mmol) of (1,1-difluoroethyl)triethylsilane 15
through a syringe at room temperature followed by heating
at 110 8C for 18 h. The reaction mixture was analyzed by
NMR, and confirmed that 2,2-difluoro-1-(naphthalen-7-
yl)propan-1-ol 20a was formed. The yield based on 1H
NMR analyses was 71%. 1H NMR (CDCl3): d 1.54 (dd,
J = 18.9, 18.9 Hz, 3H), 5.03 (dd, J = 9.4, 9.4 Hz, 1H), 7.48–
7.56 (m), 7.83–7.93 (m). 19F NMR (CDCl3): d ꢀ101.1 (dqd,
J = 246, 19.8, 9.2 Hz, 1F), ꢀ100.2 (dqd, J = 246, 19.8,
9.2 Hz, 1F). MS (m/z): 222 (M+), 157 (M+ ꢀ CF2CH3), 129,
2,2-Difluoro-1-phenylpropan-1-ol 20b. 1H NMR (CDCl3): d
1.51 (dd, J = 18.9, 18.9 Hz, 3H), 4.86 (dd, J = 9.5, 9.5 Hz, 1H),
7.34–7.40 (m, 3H), 7.44–7.48 (m, 2H). 19F NMR (CDCl3): d
ꢀ101.6 (dqd, J = 247, 18.3, 9.2 Hz, 1F), ꢀ100.6 (dqd, J = 247,
18.3, 9.2 Hz, 1F). MS (m/z): 172 (M+), 107 (M+ ꢀ CF2CH3),
77.
1
an internal standard for H and 13C, and CFCl3 as an internal
standard for 19F. GCMS data were recorded on a Thermo
Finnigan TRACE GC/DSQ spectrometer at 70 eV.
3.2. Typical procedure for preparation of 1,1-
difluoroethylsilanes
Into
a flame-dried Schlenk flask containing 2.92 g
(120 mmol) of magnesium granule and 20 ml of THF/HMPA
(1:1 volume) mixture under nitrogen was added 12.06 g
(80 mmol) of triethylsilyl chloride 14. The mixture was stirred
in an ice bath and a solution of 4.12 g (20 mmol) of 1,1-
difluoroethyl phenyl sulfone 6 in 40 ml of THF/HMPA (1:1
volume) was added drop-wise through a dropping funnel. After
1 h, 120 ml of cold satd. NaHCO3 aq was added, and the
solution was extracted with ether (3 ꢂ 120 ml). The ether phase
was washed with 120 ml of water, and dried over anhydrous
magnesium sulfate. The solvent was removed under vacuum,
11.22 g of white oil was obtained. The crude product contained
TES–O–TES 17 and TESOH 18, and purified by silica gel
column chromatography (hexane). Resulting colorless oil still
contained TES–O–TES 17, and was purified by vacuum
distillation to give 1.22 g (35% yield) of (1,1-difluoroethyl)-
+
128, 127, 65 (C2F5 ).
2,2-Difluoro-1-(4-ethylphenyl)propan-1-ol 20c. 1H NMR
(CDCl3): d 1.24 (t, J = 7.6 Hz, 3H), 1.52 (dd, J = 19.0, 19.0 Hz,
3H), 2.65 (q, J = 7.6 Hz, 2H), 4.82 (dd, J = 9.7, 9.7 Hz, 1H),
7.20 (d, J = 8.1 Hz, 2H), 7.35 (d, J = 8.1 Hz, 2H). 19F NMR
(CDCl3): d ꢀ101.7 (dqd, J = 246, 18.3, 9.2 Hz, 1F), ꢀ100.7
(dqd, J = 246, 18.3, 9.2 Hz, 1F). MS (m/z) 200 (M+), 135
(M+ ꢀ CF2CH3), 79.
1
triethylsilane 15, bp = 30–32 8C/10 Torr. H NMR (CDCl3): d
0.71 (q, J = 8.1 Hz, 6H), 1.02 (t, J = 8.1 Hz, 9H), 1.55 (t,
J = 24.4 Hz, 3H). 19F NMR (CDCl3): d ꢀ99.9 (q, J = 24.4 Hz).
13C NMR (CDCl3): d 1.0 (s), 7.0 (s), 23.8 (t, J = 22.9 Hz), 130.5
(t, J = 256.3 Hz). MS (m/z): 115 (M+ ꢀ CF2CH3), 87.
(1,1-Difluoroethyl)trimethylsilane (8): Its formation was
only confirmed by analyzing the NMR spectra of reaction
mixture. 1H NMR (CDCl3): d 0.16 (s, 9H), 1.53 (t, J = 24.0 Hz,
3H). 19F NMR (CDCl3): d ꢀ106.2 (q, J = 24.4 Hz).
2,2-Difluoro-1-(4-methoxyphenyl)propan-1-ol 20d. 1H
NMR (CDCl3): d 1.51 (dd, J = 18.9, 18.9 Hz, 3H), 3.81 (s,
3H), 4.80 (dd, J = 9.7, 9.7 Hz, 1H), 6.91 (m, 2H), 7.37 (m, 2H).
19F NMR (CDCl3): d ꢀ101.8 (dqd, J = 246, 18.3, 9.2 Hz, 1F),
ꢀ101.1 (dqd, J = 246, 18.3, 9.2 Hz, 1F). MS (m/z): 202 (M+),
137 (M+ ꢀ CF2CH3), 109, 94, 77.
1
2,2-Difluoro-1-(4-bromophenyl)propan-1-ol 20e. H NMR
(CDCl3): d 1.50 (dd, J = 18.9, 18.9 Hz, 3H), 4.82 (dd, J = 9.2,
9.2 Hz, 1H), 7.34 (m, 2H), 7.50 (m, 2H). 19F NMR (CDCl3): d
ꢀ101.7 (dqd, J = 249, 18.3, 9.2 Hz, 1F), ꢀ100.2 (dqd, J = 249,
18.3, 9.2 Hz, 1F). MS (m/z): 252, 250 (M+), 187, 185
(M+ ꢀ CF2CH3), 159, 105, 77.
3.3. Typical procedure for the introduction of 1,1-
difluoroethyl group into carbonyl compounds
Into a flame-dried round bottom flask containing 3 mg
(0.02 mmol) of cesium fluoride and 0.5 ml of DMF under
4,4-Difluoro-1-phenylpent-1-en-3-ol 20i. 1H NMR (CDCl3):
d 1.64 (dd, J = 18.9, 18.9 Hz, 3H), 4.45 (ddd, J = 9.3, 9.3,