Catalytic asymmetric homo-1,3-dipolar cycloadditions of azomethine ylides: Diastereo- and enantioselective synthesis of imidazolidines

Article abstract of DOI:10.1016/j.tetasy.2014.03.008

The first catalytic asymmetric homo-1,3-dipolar cycloadditions of azomethine ylides have been established via SPINOL-derived chiral phosphoric acid-catalyzed pseudo four-component reactions of aldehydes and 2-aminomalonates, resulting in the stereoselective construction of chiral imidazolidine scaffolds with two stereogenic centers in generally high yields and with good stereoselectivities (up to 81% yield, all >20:1 dr, up to 93% ee). This protocol provides easy access to synthetically and pharmaceutically important chiral imidazolidines via the formation of one ring system, two stereogenic centers, and four new bonds in a single step.

Full text of DOI:10.1016/j.tetasy.2014.03.008

Tetrahedron: Asymmetry xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Catalytic asymmetric homo-1,3-dipolar cycloadditions of azomethine
ylides: diastereo- and enantioselective synthesis of imidazolidines
⇑
Ren-Yi Zhu, Cong-Shuai Wang, Fei Jiang, Feng Shi , Shu-Jiang Tu
School of Chemistry and Chemical Engineering, Jiangsu Key Laboratory of Green Synthetic Chemistry for Functional Materials, Jiangsu Normal University, Xuzhou 221116, China
a r t i c l e i n f o
a b s t r a c t
Article history:
The first catalytic asymmetric homo-1,3-dipolar cycloadditions of azomethine ylides have been estab-
lished via SPINOL-derived chiral phosphoric acid-catalyzed pseudo four-component reactions of alde-
hydes and 2-aminomalonates, resulting in the stereoselective construction of chiral imidazolidine
scaffolds with two stereogenic centers in generally high yields and with good stereoselectivities (up to
81% yield, all >20:1 dr, up to 93% ee). This protocol provides easy access to synthetically and pharmaceu-
tically important chiral imidazolidines via the formation of one ring system, two stereogenic centers, and
four new bonds in a single step.
Received 22 January 2014
Accepted 7 March 2014
Available online xxxx
Ó 2014 Elsevier Ltd. All rights reserved.
1. Introduction
On the other hand, the catalytic asymmetric 1,3-DCs of azome-
thine ylides to imines would allow for the creation of a chiral imi-
Catalytic asymmetric 1,3-dipolar cycloadditions (1,3-DCs) of
azomethine ylides to unsaturated bonds have proven to be a pow-
erful tool to access chiral nitrogenous heterocyclic motifs, which
existed in numerous natural products and artificial molecules with
pharmaceutical relevance.1 As a result, many enantioselective
transformations have been developed in the catalytic asymmetric
1,3-DCs of azomethine ylides to electron-deficient olefins, leading
to the formation of chiral pyrolidine scaffolds (Eq. 1).2 However,
in sharp contrast, only a few enantioselective variants have been
found for the catalytic asymmetric 1,3-DCs of azomethine ylides
to electronically poor carbonAnitrogen double bonds, which in-
volves the use of imines derived from anilines and aldehydes as
dipolarophiles as reported by Gong et al. and Wang et al. (Eq. 2).3
dazolidine skeleton, which constitutes the core structure of many
natural products, bioactive compounds, and important catalysts
or ligands in organic synthesis. For example, as illustrated in
Figure 1, fumiquinazolines A and B I are natural alkaloids.4 Com-
pounds II–IV possess antipyretic, anticonvulsant, and aldose
reductase inhibitory activities, respectively.5 Compounds V–VII
are well known organocatalysts or ligands, which have enabled a
variety of enantioselective transformations.6 Therefore, this trans-
formation is highly desirable for the stereoselective construction of
the imidazolidine moiety and remains a challenge with regard to
the limited examples employing carbonAnitrogen double bonds
as dipolarophiles.
We have already established a series of 1,3-DCs of azomethine
ylides to electron-deficient olefins7 or alkynes8 with excellent
enantioselectivity using chiral phosphoric acids (CPAs)9 as cata-
lysts. Inspired by this success and with the aim of synthesizing
stereoselective imidazolidines, we envisioned that the precursors
of azomethine ylides, that is, the aldimines generated from alde-
hydes and amino-esters would serve as carbonAnitrogen double
bonds to react with the same azomethine ylides via homo-1,3-
DCs under the catalysis of CPA, thus affording chiral imidazolidines
with multiple stereogenic centers (Scheme 1). In this approach,
azomethine ylides would act as both 1,3-dipoles and dipolaro-
philes to perform diastereo- and enantioselective homo-1,3-DCs,
which have not been reported so far during the development of
catalytic asymmetric 1,3-DCs of azomethine ylides.
previous work on catalytic asymmetric 1,3-DCs:
R4
EWG
R6
R5
*
R4
EWG
R6
R2
R3
R5
olefin
Cat.*
many enantioselective
*
*
(1)
(2)
*
transformations are available
R1
N
H
pyrolidine
R1
N
R3
Ar
R2
azomethine ylide
R
N
Ar
R1
only a few enantioselective
transformations are available
R
R2
R3
N
imine
Cat.*
*
*
*
N
H
Herein we report the first catalytic asymmetric homo-1,3-DCs
of azomethine ylides, which assemble aldehydes and 2-aminomal-
imidazolidine
⇑
Corresponding author. Tel./fax: +86 (516) 83500065.
E-mail address: fshi@jsnu.edu.cn (F. Shi).
onates in
a highly ordered reaction sequence to efficiently
http://dx.doi.org/10.1016/j.tetasy.2014.03.008
0957-4166/Ó 2014 Elsevier Ltd. All rights reserved.
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2
R.-Y. Zhu et al. / Tetrahedron: Asymmetry xxx (2014) xxx–xxx
SMe
Me
O
O
Ts
N
N
O
HN
Ph
Me
NH
O
N
O
NH
O
R
N
F
O
*
N
O
*
O
OH
H
O
N
OH
O
O
Et
NH
antipyretic
inhibiting aldose reductase
anticonvulsant
N
O
II
III
IV
Me
Ph
Ph
Me
N
fumiquinazoline A and B
O
Me
N
HN
NH
Ph
Ph
I
Me
N
N
N
CO2H
Bn
Bn
N
H
N
H
Bn
Me
Bn
Jogensen's catalyst
MacMillan's catalyst
PyBidine ligand
V
VI
VII
Figure 1. Selected natural alkaloids, bioactive compounds, and important catalysts or ligands containing a chiral imidazolidine skeleton.
this work: the first catalytic asymmetric homo-1,3-DCs
R1
were subsequently performed, which showed that 4 Å MS was
much superior to 3 Å and 5 Å MS, both in terms of reactivity and
enantioselective control (entry 9 vs 10 and 11).
