Squaramide-catalysed enantionselective Mannich reaction of imines bearing a heterocycle with malonates

Article abstract of DOI:10.1039/c3ra43260b

An efficient enantioselective Mannich reaction of imines bearing a heterocycle with malonates catalysed by a cinchona-based squaramide organocatalyst has been developed. This catalytic asymmetric reaction afforded the β-amino ester derivatives containing

Full text of DOI:10.1039/c3ra43260b

RSC Advances
View Article Online
View Journal | View Issue
PAPER
Squaramide-catalysed enantionselective Mannich
reaction of imines bearing a heterocycle with
Cite this: RSC Advances, 2013, 3,
1
6349
malonates3
Hai-Xiao He and Da-Ming Du*
An efficient enantioselective Mannich reaction of imines bearing a heterocycle with malonates catalysed
by a cinchona-based squaramide organocatalyst has been developed. This catalytic asymmetric reaction
afforded the b-amino ester derivatives containing a heterocycle moiety in high yields (up to 99%) and
excellent enantioselectivities (up to 98%) in most cases. The imines with an electron-withdrawing group
afforded the adducts with better yields than those bearing an electron-donating group in this reaction.
Received 6th May 2013,
Accepted 4th July 2013
DOI: 10.1039/c3ra43260b
www.rsc.org/advances
These approaches provide valuable synthetic methods for
amino acid esters and related b-amino carbonyl derivatives.
Introduction
Mannich reactions are important fundamental reactions for
the construction b-amino carbonyl derivatives, which involve
the nucleophilic addition of enolates to the CLN double bond
Although various catalysts and substrates have been
reported in Mannich reactions, there are only a few reports
about the utilization of heteroaromatic primary amine derived
imines or imines containing heterocyclic amino counterparts.
Recently, Song et al. reported an imine bearing a benzothiazole
1
of imines and related compounds. In recent years, many
studies on the catalytic asymmetric Mannich reaction have
2
–4
been reported. In metal-catalysed reactions, Jørgensen et al.
reported that malonates react with an activated N-tosyl-
a-imino ester catalysed by chiral tert-butyl-bisoxazoline/
10
catalysed by cinchona alkaloid thiourea. The one-pot three-
component enantioselective Mannich reaction using 2-amino-
5
-chloro-benzoxazol, benzaldehyde, and diethyl malonate was
Cu(OTf) to give the adducts in high yields and with up to
11
2
also developed. Despite these cinchona alkaloid thiourea
catalysts have been successfully reported in Mannich reac-
tions, the reaction of malonates with heteroaromatic imines
3
a
9
6% ee. Deng et al. reported the enantioselective synthesis of
b-amino acid through the Mannich reaction of malonates with
2
simple imines catalysed by cinchona alkaloid thiourea
bearing a heterocycle such as benzothiazole and isoxazole
catalysed by squaramide organocatalyst has not been
5
catalysts. Subsequently, these catalysts have been successfully
applied in the Mannich reaction with in situ generation of
carbamate-protected imines from stable a-amido sulfones and
it provided a concise and highly enantioselective route
converting aromatic and aliphatic aldehydes into optically
12
reported. In recent years, chiral squaramides have been
13,14
successfully applied in various asymmetric reactions.
Our
group also reported an efficient enantioselective aza-Henry
reaction of nitroalkanes to imines bearing a benzothiazole
6
active aryl and alkyl a-amino acids. Ricci et al. also reported
15
moiety catalysed by a cinchona-based squaramide. It is well
an organocatalytic asymmetric Mannich reaction with N-Boc
and N-Cbz protected a-amido sulfones by phase-transfer
catalysis which proceeds under very mild and user-friendly
known that benzothiazole and their derivatives represent an
important class of compounds possessing a variety of
biological activities. Several compounds containing a ben-
zothiazole ring system exhibit significant antitumour, anti-
microbial, antidiabetic, anti-inflammatory, anticonvulsant,
antiviral, antioxidant, antitubercular, antimalarial, antiasth-
7
conditions. Lu et al. developed a tryptophan-derived bifunc-
tional thiourea catalyst and used it in an asymmetric Mannich
reaction of fluorinated ketoesters with an N-Boc protected
8
imine. Nagasawa et al. also reported a solvent-dependent
16
matic, anthelmintic, diuretic, and analgesic activities.
enantiodivergent Mannich-type reaction which uses a con-
Herein, we report an efficient direct enantioselective
Mannich reaction of imines bearing a heterocycle with
malonates catalysed by a cinchona-based squaramide organo-
catalyst, and chiral b-amino ester derivatives containing
benzothiazole or isoxazole units can be obtained with excellent
enantioselectivities (up to 98% ee).
9
formationally flexible guanidine/bisthiourea organocatalyst.
School of Chemical Engineering and Environment, Beijing Institute of Technology,
Beijing 100081, People’s Republic of China. E-mail: dudm@bit.edu.cn; Tel: +86 10
6
8914985
Electronic supplementary information (ESI) available: Copies of H and
1
13
3
C
NMR spectra of new compounds, and HPLC chromatograms. See DOI: 10.1039/
c3ra43260b
This journal is ß The Royal Society of Chemistry 2013
RSC Adv., 2013, 3, 16349–16358 | 16349

View Article Online
Paper
RSC Advances
Table 1 Screening of substrate for the Mannich reaction of imine 1a bearing a
Table 2 Screening of organocatalysts for the enantioselective Mannich reaction
a
a
benzothiazole and malonates
of dibenzyl malonate 2d with imine 1a
b
c
Entry
Catalyst
Time (h)
Yield (%)
ee (%)
1
2
3
4
5
6
7
8
9
I
II
24
24
24
24
24
24
24
24
24
24
24
99
92
97
93
99
91
90
38
99
99
99
94
86
76
d
III
IV
V
VI
VII
VIII
IX
X
1
2
b
c
55
63
84
94
0
99
91
92
Entry
R
R
Time (h) Product Yield (%) ee (%)
1
2
3
4
5
6
7
8
Me
Et
iPr
Bn
Et
Et
Et
H
H
H
H
24
48
48
24
24
48
3aa
3ab
3ac
3ad
3ae
3af
99
91
59
99
90
25
—
—
92
92
89
96
95
20
—
—
1
1
0
1
NH
Et
NHAc 48
Ph 48
2
XI
3ag
3ah
a
Unless noted otherwise, reactions were carried out with imine 1a
Cl
2
Et
(47.6 mg, 0.2 mmol) and dibenzyl malonate 2d (0.6 mmol) in CH
2
b
a
(2 mL) at room temperature. Isolated yield after column
chromatography purification. Determined by chiral HPLC analysis
using Daicel Chiralpak IB column. Opposite enantiomer.
