Pyrrolidine-linker-camphor assembly: Bifunctional organocatalysts for efficient Michael addition of cyclohexanone to nitroolefins under neat conditions

Article abstract of DOI:10.1016/j.tet.2010.11.093

A simple and convenient strategy was developed to synthesize a new class of pyrrolidinyl-camphor based bifunctional organocatalysts possessing varying functional linkers. Catalytic screening of these camphor-pyrrolidine linked derivatives for asymmetric M

Full text of DOI:10.1016/j.tet.2010.11.093

Tetrahedron 67 (2011) 1171e1177
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Pyrrolidine-linker-camphor assembly: bifunctional organocatalysts for efficient
Michael addition of cyclohexanone to nitroolefins under neat conditions
*
Shaik Anwar, Pei-Hsun Lee, Tsai-Yung Chou, Chihliang Chang, Kwunmin Chen
Department of Chemistry, National Taiwan Normal University, Taipei 116, Taiwan, ROC
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 27 October 2010
Received in revised form 24 November 2010
Accepted 30 November 2010
Available online 4 December 2010
A simple and convenient strategy was developed to synthesize a new class of pyrrolidinylecamphor
based bifunctional organocatalysts possessing varying functional linkers. Catalytic screening of these
camphorepyrrolidine linked derivatives for asymmetric Michael reaction of cyclohexanone with b-ni-
trostyrene was carried out. Various aryl- and heteroaryl-nitroolefins, ketones as well as aldehydes gave
the corresponding Michael adducts in high chemical yields (up to 95%) and exceptionally high diastereo-
(syn/anti up to 99:1) and enantioselectivity (up to 95%) using catalyst 6 under solvent-free conditions.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Michael addition
Nitroolefins
Camphor
Linker
Organocatalysis
1. Introduction
productivity.7b The E factor, introduced by Sheldon, is defined as the
ratio of the weight of waste to the weight of product, while the
Michael reaction of ketones with nitroolefins represents an
unquestionable convenient access to -nitroketones, which are
volume productivity is the grams of product per liter of reaction
medium. The E factor for many pharmaceuticals has been estimated
to exceed 100.7c,d The largest contributors to the magnitude of E
factor are organic solvents, many of which are ecologically harmful
and require expensive remediation. A pressing challenge facing
organic chemists, therefore, is to advance new processes that are
not only efficient, selective, and of high yielding but also environ-
mentally friendly.7e An alternative strategy to reduce the E factor of
reactions and their impact on the environment is to conduct the
reaction under solvent-free conditions. Among the benefits of
solvent-free processes are cost savings, decreased energy con-
sumption, reduced reaction times, and a large reduction in reactor
size and capital investment. The study of asymmetric catalysis
under solvent-free conditions was inspired by the potential envi-
ronmental benefits and the economic incentives. In addition, sol-
vent-free Michael addition of cyclohexanone to nitrostyrene is
a convenient access to important intermediates in organic syn-
thesis.8,9 Accordingly considerable efforts have been directed to-
ward the development of organocatalytic systems in solvent-free
conditions. Representative catalysts include pyrrolidine based
phosphine oxide,3a aliphatic-aromatic diamine,8a recyclable pyr-
rolidine systems,8b,e,f,h thiourea derivatives,8d,i and chiral ionic
liquids.9bee Most of the above mentioned catalysts suffer from the
limitations of long reaction time, high molecular weight, and te-
dious catalyst preparation. The development of alternative trivial
and eco-friendly organocatalysts for Michael addition is desirable.
g
valuable building blocks in organic synthesis.1 The adducts serve as
useful precursors for various functionalized organic compounds
that are found to be pharmacologically active and can selectively
block presynaptic dopamine receptors.2 Much attention has been
directed toward the design and application of organocatalysts re-
cently.3 Of the developed organocatalysts in asymmetric catalysis,4
proline and its derivatives have proven to be effective protocols via
the enamine catalysis.5,6 The organocatalytic asymmetric Michael
addition of a carbonyl compound with nitroolefins was pioneered
by List and Barbas independently.3h,i Later on Alexakis3j and Kot-
suki3f have shown that 2,20-bipyrrolidine and pyrrolidineepyridine
systems could serve as powerful asymmetric catalysts. Most of the
organocatalytic reactions require the use of organic solvents, i.e.,
DMSO, DMF, i-PrOH, MeOH, hexanes, toluene, and CHCl3, which are
not environmentally friendly. Historically, the metric to measure
reaction success has been the chemical yield. Although chemical
yields will remain imperative, alternative measures include the
‘greenness’ of
a reaction, or E
factor,7a and the volume
* Corresponding author. Tel.: þ886 2 7734 6150; fax: þ886 2 2932 4249; e-mail
address: kchen@ntnu.edu.tw (K. Chen).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.11.093

1172
S. Anwar et al. / Tetrahedron 67 (2011) 1171e1177
2. Results and discussion
reducing system of Ti(i-PrO)4 and NaBH4. The reaction proceeds
through an intermediate titanium(IV) complex, which is either
reduced directly or via equilibration of transient iminium species.13
This synthetic route preparation can be carried out with ease for up
to a quantity of 4.0 g without any difficulty. The Boc-protected pro-
catalyst 5 obtained, can be easily deprotected by a known standard
protocol using TFAeDCM to inherit the pyrrolidineecamphor based
catalyst 6 with a chemical yield of 79% (Scheme 1).
The structure of the newly designed catalyst 6 was fully char-
acterised by IR, 1H, 13C NMR, HRMS analyses and the absolute ste-
reochemistry was further confirmed by a single X-ray structure
analysis (Fig. 2).18
2.1. Design and preparation of organocatalysts
In this advancing field of organocatalysis, there has always been
a high demand for more diverse organocatalysts encompassing the
qualities of enhanced stereoselectivity, inert to air as well as water
and easy preparation using readily accessible inexpensive starting
materials. Over the past few years, we have been actively involved
in the development of a series of camphor-based pyrrolidinyl
organocatalysts.10 These pyrrolidine linked camphor assembly have
proven efficacies in organocatalytic asymmetric synthesis. The
fundamental idea in designing these pyrrolidineecamphor based
catalysts relies on the assumption that the pyrrolidine moiety plays
a crucial role in enamine formation. The nucleophilic component is
accompanied by a rigid bicyclic camphor scaffold that serves as an
efficient stereocontrolling element.11 In addition, with these pyr-
rolidineecamphor derived organocatalysts available, we would like
to study the structureestereoselectivity relationship. We would
like to assess the impact of the linker functionality between the
camphor skeleton and the pyrrolidine ring on the stereoselectivity
of the reaction.