RO2C
RO2C
R1
CO2R
CO2R
Homo-1,3-DCs
Next, other reaction parameters including solvents, tempera-
ture, and catalyst loading were optimized to further improve the
enantioselectivity (Table 2). The screening of solvents (entries
1–5) found that chloroform was the most suitable one, enabling
the model reaction to proceed in a high yield of 74% and with an
excellent enantioselectivity of 90% ee (entry 3). With regard to
the temperature (entries 6 and 7), we found that 40 °C gave the
best performance in providing product 3aa in 76% yield and 91%
ee (entry 6). However, increasing the catalyst loading was detri-
mental to the enantioselectivity of the reaction without any obvi-
ous improvements in the yields (entries 8 and 9). The most suitable
reaction conditions are found in entry 6.
N
CO2R
CO2R
N
+
RO2C
*
CPA
*
N
N
H
R1
CO2R
R1
CPA
stereoselective formation
of imidazolidines
CO2R
CO2R
R1 CHO
+
H2N
Scheme 1. The design of catalytic asymmetric homo-1,3-DCs of azomethine ylides.
With the optimal reaction conditions in hand, we next investi-
gated the substrate scope of the catalytic asymmetric homo-1,3-
DCs of azomethine ylides. As shown in Table 3, this protocol was
amenable to a wide range of aromatic, heteroaromatic aldehydes
1a–1m and different amino-esters 2a,2b, providing chiral imidaz-
olidines 3 with structural diversity in generally acceptable yields
and with good stereoselectivities. Most of the electronically poor
aldehydes proved to be suitable substrates in giving the homo-
1,3-DCs with high enantioselectivities (80–93% ee, entries 1–5, 8,
10, and 14–17). Nevertheless, for some of the benzaldehydes
substituted with electron-withdrawing groups, the enantioselec-
tivities were moderate (entries 6, 7, and 9), which indicated that
the electronic nature of the substituents might have an effect on
the enantioselectivity. The position of the substituents also
affected the reactivity and enantioselectivity. For instance,
p-nitrobenzaldehyde 1a exhibited a higher reactivity and enanti-
oselectivity than its meta- or ortho-substituted counterparts
1b,1c (entry 1 vs 2 and 3). Electronically neutral or electron rich
aldehydes 1k,1l could participate in the homo-1,3-DCs with good
yields, but the enantioselectivities were unsatisfactory (entries
10 and 11), which was largely ascribed to the low reactivity of such
aldehydes in 1,3-DCs.8a,c Similarly, heteroaromatic aldehydes as
exemplified by 1m could also take part in the reaction although
the yield and enantioselectivity were not satisfactory (entry 13).
Aliphatic aldehydes such as 3-phenylpropanal could not be utilized
as suitable substrates to afford the homo-1,3-DC products, and just
generated the corresponding azomethine ylide using the current
conditions. Moreover, when dimethyl 2-aminomalonate 2b was
used in the reaction, o-nitrobenzaldehyde 1c showed the highest
capability in terms of enantioselective control (93% ee), albeit
with moderate yield (entry 14). It should be noted that all of the
construct chiral imidazolidines with two stereogenic centers in
high yields (up to 81%) and with good stereoselectivities (all
>20:1 dr, up to 93% ee). This approach also takes advantage of a
pseudo four-component reaction, which forms one ring system,
two stereogenic centers, and four new bonds in a single step.
2. Results and discussion
The initial experiments to test our hypothesis started with a
pseudo four-component reaction of 4-nitrobenzaldehyde 1a and
diethyl 2-aminomalonate 2a in the presence of various BINOL-de-
rived CPAs 4 at 25 °C in chloromethane (Table 1, entries 1–7).
Although these reactions afforded the desired imidazolidine
product 3aa, the yield was rather low, which indicated that the
homo-1,3-DCs of azomethine ylides were challenging because of
the relatively low activity of azomethine ylides acting as dipolaro-
philes. The preliminary screening of catalysts also revealed that
CPAs 4f and 4g could give product 3aa with higher enantioselectiv-
ity than others (entries 6 and 7 vs 1–5). Changing CPA 4f to H8-
BINOL-derived CPA 5a with the same 3,30-substituents of the
BINOL backbone improved the enantioselectivity to 69% ee, but
without any improvement in the yield (entry 8). Recently, SPI-
NOL-derived CPAs have been recognized as a type of chiral
Brønsted acids that possess higher capability in enantioselective
control than their BINOL-based analogues.10 Hence, we changed
the H8-BINOL backbone of catalyst 5a to a SPINOL scaffold and em-
ployed this type of spiro-CPA 6a to the same reaction. As expected,
this structurally more rigid catalyst 6a enabled the model reaction
to proceed in a much more efficient and enantioselective manner,
affording imidazolidine 3aa in 68% yield and 87% ee (entry 9). In
the presence of CPA 6a, the screening of molecular sieves (MS)
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R.-Y. Zhu et al. / Tetrahedron: Asymmetry xxx (2014) xxx–xxx
3
Table 1
Screening of catalysts and MSa
G
G
G
4a, G = 4-ClC6H4
O
O
O
4b, G = 2-naphthyl
O
4c
O
, G = 1-naphthyl
P
O
O
O
4d
P
, G = Ph3Si
OH
P
O
4e
, G = 9-anthracenyl
, G = 9-phenanthrenyl
OH
OH
4f
4g
, G = 2,4,6-(i-Pr)3C6H2
G
G
G
5a, G = 9-phenanthrenyl
6a
, G = 9-phenanthrenyl
NO2
EtO2C
CHO
, 25 oC
4-6
EtO2C
CO2Et
CO2Et
10 mol%
CO2Et
CO2Et
N
H2N
+
2
2
CH2Cl2, MS
N
H
NO2
O2N
1a
2a
MS (Å)
3aa
Entry
4
Yieldb (%)
drc
eed (%)
1
2
3
4
5
6
7
8
9
4a
4b
4c
4d
4e
4f
4g
5a
6a
6a
6a
4
4
4
4
4
4
4
4
4
3
5
31
38
15
—
20
33
33
34
68
34
10
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
43
3
20
—
48
52
65
69
87
53
56
10
11
a
Unless otherwise indicated, the reaction was carried out on a 0.1 mmol scale in CH2Cl2 (1 mL) with MS (100 mg) for 24 h, and the ratio of 1a/2a was 1.2:1.
b
c
Isolated yields.
The diastereomeric ratio (dr) was determined by 1H NMR spectroscopy.
