Asymmetric direct vinylogous Michael reaction catalyzed by self-assembled organocatalyst

Article abstract of DOI:10.1080/00397911.2011.563023

(Chemical Equation Presented) The self-assembled organocatalyst of cinchona alkaloid derivatives and amino acids has been applied to a direct asymmetric vinylogous Michael addition of α,α-dicyanoolefins to nitroolefins; the corresponding products could be obtained in moderate to good yields and enantioselectivities. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397911.2011.563023

This article was downloaded by: [Pennsylvania State University]
On: 23 July 2012, At: 06:16
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lsyc20
Asymmetric Direct Vinylogous Michael
Reaction Catalyzed by Self-Assembled
Organocatalyst
Wei-Yi Chen a , Luo Ouyang b , Rui-Ye Chen b & Xin-Sheng Li b
a College of Chemistry, Chemical Engineering, and Materials Science,
Suzhou University, Suzhou, China
b Zhejiang Key Laboratory for Reactive Chemistry on Solid Surfaces,
Institute of Physical Chemistry, Zhejiang Normal University, Jinhua,
China
Accepted author version posted online: 02 Jan 2012. Version of
record first published: 29 May 2012
To cite this article: Wei-Yi Chen, Luo Ouyang, Rui-Ye Chen & Xin-Sheng Li (2012): Asymmetric Direct
Vinylogous Michael Reaction Catalyzed by Self-Assembled Organocatalyst, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 42:17, 2585-2594
To link to this article: http://dx.doi.org/10.1080/00397911.2011.563023
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation
that the contents will be complete or accurate or up to date. The accuracy of any
instructions, formulae, and drug doses should be independently verified with primary
sources. The publisher shall not be liable for any loss, actions, claims, proceedings,

demand, or costs or damages whatsoever or howsoever caused arising directly or
indirectly in connection with or arising out of the use of this material.

Synthetic Communications1, 42: 2585–2594, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.563023
ASYMMETRIC DIRECT VINYLOGOUS MICHAEL
REACTION CATALYZED BY SELF-ASSEMBLED
ORGANOCATALYST
Wei-Yi Chen,1 Luo Ouyang,2 Rui-Ye Chen,2 and
Xin-Sheng Li2
1College of Chemistry, Chemical Engineering, and Materials Science, Suzhou
University, Suzhou, China
2Zhejiang Key Laboratory for Reactive Chemistry on Solid Surfaces,
Institute of Physical Chemistry, Zhejiang Normal University, Jinhua, China
GRAPHICAL ABSTRACT
Abstract The self-assembled organocatalyst of cinchona alkaloid derivatives and amino
acids has been applied to a direct asymmetric vinylogous Michael addition of a,a-dicyanoo-
lefins to nitroolefins; the corresponding products could be obtained in moderate to good
yields and enantioselectivities.
Keywords Dicyanoolefins; enantioselective Michael addition; nitroolefins; organo-
catalyst; self-assembled
INTRODUCTION
The Michael addition of nucleophiles to electron-deficient olefins is one of the
most important carbon–carbon bond-construction strategies in synthetic organic
chemistry.[1] Because new stereocenters are often generated, considerable efforts have
been devoted to the asymmetric Michael reactions over past decades.[2] Recently, it
has been found that a,a-dicyanoolefin compounds can selectively behave as accep-
tors or vinylogous donors in asymmetric Michael reactions in the presence of orga-
nocatalysts, which simultaneously give multifunctional products with two vicinal
chiral tertiary carbon centers.[3]
Received August 17, 2010.
Address correspondence to Wei-Yi Chen, College of Chemistry, Chemical Engineering, and
Materials Science, Suzhou University, Suzhou 215128, China. E-mail: suzhoucwy@163.com
2585

2586
W.-Y. CHEN ET AL.
Scheme 1. Representative precatalyst modules.
Nowadays bifunctional organocatalysts possessing thioureas (or ureas) and
tertiary amine groups have received special attention, for the double hydrogen-
bonding interaction of N–H of thioureas (or ureas) and reactants has been generally
recognized as having a specific role in the efficient catalysis and high enantiocon-
trol.[4] In the presence of such catalysts, the asymmetric direct vinylogous Michael
reaction of nitroolefin and a,a-dicyanoolefin could provide one of the most versatile
and attractive approaches for the generation of optically active compounds. How-
ever, when the cinchona alkaloid derivatives bearing a thiourea functionality
were used as the catalysts, only moderate enantioselectivities were achieved in the
Michael reaction of nitroolefin and a,a-dicyanoolefin.[3c] Very recently, the concept
of self-assembly has been successfully employed to construct combinatorial chiral
catalysts.[5] Herein, we report the results of asymmetric direct vinylogous Michael
reaction in the presence of self-assembled organocatalyst of cinchona alkaloid deri-
vatives and amino acids [Eq. (1)].