Unless noted otherwise, reactions were carried out with imine 1a
Cl (2
c
(
47.6 mg, 0.2 mmol) and malonates 2a–h (0.6 mmol) in CH
2
2
d
b
mL) at room temperature. Isolated yield after column
chromatography purification. Determined by chiral HPLC analysis
using Daicel Chiralpak IA, IB or AS-H column.
c
lower enantioselectivity (92% yield, 86% ee) was obtained
Table 2, entry 2). Cinchonine-based catalyst III gave the
product with opposite configuration in excellent yield (97%)
with 76% ee (Table 2, entry 3). When C -symmetric quinine- or
hydroquinine-based squaramide catalyst IV or V was used,
high yields (93% and 99% yield) were obtained, but the
enantioselectivities were very low (55% and 63% ee) (Table 2,
entries 4 and 5). Squaramide VI–VIII derived from (1S,2S)-1,2-
diaminoyclohexane were screened to explore the steric effects.
Catalyst VII gave the same enantioselectivity as catalyst I in
(
Results and discussion
2
Firstly, imine 1a bearing a benzothiazole moiety was used as a
model substrate. A series of malonates were evaluated in the
presence of 10 mol% catalyst I for 24 h at room temperature in
2 2
CH Cl . Dimethyl and diethyl malonate gave the same
excellent enantioselectivity (92% ee), but the former afforded
the corresponding product 3aa in 99% yield, which is better
than the yield of 3ab (91%) (Table 1, entries 1 and 2).
Diisopropyl malonate afforded the corresponding product 3ac
with moderate enantioselectivity and yield (89% ee and 59%
yield) (Table 1, entry 3). When the dibenzyl malonate and
diethyl 2-aminomalonate were used, products 3ad and 3ae
were obtained in high yields with excellent enantioselectivities
90% yield. When catalyst VI bearing a piperidinyl was used, no
better result was observed (Table 2, entry 6). Squaramide VIII
is a newly developed catalyst and afforded the desired product
only in 38% yield (Table 2, entry 8). As a comparison, the
classical thiourea catalyst IX–XI were also evaluated in this
reaction and these thioureas also afforded high to excellent
enantioselectivities (Table 2, entries 9–11). But considering
(99% and 90% yield, 96% and 95% ee, respectively) (Table 2,
entries 4 and 5). Diethyl 2-ethylmalonate afforded product 3af
with very low enantioselectivity (25% yield, 20% ee) (Table 1,
entry 6). Unfortunately, there were no reactions for diethyl
that the corresponding thiourea IX and its analogues have
10,11
been used in similar reactions,
the economic, non-toxic
and environment-benign synthetic procedure of squaramide,
the squaramide I was chosen as the catalyst for further
evaluation in this Mannich reaction of imine bearing a
heterocycle with dibenzyl malonate.
In order to promote the enantioselectivity of product 3ad,
we investigated the effect of catalyst loading, solvent,
temperature and the malonate loading to find optimal
conditions. The results are shown in Table 3. Four gradients
2-acetylaminomalonate
and
diethyl
2-phenylmalonate
(Table 1, entries 7 and 8). From the above evaluation, the
reaction of dibenzyl malonate with imine bearing a benzothia-
zole was selected as the optimal reactants.
Next, a series of squaramide catalysts I–VIII (Fig. 1) was
2 2
evaluated using 5 mol% catalyst loading in CH Cl for 24 h at
room temperature. When quinine-based squaramide catalyst I
was used in this reaction, the corresponding product 3ad was
achieved in excellent yield (99%) with high enantioselectivity
(5 mol%, 10 mol%, 15 mol%, and 20 mol%) of catalyst loading
were evaluated in the same reaction (Table 3, entries 1–4). It is
shown that 10 mol% catalyst loading was suitable for
obtaining the best enantioselectivity (96% ee). Further
(94% ee) (Table 2, entry 1). When mono-CF
3
substituted
catalyst II was used in the reaction, high yield and slightly
1
6350 | RSC Adv., 2013, 3, 16349–16358
This journal is ß The Royal Society of Chemistry 2013

View Article Online
RSC Advances
Paper
Table 3 Optimization of reaction conditions for the enantioselective Mannich
a
reaction of dibenzyl malonate 2d with imine 1a
b
c
Entry Solvent T/uC 1a/2d Loading (mol%) Yield (%) ee (%)
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
CH
CH
CH
CH
2
2
2
2
Cl
Cl
Cl
Cl
2
2
2
2
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
0
1 : 3
5
99
99
99
99
99
90
82
91
93
87
98
99
91
97
99
99
50
92
94
96
96
96
97
96
89
94
93
52
94
98
76
88
94
93
10
88
1 : 3 10
1 : 3 15
1 : 3 20
1 : 3 10
1 : 3 10
1 : 3 10
1 : 3 10
1 : 3 10
1 : 3 10
1 : 3 10
CHCl
Et
CCl
(CH
3
2
O
4
2
Cl)
2
PhMe
THF
0
1
2
3
4
5
6
7
8
CHCl
CHCl
CHCl
CHCl
CHCl
CHCl
CHCl
CHCl
3
3
3
3
3
3
3
3
215 1 : 3 10
230 1 : 3 10
215 1 : 1 10
215 1 : 2 10
215 1 : 4 10
215 1 : 3 10
215 1 : 3 10
d
e
a
Unless noted otherwise, reactions were carried out with imine 1a
(
(
47.6 mg, 0.2 mmol) and dibenzyl malonate 2d (0.6 mmol) in solvent
b
2 mL) for 24 h. Isolated yield after column chromatography
c
purification. Determined by chiral HPLC analysis using Daicel
Chiralpak IB column. CHCl (4 mL). CHCl (1 mL).