The enantiomeric excess (ee) was determined by HPLC.
d
Table 3
Substrate scope of the catalytic asymmetric homo-1,3-DCsa
R1
Table 2
RO2C
RO2C
Further optimization of reaction conditionsa
CHO
CO2R
CO2R
CO2R
CO2R
N
10 mol% 6a, 40 o
C
NO2
+
H2N
2
2
N
H
CHCl3, 4 Å MS
R1
R1
EtO2C
EtO2C
CHO
1
3
2
Entry
3
R1
1
R 2
Yieldb (%)
drc
eed (%)
CO2Et
CO2Et
CO2Et
N
10 mol% , T oC
solvent, 4 Å MS
6a
H2N
+ 2
2
1
2
3
4
5
6
7
8
9
3aa
3ba
3ca
3da
3ea
3fa
3ga
3ha
3ia
3ja
3ka
3la
3ma
3ab
3bb
3cb
3db
4-NO2 1a
3-NO2 1b
2-NO2 1c
4-CN 1d
Et 2a
Et 2a
Et 2a
Et 2a
Et 2a
Et 2a
Et 2a
Et 2a
Et 2a
Et 2a
Et 2a
Et 2a
Et 2a
Me 2b
Me 2b
Me 2b
Me 2b
76
66
47
81
68
61
36
49
45
51
51
62
38
72
75
45
77
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
91
87
89
85
82
47
44
87
41
87
27
23
37
84
83
93
80
CO2Et
N
H
NO2
1a
O2N
3aa
2a
3-CN 1e
4-CO2Me 1f
4-CF3 1g
4-F 1h
Entry
Solvent
T (°C)
Yieldb (%)
drc
eed (%)
1
2
3
4
5
CH2Cl2
DCE
CHCl3
CCl4
PhCH3
CHCl3
CHCl3
CHCl3
CHCl3
25
25
25
25
25
40
55
40
40
68
69
74
66
35
76
76
76
79
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
87
81
90
66
72
91
86
86
86
2-F 1i
10
11
12
13
14
15
16
17
4-F–3-CN 1j
H 1k
4-MeO 1l
2-Thiophenyl 1m
4-NO2 1a
3-NO2 1b
2-NO2 1c
4-CN 1d
6
7
8e
9f
a
Unless otherwise indicated, the reaction was carried out on a 0.1 mmol scale in
a
Unless otherwise indicated, the reaction was carried out on a 0.1 mmol scale in
chloroform (1 mL) at 40 °C with 4 Å MS (100 mg) for 24 h, and the ratio of 1/2 was
a solvent (1 mL) with 4 Å MS (100 mg) for 24 h, and the ratio of 1a/2a was 1.2:1.
b
Isolated yields.
c
The diastereomeric ratio (dr) was determined by 1H NMR.
1.2:1.
b
d
Isolated yields.
The enantiomeric excess (ee) was determined by HPLC.
Catalyzed by 15 mol % 6a.
Catalyzed by 20 mol % 6a.
The diastereomeric ratio (dr) was determined by 1H NMR.
The enantiomeric excess (ee) was determined by HPLC.
c
e
d
f
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R.-Y. Zhu et al. / Tetrahedron: Asymmetry xxx (2014) xxx–xxx
CN
EtO2C
EtO2C
5
CO2Et
CO2Et
4
3
1 N
N
2
H
NC
3da
(2S,5R)-
Figure 2. The absolute configuration of imidazolidine 3da.
CO2R
N
R1
RO2C
H
EtO2C
EtO2C
R1
O
O
R1
O
O
CO2Et
CO2Et
N
P
CO2Et
N
N
H
CO2Et
R1
H
6a
(2S,5R)-3
Scheme 2. Possible reaction pathway and transition state.
reactions proceeded in a highly diastereoselective manner with
more than 20:1 dr due to the fact that only one diastereomer could
be observed in the reaction.
The absolute configuration of compound 3da was unambigu-
ously determined to be (2S,5R) by single-crystal X-ray diffraction
analysis (Fig. 2).11 Moreover, the relative configuration of com-
pound 3da was also confirmed to be cis by its X-ray structure.
The relative and absolute configurations of other imidazolidines
3 were assigned by analogy.
Based on our experimental results and previous studies on the
reaction mechanism,3a,7,12 we propose a possible reaction pathway
and transition state to explain the stereochemistry of this catalytic
asymmetric homo-1,3-DCs of azomethine ylides. As illustrated in
Scheme 2, CPA 6a acted as a Brønsted acid/Lewis base bifunctional
catalyst to simultaneously activate both the azomethine ylide and
the aldimine via hydrogen bonding interactions, which facilitated
subsequent [3+2] cycloadditions. Due to the chiral environment
created by the (R)-SPINOL backbone and the bulky 6,60-(9-phen-
anthrenyl)-substitutents of catalyst 6a, the homo-1,3-DCs of the
azomethine ylides occurred in a diastereo- and enantioselective
mode, leading to the generation of the experimentally observed
(2S,5R)-configured imidazolidines 3.
structurally rigid SPINOL-derived CPA as the organocatalyst,
resulting in the stereoselective construction of a chiral imidazoli-
dine scaffold with two stereogenic centers in generally high yields
and with good stereoselectivities (up to 81% yield, all >20:1 dr, up
to 93% ee). This protocol takes advantage of a pseudo four-compo-
nent reaction, leading to the formation of one ring system, two
stereogenic centers, and four new bonds in a single step. There-
fore, this study will not only enrich the chemistry of catalytic
asymmetric 1,3-DCs of azomethine ylides, but also provide an
easy access to synthetically and pharmaceutically important chiral
imidazolidines.
4. Experimental
4.1. General
NMR spectra were measured respectively at 400 and 100 MHz.
The solvent used for NMR spectroscopy was CDCl3, using
tetramethylsilane as the internal reference. HRMS spectra were
recorded on a LTQ-Orbitrap mass spectrometer. Enantiomeric ex-
cess (ee) was determined by chiral high-performance liquid chro-
matography (chiral HPLC). The chiral columns used for
determination of the enantiomeric excess by chiral HPLC were
Chiralpak OD-H, IA, and IC columns. Optical rotation values were
measured with instruments operating at k = 589 nm, correspond-
ing to the sodium D line at the temperatures indicated. Analytical
grade solvents for column chromatography and commercially
available reagents were used as received.
3. Conclusion
In conclusion, we have established the first catalytic asymmet-
ric homo-1,3-DCs of azomethine ylides generated in situ
from aldehydes and 2-aminomalonates. This approach utilized a
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R.-Y. Zhu et al. / Tetrahedron: Asymmetry xxx (2014) xxx–xxx
5
4.2. General procedure for the catalytic asymmetric synthesis of
imidazolidines 3
3.57–3.48 (m, 1H), 1.41 (t, J = 7.1 Hz, 3H), 1.22 (t, J = 7.1 Hz, 3H),
1.05 (t, J = 7.1 Hz, 3H), 0.85 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz,
CDCl3) d 168.9, 167.7, 166.1, 165.9, 140.4, 139.4, 133.1, 132.8,
132.2, 131.8, 129.7, 129.0, 112.8, 112.1, 67.1, 62.7, 62.6, 61.8,
61.7, 61.6, 13.9, 13.8, 13.7, 13.4; IR (KBr): 3235, 2990, 1738,
1629, 1540, 1379, 1200, 1006, 866, 745 cmꢁ1; ESI FTMS exact mass
calcd for (C28H32N4O12ꢁH)ꢁ requires m/z 615.1939, found m/z
615.1959; enantiomeric excess: 89%, determined by HPLC (Daicel
Chiralpak IA, hexane/isopropanol = 70:30, flow rate 1.0 mL/min,
T = 30 °C, 254 nm): tR = 7.507 min (major), tR = 6.713 min (minor).
