Asymmetric synthesis of trifluoromethyl substituted dihydropyrans via organocatalytic cascade Michael-hemiketalization reaction

Article abstract of DOI:10.1016/j.tet.2011.04.086

Asymmetric conjugate addition of ethyl 4,4,4-trifluoroacetoacetate and other trifluoromethyl substituted nucleophiles to β,γ-unsaturated α-keto esters has been developed. The reaction efficiently provided dihydropyrans via cascade Michael-hemiketalization pathways. Quinine-derived thiourea was identified to be the best catalyst. A number of trifluoromethyl substituted dihydropyrans with three consecutive chiral centers were obtained in excellent yields, diastereoselectivities, and enantioselectivities. The product was readily transformed to the corresponding tetrahydropyridine without the loss of the optical purity.

Full text of DOI:10.1016/j.tet.2011.04.086

Tetrahedron 67 (2011) 4578e4583
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Asymmetric synthesis of trifluoromethyl substituted dihydropyrans via
organocatalytic cascade Michaelehemiketalization reaction
*
Jin-jia Wang, Zhi-peng Hu, Chun-liang Lou, Jun-liang Liu, Xue-ming Li, Ming Yan
Institute of Drug Synthesis and Pharmaceutical Process, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Asymmetric conjugate addition of ethyl 4,4,4-trifluoroacetoacetate and other trifluoromethyl substituted
Received 11 December 2010
Received in revised form 14 April 2011
Accepted 22 April 2011
nucleophiles to
b,g-unsaturated a-keto esters has been developed. The reaction efficiently provided
dihydropyrans via cascade Michaelehemiketalization pathways. Quinine-derived thiourea was identified
to be the best catalyst. A number of trifluoromethyl substituted dihydropyrans with three consecutive
chiral centers were obtained in excellent yields, diastereoselectivities, and enantioselectivities. The
product was readily transformed to the corresponding tetrahydropyridine without the loss of the optical
purity.
Available online 5 May 2011
Keywords:
Asymmetric conjugate addition
Trifluoroacetoacetate
Organocatalysis
Ó 2011 Elsevier Ltd. All rights reserved.
Dihydropyran
1. Introduction
trifluoromethyl substituted dihydropyrans with three consecutive
chiral centers in excellent yields, diastereoselectivities, and
Heterocycles with trifluoromethyl group have played a unique
and important role in medicinal and agricultural chemistry.1 Tri-
fluoromethyl substitution usually exerts profound effects on
chemical and physical properties of the mother compound.2 Con-
tinuous efforts have been made to develop efficient synthetic
methods of these compounds, especially in an enantioselective
enantioselectivities.
2. Results and discussion
The reaction of (E)-methyl 2-oxo-4-phenylbut-3-enoate 1a and
ethyl 4,4,4-trifluoroacetoacetate 2a was studied initially. A series of
thiourea-tertiary amine catalysts 4aed were examined and the
results are summarized in Table 1. The cyclized product 3a was
obtained in all cases, which is obviously generated via cascade
conjugate addition and intramolecular hemiketalization. Take-
moto’s catalyst 4a gave 3a in good yield and enantioselectivity
(Table 1, entry 1).7 Increasing steric hindrance of Takemoto’s cata-
lyst led to catalyst 4b, however it provided 3a with the same
enantioselectivity (Table 1, entry 2). Slight improvement in the
enantioselectivity was achieved by using catalyst 4c derived from
(1S,2S)-1,2-diphenylethane-1,2-diamine (Table 1, entry 3). Quinine-
derived thiourea 4d gave better enantioselectivity and yield (Table
1, entry 4).8 As expected, cinchonine-derived thiourea catalyst 4e
provided enantiomeric 3a in excellent enantioselectivity and yield
(Table 1, entry 5). Besides in dichloromethane, the reaction pro-
ceeded also very well in toluene, THF, and ether (Table 1, entries
6e8). Protonic solvents, such as methanol, led to the significant loss
of enantioselectivity and yield (Table 1, entry 9). Decreasing the
loading of catalyst 4d to 5 mol % resulted in small erosion of
enantioselectivity (Table 1, entry 10). The reaction at lower reaction
temperature did not provide favorable improvement in enantio-
selectivity and yield (Table 1, entry 11).
manner.3
b,g-Unsaturated a-keto esters are active Michael accep-
tors. Chiral metal-based catalysts have been used successfully for
their asymmetric conjugate additions with a number of nucleo-
philes.4 In recent years asymmetric organocatalysis has emerged as
a powerful tool for organic synthesis.5 Organocatalytic conjugate
addition of nucleophiles, such as nitroalkanes, indoles, 2-naph-
thols, malonates, malononitrile, 1,3-diketones,
-unsaturated
-keto esters had been developed.6 While cyclic
1,3-diketones,6c,l,n -oxo aldehydes,6f and -cyano ketones6i were
b-oxo aldehydes to
b,
g
a
b
a
used, cascade Michaelehemiketalization reactions occurred to give
dihydropyrans. To the best of our knowledge, the conjugate addi-
tion of acetoacetates to b,g-unsaturated a-keto esters is not suc-
cessful due to the lower reactivity of acetoacetates. We speculate
that the reactivity of acetoacetates can be improved by introducing
strong electron-withdrawing trifluoromethyl group. In this paper,
we report organocatalytic conjugate addition of ethyl 4,4,4-tri-
fluoroacetoacetate and other trifluoromethyl substituted nucleo-
philes to
b,g-unsaturated a-keto esters. The reaction provided
* Corresponding author. E-mail address: yanming@mail.sysu.edu.cn (M. Yan).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.04.086

J.-jia Wang et al. / Tetrahedron 67 (2011) 4578e4583
4579
Table 1
Table 2
Catalyst screening and optimization of reaction conditionsa
Asymmetric conjugate addition of 2a to
b
,
g
-unsaturated
a
-keto estersa
OH
F3C OH
O
F3C
4d
O
O
O
O
catalyst
(10 mol%)
solvent, rt
O
O
EtO2C
Ph
EtO2C
OR2
O
(10 mol%)
OMe
+
R1
+
Ph
F3C
OEt
F3C
OEt CH2Cl2, rt
CO2Me
O
O
R1
CO2R2
1a-l
3a-m
2a
3a
1a
2a
Entry
R1, R2
Time/h
yieldb/%
drc
eed/%
CF3
1
2
3
4
Ph, Me
15
16
17
16
15
14
14
15
20
15
18
16
18
3a, 93
3b, 84
3c, 82
3d, 82
3e, 85
3f, 91
3g, 93
3h, 90
3i, 76
3j, 90
3k, 85
3l, 88
3m, 95
>30:1
>30:1
>30:1
>30:1
>30:1
23:1
96
94
93
97
95
93
92
94
90
96
94
95
87
CF3
CF3
4-MeePh, Me
4-OMeePh, Me
4-FePh, Me
4-ClePh, Me
4-BrePh, Me
4-BrePh, Me
3-ClePh, Me
S
Ph
S
S
Ph
N
N
H
CF3
N
N
H
CF3
N
H
N
H
CF3
H
N
H
5
N
N
6
4a
4b
4c
7e
8
28:1
>30:1
>30:1
>30:1
27:1
>30:1
18:1
9
Thiophen-2-yl, Me
Ph, Et
10
11
12
13
N
N
H
H
N
H
N
H
N
i
Ph, Pr
CF3
N
CF3
H
H
Ph, allyl
MeO
S
S
iPr, Et
CF3
CF3
a
N
N
Reactions were carried out with 1ael (0.12 mmol), 2a (0.1 mmol), and 4d
4d
4e
(0.01 mmol) in CH2Cl2 (0.5 mL) at room temperature.