3 3
d
e
Fig. 1 Screened organocatalysts.
group (4-Cl, 4-Br). Imine 1b reacted smoothly with dibenzyl
malonate to afford the corresponding product 3bd in excellent
yield (99%) with high enantioselectivity (93% ee) (Table 4,
entry 2). When the halogen group was changed to 4-Br, the
yield decreased slightly (96% yield) with lower enantioselec-
tivity (83% ee) (Table 4, entry 3). Imines 1d–1f with a nitro
substituent in different locations gave different results
increasing of the catalyst loading has no beneficial effect for
the enantioselectivity. Next, the effect of the solvent was
evaluated under the same reaction conditions (Table 3, entries
5
–10). In CHCl , the product 3ad was obtained in excellent
3
yield (99%) with excellent enantioselectivity (97% ee) (Table 3,
entry 5). When the reaction was performed in Et O, CCl
ClCH CH Cl, or PhCH , the product was obtained in slightly
2
4
,
2
2
3
(
Table 4, entries 4–6). Imine 1f with 4-NO
enantioselectivity (Table 4, entry 6). Imine 1h with electron-
donating 4-CH substituent gave better yield and enantios-
electivity compared with 2-OMe substituted 1g (Table 4, entries
and 8). Generally, imines with electron-withdrawing sub-
2
gave the best
lower yield or enantioselectivity (Table 3, entries 6–9). In THF,
the enantioselectivity decreased to 52% ee (Table 3, entry 10).
Therefore, CHCl was selected as the best reaction medium.
3
The temperature is also an important factor in asymmetric
catalytic reactions. Excellent enantioselectivity (98% ee) was
obtained when running the reaction at 215 uC for 24 h.
Variations in the ratio of 1a/2d indicated that 1 : 3 was the best
ratio for these two reactants. We also observed a dependence
of the catalyst efficiency on concentration, change in volume
of solvent resulted in lower enantioselectivity (Table 3, entries
3
7
stituents gave higher yield than those with electron-donating
substituents. Imines 1i, 1j, and 1k derived from heteroaro-
matic aldehydes were also good substrates, and the desired
products were obtained in high to excellent yields with
moderate to excellent enantioselectivities (83–99% yield and
7
5–98% ee, respectively) (Table 4, entries 9–11). Imines 1l–1q
with variations on the benzothiazole ring (6-Me, 6-OMe, and
-Cl) were also examined, and excellent yields (89–99% yield)
and excellent enantioselectivities (95–98% ee) were achieved
Table 4, entries 12–17). Next, we turned our attention to the
17 and 18). From the above evaluation, the optimal reaction
conditions are: 10 mol% catalyst I, in CHCl , 1a/2d = 1 : 3, at
3
6
2
15 uC (Table 3, entry 12).
Having established the optimal reaction conditions, we
(
then evaluated the different imines via a reaction with
dibenzyl malonate to define the scope of this Mannich
reaction. The results are shown in Table 4. Imines 1b and 1c
were derived from aromatic aldehydes bearing a halogen
imines bearing other heterocycles such as benzimidazole,
oxazole, isoxazole, and pyridine. The imines derived from
2-aminobenzimidazole and 2-aminooxazole do not react in the
This journal is ß The Royal Society of Chemistry 2013
RSC Adv., 2013, 3, 16349–16358 | 16351

View Article Online
Paper
RSC Advances
Table 4 Substrate scope of the enantioselective Mannich reaction of dibenzyl
a
malonate 2d with imine 1
Scheme 1 Determine the absolute configuration by analogy.
1
2
6
b
c
Entry R
1
R
Time (h) Product Yield (%) ee (%)
C
H
5
24
24
24
48
24
24
48
48
3ad
3bd
3cd
3dd
3ed
3fd
3gd
3hd
3id
99
99
96
90
99
99
92
93
91
99
83
91
98
93
83
95
87
96
88
95
91
98
75
95
corresponding Mannich reaction. Imine derived from 2-ami-
nopyridine was decomposed strangely. When imine 1r derived
from 3-amino-5-metylisoxzole was examined, low yield (35%
yield) and low enantioselectivity (25% ee) was obtained
2
3
4
5
6
7
8
9
6 4
4-ClC H
6 4
4-BrC H
(
Table 4, entry 18). In contrast, the imine 1s with an
electron-withdrawing substituent (4-NO ) on the aldehyde side
gave the better result (41% yield and 62% ee) (Table 4, entry
9).
In order to determine the absolute configuration of
products 3, the enantioselective Mannich reaction of imine
t derived from 6-methoxybenzothiazole and 4-methylbenzal-
2
2-NO
3-NO
4-NO
2
C
6
6
6
H
H
H
4
4
4
1
2
2
C
C
1
dehyde with diethyl malonate 2b was performed according to
the procedure shown in Table 1 for 48 h at room temperature
in CH Cl (Scheme 1). The corresponding product 3td was
6 4
2-MeOC H
2
2
4-CH
3
C
6
H
4
25
D
obtained in 67% yield with 63% ee, [a] : +8.4 (c 0.5, CHCl
According to the literature
3
).
and optical rotation of com-
pound 3tb, the absolute configuration of 3tb was assigned be
R). The absolute configurations of other products 3 were
1
0a
2-Thienyl 48
3-Pyridinyl 24
(
1
1
1
0
1
2
3jd
assigned by analogy.
On the basis of the absolute configuration of the products,
we propose a possible mechanism for this Mannich reaction
2-Furyl
48
48
3kd
3ld
(Fig. 2). The squaramide organocatalyst I may act in a
C
6
H
5
bifunctional fashion. The enol form of dibenzyl malonate 2d
is activated or deprotonated by the basic nitrogen atom of the
tertiary amine. The squaramide moiety activates the hetero-
aromatic imine through double hydrogen bonding between
the two NH groups in squaramide and two N atoms in the
heteroaromatic imine. Thus nucleophilic attack of the active
methylene of dibenzyl malonate on imine 1a in the most
favored Re-face direction via the transition state. After that the
product 3ad is formed with excellent enantioselectivity.
1
1
1
1
1
1
3
4
5
6
7
8
C
6
6
H
5
5
48
48
48
48
48
72
3md
3nd
3od
3pd
3qd
3rd
93
99
99
89
99
35
98
98
96
97
96
25
C
H
4-NO
4-NO
4-NO
2
2
2
C
6
C
6
C
6
H
4
H
4
H
4
d
6 5
C H
1
9
4-NO
2
C
6
H
4
72
3sd
41
62
a
Reactions were carried out with imine 1 (0.2 mmol) and dibenzyl
b
malonate 2d (0.6 mmol) in CHCl (2 mL) at 215 uC. Isolated yield
after column chromatography purification. Determined by HPLC
using Daicel Chiralpak column. Reaction was carried out at room
3
c
d
temperature.
