152
Y.S. Sokeirik et al. / Journal of Fluorine Chemistry 127 (2006) 150–152
Table 3
evaporated under vacuum. The residue was purified with a column chro-
matography (SiO2, 5% to 20% Et2O in hexane) to give 581 mg (38%) of
compound 4. Compound 4: colorless crystals from Et2O–hexane. Mp 104–
105 8C. 1H NMR (CDCl3) d: 7.64–7.62 (1H, m), 7.42–7.36 (2H, m), 7.20–
7.16 (1H, m), 7.11 (1H, s, disappeared with D2O), 5.38 (1H, m), 4.79 (1H, s,
disappeared with D2O), 1.50 (9H, s). 19F NMR (DMSO) d: À19.52 to
À20.24 (3F, m), À52.52 (1F, m), À59.17 to À62.41 (9F, m), À64.39 to
À65.37 (2F, m). MS m/z: 591 (M+). HRMS Calcd. for C19H16F15NO3:
591.089 (M+), Found: 591.090. IR (KBr) cmÀ1: 3384, 1686, 1212, 1148.
[4] L.S. Chen, G.J. Chen, C. Tamborski, J. Fluorine Chem. 18 (1981) 117–
129.
Reaction of perfluoroalkyl phenyl ketones with lithium isopropoxide
Substrate
Reducing
agent
Temperature
Time
(h)
Yield
(%)a
(8C)
C6H5COC3F7
C6H5COC7F15
isoPrOLi (2eq)
isoPrOLi (2eq)
80
80
6
6
85
90
a
Isolated yield.
show that lithium isopropoxide is a good reducing agents for
bulky perfluoroalkyl ketones.
[5] Experimental details of Run 2 in Table 2: to a solution of freshly prepared
EtOLi (59.8 mg, 1.15 mmol) in 3 mL dry Et2O, 2,2,2-trifluoroacetophe-
none (100 mg, 0.57 mmol) was added at room temperature under argon
atmosphere. The reaction mixture was stirred at room temperature for
96 h. The mixture was cooled in an ice bath and quenched with 2 M HCl,
and extracted by Et2O three times. The combined organic extracts were
dried over MgSO4 and evaporated under vacuum. The mixture was
separated by a flash column chromatography to give about 65 mg of crude
2,2,2-trifluoro-1-phenylethanol and 15 mg of benzoic acid. The crude
2,2,2-trifluoro-1-phenylethanol was purified with a column chromatogra-
phy (SiO2, 5% to 10% Et2O in hexane) for spectral analysis. 2,2,2-
Trifluoro-1-phenylethanol: 1H NMR (CDCl3) d: 7.38–7.71 (5H, m),
4.98–5.06 (1H, m), 2.62 (1H, s, disappeared with D2O). 19F NMR (CDCl3)
d: À15.25 (3F, d, J = 6.2 Hz). IR (neat) cmÀ1: 3450. These data were
consistent with the authentic sample.
3. Conclusion
We observed abnormal reaction of aryllithiums with ethyl
perfluoroalkanoate, where aryl perfluoroalkyl carbinols were
obtained. Detailed examination of this reaction showed that
lithium ethoxide caused the reduction of the primary products,
aryl perfluoroalkyl ketone. This reduction was found to be
applicable for some aromatic perfluoroalkylketones. The
experimental procedure is simple and the yields are moderate
to excellent. So, this reaction can be used for synthesis of aryl
perfluoroalkyl carbinols.
[6] E.C. Ashby, A.B. Goel, J.N. Argyropoulos, Tetrahedron Lett. 21 (1982)
2273–2276.
[7] Experimental details of Run 12 in Table 2: in a dry flask fitted with a
calcium chloride guard tube, 2,2,2-trifluoroacetophenone (100 mg,
0.57 mmol) was added into a solution of freshly prepared isoPrOLi
(75.9 mg, 1.15 mmol) in dry toluene (3 mL) at room temperature. The
mixture was heated gradually to 80 8C. After disappearance of the peak of
the starting material on GLC, the mixture was cooled by an ice bath and the
reaction was quenched with saturated NH4Cl. The two phases were
separated, and the aqueous phase was extracted with Et2O. The combined
organic layer was dried over MgSO4 and evaporated under vacuum. The
residue was separated by a column chromatography (SiO2, 5% Et2O in
hexane) to yield about 77 mg of 2,2,2-trifluoro-1-phenylethanol. By eluat-
ing with 10% Et2O in hexane, the aldol product, 5,5,5-trifluoro-4-hydroxy-
4-phenylpentan-2-one, (about 30 mg) was obtained. 5,5,5-Trifluoro-4-
hydroxy-4-phenylpentan-2-one (purified by further chromatography): 1H
NMR (CDCl3) d: 7.58–7.54 (2H, m), 7.42–7.35 (3H, m), 5.43 (1H, s,
disappeared with D2O), 3.37 (1H, d, J = 18 Hz), 3.21 (1H, d, J = 18 Hz),
2.21 (3H, s). 19F NMR (CDCl3) d: À17.16 (s, CF3). MS m/z 232 (M+).
