Catalytic asymmetric β-hydrogen transfer reduction of α-trifluoromethyl aromatic ketones with diethylzinc

Article abstract of DOI:10.1016/j.tetasy.2015.06.017

Abstract The catalytic asymmetric β-hydrogen transfer reduction of α-trifluoromethyl ketones using diethylzinc as the β-hydrogen donor was developed with the use of phosphinamide chiral ligand. The corresponding alcohol products were afforded in good yields with up to 73% ee. This method was successfully applied to the chemo- and enantioselective reduction of α-methyl/trifluoromethyl diketone, affording 88% yield and 70% ee of the fluorinated hydroxylketone product.

Full text of DOI:10.1016/j.tetasy.2015.06.017

Tetrahedron: Asymmetry xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Catalytic asymmetric b-hydrogen transfer reduction
of
a
-trifluoromethyl aromatic ketones with diethylzinc
⇑
Huayin Huang, Hua Zong, Guangling Bian, Ling Song
The Key Laboratory of Coal to Ethylene Glycol and Its Related Technology, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou,
Fujian 350002, China
a r t i c l e i n f o
a b s t r a c t
Article history:
The catalytic asymmetric b-hydrogen transfer reduction of a-trifluoromethyl ketones using diethylzinc as
the b-hydrogen donor was developed with the use of phosphinamide chiral ligand. The corresponding
alcohol products were afforded in good yields with up to 73% ee. This method was successfully applied
Received 28 April 2015
Accepted 15 June 2015
Available online xxxx
to the chemo- and enantioselective reduction of
a-methyl/trifluoromethyl diketone, affording 88% yield
and 70% ee of the fluorinated hydroxylketone product.
Ó 2015 Published by Elsevier Ltd.
1. Introduction
the asymmetric version of the b-hydrogen transfer reduction of
-trifluoromethyl ketones with diethylzinc has never been
reported.
As already known, the selective reduction of a targeted func-
tional group in the presence of other reducible functional group
is of great interest in organic synthesis. Until recently, only a few
methods for the chemo- and enantioselective reduction of
methyl/trifluoromethyl diketone have been developed because
a
Trifluoromethylated organic compounds play a significant role
in medicinal and agrochemical products due to their particular
properties and reactivities.1–7 The ever-increasing demand of
enantiomerically enriched trifluoromethylated compounds has
dramatically promoted the development of their asymmetric syn-
theses.3,8–13 Among the developed methodologies, the enantiose-
lective reduction of trifluoromethyl ketones is of great value and
many types of approaches have been reported, such as asymmetric
transition metal-catalyzed hydrogenations,14–19 biocatalyzed
reductions,20–24 chiral organometallic reagents reductions,25–28
asymmetric borane reductions,29–33 and asymmetric b-hydrogen
transfer reductions.34–36
Compared with other asymmetric reduction transformations,
asymmetric b-hydrogen transfer reduction of trifluoromethyl
ketones is underdeveloped with few examples.34–36 In 2002,
Yong and Chong introduced a chiral organomagnesium amide as
a hydrogen source in the asymmetric b-hydrogen transfer reduc-
both the
a-methyl carbonyl group and the a-trifluoromethyl car-
bonyl group are very similar in chemical properties and are easy
to reduce simultaneously.17,42–46 As a consequence, it remains
challenging to develop an efficient method for the chemo- and
enantioselective reduction of methyl/trifluoromethyl diketone.
We have been interested in 1,2-diamino phosphinamide chiral
ligand catalyzed diorganozinc reagents that participate in asym-
metric reactions.47–52 This type of chiral ligands also shows high
efficiency in organocatalyzed asymmetric reactions.53–56 As part
of our ongoing interest in developing efficient asymmetric reac-
tions, we herein report the first asymmetric b-hydrogen transfer
tion of
a
-trifluoromethyl ketones, affording the corresponding
reduction of
a-trifluoromethyl ketones with diethylzinc catalyzed
a-trifluoromethyl secondary alcohol products with up to 96% ee
by 1,2-diamino phosphinamide chiral ligand derived from
a
and up to 95% yield.36 However, due to the high reactivity of the
diorganomagnesium reagent, a stoichiometric amount of chiral
amide ligand and a low temperature (À78 °C) were required to
achieve high enantioselectivity. Diethylzinc is as a well-known
b-hydrogen donor and was used in the reduction of trifluoromethyl
ketones by Higashiyama et al.37 some other groups also found that
trifluoromethyl ketones could be reduced by diethylzinc,38–41 but
(1R,2R)-1,2-diphenylethylenediamine and its application in the
chemo- and enantioselective reduction of methyl/trifluoromethyl
diketone.