In these catalytic systems the pyrrolidine structural unit and
camphor scaffold were linked with appropriate functionalities,
such as amine, amide, and sulfide linkers (Fig. 1). We were in-
terested to see whether the variation in the linker functionality will
have an impact on the stereoselectivity of the reaction. We have
also presumed that modification in the linker via various func-
tionalities may contribute significantly toward the diastereo- and
enantioselectivity of the reaction. Preliminary screening of these
pyrrolidinylecamphor bifunctional organocatalysts led to the
conclusion that, the newly designed organocatalyst 6 showed
promising results. The reaction of cyclohexanone 7a with various
aryl- and heteroaryl-nitroolefins proceeded smoothly with excel-
lent diastereoselectivities (up to 99:1 syn/anti) and with good to
excellent enantioselectivities (up to 95% ee) during the asymmetric
transformation.
Fig. 2. ORTEP diagram of pyrrolidinylecamphor based organocatalyst 6 as a TFA salt.
2.2. Screening of organocatalysts and optimization of
reaction conditions
Catalytic screening for the previously developed and the newly
designed pyrrolidineecamphor based organocatalyst 6 was carried
out (Table 1). It was found that organocatalysts 1, 2, and 6 catalyzed
the reaction of cyclohexanone 7a with trans-b-nitrostyrene 8a
conveniently under neat conditions.
Organocatalyst 1 having an amide linker took about 24 h to give
moderate diastereoselectivity (syn/anti) 79:21 and an enantiose-
lectivity of 57%. Whereas, sulfide linker catalyst 2 took almost 3
days to give a good diastereoselectivity (syn/anti) 94:6 and an
enantioselectivity of 85%. On the other hand, catalyst 6 out-
performed the other pyrrolidineecamphor based organocatalysts
in terms of reaction rate, chemical yield, and selectivity of the
product formation (Table 1, entries 1e3). A very high diaster-
eoselectivity (syn/anti) 97:3 and an enantioselectivity of 90% was
obtained using organocatalyst 6 for Michael addition of cyclohex-
anone 7a to trans-nitrostyrene 8a within 14 h.
Fig. 1. Structures of various pyrrolidinylecamphor based organocatalysts.
The organocatalysts 1 and 2 were easily prepared on a gram
scale quantities by means of standard protocols developed pre-
viously in our laboratory.10c,e,g The preparation of the organo-
We next carried out the optimization studies for the reaction of
cyclohexanone 7a with trans-b-nitrostyrene 8a in various solvents
(Table 2).
catalyst
6 starts with reductive amination of (S)-tert-butyl
2-formylpyrrolidine-1-carboxylate 3 and aminoketone 4.12 The
reductive amination was successfully carried out using a mild
Scheme 1. Synthesis of organocatalyst 6.

S. Anwar et al. / Tetrahedron 67 (2011) 1171e1177
1173
Table 1
Exclusive screening of various solvents did not show superior
results in comparison to reaction carried out in neat conditions
(Table 2, entry 9). The addition of a catalytic amount of an acidic
additive failed to influence the selectivity of the Michael reaction
(Table 2, entry 10). Interestingly, the use of non-nucleophilic
organic bases dramatically increased the rate of the reaction in
comparison to that of NaOH (Table 2, entries 11e13). For exam-
ple, when Hunig’s base was used as an additive, trans-nitro-
styrene was readily converted into the desired product with high
diastereoselectivity (syn/anti 98:2) and very high enantiose-
lectivity (95% ee) (Table 2, entry 13). We speculate that the or-
ganic bases played a profound role in the enamine formation, in
agreement with previous reports.14 The diastereoselectivity
reached a maximum when the reaction temperature was lowered
to 0 ꢀC (Table 2, entry 14).
Screening of organocatalysts 1, 2, and 6 for Michael addition of cyclohexanone 7a to
trans-nitrostyrene 8aa
O
O
Ph
NO2
NO2
20 mol-% Cat.
neat
+
9a
7a
8a
Entry
Cat.
Time [h]
Yieldb [%]
syn/antic
eec [%]
1
2
3
1
2
6
24
72
14
80
90
95
79:21
94:6
97:3
57
85
90
a
Unless otherwise noted, all reactions were carried out using 7a (1.0 mmol,
5.0 equiv) and 8a (0.2 mmol) in the presence of 20 mol % of catalyst at ambient
temperature.
b
Isolated yield.
c
Determined by chiral HPLC analysis (Chiralcel AS-H column).
2.3. Substrate generality
Table 2
Optimization of reaction conditions for Michael addition of cyclohexanone 7a to
Under the optimized conditions, a variety of nitroolefins with
different structures were investigated to establish the catalytic
ability of the organocatalyst 6 (Table 3).
trans-nitrostyrene 8aa
O
O
Ph
NO2
6 (20 mol-% )
NO2
+
Table 3
Solvent/Additive
temp./time
Michael addition of cyclohexanone with nitroolefins catalyzed by 6 under neat
conditionsa
9a
7a
8a
O
Cat. 6 (20-mol%)
DIPEA (20-mol%)
O
R
Entry
Solvent
Additive
Time [h]
Yieldb [%]
syn/antic
eec [%]
76
NO2
NO2
R
+
1
2
3
4
5
6
7
8
DMSO
DMF
H2O
CHCl3
EtOH
Toluene
Brine
CH3CN
Neat
Neat
Neat
Neat
Neat
d
d
d
d
d
d
d
d
d
15
14
240
72
12
48
41
15
14
20
14
14
14
14
76
77
50
72
85
58
78
86
95
96
94
95
95
94
96:4
97:3
95:5
95:5
96:4
96:4
97:3
96:4
97:3
98:2
97:3
98:2
98:2
99:1
Neat, 0
14 h
C
87
80
81
88
87
85
86
90
89
91
93
95
7a
8a-n
9a-n
Entry
R
Yieldb [%]
syn/antic
eec [%]
1
2
3
4
5
6
7
8
C6H5
9a 91
9b 88
9c 89
9d 86
9e 85
9f 90
9g 80
9h 90
9i 88
9j 95
9k 90
9l 87
9m 85
9n 92
99:1
97:3
99:1
96:4
96:4
97:3
96:4
91:9
92:8
>99
99:1
97:3
95:5
92:8
95
90
91
87
84
88
86
81
84
92
89
84
87
71
2-MeOC6H4
2-MeC6H4
4-MeC6H4
4-MeOC6H4
1-Naphthyl
4-BrC6H4
9
10
11
12
13
14d
CH3COOH
NaOH
Et3N
EtN(i-Pr)2
EtN(i-Pr)2
2-Furyl
Neat
95 (99)e
9
2-Thienyl
2-CF3C6H4
2-NO2C6H4
2-Naphthyl
4-ClC6H4
10
11
12d
13d
14
a
Unless otherwise noted, all reactions were carried out using 7a (1.0 mmol,
5.0 equiv) and 8a (0.2 mmol) in the presence of 20 mol % of catalyst at ambient
temperature.
b
Isolated yield.