Our initial studies began with reaction of vinyl malononitrile 2a and nitroolefin
3a in the presence of a catalytic amount of self-assembled organocatalyst of cinchona
alkaloid derivatives 1a–c and amino acids Schemes 1 and 2. Readily available
a-amino acids, such as proline, glycine, alanine, phenylglycine, valine, and phenyl-
alanine, were screened. Some typical results are summarized in Table 1.
The results of the investigation revealed that the reaction could proceed
smoothly to yield the desired products in dichloromethane (DCM). However, the
enantioselectivities varied greatly depending on the Cinchona alkaloid derivatives
Scheme 2. Structures of vinylmalononitriles 2.

DIRECT VINYLOGOUS MICHAEL REACTION
2587
Table 1. Screening studies of vinylogous Michael addition reactiona
b
Entry
Catalyst
Solvent
Temp. (ꢀC)
Time (h)
Conversion
Ee (%)
1
2
L-Pro=1a
L-Pro=1b
L-Pro=1c
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
THF
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
0
30
30
30
30
30
30
30
30
30
30
30
30
30
30
30
30
30
30
36
78
70
81
85
65
73
88
86
91
41
40
38
82
30
70
78
91
92
64
58
55
72
50
40
44
18
17
10
66
44
23
89
45
56
58
20
60
88
3
4
D-Pro=1a
D-Pro=1b
D-Pro=1c
5
6
7
N-Me-L-Pro=1a
N-Me-L-Pro=1b
N-Me-L-Pro=1c
L-PhGly=1a
L-PhGly=1b
L-PhGly=1c
L-Pro=1c
8
9
10
11
12
13
14
15
16
17
18
19
L-Pro=1c
L-Pro=1c
Toluene
Acetone
EA
L-Pro=1c
L-Pro=1c
MeOH
Et2O
THF
L-Pro=1c
L-Pro=1c
aThe reaction was carried out on a 0.5-mmol scale.
bDetermined by chiral HPLC analysis (Chiralcel AS).
and amino acids used (Table 1, entries 1–12). The self-assembled organocatalyst
L-Pro (1c) proved to be the most promising catalyst, giving the corresponding
product with 81% yield and 72% ee at room temperature (Table 1, entry 3).
Therefore, the self-assembled organocatalyst L-Pro(1c) was selected for the sub-
sequent studies. We next investigated the effect of the reaction medium, reaction tem-
perature, and catalyst loading in the presence of a catalytic amount of L-Pro (1c). It
was found that the reaction proceeded smoothly in both nonpolar solvent and polar
protic solvent. The most encouraging result was obtained when the reaction was car-
ried out in tetrahydrofuran (THF) (Table 1, entry 13). No significant increase in the
yield and enantioselectivity (85% yield, 88% ee) was found by increasing the catalyst
amount to 10 mol%; however, inferior result (61% yield, 74% ee) was obtained with
lower catalyst (2 mol%) loading at the same reaction conditions. By lowering the tem-
perature to 0 ꢀC, the desired product was obtained in comparable ee and poor yield
(Table 1, entry 19); for convenience, the reactions for the rest of this study were con-
ducted at room temperature. Therefore, the optimum reaction conditions were
achieved by performing the reaction of 1 equiv. of dicyanoolefin with 1.2 equiv. of
nitroolefin and 5 mol% catalyst loading at room temperature in THF.

2588
W.-Y. CHEN ET AL.
To examine the scope of the direct vinylogous Michael addition reactions in
the presence of self-assembled organocatalyst L-Pro(1c), a series of a,a-vinylmalo-
nonitriles (Scheme) and nitroolefins were evaluated under the optimized reaction
conditions, and the results are summarized in Table 2. In most of the cases, the
reactions proceeded smoothly to furnish the corresponding products in good
yields and high enantioselectivities, and only the anti-products were detected in
the reactions.
As shown in Table 2, various nitrostyrenes with electron-donating or electron-
withdrawing substituents could smoothly react with a,a-dicyanoolefins. Meanwhile,
regardless of the alkyl- and aryl- or heteroaryl-substituted nitrostyrenes, the reaction
proceeded smoothly to afford the Michael adducts with good diastereoselectivities
and enantioselectivities. This method offers several advantages such as good dia-
stereo- and enantioselectivity, good conversions, cleaner reaction profiles, and simple
experimental and workup procedures.