b
Isolated yields.
c
dr was determined by 19F NMR analysis.
Entry
Catalyst
Solvent
Time/h
Yieldb/%
drc
eed/%
d
Determined by chiral HPLC.
1
2
3
4
5
6
7
8
4a
4b
4c
4d
4e
4d
4d
4d
4d
4d
4d
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
Toluene
THF
15
15
15
15
15
15
15
15
15
18
36
92
89
89
93
91
81
86
91
41
91
81
>30:1
>30:1
>30:1
>30:1
>30:1
>30:1
>30:1
>30:1
>30:1
>30:1
>30:1
92
92
94
96
95
95
96
96
55
93
96
e
Methyl 4,4,4-trifluoroacetoacetate 2b was used instead of 2a in this reaction.
Ether
9
MeOH
CH2Cl2
CH2Cl2
10e
11f
a
Reactions were carried out with 1a (0.12 mmol), 2a (0.1 mmol), and catalyst
(0.01 mmol) in solvent (0.5 mL) at room temperature.
b
Isolated yields.
c
dr was determined by 19F NMR analysis.
d
Determined by HPLC with a Chiralpak IC column.
e
Compound 4d (5 mol %) was used.
f
The reaction was conducted at 0 ꢁC.
With the optimized reaction conditions in hand, we investigated
the reaction of a series of
4,4,4-trifluoroacetoacetate 2a. The results are summarized in Table 2.
-Unsaturated -keto esters with -phenyl or substituted -phenyl
b,g-unsaturated a-keto esters and ethyl
b,g
a
g
g
provided the products in good yields and excellent enantioselectiv-
ities. The electronic property of substituents seems to exert small
effect on the yields and enantioselectivities (Table 2, entries 1e8).
Fig. 1. X-ray crystal structure of 3g.
g
-(Thiophen-2-yl)-
b
,
g
-unsaturated
a
-keto ester gave the product in
reagent did not show significant changes, but the chemical shift of
3H moved toward downfield slightly (Dd¼þ0.10 ppm). Based on the
conformational analysis of the Mosher esters, the absolute config-
uration of 3a was assigned as (2S,3S,4R) tentatively. The same ab-
solute configurations were suggested for products 3bem.
Several structurally-related trifluoromethyl substituted nucle-
ophiles were also examined and the results are summarized in
Table 3. Methyl 4,4,4-trifluoroacetoacetate 2b provided similar
yield and enantioselectivity with 2a (Table 3, entries 1 and 2). 1,1,1-
Trifluoroacetone is also a suitable nucleophile. Good yield and
enantioselectivity were obtained (Table 3, entry 3). 4,4,4-Trifluoro-
1-phenylbutane-1,3-dione 2d showed lower reactivity. Moderate
yield and good enantioselectivity were achieved after extended
reaction time (Table 3, entry 4).
moderate yield and good enantioselectivity (Table 2, entry 9). Bulk
ester groups could be applied and did not exert significant effect on
the yield and enantioselectivity (Table 2, entries 10e12).
substituted -unsaturated -keto ester is also a suitable substrate.
Excellent yield and good enantioselectivity were achieved (Table 2,
entry 13).
A single crystal of 3g was obtained, however X-ray diffraction
analysis indicated it is a mixed crystal of two enantiomers.9,10 The
absolute configurationof 3g could notbe assignedfromthis analysis,
but the relative configuration could be obtained unambiguously
(Fig. 1). Other products were proposed to have the same relative
configurations. To determine the absolute configuration of the
products, compound 3a was treated with (R) and (S)-Mosher re-
agents, respectively. The corresponding Mosher esters were
obtained and subjected to 1H NMR analysis. The chemical shifts of
4H and 5H in the ester derived from (R)-Mosher reagent moved
toward upfield (Dd¼ꢀ0.42 and ꢀ0.27 ppm). On the other hand, the
chemical shifts of 4H and 5H in the ester derived from (S)-Mosher
g-Alkyl
b,g
a
The product 3n was treated with ammonium acetate according
to the procedure developed by Zhao and co-workers.6i Tetrahy-
dropyridine 5 was obtained in acceptable yield and excellent
enantioselectivity (Scheme 1). Its absolute configuration was hy-
pothesized to be similar with 3n.

4580
J.-jia Wang et al. / Tetrahedron 67 (2011) 4578e4583
Table 3
4.2. Typical procedure for asymmetric conjugate addition of
ethyl 4,4,4-trifluoroacetoacetate to b,g-unsaturated a-keto
esters
Conjugate addition of trifluoromethyl substituted nucleophiles 2aed to 1aa
F3C OH
4d
O
O
O
R3
Ph
(10 mol%)
O
OMe
+
Ph
F3C
R3
A
solution of (E)-methyl 2-oxo-4-phenylbut-3-enoate 1a
CH2Cl2, rt
CO2Me
O
(0.12 mmol), ethyl 4,4,4-trifluoroacetoacetate 2a (0.1 mmol), and
4d (0.01 mmol) in CH2Cl2 (0.5 mL) was stirred at room temperature
for 14 h. After the solvent was evaporated under vacuum, the res-
idue was purified by flash column chromatography over silica gel to
afford 3a as a colorless oil.
