Simple primary β-amino alcohols as organocatalysts for the asymmetric Michael addition of β-keto esters to nitroalkenes

Article abstract of DOI:10.1039/d0ra09041g

Simple primary β-amino alcohols act as an efficient organocatalysts in the asymmetric Michael addition of β-keto esters with nitroalkenes affording highly pure chiral Michael adducts. Also, both enantiomers of the adducts were obtained, depending on the specific catalyst used and reaction temperature.

Full text of DOI:10.1039/d0ra09041g

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Simple primary b-amino alcohols as
organocatalysts for the asymmetric Michael
Cite this: RSC Adv., 2021, 11, 203
addition of b-keto esters to nitroalkenes†
Zubeda Begum,a Haruka Sannabe,a Chigusa Seki,a Yuko Okuyama,b Eunsang Kwon,c
Koji Uwai,a Michio Tokiwa,d Suguru Tokiwa,d Mitsuhiro Takeshitad
a
*
and Hiroto Nakano
Received 23rd October 2020
Accepted 3rd December 2020
Simple primary b-amino alcohols act as an efficient organocatalysts in the asymmetric Michael addition of
b-keto esters with nitroalkenes affording highly pure chiral Michael adducts. Also, both enantiomers of the
adducts were obtained, depending on the specific catalyst used and reaction temperature.
DOI: 10.1039/d0ra09041g
rsc.li/rsc-advances
route for the synthesis of chiral compounds which act as
precursor for a range of biologically and pharmaceutically
1. Introduction
important compounds. Furthermore, this addition is also
useful for the construction of chiral building blocks containing
quaternary carbon stereocenters, which act as a key synthetic
intermediates for the complex compounds and synthetic drug
candidates.7 Consequently, several efforts have been made in
recent years to develop an efficient organocatalyst for this
reaction.8 Our group has reported that the cage type 2-
azanorbornane-based amino alcohols Y act as an efficient
organocatalyst in this addition.10 However, this catalyst Y has
a complex structure and requires a multistep route for the
synthesis, although efficient catalytic activity is observed. Based
on these backgrounds, we have planned to try the asymmetric
Michael addition of b-keto esters A with nitroalkenes B using
more simplied b-amino alcohol organocatalyst X (Scheme 1).
In this paper, we describe an efficient catalytic activity dis-
played by b-amino alcohol organocatalyst catalyst X in the
Michael addition of A with B to afford chiral Michael adducts C
at satisfactory chemical yields and stereoselectivities (up to
From the last decade, the development of new optically active
multifunctional organocatalysts and their use in asymmetric
synthesis as independent chiral sources have drawn consider-
able interest in the scientic community.1 A lot of excellent
covalent and non-covalent organocatalysts have been developed
for use in a wide range of asymmetric reactions.2 However, it is
always a challenging task to design and synthesize a new class
of multifunctional organocatalysts and to explore them as self-
determining and eco-friendly catalysts in asymmetric synthesis.
In recent years, we are continuously exploring the multifunc-
tional b-amino alcohol organocatalysts X (Scheme 1),3 that are
easily derived from commercially available amino acids in one
or two steps and are less sensitive to air, show low toxicity and
are eco-friendly. This amino alcohol X contains an amino group
acting as a basic or covalent enamine formation site, a non-
covalent hydroxyl group acting as a hydrogen bonding site in
a single molecule and also the substituents at a- and b-posi-
tions, which might also be effective in controlling the enantio-
selective reaction course (Scheme 1). In our previous study, this
catalyst has worked as an efficient organocatalyst in 1,3-dipolar
cycloaddition,4 Diels–Alder reactions5 and aldol reactions.6
Asymmetric Michael addition is recognized as a versatile and
powerful key carbon–carbon bond and also a powerful tool for
constructing carbon–heteroatom bond providing an effective
aDivision of Sustainable and Environmental Engineering, Graduate School of
Engineering, Muroran Institute of Technology, 27-1 Mizumoto-cho, Muroran
050-8585. E-mail: catanaka@mmm.muroran-it.ac.jp
bTohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-Ku,
Sendai 981-8558, Japan
cResearch and Analytical Center for Giant Molecules, Graduate School of Sciences,
Tohoku University, 6-3 Aoba, Aramaki, Aoba-Ku, Sendai 980-8578, Japan
dTokiwakai Group, 62 Numajiri Tsuduri-Chou Uchigo, Iwaki 973-8053, Japan
† Electronic supplementary information (ESI) available: Experimental details and
HPLC data. See DOI: 10.1039/d0ra09041g
Scheme
nitroalkenes.
