Asymmetric conjugate addition of carbonyl compounds to nitroalkenes catalyzed by chiral bifunctional thioureas

Article abstract of DOI:10.1016/j.tetasy.2009.06.003

Readily available chiral thioureas derived from cyclohexane-1,2-diamine were prepared and found to be highly effective organocatalysts for the conjugate addition of aldehydes and ketones to nitroalkenes. Excellent enantioselectivities and yields were obtained for a variety of aryl and heteroaryl nitroalkenes. The base additives are essential for good yields and excellent enantioselectivities in this transformation. Based on new experimental evidence, a modified catalytic mechanism was proposed to rationalize the important role of the base additives.

Full text of DOI:10.1016/j.tetasy.2009.06.003

Tetrahedron: Asymmetry 20 (2009) 1451–1458
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Asymmetric conjugate addition of carbonyl compounds to nitroalkenes
catalyzed by chiral bifunctional thioureas
a,b
Xue-jing Zhang a, Sheng-ping Liu a, Jin-hua Lao a, Guang-jian Du a, Ming Yan a, , Albert S. C. Chan
*
a Industrial Institute of Fine Chemicals and Synthetic Drugs, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
b Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hong Kong, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Readily available chiral thioureas derived from cyclohexane-1,2-diamine were prepared and found to be
highly effective organocatalysts for the conjugate addition of aldehydes and ketones to nitroalkenes.
Excellent enantioselectivities and yields were obtained for a variety of aryl and heteroaryl nitroalkenes.
The base additives are essential for good yields and excellent enantioselectivities in this transformation.
Based on new experimental evidence, a modified catalytic mechanism was proposed to rationalize the
important role of the base additives.
Received 5 May 2009
Accepted 4 June 2009
Available online 27 June 2009
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
In recent years, asymmetric organocatalysis has emerged as a
powerful tool for the synthesis of valuable chiral compounds.1
Organocatalytic conjugate additions of aldehydes and ketones to
nitroalkenes are an important strategy for asymmetric carbon–car-
bon bond formation.2,3 The resulting products are readily con-
Chiral organocatalysts 1a–1g were prepared via simple proce-
dures (Scheme 1). Compound 1b, which has a strongly electron-
withdrawing 3,5-ditrifluoromethylaryl group, was designed to
investigate the effect of N-H acidity on catalytic activity. For com-
parison, compound 1f, which is free of the thiourea group, and sec-
ondary amine 1g were also prepared.
verted to chiral
c-amino acids and to other useful compounds.
Chiral primary amines, secondary amines and bifunctional organo-
catalysts have been used with great success.4 Jacobsen’s thiourea-
primary amine organocatalysts have been reported to be highly
efficient for the transformation.3p,q These catalysts consist of chiral
cyclohexane-1,2-diamine and tert-leucine derivatives. The match
of the multiple stereogenic centres in the catalysts is crucial for
excellent enantioselectivity. Unfortunately these catalysts require
tedious synthesis and are not readily available. Recently we found
that chiral bifunctional sulfamide–primary amines are highly effi-
cient catalysts for the conjugate addition of aldehydes to nitroal-
kenes.5 During the study we also found that the ability for
enantioselective induction is mainly governed by the cyclohex-
ane-1,2-diamine motif of the catalysts. Therefore, we presume that
structurally simplified chiral thiourea–primary amines based on
cyclohexane-1,2-diamine are efficient catalysts for the reaction.
Herein we report on the synthesis and application of these thio-
urea–primary amines in the asymmetric conjugate addition of
aldehydes and ketones to nitroalkenes. The present research re-
sults provide an interesting comparison with the results obtained
using Jacobsen’s catalysts.
In a previous study of chiral sulfamide-primary amine catalysts,
we found that the conjugate addition of aldehydes to nitroalkenes
is very slow in the absence of base additives.5 Thus, catalysts 1a–1g
were examined for the conjugate addition of isobutyraldehyde to
nitrostyrene in the presence of DMAP (20 mol %). The results are
summarized in Table 1. The reactions were monitored by GC to ob-
tain chromatographic yields. The isolated yields of the product
were obtained by flash column chromatography after the reaction.
It is interesting to note that the GC yields were generally lower
than the corresponding isolated yields in most cases (Table 1).
We supposed that the intermediates from the product 4a and the
catalysts were formed; the intermediates were decomposed during
column chromatography and an additional amount of product was
released.
Catalyst 1a provided the product 4a with excellent yield and
enantioselectivity (Table 1, entry 1).6 Decreasing the reaction tem-
perature did not improve enantioselectivity furthermore, but re-
sulted in lower yields (Table 1, entry 2). Catalyst 1b provided
almost the same results as 1a (Table 1, entry 3). The acidity of
the N–H of the thiourea group seems to have a small effect on
the catalytic activity and enantioselectivity in the reaction. In
many other reactions with thiourea catalysts, the acidity of the
N–H is crucial for the catalytic activity.7 The enantioselective
induction of the catalysts was dominated by the chiral cyclohex-
ane-1,2-diamine motif. The additional stereogenic centre in
* Corresponding author. Tel./fax: +86 20 39943049.
E-mail address: yanming@mail.sysu.edu.cn (M. Yan).
0957-4166/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2009.06.003

1452
X. Zhang et al. / Tetrahedron: Asymmetry 20 (2009) 1451–1458
H
N
H
N
H
N
H
N
H
N
H
N
H
N
H
N
F3C
S
S
S
S
H2N
H2N
H2N
H2N
CF3
1c
1b
1d
1a
H
N
H
N
Ph Ph
OTMS
NHBoc
NH2
R
N
tBu
S
Ph
S
N
H
N
H
N
H2N
H
O
NH2
1e
1f
1g
Jacobsen's catalyst
Scheme 1. Chiral organocatalysts 1a–1g and Jacobsen’s catalyst.
Table 2
catalysts 1d and 1e did not have an obvious effect on the enanti-
oselectivity (Table 1, entries 5 and 6). Catalyst 1f afforded good
enantioselectivity, however the reaction was significantly slower
and gave 4a in low yield (Table 1, entry 7). The double H-bond acti-
vation by the thiourea motif seems to be important for good cata-
lytic activity. Prolinol silyl ether 1g provided almost racemic 4a in
low yield (Table 1, entry 8). In the previous study, 1g was reported
to provide good enantioselectivity for the reaction in the presence
of acid additives.8 This emphasizes the importance of the match of
the catalysts with the additives.
Solvent screening for 1a-catalyzed addition of isobutyraldehyde to trans-b-
nitrostyrenea
Entry
Solvent
Yieldb (%)
ee (%)
1
2
3
n-Hexane
Toluene
Et2O
CH2Cl2
CHCl3
EtOAc
THF
Acetone
CH3CN
Methanol
DMF
42
61
54
55
92
68
54
63
75
50
29
83
95
94
96
97
98
94
91
93
92
92
81
94
4
5c
6
7
8
9
10
11
12d
Table 1
Conjugate addition of isobutyraldehyde to trans-b-nitrostyrene catalyzed by 1a–1ga
O
O
Ph
H2O
1a-g
a
NO2 20 mol%
NO2
The reactions were carried out with 1a (0.04 mmol), 2a (50
l
L, 0.55 mmol), 3a
H
H
Ph
(0.2 mmol) and DMAP (4.8 mg, 0.04 mmol) in the solvent (0.3 mL) at room tem-
perature for 6 h.