2. Results and discussion
In our previous studies, inspired by Ishihara’s pioneering work
on the development of conjugated Lewis acid–base catalysts,57–61
several highly efficient 1,2-diamino phosphinamide chiral ligands
derived from quinidine, (1R,2R)-1,2-diaminocyclohexane, and
⇑
Corresponding author. Tel.: +86 591 83720913; fax: +86 591 83722697.
E-mail address: songling@fjirsm.ac.cn (L. Song).
http://dx.doi.org/10.1016/j.tetasy.2015.06.017
0957-4166/Ó 2015 Published by Elsevier Ltd.
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2
H. Huang et al. / Tetrahedron: Asymmetry xxx (2015) xxx–xxx
(1R,2R)-1,2-diphenylethylenediamine 1–4 were developed and
applied in the catalytic asymmetric addition reactions of a variety
of aromatic aldehydes and ketones with diethylzinc reagent,
affording the corresponding addition alcohol products with
excellent yields and enantioselectivities.47–51 However, when
trifluoromethylketone was used as the substrate, these ligands
provided reduction alcohol product 5a as the main product and
only a small amount of addition product 8 could be observed.
The experimental results are listed in Table 1.
Our investigation showed that the poor yield and enantioselec-
tivity of the alcohol reduction product were afforded when using
chiral ligands 1, 2a, and 2b (Table 1, entries 1–3). In addition,
(1R,2R)-1,2-diaminocyclohexane derived chiral ligand 3 gave a
nearly racemic reduction product with moderate yield (entry 4).
Interestingly, 90% yield and 48% ee value of alcohol reduction pro-
duct were obtained when using (1R,2R)-1,2-diphenylethylenedi-
amine derived N-monosubstituted 4a (entry 5). We wondered if
we could develop a better chiral 1,2-diamino phosphinamide
ligand for the catalytic asymmetric b-hydrogen transfer reduction
by further ligand structure modification. With N-nonsubstituted
ligand 4b, both the yield and ee value of the reduction product
decreased to 34% and 19%, respectively (entry 6). With N,N-dialky-
lated chiral ligands 4c and 4d, the desired reduction products were
obtained in moderate yields, but the corresponding ee values were
low with opposite configurations (entries 7 and 8). However, as
shown in entries 9–14, increasing the size of the N-monosub-
stituent had a positive effect on the yield and ee value of the reduc-
tion product. The best result was obtained with a Bn group as the
N-substituent, giving the reduction product with 95% yield and 57%
ee value.
such as the amount of diethylzinc reagent, the loading of chiral
ligand, reaction solvent, time, and temperature were also evalu-
ated with the optimized chiral ligand 4j in hand and the experi-
mental results are listed in Table 2.
When diethylzinc reagent was increased from 1.3 equiv to
3.0 equiv, the yield of the desired product slightly increased but
the ee value dropped significantly (Table 2, entries 1–3). With only
0.8 equiv of diethylzinc, both the yield and ee value of the product
decreased (entry 4). When the loading of chiral ligand 4j was
increased to 30 mol %, both the yield and ee value increased
slightly to 98% and 58%, respectively (entry 5). Changing the sol-
vent from hexane to toluene increased the enantioselectivity to
60% (entries 5–8). Lowering the temperature to À10 °C enhanced
the ee value to 62% (entry 9). When À20 °C was used and the reac-
tion mixture was stirred for 48 h, the ee value of the product was
optimized to 73% with 88% yield (entry 10). Further lowering the
reaction temperature to À50 °C, meant the reaction did not happen
at all (entry 11). On the basis of the above experimental data, the
optimized reaction conditions were in toluene at À20 °C for 48 h
using 30 mol % of 4j as the chiral ligand and 1.3 equiv of diethylz-
inc reagent as the b-hydrogen donor.
We next evaluated the effectiveness of the optimized catalytic
system in the catalytic asymmetric b-H transfer reduction of varied
a-trifluoromethyl ketones with diethylzinc, and the results are
summarized in Table 3.