To a solution of aldehyde 1 (0.24 mmol), catalyst 6a (0.01 mmol),
and 4 Å molecular sieves (100 mg) in chloroform (1 mL), amino-es-
ter 2 (0.2 mmol) was added and then stirred at 40 °C for 24 h. The
reaction mixture was then filtered to remove molecular sieves and
the solid powder was washed with ethyl acetate. The resultant
solution was concentrated under the reduced pressure to give the
residue, which was purified by flash column chromatography on sil-
ica gel to afford pure product 3.
4.3.4. (2S,5R)-Diethyl-2,5-bis(4-cyanophenyl)-1-(1,3-diethoxy-1,
3-dioxopropan-2-yl)imidazolidine-4,4-dicarboxylate 3da
(Flash column chromatography eluent, petroleum ether/ethyl
acetate = 6:1); reaction time = 24 h; yield = 81%; >20:1 dr; colorless
4.3. Characterization of compounds 3
4.3.1. (2S,5R)-Diethyl-1-(1,3-diethoxy-1,3-dioxopropan-2-yl)-2,
5-bis(4-nitrophenyl)imidazolidine-4,4-dicarboxylate 3aa
(Flash column chromatography eluent, petroleum ether/ethyl
acetate = 6:1); reaction time = 24 h; yield = 76%; >20:1 dr; colorless
solid; ½a 2D0
ꢀ
= ꢁ29 (c 0.24, CHCl3); 1H NMR (400 MHz, CDCl3) d 7.83 (d,
J = 8.2 Hz, 2H), 7.76 (d, J = 8.1 Hz, 2H), 7.71–7.62 (m, 4H), 5.69 (s, 1H),
5.37 (d, J = 7.0 Hz, 1H), 4.46–4.38 (m, 1H), 4.36–4.27 (m, 1H), 3.99 (s,
1H), 3.93–3.91 (m, 1H), 3.90–3.84 (m, 1H), 3.83–3.79 (m, 1H), 3.79–
3.73 (m, 2H), 3.54 (d, J = 8.7 Hz, 1H), 3.41–3.36 (m, 1H), 1.33 (t,
J = 5.7 Hz, 3H), 1.16 (t, J = 7.2 Hz, 3H), 1.09 (t, J = 7.1 Hz, 3H), 0.85
(t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) d 168.9, 167.6, 166.1,
165.9, 144.4, 143.0, 132.5, 131.7, 129.1, 118.5, 118.4, 113.3, 111.9,
67.4, 62.7, 62.6, 62.0, 61.6, 61.5, 55.0, 13.9, 13.8, 13.7, 13.4; IR
(KBr): 3235, 2963, 1737, 1637, 1617, 1384, 1326, 1261, 1098,
1019, 803, 617 cmꢁ1; ESI FTMS exact mass calcd for (C30H32N4O8-
ꢁH)ꢁ requires m/z 575.2143, found m/z 575.2093; enantiomeric ex-
cess: 85%, determined by HPLC (Daicel Chirapak IC, hexane/
isopropanol = 70:30, flow rate 1.0 mL/min, T = 30 °C, 254 nm):
tR = 25.700 min (major), tR = 21.570 min (minor).
solid; ½a 2D0
ꢀ
= ꢁ7 (c 0.33, CHCl3); 1H NMR (400 MHz, CDCl3) d 7.64 (d,
J = 8.3 Hz, 2H), 7.50 (d, J = 8.0 Hz, 2H), 7.41 (d, J = 8.3 Hz, 2H), 7.31 (d,
J = 8.3 Hz, 2H), 5.59 (s, 1H), 5.29 (d, J = 7.6 Hz, 1H), 4.46–4.28 (m, 1H),
4.26–4.08(m, 1H), 4.02 (s, 1H), 3.96–3.88 (m, 1H), 3.88–3.83(m, 1H),
3.83–3.79 (m, 1H), 3.79–3.73 (m, 2H), 3.53 (d, J = 8.1 Hz, 1H), 3.44–
3.28 (m, 1H), 1.30 (t, J = 7.1 Hz, 3H), 1.15 (t, J = 7.1 Hz, 3H), 1.10
(t, J = 7.1 Hz, 3H), 0.86 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 168.9, 167.5, 166.0, 165.8, 148.6, 147.7, 146.4, 144.9, 129.3, 123.9,
123.0, 67.3, 62.8, 62.6, 62.0, 61.72, 61.6, 13.9, 13.8, 13.7, 13.4; IR
(KBr): 3273, 2985, 1734, 1629, 1523, 1385, 855, 747 cmꢁ1; ESI FTMS
exact mass calcd for (C28H32N4O12ꢁH)ꢁ requires m/z 615.1939,
found m/z 615.1917; enantiomeric excess: 91%, determined by HPLC
(Daicel Chiralpak OD-H, hexane/isopropanol = 80:20, flow rate
1.0 mL/min, T = 30 °C, 254 nm): tR = 9.410 min (major), tR = 7.793 -
min (minor).
4.3.5. (2S,5R)-Diethyl-2,5-bis(3-cyanophenyl)-1-(1,3-diethoxy-1,
3-dioxopropan-2-yl)imidazolidine-4,4-dicarboxylate 3ea
(Flash column chromatography eluent, petroleum ether/ethyl
acetate = 6:1); reaction time = 24 h; yield = 68%; > 20:1 dr; colorless
4.3.2. (2S,5R)-Diethyl-1-(1,3-diethoxy-1,3-dioxopropan-2-yl)-2,
5-bis(3-nitrophenyl)imidazolidine-4,4-dicarboxylate 3ba
(Flash column chromatography eluent, petroleum ether/ethyl
acetate = 6:1); reaction time = 24 h; yield = 66%; >20:1 dr; colorless
sticky oil; ½a 2D0
ꢀ
= +36 (c 0.39, CHCl3); 1H NMR (400 MHz, CDCl3) d
7.98 (d, J = 6.8 Hz, 2H), 7.85 (d, J = 7.5 Hz, 2H), 7.73 (d, J = 7.6 Hz,
1H), 7.61 (d, J = 7.4 Hz, 2H), 7.50 (t, J = 7.8 Hz, 1H), 5.65 (s, 1H),
5.36 (s, 1H), 4.51 (s, 1H), 4.48–4.42 (m, 1H), 4.27–4.22 (m, 1H),
3.99 (s, 1H), 3.93–3.72 (m, 5H), 3.48–3.41 (m, 1H), 1.33 (t,
J = 6.9 Hz, 3H), 1.19 (t, J = 7.1 Hz, 3H), 1.13 (t, J = 7.1 Hz, 3H), 0.86
(t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) d 168.9, 167.7, 166.1,
165.9, 140.4, 139.4, 133.1, 132.8, 132.2, 131.8, 129.7, 129.0, 118.4,
118.4, 112.8, 112.1, 67.1, 62.7, 62.6, 61.8, 61.7, 61.6, 13.9, 13.8,
13.7, 13.4; IR (KBr): 3230, 2988, 1736, 1629, 1504, 1285, 1100,
1007, 995, 747 cmꢁ1; ESI FTMS exact mass calcd for (C30H32N4O8+-
Na)+ requires m/z 599.2118, found m/z 599.2111; enantiomeric ex-
cess: 82%, determined by HPLC (Daicel Chirapak IC, hexane/
isopropanol = 70:30, flow rate 1.0 mL/min, T = 30 °C, 254 nm):
tR = 7.827 min (major), tR = 4.887 min (minor).