A possible mechanism for the enantioselective direct vinylogous Michael
addition reaction of vinylmalononitriles to nitrostyrene is shown in Scheme 3. First,
a self-assembled organocatalyst was formed by ionic interaction of proline and chiral
Table 2. Asymmetric vinylogous Michael addition of a,a-dicyanoolefins to nitroolefinsa
b
c
Entry
2
R
Product
Yield (%)
Ee (%)
1
2
2a
2a
2a
2a
2a
2b
2b
2c
2c
2c
2c
2c
2c
2d
2e
Ph (3a)
4-MeOC6H4(3b)
2-Furanyl (3c)
4-Me2NC6H4 (3d)
i-Propyl (3e)
4aa
4ab
4ac
4ad
4ae
4ba
4bb
4ca
4cb
4cd
4cf
82
65
58
64
35
80
62
78
60
56
76
80
81
65
63
89
85
90
91
61
88
89
85
80
86
82
88
85
71
63
3
4
5
6
Ph (3a)
4-MeOC6H4 (3b)
Ph (3a)
7
8
9
4-MeOC6H4 (3b)
4-Me2NC6H4 (3d)
4-MeC6H4 (3f)
4-ClC6H4 (3g)
4-BrC6H4 (3h)
Ph (3a)
10
11
12
13
14
15
4cg
4ch
4da
4eb
4-MeOC6H4 (3b)
aThe reaction was carried out on a 0.5-mmol scale in THF at rt.
bIsolated yields.
cDetermined by chiral HPLC analysis.
dAll the products are characterized by 1HNMR, 13C NMR, FTIR, and mass spectrometry, and the
absolute configurations of products were assigned by comparison with optical rotation and=or retention
time on chiral HPLC with the literature value.[3d,3f]

DIRECT VINYLOGOUS MICHAEL REACTION
2589
Scheme 3. Possible mechanism of the vinylogous Michael reaction.
thiourea, which incorporated both the proline reaction center and stereocontrolling
moiety. Nitroolefin was activated by the double hydrogen-bonding interaction of
N–H of chiral thiourea; meanwhile the deprotonation of a,a-dicyanoolefin could
occur in the presence of proline. Then vinylogous Michael addition could take place
from a,a-dicyanoolefin to nitroolefin, giving the corresponding product with good
diastereo- and enantioselectivity.
In summary, we have found that a self-assembled organocatalyst of proline
and chiral thiourea can catalyze direct vinylogous Michael reaction at room tem-
perature with good diastereo- and enantioselectivities. These results demonstrate
the enormous effect of the thiourea and proline on the reactivity and selectivity.
More detailed studies on the mechanism and synthetic applications of this self-
assembled catalyst for enantioselective organocatalytic reactions are currently under
investigation.
EXPERIMENTAL
Proton nuclear magnetic resonance spectra (1H NMR) and carbon nuclear
magnetic resonance spectra (13C NMR) were obtained for solution in CDCl3 with
Me4Si as internal standard on a Bruker Avance DPX 300 spectrometer. Infrared (IR)
Spectra were obtained on a Nicolet Fourier tranform (FT)–IR500 spectrophoto-
meter using KBr pellets. Optical rotations were measured in CH2Cl2 on a Schmidt þ
Haensdch polarimeter (Polartronic MH8) with a 1-cm cell (c given in g=100 mL).
Mass spectral analyses were carried out on a VG 7035 micromass mass spectro-
photometer.
General Procedure
A mixture of 2 (0.5 mmol), 3 (0.6 mmol), 1c (0.025 mmol), and proline (0.02
5 mmol) in THF (1 mL) was stirred for 30 h at rt. Then the reaction was quenched
by adding 0.5 mL 1 M HCl. The mixture was extracted with EtOAc and dried with
anhydrous sodium sulfate. The crude product was purified by column chromato-
graphy on silica gel to give the desired product 4.

2590
W.-Y. CHEN ET AL.
2-[3-(1-Phenyl-2-nitroethyl)-thiochroman-4-ylidene]-
malononitrile (4aa)
[a] ¼ ꢁ648 (c 0.15, CHCl3); 1H NMR(CDCl3, 400 MHz): d 7.95 (d, J ¼ 8.0 Hz,
1H), 7.53–7.27 (m, 8H), 4.73 (dd, J ¼ 10.0, 12.6 Hz, 1H), 4.36 (dd, J ¼ 4.9, 12.6 Hz,
1H), 3.88–3.81 (m, 1H), 3.77–3.72 (m, 1H), 3.35(dd, J ¼ 3.2, 13.9 Hz, 1H), 2.63
(dd, J ¼ 3.2, 14.0 Hz, 1H); 13C NMR (CDCl3, 100 MHz): d 170.4, 137.9, 135.3,
134.6, 130.4, 129.6, 129.1, 127.9, 127.4, 125.4, 124.3, 112.7, 112.5, 83.0, 77.9, 43.5,
41.6, 28.9; IR (KBr): n 2226, 1556, 1460 cmꢁ1; MS: C20H15N3O2S 361.09 [M]þ.
The enantiomeric ratio was determined by high-performance liquid chromatography
(HPLC) on a Chiralpak AS column (20% 2-propanol=hexane, 1 mL=min), t minor ¼
18.756 min, t major ¼ 26.674 min.
