Highly enantioselective Michael addition of isobutyraldehyde to nitroalkenes

Article abstract of DOI:10.1016/j.tet.2010.02.069

The asymmetric catalytic Michael reaction between isobutyraldehyde and nitroalkanes with chiral primary amine thiourea organocatalysts was described. In the presence of 10 mol % of 1-((1R,2R)-2-amino-1,2-diphenylethyl)-3-benzylthiourea, the desired produc

Full text of DOI:10.1016/j.tet.2010.02.069

Tetrahedron 66 (2010) 3195–3198
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Highly enantioselective Michael addition of isobutyraldehyde to nitroalkenes
*
Tianxiong He, Qing Gu, Xin-Yan Wu
Key Laboratory for Advanced Materials and Institute of Fine Chemicals, East China University of Science and Technology, Shanghai 200237, China
a r t i c l e i n f o
a b s t r a c t
Article history:
The asymmetric catalytic Michael reaction between isobutyraldehyde and nitroalkanes with chiral pri-
mary amine thiourea organocatalysts was described. In the presence of 10 mol % of 1-((1R,2R)-2-amino-
1,2-diphenylethyl)-3-benzylthiourea, the desired products were achieved in excellent enantioselectivity
(up to>99% ee) with up to 98% yield.
Received 18 December 2009
Received in revised form 8 February 2010
Accepted 22 February 2010
Available online 25 February 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Asymmetric catalysis
Bifunctional organocatalysts
Michael reaction
Isobutyraldehyde
1. Introduction
based bifunctional primary amine thioureas, which were excel-
lently enantioselective for Michael addition of aromatic ketones to
As versatile synthetic intermediates, nitroalkanes are of sig-
nificant interest in organic chemistry due to the various trans-
formations of the nitro group into other useful functional groups.1
The Michael addition of carbonyl compounds to nitroalkenes is
a useful way in obtaining nitroalkanes. Since the pioneering works
of asymmetric organocatalysis,2 many catalytic systems have been
developed for the asymmetric Michael addition between alde-
hydes/ketones and nitroalkenes to produce enantiomerically
enriched nitroalkanes.3 The synthesis of all-carbon quaternary
stereogenic centers is considered a challenging topic in asym-
metric synthesis. Although various chiral organocatalysts were
highly efficient for the Michael addition of aldehydes to nitro-
olefins, only several organocatalysts provided excellent enantio-
nitroolefins. Later, cyclohexanediamine-derived chiral primary
amine thioureas bearing cinchona alkaloid7 or dehydroabietic
amine8 backbone were developed for the enantioselective Michael
additions. As the loading of the catalyst is usually large amount (20–
30 mol %) in the asymmetric organocatalysis, we are eager to de-
velop the economical catalysts. Although Tsogoeva described the
chiral arylethyl moiety adjacent to a thiourea was expected to shield
one side of the activated nitroolefin, we found that the non-chiral
benzyl moiety also can do it effectively. Herein, we report the
asymmetric nitro-Michael additions of isobutyraldehyde to nitro-
olefins catalyzed by the chiral primary amine thiourea. The present
research results provide an interesting comparison with the results
obtained using Tsogoeva’s catalysts.
selectivities for the Michael reaction between
a,a-disubstitued
aldehydes and nitroolefins.4
In recent years, considerable effort has been directed to the de-
velopment of chiral primary amine thiourea catalysts (Scheme 1).
Jacobsen’s group4c,5a firstly reported cyclohexanediamine-derived
chiral primary amine thioureas as organocatalyst for the highly
enantioselective direct conjugate addition of both ketones and al-
dehydes to nitroalkenes. Tsogoeva et al.5b–d presented a successful
application of the diphenylethyldiamine-derived bifunctional pri-
mary amine thioureas in the asymmetric Michael addition of ke-
tones to nitroolefins. Ma et al.6 developed a class of saccharide-
Scheme 1. Examples of bifunctional primary amine thioureas.
2. Results and discussion
Initially, the addition of isobutyraldehyde to
b-nitro-p-nitro-
styrene was selected as a model reaction. We were pleased to find
that all the primary amine thiourea derivatives could catalyze the
Michael reaction with excellent enantioselectivities (Scheme 2).
However, the catalytic activities of organic molecules 1a–h were
* Corresponding author. Tel.: þ86 21 64252011; fax: þ86 21 64252758.
