Efficient enantioselective michael addition of nitroalkenes catalyzed by a surfactant-type bifunctional thiourea organocatalyst in the presence of water

Article abstract of DOI:10.2174/157017812799304024

New surfactant-type bifunctional thiourea organocatalysts 3 were synthesized. It was found that in the presence of 10 mol% PhCOOH, bifunctional thiourea bearing a long chain 3b in 10 mol% loading could smoothly catalyze the asymmetric Michael reaction of

Full text of DOI:10.2174/157017812799304024

Letters in Organic Chemistry, 2012, 9, 51-55
51
Efficient Enantioselective Michael Addition of Nitroalkenes Catalyzed by a
Surfactant-Type Bifunctional Thiourea Organocatalyst in the Presence of
Water
Jian Lia, Yang Liub and Li Liu*,c
aSchool of Pharmaceutical Engineering & Life Sciences, Chang Zhou University, Changzhou, 213164, P.R.China
bResearch Center of Functional Materials, Kaifeng University, Kaifeng, 475004, P.R.China
cAnalytical center, Chang Zhou University, Changzhou, 213164, P.R. China
Received May 16, 2011: Revised September 08, 2011: Accepted October 26, 2011
Abstract: New surfactant-type bifunctional thiourea organocatalysts 3 were synthesized. It was found that in the presence
of 10 mol% PhCOOH, bifunctional thiourea bearing a long chain 3b in 10 mol% loading could smoothly catalyze the
asymmetric Michael reaction of nitroalkenes 4 with cyclohexanone at room temperature in the presence of water, giving
the desired adducts 5a-i in good yields (80 - 93%) with high diastereoselectivities (syn/anti = 95/5 - > 99/1) and
enantioselectivities (up to 92% ee).
Keywords: Bifunctional thiourea, enantioselective michael addition, organocatalysts, surfactant-type, water.
INTRODUCTION
RESULTS AND DISCUSSION
In recent years, great advances have been made in
organocatalysis and asymmetric organocatalysts were
recognized as the ‘‘simplest enzyme’’ mimics [1, 2].
Meanwhile, aqueous reactions have drawn much attention
because water is environmentally benign, safe and cheap
compared to organic solvents. Moreover, water is necessary
in most biological transformations, and thus it is highly
desirable to develop a chemical system that can mimic the
action of enzymes and affect organic reactions in water with
high reactivities and excellent stereoselectivities. However,
the reactive activities and selectivities of many
organocatalysts reduce dramactically in water [3-6].
Recently, the surfactant organocatalysts, which contain both
hydrophilic and hydrophobic moities, were proved very
effective in aqueous organocatalytic reactions [7-14].
Although there are several reports on the utilities of
surfactant-type organocatalysts in the Michael reaction in the
presence of water, these surfactant-type organocatalysts are
pyrrolidine organocatalysts [9-14], and to the best of our
knowledge, only little work has been reported on the
synthesis and the utility of a surfactant-type thiourea.
Considering that pyrrolidine derived thioureas are very
important type of organocatalysts and Michael addition is
one of the most important C-C bond-forming reactions in
organic synthesis [15-19], we carried out the investigation on
the synthesis of surfactant-type bifunctional thiourea
organocatalysts and their applications in highly
enantioselective Michael addition of nitroalkenes in the
presence of water without any organic solvent.
Initially, aminomethylpyrrolidine 1 and long-chain
isothiocyanate 2 were chosen as starting materials, which can
be prepared from L-proline [20] and by the reaction of long-
chain amine with thiophosgene [21], respectively. It was
found that the reaction of 1 with 2 in CH2Cl2 at room
temperature for 3 h, followed by stirring the resulting
mixture with trifluoroacetic acid for 2 h, afforded the desired
bifunctional thiourea bearing a long chain 3a and 3b in 92%
and 95% yield, respectively (Scheme 1) [22].