2-[3-(1-p-Methoxy-phenyl-2-nitroethyl)-thiochroman-4-ylidene]-
malononitrile (4ab)
22
1
½aꢂD ¼ ꢁ464 (c 0.11, EA); H NMR (CDCl3, 400 MHz): d7.92 (d, J ¼ 8.2 Hz,
1H), 7.51 (t, J ¼ 7.8 Hz, 1H), 7.34-7.29 (m, 4H), 6.94 (d, J ¼ 8.8 Hz, 2H), 4.70 (dd,
J ¼ 10.2, 12.6 Hz, 1H), 4.34 (dd, J ¼ 4.8, 12.6 Hz, 1H), 3.82 (s, 3H), 3.78–3.69 (m,
1H), 3.66–3.58 (m, 1H), 3.34 ( dd, J ¼ 3.2, 13.8 Hz, 1H), 2.65 (dd, J ¼ 3.1, 13.6 Hz,
1H); 13C NMR (CDCl3, 100 MHz): d 170.6, 143.3, 134.6, 131.6, 130.5, 130.3,
129.6, 129.1, 127.8, 127.4, 125.4, 124.3, 112.8, 112.5, 83.1, 77.8, 55.6, 42.9, 41.6,
28.9; IR (KBr): n2216, 1640, 1518 cmꢁ1; MS: C21H17N3O3S 391.46 [M]þ. The enan-
tiomeric ratio was determined by HPLC on Chiralpak AS column (20% 2-propanol=
hexane, 1 mL=min), t minor ¼ 20.156 min, t major ¼ 27.678 min.
2-[3-(1-Furan-2-yl-2-nitroethyl)-thiochroman-4-ylidene]-
malononitrile (4ac)
22
1
½aꢂD ¼ ꢁ582 (c 0.11, EA); H NMR( CDCl3, 400 MHz): d 7.91 (d, J ¼ 8.1 Hz,
1H), 7.52–7.48 (m, 2H), 7.31–7.24 (m, 2H), 6.45 (d, J 3.9 Hz, 1H), 6.37–6.35 (m, 1H),
4.75 (dd, J ¼ 9.8, 12.6 Hz, 1H), 4.31 (dd, J ¼ 4.6, 12.8 Hz, 1H), 3.98–3.84 (m, 1H),
3.84–3.78 (m, 1H), 3.39(dd, J ¼ 3.4, 13.9 Hz, 1H), 2.69 (dd, J ¼ 3.4, 14.0 Hz, 1H);
13C NMR (CDCl3, 100 MHz): d170.2, 144.6, 143.7, 134.3, 130.4, 129.1, 127.3,
126.5, 112.8, 111.7, 111.2, 110.8, 82.9, 76.8, 39.8, 37.9, 28.7; IR (KBr): n 2228,
1562, 1432 cmꢁ1; MS: C18H13N3O3S 351.41 [M]þ. The enantiomeric ratio was deter-
mined by HPLC on Chiralpak AS column (20% 2-propanol=hexane, 1 mL=min),
t minor ¼ 14.856 min, t major ¼ 23.694 min.
2-f3-[1-(4-Dimethylamino-phenyl)-2-nitroethyl]-
thiochroman-4-ylideneg-malononitrile (4ad)
22
1
½aꢂD ¼ ꢁ388 (c 0.11, EA); H NMR (CDCl3, 400 MHz): d 8.02 (d, J ¼ 8.1 Hz,
1H), 7.46 (t, J ¼ 7.7 Hz, 1H), 7.32 (d, J ¼ 8.5 Hz, 1H), 7.29–7.24 (m, 1H), 7.20
(d, J ¼ 8.5 Hz, 2H), 6.71 (d, J ¼ 8.5 Hz, 2H), 4.68 (dd, J ¼ 9.6, 12.1 Hz, 1H), 4.31

DIRECT VINYLOGOUS MICHAEL REACTION
2591
(dd, J ¼ 4.6, 12.6 Hz, 1H), 3.84-3.68 (m, 2H), 3.32 (dd, J ¼ 3.2, 13.9 Hz, 1H), 2.95
(s, 6H), 2.72 (dd, J ¼ 3.4, 14.0 Hz, 1H); 13C NMR (CDCl3, 100 MHz): d 170.8,
150.5, 136.3, 134.5, 130.4, 128.6, 127.4, 125.2, 124.4, 121.9, 112.7, 112.6, 81.9,
78.3, 43.1, 42.3, 40.1, 28.9; IR (KBr): n 2225, 1623, 1558 cmꢁ1; MS: C22H20N4O2S
404.52 [M]þ. The enantiomeric ratio was determined by HPLC on Chiralpak OD
column (20% 2-propanol=hexane, 1 mL=min), t minor ¼ 18.928 min, t major ¼
29.621 min.