1a
2a-d
3a, 3n-p
Entry
R3
Time/h
Yieldb/%
drc
eed/%
1
2
OEt, 2a
OMe, 2b
Me, 2c
Ph, 2d
15
14
24
45
3a, 93
3n, 96
3o, 77
3p, 57
>30:1
22:1
>30:1
>30:1
96
97
92
81
3
4e
4.3. Spectral data of products 3aep
a
Reactions were carried out with 1a (0.12 mmol), 2aed (0.1 mmol), and 4d
4.3.1. 3-Ethyl 6-methyl 2-hydroxy-4-phenyl-2-(trifluoromethyl)-3,4-
(0.01 mmol) in CH2Cl2 (0.5 mL) at room temperature.
20
b
dihydro-2H-pyran-3,6-dicarboxylate (3a). Colorless oil,
[a]
Isolated yields.
D
þ131.4 (c 1.02, CH2Cl2). 1H NMR (400 MHz, CDCl3):
d 7.34e7.31 (m,
c
Determined by 19F NMR analysis.
d
Determined by chiral HPLC.
Compound 1a (0.2 mmol) was used in this case.
3H), 7.18e7.16 (m, 2H), 6.30 (d, J¼2.4 Hz, 1H), 5.40 (s, 1H), 4.03 (dq,
J¼7.2, 1.6 Hz, 2H), 3.98 (dd, J¼11.6, 2.4 Hz, 1H), 3.83 (s, 3H), 2.93 (d,
J¼11.6 Hz, 1H), 0.99 (t, J¼7.2 Hz); 13C NMR (100 MHz, CDCl3):
e
d
172.4, 161.7, 140.0, 138.3, 129.0, 128.2, 127.9, 121.9 (q,
F3C OH
O
F3C OH
2
1JCF3¼285 Hz), 114.0, 94.1 (q, JCF3¼34 Hz), 62.3, 52.6, 47.3, 40.2,
MeO2C
MeO2C
NH4OAc
NH
13.6; 19F NMR (376 MHz, CDCl3):
(w), 1741 (s), 1662 (m), 1496 (m), 1442 (m), 1190 (s), 763 (m), 703
(m); HRMS (ESI) calcd for C17H16F3O6 (MꢀH)ꢀ: 373.0899, found:
373.0907. The enantiomeric excess was determined by HPLC with
d
ꢀ83.92; IR (KBr): 3400 (m), 2959
OMe
OMe
AcOH, EtOAc
rt, 5 d
O
O
3n
5
a Chiralpak IC column (hexane/2-propanol¼95:5,
l
¼220 nm,
97% ee
62% yield, 95% ee
0.8 mL/min); tR (major enantiomer)¼10.78 min, tR (minor
enantiomer)¼18.01 min, 96% ee.
Scheme 1. Transformation of product 3n to tetrahydropyridine 5.
4.3.2. 3-Ethyl 6-methyl 2-hydroxy-4-p-tolyl-2-(trifluoromethyl)-3,4-
20
dihydro-2H-pyran-3,6-dicarboxylate (3b). Light yellow oil, [
a]
3. Conclusion
D
93.2 (c 0.50, CH2Cl2). 1H NMR (400 MHz, CDCl3):
d
7.21 (d, J¼8.0 Hz,
2H), 7.05 (d, J¼8.0 Hz, 2H), 6.27 (d, J¼2.4 Hz, 1H), 5.38 (s, 1H),
4.09e3.99 (m, 2H), 3.94 (dd, J¼11.6, 2.4 Hz, 1H), 3.83 (s, 3H), 2.91 (d,
J¼12.0 Hz, 1H), 2.34 (s, 3H), 1.01 (t, J¼7.2 Hz, 3H); 13C NMR
In conclusion, we have developed an efficient cascade
Michaelehemiketalization reaction of trifluoromethyl substituted
nucleophiles with
thiourea was identified to be the best catalyst. A range of
saturated -keto esters are compatible with this transformation.
b
,
g
-unsaturated
a
-keto esters. Quinine-derived
(100 MHz, CDCl3):
d 172.6, 161.7, 140.0, 137.9, 135.2, 129.7, 127.7,
b,g-un-
121.9 (q, 1JCF3¼285 Hz), 114.3, 94.1 (q, 2JCF3¼33 Hz), 62.3, 52.5, 47.3,
a
39.8, 21.0, 13.6; 19F NMR (376 MHz, CDCl3):
d
ꢀ83.98; IR (KBr): 3402
Trifluoromethyl substituted dihydropyrans with three consecutive
chiralcenterswerepreparedinexcellentyields,diastereoselectivities,
and enantioselectivities. The products could be transformed to the
corresponding chiral tetrahydropyridines conveniently.
(m), 2957 (w), 1173 (s), 1661 (m), 1515 (m), 1441 (m), 1188 (s), 815
(m), 700 (m); HRMS (ESI) calcd for C18H19F3NaO6 (MþNa)þ:
411.1031, found: 411.1012. The enantiomeric excess was determined
by HPLC with a Chiralpak IC column (hexane/2-propanol¼95:5,
l
¼220 nm, 0.8 mL/min); tR (major enantiomer)¼10.98 min, tR
(minor enantiomer)¼21.24 min, 94% ee.
4. Experimental section
4.1. General information
4.3.3. 3-Ethyl 6-methyl 2-hydroxy-4-(4-methoxyphenyl)-2-(tri-
fluoromethyl)-3,4-dihydro-2H-pyran-3,6-dicarboxylate (3c). Yellow
oil, [
a
]
D
20 þ90.9 (c 0.58, CH2Cl2). 1H NMR (400 MHz, CDCl3):
d 7.09
1H NMR, 13C NMR, and 19F NMR spectra were recorded on Bruker
AVANCE 400 spectrometer. Chemical shifts of protons are reported
(d, J¼8.8 Hz, 2H), 6.86 (d, J¼8.8 Hz, 2H), 6.26 (d, J¼2.4 Hz, 1H), 5.42
(s, 1H), 4.09e4.00 (m, 2H), 3.94 (dd, J¼8.0, 2.4 Hz, 1H), 3.82 (s, 1H),
3.80 (s, 3H), 2.90 (d, J¼8.0 Hz, 1H), 1.03 (t, J¼7.2 Hz, 3H); 13C NMR
in parts per million (ppm,
¼0.00 ppm). Chemical shifts of carbons are referenced to the
central line of the chloroform signal (
¼77.00 ppm). Peaks are la-
d) downfield from tetramethylsilane
(d
(100 MHz, CDCl3): d 172.4, 161.8, 159.4, 139.9, 130.2, 129.0, 121.9 (q,
2
d
1JCF3¼285 Hz), 114.5, 114.4, 94.1 (q, JCF3¼34 Hz), 62.2, 55.3, 52.5,
beled as singlet (s), doublet (d), triplet (t), quartet (q), and multiplet
(m). Optical rotations were measured on a PerkineElmer 341 dig-
ital polarimeter. Melting points were measured on a WRS-2A
melting point apparatus and are uncorrected. High-resolution
mass spectra were obtained with Shimadzu LCMS-IT-TOF spec-
trometer. Infrared (IR) spectra were recorded on a Bruker Tensor 37
spectrophotometer. Data are represented as follows: frequency of
47.5, 39.4, 13.6; 19F NMR (376 MHz, CDCl3):
d
ꢀ84.00; IR (KBr): 3419
(m), 2958 (w), 1740 (s), 1660 (m), 1612 (m), 1514 (s), 1441 (m), 1185
(s), 829 (m); HRMS (ESI) calcd for C18H19F3NaO7 (MþNa)þ:
427.0981, found: 427.0966. The enantiomeric excess was de-
termined by HPLC with a Chiralpak IC column (hexane/2-prop-
anol¼95:5,
l
¼220 nm, 0.8 mL/min); tR (major enantiomer)¼
17.56 min, tR (minor enantiomer)¼28.47 min, 93% ee.
