4640
F. Zhang et al. / Tetrahedron 63 (2007) 4636–4641
1
and environmentally friendly route to prepare b-hydroxy-b-
trifluoromethyl carbonyl compounds in good to excellent
yields. The key step for the catalytic aldol reaction seemed
to be the formation of enamine intermediates. The utility
of nonpolar or weakly polar solvents would be helpful for
the reaction.
in dichloromethane); H NMR (TMS, CDCl ): d 4.55 (1H,
3
dq, J ¼7.2 Hz, J ¼1.6 Hz, CHCF ), 3.41 (1H, br s, OH),
1
2
3
2.36–2.45 (2H, m), 2.07–2.20 (4H, m), 1.74–1.86 (1H, m);
C NMR (100 MHz, CDCl ): d 218.9, 125.2 (CF , q,
1
3
3
3
J ¼280 Hz), 67.6 (CHCF , q, J ¼32 Hz), 49.3, 38.0,
CF
3
CF
1
22.4, 20.6. H NMR data observed for its anti isomer:
d 4.16 (1H, dq, J ¼9.2 Hz, J ¼6.4 Hz, CHCF ).
1
2
3
6
4. Experimental
4.3.4. 5,5,5-Trifluoro-4-hydroxypentanone (9). Yield:
6% (isolated yield from the reaction in excess acetone);
7
1
4
.1. General
H NMR (TMS, CDCl ): d 4.45–4.53 (1H, m, CHCF ),
3 3
3
.60 (1H, br s, OH), 2.87 (1H, dd, J ¼18.0 Hz, J ¼9.4 Hz,
1
2
1
H NMR spectra were measured on Bruker AC 200E
400 MHz) spectrometer at ambient temperature. Data
were recorded by using TMS as the internal standard on
CHC]O), 2.77 (1H, dd, J ¼18.0 Hz, J ¼2.8 Hz, CHC]O),
1 2
1
3
3 3
(
2.25 (3H, s, CH ); C NMR (100 MHz, CDCl ): d 206.4,
124.7 (CF , q, J ¼279 Hz), 66.4 (CHCF , q, J ¼32 Hz),
3
CF
3
CF
1
3
the d scale. C NMR spectra were recorded on Bruker AC
00E (100 MHz) spectrometer at ambient temperature.
42.8, 30.6.
2
Chemical shifts are recorded from the solvent resonance
employed as the internal standard (deuterated chloroform
at 77.07 ppm). The crude products were purified by prepar-
ative column chromatography on silica gel with 100–200
mesh. All the reagents including trifluoroacetaldehyde ethyl
hemiacetal, amines, ketones, and aldehydes were all com-
mercially available and used without further purification.
4.3.5. 1,1,1-Trifluoro-2-hydroxy-6-methylheptan-4-one
(10). Yield: 68% (isolated yield from the reaction in di-
chloromethane); H NMR (TMS, CDCl ): d 4.48–4.53
3
8
1
(1H, m, CHCF ), 3.71 (1H, br s, OH), 2.82 (1H, dd, J ¼
3
1
17.6 Hz, J ¼9.2 Hz, CHC]O), 2.71 (1H, dd, J ¼17.6 Hz,
2
1
J ¼2.4 Hz, CHC]O), 2.37 (2H, d, J¼6.8 Hz, CH CO),
2
2
2.13–2.19 (1H, m, CH), 0.94 (3H, d, J¼6.6 Hz, CH ), 0.93
3
1
3
(
3H, d, J¼6.6 Hz, CH ); C NMR (100 MHz, CDCl ):
3
3
4.2. A typical procedure for pyrrolidine-catalyzed aldol
reaction of the hemiacetal 1
d 208.6, 124.7 (CF , q, J ¼279 Hz), 66.5 (CHCF , q,
CF
3 CF 3
J ¼32 Hz), 52.6, 42.3, 24.5, 22.4, 22.3.
A typical procedure was as follows: to a solution of the hemi-
acetal 1 (1.0 mmol) in dichloromethane (2 mL), pyrrolidine
4.3.6. 4,4,4-Trifluoro-3-hydroxy-1-phenylbutanone
(11). Mp 79.4–79.8 C (recrystallized from hexane/ethyl
2
b
ꢀ
acetate); yield: 49% (isolated yield from the reaction in
(
0.20 mmol) was added and the resulting mixture was stirred
at room temperature for 30 min. Then cyclohexanone
1.0 mmol) was poured into the solution. The reaction mix-
1
THF); H NMR (TMS, CDCl ): d 7.98 (2H, d, J¼7.6 Hz,
3
(
ortho), 7.64 (1H, t, J¼7.6 Hz, para), 7.51 (2H, t, J¼7.6 Hz,
ture was stirred at room temperature for a specified period.