E-mail address: xinyanwu@ecust.edu.cn (X.-Y. Wu).
0040-4020/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.02.069

3196
T. He et al. / Tetrahedron 66 (2010) 3195–3198
Table 2
significantly different. The results summarized in Table 1 indicated
thioureas 1d and 1e (entries 4 and 5) could catalyze the reaction
smoothly in high yield. While their analogue 1f gave poor yield
(entry 6). Compared with thiourea 1d, organocatalyst 1g with
methoxyl substitution at the para-position of phenyl also gave good
yield, but the reaction took a long time (entry 7). Bearing an alkyl
group, the catalyst 1h afforded good yield and excellent enantio-
selectivity (entry 8). Surprisingly, the chemical yields became low
when bearing aryl groups at the thiourea moieties (entries 1–3).
Effect of solvents and isobutyraldehyde loading on the asymmetric Michael addition
of isobutyraldehyde to
-nitro-p-nitrostyrenea
b
Entry
Solvent
3/2a
Time (d)
Yield (%)b
ee (%)c
1
2
3
4
5
6
7
8
9
CH2Cl2
CH2Cl2
CH2Cl2
EtOH
5
3
2
3
3
3
3
3
3
3
1
2
3
2
3
2
2
3
2
2
75
90
85
10
30
80
65
32
20
38
>99
>99
>99
97
96
98
99
>99
90
THF
i-PrOH
CHCl3
Ether
n-Hexane
Toluene
Scheme 2. The screened chiral primary amine thioureas.
10
96
Table 1
a
All reactions were conducted in solvent (2 mL) using 2a (0.2 mmol) and 3 in the
presence of 10 mol % 1d.
Catalytic asymmetric Michael addition of isobutyraldehyde to
nitrostyrenea
b
-nitro-p-
b
Isolated yield.
c
Determined by chiral HPLC analysis (Chiralpak AD-H, hexane/2-propanol¼80/20).
than that with electron-donating aryl group or unsubstituted aryl
group (entries 1–13 vs 14–19). The less reactive substrates could
provide good chemical yields while increasing the catalyst loading
to 30 mol % (entries 15, 17, and 19).
Entry
Catalyst
Time (d)
Yieldb (%)
eec (%)
Table 3
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
4
4
4
1
1
1
3
3
20
15
13
75
75
28
73
65
99
96
99
99.3
99.7
95
>99
>99
Catalytic asymmetric Michael addition of isobutyraldehyde to different nitroolefinsa
1g
1h
a
All reactions were conducted in CH2Cl2 (2 mL) using 2a (0.2 mmol) and 3
Entry
Substrate
1d (mol %)
Time (d)
Yieldb (%)
eec (%)
(1 mmol, 5 equiv) in the presence of 10 mol % catalyst.
b
1
2
3
4
5
6
7
8
4-NO2C6H4
4-NO2C6H4
3-NO2C6H4
3-NO2C6H4
2-NO2C6H4
2-NO2C6H4
4-CNC6H4
4-FC6H4
4-ClC6H4
4-ClC6H4
2-ClC6H4
4-BrC6H4
2-furyl
C6H5
C6H5
4-MeC6H4
4-MeC6H4
4-MeOC6H4
4-MeOC6H4
10
15
10
15
10
15
15
15
10
15
15
15
15
15
30
15
30
15
30
2
1
2
2
2
2
2
2
2
2
2
2
2
3
2
3
2
3
2
90
98
85
95
72
80
90
72
65
85
85
75
90
47
77
50
75
50
76
>99
>99
>99
>99
98
Isolated yield.
c
Determined by chiral HPLC analysis (Chiralpak AD-H, hexane/2-propanol¼80/20).
The Michael reaction of isobutyraldehyde to
b-nitro-p-nitro-
98
styrene was next examined with thiourea 1d under various
reaction conditions (Table 2). The ratio of aldehyde to nitroolefin
was investigated first. Using only threefold of aldehyde relative to
nitrostyrene improved the chemical yield (entry 2). However,
decreasing the amount of aldehyde to twofolds could not increase the
yield further (entry 3). Then we explored the effects of the solvents.
As shown in Table 2, the chemical yields varied significantly in the
solvents tested. Polar solvents, such as EtOH and THF afforded poor
yields (entries 4 and 5). Moderate yield was obtained when using
chloroform as solvent (entry 7). Due to the poor solubility of sub-
strate, rather low conversion was observed in ethyl ether, hexane
and toluene (entries 8–10). The use of CH2Cl2 led to the highest
yield and enantioselectivity (entry 2, 90% yield, 99.7% ee). In gen-
eral, the reactions were displayed highly enantioselective in all the
screened solvents (90–99.7% ee).