absorption (cmꢀ1
)
and intensity of absorption (s¼strong,
m¼medium, and w¼weak). Enantiomeric excesses were de-
termined by HPLC using Daicel Chiralpak IC or AD-H column and
eluting with a hexane/iPrOH solution. Flash chromatography was
performed over silica gel (230e400 mesh), purchased from Qing-
dao Haiyang Chemical Co., Ltd.
4.3.4. 3-Ethyl 6-methyl 4-(4-fluorophenyl)-2-hydroxy-2-(tri-
fluoromethyl)-3,4-dihydro-2H-pyran-3,6-dicarboxylate
20
(3d). Colorless oil,
(400 MHz, CDCl3):
[
a
]
D
þ105.4 (c 0.48, CH2Cl2). 1H NMR
d
7.18e7.14 (m, 2H), 7.06e7.01 (m, 2H), 6.25 (d,
J¼2.0 Hz, 1H), 5.34 (s, 1H), 4.06e3.98 (m, 3H), 3.83 (s, 3H), 2.89 (d,

J.-jia Wang et al. / Tetrahedron 67 (2011) 4578e4583
4581
J¼11.6 Hz, 1H), 1.03 (t, J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3):
62.5, 52.6, 47.1, 39.9, 13.6; 19F NMR (376 MHz, CDCl3):
d
ꢀ83.92; IR
d
172.1, 162.5 (d, J¼246 Hz), 161.6, 140.1, 134.1 (d, J¼3.0 Hz), 129.6 (d,
(KBr): 3402 (m), 2966 (w),1740 (s),1661 (m),1587 (w),1440 (m),1197
(s), 780 (m), 697 (m); HRMS (ESI) calcd for C17H16ClF3NaO6 (MþNa)þ:
431.0485, found: 431.0478. The enantiomeric excess was determined
by HPLC with a Chiralpak AD-H column (hexane/2-propanol¼98:2,
J¼8.0 Hz), 121.9 (q, 1JCF3¼285 Hz), 116.0 (d, J¼21 Hz), 113.7, 94.1 (q,
2JCF3¼34 Hz), 62.3, 52.6, 47.4, 39.4, 13.6; 19F NMR (376 MHz, CDCl3):
d
ꢀ83.96, ꢀ113.60; IR (KBr): 3377 (m), 2926 (w), 1741 (m), 1710 (m),
1652 (m), 1515 (m), 1452 (m), 1194 (s), 836 (m); HRMS (ESI) calcd
for C17H16F4NaO6 (MþNa)þ: 415.0781, found: 415.0768. The enan-
tiomeric excess was determined by HPLC with a Chiralpak IC col-
l
¼220 nm, 0.6 mL/min); tR (major enantiomer)¼41.79 min, tR (minor
enantiomer)¼45.51 min, 94% ee.
umn (hexane/2-propanol¼95:5,
l
¼220 nm, 0.8 mL/min); tR (major
4.3.9. 3-Ethyl 6-methyl 2-hydroxy-4-(thiophen-2-yl)-2-(tri-
enantiomer)¼10.62 min, tR (minor enantiomer)¼13.52 min, 97% ee.
fluoromethyl)-3,4-dihydro-2H-pyran-3,6-dicarboxylate
(3i). Light
20
yellow oil, [
CDCl3):
a
]
þ62.2 ( c 0.54, CH2Cl2). 1H NMR (400 MHz,
D
4.3.5. 3-Ethyl 6-methyl 4-(4-chlorophenyl)-2-hydroxy-2-(tri-
fluoromethyl)-3,4-dihydro-2H-pyran-3,6-dicarboxylate
d
7.27e7.25 (m, 1H), 6.96e6.92 (m, 2H), 6.31 (d, J¼2.4 Hz,
1H), 5.28 (s, 1H), 4.36 (dd, J¼11.6, 2.4 Hz, 1H), 4.12 (q, J¼7.2 Hz,
(3e). Colorless oil, [
CDCl3):
a
]
20 þ113.1 (c 0.42, CH2Cl2). 1H NMR (400 MHz,
2H), 2.99 (d, J¼12.0 Hz, 1H), 1.10 (t, J¼7.2 Hz, 3H); 13C NMR
D
d
7.32 (d, J¼8.4 Hz, 2H), 7.12 (d, J¼8.4 Hz, 2H), 6.23 (d,
(100 MHz, CDCl3): d 172.0, 161.6, 140.6, 139.6, 127.0, 126.2, 126.1,
J¼2.0 Hz, 1H), 5.37 (s, 1H), 4.10e4.02 (m, 2H), 3.99 (dd, J¼12.0,
121.5 (q, 1JCF3¼285 Hz), 113.5, 94.1 (q, 2JCF3¼34 Hz), 62.5, 52.6, 47.8,
2.4 Hz, 1H), 2.89 (d, J¼12.0 Hz, 1H), 1.04 (t, J¼7.2 Hz, 3H); 13C NMR
35.5, 13.6; 19F NMR (376 MHz, CDCl3):
d
ꢀ83.90; IR (KBr): 3422
(100 MHz, CDCl3):
d
171.9, 161.6, 140.2, 136.9, 134.1, 129.3, 129.2,
(m), 2989 (w), 1738 (s), 1658 (m), 1446 (m), 1196 (s), 703 (m);
HRMS (ESI) calcd for C15H15F3NaO6S (MþNa)þ: 403.0439, found:
403.0446. The enantiomeric excess was determined by HPLC with
121.8 (q, 1JCF3¼285 Hz), 113.5, 94.1(q, 2JCF3¼34 Hz), 62.4, 52.6, 47.3,
39.5, 13.6; 19F NMR (376 MHz, CDCl3):
d
ꢀ83.91; IR (KBr): 3393 (m),
2959 (w), 1740 (s), 1662 (m), 1492 (m), 1441 (m), 1191 (s), 822 (m),
709 (m); HRMS (ESI) calcd for C17H16ClF3NaO6 (MþNa)þ: 431.0485,
found: 431.0480. The enantiomeric excess was determined by HPLC
a Chiralpak IC column (hexane/2-propanol¼95:5,
l
¼220 nm,
0.8 mL/min); tR (major enantiomer)¼11.47 min, tR (minor
enantiomer)¼15.74 min, 90% ee.