1 Asymmetric Michael addition of b-keto esters with
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80%, up to dr ¼ 99 : 1, up to 99% ee). In addition, an interesting diastereoselectivity and low enantioselectivity (62%, dr ¼
property was observed that both enantiomers of the adducts 83 : 17, 45% ee) (entry 1). Similar reaction using catalyst 1b with
were obtained depending on used specic catalyst and a reac- isopropyl group did not show a much change in the chemical
tion temperature with excellent stereoselectivities (up to 99 : 1, yield and diastereoselectivity, but enantioselectivity was quite
up to 99% ee).
increased (64%, dr ¼ 88 : 12, 56% ee) (entry 2). Interestingly, the
use of catalyst 1c with bulky tert-butyl group afforded the
enantiomer adduct [2S,3R]-40 of 4 in moderate chemical yield,
diastereoselectivity and good enantioselectivity (68%, dr ¼
91 : 9, 88% ee) (entry 3). In addition, catalyst 1d with more
sterically inuential phenyl group provided adduct 4 with
moderate chemical yield, good diastereoselectivity and low
enantioselectivity (65%, dr ¼ 83 : 17, 11% ee) (entry 4).
Furthermore, catalyst 1e with benzyl group also did not show
satisfactory enantioselectivity, although chemical yield and
diastereoselectivity were moderate (55%, dr ¼ 86 : 14, 10% ee)
(entry 5). On the other hand, the decrease of temperature to
ꢁ30 ꢀC substantially improved diastereoselectivity and enan-
tioselectivities (entries 1–5). Catalyst 1a afforded adduct 4 with
good chemical yield, excellent diastereoselectivity and enan-
tioselectivity (75%, dr ¼ 99 : 1, 99% ee) (entry 1). Catalyst 1b
also afforded 4 with good chemical yield and in excellent dia-
stereoselectivity and enantioselectivity (70%, dr ¼ 96 : 4, 98%
ee) (entry 2). Interestingly, the enantiomer adduct 40 of 4 was
obtained at 0 ꢀC using 1b, but the decrease to ꢁ30 ꢀC afforded 4,
although the reason is not clear. Similarly, the use of catalyst 1c
gave 40 in good chemical yield and diastereoselectivity with
excellent enantioselectivity (80%, dr ¼ 98 : 2, 99% ee) (entry 3).
The use of bulky catalyst 1d signicantly increased the enan-
tioselectivity with good chemical yield and diastereoselectivity
(65%, dr ¼ 96 : 4, 98% ee) (entry 4). Bulkier catalyst 1e brought
about the increase of enantioselectivity to afford 40, but satis-
factory chemical yield and stereoselectivities were not obtained
2. Results and discussion
2.1. Preparation and screening of catalysts
b-Amino alcohol organocatalysts 1a–e with different substitu-
ents at the a- and b-position were prepared from the corre-
sponding amino acids (Scheme 2). The reaction of amino acids
with thionyl chloride in methanol, followed by Grignard reac-
tion of the obtained methyl esters afforded the desired 1a–e.5a
In order to investigate the asymmetric catalytic activity of the
obtained amino alcohols 1a–e, model reaction was carried out
using methyl-2-oxocyclopentanecarboxylate 2a and nitrostyrene
3a in toluene at 0 ꢀC and ꢁ30 ꢀC for 48 h (Table 1) respectively.
All catalysts showed a catalytic activity in this reaction (entries
1–5). When the reaction was carried out at 0 ꢀC using catalyst 1a
with methyl group at b-position, the desired Michael adduct
[2S,3R]-4 was obtained with moderate chemical yield,
Scheme 2 Preparations of b-amino alcohols 1a–e.
Table 1 Asymmetric Michael addition of b-keto ester 2a with nitrostyrene 3a using amino alcohol organocatalysts 1a–e
Adduct 4,40
Yielda (%)
drb 4 : 400
0 ꢀ
eec (%)
Entry
Catalyst 1a–e
0
ꢀC
–30 ꢀC
0 ꢀ
C
–30 ꢀC
C
–30 ꢀ
C
0 ꢀ
C
ꢁ30 ꢀ
C
1
2
3
4
5
a
b
c
d
e
4
4
62
64
68
65
55
75
70
80
65
50
83 : 17
88 : 12
91 : 9
83 : 17
86 : 14
99 : 1
96 : 4
98 : 2
96 : 4
85 : 15
45
56
88
11
10
99
98
99
98
60
40
40
4
4
40
4
4
40
a
1
Isolated yields. b Determined by H NMR of the crude reaction mixture. c Determined by HPLC using Daicel Chiralcel OD-H column.