CHCl3/DMAP
3a
2a
b
4a
Isolated yields.
Reaction time was 2 h.
Reaction time was 24 h.
c
Entry
Cat.
Time (h)
GC yield (%)
Isolated yield (%)
eeb,c (%)
d
1
2d
3
4
5
6
7
8
1a
1a
1b
1c
1d
1e
1f
2
8
2
2
5
5
26
26
88
64
88
81
69
73
49
41
92
78
92
93
67
76
52
60
98
98
97
98
98
98
83
4
Table 3
Effect of additives on the reactiona
Entry
Additive
Time (h)
Yieldb (%)
ee (%)
1
—
H2O
24
24
6
6
2
3
3
3
3
35
31
21
10
92
88
71
75
86
31
97
98
96
96
98
97
97
96
97
96
2c
3
1g
PhCOOH
HOAc
DMAP
DABCO
Imidazole
TEA
a
The reactions were carried out with 1a–1g (0.04 mmol), 2a (50 lL, 0.55 mmol),
4
5
6
7
8
9
10
3a (0.2 mmol) and DMAP (4.8 mg, 0.04 mmol), in CHCl3 (0.3 mL) at room
temperature.
b
Ee values were determined by HPLC with a Diacel chiralpak-AD column.
The absolute configuration of 4a was determined as (R) by comparing the
c
specific rotation with reported data.
DIPEA
Sparteine
d
The reaction was carried out at 0 °C.
3
a
The reactions were carried out with 1a (0.04 mmol), 2a (50
l
L, 0.55 mmol), 3a
Catalyst 1a was selected for further optimization. The results of
the solvent screening are listed in Table 2. Although excellent
enantioselectivities were obtained in most solvents tested, the
reaction yields were highly variable. Acetone could also be used
as the reaction solvent, and no adduct from acetone and nitrosty-
rene was observed (Table 2, entry 8). MeOH and DMF had a detri-
mental effect on the yield and enantioselectivity (Table 2, entries
10 and 11). It is interesting to note that water was found to be a
suitable solvent for the reaction. Excellent enantioselectivity and
good yield were achieved (Table 2, entry 12). Catalyst 1a and nitro-
styrene are almost insoluble in water, and tiny ‘oil’ droplets float-
ing on water were formed during the reaction. The ‘on water’ effect
was highly possible in this case.9 Finally chloroform was identified
as the best solvent concerning excellent enantioselectivity, good
yield and short reaction time (Table 2, entry 5).
(0.2 mmol) and additive (0.04 mmol) in chloroform (0.3 mL) at room temperature.
b
Isolated yields.
c
The reaction was carried out with 1a (0.04 mmol), 2a (50 lL, 0.55 mmol), 3a
(0.2 mmol) and water (18 mg, 1 mmol) in dichloromethane (0.3 mL) at room
temperature.
oselectivity in the absence of any additives, however the yield was
rather low (Table 3, entry 1). Jacobsen et al. reported that the con-
jugate addition of aldehydes to nitroalkenes was achieved with
excellent yields and enantioselectivities, using the thiourea–pri-
mary amines as the catalysts and 500 mol % water as the addi-
tive.3q We examined the 1a-catalyzed reaction under the reaction
conditions used by Jacobsen et al., however no substantial
improvement was observed concerning the yield and enantioselec-
tivity (Table 3, entry 2). It should be noted that the structure of 1a
is highly similar with that of Jacobsen’s catalysts. The great
difference in the catalytic behaviours cannot be rationalized at
The influence of additives was studied further and the results
are summarized in Table 3. The reaction provided excellent enanti-

X. Zhang et al. / Tetrahedron: Asymmetry 20 (2009) 1451–1458
1453
the present stage. Benzoic acid and acetic acid showed the detri-
mental effect on the yield (Table 3, entries 3 and 4). Most of base
additives gave excellent yields and enantioselectivities (Table 3,
entries 5–9). DMAP was identified as the best additive (Table 3,
entry 5). In the case of sparteine (Table 3, entry 10), a large amount
of polymerized product of nitrostyrene was formed.5
Interesting results were obtained by monitoring the reaction
with GC (Fig. 1). While benzoic acid was used as the additive, the
reaction was almost stopped after 0.5 h and the conversion was
not increased during the prolonged reaction time. However, in
the presence of DMAP, the reaction proceeded until all the nitro-
styrenes were consumed. The deactivation of the catalyst in the
presence of acid additives was supposed to result in the observed
low yield. LC–MS analysis of the reaction mixture showed a prom-
inent peak at m/z 453 with DMAP as the additive, however a prom-
inent peak at m/z 467 was observed with benzoic acid as the
additive.
(intermediate C) activates nitrostyrene towards the attack of the
enamine. The resulting intermediate D is transformed into E after
the proton transfer. Intermediate E is hydrolyzed to give the prod-
uct and regenerate the catalyst 1a. The MS peak at m/z 453 corre-
sponds to intermediate E (M+H+). The intermediate D probably
undertakes an intramolecular addition to give 1,2-oxazine-N-oxide
(intermediates F).3q,5,10 Then F is further converted to the interme-
diate G (m/z 467) in the presence of acid and methanol (MeOH/H2O
is used as the eluting solvent for LC–MS analysis). The formation of
intermediate G was further supported by mixing 4a, 1a and ben-
zoic acid in CDCl3/CD3OD and by analyzing the mixture with LC–
MS. A prominent MS peak at m/z 470, corresponding to the
replacement of CH3O with CD3O, was observed. The generation of
intermediate F is proposed to result in the catalyst deactivation.
The acid additives promote the transformation of D to F, however
base additives promote the transformation of D to E by removing
the proton from the iminium cation.
The application scope of 1a was examined in the reaction of a
range of aldehydes and ketones with b-aryl-nitroethenes. The re-
sults are summarized in Table 4. Excellent enantioselectivities
and yields were achieved for the conjugate addition of isobutyral-
dehyde to various b-aryl-nitroethenes (Table 4, entries 1–10). The
substitution of the electron-withdrawing group on the phenyl ring
accelerated the reaction (Table 4, entry 6). 2-Furanyl-nitroethene
and 2-thiophenyl-nitroethene afforded excellent yields and enanti-
oselectivities (Table 4, entries 7 and 8). trans-b-Styryl-nitroethene
gave the 1,4-addition product with excellent enantioselectivity,
however in low yield (Table 4, entry 9). 1-Naphthyl-nitroethene
also provided excellent enantioselectivity and yield. The conjugate
addition of propionaldehyde and butyraldehyde to b-nitrostyrene
provided two diastereoisomers (dr = 2/1) with moderate yields
and excellent enantioselectivities (Table 4, entries 11 and 12).
