Highly enantioselective Michael addition of aldehy des to nitroolefins catalyzed by primary amine thiourea organocatalysts

Article abstract of DOI:10.1016/j.tet.2010.05.056

Asymmetric Michael addition reactions of aldehydes to nitroolefins have been successfully initiated by a series of primary amine thiourea bifunctional catalysts, with high enantioselectivities (90-98% ee) and excellent yields (80-96%).The privileged quini

Full text of DOI:10.1016/j.tet.2010.05.056

Tetrahedron 66 (2010) 5367e5372
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Highly enantioselective Michael addition of aldehydes to nitroolefins catalyzed
by primary amine thiourea organocatalysts
*
*
Jia-Rong Chen , You-Quan Zou, Liang Fu, Fan Ren, Fen Tan, Wen-Jing Xiao
Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, 152 Luoyu Road, Wuhan, Hubei 430079, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Asymmetric Michael addition reactions of aldehydes to nitroolefins have been successfully initiated by
a series of primary amine thiourea bifunctional catalysts, with high enantioselectivities (90e98% ee) and
excellent yields (80e96%). The privileged quinine scaffold was found to be essential to the reaction
efficiency and enantioselectivity.
Received 7 April 2010
Received in revised form
13 May 2010
Accepted 14 May 2010
Available online 20 May 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Organocatalysis
Michael addition
Amine thiourea
Nitroolefin
1. Introduction
achieve high reactivity and enantioselectivity for difficult sub-
strates and transformations is still challenging and desirable.
During the past decade, there have been remarkable advances in
the development of organocatalysts for enantioselective carbon-
carbon bond-forming reactions,1 particularly for asymmetric Mi-
chael addition reactions.2 In this endeavor, the conjugate addition
of ketones/aldehydes to nitroolefins has received extensive atten-
One part of our research is focused on the development of
bifunctional organocatalysts for asymmetric organic reactions by
the rational combination of privileged chiral scaffolds,8,9 and we
have recently identified chiral amines 1a,b and 2a,b as efficient
catalysts for direct aldol reactions of acetones and Michael addi-
tions of cyclohexanones, respectively (Fig. 1).9 These organo-
catalysts, however, appeared unsuitable for the Michael addition of
tion since the resulting
synthetic building blocks, which can be readily converted into, for
example, chiral pyrrolidines, -amino acids, -butyrolactones, and
g-nitro carbonyl compounds are versatile
g
g
a,
a-disubstitued aldehydes to nitroolefins. While the catalyst 2a
tetrahydropyrans.3 Stimulated by the seminal reports of chiral
amine-catalyzed asymmetric addition of ketones to nitroolefins by
List, Barbas and co-workers,4 several research groups focused on
the development of more efficient primary5 and secondary6 amine-
based catalysts with a critical objective for the improvement of
both stereoselectivity and substrate scope. Although extensive
studies on conjugate additions of ketones to nitroolefins have been
well documented, the reactions with sterically demanding alde-
could, for example, promote the Michael addition of iso-
3
butyraldehyde
to trans-b-nitrostyrene 4a in good yield and
enantioselectivity, 4 days were required to reach the full conversion
"privileged structur s"
e
N
N
O
N
O
N
O
N
H
N
H
N
H
OH
H
H
hydes, such as
a,a-disubstituted aldehydes, have only been ex-
L-proline
N
N
plored with very limited success.5c,n,6q,r,7 Recently, the Jacobsen
group successfully applied primary amine thiourea catalysts to
N
1a
1b
N
N
Michael addition of racemic
a,a-disubstituted aldehydes to
S
N
S
N
HO
b
-substituted Michael acceptors, which provided an important
N
H
N
H
N
H
N
design concept for new bifunctional organocatalysts.7c,d Despite
these elegant works, the search for new organocatalysts that could
H
N
H
H
N
N
cinchonidine
2a
2b
* Corresponding authors. Tel./fax: þ86 27 67862041; e-mail addresses:
Figure 1. Chiral amine catalysts based on ‘rational combination of two privileged
chiral backbones into one’.
jiarongchen2003@yahoo.com.cn (J.-R. Chen), wxiao@mail.ccnu.edu.cn (W.-J. Xiao).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.05.056

5368
J.-R. Chen et al. / Tetrahedron 66 (2010) 5367e5372
Table 1
(Eq.1). Inspired by the recent successful use of chiral primary amine
thioureas and related tertiary amine thioureas as bifunctional
organocatalysts for a wide range of enantioselective reactions,7c,d,9
we speculated that the strategy, combining two privileged scaffolds
into one, may be additionally exploited to design a new class of
thiourea/amine catalysts for this reaction. Our current study shows
that such combinatorial design of catalyst does indeed work and
a series of primary amine thioureas 6e9 have proved to be highly
Effects of the additives on the asymmetric Michael addition of isobutyraldehyde 3 to
trans-
b
-nitrostyrene 4a catalyzed by 6aa
O
O
Ph
6a
catalyst
(10 mol %)
NO2
+
NO2
Ph
H
H
Additive (x mol %)
CHCl3, r.t.
5a
3
4a
efficient and enantioselective for Michael addition of
stitued aldehydes to a range of nitroolefins (Fig. 2).
a
,
a
-disub-
Entry
Additive
x
T (h)
Yieldb (%)
eec (%)
1
2
3
4
d
d
10 days
10 days
<10
48
90
70
68
91
78
97
91
89
82
79
91
85
90
79
75
ND
66
93
94
90
83
92
91
93
92
94
94
95
95
96
96
95
PhCO2H
DIPEA
Et3N
Pyridine
Imidazole
TMG
DMAP
DABCO
DMAP
DMAP
DMAP
DABCO
DABCO
DABCO
DABCO
DABCO
10
10
10
10
10
10
10
10
20
30
40
20
30
40
50
100
7
7
7
7
5
5
5
8
8
8
8
8
8
8
8
O
O
Ph
catalyst 2a (20 mol %)
NO2
NO2
H
H
5
(1)
Ph
+
PhCO2H (20 mol%)
neat, r.t., 4 days
6
3
4a
5a
7d
8
91% yield; 85% ee
9
N
N
N
10
11
12
13
14
15
16
17
S
N
S
N
S
N
H
N
H
H2N
H2N
H2N
N
N
H
H
OMe
H
H
N
N
N
6a
6b
7a
N
N
N
S
S
S
N
H
N
H
N
H
H2N
H2N
H2N
a
Reactions were carried out with isobutyraldehyde 3 (1.5 mmol), trans-b-nitro-
N
N
H
N
H
OMe
OMe
H
styrene 4a (0.5 mmol) and 10 mol % 6a and x mol % additive in CHCl3 (0.75 mL).