2-[3-(1-Isopropyl-2-nitroethyl)-thiochroman-4-ylidene]-
malononitrile (4ae)
22
1
½aꢂD ¼ þ201 (c 0.09, EA); H NMR (CDCl3, 400 MHz): d 7.85 (d, J ¼ 8.5 Hz,
1H), 7.48 (t, J ¼ 8.2 Hz, 1H), 7.25–7.18 (m, 2H), 4.42 (dd, J ¼ 4.6, 13.2 Hz, 1H), 4.21
(dd, J ¼ 6.6, 13.6 Hz, 1H), 3.57–3.46 (m, 2H), 3.23–3.19 (m, 1H), 2.88–2.69 (m, 1H),
2.29–2.20 (m, 1H), 1.04 (d, J ¼ 6.9 Hz, 3H), 0.95(d, J ¼ 6.9 Hz, 3H); 13C NMR
(CDCl3, 100 MHz): d 171.3, 137.2, 134.1, 130.9, 126.9, 125.4, 125.2, 112.8, 112.6,
78.9, 74.5, 42.1, 39.8, 29.8, 27.4, 20.7; IR (KBr): n 2228, 1562, 1438 cmꢁ1; MS:
C17H17N3O2S 327.42 [M]þ. The enantiomeric ratio was determined by HPLC on
Chiralpak OD column (30% 2-propanol=hexane, 1 mL=min), t major ¼ 10.674 min,
t minor ¼ 28.456 min.
2-[3-(1-Phenyl-2-nitroethyl)-chroman-4-ylidene]-malononitrile (4ba)
22
1
½aꢂD ¼ þ172 (c 0.12, EA); H NMR(CDCl3, 400 MHz): d 8.25 (d, J ¼ 8.2 Hz,
1H), 7.61 (t, J ¼ 7.8 Hz, 1H), 7.51–7.44 (m, 3H), 7.39–7.36 (m, 2H), 7.15 (t, J ¼ 7.7 Hz,
1H), 7.06 (d, J ¼ 4.2 Hz, 1H), 4.87–4.63 (m, 1H), 4.61–4.48 (m, 1H), 4.14–4.05
(m, 2H), 3.76–3.69 (m, 1H), 3.45 (d, J ¼ 6.9 Hz, 1H); 13C NMR (CDCl3, 100 MHz):
d 165.3, 156.1, 137.7, 135.4, 129.7, 129.1, 128.1, 127.9, 122.5, 118.5, 114.9, 113.1,
112.8, 78.9, 77.5, 66.6, 43.5, 42.9; IR (KBr): n 2224, 1612, 1556 cmꢁ1; MS:
C20H15N3O3 345.36 [M]þ. The enantiomeric ratio was determined by HPLC on
Chiralpak OD column (20% 2-propanol=hexane, 1 mL=min), t major ¼ 20.674 min,
t minor ¼ 26.756 min.
2-[3-(1-p-Methoxy-phenyl-2-nitroethyl)-chroman-
4-ylidene]-malononitrile (4bb)
22
½aꢂD ¼ ꢁ198 (c 0.12, CHCl3); 1H NMR (CDCl3, 400 MHz): d 8.18 (d,
J ¼ 8.2 Hz, 1H), 7.66–7.59 (m, 1H), 7.21 (d, J ¼ 8.5 Hz, 2H), 7.19–7.15 (m, 1H),
7.06(d, J ¼ 8.5 Hz, 2H), 6.98 (d, J ¼ 8.3 Hz, 1H), 4.86–4.78 (m, 1H), 4.48 (dd,
J ¼ 4.8, 12.6 Hz, 1H), 4.15-4.05 (m, 2H), 3.82 (s, 3H), 3.75–3.69 (m, 1H), 3.41 (d,
J ¼ 6.9 Hz, 1H); 13C NMR (CDCl3, 100 MHz): d 165.3, 160.2, 156.1, 137.7, 129.7,
127.9, 122.4, 122.5, 118.5, 114.9, 114.8, 113.1, 112.8, 78.8, 77.5, 66.6, 55.5, 43.5,
42.9; IR (KBr): n 2219, 1612, 1569 cmꢁ1; MS: C21H17N3O4 375.39 [M]þ; The enan-
tiomeric ratio was determined by HPLC on Chiralpak AS column (20% 2-propanol=
hexane, 1 mL=min), t minor ¼ 24.556 min, t major ¼ 36.678 min.

2592
W.-Y. CHEN ET AL.
2-[2-(1-Phenyl-2-nitroethyl)-3,4-dihydro-2H-naphthalen-
1-ylidene]-malononitrile (4ca)
22
1
½aꢂD ¼ ꢁ178 (c 0.10, EA); H NMR (CDCl3, 400 MHz): d 8.08 (d, J ¼ 8.0 Hz,
1H), 7.62–7.59 (m, 1H), 7.45–7.34(m, 4H), 7.29–7.27 (m, 3H), 4.74-4.68 (m, 1H),
4.46-4.41 (m, 1H), 3.67–3.63 (m, 1H), 3.51–3.44 (m, 1H), 3.08-2.99 (m, 1H),
2.92-2.86 (m, 1H), 2.03–1.95 (m, 1H), 1.84–1.80 (m, 1H); 13C NMR (CDCl3,
100 MHz): d174.6, 159.8, 139.5, 136.0, 134.6, 130.1, 129.5, 128.8, 128.7, 127.9,
127.8, 127.4, 113.1, 113.0, 81.1, 78.7, 44.8, 44.5, 25.6, 24.1; IR (KBr): n 2218,
1624, 1560 cmꢁ1; MS: C21H17N3O2 343.41 [M]þ. The enantiomeric ratio was deter-
mined by HPLC on Chiralpak AS column (20% 2-propanol=hexane, 1 mL=min),
t minor ¼ 19.856 min, t major ¼ 27.678 min.