The conjugate addition of acetone afforded moderate yield and
enantioselectivity (Table 4, entries 13). Low yield and enantioselec-
tivity were obtained when cyclopentanone was used (Table 4, en-
try 14). The reaction of methoxyacetone occurred regioselectively
Figure 1. Conversion–reaction time curves in the presence of PhCOOH and DMAP.
Based on the present experimental observation and previous
suggestions, an improved catalytic mechanism was proposed
(Scheme 2).3q,5 Imine intermediate A is generated from catalyst
1a and isobutyraldehyde. The tautomerization of A is promoted
by the base additive and provides the enamine B. The formation
of hydrogen bond between the nitro group and the thiourea group
S
S
H2O
O
Ph
N
H
N
H
N
H
N
H
NH
N
NO2
H
ESI-MS
O
O
f
ESI-MS
m/z 467 [M+]
e
m/z 453 [M+H]+
Me
N
H
Me
S
O
N
Me
Me
E
H
H3CO
Ph
S
Ph
G
N
N
H
H+ CH3OH
S
N
H
N
H
Base
H
NH2
N
H
O
O
O
H
H
Me
Me
N
Me
H
N
H
N
H
a
Me
NH
- H2O
D
d
Ph
O
S
N
S
O
Ph
N
H
N
H
F
N
H
N
H
N
A
Me
Me
HN
O
H
O
Me
H
N
S
b
H
Base
C
Me
c
H
N
N
H
H
Ph
NH
NO2
Me
Me
B
Ph
H
Scheme 2. Proposed catalytic mechanism.

1454
X. Zhang et al. / Tetrahedron: Asymmetry 20 (2009) 1451–1458
Table 4
Conjugate addition of aldehydes and ketones to b-aryl-nitroethenes catalyzed by 1aa
O
1a (20 mol%)
DMAP (20 mol%)
O
Ar
R3
NO2
R1
R1
NO2
Ar
CHCl3, rt
R2
2a-f
R3
R2
3a-j
4a-o
Entry
Aldehyde or ketone
Ar
Ph 3a
p-CH3OC6H53b
p-CH3C6H5 3c
p-ClC6H5 3d
m-ClC6H5 3e
p-NO2C6H5 3f
2-Furanyl 3g
2-Thiophenyl 3h
PhCH@CH 3i
1-Naphthyl 3j
Ph 3a
Product
Time (h)
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
(CH3)2CHCHO 2a
(CH3)2CHCHO 2a
(CH3)2CHCHO 2a
(CH3)2CHCHO 2a
(CH3)2CHCHO 2a
(CH3)2CHCHO 2a
(CH3)2CHCHO 2a
(CH3)2CHCHO 2a
(CH3)2CHCHO 2a
(CH3)2CHCHO 2a
CH3CH2CHO 2b
CH3(CH2)2CHO 2c
CH3COCH3 2d
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
2
3
9
2.5
2
1
1
2
9
5
2.5
6
23
45
22
92
93
96
90
83
85
90
98
43
96
75
50
59
27
80
98
97
98
97
98
97
97
95
96
95
96/97 (2:1)d
95/96 (2:1)d
78
Ph 3a
Ph 3a
Ph 3a
Ph 3a
(CH2)4CO 2e
CH3OCH2COCH32f
54/52 (2:1)d
41/62 (2:1)d
a
The reactions were carried out with 1a (0.04 mmol), 2a–f (0.55 mmol), 3a–j (0.2 mmol) and DMAP (0.04 mmol) in chloroform (0.3 mL) at room temperature.
Isolated yields.
Determined by chiral HPLC.
The diastereoisomeric ratio in parentheses was determined by HPLC.
b
c
d
at the
a
-methoxymethylene side and provided the adduct in good
Chiralcel AD-H OD-H, column and eluting with a hexane/i-PrOH
yield, however with low enantioselectivity and diastereoselectivity
(Table 4, entry 15).
solution.
4.2. Typical procedure for the preparation of thioureas 1a–
1e11,12
3. Conclusion
A 50-mL round-bottomed flask was charged with benzylamine
(1.07 g, 10.0 mmol), triethylamine (2.42 g, 24.0 mmol) and THF
(10 mL). The mixture was cooled with an ice bath under a N2 atmo-
sphere. Carbon disulphide (760 mg, 10 mmol) was added to the
reaction mixture by syringe pump over 0.5 h. After the addition
was completed, the mixture was stirred at room temperature for
1 h. The reaction mixture was cooled under an ice bath and tosyl
chloride (2.28 g, 12 mmol) was added. The reaction mixture was
warmed to room temperature and was stirred for 0.5 h. Next 1 M
hydrochloride (10 mL) and MTBE (10 mL) were added to the mix-
ture. The aqueous layer was separated and extracted with MTBE
(10 mL). The combined organic layer was dried over Na2SO4. After
the solvent was evaporated under vacuum, the residue was passed
through a silica plug, which was washed with hexane. After the
solvent was evaporated, the crude benzyl isothiocyanate was
obtained.
A solution of benzyl isothiocyanate (745 mg, 5 mmol) in 10 mL
CH2Cl2 was added dropwise to a solution of a (1R,2R)-cyclohexane-
1,2-diamine (570 mg, 5 mmol) in CH2Cl2 (10 mL). The reaction
solution was stirred at room temperature for 4 h. After the solvent
was evaporated, the residue was purified by column chromatogra-
phy (petroleum ether/CHCl3 = 1/1–0/100) to afford thiourea 1c
(536 mg, 72% yield).
In conclusion, we have found that readily available chiral thio-
ureas derived from cyclohexane-1,2-diamine are highly effective
organocatalysts for the conjugate addition of aldehydes to nitroal-
kenes. Excellent enantioselectivities and yields were obtained for a
variety of aryl and heteroaryl nitroalkenes. The catalysts are also
applicable for ketones, however in lower enantioselectivities and
yields. The use of base additives in the transformation is essential
for good yield and excellent enantioselectivity. This new experi-
mental observation sheds light on the exact function of base
additives.
4. Experimental
4.1. General method
1H NMR and 13C NMR spectra were recorded on Bruker AVANCE
400 spectrometer. Chemical shifts of protons are reported in parts
per million downfield from tetramethylsilane and are referenced to
residual protium in the NMR solvent (CHCl3: d 7.26). Chemical
shifts of carbon are referenced to the carbon resonances of the sol-
vent (CHCl3: d 77.0 and CH3OH: d 46.0). Peaks are labelled as sin-
glet (s), doublet (d), triplet (t), quartet (q) and multiplet (m).
Optical rotations were measured on a Perkin Elmer digital polarim-
eter. Melting points were measured on a WRS-2A melting point
apparatus and are uncorrected. The mass spectroscopic data were
obtained at the Thermo DSQII and Agilent 6120 mass spectrometer.