Fig. 2 Proposed mechanism for the asymmetric Mannich reaction of dibenzyl
malonate 2d with imine 1a.
1
6352 | RSC Adv., 2013, 3, 16349–16358
This journal is ß The Royal Society of Chemistry 2013

View Article Online
RSC Advances
Paper
1
1
3
2
66.7, 143.7, 134.2, 133.9, 133.6, 132.4, 131.9, 131.3, 131.1,
30.7, 126.6, 123.9, 119.2, 116.4, 80.2, 68.7, 59.2, 55.4, 54.5,
6.8, 25.7, 25.4, 25.2 ppm. 1IR (KBr): n 3436, 3190, 3086, 2938,
863, 2807, 1797, 1669, 1583, 1559, 1474, 1455, 1375, 1328,
Conclusions
In conclusion, we have developed a squaramide-catalysed
highly enantioselective Mannich reaction of malonates with
imines bearing a benzothiazole or isoxazole. The correspond-
ing products were obtained in high yields with excellent
enantioselectivities in most cases. This asymmetric reaction
provided a convenient route for synthesis of chiral b-amino
ester derivatives containing a heterocycle moiety. Futher
studies on squaramide-catalysed asymmetric reactions are
under way in our laboratory.
2
1
1278, 1184, 1133, 1027, 935, 879, 745, 698, 684, 618 cm
HRMS (ESI): m/z calcd.for C H F N O [M + H] : 602.2210,
found 602.2223.
;
+
2
9
32 6 2 5
General procedure for the asymmetric Mannich reaction
Imine 1a (47.6 mg, 0.2 mmol), dibenzyl malonate (170 mg, 0.6
mmol), and catalyst I (12.6 mg, 0.02 mmol) in CHCl (2 mL)
3
were stirred at 215 uC for 24–72 h. After the reaction was
complete, the mixture was separated directly by silica gel
column chromatography with petroleum ether–ethyl acetate
Experimental
(5 : 1) as eluant, and the product was obtained as pure form.
General methods
Dibenzyl 2-((benzo[d]thiazol-2ylamino)(phenyl)methyl)ma-
lonate (3ad). Compound 3ad was obtained according to the
general procedure as a yellow solid (103.3 mg, 99% yield); mp
Commercially available compounds were used without further
purification. Solvents were dried according to standard
procedures. Column chromatography was carried out using
silica gel (200–300 mesh). Melting points were measured on a
113–116 uC. The enantiomeric excess was determined by HPLC
with a Daicel Chiralpak IB column (n-hexane–2-propanol
2
1
1
80 : 20 v/v, flow rate 1.0 mL min , detection at 254 nm):
XT-4 melting point apparatus and uncorrected. The H NMR
minor enantiomer t = 8.2 min, major enantiomer tR = 7.5
R
spectra were recorded with Varian Mercury-plus 400 or Brucker
2
D
5
1
1
3
min, 98% ee; [a] : +8.6 (c 1.12, CH
2
Cl
): d = 7.49 (d, J = 6.8 Hz, 2H, ArH), 7.35–7.30 (m, 4H,
ArH), 7.25–7.15 (m, 10H, ArH), 7.09–7.03 (m, 3H, ArH), 5.76 (d,
J = 5.2 Hz, 1H, CH), 5.13–5.00 (m, 4H, CH ), 4.66 (brs, 1H, NH),
.15 (d, J = 5.6 Hz, 1H, CH) ppm. C NMR (100 MHz, CDCl ): d
2
). H NMR (400 MHz,
AVIII 400 MHz spectrometers, while the C NMR spectra were
recorded at 100 MHz. Infrared spectra were obtained with a
Perkin Elmer Spectrum One FT-IR spectrometer. The HRMS
CDCl
3
2
(ESI) spectra were obtained with a Bruker APEX IV Fourier
1
3
4
=
1
1
3
1
9
3
Transform mass spectrometer. Optical rotations were mea-
sured on a WZZ-3 or Kr u¨ ss P8000 polarimeter at the indicated
concentration with unit g/100 mL. The enatiomeric excesses
167.7, 166.4, 166.1, 151.5, 138.0, 134.6, 130.4, 128.7, 128.4,
28.35, 128.26, 128.0, 127.9, 127.4, 126.9, 126.4, 125.8, 121.8,
20.7, 119.0, 67.8, 67.5, 57.8, 57.0 ppm. IR (KBr): n 3361, 3063,
031, 2952, 1744, 1716, 1596, 1563, 1536, 1487, 1454, 1379,
348, 1312, 1255, 1233, 1199, 1172, 1069, 1030, 1019, 995, 971,
27, 913, 884, 833, 753, 735, 696, 643, 613, 581, 540, 507, 477
(ee) of the products were determined by chiral HPLC analysis
using Aglient HP 1200 instrument (n-hexane–2-propanol as
eluent).
2
1
+
Materials
31 27 2 4
cm ; HRMS (ESI): m/z calcd.for C H N O S [M + H] :
1
4d
17
14j
523.1686, found 523.1689.
The squaramide catalysts I–III,
were prepared according to literature procedures, respectively.