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
9
10
11
12
13
14
15
16
17
18
19
a
All reactions were conducted in CH2Cl2 (2 mL) using 2 (0.2 mmol) and 3
(0.6 mmol, 3 equiv) in the presence of 1d.
b
Isolated yield.
c
Determined by chiral HPLC analysis (Chiralpak AD-H or AS-H column).
When the optimal reaction conditions were established, a vari-
ety of nitroolefins were then evaluated as substrates and the results
are summarized in Table 3. The results indicated the reaction had
a wide substrate scope with respect to nitroolefins. The Michael
adducts were obtained in nearly optically pure form (>99% ee) in
most of the cases examined (Table 3, entries 1–4, 7–19). Nitro-
olefins with electron-withdrawing aryl group were more reactive
3. Conclusion
In conclusion, we have developed a simple thiourea-based bi-
functional organocatalysts for the highly enantioselective Michael
reaction of isobutyraldehyde to nitroolefins in good yields. This

T. He et al. / Tetrahedron 66 (2010) 3195–3198
3197
reaction has several noteworthy features: (1) These primary amine
derived chiral thioureas are easily attainable; (2) The Michael ad-
ducts were obtained in nearly optically pure form in almost all
cases examined.
1727, 1557, 1525, 1472, 1439, 1383, 1355, 1307, 1209, 885, 857, 791,
671; HRMS (ESI) calcd for C12H15N2O5 [MþH]þ: 267.0981, found:
267.0974. HPLC analysis (AD-H column,
PrOH¼80/20, flow rate 1.0 mL/min): tR¼11.4 min (minor), 12.3 min
l
¼254 nm, hexane/i-
25
(major). [
a]
þ102.9 (c 0.55, CHCl3).
D
4. Experimental
4.2.4. (R)-4-(3,3-Dimethyl-1-nitro-4-oxobutan-2-yl)benzonitrile
(entry 7). 1H NMR (CDCl3, 400 MHz):
9.74 (s, 1H), 7.65–7.63 (m,
4.1. General methods
d
2H), 7.37–7.35 (m, 2H), 4.92–4.85 (m, 1H), 4.75 (dd, J¼4.0, 12.8 Hz,
Optical rotations were measured on a WZZ-2A digital polarim-
eter at the wavelength of the sodium D-line (589 nm) at 25 ꢀC. 1H
NMR and 13C NMR spectra were recorded on Bruker 500 or 400
spectrometer. 1H NMR spectra were referenced to tetramethylsi-
1H), 3.86 (dd, J¼4.0, 11.6 Hz, 1H), 1.32 (s, 3H), 1.02 (s, 3H); 13C NMR
(CDCl3, 125 MHz): d 204.0, 142.0, 133.1, 130.6, 118.8, 112.9, 76.4, 48.9,
48.8, 22.5, 19.7; IR (KBr, cmꢁ1):
n 2976, 2721, 2230, 1728, 1609, 1555,
1506, 1469, 1379, 1208, 883, 849, 737, 566; HRMS (EI) calcd for
lane (
d
, 0.00 ppm) using CDCl3 as solvent. 13C NMR spectra were
C13H15N2O3 [MꢁNO2]þ: 200.1075, found: 200.1078. HPLC analysis
referenced to solvent carbons (77.0 ppm for CDCl3). IR spectra were
recorded on Nicolet Magna-I 550 spectrometer. High Resolution
Mass spectra (HRMS) were recorded on Micromass GCT spec-
trometer with EI or ESI resource. HPLC analysis was performed on
Waters 510 with 2487 detector using Daicel Chiralpak AS-H or
Chiralpak AD-H column.
(AD-H column,
l
¼220 nm, hexane/i-PrOH¼85/15, flow rate 1.0 mL/
25
min): tR¼17.1 min (major), 21.3 min (minor). [
a
]
þ15.1 (c 0.46,
D
CHCl3).