As shown in Table 3, the reactions between diethylzinc and p-F,
Cl, Me substituted aryl
a-trifluoromethyl ketones gave the corre-
sponding reduction products 5b–5d in over 70% yield with over
60% enantioselectivity (Table 3, entries 2–4). When the aromatic
group was 2-naphthyl, the desired product was afforded with
87% yield and 40% ee value. When one fluorine atom of the triflu-
oromethyl group was replaced by a chloride atom, the desired
In order to further enhance the enantioselectivity of the asym-
metric b-H transfer reduction reaction, various reaction conditions
Table 1
Evaluation of 1,2-diamino phosphinamide chiral ligands in the catalytic asymmetric b-H transfer reduction of
a
-trifluoromethyl ketone with diethylzinca
OH
OH
O
chiral ligand (20 mol%)
hexane, 0 oC, 5 h
Et2Zn
+
+
Ph
Ph
CF3
Ph
CF3
*
(1.3 equiv)
CF3
5a
8
O
H
S
Ph
PPh2
O
Ph
P
Ph
HN
H
N
H
N
H
Ph2P
N
N
O
Ph
R2
H
Ph
Ph
Ph
Ph2P NH
N
R2
N
MeO
N
R1
R2
N
i-Pr
H
R1
4a-4j
R1
N
1
3
2a-2b
Entry
Ligand
R1
R2
Yieldb of 5a (%)
eec of 5a (%)
Config.d
Ratio of 5a:8e
1
2
3
4
5
6
7
8
1
—
Me
H
—
H
—
13
18
17
60
90
34
60
50
76
96
80
86
92
95
17
11
10
2
(S)
(S)
(S)
(R)
(R)
(R)
(S)
(S)
(R)
(R)
(R)
(R)
(R)
(R)
65:35
79:21
77:23
94:6
97:3
87:13
94:6
94:6
96:4
98:2
96:4
96:4
97:3
98:2
2a
2b
3
i-Pr
Cbz
—
i-Pr
H
Me
Et
Et
CH2i-Pr
Bu
CH2Bu
c-Hex
Bn
4a
4b
4c
4d
4e
4f
4g
4h
4i
48
19
10
11
50
51
51
52
53
57
H
Me
Me
H
H
H
H
H
H
9
10
11
12
13
14
4j
a
b
c
Unless otherwise noted, all reactions were carried out in 1 mmol scale.
Isolated yields.
Determined by chiral GC analysis.
d
e
The configuration was determined by comparing the sign of specific rotation value with the literature value.
The ratio was determined by 19F NMR spectroscopic analysis of unpurified reaction products.
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H. Huang et al. / Tetrahedron: Asymmetry xxx (2015) xxx–xxx
3
Table 2
O
O
conditions
conditions
(a)
no reaction
Optimization of reaction conditions for the catalytic asymmetric b-H transfer
reduction of trifluoroacetophenone with diethylzinc using chiral ligand 4ja
Ph
Ph
OH
CF3
O
O
O
OH
chiral ligand 4j (Y mol%)
+
Ph
Ph
+
+
Et2Zn
(X equiv)
(b)
(c)
80% yield
82% yield
Ph
CF3
CF3
Ph
CF3
solvent, temp., time
Ph
CF3
recovered
70% ee
O
OH
Entry
X
Y
Solvent
Time (h)
Temp (°C)
Yieldb (%)
eec (%)
conditions
CF3
1
2
3
4
5
6
1.3
2.0
3.0
0.8
1.3
1.3
1.3
1.3
1.3
1.3
1.3
20
20
20
20
30
30
30
30
30
30
30
Hexane
Hexane
Hexane
Hexane
Hexane
CH2Cl2
Toluene
Toluene
Toluene
Toluene
Toluene
5
5
0
0
95
96
99
42
98
86
96
95
76
57
44
22
55
58
51
60
58
62
73
—
88% yield
5
0
O
70% ee
6
7
O
5
0
5
0
Figure 1. Chemo- and enantioselective reduction of methyl/trifluoromethyl dike-
tone 6. Conditions: ligand 4j (30 mol %), Et2Zn (1.3 equiv), toluene as solvent,
À20 °C, 48 h.
5
0
7
5
0
8d
9
5
0
12
48
48
À10
À20
À50
10
11
88
N.R.e
a
-trifluoromethyl ketone was reduced. The reduction alcohol pro-
a
b
c
duct was obtained with 82% yield and 70% ee value and 80% yield
of acetophenone was recovered (Fig. 1b). These results indicated
Unless otherwise noted, all reactions were carried out on a 1 mmol scale.
Isolated yields.
Determined using chiral GC analysis.
Et2Zn (1.0 mol/L in toluene) was used.
No reaction after 48 h.
that this method selectively reduced the
bonyl group in the presence of an -methyl carbonyl group.