-((3,5-Bis(trifluoromethyl)phenyl)amino)-4-(((1S,2S)-2-
(
(
(
IV and V, VI and VII,
Dibenzyl 2-((benzo[d]thiazol-2-ylamino)(4-chlorophenyl)-
methyl)malonate (3bd). Compound 3bd was obtained accord-
ing to the general procedure as a white solid (110.1 mg, 99%
yield); mp 125–127 uC. The enantiomeric excess was deter-
mined by HPLC with a Daicel Chiralpak IB column (n-hexane–
3
dibenzylamino)cyclohexyl)amino)cyclobut-3-ene-1,2-dione
VIII). To a solution of 3,4-dimethoxycyclobut-3-ene-1,2-dione
0.71 g, 5.0 mmol) in MeOH (20 mL) was added 3,5-
bis(trifluoromethyl)benzenamine (1.145 g, 5.0 mmol). The
reaction mixture was stirred for 48 h at room temperature and
a white precipitation formed. The mono-squaramide was
obtained by filtration as a white solid (1.06 g, 60% yield). To
solution of (1S,2S)-N,N-dibenzylcyclohexane-1,2-diamine
88.2 mg, 0.3 mmol) in CH Cl (5 mL) was added mono-
squaramide (105.9 mg, 0.3 mmol). After stirring for 48 h at
room temperature, the squaramide catalyst VIII was obtained
by filtration as a white solid (100 mg, 55% yield); mp 273–276
2
1
2
2
=
-propanol 80 : 20 v/v, flow rate 1.0 mL min , detection at
54 nm): minor enantiomer t = 9.8 min, major enantiomer t
R
R
2
5
1
8.0 min, 93% ee; [a] : +28.6 (c 1.05, CH
2
Cl
): d = 7.52 (d, J = 8.0 Hz, 1H, ArH), 7.49 (d, J = 8.0
Hz, 1H, ArH), 7.32–7.15 (m, 12H, ArH), 7.07 (t, J = 7.4 Hz, 4H,
ArH), 5.78 (d, J = 4.8 Hz, 1H, CH), 5.16–5.02 (m, 5H, CH and
NH), 4.09 (d, J = 5.2 Hz, 1H, CH) ppm. C NMR (100 MHz,
CDCl ): d = 167.7, 166.3, 165.6, 152.0, 136.8, 134.5, 133.8,
30.8, 128.8, 128.4, 128.3, 128.1, 127.9, 125.8, 121.9, 120.7,
119.4, 67.9, 67.6, 57.0, 56.9 ppm. IR (KBr): n 3376, 3064, 3033,
2
). H NMR (400
D
MHz, CDCl
3
a
(
2
2
2
1
3
3
1
2
D
5
1
uC. [a] : 226.0 (c 0.5, CH OH).
H
NMR (400 MHz,
3
2
1
956, 1732, 1598, 1536, 1491, 1455, 1444, 1379, 1346, 1261,
215, 1153, 1091, 1014, 906, 825, 752, 725, 696 cm ; HRMS
CD
3
COCD
3
): d = 8.68 (s, 1H, NH), 8.27 (s, 2H, ArH), 8.03 (s,
NH), 7.97 (br s, 2H, ArH), 7.83 (s, 1H, NH), 7.58 (s, 3H, ArH),
.46 (s, 3H, ArH) 7.29 (s, 3H, ArH), 4.90 (d, J = 13.6 Hz, 1H),
.73 (ABq, J = 13.0 Hz, 2H), 4.58(d, J = 14.0 Hz, 1H), 4.28–4.21
2
1
+
2 4
(ESI): m/z calcd. for C31H26ClN O S [M + H] : 557.1296, found
7
4
557.1303.
(
(
1
m, 1H), 3.80 (t, J = 10.4 Hz, 1H), 2.59 (d, J = 11.2 Hz, 1H), 2.29
d, J = 10.8 Hz, 1H), 2.15–2.08 (m, 1H), 1.96 (d, J = 12.8 Hz, 1H),
Dibenzyl 2-((benzo[d]thiazol-2-ylamino)(4-bromophenyl)-
methyl)malonate (3cd). Compound 3cd was obtained accord-
ing to the general procedure as a white solid (115.3 mg, 96%
yield); mp 137–139 uC. The enantiomeric excess was deter-
.75 (d, J = 12.8 Hz, 1H), 1.66–1.44 (m, 2H), 1.39–1.29 (m, 1H)
1
3
3
ppm. C NMR (100 MHz, CDCl ): d = 185.5, 182.5, 171.1,
This journal is ß The Royal Society of Chemistry 2013
RSC Adv., 2013, 3, 16349–16358 | 16353

View Article Online
Paper
RSC Advances
mined by HPLC with a Daicel Chiralpak IB column (n-hexane–
ing to the general procedure as a yellow solid (112.2 mg, 99%
yield); mp 98–100 uC. The enantiomeric excess was determined
by HPLC with a Daicel Chiralpak IA column (n-hexane–2-
2
1
2
2
=
-propanol 80 : 20 v/v, flow rate 1.0 mL min , detection at
54 nm): minor enantiomer t = 9.9 min, major enantiomer t
R
R
2
5
1
21
8.1 min, 83% ee; [a] : +24.4 (c 1.95, CH
2
Cl
): d = 7.52 (d, J = 8.0 Hz, 1H, ArH), 7.48 (d, J = 8.0
Hz, 1H, ArH), 7.34–7.15 (m, 12H, ArH), 7.11–7.05 (m, 4H, ArH),
2
). H NMR (400
propanol 70 : 30 v/v, flow rate 1.0 mL min , detection at 254
D
MHz, CDCl
3
R R
nm): minor enantiomer t = 46.7 min, major enantiomer t =
2
D
5
1
26.7 min, 96% ee; [a] : +24.2 (c 2.41, CH Cl ). H NMR (400
2
2
5
4
=
1
5
1
1
6
.77 (d, J = 4.8 Hz, 1H, CH), 5.16–5.02 (m, 5H, CH and NH),
MHz, CDCl ): d = 8.00 (d, J = 8.4 Hz, 2H, ArH), 7.53 (d, J = 8.0
Hz, 1H, ArH), 7.46 (d, J = 8.8 Hz, 3H, ArH), 7.27–7.06 (m, 12H,
2
3
1
3
.09 (d, J = 5.2 Hz, 1H, CH) ppm. C NMR (100 MHz, CDCl ): d
3
167.6, 166.3, 165.5, 152.0, 137.3, 134.5, 131.8, 130.8, 128.5,
28.4, 128.3, 128.2, 128.1, 125.8, 121.9, 120.7, 119.4, 67.9, 67.6,
7.0, 56.8 ppm. IR (KBr): n 3392, 3062, 3035, 2964, 2924, 1747,
723, 1596, 1536, 1483, 1455, 1386, 1344, 1306, 1289, 1256,
190, 1156, 1076, 1030, 1009, 975, 895, 820, 790, 751, 725, 698,
ArH), 5.96 (d, J = 4.8 Hz, 1H, CH), 5.17–5.03 (m, 5H, CH
2
and
NH), 4.15 (d, J = 5.2 Hz, 1H, CH) ppm. C NMR (100 MHz,
CDCl ): d = 167.5, 166.0, 165.0, 151.8, 147.3, 145.6, 134.3,
1
3
3
130.7, 128.6, 128.5, 128.4, 128.3, 127.5, 125.9, 123.7, 122.2,
120.7, 119.5, 68.1, 67.8, 56.8, 56.4 ppm. IR (KBr): n 3376, 3364,
2
1
33, 601, 587, 492, 480 cm ; HRMS (ESI): m/z calcd.for
3033, 2960, 1736, 1598, 1538, 1496, 1455, 1444, 1380, 1348,
+
21
C H BrN O S [M + H] : 601.0791, found 601.0798.