4.2.5. (R)-3-(4-Fluorophenyl)-2,2-dimethyl-4-nitrobutanal (entry 8). 1H
NMR (CDCl3, 400 MHz): 9.50 (s, 1H), 7.20–7.17 (m, 2H), 7.16–7.14
d
All the starting chemicals were commercial products of ana-
lytical grade. Organic solvents were dried and purified according to
standard methods prior to use. The chiral primary amine thioureas
were prepared as our previous work.9
(m, 2H), 4.86–4.79 (m, 1H), 4.69 (dd, J¼4.0, 13.2 Hz, 1H), 3.77 (dd,
J¼4.0, 11.2 Hz, 1H), 1.12 (s, 3H), 1.02 (s, 3H); 13C NMR (CDCl3,
125 MHz):
d 204.7, 164.0, 162.1, 131.4, 131.3, 116.4, 116.3, 77.0, 48.9,
48.4, 22.3, 19.5; IR (KBr, cmꢁ1):
n 2976, 2718, 1905. 1723, 1605, 1554,
1512, 1468, 1437, 1379, 1228, 1164, 1101, 882, 843, 545; HRMS (ESI)
4.2. Typical experimental procedure for the asymmetric
Michael addition of isobutyraldehyde to nitroalkenes (Table 3)
calcd for C12H14FNO3Na [MþNa]þ: 262.0855, found: 262.0845.
HPLC analysis (AD-H column,
l
¼220 nm, hexane/i-PrOH¼85/15,
25
flow rate 1.0 mL/min): tR¼7.4 min (major), 8.5 min (minor). [
a]
D
The catalyst 1d (10.8 mg, 0.03 mmol) was added to a vial con-
taining isobutyraldehyde (0.6 mmol) and CH2Cl2 (2 mL) at room
temperature. The mixture was stirred vigorously for 10 min, and
þ1.8 (c 0.40, CHCl3).
4.2.6. (R)-3-(4-Chlorophenyl)-2,2-dimethyl-4-nitrobutanal (entry
10). 1H NMR (CDCl3, 400 MHz):
9.50 (s, 1H), 7.33–7.30 (m, 2H),
then
b
-nitro-p-nitrostyrene (38.8 mg, 0.2 mmol) was added. The
d
reaction mixture was stirred at room temperature for 24 h. The
solvent was then evaporated and the residue was purified by flash
silica gel chromatography (hexane/ethyl acetate, 4/1) to afford
52.1 mg (98% yield) of the product as a light yellow crystal.
7.16–7.14 (m, 2H), 4.86–4.79 (m, 1H), 4.69 (dd, J¼4.0, 13.2 Hz, 1H),
3.77 (dd, J¼4.0, 11.2 Hz, 1H), 1.12 (s, 3H), 1.02 (s, 3H); 13C NMR
(CDCl3, 125 MHz): d 204.5, 134.8, 134.6, 131.1, 129.6, 76.8, 48.8, 48.5,
22.4,19.6; IR (KBr, cmꢁ1):
n 3434, 2976, 2937, 2819, 2721,1729,1558,
1494, 1382, 1095, 1014, 837; HRMS (ESI) calcd for C12H14ClNO3Na
4.2.1. (R)-2,2-Dimethyl-4-nitro-3-(4-nitrophenyl) butanal (entry 2). 1H
[MþNa]þ: 278.0560, found: 278.0551. HPLC analysis (AD-H column,
NMR (CDCl3, 500 MHz):
d
9.50 (s, 1H), 8.22–8.21 (m, 2H), 7.45–7.43
l
¼220 nm, hexane/i-PrOH¼80/20, flow rate 1.0 mL/min):
25
(m, 2H), 4.93 (dd, J¼11.5, 13.4 Hz, 1H), 4.78 (dd, J¼14.0, 13.4 Hz, 1H),
tR¼7.4 min (major), 8.4 min (minor). [
a
]
þ2.5 (c 0.46, CHCl3).
