Enantioselective aldol reactions of α,β-unsaturated ketones with trifluoroacetophenone catalyzed by a chiral primary amine

Article abstract of DOI:10.1016/j.tetasy.2014.05.005

Chiral primary amine catalyzed direct asymmetric aldol reactions of ketones with trifluoroacetophenone, afforded trifluoromethylated β-hydroxycarbonyl aldol products bearing a quaternary carbon stereogenic center in high yields (up to 93% yield) and with high to excellent enantioselectivities of up to 99% ee.

Full text of DOI:10.1016/j.tetasy.2014.05.005

Tetrahedron: Asymmetry 25 (2014) 949–955
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Enantioselective aldol reactions of
a,b-unsaturated ketones
with trifluoroacetophenone catalyzed by a chiral primary amine
⇑
⇑
Jing Lin, Tairan Kang, Quanzhong Liu , Long He
Chemical Synthesis and Pollution Control Key Laboratory of Sichuan Province, College of Chemistry and Chemical Engineering, China West Normal University, Nanchong 637002,
PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Chiral primary amine catalyzed direct asymmetric aldol reactions of ketones with trifluoroacetophenone,
afforded trifluoromethylated b-hydroxycarbonyl aldol products bearing a quaternary carbon stereogenic
center in high yields (up to 93% yield) and with high to excellent enantioselectivities of up to 99% ee.
Ó 2014 Elsevier Ltd. All rights reserved.
Received 2 April 2014
Accepted 12 May 2014
Available online 18 June 2014
1. Introduction
catalyzed aldol reactions with ketones and synthesizing trifluo-
romethylated organic compounds, we herein report a cross aldol
The development of highly efficient and enantioselective chiral
catalysts for organic transformations that proceed under mild
conditions and tolerate a wide scope of substrates is an important
subject. Asymmetric aminocatalysis has received much attention
and significant advancements have been made over the past few
years.1 Organocatalytic aldol reactions are one of the most power-
ful methods for rapid access to b-hydroxycarbonyl compounds and
the formation of CAC bonds in organic synthesis.2 Since the pio-
neering work of List and Barbas III et al., direct aldol reactions have
been investigated intensively over the past decade.3–5 However,
of a,b-unsaturated ketones with trifluoroacetophenone to allow
the synthesis of trifluoromethylated b-hydroxycarbonyl com-
pounds bearing a quaternary carbon stereogenic center.
2. Results and discussion
In our initial studies, we undertook an investigation of proline
1a as the catalyst for the cross aldol reaction of
a,b-unsaturated
ketone 2a12 with trifluoroacetophenone 3a in the presence of
TFA at room temperature. Unfortunately, commonly used proline
1a was found to be unreactive and no aldol product was isolated
even after 96 h (entry 1). We decided to investigate whether pri-
mary amine catalyst 1b would be more amenable to this cross
aldol reaction (Fig. 1); the results are summarized in Table 1. The
reaction proceeded smoothly to generate trifluoromethylated
b-hydroxycarbonyl compound 4a in high yield but with low
enantioselectivity (84% yield and 28% ee, entry 2). A catalyst survey
showed that the catalyst has a significant effect on the reactivity
and enantioselectivity of the aldol reaction (entries 1–6). For
instance, cinchona derived primary amines 1e–1g furnished poor
yields and enantioselectivity (entries 5 and 6). Primary amine 1d,
developed by our group10 turned out to be the most efficient in
terms of enantioselectivities (entry 4).
direct asymmetric aldol reactions using
a,b-unsaturated ketones
as the nucleophile have been less explored. Furthermore, using
ketones as the electrophile has received less attention due to their
low electrophilicity relative to aldehydes.6
Trifluoromethylated organic compounds have received increas-
ing attention because the trifluoromethyl motif plays a pivotal role
in the enhancement and modification of biological activities.7,8
Consequently, efficient approaches to valuable CF3-bearing organic
compounds are of considerable synthetic and biological impor-
tance.9 In 2008, we developed a new family of chiral primary
amines from enantiomerically pure binaphthol and amino acids.
This family was found to be effective in asymmetric aldol reactions
of ketone with aldehydes and keto-esters.10 Very recently, these
chiral amines were successfully applied in cross aldol reactions
of acetaldehyde with unsaturated keto-esters, yielding enantiome-
rically enriched tertiary alcohols with excellent enantioselectivi-
ty.11 In our continuous efforts toward exploring primary amine
Primary amine 1d was found to be the best for the reaction in
terms of enantioselectivity among all of the organocatalysts tested
(Table 1), but it gave only moderate yield and enantioselectivity. In
order to further optimize the procedure, we next studied the influ-
ence of the acid and solvent on the reaction outcome (Table 2). It
was found that no desired product was isolated when TfOH was
used or in the absence of an acid (entries 1 and 2); when the reaction
⇑
Corresponding authors. Tel.: +86 817 2568636.
E-mail addresses: quanzhongliu@cwnu.edu.cn (Q. Liu), longhe@cwnu.edu.cn
was carried out in the presence of TsOH or N-Boc-L-phenylglycine,
(L. He).
http://dx.doi.org/10.1016/j.tetasy.2014.05.005
0957-4166/Ó 2014 Elsevier Ltd. All rights reserved.

950
J. Lin et al. / Tetrahedron: Asymmetry 25 (2014) 949–955
R
N
R
N
NH2
N
NH2
CO2H
NH2
R
N
N
H
N
R
NH2
N
Ph
1a
1b
R = CH3
1g
R = OMe
1e
1f
R = OMe
R = H
1c R = H
1h R = H
1d
Figure 1. Catalysts evaluated herein.
Table 1
Direct asymmetric aldol reaction of
a
,b-unsaturated ketone 2a and trifluoroacetophenone 3aa
O
O
O
HO
CF3
10 mol% 1,
CF3
10 mol% TFA
MeCN, rt
4a
2a
3a
Entry
Catalyst 1
Time (h)
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
96
64
54
54
48
48
48
48
—
—
28
46
56
35
43
39
35
84
36
53
29
24
29
47
1g
1h
a
The reaction was performed with 2a (0.1 mmol), 3a (0.3 mmol), 1 (10 mol %), TFA (10 mol %) in MeCN (0.2 mL) at room temperature.
Isolated yield.