S
1.SCN-R 2
NH2
N
N
R
H
H
N
N
H
2. TFA, CH2Cl2
Boc
1
3
a: R = C12H25-n, b: R =
C12H25-n
Scheme 1. Synthesis of Bifunctional Thiourea Bearing A Long
Chain 3.
With the new chiral organocatalysts 3 in hand, we chose
the Michael addition of cyclohexanone to trans-nitrostyrene
4a as a model reaction to probe optimal reaction conditions.
It was found that, when 10 mol% bifunctional thiourea
bearing a long chain 3a or 3b was employed, the Michael
reaction could occur smoothly at room temperature in pure
water, giving desired adduct 5a with low enantioselectivities
(entries 1-2, Table 1). Gratifyingly, using equal molar of
benzoic acid, which formed surfactant with the long chain
amine 3a or 3b, resulted in significant increase of the yield
and great improvement of enantioselectivities up to 92% ee
(compare entry 3 or 4 with 1 or 2 respectively, Table 1). In
view of the yields and the stereoselectivities, it can be
*Address correspondence to this author at the Analytical center, Chang
Zhou University, Changzhou, 213164, P.R. China; Fax: +86-519-86330227;
E-mail: li.liu2007@yahoo.com.cn
1875-6255/12 $58.00+.00
© 2012 Bentham Science Publishers

52 Letters in Organic Chemistry, 2012, Vol. 9, No. 1
Li et al.
Table 1. Optimization of the Michael Reaction of Cyclohexanone to trans-Nitrostyrenea
O
O
Ph
3 (10mol%)
NO2
acid
NO2
H2O , r.t.
5a
4a
Entry
Cat.
Acid
t (h)
Yield (%)b
syn/antic
ee (%)d
1
2
3a
3b
--
24
24
12
8
85
89
87
91
70
81
65
41
90
61
90
70
95:5
99:1
99:1
100:0
94:6
99:1
100:0
99:1
99:1
99:1
94:6
99:1
42
34
87
92
84
70
54
88
90
86
47
80
--
3
3a
PhCO2H
PhCO2H
HCO2H
AcOH
4
3b
5
3b
8
6
3b
8
7
3b
n-PrCO2H
TFA
8
8
3b
8
9
3b (20%)
3b (5%)
3b (35ꢀ)
3b (0ꢀ)
PhCO2H
PhCO2H
PhCO2H
PhCO2H
8
10
11
12
24
24
24
aThe mixture of cyclohexanone (1.0 mmol), nitrostyrene 4a (0.5 mmol), organocatalyst (10 mol%) and PhCOOH (10 mol%) in water (1.0 mL) was stirred at room temperature.
bIsolated yields.
csyn/anti values were determined by 1H NMR or HPLC.
dDetermined by chiral HPLC using a Chiralcel AD-H or AS-H column.
concluded that bifunctional thiourea bearing a long chain 3b
is better than 3a. Under the catalysis of 3b, other acids such
as HCOOH, AcOH, n-butyric acid and TFA were screened,
and no improvement was achieved in yield or
stereoselectivity as compared to PhCOOH (entries 5-8, Table
1). Increasing the amount of 3b to 20mol% led to similar
yield and enantioselectivity (entry 9, Table 1), and
decreasing the amount of catalyst 3b led to the reduction of
yields (entry 10, Table 1). Moreover, when reaction
temperature was lowered to 0 ºC or elevated to 35 ºC, no
further improvement of enantioselectivity was observed
(entries 11 and 12, Table 1).
81% yield with 37% ee, and cyclopentanone gave the adduct
5k in 90% yield with 84% ee.