with a Chiralpak IC column (hexane/2-propanol¼95:5, ¼220 nm,
l
0.8 mL/min); tR (major enantiomer)¼11.04 min, tR (minor
enantiomer)¼12.99 min, 95% ee.
4.3.10. Diethyl 2-hydroxy-4-phenyl-2-(trifluoromethyl)-3,4-dihydro-
20
2H-pyran-3,6-dicarboxylate (3j). Colorless oil, [
a
]
D
86.7 (c 0.58,
CH2Cl2). 1H NMR (400 MHz, CDCl3):
d
7.36e7.31 (m, 3H), 7.19e7.17
4.3.6. 3-Ethyl
6-methyl
4-(4-bromophenyl)-2-hydroxy-2-(tri-
(m, 2H), 6.27 (d, J¼2.4 Hz, 1H), 5.39 (s, 1H), 4.32e4.25 (m, 2H), 4.02
(qd, J¼7.2, 1.2 Hz, 2H), 3.98 (dd, J¼12.0, 2.4 Hz, 1H), 2.94 (d,
J¼12.0 Hz, 1H), 1.32 (t, J¼7.2 Hz, 3H), 0.98 (t, J¼7.2 Hz, 3H); 13C NMR
fluoromethyl)-3,4-dihydro-2H-pyran-3,6-dicarboxylate
(3f). Colorless oil,
(400 MHz, CDCl3):
20
[
a]
þ96.7 (c 0.72, CH2Cl2). 1H NMR
D
d
7.47 (d, J¼8.4 Hz, 2H), 7.07 (d, J¼8.4 Hz, 2H),
(100 MHz, CDCl3): d 172.4, 161.2, 140.2, 138.4, 129.0, 128.1, 127.9,
6.22 (d, J¼2.4 Hz, 1H), 5.35 (s, 1H), 4.10e4.01 (m, 2H), 3.98 (dd,
J¼12.0, 2.4 Hz, 1H), 3.83 (s, 3H), 2.89 (d, J¼12.0 Hz, 1H), 1.04 (t,
121.9 (q, 1JCF3¼285 Hz), 113.7, 94.1 (q, 2JCF3¼34 Hz), 62.2, 61.7, 47.3,
40.2, 14.0, 13.6; 19F NMR (376 MHz, CDCl3):
(m), 2988 (w), 1737 (s), 1658 (m), 1459 (m), 1197 (s), 760 (m), 702
(m); HRMS (ESI) calcd for C18H19F3NaO6 (MþNa)þ: 411.1031, found:
411.1023. The enantiomeric excess was determined by HPLC with
d
ꢀ83.91; IR (KBr): 3432
J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d
171.8, 161.6, 140.2,
1
137.4, 132.2, 129.6, 122.1, 121.8 (q, JCF3¼285 Hz), 113.4, 94.1 (q,
2JCF3¼34 Hz), 62.4, 52.6, 47.2, 39.6, 13.6; 19F NMR (376 MHz,
CDCl3):
d
ꢀ83.87; IR (KBr): 3359 (m), 2982 (w), 1741 (s), 1715 (s),
a Chiralpak IC column (hexane/2-propanol¼95:5,
l
¼220 nm,
1668 (m), 1486 (m), 1446 (m), 1196 (s), 824 (m), 706 (m); HRMS
(ESI) calcd for C17H16BrF3NaO6 (MþNa)þ: 474.9980, found:
474.9978. The enantiomeric excess was determined by HPLC with
0.8 mL/min); tR (major enantiomer)¼9.40 min, tR (minor
enantiomer)¼13.84 min, 96% ee.
a Chiralpak IC column (hexane/2-propanol¼95:5,
l
¼220 nm,
4.3.11. 3-Ethyl 6-isopropyl 2-hydroxy-4-phenyl-2-(trifluoromethyl)-
0.8 mL/min); tR (major enantiomer)¼11.90 min, tR (minor
enantiomer)¼13.03 min, 93% ee.
20
3,4-dihydro-2H-pyran-3,6-dicarboxylate (3k). Colorless oil, [
a]
D
73.6 (c 0.62, CH2Cl2). 1H NMR (400 MHz, CDCl3):
d
7.36e7.31 (m,
3H), 7.20e7.18 (m, 2H), 6.23 (d, J¼2.0 Hz,1H), 5.49 (s,1H), 5.17e5.09
4.3.7. Dimethyl 4-(4-bromophenyl)-2-hydroxy-2-(trifluoromethyl)-
(m, 1H), 4.04e3.98 (m, 3H), 2.94 (d, J¼12.0 Hz, 1H), 1.29 (t, J¼6.0 Hz,
20
3,4-dihydro-2H-pyran-3,6-dicarboxylate (3g). Colorless oil, [
a]
D
6H), 0.98 (t, J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d 172.1, 160.7,
81.3 (c 0.52, CH2Cl2). 1H NMR (400 MHz, CDCl3):
d
7.47 (d, J¼8.4 Hz,
140.3, 138.5, 128.5, 128.1, 127.9, 121.9 (q, 1JCF3¼285 Hz), 113.4, 94.0
2H), 7.06 (d, J¼8.4 Hz, 2H), 6.22 (d, J¼2.4 Hz, 1H), 5.36 (s, 1H), 4.02
(dd, J¼12.0, 2.4 Hz, 1H), 3.82 (s, 3H), 3.58 (s, 3H), 2.92 (d, J¼11.6 Hz,
2
(q, JCF3¼33 Hz), 69.5, 62.1, 47.4, 40.1, 21.6, 21.5, 13.5; 19F NMR
(376 MHz, CDCl3):
d
ꢀ83.96; IR (KBr): 3438 (m), 2985 (w), 2930 (w),
1H); 13C NMR (100 MHz, CDCl3):
d 171.8, 161.7, 140.1, 137.4, 132.2,
1734 (m), 1665 (m), 1502 (w), 1458 (m), 1194 (m), 762 (m), 703 (m);
HRMS (ESI) calcd for C19H21F3NaO6 (MþNa)þ: 425.1188, found:
425.1200. The enantiomeric excess was determined by HPLC with
1
2
129.5, 122.2, 121.7 (q, JCF3¼285 Hz), 94.1 (q, JCF3¼34 Hz), 52.9,
52.6, 47.4, 39.4; 19F NMR (376 MHz, CDCl3):
d
ꢀ83.91; IR (KBr);
HRMS (ESI) calcd for C16H14BrF3NaO6 (MþNa)þ: 460.9824, found:
a Chiralpak IC column (hexane/2-propanol¼95:5,
l
¼220 nm,
460.9807. The enantiomeric excess was determined by HPLC with
0.8 mL/min); tR (major enantiomer)¼7.85 min, tR (minor
enantiomer)¼11.35 min, 94% ee.