The high-resolution mass spectroscopic data were obtained at the
Thermo MAT 95XP mass spectrometer. Infrared (IR) spectra were
recorded on a Bruker Tensor 37 spectrophotometer. Data are repre-
sented as follows: frequency of absorption (cmꢀ1), and intensity of
absorption (vs = very strong, s = strong, m = medium, w = weak).
Enantiomeric excesses were determined by HPLC using a Daicel
4.3. Spectroscopic data of thiourea 1
4.3.1. 1-[(1R,2R)-2-Aminocyclohexyl]-3-phenylthiourea 1a
Prepared from phenyl isothiocyanate and (1R,2R)-cyclohexane-
1,2-diamine (77% yield). Yellow solid, mp: 54–57 °C; ½a D24
¼ þ11:0
ꢁ
(c 1.0, CH3OH); 1H NMR (400 MHz, CDCl3) d: 7.27–7.07 (m, 5H, Ar–
H), 4.13–4.09 (m, 1H, CH), 2.46–2.42 (m, 1H, CH), 1.97–1.86 (m, 2H,
CH2), 1.65–1.63 (m, 2H, CH2), 1.21–1.11 (m, 4H, 2CH2); 13C NMR

X. Zhang et al. / Tetrahedron: Asymmetry 20 (2009) 1451–1458
1455
(100 MHz, CD3OD) d: 179.5, 136.9, 127.1, 123.5, 122.6, 58.8, 52.7,
32.3, 29.6, 23.1, 22.9; MS (ESI, M+1): 250; IR (thin film)
/cmꢀ1
4.5. Spectroscopic data of conjugate addition products 4
m
:
3272 (m), 3028 (w), 2925 (s), 2852 (m), 1533 (vs), 1496 (s), 1446
4.5.1. (R)-2,2-Dimethyl-4-nitro-3-phenyl-butanal 4a
(m), 1330 (s), 1141 (m), 941 (m), 709 (s).
The title compound was prepared from trans-b-nitrostyrene and
isobutyraldehyde according to the representative procedure.
4.3.2. 1-[(1R,2R)-2-Aminocyclohexyl]-3-[3,5-
bis(trifluoromethyl) phenyl] thiourea 1b
Prepared from 3,5-bis(trifluoromethyl) phenyl isothiocyanate
and (1R,2R)-cyclohexane-1,2-diamine (yield: 95%). Yellow solid,
½
a 2D4
ꢁ
¼ þ7:0 (c 1.0, CHCl3); 1H NMR (300 MHz, CDCl3) d: 9.51 (s,
1H, CHO), 7.31–7.24 (m, 5H, Ar–H), 4.85 (dd, 2J(H,H) = 12.9 Hz,
3J(H,H) = 11.1 Hz, 1H, CH2), 4.68 (dd, 2J(H,H) = 12.9 Hz, 3J(H,H) =
4.2 Hz, 1H, CH2), 3.78 (dd, 3J(H,H) = 11.1 Hz, 3J(H,H) = 4.2 Hz, 1H,
CH), 1.14 (s, 3H, CH3), 1.01 (s, 3H, CH3); 13C NMR (75 MHz, CDCl3)
d: 204.0, 135.2, 129.0, 128.6, 128.0, 76.3, 48.5, 48.2, 21.7, 19.0; MS
(EI): m/z = 221 (M+), 187, 170, 159, 145, 117, 105, 91, 77, 72; IR
mp: 69–71 °C; ½a 2D4
ꢁ
¼ ꢀ3:0 (c 1.0, CH3OH); 1H NMR (400 MHz,
CD3OD) d: 8.11 (s, 2H, Ar–H), 7.52 (s, 1H, Ar–H), 4.21–4.16 (m,
1H, CH), 2.61–2.59 (m, 1H, CH), 2.03–1.91 (m, 2H, CH2), 1.69–
1.67 (m, 2H, CH2), 1.31–1.14 (m, 4H, 2CH2); 13C NMR (100 MHz,
CD3OD) d: 179.0, 140.4, 129.7, 129.3, 123.1, 121.0, 120.4, 108.7,
60.2, 53.8, 31.6, 29.5, 23.9, 23.7; MS (ESI, M+1): 386; IR (thin film)
(thin film) m
/cmꢀ1: 2925 (w), 1726 (m), 1638 (m), 1556 (s), 1456
(w), 1380 (m), 705 (m). The enantiomeric excess was determined
by HPLC with Chiralpak AD-H column at 208 nm (hex-
m
/cmꢀ1: 2939 (m), 1544 (w), 1474 (w), 1384 (m), 1278 (s), 1178
ane/i-PrOH = 98/2, 0.5 mL/min; tR(major) = 24.9 min, tR(minor)
=
(m), 1133 (s), 968 (w), 886 (w), 681 (m).
25.9 min).
4.3.3. 1-[(1R,2R)-2-Aminocyclohexyl]-3-benzylthiourea 1c
Prepared from benzylamine and (1R,2R)-cyclohexane-1,2-dia-
4.5.2. (R)-3-(4-Methoxyphenyl)-2,2-dimethyl-4-nitrobutanal 4b
The title compound was prepared from trans-1-methoxy-4-(2-
nitrovinyl) benzene and isobutyraldehyde according to the repre-
mine (yield: 72%). Yellow solid, mp: 114–115 °C; ½a D24
¼ ꢀ16:0 (c
ꢁ
1.0, CH3OH); 1H NMR (400 MHz, CD3OD) d: 7.33–7.25 (m, 5H,
Ar–H), 4.09–4.01 (m, 1H, CH), 2.50–2.47 (m, 1H, CH), 2.01–1.94
(m, 2H, CH2), 1.74–1.71 (m, 2H, CH2), 1.33–1.15 (m, 4H, 2CH2);
13C NMR: (100 MHz, CD3OD) d: 181.8, 137.5, 128.0, 127.0, 126.8,
sentative procedure.
½
a 2D5
ꢁ
¼ ꢀ3:0 (c 1.0, CHCl3); 1H NMR
(300 MHz, CDCl3) d: 9.51 (s, 1H, CHO), 7.11 (d, 3J(H,H) = 8.7 Hz,
2H, 3,5-Ar–H), 6.84 (d, 3J(H,H) = 8.7 Hz, 2H, 2,6-Ar–H), 4.81 (dd,
2J(H,H) = 12.6 Hz, 3J(H,H) = 11.4 Hz, 1H, CH2), 4.66 (dd, 2J(H,H)=
12.6 Hz, 3J(H,H) = 4.2 Hz, 1H, CH2), 3.79 (s, 3H, OCH3), 3.74 (dd,
3J(H,H) = 11.4 Hz, 3J(H,H) = 4.5 Hz, 1H, CH), 1.13 (s, 3H, CH3), 1.01
(s, 3H, CH3); 13C NMR (125 MHz, CDCl3) d: 204.3, 159.3, 130.1,
127.1, 114.1, 76.5, 55.2, 48.3, 47.9, 21.5, 18.9; MS (EI): m/z = 251
(M+), 180, 135, 134, 121, 119, 91; HRMS (EI) calcd for
60.2, 54.8, 34.2, 31.6, 24.3, 24.1; IR (thin film) m
/cmꢀ1: 3338 (m),
2935 (m), 2856 (m), 1568 (s), 1515 (vs), 1444 (m), 1372 (s), 1274
(vs), 1211 (m), 829 (m), 620 (s); MS (ESI, M+1): 264; HRMS (ESI)
calcd for C14H21N3S1 (M+1)+: 264.1534, found: 264.1531.