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(50%, dr ¼ 85 : 15, 60% ee) (entry 5). However, similarly to the solvent (45%, dr ¼ 83 : 17, 64% ee) (entry 8). From these results,
adduct from catalyst 1b, the use of catalyst 1e also afforded the toluene was observed to be the best solvent for this reaction
enantiomer adduct 40 of 4, although the reason is not clear. using 1a (76%, dr ¼ 99 : 1, 99% ee) (entry 9). Next, the molar
Each catalyst showed satisfactory asymmetric catalytic activity ratio of catalyst 1a was examined in this reaction (entries 10–
at ꢁ30 ꢀC. It might be for a reason that the conformation of the 12). The reaction was carried out using 20 mol%, 5 mol% and
ꢀ
transition state of this Michael addition reaction using catalyst 2.5 mol% of 1a at ꢁ30 C in toluene, respectively. The use of
1a with substrates 2a, 3a was xed at the decrease of reaction 20 mol% of 1a afforded almost same results (75%, dr ¼ 97 : 3,
temperature at ꢁ30 ꢀC affording high enantioselectivity, 98% ee) as that of 10 mol% of 1a (entry 10). The reaction using
although the reason is not clear. Especially, catalyst 1a with 5 mol% of 1a brought about the signicant decrease of chem-
methyl group and 1c with bulky tert-butyl group at b-position ical yield, but the diastereoselectivity and enantioselectivity
showed better catalytic activity than others. The determination were kept a high level of value (45%, dr ¼ 95 : 5, 94% ee) (entry
of absolute conguration and stereoselectivity of 4, 40 were 11). However, the use of 2.5 mol% of 1a brought about decrease
conrmed on comparision with previous data.10
in chemical yield and enantioselectivity except for diaster-
To further improve the results, we evaluated the effect of eoselectivity (36%, dr ¼ 93 : 7, 50% ee) (entry 12). From the
solvents, molar ratio of catalyst or substrates, and reaction time above results, it was revealed that the optimum amount of 1a
using the simplest superior catalyst 1a (Table 2). Initially, was 10 mol%. The ratio of substrate amounts of 2a and 3a
solvent effect was examined (entries 1–9). The reaction of 2a (2 (2a : 3a ¼ 1 : 1 and 2a : 3a ¼ 1 : 2) were examined in the pres-
eq.) with 3a (1 eq.) using 10 mol% of catalyst 1a was performed ence of 1a (10 mol%) (entries 13 and 14). However, these ratios
at ꢁ30 ꢀC for 48 h in polar solvents (CH3CN, DMSO and MeOH), brought about a decrease of chemical yield and enantiose-
respectively (entries 1–3). However, catalyst 1a did not show lectivity, except for diastereoselectivity (38%, dr ¼ 93 : 7, 52%
satisfactory catalytic activity in those solvents (CH3CN: 26%, dr ee) (56%, dr ¼ 94 : 6, 90% ee) (entries 13 and 14). Furthermore,
¼ 88 : 19, 38% ee) (DMSO: 40%, dr ¼ 75 : 25, 9% ee) (MeOH: the effect of reaction times (24 h and 72 h) also did not afford
45%, dr ¼ 83 : 17, 9% ee) (entries 1–3). In addition, non-polar better results, as the yields and stereoselectivities (42%, dr ¼
hexane also did not work as better solvent for this reaction 95 : 5, 88% ee) (60%, dr ¼ 84 : 16, 95% ee) (entries 15 and 16)
(hexane, 40%, dr ¼ 90 : 10, 46% ee) (entry 4). On the other hand, were observed to be inferior compared to 48 h. Based on the
catalyst 1a showed enough catalytic activity in ether solvents above results, it was revealed that 10 mol% of catalyst 1a, 2 eq.