sticky oil; ½a 2D0
ꢀ
= +27 (c 0.36, CHCl3); 1H NMR (400 MHz, CDCl3) d
8.59 (s, 1H), 8.44 (s, 1H), 8.30 (t, J = 8.9 Hz, 1H), 8.19 (d, J = 7.8 Hz,
1H), 8.12 (d, J = 7.6 Hz, 1H), 7.96 (d, J = 7.6 Hz, 1H), 7.69 (t,
J = 7.9 Hz, 1H), 7.62–7.52 (m, 1H), 5.75 (s, 1H), 5.45 (d, J = 9.7 Hz,
1H), 4.49–4.44 (m, 1H), 4.41–4.27 (m, 1H), 4.06 (s, 1H), 4.01–3.98
(m, 1H), 3.95–3.87 (m, 1H), 3.86–3.77 (m, 2H), 3.77–3.68 (m, 1H),
3.58 (d, J = 9.8 Hz, 1H), 3.46–3.38 (m, 1H), 1.36 (t, J = 7.1 Hz, 3H),
1.19 (t, J = 7.1 Hz, 3H), 1.10 (t, J = 7.1 Hz, 3H), 0.85 (t, J = 7.1 Hz,
3H); 13C NMR (100 MHz, CDCl3) d 168.8, 167.3, 166.1, 165.9, 148.4,
147.9, 141.3, 140.2, 134.6, 134.4, 129.9, 129.0, 124.4, 123.6, 123.5,
123.1, 67.1, 62.8, 62.6, 61.9, 61.7, 61.7, 14.0, 13.8, 13.6, 13.3; IR
(KBr): 3255, 2963, 1737, 1629, 1532, 1388, 1008, 869, 747 cmꢁ1
;
ESI FTMS exact mass calcd for (C28H32N4O12ꢁH)ꢁ requires m/z
615.1939, found m/z 615.1873; enantiomeric excess: 87%, deter-
mined by HPLC (Daicel Chirapak IA, hexane/isopropanol = 70:30,
flow rate 1.0 mL/min, T = 30 °C, 254 nm): tR = 8.200 min (major),
tR = 5.800 min (minor).
4.3.6. (2S,5R)-Diethyl-1-(1,3-diethoxy-1,3-dioxopropan-2-yl)-2,
5-bis(4-(methoxycarbonyl)phenyl)imidazolidine-4,4-dicarbox-
ylate 3fa
(Flash column chromatography eluent, petroleum ether/ethyl
acetate = 6:1); reaction time = 24 h; yield = 61%; >20:1 dr;
4.3.3. (2S,5R)-Diethyl-1-(1,3-diethoxy-1,3-dioxopropan-2-yl)-2,
5-bis(2-nitrophenyl)imidazolidine-4,4-dicarboxylate 3ca
(Flash column chromatography eluent, petroleum ether/ethyl
acetate = 6:1); reaction time = 24 h; yield = 47%; >20:1 dr; color-
colorless sticky oil;
½
a 2D0
ꢀ
= ꢁ15 (c 0.27, CHCl3); 1H NMR
(400 MHz, CDCl3) d 8.12 (d, J = 8.1 Hz, 2H), 8.01 (d, J = 8.2 Hz, 2H),
7.79 (d, J = 8.1 Hz, 2H), 7.64 (d, J = 7.7 Hz, 2H), 5.71 (s, 1H), 5.36
(d, J = 8.8 Hz, 1H), 4.47–4.39 (m, 1H), 4.37–4.23 (m, 1H), 4.02 (s,
1H), 3.96 (s, 3H), 3.93 (s, 3H), 3.91–3.80 (m, 2H), 3.79–3.73 (m,
1H), 3.69 (q, J = 7.1 Hz, 2H), 3.61 (d, J = 9.3 Hz, 1H), 3.34–3.13 (m,
1H), 1.32 (t, J = 7.1 Hz, 3H), 1.15 (t, J = 7.1 Hz, 3H), 1.06 (t,
J = 7.1 Hz, 3H), 0.82 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 169.1, 167.8, 166.8, 166.7, 166.3, 166.1, 144.3, 142.8, 131.1,
129.9, 129.8, 129.1, 128.4, 67.4, 62.5, 62.4, 62.0, 61.4, 61.3, 352.2,
less sticky oil; ½a D20
ꢀ
= ꢁ109 (c 0.24, CHCl3); 1H NMR (400 MHz,
CDCl3) d 8.25 (d, J = 7.7 Hz, 1H), 8.17 (d, J = 8.0 Hz, 1H), 7.99 (d,
J = 8.1 Hz, 1H), 7.86 (d, J = 7.9 Hz, 1H), 7.75 (t, J = 7.6 Hz, 1H), 7.62
(t, J = 7.5 Hz, 1H), 7.56 (t, J = 7.6 Hz, 1H), 7.44 (t, J = 7.6 Hz, 1H),
6.36 (s, 1H), 5.72 (d, J = 5.8 Hz, 1H), 4.47–4.38 (m, 2H), 4.37–4.22
(m, 2H), 4.20 (s, 1H), 4.08–4.03 (m, 1H), 3.86–3.74 (m, 3H),
Please cite this article in press as: Zhu, R.-Y.; et al. Tetrahedron: Asymmetry (2014), http://dx.doi.org/10.1016/j.tetasy.2014.03.008

6
R.-Y. Zhu et al. / Tetrahedron: Asymmetry xxx (2014) xxx–xxx
52.1, 13.9, 13.8, 13.7, 13.3; IR (KBr): 3238, 2996, 1733, 1630, 1614,
1390, 1318, 1044, 868, 747 cmꢁ1; ESI FTMS exact mass calcd for
(C32H38N2O12+Na)+ requires m/z 665.2317, found m/z 665.2355;
enantiomeric excess: 47%, determined by HPLC (Daicel Chirapak
IC, hexane/isopropanol = 70:30, flow rate 1.0 mL/min, T = 30 °C,
254 nm): tR = 15.263 min (major), tR = 13.583 min (minor).
enantiomeric excess: 41%, determined by HPLC (Daicel Chirapak
IC, hexane/isopropanol = 70:30, flow rate 1.0 mL/min, T = 30 °C,
254 nm): tR = 8.103 min (major), tR = 7.433 min (minor).