1288, 1261, 1216, 1154, 1015, 907, 854, 753, 727, 696 cm
;
3
1
26
2 4
+
Dibenzyl 2-((benzo[d]thiazol-2-ylamino)(2-nitrophenyl)-
methyl)malonate (3dd). Compound 3dd was obtained accord-
ing to the general procedure as a yellow solid (102.1 mg, 90%
yield); mp 47–49 uC. The enantiomeric excess was determined
by HPLC with a Daicel Chiralpak IA column (n-hexane–2-
HRMS (ESI): m/z calcd.for C31H N O S [M + H] : 568.1537,
26 3 6
found 568.1543.
Dibenzyl 2-((benzo[d]thiazol-2-ylamino)(2-methoxyphenyl)-
methyl)malonate (3gd). Compound 3gd was obtained accord-
ing to the general procedure as a white solid (101.9 mg, 92%
yield); mp 51–52 uC. The enantiomeric excess was determined
by HPLC with a Daicel Chiralpak IB column (n-hexane–2-
2
1
propanol 70 : 30 v/v, flow rate 1.0 mL min , detection at 254
nm): minor enantiomer t = 22.0 min, major enantiomer t =
R
R
2
5
1
21
17.9 min, 95% ee; [a] : 253.1 (c 0.52, CH Cl ). H NMR (400
propanol 80 : 20 v/v, flow rate 1.0 mL min , detection at 254
D
2
2
MHz, CDCl
3
): d = 8.01 (dd, J
1
= 7.6 Hz, J
2
= 2.0 Hz, 1H, ArH),
R R
nm): minor enantiomer t = 8.2 min, major enantiomer t =
25
1
7
.60 (d, J = 7.6 Hz, 1H, ArH), 7.50–7.45 (m, 2H, ArH), 7.41–7.32
m, 3H, ArH), 7.26–7.20 (m, 6H, ArH), 7.17–7.12 (m, 4H, ArH),
.05 (t, J = 7.4 Hz, 1H, ArH), 6.36 (brs, 1H, CH), 5.25 (d, J = 12.0
Hz, 1H, CH ), 5.12–5.05 (m, 4H, CH and NH), 4.42 (d, J = 4.0
Hz, 1H, CH) ppm. C NMR (100 MHz, CDCl ): d = 168.2, 166.2,
64.8, 151.9, 148.3, 134.6, 134.4, 134.3, 133.8, 130.8, 129.1,
7.0 min, 88% ee; [a] : +15.8 (c 0.93, CH
MHz, CDCl
3
2
Cl
): d = 7.50 (t, J = 7.0 Hz, 2H, ArH), 7.31 (d, J = 8.0
Hz, 1H, ArH), 7.26–7.02 (m, 12H, ArH), 6.95 (d, J = 10.0 Hz, 1H,
ArH), 6.86–6.82 (m, 2H, ArH), 5.75 (dd, J = 9.6 Hz, J = 6.8 Hz,
1H, CH), 5.11–4.99 (m, 5H, CH and NH), 4.43 (d, J = 6.4 Hz,
2
). H NMR (400
D
(
7
2
2
1
2
1
3
3
2
1
3
1
1
1
2
1
7
+
1H, CH), 3.84 (s, 3H, OCH ) ppm. C NMR (100 MHz, CDCl3):
3
29.0, 128.5, 128.35, 128.26, 128.1, 125.8, 125.3, 121.9, 120.6,
19.6, 67.8, 67.6, 54.9, 54.1 ppm. IR (KBr): n 3385, 3065, 3032,
960, 1745, 1720, 1597, 1562, 1532, 1498, 1477, 1456, 1443,
361, 1335, 1286, 1221, 1160, 1142, 1125, 1066, 1018, 905, 787,
d = 167.8, 166.7, 166.4, 156.5, 152.2, 134.8, 130.8, 129.4, 128.5,
128.4, 128.2, 128.14, 128.08, 125.7, 125.4, 121.5, 120.7, 119.2,
110.5, 67.4, 67.3, 55.8, 55.4, 55.0 ppm. IR (KBr): n 3368, 3184,
3064, 3033, 2959, 2937, 2834, 1754, 1725, 1599, 1548, 1495,
1456, 1444, 1351, 1291, 1252, 1183, 1121, 1083, 1017, 942, 910,
2
1
56, 725, 602 cm ; HRMS (ESI): m/z calcd.for C31
H
26
N
3
O
6
S [M
+
21
H] : 568.1537, found 568.1549.
876, 751, 726, 698, 607, 495 cm ; HRMS (ESI): m/z calcd.for
+
Dibenzyl 2-((benzo[d]thiazol-2-ylamino)(3-nitrophenyl)-
C
32
H
29
N
2
O
5
S [M + H] : 553.1792, found 553.1788.