Next, we applied the method in the chemo- and enantioselective
reduction of 6 containing both -trifluoromethyl carbonyl and
-methyl carbonyl groups (Fig. 1c). Compound 6 was chemo-
a-trifluoromethyl car-
d
e
a
a
a
Table 3
Enantioselective reduction of trifluoromethyl ketones with diethylzinc catalyzed by
and enantioselectively reduced and the corresponding product of
fluorinated chiral hydroxyketone 7 was afforded with 88% yield
and 70% ee value.
Based on Ishihara’s conjugate Lewis acid–base double activated
transition state model57 and our experimental results, a plausible
transition state is proposed as shown in Figure 2.
chiral ligand 4ja
OH
O
chiral ligand 4j (30 mol%)
toluene, -20 oC, 48 h
+
Et2Zn
Ar
5a-5f
Rf
Ar
Rf
(1.3 equiv)
Entry
1
Product
Number
Yieldb (%)
eec (%)
73
OH
F
Ph
H
F3C
H
F
H
Ph
5a
88
CF3
F
O
O
Zn
OH
Zn
O
N
N
Zn
N
Zn
N
Ph
Ph
CF3
O
2
3
4
5b
5c
5d
75
71
70
61
60
61
Et
Et
P
P
F
Ph
Ph
Ph
Ph
Ph
OH
Ph
Si-face attack
Re-face attack
less favored
CF3
favored
Cl
Me
Figure 2. Proposed transition states.
OH
CF3
The zinc metal center of the 1,2-diamino phosphinamide–Zn(II)
complex serves as a Lewis acid to active the carbonyl group of
a-
OH
trifluoromethyl ketone and the P@O moiety of the complex serves
as a Lewis base to coordinate the diethylzinc reagent, after which
b-H of the diethylzinc reagent could be transferred to the carbonyl
group of trifluoromethyl ketone via a six-membered ring transition
state. The (R)-product was formed via Si-face attack of trifluo-
romethyl ketone, which should be highly preferred without steric
repulsion between the Bn group of chiral metallic complex and
the Ph group of trifluoromethyl ketone. In addition, the
Ar–HÁ Á ÁF–C interaction could help to stabilize the Si-face attack
transition state.36
5
6
5e
5f
87
86
40
71
CF3
OH
CF2Cl
a
b
c
Unless otherwise noted, all reactions were carried out in 1 mmol scale.
Isolated yield.
Determined by chiral GC.
product was afforded with 86% yield and 71% ee value (Table 3,
entry 6).
3. Conclusion
Further investigation showed that acetophenone did not react
with diethylzinc under the reaction conditions (Fig. 1a). When a
In conclusion, with the use of diethylzinc as a b-hydrogen
donor, we developed an efficient catalytic asymmetric b-H transfer
1:1 mixture of acetophenone and
treated with diethylzinc under the reaction conditions, only
a-trifluoromethyl ketone was
reduction of
a-trifluoromethyl aromatic ketones. Chiral ligand
structure modification gave us 1,2-diamino phosphinamide 4j as
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4
H. Huang et al. / Tetrahedron: Asymmetry xxx (2015) xxx–xxx
the best catalyst, which afforded good yields and up to 73% ee
value of the resulting -trifluoromethyl alcohol products. This
method was successfully applied in the chemo- and enantioselec-
tive reduction of -methyl/trifluoromethyl diketone and a possible
CH2Cl2) for 45% ee (R)}; 1H NMR (400 MHz, CDCl3): d 3.12 (s, 1H),
5.01 (q, J = 6.5 Hz, 1H), 7.00–7.17 (m, 2H), 7.35–7.53 (m, 2H); 13C
a
NMR (100 MHz, CDCl3):
d 72.2 (q, J = 32.2 Hz), 115.6 (d,
a
J = 21.9 Hz), 124.1 (q, J = 282.1 Hz), 129.3 (d, J = 8.2 Hz), 129.7,
163.4 (d, J = 248.9 Hz); 19F NMR (376 MHz, CDCl3): d À78.6 (d,
J = 6.7 Hz, 3F), À112.4 (m, 1F).
transition state was also proposed.
4. Experimental section
4.1. General methods
4.2.3. (R)-1-(4-Chlorophenyl)-2,2,2-trifluoroethanol 5c63
Colorless oil, 150 mg (71% yield); the 60% ee value was deter-
mined by Chiral GC Chirasil Dex CB [column temperature:
125 °C, tR = 10.9 min (minor, S), tR = 11.7 min (major, R)].