4.3.10. (2S,5R)-Diethyl-2,5-bis(3-cyano-4-fluorophenyl)-1-(1,3-
diethoxy-1,3-dioxopropan-2-yl)imidazolidine-4,4-dicarboxyl-
ate 3ja
4.3.7. (2S,5R)-Diethyl-1-(1,3-diethoxy-1,3-dioxopropan-2-yl)-2,
5-bis(4-(trifluoromethyl)phenyl)imidazolidine-4,4-dicarbo
xylate 3ga
(Flash column chromatography eluent, petroleum ether/ethyl
acetate = 6:1); reaction time = 24 h; yield = 51%; >20:1 dr; color-
less sticky oil; ½a D20
ꢀ
= +21 (c 0.11, CHCl3); 1H NMR (400 MHz, CDCl3)
(Flash column chromatography eluent, petroleum ether/ethyl
acetate = 6:1); reaction time = 24 h; yield = 36%; >20:1 dr; color-
d 8.26–8.08 (m, 1H), 8.04–7.90 (m, 1H), 7.87–7.74 (m, 1H), 7.45 (t,
J = 8.4 Hz, 1H), 7.41–7.30 (m, 1H), 7.27–7.18 (m, 1H), 5.58 (s, 1H),
5.33 (d, J = 5.3 Hz, 1H), 4.53–4.40 (m, 1H), 4.29–4.19 (m, 4H),
3.96–3.83 (m, 2H), 3.82–3.71 (m, 1H), 3.60–3.49 (m, 1H), 3.47–
3.40 (m, 1H), 1.29 (t, J = 7.1, 3H), 1.21 (t, J = 7.1, 3H), 1.16 (t,
J = 7.1 Hz, 3H), 0.92 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 168.8, 167.7, 165.8, 161.5, 135.6, 135.2, 135.1, 133.7, 132.3,
117.1, 116.9, 116.3, 113.5, 101.7, 101.2, 97.4, 93.7, 90.4, 66.5,
62.8, 62.4, 62.0, 61.8, 6, 58.4, 55.0, 18.4, 14.5, 13.9, 13.8, 13.5; IR
(KBr): 3316, 2965, 1738, 1630, 1585, 1500, 1447, 1260, 1095,
1027, 948 cmꢁ1; ESI FTMS exact mass calcd for (C30H30F2N4O8+
Na)+ requires m/z 635.1930, found m/z 635.1960; enantiomeric ex-
cess: 87%, determined by HPLC (Daicel Chirapak IC, hexane/isopro-
panol = 80:20, flow rate 1.0 mL/min, T = 30 °C, 254 nm):
tR = 13.420 min (major), tR = 14.597 min (minor).
less sticky oil; ½a D20
ꢀ
= ꢁ13 (c 0.21, CHCl3); 1H NMR (400 MHz,
CDCl3) d 7.85 (d, J = 8.0 Hz, 2H), 7.75–7.68 (m, 4H), 7.61 (d,
J = 8.1 Hz, 2H), 5.71 (s, 1H), 5.40 (d, J = 9.5 Hz, 1H), 4.47–4.39 (m,
1H), 4.37–4.27 (m, 1H), 4.03 (s, 1H), 3.95–3.86 (m, 1H), 3.85–
3.81 (m, 1H), 3.80–3.69 (m, 3H), 3.59 (d, J = 10.0 Hz, 1H), 3.40–
3.29 (m, 1H), 1.32 (t, J = 7.2 Hz, 3H), 1.14 (t, J = 7.1 Hz, 3H), 1.07
(t, J = 6.4 Hz, 3H), 0.79 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 169.1, 167.9, 166.3, 166.1, 143.0, 141.9, 131.7, 131.4, 130.5,
130.2, 129.1, 128.9, 125.6, 125.6, 125.3, 125.2, 124.8, 124.8,
122.6, 122.5, 67.4, 62.5, 62.0, 61.4, 58.4, 55.0, 53.4, 13.9, 13.7,
13.6, 13.1; IR (KBr): 3274, 2986, 1733, 1630, 1617, 1384, 1318,
1047, 868, 717 cmꢁ1; ESI FTMS exact mass calcd for (C30H32F6N2-
O8+Na)+ requires m/z 685.1955, found m/z 685.1993; enantiomeric
excess: 44%, determined by HPLC (Daicel Chirapak IA, hexane/iso-
propanol = 70:30, flow rate 1.0 mL/min, T = 30 °C, 254 nm):
tR = 5.683 min (major), tR = 4.537 min (minor).
4.3.11. (2S,5R)-Diethyl-1-(1,3-diethoxy-1,3-dioxopropan-2-yl)-2,
5-diphenylimidazolidine-4,4-dicarboxylate 3ka
(Flash column chromatography eluent, petroleum ether/ethyl
acetate = 6:1); reaction time = 24 h; yield = 51%; >20:1 dr; color-
4.3.8. (2S,5R)-Diethyl-1-(1,3-diethoxy-1,3-dioxopropan-2-yl)-2,
5-bis(4-fluorophenyl)imidazolidine-4,4-dicarboxylate 3ha
(Flash column chromatography eluent, petroleum ether/ethyl
acetate = 6:1); reaction time = 24 h; yield = 49%; >20:1 dr; color-
less sticky oil; ½a D20
ꢀ
= +108 (c 0.08, CHCl3); 1H NMR (400 MHz,
CDCl3) d 7.72 (d, J = 7.5 Hz, 2H), 7.57 (d, J = 7.0 Hz, 2H), 7.47–7.38
(m, 3H), 7.32 (t, J = 7.4 Hz, 2H), 7.25 (d, J = 6.9 Hz, 1H), 5.65 (s,
1H), 5.31 (s, 1H), 4.47–4.39 (m, 1H), 4.34–4.22 (m, 1H), 4.09 (s,
1H), 3.94–3.85 (m, 1H), 3.83–3.81 (m, 1H), 3.80–3.72 (m, 1H),
3.73–3.57 (m, 3H), 3.33–3.29 (m, 1H), 1.31 (t, J = 7.1 Hz, 3H), 1.14
(t, J = 7.1 Hz, 3H), 1.07 (t, J = 7.1 Hz, 3H), 0.80 (t, J = 7.1 Hz, 3H);
13C NMR (100 MHz, CDCl3) d 169.5, 168.3, 166.7, 166.6, 138.8,
137.9, 129.2, 128.5, 128.50, 127.9, 127.8, 67.6, 62.2, 62.1, 62.0,
61.1, 55.0, 13.9, 13.8, 13.7, 13.3; IR (KBr): 3236, 2980, 1734,
1629, 1285, 1007, 986, 747 cmꢁ1; ESI FTMS exact mass calcd for
(C28H34N2O8+Na)+ requires m/z 549.2207, found m/z 549.2259;
enantiomeric excess: 27%, determined by HPLC (Daicel Chirapak
IC, hexane/isopropanol = 70:30, flow rate 1.0 mL/min, T = 30 °C,
254 nm): tR = 6.847 min (major), tR = 5.913 min (minor).