HRMS Calcd. for C12H15F3O: 232.071 (M+), Found: 232.070. IR (neat)
cmÀ1: 3500, 1712.
References
[1] Concerning the synthesis and application of chiral ligands containing
perfluoroalkyl groups by our group, see: M. Omote, Y. Nishimura, K.
Sato, A. Ando, I. Kumadaki, J. Fluorine Chem. 126 (2005) 407–409, and
references therein.
[2] Detailed description of the first reaction in Table 1; To a stirred solution of
tert-butyl N-(2-bromophenyl)carbamate (272 mg, 1 mmol) in 5 mL dry
Et2O at À80 8C was added over a period of 30 min a hexane solution of n-
BuLi (1.64 mL, 1.58 M solution, 2.6 mmol). After 2 h’s stirring at the same
temperature, ethyl pentadecafluorooctanoate (486 mg, 1.1 mmol) was
added slowly. The resulting mixture is kept under stirring at the same
temperature for 24 h. The reaction mixture is quenched with 2 M HCl and
stirred at room temperature for 1 h. After separation of the two phases, the
aqueous phase was extracted with Et2O three times. The combined organic
extracts were dried over MgSO4 and evaporated under vacuum to yield an
oily mass, which was purified with a column chromatography (SiO2, 5%
Et2O in hexane) to yield 206 mg (35%) of compound 3 and 82 mg (33%) of
1
[8] Detailed description of the second reaction in Table 3: in a dry flask fitted
with calcium chloride guard tube, 1-phenylpentadecafluorooctan-1-one
(100 mg, 0.21 mmol) was added to a solution of freshly prepared isoPrOLi
(27.8 mg, 0.42 mmol) in dry toluene (3 mL) at room temperature. The
mixture was heated gradually to 80 8C. After disappearance of the peak of
the starting material on GLC, the mixture was cooled in an ice bath and the
reaction was quenched with saturated NH4Cl. The two phases were
separated, and the aqueous phase was extracted with Et2O. The combined
organic layer was dried over MgSO4, and evaporated under vacuum. The
residue was purified by a column chromatography (SiO2, 5% Et2O in
hexane) to yield 90 mg (90%) of 1-phenyl-1H-perfluorooctan-1-ol as white
solid, which was recrystallized from hexane to give colorless crystals. M.p.
60 8C. 1H NMR (CDCl3) d: 7.49–7.36 (5H, m), 5.23–5.18 (1H, m), 2.53
(1H, s, disappeared with D2O). 19F NMR (CDCl3) d: À18.36 (3F, m), À53.50
(1F, m), À57.10 to À60.35 (8F, m), À62.50 (2F, m), À63.25 (1F;m). IR(neat)
cmÀ1: 3480. A similar reaction of 1-phenylperfluorobutan-1-one gave
1-phenyl-1H-perfluorobutan-1-ol: colorless oil. 1HNMR (CDCl3) d: 7.48–
7.39 (5H, m), 5.06-4.98 (1H, m), 2.62 (1H, s, disappeared with D2O). 19F
NMR (CDCl3) d: À18.75 (3F, m), À55.31 (1F, m), À62.21 (2F, m), À64.52
(1F, m). IR (neat) cmÀ1: 3450.
compound 5. Compound 3. H NMR (400 MHz, CDCl3) d: 10.15 (1H, s,
disappeared with D2O), 8.52–8.50 (1H, m), 7.94–7.88 (1H, m), 7.66–7.54
(1H, m), 7.04–6.98 (1H, m), 1.46 (9H, s). 19F NMR (56.4 MHz, CDCl3) d
(from C6H5CF3): À17.30 to À18.50 (3F, m), À58.22 to À62.53 (10F, m),
À63.12 to À64.17 (2F, m). HRMS Calcd. for C19H14F15NO3: 589.073 (M+ ),
Found: 589.074. IR (neat) cmÀ1: 3325, 1744, 1678, 1242. Compound 5. 1H
NMR (CDCl3) d: 7.67–7.66 (1H, m), 7.12–7.05 (2H, m), 6. 96–6. 92 (1H, m),
6. 23 (1H, s, disappeared with D2O), 2.25 (2H, t, J = 7.5 Hz), 1.52–1.44
(11H, m), 1.31 (2H, sex, J = 7.5 Hz), 0. 87 (3H, t, J = 7.3 Hz). MS m/z 249
(M+). HRMS Calcd. for C15H23NO2: 249.173 (M+ ), Found: 249.173. IR
(neat) cmÀ1: 3360, 1706.
[3] Detailed description of Run 3 in Table 1: a solution of tert-BuLi in pentane
(4.17 mL, 1.49 M solution, 6.21 mmol) was added slowly to a stirred
solution of tert-butyl N-phenylcarbamate (500 mg, 2.59 mmol) in dry
Et2O (10 mL) at 0 8C. The solution was stirred at 0 8C for further 2 h.
To this solution was added ethyl pentadecafluorooctanoate (1259 mg,
2.85 mmol). The resulting mixture was stirred at 0 8C for additional 2 h
and at room temperature for 24 h. The reaction was quenched with 2 M
HCl. The organic phase was separated and the acidic phase was extracted
with Et2O. The combined organic extracts were dried over MgSO4, and