All experiments were carried out in dried glassware with mag-
netic stirring under an atmosphere of dry nitrogen. 1H NMR
(400 MHz), 13C NMR (100 MHz), and 19F NMR (376 MHz) spectra
are recorded in CDCl3 solutions using a 400 MHz spectrometer.
Chemical shifts were reported in parts per million (ppm, d) relative
to CDCl3 (d 7.26 for 1H NMR), or CDCl3 (d 77.0 for 13C NMR).
Multiplicities are indicated as s (singlet), d (doublet), t (triplet), q
(quartet), m (multiplet), and br (broad). Commercial reagents were
used as received unless otherwise indicated. All solvents were
purified and dried prior to use according to the literature.62
Optical rotations were measured on a polarimeter and specific
rotations are reported as follows: [
analysis was performed using Chiral column. Chiral 1,2-diamino
phosphinamide ligands 1,49 2a–2b,51 3,47 4a–4i,50 4j,52 compound
6,46 and 838 were prepared according to the literature.
[a]
30.6 = À10.8 (c 0.50, CH2Cl2) {literature63
[
a]
25 = À18.3 (c 0.13,
D
D
CH2Cl2) for 51% ee (R)}; 1H NMR (400 MHz, CDCl3): d 3.01 (s, 1H),
5.01 (q, J = 6.6 Hz, 1H), 7.34–7.47 (m, 4H); 13C NMR (100 MHz,
CDCl3): d 72.1 (q, J = 32.0 Hz), 124.1 (q, J = 283.5 Hz), 128.8,
129.6, 132.4, 135.5; 19F NMR (376 MHz, CDCl3): d À78.5 (d,
J = 6.8 Hz, 3F).
4.2.4. (R)-2,2,2-Trifluoro-1-p-tolylethanol 5d63
Colorless oil, 133 mg (70% yield); the 61% ee value was deter-
mined by Chiral GC Chirasil Dex CB [column temperature:
125 °C, tR = 10.1 min (minor, S), tR = 10.6 min (major, R)].
T
D
a]
(c g/100 mL, solvent). GC
[
a
]
28.5 = À14.7 (c 0.50, CH2Cl2) {literature63
[
a
]
25 = À12.7 (c 0.18,
D
D
CH2Cl2) for 68% ee (R)}; 1H NMR (400 MHz, CDCl3): d 2.41 (s, 3H),
2.87 (br, 1H), 4.98 (m, 1H), 7.16–7.30 (m, 2H), 7.33–7.47 (m, 2H);
13C NMR (100 MHz, CDCl3): d 21.1, 72.6 (q, J = 31.8 Hz), 124.4 (q,
J = 281.1 Hz), 127.4, 129.3, 131.1, 139.6; 19F NMR (376 MHz,
CDCl3): d À78.4 (d, J = 6.9 Hz, 3F).
4.2. Typical procedure for the catalytic asymmetric b-hydrogen
transfer reduction of
a-trifluoromethyl ketone
4.2.5. (R)-2,2,2-Trifluoro-1-(naphthalen-2-yl)ethanol 5e63
White solid, 197 mg (87% yield); the 40% ee value was deter-
mined by Chiral GC Chirasil Dex CB [column temperature:
165 °C, tR = 15.0 min (minor, S), tR = 15.5 min (major, R)].
O
OH
chiral ligand (30 mol%)
toluene, -20 oC, 48 h
+
Et2Zn
Ar
CF3
Ar
CF3
[a]
29.9 = À11.8 (c 1.00, CH2Cl2) {literature63
[a
]
D
25 = À24.7 (c 0.21,
(1.3 equiv)
D
CH2Cl2) for 75% ee (R)}; 1H NMR (400 MHz, CDCl3): d 3.34 (s, 1H),
5.16 (q, J = 6.8 Hz, 1H), 7.48–7.68 (m, 3H), 7.80–8.05 (m, 4H); 13C
NMR (100 MHz, CDCl3): d 73.0 (q, J = 31.8 Hz), 124.4, 124.5 (q,
J = 280.0 Hz), 126.6, 126.9, 127.4, 127.8, 128.3, 128.6, 131.4,
133.0, 133.8; 19F NMR (376 MHz, CDCl3): d À77.6 (d, J = 6.7 Hz, 3F).