methyl)malonate (3ed). Compound 3ed was obtained accord-
ing to the general procedure as a yellow solid (112.2 mg, 99%
yield); mp 53–55 uC. The enantiomeric excess was determined
by HPLC with a Daicel Chiralpak IA column (n-hexane–2-
Dibenzyl 2-((benzo[d]thiazol-2-ylamino)(p-tolyl)methyl)ma-
lonate (3hd). Compound 3hd was obtained according to the
general procedure as a white solid (99.7 mg, 93% yield); mp
44–46 uC. The enantiomeric excess was determined by HPLC
with a Daicel Chiralpak IB column (n-hexane–2-propanol
2
1
propanol 80 : 20 v/v, flow rate 1.0 mL min , detection at 254
nm): minor enantiomer t = 29.9 min, major enantiomer t
2
1
R
R
=
80 : 20 v/v, flow rate 1.0 mL min , detection at 254 nm):
minor enantiomer t = 8.9 min, major enantiomer t = 7.6
). H NMR (400 MHz,
2
D
5
1
2
6.0 min, 87% ee; [a] : +17.0 (c 1.01, CH
2
Cl
2
). H NMR (400
R
R
2
5
1
MHz, CDCl
3
): d = 8.23 (s, 1H, ArH), 8.03 (d, J = 8.4 Hz, 1H, ArH),
D
2 2
min, 95% ee; [a] : +19.2 (c 0.72, CH Cl
7.68 (d, J = 8.0 Hz, 1H, ArH), 7.53 (d, J = 7.6 Hz, 1H, ArH), 7.47
CDCl ): d = 7.49 (d, J = 8.4 Hz, 2H, ArH), 7.25–7.15 (m, 11H,
3
(d, J = 8.0 Hz, 1H, ArH), 7.36 (t, J = 8.2 Hz, 1H, ArH), 7.27–7.06
ArH), 7.13–7.02 (m, 5H, ArH), 5.73 (br s, 1H, CH), 5.13–5.00 (m,
(
m, 12H, ArH), 5.99 (d, J = 4.0 Hz, 1H, CH), 5.16–5.02 (m, 5H,
5H, CH and NH), 4.13 (d, J = 5.6 Hz, 1H, CH), 2.27 (s, 3H, CH )
2
13
3
1
3
CH
MHz, CDCl
1
1
3
1
2
and NH), 4.19 (d, J = 5.6 Hz, 1H, CH) ppm. C NMR (100
): d = 167.5, 166.1, 165.0, 151.8, 148.2, 140.7, 134.4,
32.8, 130.8, 129.6, 128.5, 128.2, 125.8, 122.9, 122.1, 121.6,
ppm. C NMR (100 MHz, CDCl
3
): d = 167.7, 166.5, 166.1,
3
152.1, 137.6, 135.1, 134.6, 130.8, 129.3, 128.3, 128.2, 128.0,
126.3, 125.7, 121.6, 120.6, 119.2, 67.7, 67.4, 57.6, 57.2, 21.0
ppm. IR (KBr): n 3372, 3195, 3063, 3032, 2960, 1735, 1599,
1538, 1497, 1455, 1444, 1379, 1346, 1262, 1216, 1185, 1153,
20.7, 119.5, 68.1, 67.8, 56.6, 56.5 ppm. IR (KBr): n 3371, 3195,
065, 3034, 2960, 1733, 1598, 1534, 1498, 1456, 1444, 1379,
350, 1287, 1261, 1216, 1155, 1017, 907, 807, 753, 735, 696
2
1
1018, 907, 818, 752, 727, 696, 574, 500 cm ; HRMS (ESI): m/z
2
1
+
+
cm ; HRMS (ESI): m/z calcd.for C H N O S [M + H] :
calcd.for C H N O S [M + H] : 537.1843, found 537.1841.
3
1
26
3
6
32 29 2 4
5
68.1537, found 568.1525.
Dibenzyl 2-((benzo[d]thiazol-2-ylamino)(4-nitrophenyl)-
methyl)malonate (3fd). Compound 3fd was obtained accord-
Dibenzyl 2-((benzo[d]thiazol-2-ylamino)(2-thienyl)methyl)-
malonate (3id). Compound 3id was obtained according to
the general procedure as a yellow solid (96.1 mg, 91% yield);
1
6354 | RSC Adv., 2013, 3, 16349–16358
This journal is ß The Royal Society of Chemistry 2013

View Article Online
RSC Advances
Paper
mp 38–40 uC. The enantiomeric excess was determined by
to the general procedure as a white solid (97.5 mg, 91% yield);
mp 135–137 uC. The enantiomeric excess was determined by
HPLC with a Daicel Chiralpak IA column (n-hexane–2-
HPLC with a Daicel Chiralpak IB column (n-hexane–2-
2
1
propanol 90 : 10 v/v, flow rate 1.0 mL min , detection at
54 nm): minor enantiomer t = 13.2 min, major enantiomer
2
1
2
R
propanol 70 : 30 v/v, flow rate 1.0 mL min , detection at
2
D
5
1
t
(
(
R
= 14.3 min, 91% ee; [a] : +35.5 (c 0.53, CH
2
Cl
2
). H NMR
254 nm): minor enantiomer t = 17.4 min, major enantiomer
R
2
5
1
400 MHz, CDCl ): d = 7.53 (d, J = 8.0 Hz, 2H, ArH), 7.29–7.14
m, 10H, ArH), 7.08 (t, J = 7.6 Hz, 2H, ArH), 6.96 (br s, 2H,
D
R 2 2
t = 20.0 min, 95% ee; [a] : +9.1 (c 1.02, CH Cl ). H NMR (400
3
MHz, CDCl ): d = 7.39–7.32 (m, 4H, ArH), 7.28–7.17 (m, 10H,
3
Thiophene-H), 6.87–6.84 (m, 1H, Thiophene-H), 6.13 (d, J = 4.0
Hz, CH), 5.16–5.02 (m, 5H, CH and NH), 4.27 (d, J = 5.0 Hz,
H, CH) ppm. C NMR (100 MHz, CDCl ): d = 167.7, 166.2,
ArH), 7.08–7.05 (m, 3H, ArH), 6.97 (br s, 1H, ArH), 5.79 (br s,
2
1H, CH), 5.14–5.02 (m, 5H, CH and NH), 4.14 (d, J = 4.8 Hz,
2
1
3
13
1
1
1
5
1
7
3
1H, CH), 2.36 (s, 3H, CH ) ppm. C NMR (100 MHz, CDCl ): d
3
3
65.4, 152.0, 142.2, 134.6, 134.5, 130.9, 128.5, 128.4, 128.3,
28.2, 126.9, 125.8, 125.1, 121.9, 120.7, 119.4, 67.9, 67.6, 56.9,
3.9 ppm. IR (KBr): n 3349, 3062, 2953, 1748, 1723, 1536, 1483,
452, 1443, 1378, 1344, 1278, 1254, 1237, 1223, 1193, 1171,
= 167.8, 166.6, 165.3, 149.9, 138.3, 134.6, 131.4, 130.8, 128.7,
128.4, 128.3, 128.1, 127.9, 126.9, 126.4, 120.7, 118.9, 67.8, 67.4,
57.6, 57.0, 21.2 ppm. IR (KBr): n 3361, 3063, 3035, 2962, 2919,
1746, 1723, 1604, 1586, 1567, 1538, 1487, 1461, 1386, 1372,
1350, 1308, 1278, 1262, 1229, 1200, 1173, 1137, 1075, 1029,
2
1
53, 736, 723, 697 cm
; HRMS (ESI): m/z calcd.for
+
21
C H N O S [M + H] : 529.1250, found 529.1253.
1008, 971, 916, 819, 763, 753, 739, 701, 612, 574 cm ; HRMS
2
9
25 2 4 2
+
Dibenzyl 2-((benzo[d]thiazol-2-ylamino)(pyridin-3-
yl)methyl)malonate (3jd). Compound 3jd was obtained accord-
ing to the general procedure as a white solid (103.6 mg, 99%
yield); mp 100–102 uC. The enantiomeric excess was deter-
mined by HPLC with a Daicel Chiralpak IB column (n-hexane–
(ESI): m/z calcd.for C32
H
29
N
2
O
4
S [M + H] : 537.1843, found
537.1853.