2-f2-[1-(4-Methoxy-phenyl)-2-nitro-ethyl]-3,4-dihydro-2H-
naphthalen-1-ylideneg-malononitrile (4cb)
22
½aꢂD ¼ ꢁ159 (c 0.14, CHCl3); 1H NMR(CDCl3, 400 MHz): d 8.06 (d,
J ¼ 7.8 Hz, 1H), 7.60–7.69 (m, 1H), 7.44–7.33 (m, 2H), 7.19 (d, J ¼ 6.8 Hz, 2H),
6.91 (d, J ¼ 6.8 Hz, 2H), 4.62 (dd, J ¼ 10.2, 12.6 Hz, 1H), 4.40 (dd, J ¼ 5.2,
12.6 Hz, 1H), 3.81 (s, 3H), 3.62–3.55 (m, 1H), 3.46–3.40 (m, 1H), 2.92–2.87 (m,
2H), 1.99–1.97 (m, 1H), 1.87–1.84 (m, 1H); 13C NMR (CDCl3, 100 MHz): d 175.1,
159.8, 139.4, 134.6, 130.1, 129.0, 128.7, 127.8, 127.6, 114.9, 113.1, 113.0, 80.7,
78.6, 55.4, 44.8, 43.7, 25.4, 24.1; IR (KBr): n 2228, 1608, 1518 cmꢁ1; MS:
C22H19N3O3 373.48 [M]þ. The enantiomeric ratio was determined by HPLC on
Chiralpak AS column (20% 2-propanol=hexane, 1 mL=min), t minor ¼ 24.758 min,
t major ¼ 32.694 min.
2-f2-[1-(4-Dimethylamino-phenyl)-2-nitro-ethyl]-3,4-dihydro-2H-
naphthalen-1-ylideneg-malononitrile (4cd)
22
½aꢂD ¼ ꢁ110:4 (c 0.12, CHCl3); 1H NMR (CDCl3, 400 MHz): d 8.04 (d,
J ¼ 8.0 Hz, 1H), 7.62–7.56 (m, 1H), 7.45–7.33 (m, 2H), 7.10 (d, J ¼ 8.2 Hz, 2H),
6.71 (d, J ¼ 8.2 Hz, 2H), 4.71–4.63 (m, 1H), 4.42–4.36 (m, 1H), 3.61–3.56 (m, 1H),
3.38–3.31 (m, 1H), 3.05–3.01 (m, 1H), 2.97 (s, 6H), 2.88–2.82 (m, 1H), 1.98–1.87
(m, 2H); 13C NMR (CDCl3, 100 MHz): d 176.3, 150.4, 139.8, 134.5, 130.1, 128.8,
128.4, 127.8, 127.1, 113.2, 112.8, 79.9, 78.8, 45.2, 43.8, 40.5, 25.6, 24.5; IR (KBr):
n 2226, 1618, 1562 cmꢁ1; MS: C23H22N4O2 386.48 [M]þ. The enantiomeric ratio
was determined by HPLC on Chiralpak AS column (20% 2-propanol=hexane,
1 mL=min), t minor ¼ 21.766 min, t major ¼ 36.684 min.
2-[2-(1-p-Tolyl-2-nitroethyl)-3,4-dihydro-2h-naphthalen-1-ylidene]-
malononitrile (4cf)
22
½aꢂD ¼ ꢁ192 (c 0.11, CHCl3); 1H NMR (CDCl3, 400 MHz): d 8.05 (d,
J ¼ 8.1 Hz, 1H), 7.61 (t, J ¼ 7.6 Hz, 1H), 7.48–7.19 (m, 6H), 4.69–4.62 (m, 1H),
4.42–4.36 (m, 1H), 3.66–3.61 (m, 1H), 3.50–3.45 (m, 1H), 3.05–3.01 (m, 1H),
2.92–2.87 (m, 1H), 2.41 (s, 3H), 2.01–1.97 (m, 1H), 1.87–1.84 (m, 1H); 13C NMR

DIRECT VINYLOGOUS MICHAEL REACTION
2593
(CDCl3, 100 MHz): d 175.1, 139.6, 138.6, 134.5, 132.8, 130.2, 129.8, 128.7, 127.8,
127.6, 127.3, 113.2, 113.0, 80.8, 78.6, 44.9, 44.2, 25.6, 24.2, 20.9; IR (KBr): n 2225,
1558, 1518 cmꢁ1; MS: C22H19N3O2 357.42 [M]þ. The enantiomeric ratio was deter-
mined by HPLC on Chiralpak AS column (20% 2-propanol=hexane, 1 mL=min),
t minor ¼ 16.766 min, t major ¼ 23.074 min.