To a solution of chiral phosphinamide chiral ligand (0.3 mmol)
in toluene (1.3 mL), Et2Zn (1.3 mL, 1 M in n-hexane, 1.3 mmol)
was added and the resulting mixture was stirred for 10 min at
0 °C under an atmosphere of nitrogen. Next, the reaction mixture
4.2.6. (R)-2-Chloro-2,2-difluoro-1-phenylethanol 5f64
Colorless oil, 166 mg (86% yield); the 71% ee value was deter-
mined by Chiral GC Chirasil Dex CB [column temperature:
125 °C, tR = 24.0 min (minor, S), tR = 24.4 min (major, R)].
was cooled to À20 °C, and
a-trifluoromethyl ketone (1.0 mmol)
was added dropwise. After being stirred for 48 h, the reaction
was quenched by saturated NH4Cl solution (15 mL) and the mix-
ture was extracted with EtOAc (15 mL Â 3). The combined organic
layer was dried over MgSO4, filtered, and concentrated in vacuo to
give a residue, which was purified by flash column chromatogra-
phy on silica gel (hexane/EtOAc = 10:1) to give the corresponding
product.
[
a
]
30.1 = À9.1 (c 0.50, CHCl3) {literature64
[
a
]
21 = À13.8 (c 1.01,
D
D
CHCl3) for 73% ee (R)}; 1H NMR (400 MHz, CDCl3): d 3.07 (s, 1H),
5.07 (t, J = 6.6 Hz, 1H), 7.32–7.62 (m, 5H); 13C NMR (100 MHz,
CDCl3): d 77.6, 127.8, 128.4, 129.0 (t, J = 297.0 Hz), 129.5, 131.9,
134.3; 19F NMR (376 MHz, CDCl3): d À62.3 (dd, J = 7.4, 164.0 Hz,
1F), À64.3 (dd, J = 8.4, 164.0 Hz, 1F).
4.2.1. (R)-2,2,2-Trifluoro-1-phenylethanol 5a63
Colorless oil, 155 mg (88% yield); the 73% ee value was deter-
mined by Chiral GC Chirasil Dex CB [column temperature:
125 °C, tR = 11.5 min (minor, S), tR = 12.0 min (major, R)].
4.2.7. (R)-1-(4-(2,2,2-Trifluoro-1-hydroxyethyl)phenyl)ethanone 746
White solid, 179 mg (82% yield); the 70% ee value was deter-
mined by Chiral GC Chirasil Dex CB [column temperature:
165 °C, tR = 15.9 min (minor, S), tR = 16.4 min (major, R)].
[a
]
D
30.5 = À16.1 (c 0.50, CH2Cl2) {literature63
[a]
25 = À13.1 (c 0.28,
D
CH2Cl2) for 60% ee (R)}; 1H NMR (400 MHz, CDCl3): d 2.73 (s, 1H),
5.02 (q, J = 6.6 Hz, 1H), 7.38–7.53 (m, 5H); 13C NMR (100 MHz,
CDCl3): d 72.9 (q, J = 32.2 Hz), 124.3 (q, J = 281.0 Hz), 127.5,
128.6, 129.6, 134.0; 19F NMR (376 MHz, CDCl3): d À78.2 (d,
J = 6.7 Hz, 3F).
[a]
30.2 = À13.1 (c 1.00, CH2Cl2); 1H NMR (400 MHz, CDCl3): d 2.61
D
(s, 3H), 3.21 (s, 1H), 5.11 (m, 1H), 7.50–7.65 (m, 2H), 7.90–8.05
(m, 2H); 13C NMR (100 MHz, CDCl3): d 26.6, 72.2 (q, J = 32.1 Hz),
124.1 (q, J = 282.3 Hz), 127.7, 128.5, 137.7, 139.2, 198.3; 19F NMR
(376 MHz, CDCl3): d À78.2 (d, J = 6.4 Hz, 3F).
4.2.2. (R)-2,2,2-Trifluoro-1-(4-fluorophenyl)ethanol 5b63
Colorless oil, 146 mg (75% yield); the 61% ee value was deter-
mined by Chiral GC Chirasil Dex CB [column temperature:
125 °C, tR = 11.2 min (minor, S), tR = 12.3 min (major, R)].
Acknowledgments
The authors would like to thank The Key Laboratory of Coal to
Ethylene Glycol and Its Related Technology, Fujian Institute of
[a
]
D
29.5 = À16.5 (c 0.50, CH2Cl2) {literature63
[
a]
D
19 = À11.5 (c 0.07,
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Research on the Structure of Matter, Chinese Academy of Sciences
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