ND¼Not determined.
N
N
N
b
7b
8
9
Isolated yield.
Determined by chiral HPLC.
TMG¼1,1,3,3-Tetramethylguanidine.
c
d
Figure 2. Primary amine thiourea organocatalysts examined.
2. Results and discussion
reaction time (Table 1, entry 2). For Michael reactions with chiral
amine catalysts, it was found that the nature of base cocatalyst
strongly influenced both the reaction activity and the enantiose-
lectivity.7,5c Accordingly, the use of different bases was probed. In
all cases, the reactions proceeded smoothly in the presence of 6a
while the reactivity and enantioselectivity varied significantly with
different bases, such as DIPEA, Et3N, pyridine, imidazole, TMG,
DMAP, and DABCO (Table 1, entries 3e9). For instance, under oth-
erwise identical conditions, replacing PhCO2H with base DIPEA led
According to our previous method,9b organocatalyst 7a was
readily prepared from monoprotected chiral diamine 10 and qui-
nine-derived amine 12 in three steps with good overall yields
(Scheme 1).10 Other primary amine thioureas were also synthesized
via this three-step procedure without incident. Notably, the prep-
aration of these catalysts can be easily scaled up on grams. Then,
the catalytic performances were examined in the Michael addition
reaction of isobutyraldehyde to nitroolefins.
to the full conversion of trans-b-nitrostyrene 4a within 7 h and
allowed the reaction to proceed at room temperature with 90%
yield and 93% ee (Table 1, entry 3). Further investigation indicated
that DABCO and DMAP were the best two base additives and
therefore were used for other condition optimizations (Table 1,
entries 8 and 9). Interestingly, when the ratio of DABCO and catalyst
rose to 4:1, the highest reactivity and enantioselectivity could be
obtained. Further increase of the amount of DABCO proved less
effective. Therefore, an optimal of 4:1 ratio of DABCO/6a was used
in our subsequent experiments (Table 1, entry 15).
N
O
O
Et3N, THF
rt, 78%
H2N
N
SCN
N
+
SCCl2
H2N
O
O
OMe
N
10
11
12
CH2Cl2, rt
84%
N
N
Next, a brief survey of reaction media for this organocatalytic
transformation was carried out by the combination of 6a and
DABCO. The yield and enantioselectivity/solvent profile showed
that the CHCl3 was the ideal reaction medium (Table 2, entries
1e9). Then, the catalytic performances of the other catalysts were
evaluated in CHCl3. It was found that catalysts 6be9 catalyzed this
Michael addition efficiently with variant yields and ee. For instance,
by the use of 6b, 80% yield and 96% ee were obtained while almost 2
days were required (Table 2, entry 10). Gratifyingly, we found that
7a showed the superior ee over 6a with shorter reaction time. The
absolute configuration of the Michael adduct was determined by
the chiral diamine backbone. As anticipated, the use of catalysts 8
and 9 (pseudoenantiomers of 6a and 7a, respectively), gave the
corresponding products with opposite configuration with 80% and
86% ee (Table 2, entries 13 and 14). Interestingly, the addition of
5 equiv of H2O has no detrimental effect on the enantioselectivity
S
S
O
.
N2H4 H2O
H2N
HN
N
HN
HN
HN
MeOH, reflux
90%
O
OMe
OMe
N
N
7a
13
Scheme 1. Synthesis of primary amine thiourea organocatalyst 7a.
Initially, the Michael addition of isobutyraldehyde to trans-b-
nitrostyrenes was chosen as the model reaction using 6a as the
catalyst and a variety of additives were examined. As shown in
Table 1, additives played an important role on the reaction effi-
ciency and enantioselectivity. For example, without any additive,
the use of 6a only gave a trace amount of the Michael adduct even
after 10 days (Table 1, entry 1). With the addition of PhCO2H as the
cocatalyst, moderate yield and ee were obtained albeit with long

J.-R. Chen et al. / Tetrahedron 66 (2010) 5367e5372
5369
Table 2
Table 3
Screening of the solvents and catalysts 6e9a
Asymmetric Michael addition of isobutyraldehyde 3e4 catalyzed by catalyst 7a
and 9a
O
O
Ph
catalyst(10 mol %)
O
NO2
O
Ar
+
NO2
7a
9
or (10 mol %)
catalyst
Ph
H
H
DABCO (40 mol %)
solvent, r.t.
NO2
+
NO2
Ar
H
H
DABCO (40 mol %)
CHCl3, r.t.
3
4a
5a
3
4
5
Entry
Cat.
Solvent
T (h)
Yieldb (%)
eec (%)
Entry
Nitroolefin, Ar
Cat.
5
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
8
6a
6a
6a
6a
6a
6a
6a
6a
6a
6b
7a
7b
8
CHCl3
CH2Cl2
EtOAc
Toluene
Et2O
8
9
7
9
9
24
24
24
24
45
7
29
45
45
15
15
90
88
85
80
82
72
<5
51
<5
80
88
70
77
89
81
90
96
95
92
95
92
90
ND
75
ND
96
97
92
ꢀ80
ꢀ86
97
1
2
3
4
5
6
7
8
Ph (4a)
7a
7a
7a
7a
7a
7a
7a
6b
7a
7a
7a
7a
7a
7a
7a
7a
7a
9
5a
5b
5c
5d
5e
5f
5g
5g
5h
5i
5j
5k
5l
5m
5n
5o
5p
5d
5e
5j
88
96
93
87
86
91
80
85
86
85
91
95
93
93
84
95
92
84
85
85
86
96
85
88
97
96
92
95
96
95
95
98
95
90
96
96
94
96
95
97
95
-91
-91
-95
-93
-93
ꢀ97
ꢀ90
4-NO2ePh (4b)
2-NO2ePh (4c)
4-FePh (4d)
THF
DMF
4-BrePh (4e)
2-BrePh (4f)
4-ClePh (4g)
4-ClePh (4g)
2-ClePh (4h)
4-CF3ePh (4i)
4-MeePh (4j)
4-MeOePh (4k)
2-MeOePh (4l)
3,4e(MeO)2ePh (4m)
1-Naphthyl (4n)
2-Furyl (4o)
CH3CN
MeOH
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
9
10
11
12
13
14
15d
16e
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
9
7a
7a
92
a
Reactions were carried out with isobutyraldehyde 3 (1.5 mmol), trans-b-nitro-
2-Thienyl (4p)
4-FePh (4d)
styrene 4a (0.5 mmol) and 10 mol % catalyst and 40 mol % DABCO in solvent
(0.75 mL). ND¼Not determined.