4.3.4. 1-[(1R,2R)-2-Aminocyclohexyl]-3-[(S)-1-phenylethyl]
thiourea 1d
C13H17O4N1 (M+): 251.1152, found: 251.1150; IR (thin film)
m/
cmꢀ1: 2927 (w), 1725 (m), 1611 (w), 1556 (vs), 1514 (s), 1465
(w), 1380 (m), 1252 (m), 1033 (w), 836 (w). The enantiomeric ex-
cess was determined by HPLC with Chiralpak OD-H column at
208 nm (hexane/i-PrOH = 75/25, 0.8 mL/min; tR(major) = 15.0 min,
tR(minor) = 21.1 min).
Prepared from (S)-1-phenylethylamine and (1R,2R)-cyclohex-
ane-1,2-diamine (yield: 90%). Yellow liquid, ½a D24
¼ þ5:0 (c 1.0,
ꢁ
CH3OH); 1H NMR (400 MHz, CD3OD) d: 7.31–7.21 (m, 5H, Ar–H),
4.09–3.97 (m, 1H, CH), 2.46–2.41 (m, 1H, CH), 1.93–1.86 (m, 2H,
CH2), 1.68–1.65 (m, 2H, CH2), 1.47 (d, J = 6.8 Hz, 3H, CH3), 1.28–
1.22 (m, 4H, 2CH2); 13C NMR (100 MHz, CD3OD) d: 142.1, 137.4,
127.8, 126.5, 125.1, 125.0, 124.2, 58.1, 53.1, 32.0, 30.0, 23.1, 22.9,
4.5.3. (R)-2,2-Dimethyl-4-nitro-3-(4-tolyl)-butanal 4c
The title compound was prepared from trans-1-methyl-4-(2-
nitrovinyl) benzene and isobutyraldehyde according to the repre-
18.5; IR (thin film) m
/cmꢀ1: 3257 (m), 2930 (s), 2857 (m), 1543
(s), 1449 (m), 1333 (m), 1157 (w), 1090 (w); MS (ESI, M+1): 278.
sentative procedure.
½
a 2D5
ꢁ
¼ ꢀ5:0 (c 1.0, CHCl3); 1H NMR
(400 MHz, CDCl3) d: 9.53 (s, 1H, CHO), 7.13 (d, 3J(H,H) = 8.0 Hz,
2H, Ar–H), 7.07 (d, 3J(H,H) = 8.0 Hz, 2H, Ar–H), 4.82 (dd, 2J(H,H) =
12.8 Hz, 3J(H,H) = 11.2 Hz, 1H, CH2), 4.67 (dd, 2J(H,H) = 12.8 Hz,
3J(H,H) = 4.0 Hz, 1H, CH2), 3.74 (dd, 3J(H,H) = 11.2 Hz, 3J(H,H) =
4.0 Hz, 1H, CH), 2.32 (s, 3H, CH3), 1.12 (s, 3H, CH3), 1.00 (s, 3H,
CH3); 13C NMR (100 MHz, CDCl3) d: 204.4, 137.9, 132.1, 129.4,
128.9, 76.4, 48.2, 48.1, 21.6, 21.0, 18.9; MS (EI): m/z = 235 (M+),
4.3.5. 1-[(1R,2R)-2-Aminocyclohexyl]-3-[(R)-1-phenylethyl]
thiourea 1e
Prepared from (R)-1-phenylethylamine and (1R,2R)-cyclohex-
ane-1,2-diamine (yield: 77%). Yellow liquid, ½a D24
¼ ꢀ30:0 (c 1.0,
ꢁ
CH3OH); 1H NMR (400 MHz, CD3OD) d: 7.31–7.21 (m, 5H, Ar–
H), 4.09–3.97 (m, 1H, CH), 2.46–2.41 (m, 1H, CH), 1.93–1.86 (m,
2H, CH2), 1.68–1.65 (m, 2H, CH2), 1.47 (d, J = 6.8 Hz, 3H, CH3),
1.28–1.22 (m, 4H, 2CH2); 13C NMR (100 MHz, CD3OD) d: 142.1,
137.4, 127.8, 126.5, 125.1, 125.0, 124.2, 58.1, 53.1, 32.0, 30.0,
173, 164, 118, 105, 119, 91; IR (thin film)
m
/cmꢀ1: 2973 (w),
2925 (w), 1726 (m), 1556 (vs), 1516 (w), 1381 (m), 1120 (w),
824 (w). The enantiomeric excess was determined by HPLC with
Chiralpak OD-H column at 208 nm (hexane/i-PrOH = 75/25,
0.8 mL/min; tR(major) = 12.2 min, tR(minor) = 17.0 min).
23.1, 22.9, 18.5; MS (ESI, M+1): 278; IR (thin film)
m :
/cmꢀ1
3257 (m), 2930 (s), 2857 (m), 1543 (s), 1449 (m), 1333 (m),
1157 (w), 1090 (w).
4.5.4. (R)-3-(4-Chlorophenyl)-2,2-dimethyl-4-nitrobutanal 4d
The title compound was prepared from trans-1-chloro-4-(2-
nitrovinyl) benzene and isobutyraldehyde according to the repre-
4.4. Typical procedure for the conjugate addition of aldehydes
to nitroalkenes
sentative procedure.
½
a 2D4
ꢁ
¼ þ3:0 (c 1.0, CHCl3); 1H NMR
A
mixture of trans-b-nitrostyrene (30.0 mg, 0.2 mmol), 1a
(10.0 mg, 0.04 mmol), DMAP (4.8 mg, 0.04 mmol), isobutyralde-
hyde (50 L, 0.55 mmol) and chloroform (0.3 mL) in a 5 mL
(300 MHz, CDCl3) d: 9.48 (s, 1H, CHO), 7.32 (t, 3J(H,H) = 2.4 Hz,
1H, 2-Ar–H), 7.29 (t, 3J(H,H) = 2.4 Hz, 1H, 6-Ar–H), 7.15 (t,
3J(H,H) = 2.4 Hz, 1H, 3-Ar–H), 7.12 (t, 3J(H,H) = 2.4 Hz, 1H, 5-Ar–
H), 4.82 (dd, 2J(H,H) = 13.2 Hz, 3J(H,H) = 11.4 Hz, 1H, CH2), 4.68
(dd, 2J(H,H) = 13.2 Hz, 3J(H,H) = 4.2 Hz, 1H, CH2), 3.77 (dd,
3J(H,H) = 11.4 Hz, 3J(H,H) = 4.2 Hz, 1H, CH), 1.13 (s, 3H, CH3), 1.01
(s, 3H, CH3); 13C NMR (75 MHz, CDCl3) d: 203.5, 134.0, 133.9,
130.3, 128.8, 76.1, 48.2, 48.0, 21.8, 19.0; MS (EI): m/z = 255 (M+),
l
flask was stirred at room temperature for 2 h. After the evapo-
ration of the solvent under vacuum, the residue was separated
by flash chromatography over silica gel (petroleum ether/ethyl
acetate = 10/1) to give 4a as
a colourless oil (40.7 mg, 92%
yield).