2-f2-[1-(p-Chloro-phenyl)-2-nitroethyl]-3,4-dihydro-2H-naphthalen-
1-ylideneg-malononitrile (4cg)
22
½aꢂD ¼ ꢁ198 (c 0.12, CHCl3); 1H NMR (CDCl3, 400 MHz): d 8.07 (d,
J ¼ 8.1 Hz, 1H), 7.62–7.59 (m, 1H), 7.44–7.35 (m, 4H), 6.98 (d, J ¼ 7.2 Hz, 2H),
4.71–4.67 (m, 1H), 4.49–4.41 (m, 1H), 3.58–3.54 (m, 1H), 3.50–3.42 (m, 1H),
2.94–2.90 (m, 2H), 2.01–1.97 (m, 1H), 1.86–1.81 (m, 1H); 13C NMR (CDCl3,
100 MHz): d 176.2, 141.1, 134.8, 134.6, 134.4, 130.2, 129.8, 129.2, 128.7, 127.8,
127.5, 113.2, 112.9, 80.9, 79.0, 44.6, 43.8, 25.5, 24.1; IR (KBr): n 2228, 1578,
1556 cmꢁ1; MS: C21H16ClN3O2 377.92 [M]þ. The enantiomeric ratio was deter-
mined by HPLC on Chiralpak AS column (20% 2-propanol=hexane, 1 mL=min),
t minor ¼ 18.956 min, t major ¼ 27.684 min.
2-f2-[1-(p-Bromo-phenyl)-2-nitro-ethyl]-3,4-dihydro-2H-
naphthalen-1-ylideneg-malononitrile (4ch)
22
½aꢂD ¼ ꢁ186 (c 0.18, CHCl3); 1H NMR (CDCl3, 400 MHz): d 8.08 (d,
J ¼ 8.0 Hz, 1H), 7.63–7.52 (m, 3H), 7.43–7.32 (m, 2H), 7.11 (d, J ¼ 7.2 Hz, 2H),
4.71–4.67 (m, 1H), 4.43–4.41 (m, 1H), 3.62–3.57 (m, 1H), 3.47–3.42 (m, 1H),
2.97–2.93 (m, 2H), 2.02–1.99 (m, 1H), 1.88–1.86 (m, 1H); 13C NMR (CDCl3,
100 MHz): d 174.2, 140.2, 135.1, 134.6, 132.8, 130.1, 129.5, 128.8, 127.8, 127.5,
122.9, 113.1, 112.9, 79.9, 77.5, 45.1, 43.8, 25.4, 23.8; IR (KBr): n 2229, 1582,
1558 cmꢁ1; MS: C21H16BrN3O2 422.25 [M]þ. The enantiomeric ratio was determined
by HPLC on Chiralpak AS column (20% 2-propanol=hexane, 1 mL=min), t minor ¼
25.758 min, t major ¼ 32.678 min.
2-(4-Nitro-1,3-diphenyl-butylidene)-malononitrile (4da)
22
1
½aꢂD ¼ ꢁ154 (c 0.15, CHCl3); H NMR(CDCl3, 400 MHz): d 7.65–7.59 (m,
3H), 7.43–7.36 (m, 5H), 7.26–7.19 (m, 2H), 4.72–4.69 (m, 1H), 4.69–4.62 (m, 1H),
3.62–3.58 (m, 2H), 0.98 (d, J ¼ 6.8 Hz, 3H); 13C NMR (CDCl3, 100 MHz): d
181.6, 135.8, 133.2, 131.6, 129.5, 129.3, 128.6, 128.0, 126.9, 112.1, 111.9, 82.8,
79.2, 47.9, 44.2, 16.9; IR (KBr): n 2229, 1559, 1498 cmꢁ1; MS: C20H17N3O2 331.41
[M]þ. The enantiomeric ratio was determined by HPLC on Chiralpak AS column
(20% 2-propanol=hexane, 1 mL=min), t minor ¼ 18.796 min, t major ¼ 22.874 min.
2-f2-[1-(4-Methoxy-phenyl)-2-nitro-ethyl]-cyclohexan-1-ylideneg-
malononitrile (4eb)
22
½aꢂD ¼ ꢁ20:1 (c 0.15, CHCl3); 1H NMR (CDCl3, 400 MHz): d 7.09 (d,
J ¼ 8.8 Hz, 2H), 6.92 (d, J ¼ 8.8 Hz, 2H), 4.61 (dd, J ¼ 12.6, 10.8 Hz, 1H), 4.31 (dd,

2594
W.-Y. CHEN ET AL.