a Chiralpak AD-H column (hexane/2-propanol¼95:5, ¼220 nm,
l
0.7 mL/min); tR (minor enantiomer)¼19.4 min, tR (major
enantiomer)¼20.9 min, 92% ee.
4.3.12. 6-Allyl 3-ethyl 2-hydroxy-4-phenyl-2-(trifluoromethyl)-3,4-
dihydro-2H-pyran-3,6-dicarboxylate (3l). Colorless oil, [
a
]
20 þ75.7
D
4.3.8. 3-Ethyl
6-methyl
4-(3-chlorophenyl)-2-hydroxy-2-(tri-
(c 0.70, CH2Cl2). 1H NMR (400 MHz, CDCl3):
d
7.36e7.30 (m, 3H),
fluoromethyl)-3,4-dihydro-2H-pyran-3,6-dicarboxylate
(3h). Colorless oil, [
a
]
20 þ87.7 (c 0.62, CH2Cl2). 1H NMR (400 MHz,
7.19e7.17 (m, 2H), 6.30 (d, J¼2.4 Hz, 1H), 5.96e5.90 (m, 1H), 5.46 (s,
1H), 5.39e5.34 (m, 1H), 5.28e5.25 (m, 1H), 4.77e4.67 (m, 2H), 4.04
(qd, J¼7.2, 1.6 Hz, 2H), 4.00 (dd, J¼12.0, 2.4 Hz, 1H), 2.94 (d,
J¼12.0 Hz, 1H), 0.98 (t, J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3):
D
CDCl3):
d
7.30e7.26 (m, 2H), 7.17 (m, 1H), 7.09e7.06 (m, 1H), 6.25 (d,
J¼2.0 Hz,1H), 5.29(s,1H), 4.07 (qd, J¼7.2, 0.4 Hz, 2H), 3.97 (dd, J¼12.0,
2.4 Hz, 1H), 3.84 (s, 3H), 2.89 (d, J¼11.6 Hz, 1H), 1.04 (t, J¼7.2 Hz, 3H);
13C NMR (100 MHz, CDCl3):
d 172.1, 161.5, 140.4, 140.3, 134.9, 130.3,
d
172.2, 160.9, 140.0, 138.3, 131.4, 129.0, 128.1, 127.9, 121.9 (q,
2
1JCF3¼285 Hz), 118.8, 114.2, 94.1 (q, JCF3¼34 Hz), 66.1, 62.2, 47.4,
128.5, 128.1, 126.1, 121.8 (q, 1JCF3¼285 Hz),113.0, 94.0 (q, 2JCF3¼34 Hz),

4582
J.-jia Wang et al. / Tetrahedron 67 (2011) 4578e4583
40.2, 13.6; 19F NMR (376 MHz, CDCl3):
d
ꢀ83.98; IR (KBr): 3411 (m),
0.8 mL/min); tR (major enantiomer)¼14.95 min, tR (minor
enantiomer)¼47.41 min, 81% ee.
2985 (w), 2937 (w), 1734 (s), 1660 (m), 1495 (m), 1455 (m), 1188 (s),
762 (m), 702 (m); HRMS (ESI) calcd for C19H19F3NaO6 (MþNa)þ:
423.1031, found: 423.1031. The enantiomeric excess was de-
termined by HPLC with a Chiralpak IC column (hexane/2-prop-
4.4. Preparation of dimethyl 6-hydroxy-4-phenyl-6-
(trifluoromethyl)-1,4,5,6-tetrahydropyridine-2,5-
dicarboxylate (5)
anol¼95:5,
l
¼220 nm, 0.8 mL/min); tR (major enantiomer)¼
8.69 min, tR (minor enantiomer)¼11.89 min, 95% ee.
4.3.13. Diethyl 2-hydroxy-4-isopropyl-2-(trifluoromethyl)-3,4-dihy-
Compound 3n (36.0 mg, 0.1 mmol) was dissolved in ethyl ace-
tate/acetic acid (v/v¼1:1, 2.5 mL) and stirred at room temperature
for 15 min. After ammonium acetate (92.4 mg,1.2 mmol) was added
in portions, the reaction solution was stirred at room temperature
for 5 days. Water (2.0 mL) was added and the aqueous layer was
extracted with ethyl acetate (3.0 mLꢂ2). The combined organic layer
was washed with brine (2.0 mL) and dried over anhydrous Na2SO4.