1456
X. Zhang et al. / Tetrahedron: Asymmetry 20 (2009) 1451–1458
193, 184, 140, 138, 125, 103, 77, 72; HRMS (EI) calcd for
1.08 (s, 3H, CH3); 13C NMR (75 MHz, CDCl3) d: 203.8, 138.0,
128.1, 127.2, 125.7, 78.1, 48.7, 44.3, 21.9, 19.2; MS (EI): m/
C12H14O3N1Cl1 (M+): 255.0657, found: 255.0658; IR (thin film)
m/
cmꢀ1: 2926 (w), 1728 (m), 1556 (s), 1494 (w), 1378 (m), 1094
(w), 835 (w). The enantiomeric excess was determined by HPLC
with Chiralpak OD-H column at 208 nm (hexane/i-PrOH = 75/25,
0.8 mL/min; tR(major) = 13.5 min, tR(minor) = 20.0 min).
z = 227 (M+), 207, 180, 165, 156, 110, 97, 84; IR (thin film)
m/
cmꢀ1: 2925 (w), 1725 (m), 1557 (s), 1433 (w), 1378 (m), 882
(w), 704 (m). The enantiomeric excess was determined by HPLC
with Chiralpak OD-H column at 208 nm (hexane/ i-PrOH = 75/25,
0.8 mL/min; tR(major) = 12.8 min, tR(minor) = 19.9 min).
4.5.5. (R)-3-(3-Chlorophenyl)-2,2-dimethyl-4-nitrobutanal 4e
The title compound was prepared from trans-1-chloro-3-(2-
nitrovinyl) benzene and isobutyraldehyde according to the repre-
4.5.9. (R)-E-2,2-Dimethyl-3-(nitromethyl)-5-phenylpent-4-enal
4i
sentative procedure.
½
a 2D4
ꢁ
¼ þ10:0 (c 1.0, CHCl3); 1H NMR
The title compound was prepared from (1E,2E)-4-nitrobuta-1,3-
dienyl benzene and isobutyraldehyde according to the representa-
(400 MHz, CDCl3) d: 9.51 (s, 1H, CHO), 7.29–7.10 (m, 4H, Ar–H),
4.83 (dd, 2J(H,H) = 13.2 Hz, 3J(H,H) = 11.2 Hz, 1H, CH2), 4.69 (dd,
tive procedure. ½a D24
ꢁ
¼ ꢀ5:0 (c 1.0, CHCl3); 1H NMR (400 MHz,
2J(H,H) = 13.2 Hz,
3J(H,H) = 4.0 Hz,
1H,
CH2),
3.77
(dd,
CDCl3) d: 9.52 (s, 1H, CHO), 7.35–7.26 (m, 5H, Ar–H), 6.53 (d,
3J(H,H) = 15.6 Hz, 1H, @CH), 6.02 (dd, 3J(H,H) = 10.2 Hz, 3J(H,H) =
15.6 Hz, 1H, @CH), 4.52 (dd, 3J(H,H) = 4.0 Hz, 2J(H,H) = 12.0 Hz,
1H, CH2), 4.45 (dd, 3J(H,H) = 4.0 Hz, 2J(H,H) = 12.0 Hz, 1H, CH2),
3.28 (dt, 3J(H,H) = 4.0 Hz, 3J(H,H) = 10.2 Hz, 1H, CH), 1.17 (s, 3H,
CH3), 1.16 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3) d: 203.8,
136.3, 136.0, 128.6, 128.2, 126.6, 122.9, 47.8, 47.2, 21.0, 19.1; MS
(EI): m/z = 247 (M+), 200, 157, 129, 115, 104, 91, 77; HRMS (EI)
3J(H,H) = 11.2 Hz, 3J(H,H) = 4.0 Hz, 1H, CH), 1.15 (s, 3H, CH3), 1.03
(s, 3H, CH3); 13C NMR (100 MHz, CDCl3) d: 203.7, 137.7, 134.6,
130.0, 129.3, 128.4, 127.3, 76.1, 48.2, 48.1, 21.8, 18.9; MS (EI): m/
z = 255 (M+), 193, 166, 138, 125, 103, 77, 72; HRMS (ESI) calcd for
C12H14O3N1Cl1 (MꢀH)ꢀ: 254.0584, found: 254.0586; IR (thin film)
m
/cmꢀ1: 2975 (w), 1726 (s), 1556 (vs), 1478 (w), 1435 (w), 1379
(m), 1085 (w), 703 (m). The enantiomeric excess was determined
by HPLC with Chiralpak OD-H column at 208 nm (hexane/
i-PrOH = 75/25, 0.8 mL/min;tR(major) = 15.0 min, tR(minor) = 22.7 min).
calcd for C14H17O3N1 (M)+ 247.1203, found: 247.1206; IR (thin
:
film)
m
/cmꢀ1: 2974 (w), 1723 (m), 1554 (s), 1450 (w), 1380 (m),
972 (m), 887 (w), 749 (m). The enantiomeric excess was deter-
mined by HPLC with Chiralpak OD-H column at 208 nm (hexane/
i-PrOH = 80/20, 0.8 mL/min; tR(major) = 15.4 min, tR(minor) = 16.5 min).
4.5.6. (R)-2,2-Dimethyl-4-nitro-3-(4-nitrophenyl)-butanal 4f
The title compound was prepared from trans-1-nitro-4-(2-
nitrovinyl) benzene and isobutyraldehyde according to the repre-
sentative procedure.