Determined by HPLC analysis.
b
c
Table 2
Optimization of reaction conditionsa
O
O
O
10 mol% 1d,
HO
CF3
10 mol% acid
CF3
solvent, rt
2a
4a
3a
Entry
Acid
Solvent
Time (h)
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
8
—
TfOH
TsOH
TFA
2-FC6H4CO2H
4-NO2C6H4CO2H
PhCOOH
CH3CO2H
N-Boc-
N-Boc-
PhCOOH
PhCOOH
PhCOOH
PhCOOH
PhCOOH
PhCOOH
PhCOOH
PhCOOH
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CHCl3
CH2Cl2
Toluene
Xylene
THF
Et2O
Toluene
Toluene
64
64
64
64
64
64
64
64
64
64
64
64
64
64
72
72
64
64
—
Trace
83
55
79
74
69
53
80
71
66
68
75
78
34
47
85
—
—
47
56
51
42
56
53
39
37
83
83
84
79
67
70
82d
82e
9
L
-phenylglycine
-tert-leucine
10
11
12
13
14
15
16
17
18
L
87
a
All reactions were performed with 2a (0.1 mmol), 3a (0.3 mmol), 1d (10 mol %), acid (10 mol %) in solvent (0.2 mL) at room temperature for 64–72 h unless otherwise
indicated.
b
Isolated yield.
Determined by HPLC analysis.
20 mol % PhCO2H.
c
d
e
30 mol % PhCO2H was used.

J. Lin et al. / Tetrahedron: Asymmetry 25 (2014) 949–955
951
Table 3
donating substituents in the phenyl motif were examined for a
reaction with trifluoroacetophenone. As recorded in Table 3, the
primary amine 1d exhibited generally high to excellent enantiose-
lectivities ranging from 83% to 93% ee and good yields for most of
Scope of the substratesa
O
O
O
10 mol% 1d,
HO
CF3
Ar
20 mol% PhCOOH
Ar
CF3
R1
R1
toluene/0.2mL, rt
a,b-unsaturated ketones tested (entries 1–11), with the exception
of the case involving heteroaromatic substrates, in which moderate
yields were obtained (entries 12 and 13). Extending these reaction
conditions to other trifluoroacetophenones was highly successful,
giving rise to trifluoromethylated b-hydroxycarbonyl compounds
with 86–99% ee (entries 14–17). The heteroaromatic trifluoroace-
tophenone could also be tolerated with high stereoselectivity and
moderate yield, as exemplified by trifluoromethyl 2-thiophenyl
3
4
2
Entry R1
Ar
4
Time (h) Yieldb (%) eec (%)
1
2
3
4
5
6
7
8
4-FC6H4
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
4q
4r
36
36
36
36
36
36
36
36
36
36
36
64
64
48
48
48
48
48
48
48
36
72
75
85
74
76
74
79
74
72
72
82
54
57
77
93
82
68
65
64
64
80
87
86
87
91
87
83
83
85
83
87
87
85
87
92
93
99
86
81
93
92
92
4-ClC6H4
4-BrC6H4
4-CH3C6H4
4-CH3OC6H4
2-ClC6H4
2-BrC6H4
3-ClC6H4
3-BrC6H4
3-CH3C6H4
3-CH3OC6H4
2-Furyl
ketone (entry 18). Aliphatic substituted
a,b-unsaturated ketones
could also be used in the aldol reaction, providing the aldol product
with good results (entries 19–21). The absolute configuration of the
product was unambiguously assigned to be (R) by single-crystal
X-ray diffraction of 4c and the other aldol products were assigned
by analogy (Fig. 2).13 Based on the absolute configuration and our
early work,11 a possible activation model via a putative transition
state was proposed (Fig. 2). The conjugated amino diene formed
9
10
11
12
13
14
15
16
17
18
19
20
21
2-Thiophenyl C6H5
C6H5
4-CH3C6H4
C6H5
C6H5
C6H5
n-C3H7
n-C6H13
i-C3H7
4-ClC6H4
4-ClC6H4
4-BrC6H4
4-CH3C6H4
from the chiral amine and
a,b-unsaturated ketone approaches
the trifluoroacetophenone from the Si-face, which is activated by
the hydrogen bonding shown in Figure 2, thus forming the
corresponding (R)-isomer.
2-Thiophenyl 4s
C6H5
C6H5
C6H5
4t
4u
4v
3. Conclusions
a
All reactions was performed with 2 (0.1 mmol), 3 (0.3 mmol), 1d (10 mol %),
PhCOOH (20 mol %) in toluene (0.2 mL) at room temperature for 36–64 h.
b
In conclusion, we have discovered a primary amine 1d cata-
lyzed cross aldol reaction of a,b-unsaturated ketones with trifluo-
Isolated yield.
Determined by HPLC analysis.
c
roacetophenone (ketone–ketone) in the presence of benzoic acid,
affording trifluoromethylated b-hydroxycarbonyl aldol products
bearing a quaternary carbon stereogenic center in high yields (up
to 93% yield) and with high to excellent enantioselectivities of up
to 99% ee. The discovery of the current protocol is complementary
to the aldol reaction with ketones as electrophiles.
the desired aldol product 4a was afforded in high yield but with
low enantioselectivity (entries 3 and 9). In terms of yield and
enantioselectivity, PhCO2H was the optimal acid giving the desired
aldol product 4a in 69% yield and 56% ee (entry 7). Studies on the
solvent effect revealed that the use of CH2Cl2 or CHCl3 as the sol-
vent gave moderate yield and high enantioselectivity (entries 11
and 12). Neither THF nor Et2O was a good solvent for the reaction
(entries 15 and 16). Performing the reaction in toluene gave the
best results in terms of both yield and enantioselectivity (entry
13). Additional studies on the amount of acid indicated that
20 mol % 1d was the best choice, affording the desired aldol prod-
uct 4a in 85% yield and 82% ee (entry 17). Performing the reaction
in the presence of 30 mol % 1d resulted in the same yield accompa-
nied with no improvement in enantioselectivity (entry 18).
4. Experimental
4.1. General
1H NMR spectra and 13C NMR spectra were recorded in CDCl3 on
a
spectrometer operating at 400 and 100 MHz, respectively.
Chemical shifts are reported in parts per million relative to the
appropriate standard: TMS for 1H and 13C NMR spectra. Coupling
constants (J) are reported in Hz and refer to apparent peak
multiplications. Melting points were recorded using Reichert melt-
ing point apparatus and temperatures are uncorrected. Optical
Under the optimal conditions, a range of
a,b-unsaturated
ketones with electron withdrawing substituents, as well as electron
O
HO CF3
4c
Cl
N
H
H
N
O
Ph
Si-facial
CF3
Figure 2. Activation model and absolute configuration of 4c.