4-BrePh (4e)
4-MeePh (4j)
4-MeOePh (4k)
2-MeOePh (4l)
2-Furyl (4o)
9
9
9
9
9
9
b
Isolated yield.
Determined by chiral HPLC.
H2O (5 equiv) was added.
Compounds 7a (5 mol %) and 20 mol % of DABCO were used.
c
5k
5l
5o
5p
d
e
2-Thienyl (4p)
a
Unless otherwise noted, the reactions were carried out with 0.5 mmol of 4,
1.5 mmol of isobutyraldehyde 3 in 0.75 mL of CHCl3 in the presence of 10 mol % of
catalyst 7a or 9 and 40 mol % of DABCO for the indicated time.
(Table 2, entry 15). And, the reaction still proceeded smoothly when
the amount of 7a was reduced from 10 mol % to 5 mol % giving 5a in
comparable yield but somewhat decreased ee (92%) (Table 2, entry
16 vs entry 11).
b
Isolated yield.
Determined by chiral HPLC.
c
With reaction parameters being optimized to a 7a and DABCO
ratio of 1:4 in CHCl3 at room temperature, we next investigated
the scope of the Michael addition with a variety of nitroolefins.
As highlighted in Table 3, the reaction demonstrated broad
applicability with respect to the nitroolefins. A wide range of
electron-poor and -rich aromatic nitroolefins with variable sub-
stitution patterns reacted well with isobutyraldehyde, affording
the corresponding adducts in generally high yields (80e96%) and
excellent enantioselectivities (90e98% ee) (Table 3, entries
1e14). Fused aromatic nitroolefins, such as 4n, could also be
successfully used in this reaction and high yield (84%) and
excellent ee (95%) were obtained (Table 3, entry 15). Hetero-
aromatic nitroolefins, such as 2-furyl- and 2-thienyl-nitroolefins,
were also well tolerated and gave the products in 97% and 95%
ee, respectively (Table 3, entries 16 and 17). Significantly, the
opposite enantiomeric Michael adducts can be obtained with
comparable high ee when 9/DABCO was used as the catalytic
system under the same conditions (Table 3, entries 18e24).
Therefore, our current protocol should be applicable to doubly
stereo-controlled asymmetric Michael additions for the synthesis
of both enantiomers.11 However, primary amine thiourea 7a
proved unsuitable for the aliphatic nitroolefin at this stage
probably because of the less reactivity.
stereoselectivities of asymmetric Michael addition of isobutyraldehyde
to nitroolefins (Fig. 3). Mechanistically, the in situ formed enamine in-
O
O
Ph
catalyst 7a (10 mol %)
NO2
NO2
H
H
(2)
Ph
+
DABCO (40 mol %)
CHCl3, -30 oC, 5 h
Ph
Ph
14
4a
15
82% yield
syn/anti: 97:3
sy n: 47% ee
termediate between isobutyraldehyde 3 and catalyst 7a attacked the Si-
face of nitroolefin 4a to give the corresponding product (R)-5a. The
beneficial role of the base DABCO may lie in accelerating the tautome-
rization of imine to the enamine by deprotonation.7,5c
N
S
H
N
N
H
O
Ph
N
H
NO2
OMe
(R)
H
O
N
N+
O-
5a
(R)-
In addition, we have preliminarily examined the feasibility of using
other a,a-disubstituted aldehydes as Michael donors in the presence of
Ph
7a. For example, in the case of 2-phenylpropionaldehydes, excellent
diastereomeric ratio of syn/anti (97:3) was obtainedwhilethe ee of major
syn-isomer was moderate (Eq. 2). Further structural modification of
primary amine thiourea catalysts of this type to improve the enantio-
selectivity is underway in our laboratory.
Figure 3. Proposed transition state.
3. Conclusion
Although the precise reaction mechanism needs further study,
a possible transition state was proposed based on the observed
In summary, we have developed a highly enantioselective Mi-
chael addition of isobutyraldehyde to nitroolefins by the use of

5370
J.-R. Chen et al. / Tetrahedron 66 (2010) 5367e5372
cinchona alkaloid-based bifunctional thiourea catalysts. For most
nitroolefins, the designed catalysts exhibited great catalytic effi-
ciency and enantioselectivity (up to 96% yield and 98% ee). Further
modification of the catalyst structure for broader substrate scopes
and investigation of the capacity of these catalysts toward other
asymmetric conjugate addition reactions are in progress.
149.9, 182.3; MS (EI) m/z 449 (rel intensity) (Mþ); C26H35N5S: C,
69.45; H, 7.85; N, 15.57. Found: C, 68.40; H, 7.81; N, 15.60.
4.2.3. Catalyst 7a. 1H NMR (400 MHz, CDCl3, TMS):
d 0.80e1.05 (m,
2H), 1.22e1.76 (m, 10H), 1.97e2.00 (m, 2H), 2.40e2.41 (m, 1H),
2.78e3.24 (m, 3H), 3.67e3.96 (m, 2H), 4.04 (s, 3H), 4.26 (br s, 1H),
5.01e5.08 (m, 2H), 5.70e5.78 (m, 1H), 5.92 (br s, 1H), 7.38 (dd,
J¼2.8, 9.6 Hz, 1H), 7.54 (s, 1H), 7.99 (d, J¼9.2 Hz, 1H), 8.08 (br s, 1H),
4. Experimental section
4.1. General methods
8.76 (d, J¼4.8 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d 24.4, 24.5, 25.7,
26.7, 26.9, 32.1, 38.5, 41.7, 45.8, 54.7, 54.9, 55.8, 57.2, 59.6, 77.2,
102.6, 115.0,119.3, 122.0, 128.1, 131.0, 139.9, 144.4,147.5, 157.8, 181.5;
MS (EI) m/z 479 (rel intensity) (Mþ). Anal. Calcd for C27H37N5OS: C,
67.61; H, 7.77; N, 14.60. Found: C, 67.59; H, 7.74; N, 14.65.
Unless otherwise noted, material were purchased from com-
mercial suppliers and used without further purification. Chloro-
form and dichloromethane were freshly distilled from calcium
hydride. Toluene, ethyl ether and tetrahydrofuran (THF) were dis-
tilled from sodium/benzophenone. Reactions were monitored by
thin layer chromatography (TLC), and column chromatography
purifications were performed using 200e300 mesh silica gel.