EXPERIMENTAL
1. Synthesis of Bifunctional Thiourea Bearing A Long
Chain 3 [18-20]
To a solution of aminomethylpyrrolidine 1 (0.60 g, 3.0
mmol) in CH2Cl2 (20 mL) was added isothiocyanate bearing
a long chain 2 (3.0 mmol), and the reaction mixture was
stirred at room temperature for 3 h. After concentration, the
resulting residue was purified by column chromatography
(silica gel, AcOEt/Et3N = 100/1 as eluent) to give a crude
solid. The solid was solved in the mixed solvent of
CF3COOH/CH2Cl2 (25 mL, v/v = 1:1) and the reaction
mixture was stirred at room temperature for 3 h. The pH was
adjusted to 8 with aqueous NaHCO3. The mixture was
extracted with dichloromethane (3ꢀ20 mL). The combined
organic layers were dried with Na2SO4. After concentration,
the residues was purified by column chromatography (silica
gel, methanol/CH2Cl2 = 1/7 as elution) to give 3.
In view of the condition experiment, the optimized
reaction should be catalyzed by 10 mol% organocatalyst 3b
with equal molar of PhCOOH at room temperature. Our
experiment demonstrated that under the optimal conditions,
various trans-nitroalkenes 4a-i could undergo Michael
addition smoothly with cyclohexanone at room temperature
for 12-18 h, giving the desired adducts 5a-i in good yields
(80–93%) with high diastereoselectivities (syn/anti = 95/5 –
> 99/1) and enantioseletivities (up to 92% ee) (Table 2). It
should be noted that the physical appearances of the reaction
mixtures were emulsions under stirring. The absolute
configurations of the adducts 5a-i were assigned by
comparison the results of optical rotation and chiral HPLC
with those of known compounds and all adducts 5a-i are
levorototary in CHCl3 [22]. The asymmetric Michael
addition of other ketones with nitrostyrene 4a using
surfactant-type organocatalyst 3b was also investigated. As
shown in Scheme 2, acetone gave the desired adduct 5j in
3a. Yellow solid. Yield: 92%. mp: 64-67 ºC. [ꢁ]25D = -7.3
1
(c = 0.75, MeOH). H NMR (CD3OD, 300 MHz) ꢀ (ppm):
3.70-3.20 (m, 5 H), 3.01-2.80 (m, 2 H), 1.95-1.60 (m, 3 H),
1.55-1.35 (m, 2 H), 1.20 (s, 18 H) , 0.80 (t, J = 6.4 Hz, 3 H) ;
13C NMR (CD3OD, 75 MHz): 183.0, 59.5, 55.9, 46.3, 45.3,
44.2, 31.7, 30.2, 29.4, 29.1, 28.8， 27.9, 26.7, 25.8, 24.3,
23.5, 22.4, 13.1; MS (ESI) m/z，Calcd for C18H37N3S
(MH+): 328.27, found: 328.42.

Efficient Enantioselective Michael Addition of Nitroalkenes
Letters in Organic Chemistry, 2012, Vol. 9, No. 1
53
Table 2. 3b/PhCOOH Catalyzed Michael Addition of trans-Nitroalkenes in The Presence of Watera
O
O
Ar
3b (10mol%)
PhCOOH(10mol%)
NO2
NO2
Ar
H2O , r.t.
4a-i
5a-i
Entry
Ar
5
Yield (%)b
syn:antic
ee(%)d
1
2
3
4
5
6
7
8
9
C6H5
5a
5b
5c
5d
5e
5f
91
90
91
89
87
93
80
88
81
>99:1
99:1
97:3
95:5
95:5
99:1
97:3
>99:1
97:3
92
89
90
87
82
91
81
73
85
2-NO2C6H4
4-FC6H4
4-ClC6H4
4-Br C6H4
2,4-Cl2 C6H3
4-CH3C6H4
5g
5h
5i
4-CH3OC6H4
2-Furyl
aThe mixture of nitroalkene 4 (0.5 mmol), cyclohexanone (1.0mmol), organocatalyst (10 mol%) and PhCOOH (10 mol%) in water (1.0 mL) was stirred at room temperature for 6-24
h.
bIsolated yields.
csyn/anti values were determined by 1H NMR or HPLC.
dDetermined by chiral HPLC using a Chiralcel AD-H or AS-H column.