952
J. Lin et al. / Tetrahedron: Asymmetry 25 (2014) 949–955
rotations were performed on an OA PLAAR 3005 (589 nm)
using a 700- L cell with a path length of 1 dm. Enantiomeric excesses
(ee) were determined by HPLC analysis on Shimadzu
4.6. (R,E)-1-(4-Bromophenyl)-6,6,6-trifluoro-5-hydroxy-5-phe-
nylhex-1-en-3-one 4d
l
a
LC-20A, using Daicel Chiralcel AD and OD columns. Flash column
chromatography was performed using 200–300 mesh silica gel.
Rf = 0.30 (PE/CH2Cl2 = 1:1), yield: 85%, white solid, mp 59–61 °C,
[a]
25 = À233.2 (c 0.22, CH2Cl2). 87% ee determined by HPLC anal-
D
ysis (chiral AD-H column, 5% IPA in hexane, rate: 1.0 mL/min,
254 nm). Retention time: t(minor) = 27.9 min, t(major) = 30.4 min.
1H NMR (400 MHz, CDCl3): d (ppm) 7.63–7.53 (m, 5H), 7.44–7.36
(m, 5H), 6.71 (d, J = 16.1 Hz, 1H), 3.65 (d, J = 16.9 Hz, 1H), 3.40 (d,
J = 16.9 Hz, 1H); 13C NMR (100 MHz, CDCl3): d (ppm) 198.9,
143.9, 137.6, 132.6, 132.4, 130.0, 128.8, 128.4, 126.3, 126.1,
125.9, 124.6 (J = 283.1 Hz), 76.2 (J = 28.9 Hz), 42.7; ESI-HRMS for
4.2. General procedure for the asymmetric aldol reaction (Table 3)
To a solution of a,b-unsaturated ketones 2 (0.1 mmol) and chiral
primary amines 1 (0.01 mmol) in toluene (0.2 mL) were added
trifluoroacetophenone 3 (0.3 mmol) and PhCO2H (0.02 mmol). The
reaction mixture was stirred at room temperature until the reaction
was complete (monitored by TLC), after which it was quenched
with saturated sodium bicarbonate solution and the mixture was
extracted with dichloromethane (3 Â 10 mL). The combined
organic layers were washed with brine (20 mL) and were dried
over anhydrous Na2SO4. After removal of the solvent under
reduced pressure, the residue was purified through flash column
chromatography on silica gel (petroleum ether/dichloromethane =
3:1–2:1) to afford aldol products 4.
C
18H14BrF3O2 (M+Na)+: 421.0021, Found: 421.0025.
4.7. (R,E)-6,6,6-trifluoro-5-hydroxy-5-phenyl-1-(p-tolyl)hex-1-
en-3-one (4e)
Rf = 0.34 (PE/CH2Cl2 = 1:1), yield: 74%, white solid, mp 64–66 °C,
[a]
25 = À283.0 (c 0.10, CH2Cl2). 91% ee determined by HPLC anal-
D
ysis (chiral OD-H column, 5% IPA in hexane, rate: 1.0 mL/min,
254 nm). Retention time: t(minor) = 16.5 min, t(major) = 22.1 min.
1H NMR (400 MHz, CDCl3): d (ppm) 7.65–7.59 (m, 3H), 7.48–7.34
(m, 5H), 7.26–7.24 (m, 2H), 6.69 (d, J = 16.1 Hz, 1H), 3.66 (d,
J = 16.8 Hz, 1H), 3.39 (d, J = 16.8 Hz, 1H), 2.42 (s, 3H); 13C NMR
(100 MHz, CDCl3): d (ppm) 199.3, 145.6, 142.2, 137.7, 130.9,
129.9, 128.8, 128.7, 128.4, 126.3, 124.8, 123.2 (J = 283.2 Hz), 76.4
4.3. (R,E)-6,6,6-Trifluoro-5-hydroxy-1,5-diphenylhex-1-en-3-one
4a
Rf = 0.32 (PE/CH2Cl2 = 1:1), yield: 85%, white solid, mp 40–42 °C,
[a
]
D
25 = À228.2 (c 0.11, CH2Cl2). 82% ee determined by HPLC anal-
C
19H17F3O2 (M+Na)+:
ysis (chiral AD-H column, 5% IPA in hexane, rate: 1.0 mL/min,
254 nm). Retention time: t(minor) = 14.8 min, t(major) = 16.4 min.
1H NMR (400 MHz, CDCl3): d (ppm) 7.65–7.61 (m, 3H), 7.59–7.57
(m, 2H), 7.49–7.34 (m, 6H), 6.74 (d, J = 16.1 Hz, 1H), 3.68 (d,
J = 16.9 Hz, 1H), 3.41 (d, J = 16.8 Hz, 1H); 13C NMR (100 MHz,
CDCl3): d (ppm) 199.2, 145.5, 137.6, 133.6, 131.4, 129.1, 128.7,
128.6, 128.4, 126.3, 125.8, 124.6 (J = 282.9 Hz), 76.4 (J = 28.8 Hz),
(J = 28.9 Hz), 42.2, 21.6; ESI-HRMS for
357.1075, Found: 357.1071.
4.8. (R,E)-6,6,6-Trifluoro-5-hydroxy-1-(4-methoxyphenyl)-5-phe-
nylhex-1-en-3-one 4f
Rf = 0.34 (PE/CH2Cl2 = 1:1), yield: 76%, white solid, mp 64–66 °C,
25 = À251.9 (c 0.16, CH2Cl2). 87% ee determined by HPLC anal-
42.3; ESI-HRMS for
321.1093.
C
18H15F3O2 (M+H)+: 321.1096, Found:
[a]
D
ysis (chiral AD-H column, 10% IPA in hexane, rate: 1.0 mL/min,
254 nm). Retention time: t(minor) = 24.6 min, t(major) = 29.1 min.