3,4-(OCH2O)eC6H3
c
Determined by chiral HPLC analysis (Chiralcel AS-H column).
Reaction was carried out at 0 ꢀC.
ee was determined after recrystallisation using CH2Cl2/i-PrOH.
d
a
Unless otherwise noted, all reactions were carried out using 7a (1.0 mmol,
5.0 equiv) and 8a (0.2 mmol) in the presence of 20 mol-% of catalyst 6 under neat
conditions with 20-mol % of DIPEA at 0 ꢀC.
e
b
Isolated yield.
Determined by chiral HPLC analysis.
Reaction was carried out at ambient temperature.
We first examined the reaction with polar aprotic solvents, such
as DMSO and DMF. The desired Michael adduct 9awas obtained with
high diastereoselectivity (syn/anti 96:4) and a moderate stereo-
selectivity of 76% ee using DMSO (Table 2, entry 1). Whereas, an
increase in the diastereo- (syn/anti 97:3) and enantioselectivity (87%
ee) was observed when DMF as solvent (Table 2, entry 2). The use of
H2O as a solvent decreased the reaction rate with a dramatical drop
in enantioselectivity, however the diastereoselectivity maintained
(Table 2, entry 3). The use of a chlorinated solvent, such as CHCl3 led
to a slight increase in reaction rate and enantioselectivity (Table 2,
entry 4). Next, the use of a polar protic solvent, such as EtOH showed
encouraging results, with an increase in enantioselectivity (88% ee)
and a slight increase in diastereoselectivity (syn/anti 96:4) was also
observed (Table 2, entry 5). The reaction proceeded sluggishly when
toluene was used in comparison to the use of ethanol, although the
stereoselectivity was maintained (Table 2, entry 6). When the re-
action was carried out in brine resulted in a drop in enantiose-
lectivity of the Michael adduct 9a (Table 2, entry 7). Reaction
proceeded in CH3CN failed to improve the stereoselectivity to
a greater extent except for the time factor (Table 2, entry 8).
c
d
To test the generality of the catalytic system, various aromatic
nitroolefins were reacted with cyclohexanone 7a in the presence of
catalyst 6. The corresponding adducts 9aen were obtained in high
chemical yields and with outstanding diastereoselectivity. The
orientation of the substituent on the aryl group slightly influenced
the selectivity of the reaction, with ortho-substituents performing
better over the para-substituents (Table 3, entries 2, 3, 10, 11 vs 4, 5,
7, and 13). Nitroolefins with ortho-substituted electron donating or
withdrawing substituent in an aromatic ring, especially 8c and 8j,
afforded the corresponding adducts 9c and 9j with a high ee of 91%
and 92%, respectively (Table 3, entries 3 and 10). Heteroaryl sub-
strates, such as 8h and 8i also yielded the corresponding adducts
with good selectivity (81% and 84% ee) (Table 3, entries 8 and 9).
The substrate 8n having a [1,3]dioxole substituent provided mod-
erate selectivity, presumably due to steric factors (syn/anti 92:8,
71% ee) (Table 3, entry 14).

1174
S. Anwar et al. / Tetrahedron 67 (2011) 1171e1177
Asymmetric addition of other ketones (7b and 7c) and alde-
camphor). Undoubtedly, the observed enantioselectivity points to-
ward the necessity of an amine functionality linker (cat. 6) in prefer-
ence to amide (cat. 1) and sulfide (cat. 2). The resulting enamine
therefore attacks the nitroolefin from the re-face to afford the product
9, which is consistent with the experimental results. On the other
hand, more studies are required to elucidate the reaction mechanism
for the acylic aldehyde (7e), which provided (R,S)-9r as the major
product. It can be presumed that the b-nitrostyrene approaches from
the less hindered bottom face followed by the attack of nucleophilic
enamine from the si-face to generate the desired product.
hydes (7d and 7e) to nitrostyrene 8a using 6 was also investigated
(Scheme 2). Tetrahydrothiopyran-4-one 7b reacted smoothly
yielding the desired product 9o, thereby maintaining excellent
stereoselectivities (syn/anti 99:1, 85% ee). On the other hand
cyclopentanone 7c failed to react at low reaction temperature. A
moderate selectivity (syn/anti 82:18, 69% ee) was obtained when
the reaction was carried out at ambient temperature. The use of
isobutyraldehyde 7d furnished the corresponding adduct 9q with
79% ee in moderate chemical yield (65%). Reaction with propio-
naldehyde 7e gave the desired product with a low dr of 64: 36 with
an enantioselectivity of 50% ee with the syn one.
As pointed out earlier g-nitroketone 9a is potentially useful and
has wide applications in organic synthesis.1 The preparation of 3-
phenyl-hexahydro-2H-indole-1-oxide 10 can easily be accessed
using 9a as a starting material (Scheme 4).16 These are potential
synthons for the total synthesis of the montanine-like Amar-
yllidaceae alkaloids.17 We reasoned that the
g-nitroketone 9a should
be readily converted to the corresponding nitrone 10, although this
has been previously demonstrated.8i Indeed, the hydrogenation of
9a in the presence of Pd/C furnished the desired nitrone 10 in 88%
yield without a loss of stereoselectivity. Likewise, other isomeric
products, such as hydroindole and imidazole can also be readily
accessed using Michael adduct 9a as the starting synthon.
O
O
Ph
N
NO2
Pd/C, H2
Ph
MeOH, r.t.
88 %
9a (99% ee)
10 (99% ee)
Scheme 4. Synthetic utility of
g-nitroketone 9a.