½
a 2D4
ꢁ
¼ þ10:0 (c 1.0, CHCl3); 1H NMR
(300 MHz, CDCl3) d: 9.48 (s, 1H, CHO), 8.21 (d, 3J(H,H) = 8.7 Hz,
2H, 3, 5-Ar–H), 7.42 (d, 3J(H,H) = 8.7 Hz, 2H, 2, 6-Ar–H), 4.90 (t,
2,3J(H,H) = 13.5 Hz, 1H, CH2), 4.77 (dd, 2J(H,H) = 13.5 Hz, 3J(H,H) =
3.9 Hz, 1H, CH2), 3.94 (dd, 3J(H,H) = 13.5 Hz, 3J(H,H) = 3.9 Hz, 1H,
CH), 1.17 (s, 3H, CH3), 1.06 (s, 3H, CH3); 13C NMR (75 MHz, CDCl3)
d: 203.3, 147.8, 143.5, 130.4, 124.1, 76.1, 48.6, 48.3, 22.3, 19.4; MS
(EI): m/z = 267 (M+1)+, 220, 204, 190, 177, 164, 149, 129, 115, 103,
4.5.10. (R)-2,2-Dimethyl-3-(naphthalene-1-yl)-4-nitrobutanal
4j
The title compound was prepared from (E)-1-(2-nitrovi-
nyl)naphthalene and isobutyraldehyde according to the represen-
tative procedure. White solid, mp: 103–104 °C; ½a D24
¼ þ87:0 (c
ꢁ
1.0, CHCl3); 1H NMR (400 MHz, CDCl3) d: 9.59 (s, 1H, CHO), 8.23
(d, 3J(H,H) = 8.4 Hz, 1H, Ar–H), 7.86 (d, 3J(H,H) = 8.0 Hz, 1H, Ar–
H), 7.81 (d, 3J(H,H) = 8.0 Hz, 1H, Ar–H), 7.59 (dd, 3J(H,H) = 8.4 Hz,
3J(H,H) = 7.2 Hz,1H, Ar–H), 7.53–7.41 (m, 3H, Ar–H), 5.03–4.91
(m, 2H, CH2), 4.88–4.85 (m, 1H, CH), 1.21 (s, 3H, CH3), 0.97 (s,
3H, CH3); 13C NMR (100 MHz, CDCl3) d: 204.4, 133.0, 132.9,
132.3, 129.1, 128.8, 126.8, 126.0, 125.0,124.9, 122.1, 77.0, 49.1,
40.3, 21.7, 18.8; MS (EI): m/z = 271 (M+), 200, 154, 141; HRMS
91, 77; HRMS (EI) calcd for C12H15O5N2 (M+1)+ 267.0975, found:
:
267.0973; IR (thin film)
m
/cmꢀ1: 2923 (w), 1725 (m), 1604 (w),
1556 (s), 1522 (s), 1377 (w), 1348 (s), 858 (m), 703 (w). The
enantiomeric excess was determined by HPLC with Chiralpak
OD-H column at 208 nm (hexane/i-PrOH = 75/25, 0.8 mL/min;
tR(major) = 25.9 min, tR(minor) = 39.7 min).
(EI) calcd for C16H17O3N1 (MꢀH)ꢀ 270.1130, found: 270.1136; IR
:
(thin film)
m
/cmꢀ1: 2971 (w), 2815 (w), 1717 (m), 1551 (vs),
4.5.7. (R)-3-(Furan-2-yl)-2,2-dimethyl-4-nitrobutanal 4g
The title compound was prepared from trans-2-(2-nitrovinyl)
furan and isobutanaldehyde according to the representative proce-
1471 (w), 1433 (w), 1377 (m), 796 (m), 782 (m). The enantiomeric
excess was determined by HPLC with Chiralpak OD-H column at
208 nm (hexane/i-PrOH = 75/25, 1.0 mL/min; tR(major) = 9.3 min,
tR(minor) = 10.4 min).
dure. ½a 2D5
ꢁ
¼ ꢀ20:5 (c 1.0, CHCl3); 1H NMR (300 MHz, CDCl3) d: 9.50
(s, 1H, CHO), 7.36 (s, 1H, Ar–H), 6.30 (s, 1H, Ar–H), 6.21 (d,
3J(H,H) = 3.0 Hz, 1H, Ar–H), 4.75 (dd, 2J(H,H) = 12.6 Hz, 3J(H,H) =
11.1 Hz, 1H, CH2), 4.57 (dd, 2J(H,H) = 12.6 Hz, 3J(H,H) = 3.6 Hz, 1H,
CH2), 3.92 (dd, 3J(H,H) = 11.1 Hz, 3J(H,H) = 3.6 Hz, 1H, CH), 1.18 (s,
3H, CH3), 1.05 (s, 3H, CH3); 13C NMR (75 MHz, CDCl3) d: 203.7,
149.9, 142.9, 110.7, 109.9, 75.2, 48.5, 42.5, 21.5, 19.4; MS (EI): m/
4.5.11. (2R/2S,3R)-2-Methyl-4-nitro-3-phenylbutanal 4k
The title compound was prepared from trans-b-nitrostyrene and
propionaldehyde according to the representative procedure.
½
a 2D9
ꢁ
¼ þ6:0 (c 1.0, CHCl3); 1H NMR (400 MHz, CDCl3) signals corre-
z = 211 (M+), 181, 164, 149, 121, 94, 81; IR (thin film)
m :
/cmꢀ1
sponding to the major diastereomer d: 9.69 (s, 1H, CHO), 7.32–7.13
(m, 5H, Ar–H), 4.82–4.63 (m, 2H, CH2), 3.86–3.76 (m, 1H, CH),
2.81–2.74 (m, 1H, CH), 1.21 (d, 3J(H,H) = 7.2 Hz, 3H, CH3); signals
corresponding to the minor diastereomer d: 9.51 (s, 1H, CHO),
7.32–7.13 (m, 5H, Ar–H), 4.82–4.63 (m, 2H, CH2), 3.86–3.76 (m,
1H, CH), 2.81–2.74 (m, 1H, CH), 1.00 (d, 3J(H,H) = 7.2 Hz, 3H,
CH3); 13C NMR (100 MHz, CDCl3) d: 202.3, 136.6, 130.9, 129.0,
128.0, 78.1, 48.7, 44.0, 12.0; MS (EI): m/z = 207 (M+), 160, 145,
2925 (w), 1728 (m), 1557 (s), 1376 (m), 1148 (m), 740 (m). The
enantiomeric excess was determined by HPLC with Chiralpak
OD-H column at 208 nm (hexane/i-PrOH = 75/25, 0.8 mL/min;
tR(major) = 9.7 min, tR(minor) = 14.3 min).
4.5.8. (R)-2,2-Dimethyl-4-nitro-3-(thiophen-2-yl) butanal 4h
The title compound was prepared from trans-2-(2-nitrovinyl)
thiophene and isobutanaldehyde according to the representative
131, 117, 104, 91, 77; IR (thin film) m
/cmꢀ1: 3032 (w), 2973 (w),
procedure. ½a 2D5
ꢁ
¼ þ13:0 (c 1.0, CHCl3); 1H NMR (300 MHz, CDCl3)
2929 (w), 1724 (m), 1603 (w), 1555 (s), 1456 (m), 1377 (m), 702
(m). The enantiomeric excess and diastereomeric ratio were deter-
mined by HPLC with Chiralpak OD-H column at 208 nm (hex-
ane/i-PrOH = 80/20, 0.8 mL/min; signals corresponding to the
major diastereomer: tR(major) = 25.1 min, tR(minor) = 19.1 min; signals
d: 9.52 (s, 1H, CHO), 7.23–7.22 (m, 1H, 5-Ar–H), 6.95 (dd,
3J(H,H) = 5.1 Hz, 3J(H,H) = 3.6 Hz, 1H, 4-Ar–H), 6.91 (dd, 3J(H,H) =
3.6 Hz, 4J(H,H) = 0.9 Hz, 1H, 3-Ar–H), 4.76–4.62 (m, 2H, CH2), 4.14
(dd, 3J(H,H) = 10.5 Hz, 3J(H,H) = 4.5 Hz, 1H, CH), 1.22 (s, 3H, CH3),

X. Zhang et al. / Tetrahedron: Asymmetry 20 (2009) 1451–1458
1457
corresponding to the minor diastereomer: tR(major) = 28.8 min,
tR(minor) = 23.0 min).