1H NMR (400 MHz, CDCl3): d (ppm) 7.65–7.52 (m, 5H), 7.43–7.36
(m, 3H), 7.02–6.93 (m, 2H), 6.62 (d, J = 16.0 Hz, 1H), 3.88 (s, 3H),
3.64 (d, J = 16.8 Hz, 1H), 3.38 (d, J = 16.8 Hz, 1H); 13C NMR
(100 MHz, CDCl3): d (ppm) 199.1, 162.4, 145.4, 137.8, 130.7,
128.7, 128.4, 126.4, 126.3, 124.6 (J = 283.1 Hz), 123.5, 114.6, 76.4
4.4. (R,E)-6,6,6-Trifluoro-1-(4-fluorophenyl)-5-hydroxy-5-
phenylhex-1-en-3-one 4b
Rf = 0.35 (PE/CH2Cl2 = 1:1), yield: 72%, white solid, mp 54–56 °C,
[
a
]
25 = À256.3 (c 0.16, CH2Cl2). 87% ee determined by HPLC anal-
D
C
19H17F3O3 (M+Na)+:
ysis (chiral OD-H column, 5% IPA in hexane, rate: 1.0 mL/min,
254 nm). Retention time: t(minor) = 22.2 min, t(major) = 27.9 min.
1H NMR (400 MHz, CDCl3): d (ppm) 7.64–7.55 (m, 5H), 7.43–7.36
(m, 3H), 7.15–7.11 (m, 2H), 6.66 (d, J = 16.1 Hz, 1H), 3.65 (d,
J = 16.9 Hz, 1H), 3.40 (d, J = 16.9 Hz, 1H); 13C NMR (100 MHz,
(J = 29.0 Hz), 55.5, 42.0; ESI-HRMS for
373.1022, Found: 373.1028.
4.9. (R,E)-1-(2-Chlorophenyl)-6,6,6-trifluoro-5-hydroxy-5-phe-
nylhex-1-en-3-one 4g
CDCl3):
d (ppm) 198.9, 165.8, 163.3, 144.0, 137.6, 130.7
Rf = 0.35 (PE/CH2Cl2 = 1:1), yield: 74%, colorless oil,
(J = 8.7 Hz), 129.9 (J = 3.5 Hz), 128.7, 128.4, 126.3, 125.4
(J = 2.2 Hz), 123.2 (J = 283.1 Hz), 116.5, 116.3, 76.4 (J = 29.0 Hz),
42.6; ESI-HRMS for
339.0995.
[
a
]
25 = À131.6 (c 0.19, CH2Cl2). 83% ee determined by HPLC anal-
D
C
18H14F4O2 (M+H)+: 339.1002, Found:
ysis (chiral OD-H column, 3% IPA in hexane, rate: 1.0 mL/min,
254 nm). Retention time: t(minor) = 22.2 min, t(major) = 34.3 min.
1H NMR (400 MHz, CDCl3): d (ppm) 8.06 (d, J = 16.2 Hz, 1H), 7.72–
7.59 (m, 3H), 7.49–7.46 (m, 1H), 7.44–7.31 (m, 5H), 6.69 (d,
J = 16.2 Hz, 1H), 3.73 (d, J = 16.8 Hz, 1H), 3.43 (d, J = 16.8 Hz, 1H);
13C NMR (100 MHz, CDCl3): d (ppm) 199.2, 141.1, 137.5, 135.8,
132.1, 131.9, 130.4, 128.8, 128.5, 128.2, 127.8, 127.3, 126.3, 123.1
(J = 282.9 Hz), 76.3 (J = 29.1 Hz), 42.2; ESI-HRMS for C18H14ClF3O2
(M+Na)+: 377.0526, Found: 377.0525.
4.5. (R,E)-1-(4-Chlorophenyl)-6,6,6-trifluoro-5-hydroxy-5-phenyl-
hex-1-en-3-one 4c
Rf = 0.32 (PE/CH2Cl2 = 1:1), yield: 75%, white solid, mp 53–55 °C,
[
a
]
25 = À217.2 (c 0.18, CH2Cl2). 86% ee determined by HPLC anal-
D
ysis (chiral AD-H column, 5% IPA in hexane, rate: 1.0 mL/min,
254 nm). Retention time: t(minor) = 27.3 min, t(major) = 30.5 min.
1H NMR (400 MHz, CDCl3): d (ppm) 7.71–7.62 (m, 2H), 7.57 (d,
J = 16.1 Hz, 1H), 7.51–7.49 (m, 2H), 7.45–7.32 (m, 5H), 6.70 (d,
J = 16.1 Hz, 1H), 3.66 (d, J = 16.9 Hz, 1H), 3.41 (d, J = 16.9 Hz, 1H);
4.10. (R,E)-1-(2-Bromophenyl)-6,6,6-trifluoro-5-hydroxy-5-phe-
nylhex-1-en-3-one 4h
13C NMR (100 MHz, CDCl3):
d (ppm) 198.9, 143.8, 137.6,
Rf = 0.30 (PE/CH2Cl2 = 1:1), yield: 79%, colorless oil,
137.5, 132.1, 129.8, 129.4, 128.8, 128.4, 126.3, 126.1, 124.6
(J = 283.2 Hz), 76.4 (J = 29.0 Hz), 42.7; ESI-HRMS for C18H14ClF3O2
(M+Na)+: 377.0526, Found: 377.0520.
[a
]
25 = À142.3 (c 0.26, CH2Cl2). 83% ee determined by HPLC anal-
D
ysis (chiral AD-H column, 1% IPA in hexane, rate: 1.0 mL/min,
254 nm). Retention time: t(minor) = 19.6 min, t(major) = 25.2 min.

J. Lin et al. / Tetrahedron: Asymmetry 25 (2014) 949–955
953
1H NMR (400 MHz, CDCl3): d (ppm) 8.03 (d, J = 16.2 Hz, 1H), 7.68–
7.61 (m, 4H), 7.44–7.30 (m, 5H), 6.64 (d, J = 16.2 Hz, 1H), 3.73 (d,
J = 16.8 Hz, 1H), 3.42 (d, J = 16.8 Hz, 1H); 13C NMR (100 MHz,
CDCl3): d (ppm) 199.1, 143.8, 142.9, 137.5, 133.7, 132.2, 128.8,
128.5, 128.4, 127.9, 127.8, 126.3, 126.2, 123.1 (J = 283.2 Hz), 76.4
(J = 29.0 Hz), 42.1; ESI-HRMS for C18H14BrF3O2 (M+H)+: 399.0210,
Found: 399.0206.
130.1, 128.7, 128.4, 126.3, 126.0, 123.2 (J = 283.2 Hz), 121.5,
117.4, 113.4, 76.3 (J = 29.0 Hz), 55.4, 42.3; ESI-HRMS for
C
19H17F3O3 (M+Na)+: 373.1022, Found:373.1029.