D
3.94 (dd, J¼3.9, 11.5 Hz, 1H), 1.17 (s, 3H), 1.05 (m, 3H); 13C NMR
(CDCl3, 125 MHz,):
d
203.8, 148.3, 144.0, 130.8, 124.5, 76.4, 48.9,
4.2.7. (R)-3-(2-Chlorophenyl)-2,2-dimethyl-4-nitrobutanal
(entry
48.8, 22.6, 19.7; IR (KBr, cmꢁ1):
n
3423, 2965, 1722, 1555, 1516, 1381,
11). 1H NMR (CDCl3, 400 MHz):
9.54 (s, 1H), 7.43–7.41 (m, 1H),
d
1351, 887, 861, 704; HRMS (EI) calcd for C12H14NO3 [MꢁNO2]þ:
7.29–7.21 (m, 3H), 4.87–4.81 (m, 1H), 4.73 (dd, J¼3.6, 13.2 Hz, 1H),
220.0974, found: 220.0976. HPLC analysis (AD-H column,
4.63 (d, J¼8.8 Hz, 1H), 1.16 (s, 3H), 1.07 (s, 3H); 13C NMR (CDCl3,
l
¼254 nm, hexane/i-PrOH¼80/20, flow rate 1.0 mL/min):
125 MHz): d 203.8, 135.8, 133.8, 130.5, 129.2, 128.3, 127.2, 76.2, 49.0,
25
tR¼15.0 min (major), 20.5 min (minor). [
a]
þ13.8 (c 0.64, CHCl3).
42.5, 20.9, 18.7; IR (KBr, cmꢁ1):
n 2975, 2821, 2721, 1729, 1555, 1471,
D
1438, 1378, 1037, 881, 757, 706, 684; HRMS (ESI) calcd for
4.2.2. (R)-2,2-Dimethyl-4-nitro-3-(3-nitrophenyl)butanal(entry4). 1H
C12H14ClNO3Na [MþNa]þ: 278.0560, found: 278.0548. HPLC anal-
NMR (CDCl3, 400 MHz): 9.50 (s, 1H), 8.19–8.13 (m, 2H), 7.61–7.53
d
ysis (AD-H column,
l
¼220 nm, hexane/i-PrOH¼95/5, flow rate
25
(m, 2H), 4.97–4.91 (m, 1H), 4.78 (dd, J¼4.0, 13.6 Hz, 1H), 3.95 (dd,
1.0 mL/min): tR¼11.8 min (minor), 12.3 min (major). [
a
]
þ22.0 (c
D
J¼4.0, 10.0 Hz, 1H), 1.17 (s, 3H), 1.05 (s, 3H); 13C NMR (CDCl3,
0.57, CHCl3).
125 MHz): d 203.8, 149.0, 138.8, 136.0, 130.5, 124.5, 123.9, 76.5, 48.9,
48.7, 22.5, 19.7; IR (KBr, cmꢁ1):
n
3099, 2976, 1728, 1555, 1536, 1469,
4.2.8. (R)-3-(4-Bromophenyl)-2,2-dimethyl-4-nitrobutanal (entry
12)10 1H NMR (CDCl3, 500 MHz):
9.50 (s, 1H), 7.48–7.46 (m, 2H),
1379, 1349, 1307, 1093, 882, 813, 794, 737, 696; HRMS (EI) calcd for
.
d
C12H14NO3 [MꢁNO2]þ: 220.0974, found: 220.0977. HPLC analysis
7.10–7.09 (m, 2H), 4.90–4.85 (m, 1H), 4.69 (dd, J¼4.1, 13.2 Hz, 1H),
(AS-H column,
l
¼254 nm, hexane/i-PrOH¼90/10, flow rate 1.0 mL/
3.76 (dd, J¼4.1, 11.4 Hz, 1H), 1.12 (s, 3H), 1.01 (s, 3H). HPLC analysis
25
min): tR¼34.7 min (minor), 38.5 min (major). [
a]
ꢁ7.3 (c 0.56,
(AD-H column,
l
¼220 nm, hexane/i-PrOH¼85/15, flow rate 1.0 mL/
D
25
CHCl3).
min): tR¼10.2 min (major), 13.2 min (minor). [
a
]
þ3.2 (c 0.48,
D
CHCl3).
4.2.3. (R)-2,2-Dimethyl-4-nitro-3-(2-nitrophenyl)butanal(entry6). 1H
NMR (CDCl3, 400 MHz): 9.51 (s, 1H), 7.86–7.84 (m, 1H), 7.64–7.60
d
4.2.9. (R)-3-(Furan-2-yl)-2,2-dimethyl-4-nitrobutanal (entry 13)10
.