The solvent was evaporated under a reduced pressure and
the residue was subjected to flash silica gel column chroma-
tography (eluting with n-hexane/ethyl acetate, 10:1 v/v) to
give 2 as a colorless oily liquid in 80% yield.
meta), 4.68–4.72 (1H, m, CHCF ), 3.51 (1H, br s, OH), 3.39
3
(1H, dd, J ¼18.0 Hz, J ¼9.0 Hz, CHC]O), 3.33 (1H, dd,
1
2
1
3
J ¼18.0 Hz, J ¼3.2 Hz, CHC]O); C NMR (100 MHz,
1
2
CDCl ): d 197.6, 136.0, 134.2, 128.9, 128.2, 124.5 (CF , q,
3
3
J ¼278 Hz), 67.1 (CHCF , q, J ¼32 Hz), 38.3.
CF
3
CF
4
4
.3. Spectrum data for the aldol products
4.3.7. 4,4,4-Trifluoro-3-hydroxy-1-(4-nitrophenyl)-1-
butanone (12). Mp 104.5–105.0 C (recrystallized from
2
b
ꢀ
hexane/ethyl acetate); yield: 55% (isolated yield from the
0
b
0
0
0
.3.1. anti-2-(1 -Hydroxy-2 ,2 ,2 -trifluoroethyl)cyclohexa-
7
1
none (anti-2). Yield: 55% (isolated yield from the reaction
in chloroform); H NMR (TMS, CDCl ): d 4.33 (1H, br s,
OH), 4.03–4.07 (1H, m, CHCF ), 2.74–2.78 (1H, m, C –H),
3
2.40–2.48 (2H, m), 2.23–2.24 (1H, m), 2.14–2.18 (1H,
m), 1.95–1.98 (1H, m), 1.68–1.78 (3H, m); C NMR
reaction in THF); H NMR (TMS, CDCl ): d 8.35 (2H, d,
3
1
J¼8.8 Hz, meta), 8.14 (2H, d, J¼8.8 Hz, ortho), 4.71–4.79
3
(1H, m, CHCF ), 3.47 (1H, dd, J ¼18.0 Hz, J ¼9.6 Hz,
2
3
1
2
CHC]O), 3.32 (1H, dd, J ¼18.0 Hz, J ¼2.4 Hz, CHC]O),
1
2
1
3
13
3.18 (1H, br s, OH); C NMR (100 MHz, CDCl ): d 195.6,
3
(
7
100 MHz, CDCl ): d 213.6, 124.7 (CF , q, J ¼280 Hz),
150.9, 140.3, 129.3, 124.6 (CF , q, J ¼278 Hz), 66.8
3
3
CF
3
CF
1.7 (CHCF , q, J ¼31 Hz), 50.4, 43.0, 31.6, 28.1, 24.9.
(CHCF , q, J ¼32 Hz), 39.1.
3
CF
3
CF
0
none (syn-2). Yield: 49% (isolated yield from the reaction
in dichloromethane); H NMR (TMS, CDCl ): d 4.70 (1H,
3
0
0
0
4
.3.2. syn-2-(1 -Hydroxy-2 ,2 ,2 -trifluoroethyl)cyclohexa-
4.3.8. 1-(2,2,2-Trifluoro-1-hydroxyethyl)cyclohexane-
carbaldehyde (14). Yield: 61% (isolated yield from the
reaction in dichloromethane); H NMR (TMS, CDCl ): d
3
1
1
q, J¼8.0 Hz, CHCF ), 2.96 (1H, br s, OH), 2.73 (1H, dd,
9.72 (1H, s, CHO), 3.99 (1H, q, J¼8.0 Hz, CHCF ), 3.47
3
3
J ¼12.8 Hz, J ¼5.6 Hz, C –H), 2.50 (1H, d, J¼13.6 Hz,
(1H, br s, OH), 2.01–2.09 (2H, m), 1.58–1.68 (4H, m),
1.30–1.46 (4H, m); C NMR (100 MHz, CDCl ): d 206.3,
1
2
2
1
3
C –H), 2.33–2.41 (1H, m, C –H), 2.23–2.27 (1H, d, C –
5
6
6
3
H), 2.13–2.15 (1H, m), 1.97–1.99 (1H, m), 1.83–1.93 (1H,
m), 1.67–1.77 (3H, m); C NMR (100 MHz, CDCl3):
124.7 (CF , q, J ¼283 Hz), 74.9 (CF , q, J ¼29 Hz),
3
CF
3
CF
1
3
50.6, 28.6, 28.0, 25.0, 21.9, 21.8.
d 211.2, 125.0 (CF , q, J ¼280 Hz), 67.5 (CHCF , q,
3
CF
3
J ¼31 Hz), 50.4, 42.2, 27.3, 26.2, 24.5.
Acknowledgements
CF
0
tanone (8). Yield: 62% (isolated yield from the reaction
0
0
0
4
.3.3. syn-2-(1 -Hydroxy-2 ,2 ,2 -trifluoroethyl)cyclopen-
This work was supported by National Natural Science Foun-
dation of China (B20572028).
7
a