3b (10mol%)
PhCOOH(10mol%)
O
Ph
O
NO2
81% yield
37% ee
NO2
Ph
H2O , r.t.,24 h
5j
4a
O
3b (10mol%)
O
Ph
PhCOOH(10mol%)
NO2
90% yield
75:25 dr
84% ee
NO2
Ph
H2O , r.t.,24 h
4a
5k
Scheme 2. Michael Addition of Nitrostyrene with Other Ketones.
3b. White solid. Yield: 95%. mp: 85-88 ºC. [ꢀ]25
=
or column chromatography (silica gel, petroleum
ether/AcOEt = 10:1 as eluent), affording the desired adduct
5a-i.
D
1
+28.0 (c = 0.10, MeOH). H NMR (CD3OD, 300 MHz) ꢀ
(ppm): 7.25-7.10 (m, 4 H), 3.80-3.65 (m, 3 H), 3.20-3.05 (m,
2 H), 2.61 (t, J = 7.6 Hz, 2 H), 2.15-1.80 (m, 3 H), 1.70-1.55
(m, 3 H), 1.29 (m, 18 H), 0.90 (t, J = 6.7 Hz, 3 H). 13C NMR
(CD3OD, 75 MHz) ꢀ (ppm): 181.4, 140.7, 136.5, 128.9,
124.5, 59.1, 46.1, 45.4, 35.1, 31.8, 31.4, 30.4, 29.5, 29.3,
29.2, 29.1, 28.2, 25.8, 24.5, 22.4, 13.2; MS (ESI) m/z, Calcd
for C24H41N3S (MH+): 404.30, found: 404.58.
2. General Procedure of Michael Reaction with
Nitroalkene 4 for 5a-i [23]
To the solution of bifunctional thiourea organocatalyst 3b
(20 mg, 0.05 mmol) in H2O (1 mL) was added
cyclohexanone (98 mg, 1 mmol), nitroalkene 4 (0.5 mmol)
and PhCOOH (6.1 mg, 0.05 mmol). The reaction mixture
was stirred to form emulsion (Fig. 1) and continued to be
stirred at r.t. for 6-24 h (monitored by TLC). After
concentration, the residue was purified by preparative TLC
Fig. (1). Photograph of Reaction Mixtures of Bifunctional Thiourea
Organocatalyst 3b.

54 Letters in Organic Chemistry, 2012, Vol. 9, No. 1
Li et al.
(S)-2- ((R)-2-nitro-1-phenylethyl)cyclohexanone 5a
(S)-2-((R)-2-nitro-1-p-tolylethyl)cyclohexanone 5g
1H NMR (CDCl3, 300 MHz) ꢀ (ppm): 7.40-7.25 (m, 3H),
7.24-7.15 (m, 2H), 4.95 (dd, J = 12.3, 4.5 Hz, 1H), 4.66 (dd,
J = 12.3, 9.6 Hz, 1H), 3.85-3.70 (m, 1H), 2.80-2.60 (m, 1H),
2.55-2.35 (m, 2H), 2.20-2.05 (m, 1H), 1.90-1.50 (m, 4H),
1H NMR (CDCl3, 300 MHz) ꢀ (ppm): 7.14 (d, J = 7.7
Hz, 2H), 7.06 (d, J = 8.2 Hz, 2 H), 4.93 (dd, J = 12.3, 4.5 Hz,
1H), 4.63 (dd, J = 12.0, 9.6Hz, 1H), 3.80-3.65 (m, 1H), 2.75-
2.60 (m,1H), 2.55–2.35 (m, 2H), 2.33 (s, 3H), 2.15-2.00 (m,
1H), 1.85–1.45 (m, 4H), 1.35–1.15 (m, 1H). [ꢁ]25D = -14.1 (c
= 1.31, CHCl3). HPLC analysis (Chiralpak AS-H column,
hexane/i-PrOH = 90/10, 0.7 ml/min, 238 nm): tr (minor) =
12.70 min, tr (major) = 18.99 min, 82%ee.