less sticky oil; ½a D20
ꢀ
= ꢁ49 (c 0.12, CHCl3); 1H NMR (400 MHz,
CDCl3) d 7.71–7.67 (m, 2H), 7.58–7.51 (m, 2H), 7.12 (t, J = 8.5 Hz,
2H), 7.03 (t, J = 8.4 Hz, 2H), 5.60 (s, 1H), 5.29 (d, J = 9.6 Hz, 1H),
4.46–4.39 (m, 1H), 4.32–4.23 (m, 1H), 4.03 (s, 1H), 3.95–3.88 (m,
1H), 3.87–3.75 (m, 4H), 3.54 (d, J = 10.4 Hz, 1H), 3.48–3.35 (m,
1H), 1.31 (t, J = 4.8 Hz, 3H), 1.15 (t, J = 7.1 Hz, 3H), 1.11 (t,
J = 7.1 Hz, 3H), 0.86 (t, J = 6.9 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 169.4, 168.3, 166.5, 166.4, 134.3, 133.6, 130.2, 115.6, 115.4,
114.9, 114.6, 97.4, 67.0, 62.3, 61.9, 61.3, 61.2, 55.0, 18.4, 13.9,
13.8, 13.7, 13.4; IR (KBr): 3273, 2963, 1734, 1629, 1509, 1370,
1261, 1096, 1021, 801 cmꢁ1; ESI FTMS exact mass calcd for
(C30H32F6N2O8+Na)+ requires m/z 585.2019, found m/z 585.2025;
enantiomeric excess: 87%, determined by HPLC (Daicel Chirapak
IC, hexane/isopropanol = 95:5, flow rate 1.0 mL/min, T = 30 °C,
254 nm): tR = 9.197 min (major), tR = 6.190 min (minor).
4.3.12. (2S,5R)-Diethyl-1-(1,3-diethoxy-1,3-dioxopropan-2-yl)-2,
5-bis(4-methoxyphenyl)imidazolidine-4,4-dicarboxylate 3la
(Flash column chromatography eluent, petroleum ether/ethyl
acetate = 6:1); reaction time = 24 h; yield = 62%; >20:1 dr; color-
4.3.9. (2S,5R)-Diethyl-1-(1,3-diethoxy-1,3-dioxopropan-2-yl)-5-
(2-fluorophenyl)-2-(o-tolyl)imidazolidine-4,4-dicarboxylate 3ia
(Flash column chromatography eluent, petroleum ether/ethyl
acetate = 6:1); reaction time = 24 h; yield = 45%; >20:1 dr; color-
less sticky oil; ½a D20
ꢀ
= +5 (c 0.21, CHCl3); 1H NMR (400 MHz, CDCl3)
d 7.62 (d, J = 8.5 Hz, 2H), 7.47 (d, J = 7.6 Hz, 2H), 6.94 (d, J = 8.5 Hz,
2H), 6.86 (d, J = 8.4 H z, 2H), 5.55 (s, 1H), 5.24 (s, 1H), 4.45–4.39 (m,
1H), 4.33–4.17 (m, 1H), 4.06 (s, 1H), 3.93–3.87 (m, 2H), 3.84 (s, 3H),
3.80 (s, 3H), 3.79–3.71 (m, 3H), 3.55 (s, 1H), 3.40–3.29 (m, 1H), 1.29
(t, J = 7.1 Hz, 3H), 1.14 (t, J = 7.1 Hz, 3H), 1.10 (t, J = 7.1 Hz, 3H), 0.85
(t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) d 169.7, 169.5, 166.4,
162.0, 132.0, 130.7, 130.6, 129.9, 114.3, 113.9, 113.2, 67.0, 62.1,
62.1, 62.0, 61.9, 61.0, 58.5, 55.4, 14.05 13.9, 13.8, 13.7, 13.4; IR
(KBr): 3233, 2984, 1735, 1629, 1509, 1283, 1109, 1007, 994,
747 cmꢁ1; ESI FTMS exact mass calcd for (C30H38N2O10+Na)+ re-
quires m/z 609.2416, found m/z 609.2416; enantiomeric excess:
23%, determined by HPLC (Daicel Chirapak IC, hexane/isopropa-
nol = 70:30, flow rate 1.0 mL/min, T = 30 °C, 254 nm): tR = 11.140 -
min (major), tR = 7.263 min (minor).
less sticky oil; ½a D20
ꢀ
= ꢁ20 (c 0.21, CHCl3); 1H NMR (400 MHz,
CDCl3) d 7.85 (s, 1H), 7.75 (s, 1H), 7.38–7.30 (m, 1H), 7.24–7.16
(m, 2H), 7.12–7.08 (m, 2H), 7.05–6.95 (m, 1H), 6.09 (s, 1H), 5.59
(d, J = 11.0 Hz, 1H), 4.51–4.45 (m, 1H), 4.40–4.24 (m, 1H), 4.10–
3.94 (m, 3H), 3.89–3.56 (m, 4H), 3.44 (s, 1H), 1.34 (t, J = 7.1 Hz,
3H), 1.20 (t, J = 7.1 Hz, 3H), 1.08 (t, J = 7.1 Hz, 3H), 0.89 (t,
J = 6.9 Hz, 3H); 13C NMR (100 MHz, CDCl3) d 168.7, 166.54, 163.3,
160.8, 130.8, 130.7, 129.6, 129.3, 129.0, 124.6, 124.5, 123.7,
115.9, 97.4, 62.4, 62.3, 61.3, 55.0, 53.4, 31.6, 22.6, 14.1, 13.9,
13.8, 13.5, 13.3; IR (KBr): 3275, 2960, 1738, 1632, 1500, 1374,
1260, 1095, 1022, 747 cmꢁ1; ESI FTMS exact mass calcd for (C30
H32F6N2O8+Na)+ requires m/z 585.2019, found m/z 585.1976;
Please cite this article in press as: Zhu, R.-Y.; et al. Tetrahedron: Asymmetry (2014), http://dx.doi.org/10.1016/j.tetasy.2014.03.008

R.-Y. Zhu et al. / Tetrahedron: Asymmetry xxx (2014) xxx–xxx
7
4.3.13. (2S,5S)-Diethyl-1-(1,3-diethoxy-1,3-dioxopropan-2-yl)-
2,5-di(thiophen-2-yl)imidazolidine-4,4-dicarboxylate 3ma
(Flash column chromatography eluent, petroleum ether/ethyl
acetate = 6:1); reaction time = 24 h; yield = 38%; >20:1 dr; colorless
5.68 (s, 1H), 4.24–4.12 (m, 2H), 3.97 (s, 3H), 3.66 (s, 3H), 3.33 (s,
3H), 3.25 (s, 3H); 13C NMR (100 MHz, CDCl3) d 169.5, 167.2,
166.1, 163.0, 148.1, 147.5, 141.4, 139.9, 134.7, 134.1, 130.0,
129.2, 124.8, 123.6, 123.4, 123.0, 67.0, 64.5, 61.8, 53.8, 53.2, 52.5,
52.1; IR (KBr): 3237, 2966, 1735, 1620, 1519, 1384, 1369, 1260,
1099, 808, 767 cmꢁ1; ESI FTMS exact mass calcd for (C24H24N4
O12+Na)+ requires m/z 583.1283, found m/z 583.1245; enantio-
meric excess: 93%, determined by HPLC (Daicel Chirapak IA, hex-
ane/isopropanol = 70:30, flow rate 1.0 mL/min, T = 30 °C,
254 nm): tR = 10.033 min (major), tR = 8.847 min (minor).