After the evaporation of the solvent under reduced pressure, the
20
dro-2H-pyran-3,6-dicarboxylate (3m). Colorless oil, [
a
]
þ59.3 (c
D
0.56, CH2Cl2). 1H NMR (400 MHz, CDCl3):
d
6.16 (d, J¼1.2 Hz, 1H),
5.23 (s, 1H), 4.33e4.21 (m, 4H), 2.83e2.76 (m, 2H), 1.81e1.75 (m,
1H), 1.34e1.30 (m, 6H), 1.09 (d, J¼6.8 Hz, 3H), 0.86 (d, J¼6.8 Hz,
3H); 13C NMR (100 MHz, CDCl3):
d 173.2, 161.2, 140.8, 122.0 (q,
2
1JCF3¼285 Hz), 111.1, 93.9 (q, JCF3¼33 Hz), 62.4, 61.5, 42.7, 39.4,
28.3, 20.2, 16.8, 14.0, 13.8; 19F NMR (376 MHz, CDCl3):
d
ꢀ83.98; IR
(KBr): 3411 (m), 2967 (m), 2932 (m), 1738 (s), 1662 (m), 1468 (m),
1185 (s), 761 (m), 703 (m); HRMS (ESI) calcd for C15H21F3NaO6
(MþNa)þ: 377.1188, found: 377.1179. The enantiomeric excess was
determined by HPLC with a Chiralpak IC column (hexane/2-
crude product was purified by column chromatography over silica
20
gel to afford 5 as a light yellow oil, [
NMR (400 MHz, CDCl3):
a]
35.0 (c 0.08, CH2Cl2). 1H
D
d
7.33e7.29 (m, 3H), 7.19e7.17 (m, 2H), 5.86
(d, J¼2.0 Hz,1H), 5.14 (s,1H), 4.98 (s,1H), 3.99 (dd, J¼12.0, 2.4 Hz,1H),
propanol¼95:5, ¼220 nm, 0.8 mL/min); tR (major enantiomer)¼
l
3.82 (s, 3H), 3.48 (s, 3H), 2.98 (d, J¼12.0 Hz,1H); 13C NMR (100 MHz,
7.33 min, tR (minor enantiomer)¼9.64 min, 87% ee.
CDCl3):
d 174.6, 163.4, 139.8, 129.9, 128.9, 127.9, 123.5 (q,
1JCF3¼285 Hz), 110.0, 80.5 (q, 2JCF3¼31 Hz), 52.6, 52.5, 48.3, 41.8; 19
F
4.3.14. Dimethyl 2-hydroxy-4-phenyl-2-(trifluoromethyl)-3,4-dihy-
NMR (376 MHz, CDCl3):
d
ꢀ83.36; IR (KBr): 3396 (m), 2957 (w),1731
20
dro-2H-pyran-3,6-dicarboxylate (3n). Colorless oil, [
a
]
D
þ98.8 (c
(s), 1663 (m), 1492 (m), 1438 (s), 762 (m), 703 (m); HRMS (ESI) calcd
for C16H15F3NO5 (MꢀH)ꢀ: 358.0902, found: 358.0899. The enan-
tiomeric excess was determined by HPLC with a Chiralpak IC column
0.68, CH2Cl2). 1H NMR (400 MHz, CDCl3):
d
7.36e7.30 (m, 3H),
7.18e7.16 (m, 2H), 6.29 (d, J¼2.0 Hz, 1H), 6.29 (s, 1H), 4.04 (dd,
J¼12.0, 2.4 Hz, 1H), 3.81 (s, 3H), 3.54 (s, 3H), 2.97 (d, J¼12.0 Hz, 1H);
(hexane/2-propanol¼95:5,
l
¼254 nm, 0.8 mL/min); tR (major
13C NMR (100 MHz, CDCl3):
d 172.0, 161.8, 139.8, 138.3, 129.0, 128.1,
enantiomer)¼7.61 min, tR (minor enantiomer)¼9.59 min, 95% ee.
127.8, 121.8 (q, 1JCF3¼285 Hz), 114.4, 94.1 (q, 2JCF3¼33 Hz), 52.7, 52.4,
47.6, 39.8; 19F NMR (376 MHz, CDCl3):
2961 (w), 1744 (m), 1713 (m), 1651 (m), 1506 (m), 1196 (m), 760 (m),
707 (m); HRMS (ESI) calcd for C16H15F3NaO6 (MþNa)þ: 383.0718,
found: 383.0717. The enantiomeric excess was determined by HPLC
d
ꢀ84.13; IR (KBr): 3369 (m),
4.5. Preparation of the single crystal of product 3g
To a solution of enantiorich product 3g (0.27g, 92% ee) in ethyl
acetate (5 mL), was added petroleum ether (15 mL). The resulted
solution was placed in a small bottle. The mouth of the bottle was
covered with a layer of ParafilmÔ. The film was punctured with
several small holes to allow the slow evaporation of the solvent.
The solution was kept for a couple of days. Several small crystals
were formed and one of them was taken for the X-ray diffraction
analysis. The enantiomeric excess of the crystal was 25% as de-
termined by chiral HPLC.
with a Chiralpak IC column (hexane/2-propanol¼95:5, ¼220 nm,
l
0.8 mL/min); tR (major enantiomer)¼10.30 min, tR (minor
enantiomer)¼15.10 min, 97% ee.
4.3.15. Methyl 3-acetyl-2-hydroxy-4-phenyl-2-(trifluoromethyl)-3,4-
dihydro-2H-pyran-6-carboxylate (3o). Light yellow oil, [
a]
20 103.3
D
(c 0.18, CH2Cl2). 1H NMR (400 MHz, CDCl3):
d
7.39e7.33 (m, 3H),
7.17e7.15 (m, 2H), 6.26 (d, J¼2.4 Hz, 1H), 5.63 (s, 1H), 3.87 (dd,
J¼11.6, 2.4 Hz, 1H), 3.83 (s, 3H), 3.21 (d, J¼11.6 Hz, 1H), 1.81 (s, 3H);
13C NMR (100 MHz, CDCl3):
d 211.4, 161.7, 140.1, 138.3, 129.4, 128.4,
127.8, 122.1 (q, 1JCF3¼285 Hz), 114.0, 94.4 (q, 2JCF3¼33 Hz), 52.5, 51.8,
4.6. Preparation of the Mosher esters of product 3a
41.3, 32.9; 19F NMR (376 MHz, CDCl3):
2956 (w), 1736 (s), 1659 (m), 1535 (m), 1497 (m), 1191 (s), 763 (m),
709 (m); HRMS (ESI) calcd for C16H15F3NaO5 (MþNa)þ: 367.0796,
found: 367.0764. The enantiomeric excess was determined by HPLC
d
ꢀ83.26; IR (KBr): 3434 (m),
To a solution of 3a (10 mg, 27
pyridine (0.33 mg, 2.6 mol) in CH2Cl2 (0.8 mL) were added Et3N
(15 L, 0.11 mmol) and (S)-MTPA-Cl (11.2 L, 60 mol) at room
mmol) and 4-dimethylamino-
m
m
m
m
with a Chiralpak IC column (hexane/2-propanol¼95:5, ¼220 nm,
l
temperature. The mixture was stirred for 12 h and diluted with
Et2O (2.0 mL). The organic layer was washed with saturated
aqueous NH4Cl and brine and then dried over anhydrous Na2SO4.
After the solvent was evaporated, the crude product was purified by
column chromatography over silica gel (petroleum ether/
EtOAc¼20:1) to give the corresponding Mosher ester as an oil
0.8 mL/min); tR (major enantiomer)¼10.91 min, tR (minor
enantiomer)¼15.84 min, 92% ee.