1.40-1.20 (m, 1H). [ꢁ]25 = -21.3 (c = 0.75, CHCl3). HPLC
D
analysis (Chiralpak AS-H column, hexane/ i-PrOH = 90/10,
0.7 ml/min, 238 nm): tr (minor) = 13.49 min, tr (major) =
20.83 min, 92%ee.
(S)-2-((R)-2-nitro-1-(2-nitrophenyl)ethyl)cyclohexanone 5b
(S)-2-((R)-1-(4-methoxyphenyl)-2-nitroethyl)cyclohexan-
one 5h
1H NMR (CDCl3, 300 MHz) ꢀ (ppm): 7.84 (dd, J = 8.1,
0.9 Hz, 1H), 7.65-7.60 (m, 1H), 7.50-7.40 (m, 2H), 5.00-4.80
(m, 2H), 4.45-4.25 (m, 1H), 3.00-2.90 (m, 1H), 2.55-2.30
1H NMR (CDCl3, 300 MHz) ꢀ (ppm): 7.10 (d, J = 9.0 Hz,
2H) 6.86 (d, J = 8.9 Hz, 2H), 4.92 (dd, J = 7.2 Hz, 2.7 Hz,
1H), 4.60 (dd, J = 7.5, 6.3 Hz, 1H), 3.80 (s, 3H), 3.75-3.65
(m, 1H), 2.70–2.60 (m, 1H), 2.55–2.35 (m, 2H), 2.15–2.05
(m, 2H), 2.20-2.05 (m, 1H), 1.90-1.40 (m, 5H). [ꢁ]25 = -9.4
D
(c = 0.50, CHCl3). HPLC analysis (Chiralpak AD-H column,
hexane/i-PrOH = 95/5, 1.0 ml/min, 238 nm): tr (minor) =
32.66 min, tr (major) = 53.62 min, 89%ee.
(m, 1H), 1.85–1.55 (m, 4H), 1.30–1.15 (m, 1H). [ꢁ]25 = -
D
20.4 (c = 0.67, CHCl3). HPLC analysis (Chiralpak AD-H
column, hexane/i-PrOH = 75/25, 0.7 ml/min, 238 nm): tr
(minor) = 14.65 min, tr (major) = 17.17 min, 83%ee.
(S)-2-((R)-1-(4-fluorophenyl)-2-nitroethyl)cyclohexanone
5c
1H NMR (CDCl3, 300 MHz) ꢀ (ppm): 7.20-7.15 (m, 2H),
7.10-7.00 (m, 2H), 4.95 (dd, J = 7.5 , 2.7 Hz, 1H), 4.62 (dd,
J = 7.5, 6.0 Hz, 1H), 3.80-3.75 (m, 1H), 2.70-2.60 (m, 1H),
2.55-2.45 (m, 2H), 2.15-2.00 (m, 1H), 1.85–1.50 (m, 4 H),
(S)-2-((S)-1-(furan-2-yl)-2-nitroethyl)cyclohexanone 5i
1H NMR (CDCl3, 300 MHz) ꢀ (ppm): 7.36 (m, 1H), 6.30
(dd, J = 3.3, 1.8 Hz, 1H), 6.25-6.15 (m, 1H), 4.85–4.60 (m, 2
H), 3.98 (dt, J = 8.9, 4.9 Hz, 1 H), 2.85–2.70 (m, 1 H), 2.55–
2.30 (m, 2H), 2.20-2.00 (m, 1H), 1.95–1.55 (m, 4H), 1.40–
1.30-1.15 (m, 1H). [ꢁ]25 = -29.3 (c = 1.50, CHCl3). HPLC
D
analysis (Chiralpak AS-H column, hexane / i-PrOH = 90/10,
0.7 ml/min, 238 nm): tr (minor) = 19.92 min, tr (major) =
27.57 min, 90%ee.