4.15. (R,E)-6,6,6-Trifluoro-1-(furan-2-yl)-5-hydroxy-5-phenyl-
hex-1-en-3-one 4m
Rf = 0.30 (PE/CH2Cl2 = 1:1), yield: 54%, pale yellow oil,
25 = À138.0 (c 0.05, CH2Cl2). 85% ee determined by HPLC anal-
4.11. (R,E)-1-(3-Chlorophenyl)-6,6,6-trifluoro-5-hydroxy-5-phe-
nylhex-1-en-3-one 4i
[
a
]
D
ysis (chiral OD-H column, 5% IPA in hexane, rate: 1.0 mL/min,
254 nm). Retention time: t(minor) = 15.4 min, t(major) = 23.6 min.
1H NMR (400 MHz, CDCl3): d (ppm) 7.62 (d, J = 7.5 Hz, 2H), 7.56 (d,
J = 1.4 Hz, 1H), 7.42–7.34 (m, 4H), 6.78 (d, J = 3.4 Hz, 1H), 6.64 (d,
J = 15.9 Hz, 1H), 6.54 (dd, J = 1.8, 3.4 Hz, 1H), 3.58 (d, J = 16.8 Hz,
1H), 3.36 (d, J = 16.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): d (ppm)
198.8, 150.5, 146.0, 137.7, 131.0, 128.7, 128.4, 126.3, 123.2
(J = 283.0 Hz), 122.7, 118.0, 113.0, 76.3 (J = 29.0 Hz), 42.7;
ESI-HRMS for C16H13F3O3 (M+H)+: 311.0889, Found: 311.0890.
Rf = 0.36 (PE/CH2Cl2 = 1:1), yield: 74%, colorless oil,
[
a]
D
25 = À162.6 (c 0.19, CH2Cl2). 85% ee determined by HPLC anal-
ysis (chiral OD-H column, 3% IPA in hexane, rate: 1.0 mL/min,
254 nm). Retention time: t(minor) = 32.8 min, t(major) = 40.7 min.
1H NMR (400 MHz, CDCl3): d (ppm) 7.72–7.62 (m, 2H), 7.57–7.53
(m, 2H), 7.44–7.35 (m, 6H), 6.72 (d, J = 16.1 Hz, 1H), 3.66 (d,
J = 16.9 Hz, 1H), 3.41 (d, J = 16.9 Hz, 1H); 13C NMR (100 MHz,
CDCl3): d (ppm) 198.9, 143.6, 137.5, 135.5, 135.2, 131.2, 130.3,
128.8, 128.5, 128.3, 126.9, 126.8, 126.3, 124.6 (J = 282.9 Hz),
4.16. (R,E)-6,6,6-Trifluoro-5-hydroxy-5-phenyl-1-(thiophen-2-
yl)hex-1-en-3-one 4n
76.2 (J = 29.0 Hz), 42.8; ESI-HRMS for
C
18H14ClF3O2 (M+Na)+:
377.0526, Found: 377.0531.
Rf = 0.32 (PE/CH2Cl2 = 1:1), yield: 57%, pale yellow oil,
4.12. (R,E)-1-(3-Bromophenyl)-6,6,6-trifluoro-5-hydroxy-5-phe-
nylhex-1-en-3-one 4j
[
a
]
25 = À153.8 (c 0.03, CH2Cl2). 87% ee determined by HPLC anal-
D
ysis (chiral OD-H column, 5% IPA in hexane, rate: 1.0 mL/min,
254 nm). Retention time: t(minor) = 18.6 min, t(major) = 24.1 min.
1H NMR (400 MHz, CDCl3): d (ppm) 7.75 (d, J = 15.7 Hz, 1H), 7.63
(d, J = 7.5 Hz, 2H), 7.50 (d, J = 5.0 Hz, 1H), 7.43–7.35 (m, 4H), 7.12
(dd, J = 4.0, 4.8 Hz, 1H), 6.53 (d, J = 15.7 Hz, 1H), 3.60 (d,
J = 16.8 Hz, 1H), 3.36 (d, J = 16.8 Hz, 1H); 13C NMR (100 MHz,
CDCl3): d (ppm) 198.6, 139.1, 137.7, 137.6, 133.3, 130.4, 128.7,
128.6, 128.4, 126.3, 124.2, 123.2 (J = 283.3 Hz), 76.4 (J = 28.8 Hz),
25
Rf = 0.32 (PE/CH2Cl2 = 1:1), yield: 72%, colorless oil, [
a
]
D
=
À170.0 (c 0.30, CH2Cl2). 83% ee determined by HPLC analysis
(chiral AD-H column, 4% IPA in hexane, rate: 1.0 mL/min,
254 nm). Retention time: t(minor) = 16.9 min, t(major) = 18.1 min.
1H NMR (400 MHz, CDCl3): d (ppm) 7.81–7.71 (m, 1H), 7.63–7.47
(m, 5H), 7.43–7.29 (m, 4H), 6.71 (d, J = 16.1 Hz, 1H), 3.66 (d,
J = 16.9 Hz, 1H), 3.41 (d, J = 16.9 Hz, 1H); 13C NMR (100 MHz,
CDCl3): d (ppm) 198.8, 143.5, 137.5, 135.7, 134.1, 131.2, 130.6,
128.8, 128.4, 127.3, 126.8, 126.3, 123.2, 123.1 (J = 283.1 Hz),
76.4 (J = 29.0 Hz), 42.8; ESI-HRMS for C18H14BrF3O2 (M+Na)+:
421.0022, Found: 421.0023.
42.5; ESI-HRMS for
349.0490.
C
16H13F3O2S (M+Na)+: 349.0490, Found:
4.17. (R,E)-5-(4-Chlorophenyl)-6,6,6-trifluoro-5-hydroxy-1-phe-
nylhex-1-en-3-one 4o
4.13. (R,E)-6,6,6-Trifluoro-5-hydroxy-5-phenyl-1-(m-tolyl)hex-1-
en-3-one 4k
Rf = 0.31 (PE/CH2Cl2 = 1:1), yield: 77%, white solid, mp 61–63 °C,
[a
]
25 = À290.0 (c 0.13, CH2Cl2). 92% ee determined by HPLC anal-
D
ysis (chiral OD-H column, 4% IPA in hexane, rate: 1.0 mL/min,
254 nm). Retention time: t(minor) = 29.6 min, t(major) = 41.8 min.