Scheme 2. Reactions of ketones and aldehydes with trans-nitrostyrene 8a.
3. Conclusions
We have developed a new class of pyrrolidinylecamphor based
bifunctional organocatalyst that are capable of catalyzing highly
diastereo- and enantioselectivity Michael addition reaction. The cat-
On the basis of the experimental results described above, a cat-
alytic cycle was proposed to account for the high diastereoselectivity
and enantioselectivity of the present reaction (Scheme 3).
alysts were prepared easily from inexpensive L-proline and camphor
structural unit linked via amide, sulfide, and amine-linkers. It is ob-
vious that the distance between pyrrolidine and camphor scaffold is
crucial. The two atom distance is better than that of three atom sys-
tem. The exo camphor C2 hydroxy group provided additional H-bond
interaction to stabilize the transition model. Catalyst 6 possessing
a secondary amine linker has been successfully applied to the asym-
metric Michael reaction of cyclohexanone with nitroalkenes with
a broad range of aryl- and heteroaryl-substituents. The important
features are: (1) high chemical yields are generally obtained, (2) re-
markable to high diastereo- and enantioselectivity, and (3) opera-
tionallysimplereactionconditions.Theutilityofthisorganocatalystis
illustrated in the synthesis of an enantiopure nitrone. The current
protocol developed complements a related approach to the same
products that has recently been reported.8,9
Me
Me
N
N
H
H
OH
Me
H2O
NO2
O
8
Ar
Me
N
N
H
Me
OH
O
7a
H
Me
O
H
N
O
Ar
Me
Me
N
H
N
H
H
Ar
HN
N
H
NO2
6
OH
4. Experimental section
4.1. General remarks
O
Ar
H2O
NO2
9
All reagents were used as purchased from commercial suppliers
without additional purification. IR spectra were recorded on a Per-
kineElmer 500 spectrometer. NMR spectra were recorded on
a Bruker Avance 400 NMR spectrometer (400 MHz for 1H and
Scheme 3. Proposed mechanism for 6-catalyzed Michael addition.
We presume that the pyrrolidine ring first reacts with a carbonyl
compound to form a nucleophilic enamine. The rigid and bulky bi-
cyclic camphor moiety selectively shields the approach of the nitro-
styrene from the enamine si-face.15 On the other hand, the secondary
amine linker plays a vital role in stereochemical outcomes via hy-
drogen bonding in assistance with the exo hydroxyl group (on
100 MHz for 13C). Chemical shifts are reported in
d parts per million
referenced to an internal TMS standard for 1H NMR and chloro-
form-d (77.0 ppm) for 13C NMR. Optical rotations were measured on
a JASCO P-1010 polarimeter. HRMS were recorded on JEOL SX-102A.
The X-ray diffraction measurements were carried out at 298 K on

S. Anwar et al. / Tetrahedron 67 (2011) 1171e1177
1175
a KAPPA APEX II CCD area detector system equipped with a graphite
crude product was purified by flash column silica-gel chromatogra-
phy (hexanes/ethyl acetate¼8:2) to provide Michael product.
ꢀ
monochromator and a Mo K
a
fine-focus sealed tube (l¼0.71073 A).
Routine monitoring of reactions was performed using silica gel,
glass-backed TLC plates (Merck Kieselgel 60 F254) and visualized by
UV light (254 nm). Solutions were evaporated to dryness under
reduced pressure on a rotary evaporator and the residues purified
by flash column chromatography on silica gel (230e400 mesh)
with the indicated eluents. Air and/or moisture sensitive reactions
were performed under the inert atmospheric conditions.
4.3.1. (S)-2-((R)-2-Nitro-1-phenylethyl)cyclohexanone (9a). Yield
45mg, 91%. IR (CH2Cl2):
n
3008, 2937,1714,1553,1449,1347 cmꢁ1;1H
NMR (400 MHz, CDCl3, 25 ꢀC):
d
7.34e7.23 (m, 3H), 7.16 (d, J¼6.9 Hz,
2H), 4.95 (dd, J¼4.5, 12.6 Hz, 1H), 4.63 (dd, J¼9.0, 12.3 Hz, 1H), 3.76
(dt, J¼4.5, 9.9 Hz, 1H), 2.68 (ddd, J¼8.1, 8.4, 11.7 Hz, 1H), 2.49e2.33
(m, 2H), 2.10e2.04 (m, 1H), 1.79e1.52 (m, 4H), 1.52e1.19 (m, 1H);
HPLC: Chiralpak AS-H (hexanes/i-PrOH: 90/10, flow rate: 0.8 mL/
min,
l¼238 nm); retention time: 21.9 min (minor), 32.3 min (major).
4.2. Synthesis of organocatalyst (6)
4.3.2. (S)-2-((R)-1-(2-Methoxyphenyl)-2-nitroethyl)cyclohexanone
A mixture of 1-amino-7,7-dimethylbicyclo[2.2.1]heptan-2-one 4
(3.06 g, 20 mmol), Ti(i-PrO)4 (12.0 mL, 40 mmol), and N-(tert-
butoxycarbonyl)prolinal 3 (4.38 g, 22 mmol) in THF (60 mL) was
allowed to stir for 12 h at ambient temperature under N2 atmo-
sphere. NaBH4 (2.28 g, 60 mmol) and absolute EtOH (20 mL) were
then added, and the resulting mixture was stirred for an additional
12 h. The reaction mixture was then quenched with H2O (20 mL),
the resulting inorganic precipitate was filtered and washed with
EtOAc (50 mL). The organic layer was separated and the remaining
aqueous layer was extracted with EtOAc (30 mL). The combined
organic extracts were washed with brine (30 mL), dried (MgSO4),
and concentrated under reduced pressure. The crude product was
purified by flash column chromatography (hexanes/EtOAc¼2:8) to
afford the N-Boc protected 5 as a pale yellow viscous liquid (3.87 g,
(9b). Yield 49 mg, 88%. IR (CH2Cl2): 3011, 2941, 1716, 1550, 1442,
n
1245, 1042 cmꢁ1 1H NMR (400 MHz, CDCl3, 25 ꢀC):
;
d
7.26 (dd,
J¼1.6, 8.1 Hz, 1H), 7.1 (dd, J¼1.0, 7.6 Hz, 1H), 6.92e6.88 (m, 2H),
4.88e4.80 (m, 2H), 3.98 (dt, J¼5.1, 10.3 Hz, 1H), 3.85 (s, 3H),
3.02e2.96 (m,1H), 2.52e2.47 (m,1H), 2.43e2.36 (m,1H), 2.10e2.06
(m, 1H), 1.81e1.77 (m, 1H), 1.71e1.66 (m, 2H), 1.66e1.55 (m, 1H),
1.27e1.21 (m, 1H); HPLC: Chiralpak AS-H (hexanes/i-PrOH: 90/10,
flow rate: 0.5 mL/min,
nor), 34.7 min (major).