1H
(m, 1H), 7.52–7.45 (m, 2H), 4.96–4.90 (m, 1H), 4.77 (dd, J¼3.6,
NMR (CDCl3, 400 MHz):
d
9.52 (s, 1H), 7.37 (d, J¼1.2 Hz, 1H), 6.32–
13.6 Hz, 1H), 4.69 (dd, J¼3.6, 11.6 Hz, 1H), 1.20 (s, 3H), 1.14 (s, 3H);
6.31 (m, 1H), 6.22–6.21 (m, 1H), 4.75 (dd, J¼10.8, 12.8 Hz, 1H), 4.59
(dd, J¼4.0,13.2 Hz,1H), 3.92 (dd, J¼4.0,10.8 Hz,1H),1.18 (s, 3H),1.05
13C NMR (CDCl3, 125 MHz):
d 204.0, 152.1, 133.5, 131.8, 129.6, 129.5,
126.0, 77.1, 49.5, 41.4, 22.2, 20.2; IR (KBr, cmꢁ1):
n
2971, 2817, 2719,
(s, 3H). HPLC analysis (AD-H column,
l¼220 nm, hexane/i-

3198
T. He et al. / Tetrahedron 66 (2010) 3195–3198
PrOH¼95/5, flow rate 1.0 mL/min): tR¼9.7 min (major), 11.4 min
Supplementary data
25
(minor). [
a
]
ꢁ18.3 (c 0.47, CHCl3).
D
Supplementary data associated with this article can be found in
online version at doi:10.1016/j.tet.2010.02.069.
4.2.10. (R)-2,2-Dimethyl-4-nitro-3-phenylbutanal (entry 15)10
.
1H
NMR (CDCl3, 500 MHz): 9.53 (s,1H), 7.34–7.30 (m, 3H), 7.21–7.19 (m,
d
2H), 4.86 (dd, J¼11.3, 13.0 Hz, 1H), 4.69 (dd, J¼4.0, 13.0 Hz, 1H), 3.77
References and notes
(dd, J¼4.0, 11.3 Hz, 1H), 1.12 (s, 3H), 1.02 (s, 3H). HPLC analysis (AD-H
1. For recent reviews, see: (a) Norbert, K.; Hoffmann-Roder, A. Synthesis 2001,
171–196; (b) Berner, O. M.; Tedeschi, L.; Enders, D. Eur. J. Org. Chem. 2002, 1877–
1894; (c) Sibi, M. P.; Manyem, S. Tetrahedron 2000, 56, 8033–8061.
2. For selected reviews on organocatalysis, see: (a) Berkessel, A.; Groger, H.
Asymmetric Organocatalysis; Wiley-VCH: Weinheim, 2005; (b) Dalko, P. I.
Enantioselective Organocatalysis; Wiley-VCH: Weinheim, 2007; (c) Dalko, P. I.;
Moisan, L. Angew. Chem., Int. Ed. 2001, 40, 3726–3748; (d) Dalko, P. I.; Moisan, L.
Angew. Chem., Int. Ed. 2004, 116, 5138–5175; (e) Pellissier, H. Tetrahedron 2007,
63, 9267–9331; (f) Dondoni, A.; Massi, A. Angew. Chem., Int. Ed. 2008, 47,
4638–4660.
3. For recent reviews on organocatalytic asymmetric Michael addition reactions,
see: (a) Christoffers, J.; Baro, A. Angew. Chem., Int. Ed. 2003, 115, 1726–1728; (b)
Notz, W.; Tanaka, F.; Barbas, C. F., III. Acc. Chem. Res. 2004, 37, 580–591; (c)
Sulzer-Mosse, S.; Alexakis, A. Chem. Commun. 2007, 3123–3135; (d) Vicario, J. L.;
Badia, D.; Carrillo, L. Synthesis 2007, 2065–2092; (e) Tsogoeva, S. B. Eur. J. Org.
Chem. 2007, 1701–1716.
4. (a) Wang, W.; Wang, J.; Li, H. Angew. Chem., Int. Ed. 2005, 44, 1369–1371; (b)
Wang, J.; Li, H.; Lou, B.; Zhu, L.; Guo, H.; Wang, W. Chem.dEur. J. 2006, 12, 4321–
4332; (c) Yalonde, M. P.; Chen, Y.; Jacobsen, E. N. Angew. Chem., Int. Ed. 2006, 45,
6366–6370; (d) Li, P.; Wang, L.; Wang, M.; Zhang, Y. Eur. J. Org. Chem. 2008,
1157–1160; (e) Zhang, Q.; Ni, B.; Headley, A. D. Tetrahedron 2008, 64, 5091–
5097; (f) Chang, C.; Li, S.-H.; Reddy, R. J.; Chen, K. Adv. Synth. Catal. 2009, 351,
1273–1278; (g) Zhang, X.-J.; Liu, S.-P.; Li, X.-M.; Yan, M.; Chan, A. S. C. Chem.