J ¼ 12.6, 4.8 Hz, 1H), 3.86–3.81 (m, 1H), 3.79 (s, 3H), 3.35–3.32 (m, 1H), 3.09–3.05
(m, 1H), 2.59–2.56 (m, 1H), 2.31–2.19 (m, 1H), 1.711.49 (m, 5H); 13C NMR (CDCl3,
100 MHz): d 185.1, 158.7, 128.9, 127.5, 114.9, 111.2, 110.9, 83.2, 78.8, 55.3, 46.2,
44.1, 31.3, 30.1, 28.8, 19.5; IR (KBr): n 2228, 1556 cmꢁ1; MS: C18H19N3O3 325.38
[M]þ. The enantiomeric ratio was determined by HPLC on Chiralpak AS column
(20% 2-propanol=hexane, 1 mL=min), t minor ¼ 15.753 min, t major ¼ 40.677 min.
REFERENCES
1. (a) Enders, D.; Seki, A. Proline-catalyzed enantioselective Michael additions of ketones to
nitrostyrene. Synlett 2002, 26; (b) Okino, T.; Hoashi, Y.; Takemoto, Y. Enantioselective
Michael reaction of malonates to nitroolefins catalyzed by bifunctional organocatalysts.
J. Am. Chem. Soc. 2003, 125, 12672; (c) Wang, J.; Li, H.; Duan, W.; Zu, L. S.; Wang,
W. Organocatalytic asymmetric Michael addition of 2,4-pentandione to nitroolefins.
Org. Lett. 2005, 7, 4713; (d) Wu, F.; Li, H.; Hong, R.; Deng, L. Construction of quaternary
stereocenters by eEfficient and practical conjugate additions to,b-unsaturated ketones with
a chiral organic catalyst. Angew. Chem. 2006, 118, 961.
2. (a) Sibi, M. P.; Manyem, S. Enantioselective conjugate additions. Tetrahedron 2000, 56,
8033; (b) Krause, N.; Hoffmann-Roder, A. Recent advances in catalytic enantioselective
Michael additions. Synthesis 2001, 171; (c) Dalko, P. I.; Moisan, L. In the golden age of
organocatalysis. Angew. Chem., Int. Ed. 2004, 43, 5138.
3. (a) Xie, J. W.; Yue, L.; Xue, D.; Ma, X. L.; Chen, Y. C.; Wu, Y.; Zhu, J.; Deng, J. G. Orga-
nocatalytic and direct asymmetric vinylogous Michael addition of a, a-dicyanoolefins to
a,b-unsaturated aldehydes. Chem. Commun. 2006, 1563; (b) Xue, D.; Chen, Y. C.; Cun,
L. F.; Wang, Q. W.; Zhu, J.; Deng, J. G. Asymmetric direct vinylogous Michael reaction
of activated alkenes to nitroolefins catalyzed by modified cinchona alkaloids. Org. Lett.
2005, 7, 5293; (c) Jiang, L.; Zheng, H. T.; Liu, T. Y.; Yue, L.; Chen, Y. C. Asymmetric
direct vinylogous carbon-carbon bond formation catalyzed by bifunctional organocata-
lysts. Tetrahedron 2007, 63, 5123; (d) Lu, J.; Zhou, W. J.; Liu, F.; Loh, T. P. Organocata-
lytic and enantioselective direct vinylogous Michael addition to maleimides. Adv. Synth.
Catal. 2008, 350, 1796; (e) Lu, J.; Liu, F.; Loh, T. P. Enantioselective Michael addition
of dicyanoolefins to a,b-unsaturated aldehydes in aqueous medium. Adv. Synth. Catal.
2008, 350, 1781; (f) Xiong, X. F.; Jia, Z. J.; Du, W.; Jiang, K.; Liu, T. Y.; Chen, Y. C. Mer-
ging chiral organocatalysts: Enantio- and diastereoselective direct vinylogous Mannich
reaction of alkylimines. Chem. Commun. 2009, 6994.
4. (a) Pihko, P. M. Activation of carbonyl compounds by double hydrogen bonding: An
emerging tool in asymmetric catalysis. Angew. Chem., Int. Ed. 2004, 43, 2062; (b) Connon,
S. T. Organocatalysis mediated by (thio)urea derivatives. Chem.-Eur. J. 2006, 12, 5418; (c)
Taylor, M. S.; Jacobsen, E. N. Asymmetric catalysis by chiral hydrogen-bond donors.
Angew. Chem., Int. Ed. 2006, 45, 1520.
5. (a) Yang, F.; Zhao, D. B.; Lan, J. B.; Xi, P. H.; Yang, L.; Xiang, S. H.; You, J. S. Self-
assembled bifunctional catalysis induced by metal coordination interactions: An exception-
ally efficient approach to enantioselective hydrophosphonylation. Angew. Chem. Int. Ed.
2008, 47, 5646; (b) Mandal, T.; Zhao, C. G. Modularly designed organocatalytic assemblies
for direct nitro-Michael addition reactions. Angew. Chem. Int. Ed. 2008, 47, 7714; (c) Reis,
¨
O.; Eymur, S.; Reis, B.; Demir, A. S. Direct enantioselective aldol reactions catalyzed by a
proline–thiourea host–guest complex. Chem. Commun. 2009, 1088.