l¼254 nm); retention time: 30.2 min (mi-
4.3.3. (S)-2-((R)-2-Nitro-1-(o-tolyl)ethyl)cyclohexanone (9c). Yield
47 mg, 89%. IR (CH2Cl2):
3013, 2945, 1715, 1550, 1347 cmꢁ1 1H
NMR (400 MHz, CDCl3, 25 ꢀC):
n
;
d
7.21e7.11 (m, 4H), 4.95 (dd, J¼4.4,
12.8 Hz, 1H), 4.63 (dd, J¼10.4, 12.4 Hz, 1H), 3.68 (dt, J¼4.0, 10.0 Hz,
1H), 2.67e2.56 (m, 1H), 2.50e2.36 (m, 2H), 2.37 (s, 3H), 2.12e2.09
(m, 1H), 1.77e1.53 (m, 4H), 1.26e1.23 (m, 1H); HPLC: Chiralpak AD-
52%). IR (CH2Cl2):
n
3431, 2981,1738,1660,1395,1166 cmꢁ1; 1H NMR
3.80 (br s, 1H, NeH), 3.70e3.68 (m, 1H),
(400 MHz, CDCl3, 25 ꢀC):
d
3.45e3.30 (m, 2H), 2.83e2.75 (m, 1H), 2.06e1.95 (m, 1H), 1.90e1.71
(m, 7H), 1.64e1.58 (m, 2H), 1.50 (s, 9H), 1.32e1.20 (m, 3H), 1.18e1.05
(m, 1H), 1.10 (s, 3H), 0.90 (s, 3H); 13C NMR (100 MHz, CDCl3, 25 ꢀC):
H (hexanes/i-PrOH: 90/10, flow rate: 0.5 mL/min,
tention time: 16.9 min (minor), 24.3 min (major).
l¼254 nm); re-
d
162.0, 79.4, 72.8, 68.1, 58.0, 47.7, 46.4, 43.2, 39.4, 29.7, 29.4, 28.5,
4.3.4. (S)-2-((R)-2-Nitro-1-(p-tolyl)ethyl)cyclohexanone (9d). Yield
45 mg, 86%. IR (CH2Cl2):
3011, 2940,1715,1552,1349 cmꢁ1; 1H NMR
(400 MHz, CDCl3, 25 ꢀC):
7.12 (d, J¼8.0 Hz, 2H), 7.04 (d, J¼8.0 Hz,
27.0, 23.8, 20.3, 19.9. To the above N-Boc protected compound 5
(2.0 g, 6 mmol) in 15 mL of CH2Cl2 was added TFA (7 mL) at ambient
temperature. After stirring for about 19 h and the resulting solution
was adjusted to pH w7 with aqueous NaOH. The reaction mixture
was extracted with CH2Cl2 (2ꢂ20 mL) and the combined organic
layer was washed with brine, dried over MgSO4, filtered, and the
solvent was removed in vacuo. The obtained crude residue was
dissolved in CH2Cl2/hexanes (1:2) and kept for crystallization at
ambient temperature to furnish the pure organocatalyst 6 as
n
d
2H), 4.91 (dd, J¼4.8,12.4, Hz,1H), 4.62 (dd, J¼10.0,12.4 Hz, 1H), 3.72
(dt, J¼4.8,10.0 Hz,1H), 2.71e2.62 (m,1H), 2.51e2.32 (m, 2H), 2.31 (s,
3H), 2.12e2.02 (m, 1H), 1.82e1.50 (m, 4H), 1.30e1.18 (m, 1H); HPLC:
Chiralpak AS-H (hexanes/i-PrOH: 90/10, flow rate: 0.8 mL/min,
l¼254 nm); retention time: 14.6 min (minor), 26.1 min (major).
4.3.5. (S)-2-((R)-1-(4-Methoxyphenyl)-2-nitroethyl)cyclohexanone
a white crystal (1.11 g, 79%). Mp 123 ꢀC; [
(CH2Cl2):
25 ꢀC):
a
]
D
25 ꢁ20.5 (c 1, CHCl3); IR
(9e). Yield 47 mg, 85%. IR (CH2Cl2): 3011, 2942, 1715, 1552, 1443,
n
n
3424, 2934, 1642, 1530 cmꢁ1; 1H NMR (400 MHz, CDCl3,
1247, 1040 cmꢁ1 1H NMR (400 MHz, CDCl3, 25 ꢀC):
;
d
7.09 (d,
d
5.6 (br s, 3H, NeH, OH), 3.95e3.82 (m, 2H), 3.45e3.38 (m,
J¼8.0 Hz, 2H), 6.86 (d, J¼8.0 Hz, 2H), 4.91 (dd, J¼4.5, 12.0 Hz, 1H),
4.60 (dd, J¼10.1, 12.0 Hz, 1H), 3.80 (s, 3H), 3.72 (dt, J¼5.2, 10.5 Hz,
1H), 2.69e2.63 (m, 1H), 2.50e2.46 (m, 1H), 2.42e2.36 (m, 1H),
2.10e2.06 (m, 1H), 1.82e1.55 (m, 4H), 1.28e1.21 (m, 1H); Chiralpak
1H), 3.30e3.20 (m, 1H), 3.18e3.07 (m, 1H), 3.03e2.95 (m, 1H),
2.18e1.97 (m, 3H), 1.91e1.65 (m, 5H), 1.62e1.55 (m, 1H), 1.31e1.20
(m, 1H), 1.20e1.11 (m, 1H), 1.10 (s, 3H), 0.90 (s, 3H); 13C NMR
(100 MHz, CDCl3, 25 ꢀC):
d 73.4, 68.1, 59.8, 47.0, 45.5, 43.1, 42.7, 40.8,
AD-H (hexanes/i-PrOH: 75/25, flow rate: 0.7 mL/min,
retention time: 10.8 min (minor), 13.0 min (major).