(Et2O, i-Pr2O) (Et2O: 60%, dr ¼ 95 : 5, 98% ee) (i-Pr2O: 73%, dr ¼ of 2a, 1 eq. of 3a, toluene as a solvent, 48 h of reaction time and
ꢀ
98 : 2, 98% ee) (entries 5 and 6). However, cyclic etherate THF ꢁ30 C temperature are the optimum condition to obtain the
did not work as a good solvent (28%, dr ¼ 85 : 5, 20% ee) (entry Michael adduct [2R,3S]-4 with good chemical yield, excellent
7). Furthermore, halogenated CH2Cl2 also was not effective diastereoselectivity and enantioselectivity. Next, we examined
Table 2 Optimal condition examination in asymmetric Michael addition of b-keto esters 2a with nitrostyrene 3a using amino alcohol orga-
nocatalyst 1a
Entry
Catalyst 1a (mol%)
2a (eq.)
3a (eq.)
Solvent
Time (h)
Yielda (%)
drb 4 : 400
eec (%)
1
2
3
4
5
6
7
8
10
10
10
10
10
10
10
10
10
20
5
2.5
10
10
10
10
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
1.0
1.0
2.0
2.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
2.0
1.0
1.0
CH3CN
DMSO
MeOH
Hexane
Et2O
48
48
48
48
48
48
48
48
48
48
48
48
48
48
24
72
26
40
45
40
60
73
28
45
76
75
45
36
38
56
42
60
88 : 19
75 : 25
83 : 17
90 : 10
95 : 5
98 : 2
85 : 15
83 : 17
99 : 1
97 : 3
95 : 5
93 : 7
93 : 7
94 : 6
95 : 5
84 : 16
38
9
9
46
98
98
20
64
99
98
94
50
52
90
88
95
i-Pr2O
THF
CH2Cl2
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
9
10
11
12
13
14
15
16
a
1
Isolated yields. b Determined by H NMR of the crude reaction mixture. c Determined by HPLC using Daicel Chiralcel OD-H column.
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the effect of substituents on amino organocatalysts 5a-e9 in this
addition of 2a with 3a (Scheme 3, Table 3). The reaction of 2a (2
eq.) with 3a (1 eq.) was carried out in toluene at ꢁ30 ꢀC for 48 h
(Table 3). Catalyst 5a9a with no substitution at the a-position
only showed low catalytic activity (40%, dr ¼ 60 : 40, 31%) and
afforded enantiomer adduct 40 of 4 (entry 1). Furthermore, when
5b9b in which the hydroxyl group was masked by TMS group was
used, the chemical yield and, stereoselectivities were signi-
cantly less than the result that afforded by 1a with free hydroxyl
group (45%, dr ¼ 77 : 23, racemate) (entry 2). We also carried
out the reaction using 5c9c with no substitution for the hydroxyl
group at b-position, but this catalyst did not show satisfactory
catalytic activity (48%, dr ¼ 66 : 34, 20%) (entry 3). From these
results, the hydroxyl group at the a-position on catalyst 1a may
need to promote this reaction with enough enantioselectivity.
The reactions using catalysts 5d9d, 5e9e with secondary and
tertiary amino groups at the a-position were expected to be
more basic than 1a with primary amino group were examined
(entries 4 and 5). However, only racemate adduct 4 was obtained
with good chemical yield and moderate diastereoselectivity (5d:
75%, dr ¼ 68 : 32, racemate) (5e: 70%, dr ¼ 55 : 45, racemate).
In the reactions using catalysts 5a–e, no better result was ob-
tained than the result using catalyst 1a. Based on the above
results, the utility of b-amino alcohol having a primary amino
group at the b-position acting as a base and hydrobonding site,
phenyl group at the a-position performing as stereocontrolling
site and a hydroxy group forming hydrogen bonds with the
substrates was revealed in order to achieve satisfactory chemical
yield and stereoselectivities.
Table 3 Optimal condition examination in asymmetric Michael addi-
tion of b-keto ester 2a with nitrostyrene 3a using amino alcohol
organo catalysts 5a–e
Entry Catalyst 5a–e Adduct 4, 40 Yielda (%) drb 4 : 400 eec (%)
1
2
3
4
5
a
b
c
d
e
40
4
4
4
4
40
45
48
75
70
60 : 40
77 : 23
66 : 34
68 : 32
55 : 45
31
racemic
20
racemic
racemic
a
b
Isolated yields. Determined by 1H NMR of the crude reaction
mixture. c Determined by HPLC using Daicel Chiralcel OD-H column.
