7
64
H. Kawai et al. / Journal of Fluorine Chemistry 130 (2009) 762–765
ꢀ
1
+
Table 2
1
(
089, 881, 811, 749 cm ; MS (ESI, m/z) 1075 (M+Na ), 1091
Enantioselective trifluoromethylation of ketones and aldehydes 1a–j with Me
catalyzed by chiral crown ether 2b.
3
SiCF
3
+
M+K ).
3
b: off-white solid; H NMR (CDCl , 200 MHz) d 3.09–3.22 (m,
1
3
4
4
H), 3.34–3.49 (m, 10H), 3.58–3.78 (m, 6H), 3.99–4.09 (m, 2H),
.20ꢀ4.31 (m, 2H), 7.05ꢀ7.34 (m, 12H), 7.41 (d, J = 9.2 Hz, 2H), 7.74
(
d, J = 8.0 Hz, 2H), 7.83 (d, J = 7.4 Hz, 2H), 7.95 (d, J = 8.8 Hz, 2H), 8.46
1
3
(
s,2H); CNMR(CDCl
3
,150.9 MHz)
d69.4,69.6,69.9,70.6,70.7,72.4,
9
1
1
1
3.1, 114.5, 119.0, 123.8, 125.1, 125.3, 125.6, 128.0, 126.6, 126.7,
26.9, 127.9, 129.0, 130.1, 132.2, 133.7, 134.1, 138.87, 138.89, 153.7,
54.2;IR(KBr)3435, 3056, 2925, 2872,1621,1593,1509,1469,1348,
.
+
270, 1134, 1089, 1051, 811, 749; MS (ESI, m/z) 1091 (M+K ).
a
1
2
b
Entry
1
R
R
Time (h)
Yield (%)
ee
1
2
1a
1b
1c
1d
1e
1f
2-Naphthyl
Ph
H
1
1
88
84
80
84
87
72
90
91
66
80
40
44
39
43
29
24
21
34
38
31
4.2. Trifluoromethylation of aldehyde 1a catalyzed by chiral crown
ether 2b
H
c
3
4-MeC
4-MeOC
4-BrC
PhCH
PhCH5CH
6
H
4
H
14
14
2
c
4
c
6
H
4
H
Potassium phenoxide (3.3 mg, 0.025 mmol) and 2b (2.6 mg,
5
6
H
4
H
0.0025 mmol) in toluene (2.0 ml) were stirred under a nitrogen
6
2
CH
2
H
4
d
7
1g
1h
1i
H
6
atmosphere at room temperature for 30 min. Me SiCF (73.9 l,
3
3
m
e
8
2-Naphthyl
Ph
Me
Me
Me
6
0
.500 mmol) was added at ꢀ50 8C, and 1a (39.0 mg, 0.250 mmol)
e
9
6
was added to the reaction mixture. After the reaction mixture was
stirred at the same temperature by monitoring with TLC, it was
e
1
0
1j
4-BrC
6
H
4
6
a
Concentration was 0.13 M.
Determined by chiral HPLC.
quenched with sat. NH
with AcOEt, and the combined organic layers was washed with
brine, dried over Na SO and concentrated under reduced pressure
4
Cl aq. The aqueous layer was extracted
b
c
The reaction was carried out at ꢀ50 to ꢀ40 8C.
The reaction was carried out at ꢀ50 to ꢀ20 8C.
The reaction was carried out at ꢀ40 to ꢀ30 8C.
d
e
2
4
to furnish the crude 4a as trimethylsilyl ether. The trimethylsilyl
ether was treated with 1.0 ml 1N HCl aq. in THF (1.0 ml) at room
temperature for 1 h. The resulting mixture was extracted with
AcOEt, and the combined organic layers was washed with brine,
3
. Conclusion
In conclusion, we have synthesized novel C2-symmetrical
2 4
dried over Na SO and concentrated under reduced pressure to
furnish crude 4a. The residue was purified by column chromato-
chiral crown ethers and investigated their utility for the
enantioselective trifluoromethylation of aryl aldehydes and alkyl
aryl ketones. As far as we know, this is the first example of a chiral
crown ether-catalyzed enantioselective trifluoromethylation reac-
tion. The amount of chiral catalysts can be reduced to 1 mol%.
Despite the fact that the ees are still improvable, the model
reported in this work could spark the imagination of chemists to
design new chiral crown ethers to improve the stereochemical
outcome. Further structural optimization of chiral crown ethers in
combination with additives for this reaction should achieve high
enantioselectivity. We are now working in this direction.
graphy on silica gel (hexane:ethyl acetate = 9:1) to give 4a
1
(49.6 mg, 88%, 40% ee). 4a white solid;
200 MHz)
3H), 7.81–7.93 (m, 4H); C NMR (CDCl
J = 31.9 Hz), 124.09, 124.10 (d, J = 281.0 Hz), 126.4, 126.7, 127.1,
3
H NMR (CDCl ,
d
2.67 (d, J = 3.8 Hz), 5.12–5.23 (m, 1H), 7.47–7.57 (m,
1
3
3
, 50.3 MHz) d 73.0 (q,
1
9
3
127.5, 128.0, 128.3, 131.0, 132.7, 133.5; F NMR (CDCl , 188 MHz)
d
ꢀ77.9 (d, J = 6.4 Hz, 3F); IR (KBr) 3366, 3065, 1509, 1366, 1260,
ꢀ1
1197, 1175, 1125, 1067, 892, 821, 792, 752, 701 cm ; MS (EI, m/z)
226 (M ); The product was determined as 40% ee by HPLC
+
(Chiralcel OJ-H, Hexane: i-PrOH = 90:10, flow rate 1.0 ml/min,
l
= 254 nm) t
R R
(major) = 12.1 min and t (minor) = 18.4 min.
4
. Experimental
Acknowledgements
4
.1. Preparation of chiral crown ether 2b
This work was supported by KAKENHI and by a Grant-in-Aid for
Scientific Research on Priority Areas ‘‘Advanced Molecular
Transformations of Carbon Resources’’ from the Ministry of
Education, Culture, Sports, Science and Technology Japan. We
To a suspension of potassium tert-butoxide (621 mg, 5.54 mmol)
and 3-iodobinaphthol 5a (1.14 g, 2.77 mmol) in THF (23 ml) under a
nitrogen atmosphere, a solution of triethyleneglycol di-p-toluene-
sulfonate 6b (1.27 g, 2.77 mmol) in THF (7.0 ml) was added. The
reaction mixture was heated at reflux for 12 h and concentrated
under reduced pressure. The residue was shaken with water and
3 3
thank Tosoh F-Tech Ltd. for the generous gift of Me SiCF .
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Na
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Cl
SO
2
, and the organic layer was washed with brine and dried over
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(
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