1H NMR spectra were recorded on 400 MHz or 600 MHz spec-
trophotometers. Solvent for NMR is CDCl3, unless the otherwise
4.2.4. Catalyst 7b. 1H NMR (400 MHz, CDCl3, TMS):
d 0.89e1.98 (m,
6H), 1.47e1.80 (m, 8H), 2.17e2.36 (m, 4H), 2.86e3.01 (m, 3H), 3.20
(br s, 1H), 5.09e5.19 (m, 2H), 5.84e5.92 (m, 1H), 7.36e7.40 (m, 2H),
7.85 (br s,1H), 8.01 (d, J¼9.2 Hz,1H), 8.73 (d, J¼4.0 Hz,1H); 13C NMR
(100 MHz, CDCl3): d 24.2, 24.8, 25.9, 27.0, 28.9, 31.5, 33.8, 38.7, 45.7,
46.9, 48.4, 55.4, 60.1, 64.5, 77.2, 102.0, 114.5, 119.4, 122.0, 128.1,
130.8, 139.9, 144.2, 147.2, 157.5, 182.0; MS (EI) m/z 479 (rel intensity)
(Mþ). Anal. Calcd for C27H37N5OS: C, 67.61; H, 7.77; N, 14.60. Found:
C, 67.65; H, 7.79; N, 14.57.
noted. Chemical shifts are reported in delta (d) units in parts per
million (ppm) relative to the singlet (0 ppm) for tetramethylsilane
(TMS). Data are reported as follows: chemical shift, multiplicity
(s¼single, d¼doublet, t¼triplet, q¼quartet, br¼broad, m¼multiplet),
coupling constants (Hz) and integration. 13C NMR spectra were
recorded on 100 MHz or 150 MHz. Chemical shifts are reported in
ppm relative to the central line of the heptalet at 77.0 ppm for CDCl3.
The ee values determination was carried out using chiral high-
performance liquid chromatography (HPLC) with Daicel Chiracel
OD-H and AS-H column and the dr values were determined by
400 MHz 1H NMR.
4.2.5. Catalyst 8. 1H NMR (400 MHz, CDCl3, TMS):
d 0.82e0.87 (m,
2H), 1.08e1.35 (m, 6H), 1.45e1.72 (m, 6H), 1.81e1.94 (m, 2H),
2.27e2.31 (m, 1H), 2.70e3.04 (m, 4H), 3.38 (s, 1H), 4.23 (br s, 3H),
5.15e5.22 (m, 2H), 5.82e5.90 (m, 1H), 7.54 (d, J¼4.4 Hz, 1H),
7.65e7.75 (m, 3H), 8.10 (d, J¼8.4 Hz, 1H), 8.60 (br s, 1H), 8.83 (d,
J¼4.4 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d 24.4, 24.5, 24.8, 25.7,
26.9, 32.0, 34.5, 38.6, 45.7, 46.9, 48.3, 55.3, 60.1, 64.6, 77.2, 114.8,
119.3, 124.2, 126.5, 126.9, 129.0, 129.4, 139.4, 147.9, 149.7, 181.9; MS
(EI) m/z 449 (rel intensity) (Mþ). Anal. Calcd for C26H35N5S: C,
69.45; H, 7.85; N, 15.57. Found: C, 69.49; H, 7.81; N, 15.61.
4.2. General procedure for the michael addition reaction of
butyraldehyde 3 to nitroolefin 4 (Table 3)
4.2.6. Catalyst 9. 1H NMR (400 MHz, CDCl3, TMS):
d 0.88e0.99 (m,
The organocatalyst 7a (24.0 mg, 0.05 mmol), DABCO (23.0 mg,
0.20 mmol), and isobutyraldehyde 3 (139 mL, 1.5 mmol) were stir-
2H),1.06e1.13(m,2H),1.20e1.34(m, 4H),1.47e1.74(m, 8H),1.92e2.01
(m, 2H), 2.27e2.33 (m, 1H), 2.74e2.92 (m, 3H), 3.17 (s, 1H), 3.39 (br s,
1H), 4.03 (br s,1H), 4.04 (s, 3H), 5.11e5.31 (m, 2H), 5.83e5.92 (m,1H),
7.39 (dd, J¼2.4, 9.2 Hz, 1H), 7.46 (d, J¼4.4 Hz, 1H), 7.97 (d, J¼9.2 Hz,
red in 0.75 mL of CHCl3 for 10 min at room temperature. Nitroolefin
4 (0.5 mmol) was then added and the reaction mixture was stirred
for 8e48 h. After the complete consumption of the nitroolefin (as
monitored by TLC), the mixture was concentrated under reduced
pressure, and the residue was purified by flash column chroma-
tography on silica gel (petroleum ether/ethyl acetate (4:1 to 2:1)) to
give the corresponding pure Michael adduct. Absolute configura-
tions of the products were determined by comparison of HPLC data
with known literatures. Compounds 5aep and 15 are known.5
1H), 8.67 (br s,1H); 13C NMR (100 MHz, CDCl3):
d 24.4, 25.1, 25.2, 26.0,
26.8, 32.1, 34.4, 38.6, 45.9, 47.0, 48.4, 55.0, 55.5, 60.0, 77.2,102.1,114.6,
119.2, 122.1, 128.1, 130.9, 139.7, 144.2, 147.2, 157.6, 181.9; MS (EI) m/z
479 (rel intensity) (Mþ). Anal. Calcd for C27H37N5OS: C, 67.61; H, 7.77;
N, 14.60. Found: C, 67.64; H, 7.74; N, 14.64.