147, 117, 104, 91, 77; IR (KBr)
m
/cmꢀ1: 2930 (w), 2830 (w), 1715
(m), 1556 (s), 1382 (m), 1109 (m), 763 (w), 703 (m). The enantio-
meric excess and diastereomeric ratio were determined by HPLC
with Chiralpak AS-H column at 208 nm (hexane/i-PrOH = 75/25,
0.86 mL/min).
4.5.12. (2R/2S,3R)-2-Ethyl-4-nitro-3-phenylbutanal 4l
The title compound was prepared from trans-b-nitrostyrene and
butyraldehyde according to the representative procedure.
Signals corresponding to the major diastereoisomer: 1H NMR
(400 MHz, CDCl3) d: 7.35–7.28 (3H, m, Ar–H), 7.25–7.21 (2H, m,
Ar–H), 4.93 (1H, dd, 3J(H,H) = 12.8, 3J(H,H) = 8.3 Hz, CH2), 4.65
(1H, dd, 3J(H,H) = 12.8 Hz, 3J(H,H) = 6.8 Hz, CH2), 3.93–3.80 (2H,
m, CH2), 3.45 (3H, s, OCH3), 1.78 (3H, s, CH3); 13C NMR
(100 MHz, CDCl3) d 209.9, 134.5, 129.0, 128.5, 128.4, 86.4, 76.5,
59.8, 46.3, 26.4; tR(minor) = 14.9 min, tR(major) = 19.7 min.
½
a 2D5
ꢁ
¼ þ6:0 (c 1.0, CHCl3); MS (EI): m/z = 221 (M+), 175, 145, 131,
117, 105, 104, 91, 77; IR (thin film) m
/cmꢀ1: 2956 (w), 2926 (m),
2360 (w), 1718 (m), 1555 (s), 1496 (m), 1379 (m), 701 (m). The
enantiomeric excess and diastereomeric ratio were determined
by HPLC with Chiralpak OD-H column at 208 nm (hex-
ane/i-PrOH = 80/20, 0.8 mL/min).
Signals corresponding to the major diastereoisomer: 1H NMR
(400 MHz, CDCl3) d: 9.70 (d, 1H, 3J(H,H) = 2.4 Hz, CHO), 7.33–7.14
(m, 5H, Ar–H), 4.79–4.58 (m, 2H, CH2), 3.82–3.77 (m, 1H, CH),
2.69–2.66 (m, 1H, CH), 0.86–0.81 (t, 3J(H,H) = 7.5 Hz, 3H, CH3);
13C NMR (100 MHz, CDCl3) d: 202.8, 136.7, 128.9, 128.1, 127.8,
78.5, 42.7 29.7, 20.4, 10.7; tR(minor) = 16.3 min, tR(major) = 19.2 min.
Signals corresponding to the minor diastereoisomer: 1H NMR
(400 MHz, CDCl3) d: 9.46 (d, 1H, 3J(H,H) = 2.4 Hz, CHO), 7.33–7.14
(m, 5H, Ar–H), 4.79–4.58 (m, 2H, CH2), 3.82–3.77 (m, 1H, CH),
2.61–2.53 (m, 1H, CH), 1.02–0.97 (t, 3J(H,H) = 7.5 Hz, 3H, CH3);
13C NMR (100 MHz, CDCl3) d: 202.9, 136.7, 128.9, 128.1, 127.9,
77.8, 44.1, 29.7, 20.6, 11.5; tR(minor) = 17.2 min, tR(major) = 27.9 min).
Signals corresponding to the minor diastereoisomer: 1H NMR
(400 MHz, CDCl3) d: 7.35–7.28 (3H, m, Ar–H), 7.25–7.21 (2H, m,
Ar–H), 4.86 (1H, dd, 3J(H,H) = 13.1 Hz, 3J(H,H) = 5.5 Hz, CH2), 4.72
(1H, dd, 3J(H,H) = 13.1 Hz, 3J(H,H) = 8.6 Hz, CH2), 3.93–3.80 (2H,
m, CH2), 3.38 (3H, s, OCH3), 2.04 (3H, s, CH3); 13C NMR (100 MHz,
CDCl3) d: 208.1, 135.4, 129.1, 128.9, 128.1, 88.2, 76.5, 59.8, 45.9,
26.2; tR(minor) = 13.8 min, tR(major) = 26.5 min.
Acknowledgements
Financial support of this study from the National Natural Sci-
ence Foundation of China (No. 20772160), the Ministry of Educa-
tion (NCET project), the Guangzhou Bureau of Science and
Technology and the Zhuhai Bureau of Science and Technology is
gratefully acknowledged.
4.5.13. (S)-5-Nitro-4-phenylpentan-2-one 4m
The title compound was prepared from trans-b-nitrostyrene and
acetone according to the representative procedure. ½a D25
¼ ꢀ1:7 (c
ꢁ
1.0, CHCl3); 1H NMR (400 MHz, CDCl3) d: 7.35–7.20 (5H, m, Ar–
H), 4.70 (1H, dd, 3J(H,H) = 12.3 Hz, 3J(H,H) = 6.90 Hz, CH2), 4.60
(1H, dd, 3J(H,H) = 12.3 Hz, 3J(H,H) = 7.8 Hz, CH2), 4.01 (1H, m, CH),
2.92 (2H, d, 3J(H,H) = 7.0 Hz, CH2), 2.13 (3H, s, CH3); 13C NMR
(100 MHz, CDCl3) d: 205.4, 138.8, 129.1, 127.9, 127.4, 79.5, 46.1,
39.0, 30.4; MS (EI): m/z = 207 (M+), 191, 167, 133, 91, 84; IR (thin
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½
a 2D5
ꢁ
¼ ꢀ3:3 (c 1.3, CHCl3); IR (thin film)
m
/cmꢀ1: 3031 (w), 2983
(w), 2880 (w), 1730 (s), 1552 (vs), 1159 (m), 785 (m), 697 (w);
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(400 MHz, CDCl3) d: 7.34–7.30 (3H, m, Ar–H), 7.19–7.16 (2H, m,
Ar–H), 5.02–5.00 (2H, m, CH2), 3.86–3.81 (1H, m, CH), 2.55–2.49
(1H, m, CH), 2.34–1.43 (6H, m, 3CH2); 13C NMR (100 MHz, CDCl3)
d: 219.1, 137.4, 129.0, 128.5, 128.0, 78.3, 51.4, 44.0, 39.3, 27.0,
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ꢁ
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1458
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