l¼238 nm);
30.9, 28.0, 27.0, 25.3, 20.3, 20.0; HRMS (FABþ) m/z (Mþ): 238.2039
(calcd for C14H26N2O, 238.2045). Crystal data for 6 (as a TFA salt) at
293(2) K: C16H27F3N2O3, M 352.40, orthorhombic, P212121, a¼8.7370
4.3.6. (S)-2-((R)-1-(Naphthalen-1-yl)-2-nitroethyl)cyclohexanone
(9f). Yield 54 mg, 90%. IR (CH2Cl2): 3009, 2936, 1715, 1552, 1447,
1346, 810 cmꢁ1; 1H NMR (400 MHz, CDCl3, 25 ꢀC):
8.16 (br s, 1H),
3
ꢀ
ꢀ
ꢀ
ꢀ
(3) A, b¼14.0740(5) A, c¼14.9440(7) A, V¼1837.58(13) A , Z¼4,
n
3
¼0.107 mmꢁ1, 3013 reflections, 215
ꢀ
l
¼0.71073 A, D¼1.274 g/cm ,
m
d
parameters, R¼0.0855, Rw¼0.2633 for all data.
7.85 (d, J¼7.7 Hz, 1H), 7.77 (d, J¼8.1 Hz, 1H), 7.56e7.43 (m, 3H), 7.37
(d, J¼7.3, Hz, 1H), 5.06 (dd, J¼4.5, 12.5 Hz, 1H), 4.73 (m, 1H),
4.75e4.71 (m, 1H), 2.86 (br s, 1H), 2.52e2.48 (m, 1H), 2.44e2.37 (m,
1H), 2.09e2.04 (m, 1H), 1.76e1.60 (m, 3H), 1.58e1.47 (m, 1H),
1.29e1.21 (m, 1H); HPLC: Chiralpak AS-H (hexanes/i-PrOH: 70/30,
4.3. General procedure for the Michael addition reaction
The catalyst 6 (9.52 mg, 20 mol %) and DIPEA (7
mL, 20 mol %) were
added to cyclohexanone 7a (104
m
L, 1.0 mmol) at 0 ꢀC. The reaction
flow rate: 0.7 mL/min,
nor), 23.5 min (major).
l¼238 nm); retention time: 15.9 min (mi-
mixture was stirred for 30 min, and then nitroolefin 8 (0.2 mmol) was
added. The reaction mixture was stirred to completion at 0 ꢀC for 14 h.
After the disappearance of nitroalkene by TLC analysis, the reaction
was quenched with brine and extracted with CH2Cl2 (2ꢂ10 mL). The
combined organic layer was washed with brine, dried over MgSO4,
filtered, and the solvent was evaporated under reduced pressure. The
4.3.7. (S)-2-((R)-1-(4-Bromophenyl)-2-nitroethyl)cyclohexanone
(9g). Yield 52 mg, 80%. IR (CH2Cl2): 3008, 2937, 1714, 1553, 1449,
1347, 1096 cmꢁ1 1H NMR (400 MHz, CDCl3, 25 ꢀC):
7.46 (d,
J¼8.4 Hz, 2H), 7.06 (d, J¼8.4 Hz, 2H), 4.94 (dd, J¼5.2, 12.4 Hz, 1H),
n
;
d

1176
S. Anwar et al. / Tetrahedron 67 (2011) 1171e1177
4.61 (dd, J¼9.6, 12.4 Hz, 1H), 3.75 (dt, J¼4.4, 10.0 Hz, 1H), 2.69e2.60
(m, 1H), 2.51e2.32 (m, 2H), 2.15e2.05 (m, 1H), 1.83e1.57 (m, 4H),
1.26e1.22 (m, 1H); HPLC: Chiralpak AD-H (hexanes/i-PrOH: 80/20,
90/10, flow rate: 1.0 mL/min,
(minor), 21.1 min (major).
l¼254 nm); retention time: 10.4 min
flow rate: 0.5 mL/min,
nor), 23.3 min (major).
l¼254 nm); retention time: 15.9 min (mi-
4.3.14. (S)-2-((R)-1-(Benzo[d] [1,3]dioxol-5-yl)-2-nitroethyl) cyclo-
hexanone (9n). Yield 54 mg, 92%. IR (CH2Cl2): 3008, 2941, 1716,
1552, 1440, 1245, 1043 cmꢁ1 1H NMR (400 MHz, CDCl3, 25 ꢀC):
n
;
4.3.8. (S)-2-((S)-1-(Furan-2-yl)-2-nitroethyl)cyclohexanone
(9h). Yield 43 mg, 90%. IR (CH2Cl2): 3077, 2937, 1714, 1553, 1449,
1347, 916 cmꢁ1 1H NMR (400 MHz, CDCl3, 25 ꢀC):
7.36 (m, 1H),
6.30e6.28 (m, 1H), 6.19 (m, 1H), 4.82 (dd, J¼4.8, 12.4 Hz, 1H), 4.68
(dd, J¼9.2, 12.4 Hz, 1H), 4.00 (dt, J¼4.8, 9.2 Hz, 1H), 2.80e2.72 (m,
1H), 2.48e2.47 (m, 1H), 2.40e2.33 (m, 1H), 2.18e2.09 (m, 1H),
1.89e1.60 (m, 4H), 1.35e1.26 (m, 1H); HPLC: Chiralpak AS-H (hex-
d
6.74 (d, J¼7.8 Hz, 1H), 6.64 (s, 1H), 6.62 (d, J¼7.8 Hz, 1H), 5.96 (s,
n
2H), 4.90 (dd, J¼4.5, 12.3 Hz, 1H), 4.55 (dd, J¼10.2, 12.0 Hz, 1H),
3.68 (dt, J¼4.2, 9.9 Hz, 1H), 2.65e2.56 (m, 1H), 2.52e2.33 (m,
2H), 2.15e2.05 (m, 1H), 1.83e1.59 (m, 4H), 1.31e1.18 (m, 1H);
HPLC: Chiralpak AD-H (hexanes/i-PrOH: 95/5, flow rate: 0.7 mL/
min,
(major).