sticky oil; ½a 2D0
ꢀ
= ꢁ39 (c 0.20, CHCl3); 1H NMR (400 MHz, CDCl3) d
7.40 (dd, J = 5.0, 0.9 Hz, 1H), 7.32 (dd, J = 3.5, 0.8 Hz, 1H), 7.22 (dd,
J = 5.1, 1.1 Hz, 1H), 7.06 (d, J = 3.1 Hz, 1H), 7.03 (dd, J = 5.0, 3.5 Hz,
1H), 6.95 (dd, J = 5.0, 3.5 Hz, 1H), 5.91 (s, 1H), 5.48 (s, 1H), 4.52–
4.45 (m, 1H), 4.39–4.33 (m, 1H), 4.29 (s, 1H), 4.18–4.09 (m, 1H),
4.08–4.00 (m, 1H), 3.93–3.86 (m, 1H), 3.81–3.74 (m, 2H), 3.72–
3.65 (m, 2H), 1.36 (t, J = 5.8 Hz, 3H), 1.21 (t, J = 7.1 Hz, 3H), 1.09 (t,
J = 7.2 Hz, 3H), 1.01 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) d
168.8, 166.7, 166.6, 166.2, 145.1, 142.5, 127.9, 126.7, 126.6, 126.3,
125.9, 125.0, 74.6, 63.4, 62.4, 61.4, 14.13, 14.0, 13.9, 13.6, 13.5; IR
4.3.17. (2S,5R)-Dimethyl-2,5-bis(4-cyanophenyl)-1-(1,3-dime-
thoxy- 1,3-dioxopropan-2-yl)imidazolidine-4,4-dicarboxylate
3db
(KBr): 3235, 1738, 1625, 1505, 1286, 1111, 1002, 996, 745 cmꢁ1
;
(Flash column chromatography eluent, petroleum ether/ethyl
acetate = 6:1); reaction time = 24 h; yield = 77%; >20:1 dr; color-
ESI FTMS exact mass calcd for (C24H30N2O8S2+Na)+ requires m/z
561.1336, found m/z 561.1332; enantiomeric excess: 37%, deter-
mined by HPLC (Daicel Chirapak AD-H, hexane/isopropanol = 70:30,
flow rate 1.0 mL/min, T = 30 °C, 254 nm): tR = 4.723 min (major),
tR = 4.107 min (minor).
less sticky oil; ½a D20
ꢀ
= +17 (c 0.39, CHCl3); 1H NMR (400 MHz, CDCl3)
d 7.82 (d, J = 8.0 Hz, 2H), 7.77 (d, J = 8.0 Hz, 2H), 7.65 (d, J = 8.8 Hz,
4H), 5.67 (s, 1H), 5.35 (s, 1H), 4.04 (d, J = 5.5 Hz, 2H), 3.92 (s, 3H),
3.52 (s, 3H), 3.33 (s, 3H), 3.17 (s, 3H); 13C NMR (100 MHz, CDCl3)
d 169.3, 167.8, 166.5, 166.2, 144.2, 142.7, 132.9, 132.7, 131.7,
129.9, 129.2, 129.0, 118.4, 118.3, 113.4, 112.0, 97.4, 67.5, 61.6,
55.0, 53.8, 53.1, 52.4, 52.2; IR (KBr): 3269, 2989, 1733, 1629,
1556, 1384, 1436, 1021, 996, 808, 760 cmꢁ1; ESI FTMS exact mass
calcd for (C26H24N4O8+Na)+ requires m/z 543.1486, found m/z
543.1478; enantiomeric excess: 80%, determined by HPLC (Daicel
Chirapak IC, hexane/isopropanol = 70:30, flow rate 1.0 mL/min,
T = 30 °C, 254 nm): tR = 40.620 min (major), tR = 34.337 min
(minor).
4.3.14. (2S,5R)-Dimethyl-1-(1,3-dimethoxy-1,3-dioxopropan-2-
yl)-2,5-bis(4-nitrophenyl)imidazolidine-4,4-dicarboxylate 3ab
(Flash column chromatography eluent, petroleum ether/ethyl
acetate = 6:1); reaction time = 24 h; yield = 72%; >20:1 dr; colorless
sticky oil; ½a 2D0
ꢀ
= ꢁ34 (c 0.43, CHCl3); 1H NMR (400 MHz, CDCl3) d
8.35 (d, J = 8.4 Hz, 2H), 8.24 (d, J = 8.4 Hz, 2H), 7.90 (d, J = 8.4 Hz,
2H), 7.73 (d, J = 8.3 Hz, 2H), 5.74 (s, 1H), 5.42 (s, 1H), 4.13–4.00 (m,
2H), 3.95 (s, 3H), 3.55 (s, 3H), 3.34 (s, 3H), 3.20 (s, 3H); 13C NMR
(100 MHz, CDCl3) d 169.3, 167.6, 166.5, 166.2, 148.7, 147.7, 146.2,
144.5, 129.3, 124.0, 123.1, 67.3, 61.7, 53.9, 53.4, 53.1, 52.5, 52.3; IR
(KBr): 3233, 2956, 1740, 1637, 1615, 1519, 1439, 1349, 1216,
Acknowledgments
1093, 796, 747 cmꢁ1; ESI FTMS exact mass calcd for (C24H24N4O12
+
We are grateful for financial support from National Natural
Science Foundation of China (21372002 and 21232007), Open
Foundation of Jiangsu Key Laboratory of Green Synthetic Chemistry
for Functional Materials (K201314), Graduate Students Foundation
of Jiangsu Normal University (2013YYB123), and Undergraduate
Students Foundation of School of Chemistry and Chemical
Engineering (HXKY2013C002).
Na)+ requires m/z 583.1283, found m/z 583.1305; enantiomeric ex-
cess: 84%, determined by HPLC (Daicel Chirapak IC, hexane/isopro-
panol = 70:30, flow rate 1.0 mL/min, T = 30 °C, 254 nm):
tR = 28.860 min (major), tR = 23.523 min (minor).
4.3.15. (2S,5R)-Dimethyl-1-(1,3-dimethoxy-1,3-dioxopropan-2-
yl)-2,5-bis(3-nitrophenyl)imidazolidine-4,4-dicarboxylate 3bb
(Flash column chromatography eluent, petroleum ether/ethyl
acetate = 6:1); reaction time = 24 h; yield = 75%; >20:1 dr; color-
References
less sticky oil; ½a D20
ꢀ
= ꢁ63 (c 0.42, CHCl3); 1H NMR (400 MHz,
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less sticky oil; ½a D20
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= ꢁ48 (c 0.19, CHCl3); 1H NMR (400 MHz,
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