1H NMR (400 MHz, CDCl3): d (ppm) 7.64 (d, J = 16.1 Hz, 1H), 7.59–
7.56 (m, 4H), 7.50–7.37 (m, 5H), 6.74 (d, J = 16.1 Hz, 1H), 3.63 (d,
J = 17.0 Hz, 1H), 3.40 (d, J = 17.0 Hz, 1H); 13C NMR (100 MHz,
CDCl3): d (ppm) 199.0, 145.8, 136.3, 135.0, 133.5, 131.6, 129.2,
128.8, 128.7, 127.9, 125.6, 124.3 (J = 283.2 Hz), 76.0 (J = 29.1 Hz),
Rf = 0.30 (PE/CH2Cl2 = 1:1), yield: 72%, white solid, mp 43–45 °C,
[
a]
25 = À250.0 (c 0.16, CH2Cl2). 87% ee determined by HPLC anal-
D
ysis (chiral OD-H column, 5% IPA in hexane, rate: 1.0 mL/min,
254 nm). Retention time: t(minor) = 20.0 min, t(major) = 27.7 min.
1H NMR (400 MHz, CDCl3): d (ppm) 7.65–7.59 (m, 3H), 7.43–7.35
(m, 5H), 7.33–7.28 (m, 2H), 6.72 (d, J = 16.1 Hz, 1H), 3.67 (d,
J = 16.8 Hz, 1H), 3.40 (d, J = 16.8 Hz, 1H), 2.41 (s, 3H); 13C NMR
(100 MHz, CDCl3): d (ppm) 199.3, 145.8, 138.9, 137.7, 133.6,
132.3, 129.4, 129.0, 128.7, 128.4, 126.3, 126.0, 125.6, 124.6
(J = 283.0 Hz), 76.4 (J = 28.9 Hz), 42.2, 21.3; ESI-HRMS for
42.1; ESI-HRMS for
377.0529.
C
18H14ClF3O2 (M+Na)+: 377.0526, Found:
4.18. (R,E)-5-(4-Chlorophenyl)-6,6,6-trifluoro-5-hydroxy-1-(p-
tolyl)hex-1-en-3-one 4p
C
19H17F3O2 (M+H)+: 335.1253, Found: 335.1253.
4.14. (R,E)-6,6,6-Trifluoro-5-hydroxy-1-(3-methoxyphenyl)-5-phe-
nylhex-1-en-3-one 4l
Rf = 0.35 (PE/CH2Cl2 = 1:1), yield: 93%, white solid, mp 52–54 °C,
[a
]
25 = À227.2 (c 0.18, CH2Cl2). 93% ee determined by HPLC anal-
D
ysis (chiral AD-H column, 5% IPA in hexane, rate: 1.0 mL/min,
254 nm). Retention time: t(minor) = 20.1 min, t(major) = 36.8 min.
1H NMR (400 MHz, CDCl3): d (ppm) 7.62–7.54 (m, 3H), 7.50–7.45
(m, 2H), 7.40–7.35 (m, 2H), 7.25–7.13 (m, 2H), 6.68 (d,
J = 16.1 Hz, 1H), 3.60 (d, J = 16.9 Hz, 1H), 3.36 (d, J = 16.9 Hz, 1H),
2.40 (s, 3H); 13C NMR (100 MHz, CDCl3): d (ppm) 199.1, 146.0,
142.4, 136.3, 134.9, 130.8, 129.9, 128.9, 128.7, 127.9, 124.6,
124.3 (J = 283.1 Hz), 76.0 (J = 29.0 Hz), 41.9, 21.6; ESI-HRMS for
Rf = 0.32 (PE/CH2Cl2 = 1:1), yield: 82%, colorless oil,
[
a]
25 = À146.0 (c 0.10, CH2Cl2). 87% ee determined by HPLC anal-
D
ysis (chiral OD-H column, 5% IPA in hexane, rate: 1.0 mL/min,
254 nm). Retention time: t(minor) = 38.3 min, t(major) = 57.0 min.
1H NMR (400 MHz, CDCl3): d (ppm) 7.64–7.57 (m, 3H), 7.43–7.33
(m, 4H), 7.18–7.00 (m, 3H), 6.71 (d, J = 16.1 Hz, 1H), 3.86 (s, 3H),
3.68 (d, J = 16.9 Hz, 1H), 3.41 (d, J = 16.9 Hz, 1H); 13C NMR
(100 MHz, CDCl3): d (ppm) 199.2, 160.0, 145.4, 137.6, 135.0,
C
19H16ClF3O2 (M+H)+: 369.0863, Found: 369.0856.

954
J. Lin et al. / Tetrahedron: Asymmetry 25 (2014) 949–955
4.19. (R,E)-5-(4-Bromophenyl)-6,6,6-trifluoro-5-hydroxy-1-phe-
nylhex-1-en-3-one 4q
analysis (chiral OD-H column, 1% IPA in hexane, rate: 1.0 mL/min,
254 nm). Retention time: t(minor) = 10.9 min, t(major) = 9.4 min.
1H NMR (400 MHz, CDCl3): d (ppm) 7.61–7.59 (m, 2H), 7.43–7.36
(m, 3H), 7.01–6.94 (m, 1H), 6.11 (d, J = 15.9 Hz, 1H), 3.54 (d,
J = 16.8 Hz, 1H), 3.27 (d, J = 16.8 Hz, 1H), 2.30–2.24 (m, 2H), 1.38–
1.29 (m, 8H), 0.95–0.90 (m, 3H); 13C NMR (100 MHz, CDCl3): d
(ppm) 199.5, 151.4, 137.7, 130.4, 128.7, 128.3, 126.3, 123.2
(J = 282.9 Hz), 76.2 (J = 28.7 Hz), 41.4, 32.6, 31.5, 28.8, 27.8, 22.5,
Rf = 0.32 (PE/CH2Cl2 = 1:1), yield: 82%, white solid, mp 117–
119 °C, [
a
]
D
25 = À263.6 (c 0.20, CH2Cl2). 99% ee determined by
HPLC analysis (chiral OD-H column, 2% IPA in hexane, rate:
1.0 mL/min, 254 nm). Retention time: t(minor) = 45.8 min,
t(major) = 58.2 min. 1H NMR (400 MHz, CDCl3): d (ppm) 7.64 (d,
J = 16.1 Hz, 1H), 7.59–7.57 (m, 2H), 7.55–7.43 (m, 7H), 6.74 (d,
J = 16.1 Hz, 1H), 3.63 (d, J = 17.0 Hz, 1H), 3.39 (d, J = 17.0 Hz, 1H);
13C NMR (100 MHz, CDCl3): d (ppm) 199.0, 145.8, 136.8, 133.5,
131.6, 131.6, 129.2, 128.8, 128.2, 125.6, 124.3 (J = 283.2 Hz),
14.0; ESI-HRMS for
351.1656.