Commun. 2009, 833–835; (h) Zhang, X.-J.; Liu, S.-P.; Lao, J.-H.; Du, G.-J.; Yan, M.;
Chan, A. S. C. Tetrahedron: Asymmetry 2009, 20, 1451–1458.
5. (a) Huang, H.; Jacobsen, E. N. J. Am. Chem. Soc. 2006, 128, 7170–7171; (b) Tso-
goeva, S. B.; Wei, S.-W. Chem. Commun. 2006, 1451–1453; (c) Yalalov, D. A.;
Tsogoeva, S. B.; Schmatz, S. Adv. Synth. Catal. 2006, 348, 826–832; (d) Wei, S.-
W.; Yalalov, D. A.; Tsogoeva, S. B.; Schmatz, S. Catal. Today 2007, 121, 151–157.
6. Liu, K.; Cui, H.; Nie, J.; Dong, K.; Li, X.; Ma, J. Org. Lett. 2007, 9, 923–925.
7. (a) Li, P.; Wen, S.; Yu, F.; Liu, Q.; Li, W.; Wang, Y.; Liang, X.; Ye, J. Org. Lett. 2009,
11, 753–756; (b) Li, P.; Wang, Y.; Liang, X.; Ye, J. Chem. Commun. 2008,
3302–3304.
column,
l
¼220 nm, hexane/i-PrOH¼99/1, flow rate 1.0 mL/min):
25
tR¼20.7 min (major), 23.7 min (minor). [
a]
þ10.2 (c 0.48, CHCl3).
D
4.2.11. (R)-2,2-Dimethyl-4-nitro-3-p-tolylbutanal (entry 17)4b
.
1H
NMR (CDCl3, 400 MHz): 9.54 (s, 1H), 7.15–7.13 (m, 2H), 7.10–7.07
d
(m, 2H), 4.83 (dd, J¼11.2, 13.2, 1H), 4.67 (dd, J¼4.4, 13.2 Hz,1H), 3.75
(dd, J¼4.4,11.6 Hz,1H),1.13 (s, 3H),1.01 (s, 3H). HPLC analysis (AD-H
column,
l
¼220 nm, hexane/i-PrOH¼95/5, flow rate 1.0 mL/min):
25
tR¼8.9 min (major), 9.8 min (minor). [
a
]
þ4.9 (c 0.49, CHCl3).
D
4.2.12. (R)-3-(4-Methoxyphenyl)-2,2-dimethyl-4-nitrobutanal (entry
19). 1H NMR (CDCl3, 400 MHz):
d
9.53 (s, 1H), 7.12 (d, J¼8.0 Hz, 2H),
6.86 (d, J¼8.0 Hz, 2H), 4.84–4.78 (m, 1H), 4.67 (dd, J¼4.0, 12.8 Hz,
1H), 3.79 (s, 3H), 3.73 (dd, J¼4.0, 11.6 Hz, 1H), 1.12 (s, 3H), 1.01 (s,
3H); 13C NMR (CDCl3, 125 MHz):
d 205.1, 159.9, 130.8, 127.7, 114.8,
77.2, 55.9, 49.0, 48.5, 22.2, 19.6; IR (KBr, cmꢁ1):
n 2971, 2840, 2721,
2360, 1729, 1714, 1614, 1556, 1382, 1251, 1184, 1118, 1033, 883, 838;
HRMS (EI) calcd for C13H17NO4 [M]þ: 251.1158, found: 251.1160.
HPLC analysis (AD-H column,
l
¼220 nm, hexane/i-PrOH¼85/15,
25
flow rate 1.0 mL/min): tR¼8.3 min (major), 9.3 min (minor). [
a]
D
ꢁ3.8 (c 0.58, CHCl3).
Acknowledgements
We thank the National Natural Science Foundation of China
(20772029) and New Century Excellent Talents in University
(NCET-07-0286) for financial support.
8. Jiang, X. X.; Zhang, Y.; Chan, A. S. C.; Wang, R. Org. Lett. 2009, 11, 153–156.
9. He, T.; Qian, J.-Y.; Song, H.-L.; Wu, X.-Y. Synlett 2009, 3195–3197.
10. McCooey, S. H.; Connon, S. J. Org. Lett. 2007, 9, 599–602.