4.3.16. Methyl 3-benzoyl-2-hydroxy-4-phenyl-2-(trifluoromethyl)-
3,4-dihydro-2H-pyran-6-carboxylate (3p). Colorless oil, [
a]
20 101.8
D
(c 0.34, CH2Cl2). 1H NMR (400 MHz, CDCl3):
d
7.48e7.43 (m, 3H),
(8 mg, 51% yield). 1H NMR (400 MHz, CDCl3):
d 7.58e7.57 (m, 2H),
7.27e7.23 (m, 2H), 7.17e7.08 (m, 5H), 6.38 (d, J¼2.0 Hz, 1H), 6.14 (s,
7.45e7.44 (m, 3H), 7.31e7.30 (m, 3H), 7.12e7.10 (m, 2H), 6.34 (d,
J¼2.0 Hz, 1H), 4.00e3.89 (m, 2H), 3.87 (s, 3H), 3.84 (dd, J¼12.0,
2.4 Hz, 1H), 3.53 (d, J¼0.8 Hz, 3H), 3.02 (d, J¼12.0 Hz, 1H), 0.97 (t,
1H), 4.11e4.03 (m, 2H), 3.84 (s, 3H); 13C NMR (100 MHz, CDCl3):
d
203.3, 161.7, 140.4, 138.1, 136.0, 134.5, 129.0, 128.5, 128.2, 128.0,
127.8,122.1 (q, 1JCF3¼285 Hz), 114.2, 95.0 (q, 2JCF3¼33 Hz), 52.5, 46.2,
J¼7.2 Hz, 3H); 19F NMR (376 MHz, CDCl3):
d
ꢀ70.87, ꢀ78.77.
42.4; 19F NMR (376 MHz, CDCl3):
(w), 1715 (m), 1685 (m), 1497 (w), 1450 (m), 1200 (m), 765 (m), 699
(m); HRMS (ESI) calcd for C21H17F3NaO5 (MþNa)þ: 429.0926,
found: 429.0914. The enantiomeric excess was determined by HPLC
d
ꢀ83.04; IR (KBr): 3324 (m), 2955
The Mosher ester derived from (R)-MTPA-Cl was obtained
analogously (10 mg, 62% yield). 1H NMR (400 MHz, CDCl3):
d
7.61e7.59 (m, 2H), 7.40e7.38 (m, 3H), 7.28e7.26 (m, 3H),
7.01e7.99 (m, 2H), 6.02 (d, J¼2.0 Hz, 1H), 3.98e3.89 (m, 2H), 3.87 (s,
with a Chiralpak IC column (hexane/2-propanol¼95:5, ¼254 nm,
l
3H), 3.69 (d, J¼1.2 Hz, 3H), 3.47 (dd, J¼12.0, 2.4 Hz, 1H), 2.94 (d,

J.-jia Wang et al. / Tetrahedron 67 (2011) 4578e4583
4583
J¼12.0 Hz, 1H), 0.98 (t, J¼7.2 Hz, 3H); 19F NMR (376 MHz, CDCl3):
Feng, X.-M. Chem. Commun. 2010, 3601; (g) Halland, N.; Velgaard, T.; Jørgensen,
K. A. J. Org. Chem. 2003, 68, 5067.
d
ꢀ71.53, ꢀ77.07.
5. For the selected reviews of organocatalysis, see: (a) Bertelsen, S.; Jørgensen, K.
ꢀ
ꢀ
A. Chem. Soc. Rev. 2009, 36, 2178; (b) Guillena, G.; Najera, C.; Ramon, D. J. Tet-
rahedron: Asymmetry 2007, 18, 2249; (c) Dalko, P. I. Enantioselective Organo-
catalysis; Wiley-VCH: Weinheim, 2007; (d) Pellissier, H. Tetrahedron 2007, 63,
9267; (e) Dondoni, A.; Massi, A. Angew. Chem., Int. Ed. 2008, 47, 4638; (f) Gaunt,
M. J.; Johansson, C. C. C.; McNally, A.; Vo, N. T. Drug Discovery Today 2007, 12, 8.
6. (a) Zeng, M.; Kang, Q.; He, Q.-L.; You, S.-L. Adv. Synth. Catal. 2008, 350, 2169; (b)
Rueping, M.; Nachtsheim, B. J.; Moreth, S. A.; Bolete, M. Angew. Chem., Int. Ed.
2008, 47, 593; (c) Chen, X.-K.; Zheng, C.-W.; Zhao, S.-L.; Chai, Z.; Yang, Y.-Q.; Zhao,
G.; Cao, W.-G. Adv. Synth. Catal. 2010, 352, 1648; (d) Wang, X.-S.; Zheng, C.-W.;
Zhao, S.-L.; Chai, Z.; Zhao, G.; Yang, G.-S. Tetrahedron: Asymmetry 2008, 19, 2699;
(e) Xu, D.-Q.; Wang, Y.-F.; Zhang, W.; Luo, S.-P.; Zhong, A.-G.; Xia, A.-B.; Xu, Z.-Y.
Chem.dEur. J. 2010, 16, 4177; (f) Yao, W.-J.; Pan, L.-J.; Wu, Y.-H.; Ma, C. Org. Lett.
2010, 12, 2422; (g) Juhl, K.; Jørgensen, K. A. Angew. Chem., Int. Ed. 2003, 42, 1498;
(h) Zhao, S.-L.; Zheng, C.-W.; Zhao, G. Tetrahedron: Asymmetry 2009, 20, 1046; (i)
Zhao, S.-L.; Zheng, C.-W.; Wang, H.-F.; Zhao, G. Adv. Synth. Catal. 2009, 351, 2811;
(j) Zheng, C.-W.; Li, Y.-W.; Yang, Y.-Q.; Wang, H.-F.; Cui, H.-F.; Zhang, J.-K.; Zhao, G.
Adv. Synth. Catal. 2009, 351,1685; (k) Zheng, C.-W.; Wu, Y.-Y.; Wang, X.-S.; Zhao, G.
Adv. Synth. Catal. 2008, 350, 2690; (l) Calter, M. A.; Wang, J. Org. Lett. 2009, 11,
Acknowledgements
We thank National Natural Science Foundation of China (No.
20772160, 20972195) and Ministry of Health of China (No.
2009ZX09501-017) for the financial support of this study. We also
thank Professor Ming-liang Tong for the help to determine the
X-ray crystal structure.
References and notes
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