C
18H23F3O2 (M+Na)+: 351.1650, Found:
4.24. (R,E)-1,1,1-Trifluoro-2-hydroxy-7-methyl-2-phenyloct-5-
en-4-one 4v
123.2, 76.2 (J = 29.1 Hz), 42.1; ESI-HRMS for
C18H14BrF3O2
(M+Na)+: 421.0021, Found: 421.0028.
25
Rf = 0.30 (PE/CH2Cl2 = 3:1), yield: 80%, colorless oil, [
a]
=
D
À103.0 (c 0.16, CH2Cl2). 92% ee determined by HPLC analysis (chi-
ral AD-H column, 1% IPA in hexane, rate: 1.0 mL/min, 254 nm).
Retention time: t(minor) = 10.3 min, t(major) = 8.6 min. 1H NMR
(400 MHz, CDCl3): d (ppm) 7.61–7.59 (m, 2H), 7.43–7.38 (m, 3H),
6.93 (dd, J = 6.6, 16.0 Hz, 1H), 6.06 (d, J = 16.0 Hz, 1H), 4.18–4.14
(m, 1H), 3.55 (d, J = 16.8 Hz, 1H), 3.29 (d, J = 16.8 Hz, 1H), 2.00–
1.91 (m, 1H), 1.11 (s, 3H), 1.09 (s, 3H); 13C NMR (100 MHz, CDCl3):
d (ppm) 199.9, 157.1, 137.7, 128.7, 128.3, 127.7, 126.3, 124.6
(J = 283.3 Hz), 76.2 (J = 28.8 Hz), 41.5, 31.3, 21.0; ESI-HRMS for
4.20. (R,E)-6,6,6-Trifluoro-5-hydroxy-1-phenyl-5-(p-tolyl)hex-1-
en-3-one 4r
Rf = 0.30 (PE/CH2Cl2 = 1:1), yield: 68%, white solid, mp 57–59 °C,
[a
]
D
25 = À170.0 (c 0.21, CH2Cl2). 86% ee determined by HPLC anal-
ysis (chiral OD-H column, 5% IPA in hexane, rate: 1.0 mL/min,
254 nm). Retention time: t(minor) = 15.2 min, t(major) = 12.6 min.
1H NMR (400 MHz, CDCl3): d (ppm) 7.63 (d, J = 16.2 Hz, 1H), 7.59–
7.57 (m, 2H), 7.52–7.38 (m, 5H), 7.22–7.14 (m, 2H), 6.74 (d,
J = 16.1 Hz, 1H), 3.69 (d, J = 16.9 Hz, 1H), 3.38 (d, J = 16.8 Hz, 1H),
2.36 (s, 3H); 13C NMR (100 MHz, CDCl3): d (ppm) 199.4, 145.4,
138.6, 134.6, 133.6, 131.4, 129.2, 129.1, 128.8, 126.2, 125.8, 123.2
(J = 283.1 Hz), 76.2 (J = 29.0 Hz), 42.3, 21.1; ESI-HRMS for
C
15H17F3O2 (M+Na)+: 309.1181, Found: 309.1175.
Acknowledgments
C
19H17F3O2 (M+H)+: 335.1253, Found: 335.1261.
We are grateful for financial support from the Natural Science
Foundation of China (No. 21102116) and Innovative Research
Team in College of Sichuan Province (No. 14TD0016).
4.21. (S,E)-6,6,6-Trifluoro-5-hydroxy-1-phenyl-5-(thiophen-2-yl)-
hex-1-en-3-one 4s
References
Rf = 0.35 (PE/CH2Cl2 = 1:1), yield: 65%, pale yellow oil,
[
a
]
25 = À156.2 (c 0.20, CH2Cl2). 81% ee determined by HPLC anal-
D
1. For selected reviews on aminocatalysis, see: (a) Butler, R. N.; Coyne, A. G. Chem.
Rev. 2010, 110, 6302; (b) Melchiorre, P.; Marigo, M.; Carlone, A.; Bartoli, G.
Angew. Chem., Int. Ed. 2008, 47, 6138; (c) Mukherjee, S.; Yang, J. W.; Hoffmann,
S.; List, B. Chem. Rev. 2007, 107, 5471; (d) Dondoni, A.; Massi, A. Angew. Chem.,
Int. Ed. 2008, 47, 4638; (e) Pellisier, H. Tetrahedron 2007, 63, 9267; (f) Dalko, P.
I.; Moisan, L. Angew. Chem., Int. Ed. 2004, 43, 5138.
2. For selected reviews on direct aldol reaction, see: (a) Mukaiyama, T. Angew.
Chem., Int. Ed. 2004, 43, 5590; (b) Palomo, C.; Oiarbide, M.; Garcia, J. M. Chem.
Eur. J. 2002, 8, 36; (c) Machajewski, T. D.; Wong, C.-H. Angew. Chem., Int. Ed.
2000, 39, 1352; (d) Casiraghi, G.; Zanardi, F.; Appendino, G.; Rassu, G. Chem.
Rev. 2000, 100, 1929.
ysis (chiral OD-H column, 3% IPA in hexane, rate: 1.0 mL/min,
254 nm). Retention time: t(minor) = 49.1 min, t(major) = 40.8 min.
1H NMR (400 MHz, CDCl3): d (ppm) 7.65 (d, J = 16.2 Hz, 1H), 7.60–
7.58 (m, 2H), 7.48–7.42 (m, 3H), 7.34 (d, J = 5.1 Hz, 1H), 7.15 (d,
J = 3.5 Hz, 1H), 7.02 (dd, J = 3.7, 5.0 Hz, 1H), 6.75 (d, J = 16.2 Hz,
1H), 3.62 (d, J = 16.7 Hz, 1H), 3.35 (d, J = 16.7 Hz, 1H); 13C NMR
(100 MHz, CDCl3): d (ppm) 199.1, 145.8, 141.9, 133.6, 131.5,
129.1, 128.8, 127.1, 126.5, 125.8, 125.7, 123.9 (J = 283.1 Hz), 75.9
(J = 30.7 Hz), 42.9; ESI-HRMS for C16H13F3O2S (M+Na)+: 349.0490,
Found: 349.0495.