1.20 (m, 1H). [ꢁ]25 = -19.3 (c = 1.78, CHCl3). HPLC
D
analysis (Chiralpak AD-H column, hexane/ i-PrOH = 99/1,
0.5 ml/min, 220 nm): tr (major) = 38.28 min, tr (minor) =
46.41 min, 85%ee.
(S)-2-((R)-1-(4-chlorophenyl)-2-nitroethyl)cyclohexanone
5d
(R)-5-Nitro-4-phenylpentan-2-one 5j
1H NMR (CDCl3, 300 MHz) ꢀ (ppm): 7.35-7.30 (m, 2H),
7.20-7.10 (m, 2H), 4.95 (dd, J = 7.8, 2.7 Hz, 1H), 4.62 (dd, J
= 7.5, 5.7 Hz, 1H), 3.85-3.70 (m, 1H), 2.75-2.60 (m, 1H),
2.55-2.35 (m, 2H), 2.15-2.05 (m, 1H), 1.85-1.55 (m, 4H),
1H NMR (CDCl3, 300 MHz) ꢀ (ppm): 7.45-7.20 (m, 5H),
4.75-4.55 (m, 2H), 4.10-3.95 (m, 1H), 2.94 (d, J = 6.9 Hz,
2H), 2.14 (s, 3H). [ꢁ]25 = -19.7 (c = 0.55, CHCl3). HPLC
D
1.30-1.20 (m, 1H). [ꢁ]25 = -43.5 (c = 0.75, CHCl3). HPLC
analysis (Chiralpak AS-H column, hexane/i-PrOH =75/25,
1.0 ml/min, 210 nm): tr (minor) = 10.27 min, tr (major) =
12.93 min, 37%ee.
D
analysis (Chiralpak AS-H column, hexane/ i-PrOH = 90/10,
0.7 ml/min, 238 nm): tr (major) = 17.77 min, tr (minor) =
26.50 min, 87%ee.
(S)-2-((R)-2-Nitro-1-phenylethyl)cyclopentanone 5k
(S)-2-((R)-1-(4-bromophenyl)-2-nitroethyl)cyclohexanone
5e
1H NMR (CDCl3, 300 MHz) ꢀ (ppm): 7.40-7.25 (m, 3H),
7.25-7.10 (m, 2H), 5.40-5.30 (m, 1H), 4.71 (dd, J = 9.9, 12.6
1H NMR (CDCl3, 300 MHz) ꢀ (ppm): 7.47 (d, J = 5.1 Hz,
2H), 7.08 (d, J = 5.1 Hz, 2H), 4.95 (dd, J = 7.5, 2.7 Hz, 1H),
4.63 (dd, J = 7.5, 6.3 Hz, 1H), 3.80-3.70 (m, 1H), 2.70-2.60
(m, 1H), 2.55-2.35 (m, 2H), 2.15-2.05 (m, 1H), 1.80-1.55
(m, 4H), 1.30-1.20 (m, 1H). [ꢁ]25D = -11.9 (c = 0.56, CHCl3).
HPLC analysis (Chiralpak AS-H column, hexane/i-PrOH =
90/10, 0.7 ml/min, 238 nm): tr (minor) = 18.08 min, tr
(major) = 27.51 min, 80%ee.
Hz, 1H), 3.80-3.65 (m, 1H), 2.45-1.60 (m, 7H). [ꢁ]25 = -
D
26.5 (c = 0.50, CHCl3). HPLC analysis (Chiralpak AS-H
column, hexane/i-PrOH = 75/25, 1.0 ml/min, 210 nm): tr
(minor) = 7.89 min, tr (major) = 11.24 min, 84%ee.
CONCLUSION
In conclusion, we have synthesized new surfactant-type
bifunctional thiourea organocatalysts 3. It was found that in
the presence of 10 mol% PhCOOH, bifunctional thio-urea
bearing a long chain 3b with 10 mol% loading could
smoothly catalyze the asymmetric Michael reaction of
nitroalkenes 4 with cyclohexanone at room temperature in
the presence of water, giving the desired adducts 5 in good
yields (80-93%) with high diastereoselectivities (syn/anti =
95/5 - > 99/1) and enantioselectivities (up to 92% ee). Other
reaction systems are currently under study.