4.2.7. (R)-2,2-Dimethyl-4-nitro-3-phenylbutanal (5a), (Table 3, entry
1). The ee was determined by HPLC (Chiralpak OD column, hexane/
4.2.1. Catalyst 6a. 1H NMR (400 MHz, CDCl3, TMS):
d
0.82e0.87 (m,
i-PrOH 80:20, flow rate 0.8 mL/min,
l
¼210 nm, 20 ꢁC). tR (major)¼
1H), 1.15e1.35 (m, 5H), 1.51e1.73 (m, 7H), 1.83e2.08 (m, 3H), 2.30 (s,
1H), 2.41 (br s, 1H), 2.67e2.84 (m, 1H), 3.08e3.31 (m, 3H), 3.45 (br s,
1H), 4.92e5.04 (m, 2H), 5.66e5.74 (m, 1H), 7.50 (d, J¼4.4 Hz, 1H),
7.64e7.69 (m,1H), 7.74 (t, J¼7.2 Hz,1H), 8.13 (d, J¼8.4 Hz,1H), 8.60 (d,
J¼6.8 Hz, 1H), 8.88 (d, J¼4.4 Hz, 1H); 13C NMR (100 MHz, CDCl3):
18.3 min; tR (minor)¼26.8 min, ee¼97%. 1H NMR (600 MHz, CDCl3,
TMS):
d
1.01 (s, 3H), 1.14 (s, 3H), 3.78 (dd, J¼3.0, 10.8 Hz, 1H), 4.69
(dd, J¼3.6, 13.2 Hz, 1H), 4.85 (t, J¼12.6 Hz, 1H), 7.20 (d, J¼7.2 Hz,
2H), 7.29e7.34 (m, 3H), 9.53 (s, 1H); 13C NMR (100 MHz, CDCl3):
d
18.5, 21.4, 48.1, 76.1, 127.9, 128.5, 128.9, 135.1, 204.2.
d
24.5, 25.3, 26.9, 27.0, 28.9, 31.8, 34.5, 38.9, 40.9, 54.8, 55.3, 59.6, 60.5,
64.8, 76.6, 77.3, 114.5, 123.9, 126.5, 126.9, 128.9, 129.7, 129.9, 140.5,
148.1,149.8,181.9; MS (EI) m/z 449 (rel intensity) (Mþ). Anal. Calcd for
C26H35N5S:C,69.45;H,7.85;N,15.57. Found:C,68.41;H,7.89;N,15.52.
4.2.8. (R)-2,2-Dimethyl-4-nitro-3-(4-nitrophenyl) butanal (5b), (Table
3, entry 2). The ee was determined by HPLC (Chiralpak OD column,
hexane/i-PrOH 65:35, flow rate 1.0 mL/min,
l
¼254 nm, 20 ꢁC). tR
(major)¼15.6 min; tR (minor)¼25.7 min, ee¼96%.1H NMR (400 MHz,
4.2.2. Catalyst 6b. 1H NMR (400 MHz, CDCl3, TMS):
d
0.82e1.20 (m,
CDCl3, TMS):
d
1.04 (s, 3H), 1.17 (s, 3H), 3.96 (dd, J¼3.6, 11.6 Hz, 1H),
6H), 1.48e1.98 (m, 10H), 2.25e2.36 (m, 1H), 2.83e2.99 (m, 4H), 3.15
(br s, 1H), 5.12e5.15 (m, 2H), 5.81e5.90 (m, 1H), 7.43 (d, J¼4.4 Hz,
1H), 7.65 (t, J¼7.6 Hz,1H), 7.75 (t, J¼7.6 Hz,1H), 8.13 (d, J¼8.4 Hz,1H),
8.45 (br s, 1H), 8.90 (d, J¼4.4 Hz, 1H); 13C NMR (100 MHz, CDCl3):
4.79 (dd, J¼4.0, 13.6 Hz, 1H), 4.95 (dd, J¼11.6, 13.2 Hz, 1H), 7.46 (d,
J¼8.8 Hz, 2H), 8.21 (d, J¼8.8 Hz, 2H), 9.49 (s,1H); 13C NMR (100 MHz,
CDCl3):
d 18.7, 21.7, 47.7, 48.0, 75.6, 123.6, 130.0, 143.3, 147.4, 203.1.
d
24.2, 24.3, 24.6, 25.8, 27.1, 28.9, 31.7, 33.6, 38.8, 45.8, 47.2, 48.3, 55.2,
4.2.9. (R)-2,2-Dimethyl-4-nitro-3-(2-nitrophenyl)
butanal
(5c),
60.5, 77.2, 114.8, 119.6, 124.0, 126.5, 127.0, 129.0, 129.7, 139.6, 148.0,
(Table 3, entry 3). The ee was determined by HPLC (Chiralpak OD

J.-R. Chen et al. / Tetrahedron 66 (2010) 5367e5372
5371
column, hexane/i-PrOH 50:50, flow rate 1.0 mL/min,
l
¼254 nm,
column, hexane/i-PrOH 75:25, flow rate 0.8 mL/min;
l
¼210 nm,
20 ꢁC). tR (major)¼10.4 min; tR (minor)¼30.5 min, ee¼92%. 1H NMR
20 ꢁC). tR (major)¼13.1 min; tR (minor)¼19.4 min, ee¼96%. 1H NMR
(400 MHz, CDCl3, TMS):
d
1.12 (s, 3H), 1.21 (s, 3H), 4.69 (dd, J¼3.6,
(400 MHz, CDCl3, TMS): d 0.97 (s, 3H), 1.10 (s, 3H), 2.30 (s, 3H), 3.74
11.6 Hz, 1H), 4.77 (dd, J¼4.0, 14.0 Hz, 1H), 4.94 (dd, J¼11.2, 13.6 Hz,
1H), 7.45e7.49 (m, 1H), 7.53 (dd, J¼1.2, 8.0 Hz, 1H), 7.61e7.65 (m,
1H), 7.84 (dd, J¼1.6, 8.4 Hz, 1H), 9.49 (s, 1H); 13C NMR (100 MHz,
(dd, J¼4.0, 11.2 Hz, 1H), 4.66 (dd, J¼4.4, 12.8 Hz, 1H), 4.82 (dd,
J¼11.6, 12.8 Hz, 1H), 7.07 (d, J¼8.4 Hz, 2H), 7.12 (d, J¼8.4 Hz, 2H),
9.50 (s, 1H); 13C NMR (100 MHz, CDCl3):
76.2, 128.7, 129.2, 132.0, 137.6, 204.3.
d 18.6, 20.8, 21.3, 47.8, 48.0,
CDCl3):
d 19.1, 21.2, 40.3, 48.6, 76.2, 125.1, 128.7, 128.8, 130.9, 132.8,
151.2, 203.3.