nitrostyrene 6e also afforded the corresponding adduct 11, the
enantioselectivity was slightly decreased (11: 81%, dr ¼ 92 : 8,
52% ee). Furthermore, the use of 1-naphthylnitroolen 6f also
afforded 12 at good chemical yield, moderate diaster-
eoselectivity and enantioselectivity (12: 68%, dr ¼ 90 : 10, 67%
ee). Similarly, 3-methoxynitrostyrene 6g also yielded 13 at good
chemical yield and diastereoselectivity, but with low enantio-
selectivities (13: 78%, dr ¼ 85 : 15, 34% ee). Moreover, the
reaction using heterocyclic 2-1-(2-furyl)-2-nitroethylene 6h was
carried out and the corresponding 14 was obtained in good
chemical yield and diastereoselectivity with low enantiose-
lectivity (14: 70%, dr ¼ 94 : 6, 37% ee). Similarly, the use of
2.2. Substrate scope
Under the optimized reaction condition using catalyst 1a, the
generality of 1a was examined in the asymmetric Michael
addition of various b-keto esters with nitroolens (Schemes 4
and 5). First the reactions of 2a with 6a–i were carried out in
ꢀ
toluene at ꢁ30 C for 48 h (Scheme 4) respectively. As summa-
rized in Scheme 4, the desired Michael adducts 7–15 were ob-
tained at moderate to good chemical yields and
stereoselectivities. The reaction of b-keto ester 2a with p-halo-
genated nitrostyrenes 6a–d proceeded with good chemical yield
and diastereoselectivities with moderate to good enantiose-
lectivities to afford 7–10 (7, 86%, dr ¼ 94 : 6, 72% ee) (8, 88%, dr
¼ 98 : 2, 74% ee) (9, 86%, dr ¼ 98 : 2, 69% ee) (10, 51%, dr ¼
78 : 22, 49% ee). Although the reaction using p-methylated
Scheme 3 Substituted amino alcohol organocatalysts 5a–e.
206 | RSC Adv., 2021, 11, 203–209
Scheme 4 Asymmetric Michael addition of 2a with 6a–i.
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Scheme 6 Plausible reaction course for Asymmetric Michael addition.
2.3. Reaction mechanism
The uses of catalyst 1a with methyl group at a-position afforded
the Michael adduct 4a and of 1c with tert-butyl group at a-
position afforded enantiomer adduct 40 of 4 with excellent in the
reaction of methyl 2-oxocyclopentanecarboxylate 2a and nitro-
Scheme 5 Asymmetric Michael addition of 2b–h with 3a.
ꢀ
styrene 3a at ꢁ30 C, respectively (Table 1). Stereoselectivities
heterocyclic 2-[(E)-2-nitrovinyl]thiophene 6i also afforded 15 at
good chemical yield and diastereoselectivity, but with moderate
enantioselectivity (15: 74%, dr ¼ 94 : 6, 53% ee). In addition, we
also examined the reaction of various b-keto esters 2b–d or b-
diketones 2e–g with nitrostyrene 3a (Scheme 5). The reactions of
b-keto esters 2b–d with 3a respectively, afforded the corre-
sponding Michael adducts 16–18 with moderate to good
chemical yields and moderate stereoselectivities. The reaction
using cyclopentanone ethyl ester 2b afforded 16 with moderate
chemical and good stereoselectivities (16: 66%, dr ¼ 94 : 6, 72%
ee). Moreover, the use of bulky cyclopentanone tert-butyl ester
2c afforded 17, but the reaction brought about the decrease of
chemical yield and stereoselectivities (17: 46%, dr ¼ 70 : 30,
23% ee).11b On the other hand, the reaction using indanone
ester 2d proceeded to afford 18 at good chemical yield and
stereoselectivities (18: 80%, dr ¼ 83 : 17, 75% ee).11c Although,
the reaction using diketones such as 2-acetyl cyclopentanone 2e
or 2-acetyl butyrolactone 2f with 3a, respectively, also afforded
the corresponding 19, 20 the enantioselectivities were low to
moderate (19: 78%, dr ¼ 77 : 23, 40% ee)11a (20: 65%, dr ¼
66 : 34, 32% ee).11c On the other hand, the use of acycliclic
diketone 2g and gave only a trace of 21. Reaction using six
membered ring diketo ester 2h was also tried, however the
reaction did not proceed. The reaction using a large amount of
substrate (3a: 1.0 g, 2a: 1.9 g) was examined to demonstrate the
practically utility in the best reaction condition. As a result, the
Michael adduct 4 was obtained with 60% chemical yield with
good stereoselectivites (dr ¼ 91 : 9, 86% ee) at 40 h reaction
time, although a slight decrease of ee was observed. From this
result, it is expected that this Michael addition reaction using
simple primary b-Amino alcohol organocatalyst may be useful
for practical aspect.