(S)-2-((R)-1-(2,4-dichlorophenyl)-2-nitroethyl)cyclohexan-
one 5f
1H NMR (CDCl3, 300 MHz) ꢀ (ppm): 7.43 (d, J = 2.4 Hz,
1H), 7.30-7.15 (m, 2H), 4.95-4.80 (m, 2H), 4.30-4.20 (m,
1H), 2.95-2.80 (m, 1H), 2.55-2.30 (m, 2H), 2.20-2.05 (m,
1H), 1.90-1.55 (m, 4H), 1.40-1.20 (m, 1H). [ꢁ]25D = -30.1 (c
= 0.53, CHCl3). HPLC analysis (Chiralpak AS-H column,
hexane/i-PrOH = 90/10, 0.7 ml/min, 238 nm): tr (minor) =
12.51 min, tr (major) = 18.70 min, 91%ee.

Efficient Enantioselective Michael Addition of Nitroalkenes
Letters in Organic Chemistry, 2012, Vol. 9, No. 1
55
addition to nitrostyrenes in water. Chem. Commun., 2006, 3687-
3689.
ACKNOWLEDGEMENT
This work was supported by the Foundation of Chang
Zhou University (No. ZMF1002130 & ZMF1002100).
[12]
[13]
[14]
Zheng, Z.L.; Perkins, B. L.; Ni, B.K. Diarylprolinol Silyl Ether
Salts as New, Efficient, Water-Soluble, and Recyclable
Organocatalysts for the Asymmetric Michael Addition on Water. J.
Am. Chem. Soc. 2010, 132, 50-51.
Hu, F.; Guo, C.-S.; Xie, J.; Zhu, H.-L.; Huang, Z.-Z. Efficient and
Highly Enantioselective Michael Addition of Aldehydes to
Nitroalkenes Catalyzed by a Surfactant-type Organocatalyst in the
Presence of Water. Chem. Lett., 2010, 39, 412-414.
Ko, K.; Nakano, K.; Watanabe, S.; Ichikawa, Y.; Kotsuki, H.
Development of new DMAP-related organocatalysts for use in the
Michael addition reaction of ꢀ-ketoesters in water. Tetrahedron
Lett., 2009, 50, 4025-4029.
Takemoto, Y.; Okino, T.; Hoashi, Y. Enantioselective Michael
Addition to, ꢀ-Unsaturated Imides Catalyzed by a Bifunctional
Organocatalyst. Angew. Chem. Int. Ed., 2005, 44, 4032-4035.
Inokuma, T.; Hoashi, Y.; Takemoto, Y. Thiourea-catalyzed
asymmetric michael addition of activated methylene compounds to
alpha, beta-unsaturated imides: dual activation of imide by intra-
and intermolecular hydrogen bonding. J. Am. Chem. Soc., 2006,
128, 9413-9419.
REFERENCES
[1]
Dalko, P.I.; Moisan, L. In the Golden Age of Organocatalysis.
Angew. Chem. Int. Ed., 2004, 43, 5138-5175.
[2]
Berkessel, A.；Groeger, H. Asymmetric Organocatalysis: from
Biomimetic. Concepts to Applications in Asymmetric Synthesis；
Wiley-VCH: Weinheim, Germany, 2005.
[3]
[4]
Mase, N.; Nakai, Y.; Ohara, N.; Yoda, H.; Takabe, K.; Tanaka, F.;
[15]
[16]
Barbas ， III, C.F. Organocatalytic direct asymmetric aldol
reactions in water. J. Am. Chem. Soc., 2006, 128, 734–735.
Hayashi, Y.; Aratake, S.; Okano, T.; Takahashi, J.; Sumiya, T.;
Shoji, M. Combined Proline–Surfactant Organocatalyst for the
Highly Diastereo- and Enantioselective Aqueous Direct Cross-
Aldol Reaction of Aldehydes. Angew. Chem. Int. Ed., 2006, 45,
5527-5529.