4.2.17. (R)-2,2-Dimethyl-4-nitro-3-(4-methoxylphenyl) butanal (5k),
(Table 3, entry 12). The ee was determined by HPLC (Chiralpak AS
4.2.10. (R)-2,2-Dimethyl-4-nitro-3-(4-fluorophenyl) butanal (5d),
(Table 3, entry 4). The ee was determined by HPLC (Chiralpak OD col-
column, hexane/i-PrOH 75:25, flow rate 1.0 mL/min,
l
¼210 nm,
umn, hexane/i-PrOH 75:25, flow rate 0.8 mL/min,
l
¼210 nm, 20 ꢁC). tR
20 ꢁC). tR (major)¼12.7 min; tR (minor)¼20.4 min, ee¼96%. 1H NMR
(major)¼12.6 min; tR (minor)¼23.3 min, ee¼95%. 1H NMR (400 MHz,
(400 MHz, CDCl3, TMS):
11.6 Hz, 1H), 3.77 (s, 3H), 4.66 (dd, J¼4.4, 12.8 Hz, 1H), 4.81 (dd,
d
0.98 (s, 3H), 1.11 (s, 3H), 3.73 (dd, J¼4.4,
CDCl3, TMS):
d
0.98 (s, 3H), 1.11 (s, 3H), 3.79 (dd, J¼4.0, 11.6 Hz, 1H), 4.69
(dd, J¼4.0,12.8 Hz,1H), 4.83 (dd, J¼11.6,13.2 Hz,1H), 7.02 (t, J¼8.8 Hz, 2H),
J¼11.6, 12.8 Hz, 1H), 6.85 (d, J¼8.8 Hz, 2H), 7.11 (d, J¼8.4 Hz, 2H),
7.19 (dd, J¼5.2, 8.4 Hz, 2H), 9.49 (s,1H); 13C NMR (100 MHz, CDCl3):
d
18.5,
9.51 (s, 1H); 13C NMR (100 MHz, CDCl3):
76.3, 113.9, 126.8, 129.9, 159.0, 204.4.
d 18.6, 21.3, 47.5, 48.2, 55.0,
21.4, 47.4, 48.0, 76.1,115.4,115.6,130.5,130.6,131.0,131.1,160.9,163.4, 204.0.
4.2.11. (R)-2,2-Dimethyl-4-nitro-3-(4-bromophenyl) butanal (5e),
(Table 3, entry 5). The ee was determined by HPLC (Chiralpak OD
4.2.18. (R)-2,2-Dimethyl-4-nitro-3-(2-methoxylphenyl) butanal (5l),
(Table 3, entry 13). The ee was determined by HPLC (Chiralpak AS
column, hexane/i-PrOH 75:25, flow rate 0.8 mL/min,
l
¼210 nm, 20 ꢁC).
column, hexane/i-PrOH 75:25, flow rate 0.8 mL/min,
l
¼210 nm,
tR (major)¼16.7 min; tR (minor)¼26.4 min, ee¼96%. 1H NMR (400 MHz,
20 ꢁC). tR (major)¼10.5 min; tR (minor)¼17.1 min, ee¼94%. 1H NMR
CDCl3, TMS):
d
0.99 (s, 3H), 1.11 (s, 3H), 3.76 (dd, J¼4.4, 11.6 Hz, 1H), 4.69
(400 MHz, CDCl3, TMS): d 1.03 (s, 3H), 1.08 (s, 3H), 3.79 (s, 3H), 4.22
(dd, J¼4.0, 13.2 Hz, 1H), 4.82 (dd, J¼11.6, 13.2 Hz, 1H), 7.09 (d, J¼8.4 Hz,
(s, 1H), 4.72 (dd, J¼4.4, 12.8 Hz, 1H), 4.90 (dd, J¼10.8, 12.8 Hz, 1H),
6.87 (d, J¼8.4 Hz, 1H), 6.92 (t, J¼7.6 Hz, 1H), 7.12 (dd, J¼1.6, 7.6 Hz,
1H), 7.23e7.27 (m, 1H), 9.49 (s, 1H); 13C NMR (100 MHz, CDCl3):
2H), 7.46 (d, J¼8.4 Hz, 2H), 9.48 (s, 1H); 13C NMR (100 MHz, CDCl3):
d
18.6, 21.6, 47.6, 48.0, 75.9, 122.1, 130.6, 131.7, 134.4, 203.7.
d
19.7, 20.7, 42.6, 48.2, 55.1, 75.6, 111.1, 120.5, 123.8, 129.1, 129.4,
4.2.12. (R)-2,2-Dimethyl-4-nitro-3-(2-bromophenyl) butanal (5f),
(Table 3, entry 6). The ee was determined by HPLC (Chiralpak OD
157.1, 204.0.
column, hexane/i-PrOH 65:35, flow rate 1.0 mL/min,
l
¼210 nm,
4.2.19. (R)-2,2-Dimethyl-4-nitro-3-(3,4-dimethoxylphenyl) butanal
(5m), (Table 3, entry 14). The ee was determined by HPLC (Chir-
alpak AS column, hexane/i-PrOH 65:35, flow rate 1.0 mL/min,
20 ꢁC). tR (major)¼9.9 min; tR (minor)¼27.1 min, ee¼95%. 1H NMR
(400 MHz, CDCl3, TMS):
d
1.07 (s, 3H), 1.16 (s, 3H), 4.62 (dd, J¼4.0,
11.2 Hz, 1H), 4.72 (dd, J¼4.0, 13.6 Hz, 1H), 4.83 (dd, J¼11.6, 13.2 Hz,
l
¼210 nm, 20 ꢁC). tR (minor)¼14.6 min; tR (major)¼17.9 min,
1H), 7.12e7.16 (m, 1H), 7.27e7.34 (m, 2H), 7.60 (d, J¼8.0 Hz, 1H),
ee¼96%. 1H NMR (400 MHz, CDCl3, TMS):
d 1.02 (s, 3H), 1.14 (s, 3H),
9.54 (s, 1H); 13C NMR (100 MHz, CDCl3):
d
18.5, 20.7, 44.9, 48.9, 76.2,
3.72 (dd, J¼4.0, 11.6 Hz, 1H), 3.86 (s, 3H), 3.87 (s, 3H), 4.67 (dd,
J¼4.0, 12.8 Hz, 1H), 4.83 (t, J¼11.6 Hz, 1H), 6.68 (s, 1H), 6.75 (dd,
J¼2.0 Hz, 1H), 6.82 (d, J¼8.4 Hz, 1H), 9.52 (s, 1H); 13C NMR
126.8, 127.7, 128.2, 129.3, 133.7, 135.3, 203.7.