3. For selected reviews, see: (a) Notz, W.; Tanaka, F.; Barbas, C. F., III Acc. Chem.
Res. 2004, 37, 580; (b) Mukherjee, S.; Yang, J. W.; Hoffman, S.; List, B. Chem. Rev.
2007, 107, 5471.
4. For selected examples (a) List, B.; Lerner, R. A.; Barbas, C. F., III J. Am. Chem. Soc.
2000, 122, 2395; (b) Notz, W.; List, B. J. Am. Chem. Soc. 2000, 122, 7386; (c)
Sakthivel, K.; Notz, W.; Bui, T.; Barbas, C. F., III J. Am. Chem. Soc. 2001, 123, 5260;
(d) Tang, Z.; Jiang, F.; Yu, L. T.; Cui, X.; Gong, L. Z.; Mi, A. Q.; Jiang, Y. Z.; Wu, Y. D.
J. Am. Chem. Soc. 2003, 125, 5262; (e) Tang, Z.; Jiang, F.; Cui, X.; Gong, L. Z.; Mi, A.
Q.; Jiang, Y. Z.; Wu, Y. D. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 5755; (f)
Northrup, A. B.; Mangion, I. K.; Hettche, F.; MacMillan, D. W. C. Angew. Chem.,
Int. Ed. 2004, 43, 2152; (g) Northrup, A. B.; MacMillan, D. W. C. Science 2004,
305, 1752; (h) Torii, H.; Nakadai, M.; Ishihara, K.; Saito, S.; Yamamoto, H.
Angew. Chem., Int. Ed. 2004, 43, 1983; (i) Kano, T.; Takai, J.; Tokuda, O.;
Maruoka, K. Angew. Chem., Int. Ed. 2005, 44, 3055; (j) Enders, D.; Grondal, C.
Angew. Chem., Int. Ed. 2005, 44, 1210; (k) Casas, J.; Engqvist, M.; Ibrahem, I.;
Kaynak, B.; Co´rdova, A. Angew. Chem., Int. Ed. 2005, 44, 1343; (l) Mase, N.;
Nakai, Y.; Ohara, N.; Yoda, H.; Takabe, K.; Tanaka, F.; Barbas, C. F., III J. Am. Chem.
Soc. 2006, 128, 734; (m) Hayashi, Y.; Sumiya, T.; Takahashi, J.; Gotoh, H.;
Urushima, T.; Shoji, M. Angew. Chem., Int. Ed. 2006, 45, 958.
5. For selected example on primary amine catalysis, see: (a) Luo, S. Z.; Xu, H.; Li, J.
Y.; Zhang, L.; Cheng, J. P. J. Am. Chem. Soc. 2007, 129, 3074; (b) Zeng, B.; Liu, Q.;
Guo, C.; Wang, X.; He, L. Org. Biomol. Chem. 2007, 5, 2913; (c) Ma, X.; Da, C. S.;
Yi, L.; Jia, Y. N.; Guo, Q. P.; Che, L. P.; Wua, F. C.; Wang, J. R.; Li, W. P. Tetrahedron:
Asymmetry 2009, 20, 1419; (d) Li, J. Y.; Luo, S. Z.; Cheng, J. P. J. Org. Chem. 2009,
74, 1747; (e) Da, C. S.; Che, L. P.; Guo, Q. P.; Wu, F. C.; Ma, X.; Jia, Y. N. J. Org.
Chem. 2009, 74, 2541; (f) Miura, T.; Ina, M.; Imai, K.; Nakashima, K.; Yasaku, Y.;
Koyata, N.; Murakami, Y.; Imai, N.; Tada, N.; Itoh, A. Tetrahedron: Asymmetry
2011, 22, 1028; (g) Sarkar, D.; Harman, K.; Ghosh, S.; Headley, A. D. Tetrahedron:
Asymmetry 2011, 22, 1051; (h) Agarwal, J.; Peddinti, R. K. J. Org. Chem. 2011, 76,
3502; (i) Li, L.; Gou, S. H.; Liu, F. Tetrahedron Lett. 2013, 54, 6358.
4.22. (R,E)-1,1,1-Trifluoro-2-hydroxy-2-phenylnon-5-en-4-one
4t
25
Rf = 0.32 (PE/CH2Cl2 = 3:1), yield: 64%, colorless oil, [
a]
=
D
À71.8 (c 0.28, CH2Cl2). 93% ee determined by HPLC analysis (chiral
AD-H column, 1% IPA in hexane, rate: 1.0 mL/min, 254 nm). Reten-
tion time: t(minor) = 11.9 min, t(major) = 10.3 min. 1H NMR
(400 MHz, CDCl3): d (ppm) 7.61–7.59 (m, 2H), 7.43–7.36 (m, 3H),
7.01–6.93 (m, 1H), 6.11 (d, J = 15.9 Hz, 1H), 3.54 (d, J = 16.8 Hz,
1H), 3.28 (d, J = 16.8 Hz, 1H), 2.28–2.22 (m, 2H), 1.58–1.49 (m,
2H), 0.96 (t, J = 7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3): d (ppm)
199.5, 151.1, 137.7, 130.6, 128.7, 128.3, 126.3, 123.2
(J = 283.4 Hz), 76.2 (J = 28.8 Hz), 41.4, 34.6, 21.1, 13.6; ESI-HRMS
for C15H17F3O2 (M+H)+: 287.1181, Found: 287.1188.
4.23. (R,E)-1,1,1-Trifluoro-2-hydroxy-2-phenyldodec-5-en-4-one
4u
Rf = 0.30 (PE/CH2Cl2 = 3:1), yield: 64%, colorless oil,
[a
]
D
25 = À90.8 (c 0.21, CH2Cl2). 92% ee determined by HPLC

J. Lin et al. / Tetrahedron: Asymmetry 25 (2014) 949–955
955
6. For selected examples using ketones as aldol acceptors, see: (a) Paladhi, S.;
Bhati, M.; Panda, D.; Dash, J. J. Org. Chem. 2014, 79, 1473; (b) Xu, B.; Li, L.; Gou,
S. H. Tetrahedron: Asymmetry 2013, 24, 1556; (c) Bastida, D.; Liu, Y. K.; Tian, X.;
Escudero-Adan, E.; Melchiorre, P. Org. Lett. 2013, 15, 220; (d) Pearson, A. J.;
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