;
d
l
¼214 nm); retention time: 35.5 min (minor), 37.9 min
anes/i-PrOH: 85/15, flow rate: 0.5 mL/min,
time: 27.9 min (minor), 32.2 min (major).
l¼230 nm); retention
4.3.15. (S)-3-((R)-2-Nitro-1-phenylethyl)
dihydro-2H-thiopyran-4
3008, 2937, 1714,
;
1H NMR (400 MHz, CDCl3, 25 ꢀC):
(3H)-one (9o). Yield 47 mg, 88%. IR (CH2Cl2):
n
4.3.9. (S)-2-((S)-2-Nitro-1-(thiophen-2-yl) ethyl) cyclohexanone
(9i). Yield 45 mg, 88%. IR (CH2Cl2): 3070, 2937, 1714, 1553, 1449,
1347, 925 cmꢁ1 1H NMR (400 MHz, CDCl3, 25 ꢀC):
7.23 (d,
J¼5.1 Hz,1H), 6.94 (dd, J¼3.0, 5.1 Hz,1H), 6.88 (d, J¼3.2 Hz,1H), 4.90
(dd, J¼4.1, 13.0 Hz, 1H), 4.67 (dd, J¼9.1, 13.0 Hz, 1H), 4.14 (dt, J¼4.1,
9.1 Hz, 1H), 2.72e2.67 (m, 1H), 2.50e2.46 (m, 1H), 2.42e2.36 (m,
1H), 2.13e2.10 (m, 1H), 1.96e1.90 (m, 1H), 1.88e1.85 (m, 1H),
1.73e1.56 (m, 2H), 1.38e1.24 (m, 1H); HPLC: Chiralpak AS-H (hex-
1553, 1449, 1347, 698 cmꢁ1
n
d
7.40e7.32 (m, 3H), 7.22 (d, J¼7.6 Hz, 2H), 4.76 (dd, J¼4.4, 12.4 Hz,
;
d
1H), 4.63 (dd, J¼10.0, 12.8 Hz, 1H), 4.01 (dt, J¼4.4, 10.0 Hz, 1H),
3.11e2.99 (m, 3H), 2.92e2.82 (m, 2H), 2.66e2.62 (m, 1H), 2.48 (dd,
J¼9.2, 13.6 Hz, 1H); HPLC: Chiralpak AS-H (hexanes/i-PrOH: 80/20,
flow rate: 1.0 mL/min,
l
¼210 nm); retention time: 18.6 min (mi-
nor), 25.3 min (major).
anes/i-PrOH: 90/10, flow rate: 1.0 mL/min,
time: 18.2 min (minor), 24.3 min (major).
l¼254 nm); retention
4.3.16. (S)-2-((R)-2-Nitro-1-phenylethyl)cyclopentanone (9p). Yield
29 mg, 62%. IR (CH2Cl2): 3008, 2937, 1751, 1553, 1449,
1347 cmꢁ1 1H NMR (400 MHz, CDCl3, 25 ꢀC):
7.34e7.23 (m,
n
;
d
4.3.10. (S)-2-((R)-2-Nitro-1-(2-(trifluoromethyl) phenyl) ethyl) cy-
clohexanone (9j). 60 mg, 95% yield. IR (CH2Cl2): 3013, 2945, 1714,
1550, 1350 cmꢁ1 1H NMR (400 MHz, CDCl3, 25 ꢀC):
7.71 (d,
J¼7.5 Hz, 1H), 7.57 (t, J¼7.5 Hz, 1H), 7.41 (t, J¼7.5 Hz, 1H), 7.39 (d,
J¼7.5 Hz, 1H), 5.05 (dd, J¼7.0, 12.0 Hz, 1H), 4.77 (dd, J¼3.7, 12.0 Hz,
1H), 4.12e4.07 (m, 1H), 3.05e3.0 (m, 1H), 2.53e2.41 (m, 2H),
2.17e2.11 (m, 1H), 1.83e1.78 (m, 1H), 1.76e1.64 (m, 2H), 1.64e1.55
(m,1H),1.38e1.28 (m,1H); HPLC: Chiralpak AD-H (hexanes/i-PrOH:
3H), 7.20e7.15 (m, 2H), 5.37e5.30 (m, 1H), 4.71 (dd, J¼10.2,
12.6 Hz, 1H), 3.76e3.65 (m, 1H), 2.44e2.31 (m, 2H), 2.19e2.06 (m,
1H), 1.94e1.83 (m, 2H), 1.76e1.66 (m, 1H), 1.55e1.41 (m, 1H);
HPLC: Chiralpak AD-H (hexanes/i-PrOH: 90/10, flow rate: 0.5 mL/
n
;
d
min,
(major).
l
¼254 nm); retention time: 19.7 min (minor), 28.2 min
4.3.17. (R)-2,2-Dimethyl-4-nitro-3-phenylbutanal (9q). Yield 29 mg,
90/10, flow rate: 0.5 mL/min,
(minor), 19.7 min (major).
l¼254 nm); retention time: 12.8 min
65%. IR (CH2Cl2):
n
3008, 2977,1723,1604,1555,1447,1345 cmꢁ1; 1H
NMR (400 MHz, CDCl3, 25 ꢀC):
d 9.49 (s, 1H), 7.34e7.29 (m, 1H),
7.28e7.22 (m, 2H), 7.22e7.15 (m, 2H), 4.85 (dd, J¼11.3, 13.1 Hz, 1H),
4.69 (dd, J¼4.2,13.1 Hz,1H), 3.78 (dd, J¼4.2,11.3 Hz,1H),1.12 (s, 3H),
0.96 (s, 3H); HPLC: Chiralcel OD-H (hexanes/i-PrOH: 80/20, flow
4.3.11. (S)-2-((R)-2-Nitro-1-(2-nitrophenyl)ethyl)cyclohexanone
(9k). Yield 54 mg, 90%. IR (CH2Cl2): 3008, 2937, 1714, 1553, 1449,
1347, 852, 793 cmꢁ1 1H NMR (400 MHz, CDCl3, 25 ꢀC):
7.84 (d,
J¼8.0 Hz, 1H), 7.59 (t, J¼8.0 Hz, 1H), 7.48e7.42 (m, 2H), 4.98e4.87
(m, 2H), 4.32 (dt, J¼4.8, 8.8 Hz, 1H), 2.99e2.91 (m, 1H), 2.52e2.32
(m, 2H), 2.16e2.08 (m, 1H), 1.88e1.78 (m, 2H), 1.72e1.40 (m, 4H);
HPLC: Chiralpak AD-H (hexanes/i-PrOH: 95/5, flow rate: 1.0 mL/
n
;
d
rate: 0.8 mL/min,
20.8 min (minor).