4.2.13. (R)-2,2-Dimethyl-4-nitro-3-(4-chlorophenyl) butanal (5g),
(Table 3, entry 7). The ee was determined by HPLC (Chiralpak OD
(100 MHz, CDCl3): d 18.9, 21.5, 48.1, 48.2, 55.7, 55.8, 76.4, 110.8,
112.2, 120.9, 127.4, 148.5, 148.6, 204.4.
column, hexane/i-PrOH 75:25, flow rate 0.8 mL/min,
l
¼210 nm, 20 ꢁC).
tR (major)¼14.7 min; tR (minor)¼24.9 min, ee¼95%. 1H NMR (400 MHz,
4.2.20. (R)- 2,2-Dimethyl-4-nitro-3-(2-naphthyl)butanal (5n), (Table 3,
entry 15). The ee was determined by HPLC (Chiralpak OD column,
CDCl3, TMS):
d
0.98 (s, 3H), 1.10 (s, 3H), 3.78 (dd, J¼4.0, 11.6 Hz, 1H), 4.69
(dd, J¼4.4, 13.2 Hz, 1H), 4.82 (dd, J¼11.2, 12.8 Hz, 1H), 7.16 (d, J¼8.4 Hz,
hexane/i-PrOH 65:35, flow rate 1.0 mL/min,
l
¼254 nm, 20 ꢁC). tR
2H), 7.30 (d, J¼8.4 Hz, 2H), 9.48 (s, 1H); 13C NMR (100 MHz, CDCl3):
(major)¼17.1 min; tR (minor)¼29.3 min, ee¼95%. 1H NMR
d
18.5, 21.4, 47.5, 48.0, 75.9, 128.7, 130.2, 133.8, 133.9, 203.8.
(400 MHz, CDCl3, TMS):
d
0.90 (s, 3H), 1.15 (s, 3H), 4.83 (dd, J¼12.4,
22.4 Hz, 1H), 4.94 (d, J¼12.4 Hz, 1H), 4.99 (d, J¼10.8 Hz, 1H),
7.39e7.58 (m, 4H), 7.78 (d, J¼7.6 Hz, 1H), 7.84 (d, J¼8.0 Hz, 1H), 8.22
4.2.14. (R)-2,2-Dimethyl-4-nitro-3-(2-chlorophenyl) butanal (5h),
(Table 3, entry 9). The ee was determined by HPLC (Chiralpak OD
(d, J¼8.4 Hz, 1H), 9.54 (s, 1H); 13C NMR (100 MHz, CDCl3):
d 18.5,
column, hexane/i-PrOH 65:35, flow rate 1.0 mL/min,
l
¼210 nm, 20 ꢁC).
21.5, 39.9, 48.9, 76.6, 122.9, 124.7, 124.8, 125.8, 126.6, 128.6, 128.9,
132.0, 132.7, 133.8, 204.4.
tR (major)¼9.0 min; tR (minor)¼24.6 min, ee¼95%. 1H NMR (400 MHz,
CDCl3, TMS):
d
1.05 (s, 3H), 1.15 (s, 3H), 4.63 (dd, J¼4.0, 11.6 Hz, 1H), 4.73
(dd, J¼4.0, 13.2 Hz, 1H), 4.84 (t, J¼11.6 Hz, 1H), 7.20e7.29 (m, 3H), 7.41
4.2.21. (R)- 2,2-Dimethyl-4-nitro-3-(2-furyl)butanal (5o), (Table 3,
entry 16). The ee was determined by HPLC (Chiralpak OD column,
(dd, J¼1.6, 8.0 Hz, 2H), 9.53 (s, 1H); 13C NMR (100 MHz, CDCl3):
d 18.4,
20.6, 42.1, 48.9, 76.0, 127.0, 128.1, 129.0, 130.2, 133.5, 135.6, 203.7.
hexane/i-PrOH 75:25, flow rate 0.8 mL/min,
l
¼210 nm, 20 ꢁC). tR
(major)¼10.3 min; tR (minor)¼17.2 min, ee¼97%. 1H NMR
4.2.15. (R)-2,2-Dimethyl-4-nitro-3-(4-trifluoromethylphenyl) buta-
nal (5i), (Table 3, entry 10). The eewas determined by HPLC(Chiralpak OD
(400 MHz, CDCl3, TMS):
d
1.03 (s, 3H), 1.17 (s, 3H), 3.93 (dd, J¼4.0,
11.2 Hz, 1H), 4.59 (dd, J¼4.0, 12.8 Hz, 1H), 4.76 (dd, J¼11.2, 12.8 Hz,
1H), 6.22 (d, J¼3.2 Hz, 1H), 6.31 (dd, J¼4.0, 5.2 Hz, 1H), 7.37 (d,
column, hexane/i-PrOH 75:25, flow rate 0.8 mL/min,
l
¼210 nm, 20 ꢁC). tR
(major)¼12.3 min; tR (minor)¼21.8 min, ee¼90%. 1H NMR (400 MHz, CDCl3,
J¼1.6 Hz, 1H), 9.51 (s, 1H); 13C NMR (100 MHz, CDCl3):
d 18.8, 20.9,
TMS):
d
1.01 (s, 3H), 1.14 (s, 3H), 3.88 (dd, J¼4.0, 11.6 Hz, 1H), 4.74 (dd, J¼4.4,
42.0, 48.0, 74.7, 109.4, 110.2, 142.6, 149.6, 203.4.
13.2 Hz, 1H), 4.89 (dd, J¼11.6, 13.6 Hz, 1H), 7.36 (d, J¼8.0 Hz, 2H), 7.60 (d,
J¼8.4 Hz, 2H), 9.60 (s, 1H); 13C NMR (100 MHz, CDCl3):
d
18.8, 21.7, 48.0, 48.1,
4.2.22. (R)-2,2-Dimethyl-4-nitro-3-(2-thienyl)butanal (5p), (Table 3,
entry 17). The ee was determined by HPLC (Chiralpak OD column,
75.8, 125.6, 129.5, 129.7, 130.1, 130.4, 139.7, 203.5.
hexane/i-PrOH 75:25, flow rate 0.8 mL/min,
l
¼210 nm, 20 ꢁC). tR
4.2.16. (R)-2,2-Dimethyl-4-nitro-3-(4-methylphenyl) butanal (5j),
(Table 3, entry 11). The ee was determined by HPLC (Chiralpak OD
(major)¼14.0 min; tR (minor)¼23.9 min, ee¼95%. 1H NMR
(400 MHz, CDCl3, TMS):
d
1.07 (s, 3H), 1.20 (s, 3H), 4.14 (dd, J¼4.0,

5372
J.-R. Chen et al. / Tetrahedron 66 (2010) 5367e5372
N. Angew. Chem., Int. Ed. 2006, 45, 6366; (e) Xu, Y.-M.; Zou, W.-B.; Sundén, H.;
Ibrahem, I.; Córdova, A. Adv. Synth. Catal. 2006, 348, 418; (f) McCooey, S. H.;
Connon, S. J. Org. Lett. 2007, 9, 599; (g) Liu, K.; Cui, H.-F.; Nie, J.; Dong, K.-Y.; Li,
X.-J.; Ma, J.-A. Org. Lett. 2007, 9, 923; (h) Wei, S.-W.; Yalalov, D. A.; Tsogoeva, S.