(1a: dr ¼ 99 : 1, 99% ee, 1c: dr ¼ 98 : 2, 99% ee) Based on the
observed excellent stereoselectivities, we proposed the plausible
mechanism via a transition state (TS) model to rationalize the
stereochemical of Michael addition as shown in Scheme 6. In
the mentioned TS, both catalysts 1a and 1c, respectively, act as
a base and abstracts a proton on 2a to generate an enolate and
then the species is xed with the ammonium site of catalyst part
by hydrogen bonding. In addition, substrate 3a is also xed with
ammonium and hydroxyl group sites on catalyst part by
hydrogen bonding. Aer the xing of catalyst and substrates,
the reaction using catalyst 1a with less bulky methyl group
might be assumed to proceed through TS-2 that does not have
the steric interaction between phenyl group at a-position on
catalyst part and 3a than that of TS-1, to afford [2S,3R]-4 with
excellent stereoselectivities.
On the other hand, the reaction using 1c with bulky tert-butyl
group might be assumed to proceed through TS-20 that does not
have the large steric interaction of bulky tert-butyl group on
catalyst part and enolate species than that of TS-10. It may be for
a reason that the steric interaction between the bulky tert-butyl
group at b-position on catalyst species and enolate species is
prioritized in contrast with the steric interaction between
phenyl group at a-position on catalyst species and nitrostyrene
3a, to afford [2S,3R]-40 as
a major adduct with high
stereoselectivity.
3. Conclusion
We have developed simple primary b-amino alcohols, which act
as an efficient organocatalysts in the asymmetric Michael
addition of b-keto esters with nitroalkenes, affording highly
pure chiral Michael adducts. In particular, simplest b-amino
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alcohols 1a with methyl group at a-position showed the best
catalytic activity and the corresponding Michael adducts having
a quaternary chiral carbon center with good to excellent
chemical yields (up to 80%), diastereoselectivities (up to 99 : 1)
and enantioselectivities (up to 99% ee). Furthermore, we have
found that the both enantiomers of Michael adducts 4, 40 are
separately made by using specic b-amino alcohol organo-
catalysts such as catalysts 1a with methyl group and 1c with tert-
butyl group at b-position, respectively. And also, interestingly,
when b-amino alcohols 1b or 1e were used in this reaction, both
enantiomers of Michael adducts ([2R,3S]-4 and [2S,3R]-40) were
separately made, depending on the reaction temperature.
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4. Experimental
4.1. General information
All reagents and dry solvents were purchased from commercial
vendors and used directly without further purication. All
reactions were placed in dried sample vials inserted with
magnetic beads. Thin-Layer Chromatography (TLC) was per-
formed on Merck silica gel 60 F254 plates and the analytes were
identied under UV light. Flash column chromatography was
performed using silica gel pore size 60 N (40–100 mm). Infrared
(IR) spectra were measured with a JASCO FT/IR-4100 spectro-
photometer. 1H and 13C NMR spectroscopic data were recorded
using a JEOL JNM-ECA500 instrument with tetramethylsilane as
the internal standard. HPLC data were collected using the
TOSOH instrument equipped with (UV-8020, DP-8020, and SD-
8022) detectors using Daicel CHIRALCEL OD-H column. Optical
rotations were measured with a JASCO-DIP-370 digital polar-
imeter. MS were taken on a JEOL-JMS-700 V spectrometers.
4.2. General procedure for catalytic asymmetric Michael
addition of b-keto esters, ketones 2a,2b–g with nitrostyrenes
3a,6a–h using catalyst 1a
To a solution of catalyst 1a (10 mol%) in dry toluene (2 mL) with
molecular sieves 4A was added b-keto esters, ketones 2a,2b–g (0.4
mmol) at RT under inert atmosphere and the solution was stirred
at same temperature. Aer 1 h, the reaction was cooled to ꢁ30 ꢀC
and the respective nitrostyrene 3a,6a–i (0.2 mmol) was added.
The reaction was allowed to stir at ꢁ30 ꢀC for 48 h. Aer the
completion of the reaction, the solvent was removed under
reduced pressure and the residue was puried by ash chroma-
tography on silica gel (n-hexane/AcOEt ¼ 10/1) to give the corre-
sponding chiral Michael adduct. The compounds are the known
compounds and the structures were identied by spectral data
which were in good agreement with those reported.10,11
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Conflicts of interest
There are no conicts to declare.
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