l¼254 nm); retention time: 15.0 min (major),
4.3.18. (2R,3S)-2-Methyl-4-nitro-3-phenylbutanal (9r). Yield 36 mg,
86%. IR (CH2Cl2):
3008, 2977,1724,1601,1553,1449,1347 cmꢁ1; 1H
NMR (400 MHz, CDCl3, 25 ꢀC):
n
min,
(major).
l
¼238 nm); retention time: 32.3 min (minor), 54.6 min
d
9.72 (d, J¼1.5 Hz,1H), 7.36e7.29 (m,
3H), 7.17e7.16 (m, 2H), 4.80 (dd, J¼5.5, 12.9 Hz, 1H), 4.69 (dd, J¼9.2,
12.9 Hz, 1H), 3.81 (ddd, J¼5.5, 9.2, 9.2 Hz, 1H), 2.80e2.75 (m, 1H),
1.01 (d, J¼7.4 Hz, 3H); HPLC: Chiralcel OD-H (hexanes/i-PrOH: 90/
4.3.12. (S)-2-((R)-1-(Naphthalen-2-yl)-2-nitroethyl)cyclohexanone
(9l). Yield 52 mg, 87%. IR (CH2Cl2):
n
3008, 2937, 1714, 1553, 1449,
7.82e7.78 (m,
10, flow rate: 1.0 mL/min,
(major), 19.6 min (minor).
l
¼254 nm); retention time: 26.7 min
1347, 835 cmꢁ1; 1H NMR (400 MHz, CDCl3, 25 ꢀC):
d
2H), 7.63 (s, 1H), 7.50e7.45 (m, 2H), 7.28 (dd, J¼2.0, 8.5 Hz, 2H), 5.01
(dd, J¼12.0, 4.7 Hz,1H), 4.74 (dd, J¼10.0,12.0 Hz,1H), 3.95 (dt, J¼4.7,
10.0 Hz, 1H), 2.81e2.75 (m, 1H), 2.52e2.48 (m, 1H), 2.44e2.37 (m,
1H), 2.10e2.04 (m, 1H), 1.78e1.65 (m, 3H), 1.61e1.53 (m, 1H),
1.31e1.23 (m, 1H); HPLC: Chiralpak AS-H (hexanes/i-PrOH: 50/50,
4.4. Synthesis of nitrone (10)
A suspension of Pd/C (8 mg) and 9a (50 mg) in MeOH (5 mL)
was stirred at ambient temperature under hydrogen atmosphere.
After being stirred for 12 h, the mixture was filtered through
a pad of Celite and the filtrate was concentrated under reduced
pressure. The residue was purified by flash column silica-gel
chromatography (chloroform/methanol¼9:1) to provide the de-
flow rate: 0.7 mL/min,
nor), 21.1 min (major).
l¼254 nm); retention time: 10.4 min (mi-
4.3.13. (S)-2-((R)-1-(4-Chlorophenyl)-2-nitroethyl)cyclohexanone
(9m). Yield 47 mg, 85%. IR (CH2Cl2): 3009, 2937, 1714, 1553, 1448,
1348, 1089 cmꢁ1 1H NMR (400 MHz, CDCl3, 25 ꢀC):
7.31 (d,
n
;
d
sired product 10 (38 mg, 88% yield). IR (CH2Cl2): n 3009, 2981,
J¼8.4 Hz, 2H), 7.13 (d, J¼8.4 Hz, 2H), 4.96 (dd, J¼4.8, 12.8 Hz, 1H),
4.62 (dd, J¼10.0, 12.8 Hz, 1H), 3.78 (dt, J¼4.4, 10.0 Hz, 1H),
2.69e2.60 (m, 1H), 2.51e2.34 (m, 2H), 2.15e2.05 (m, 1H), 1.83e1.52
(m, 4H), 1.28e1.23 (m, 1H); HPLC: Chiralpak AS-H (hexanes/i-PrOH:
2857, 1615, 1253, 1175, 765, 704 cm-1; 1H NMR (400 MHz, CDCl3,
25 ꢀC):
7.30e7.25 (m, 2H), 7.21e7.15 (m, 3H), 4.23e4.04 (m, 2H),
d
3.19e3.01 (m, 2H), 2.73 (m, 1H), 2.05e1.87 (m, 3H), 1.77 (m, 1H),
1.33e1.14 (m, 3H); HPLC: Chiralpak AD-H (hexanes/i-PrOH: 90/10,

S. Anwar et al. / Tetrahedron 67 (2011) 1171e1177
1177
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flow rate: 0.6 mL/min,
(major), 24.7 min (minor).
l
¼238 nm); retention time: 19.1 min
Acknowledgements
We thank the National Science Council of the Republic of China
(NSC 99-2113-M-003-002-MY3 and NSC 99-2119-M-003-001-
MY2) and National Taiwan Normal University (99T3030-5 and 99-
D) for financial support of this work. Our gratitude goes to the
Academic Paper Editing Clinic at NTNU, and to the National Center
for High-Performance Computing for providing us with computer
time and facilities.
Supplementary data
9. (a) Ni, B.; Zhang, Q.; Dhungana, K.; Headley, A. D. Org. Lett. 2009, 11, 1037e1040;
(b) Ni, B.; Zhang, Q.; Headley, A. D. Tetrahedron Lett. 2008, 49, 1249e1252; (c) Li,
P.; Wang, L.; Zhang, Y.; Wang, G. Tetrahedron 2008, 64, 7633e7638; (d) Wu, L.-
Y.; Yan, Z.-Y.; Xie, Y.-X.; Niu, Y.-N.; Liang, Y.-M. Tetrahedron: Asymmetry 2007, 18,
2086e2090; (e) Luo, S.; Mi, X.; Zhang, L.; Liu, S.; Xu, H.; Cheng, J. P. Angew.
Chem., Int. Ed. 2006, 45, 3093e3097; (f) Kotrusz, P.; Toma, S.; Schmalz, H.-G.;
Adler, A. Eur. J. Org. Chem. 2004, 1577e1583.
This material includes spectral data for catalyst 6 and chiral-
phase HPLC data for various Michael adducts 9aer as well as 10.
Supplementary data associated with this article can be found in the
online version at doi:10.1016/j.tet.2010.11.093.
10. (a) Tzeng, Z.-H.; Chen, H.-Y.; Huang, C.-T.; Chen, K. Tetrahedron Lett. 2008, 49,
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