B.; Schmatz, S. Catal. Today 2007, 121, 151; (i) Xiong, Y.; Wen, Y.-H.; Wang, F.;
Gao, B.; Liu, X.-H.; Huang, X.; Feng, X.-M. Adv. Synth. Catal. 2007, 349, 2156; (j)
Xue, F.; Zhang, S.-L.; Duan, W.-H.; Wang, W. Adv. Synth. Catal. 2008, 350, 2194;
(k) Sato, A.; Yoshida, M.; Hara, S. Chem. Commun. 2008, 6242; (l) Jiang, X. X.;
10.8 Hz, 1H), 4.66 (dd, J¼4.0, 12.8 Hz, 1H), 4.73 (dd, J¼10.8, 13.2 Hz,
1H), 6.92 (dd, J¼1.2, 3.6 Hz, 1H), 6.96 (dd, J¼3.6, 5.2 Hz, 1H), 7.24
(dd, J¼1.2, 5.2 Hz, 1H), 9.52 (s, 1H); 13C NMR (100 MHz, CDCl3):
d
18.6, 21.4, 43.7, 48.2, 76.6, 125.4, 126.8, 127.7, 137.6, 203.6.
4.2.23. (2S,3R)-2-Methyl-4-nitro-2,3-diphenylbutanal (15), (Eq. 2).
The ee was determined by HPLC (Chiralpak OD column, hexane/i-
Zhang, Y.-F.; Chan, A. S. C.; Wang, R. Org.
Lett. 2009, 11, 153; (m) Uehara, H.;
PrOH 95:5, flow rate 1.0 mL/min,
l
¼210 nm, 20 ꢁC). tR (minor)¼
Barbas, C. F., III. Angew. Chem., Int. Ed. 2009, 48, 9848; (n) Li, P.-F.; Wang, Y.-C.;
Liang, X.-M.; Ye, J.-X. Chem. Commun. 2008, 3302; (o) Li, P.-F.; Wen, S.-G.; Yu, F.;
Liu, Q.-X.; Li, W.-J.; Wang, Y.-C.; Liang, X.-M.; Ye, J.-X. Org. Lett. 2009, 11, 753; (p)
Tan, B.; Zhang, X.; Chua, J. P.; Zhong, G.-F. Chem. Commun. 2009, 779; (q)
He, T.-X.; Gu, Q.; Wu, X.-Y. Tetrahedron 2010, 66, 3195.
22.0 min; tR (major)¼30.5 min, syn/anti¼97:3, syn: ee¼47%. 1H
NMR (400 MHz, CDCl3, TMS):
d
1.48 (s, 3H), 4.20 (dd, J¼4.0,
11.6 Hz, 1H), 4.84 (dd, J¼3.6, 12.8 Hz, 1H), 5.00 (dd, J¼11.6, 13.2 Hz,
1H), 6.90e6.92 (m, 2H), 7.02e7.04 (m, 2H), 7.08e7.11 (m, 2H),
6. For representative examples, see: (a) Alza, E.; Cambeiro, X. C.; Jimeno, C.;
Pericàs, M. A. Org. Lett. 2007, 9, 3717; (b) Vishnumaya; Singh, V. K. Org. Lett.
2007, 9, 1117; (c) Clarke, M. L.; Fuentes, J. A. Angew. Chem., Int. Ed. 2007, 46, 930;
(d) Liu, F.-Y.; Wang, S.-W.; Peng, Y.-G. Synlett 2007, 2415; (e) Gu, L.-Q.; Wu, Y.-Y.;
Zhang, Y.-Z.; Zhao, G. J. Mol. Catal. A. 2007, 263, 186; (f) Almasi, D.; Alonso, D. A.;
Gómez-Bengoa, E.; Nagel, Y.; Nájera, C. Eur. J. Org. Chem. 2007, 2328; (g) Diez,
D.; Gil, M. J.; Moro, R. F.; Marcos, I. S.; García, P.; Basabe, P.; Garrido, N. M.;
Broughton, H. B.; Urones, J. G. Tetrahedron 2007, 63, 740; (h) Chen, H.-B.; Wang,
Y.; Wei, S.-Y.; Sun, J. Tetrahedron: Asymmetry 2007, 18, 1308; (i) Xu, D.-Q.; Wang,
B.-T.; Luo, S.-P.; Yue, H.-D.; Wang, L.-P.; Xu, Z.-Y. Tetrahedron: Asymmetry 2007,
18, 1788; (j) Ni, B.-K.; Zhang, Q.-Y.; Headley, A. D. Tetrahedron: Asymmetry 2007,
18, 1443; (k) Cao, Y.-J.; Lai, Y.-Y.; Wang, X.; Li, Y.-J.; Xiao, W.-J. Tetrahedron Lett.
2007, 48, 21; (l) Mandal, T.; Zhao, C.-G. Tetrahedron Lett. 2007, 48, 5803; (m) Xu,
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Kuan, H.-H.; Chou, T.-Y.; Chen, K. Chem.dEur. J. 2009, 15, 9294; (aa) Wiesner,
M.; Neuberger, M.; Wennemers, H. Chem.dEur. J. 2009, 15, 10103; (ab) Xu, D.-Z.;
Shi, S. S.; Liu, Y.-J.; Wang, Y.-M. Tetrahedron 2009, 65, 9344; (ac) Freund, M.;
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G.; Angelici, G.; Wennemers, H. J. Am. Chem. Soc. 2010, 132, 6.
7.23e7.30 (m, 4H), 9.51 (s, 1H); 13C NMR (100 MHz, CDCl3):
d 16.3,
49.3, 56.4, 76.0, 127.1, 127.4, 127.9, 128.0, 128.1, 128.8, 129.5, 135.2,
136.9, 200.9.
Acknowledgements
We are grateful to the Program for Academic Leader in Wuhan
Municipality (200851430486), and the National Science Founda-
tion of China (20872043) for support of this research.
Supplementary data
Experimental details, characterization of all catalysts, NMR
spectra, and HPLC spectra of Michael addition products. Supple-
mentary data associated with this article can be found in online
version at doi:10.1016/j.tet.2010.05.056. This data include MOL files
and InChIKeys of the most important compounds described in this
article.
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