[5]
Aratake, S.; Itoh, T.; Okano, T.; Nagae, N.; Sumiya, T.; Shoji, M.;
Hayashi, Y. Highly diastereo- and enantioselective direct aldol
reactions of aldehydes and ketones catalyzed by siloxyproline in
the presence of water. Chem. Eur. J., 2007, 13, 10246-10256.
Luo, S.; Xu, H.; Li, J.; Zhang, L.; Mi, X.; Zheng, X.; Cheng, J.P.
Facile evolution of asymmetric organocatalysts in water assisted by
surfactant Brønsted acids. Tetrahedron, 2007, 63, 11307-11314.
Hayashi, Y.; Sumiya, T.; Takahashi, J.; Gotoh, H.; Urushima, T.;
Shoji, M. Highly Diastereo- and Enantioselective Direct Aldol
Reaction in Water. Angew. Chem. Int. Ed., 2006, 45, 958-961.
Lo, C.M.; Chow, H.F. Structural Effects on the Catalytic,
Emulsifying and Recycling Properties of Chiral Amphiphilic
Dendritic Organocatalysts. J. Org. Chem., 2009, 74, 5181-5191.
Mase, N.; Watanabe, K.; Yoda, H.; Takabe, K.; Tanaka, F.;
Barabas III, C.F. Organocatalytic Direct Michael Reaction of
Ketones and Aldehydes with ꢀ-Nitrostyrene in Brine. J. Am. Chem.
Soc., 2006, 128, 4966–4967.
[17]
[18]
[19]
[20]
Rossiter, B.E.; Swingle, N.M. Asymmetric conjugate addition.
Chem. Rev., 1992, 92, 771-806.
Berner, O.M.; Tedeschi, L.; Enders, D. Asymmetric Michael
Additions to Nitroalkenes. Eur. J. Org Chem., 2002, 12, 1877-1894.
Tsogoeva, S.B. Recent Advances in Asymmetric Organocatalytic
1,4-Conjugate Additions. Eur. J. Org. Chem., 2007, 11, 1701-1706.
Dahlin, N.; Boegevig, A.; Adolfsson, H. N-Arenesulfonyl-2-
aminomethyl pyrrolidines, Novel Modular Ligands and
Organocatalysts for Asymmetric Catalysis. Adv. Synth. Catal.,
2004, 346, 1101-1105.
Bhandari, K.; Srinivas, N.; Sharma, L.; Srivastava, S.; Nath A.;
Nath, C. Substituted urea/thiourea derived from fluoxetine as
potent appetite suppressants. Med. Chem. Res., 2008, 17, 103–113.
Cao, C.L.；Ye, M.C.；Sun, X.L.；Tang, Y. Pyrrolidine-thiourea
as a bifunctional organocatalyst: highly enantioselective Michael
addition of cyclohexanone to nitroolefins. Org. Lett. , 2006, 8,
2901-2904.
[6]
[7]
[8]
[9]
[21]
[22]
[10]
[11]
Palomo, C.; Landa, A.; Mielgo, A.; Oiarbide, M.; Puente, A.; Vera,
S. Water-Compatible Iminium Activation: Organocatalytic Michael
Reactions of Carbon-Centered Nucleophiles with Enals. Angew.
Chem. Int. Ed., 2007, 46, 8431-8435.
Luo, S.; Mi, X.; Liu, S.; Xu, H.; Cheng, J.-P. Surfactant-type
asymmetric organocatalyst: organocatalytic asymmetric Michael
[23]
Li, P.; Wang, L.; Zhang, Y.; Wang, G. Silica Gel Supported
Pyrrolidine-based Chiral Ionic Liquid as Recyclable Organocatalyst
for Asymmetric Michael Addition to Nitrostyrenes. Tetrahedron,
2008, 64, 7633-7638.