Dibenzyl 2-((6-methoxybenzo[d]thiazol-2-ylamino)(phenyl)-
methyl)malonate (3md). Compound 3md was obtained
according to the general procedure as a yellow solid (102.7
mg, 93% yield); mp 138–140 uC. The enantiomeric excess was
2
1
2
-propanol 90 : 10 v/v, flow rate 0.8 mL min , detection at
2
54 nm): minor enantiomer t = 23.7 min, major enantiomer
determined by HPLC with a Daicel Chiralpak IB column (n-
R
2
5
1
21
t
R
= 24.6 min, 98% ee; [a] : +8.1 (c 3.65, CH
2
Cl
2
). H NMR (400
hexane–2-propanol 95 : 5 v/v, flow rate 1.0 mL min
,
D
MHz, CDCl
3
): d = 8.69 (s, 1H, Pydine-H), 8.47 (d, J = 4.4 Hz, 1H,
R
detection at 254 nm): minor enantiomer t = 34.0 min, major
2
5
Pydine-H), 7.67 (d, J = 8.0 Hz, 1H, Pydine-H), 7.52–7.47 (m, 2H
ArH), 7.27–7.11 (m, 12H, ArH), 7.07 (t, J = 7.6 Hz, 1H, ArH),
enantiomer t = 37.1 min, 98% ee; [a] : +8.3 (c 0.82, CH Cl ).
D
R 2 2
1
H NMR (400 MHz, CDCl ): d = 7.39–7.34 (m, 3H, ArH), 7.29–
3
5
(
.93 (d, J = 4.8 Hz, CH), 5.14–5.01 (m, 5H, CH
2
and NH), 4.17
d, J = 5.6 Hz, 1H, CH) ppm. C NMR (100 MHz, CDCl ): d =
67.5, 166.2, 165.2, 151.9, 149.2, 148.4, 134.4, 134.2, 134.2,
7.15 (m, 10H, ArH), 7.11–7.04 (m, 4H, ArH), 6.83 (dd, J = 9.0
1
1
3
3
Hz, J = 2.6 Hz, 1H, ArH), 5.77 (d, J = 4.8 Hz, 1H, CH), 5.12–4.99
2
1
1
1
3
1
9
(m, 5H, CH and NH), 4.15 (d, J = 5.2 Hz, 1H, CH), 3.74 (s, 3H,
2
1
3
30.8, 128.5, 128.42, 128.39, 128.31, 128.2, 125.8, 123.4, 122.0,
20.7, 119.4, 77.2, 67.9, 67.7, 56.6, 55.3 ppm. IR (KBr): n 3164,
061, 3035, 2949, 1751, 1730, 1596, 1565, 1534, 1498, 1455,
442, 1379, 1342, 1295, 1272, 1216, 1172, 1136, 1072, 1029,
OCH ) ppm. C NMR (100 MHz, CDCl ): d = 167.7, 166.5,
3 3
164.3, 155.1, 146.2, 138.3, 134.6, 131.7, 128.6, 128.3, 128.2,
128.0, 127.8, 126.4, 119.5, 113.3, 105.0, 67.7, 67.4, 57.6, 57.1,
55.7 ppm. IR (KBr): n 3361, 3066, 3028, 3003, 2948, 2914, 2829,
1744, 1718, 1602, 1570, 1544, 1500, 1485, 1470, 1436, 1383,
1349, 1289, 1259, 1221, 1168, 1121, 1073, 1058, 1028, 1006,
2
1
06, 818, 750, 725, 710, 696 cm ; HRMS (ESI): m/z calcd.for
+
C
30
H
26
N
3
O
4
S [M + H] : 524.1639, found 524.1623.
2
1
Dibenzyl 2-((benzo[d]thiazol-2-ylamino)(furan-2-yl)methyl)-
964, 862, 828, 760, 741, 727, 698, 614, 577 cm ; HRMS (ESI):
+
malonate (3kd). Compound 3kd was obtained according to
the general procedure as a yellow solid (84.9 mg, 83% yield);
mp 45–47 uC. The enantiomeric excess was determined by
HPLC with a Daicel Chiralpak IB column (n-hexane–2-
m/z calcd.for C H N O S [M + H] : 553.1792, found 553.1783.
3
2
29 2 5
Dibenzyl 2-((6-chlorobenzo[d]thiazol-2-ylamino)(phenyl)-
methyl)malonate (3nd). Compound 3nd was obtained accord-
ing to the general procedure as a white solid (110.1 mg, 99%
yield); mp 150–152 uC. The enantiomeric excess was deter-
mined by HPLC with a Daicel Chiralpak IB column (n-hexane–
2
1
propanol 80 : 20 v/v, flow rate 1.0 mL min , detection at
R R
254 nm): minor enantiomer t = 8.6 min, major enantiomer t
2
D
5
1
21
=
14.6 min, 75% ee; [a] : +18.0 (c 0. 60, CH
2
Cl
): d = 7.54 (t, J = 6.8 Hz, 2H, ArH), 7.33–7.15 (m,
1H, ArH), 7.10 (t, J = 7.4 Hz, 1H, ArH), 6.70 (br s, 1H, Furan-
H), 6.26–6.23 (m, 2H, Furan-H), 5.96 (d, J = 4.4 Hz, CH), 5.16–
2
). H NMR (400
2-propanol 80 : 20 v/v, flow rate 1.0 mL min , detection at
MHz, CDCl
3
2
=
R R
54 nm): minor enantiomer t = 8.8 min, major enantiomer t
8.1 min, 98% ee; [a] : +16.0 (c 0.96, CH Cl ). H NMR (400
D
2 2
25
1
1
3
MHz, CDCl ): d = 7.48 (s, 1H, ArH), 7.38–7.14 (m, 14H, ArH),
5
.04 (m, 5H, CH and NH), 4.27 (d, J = 4.8 Hz, 1H, CH) ppm.
C NMR (100 MHz, CDCl ): d = 167.8, 166.4, 165.6, 152.0,
3
2
7.09–7.05 (m, 3H, ArH), 5.79 (br s, 1H, CH), 5.28–5.03 (m, 5H,
1
3
1
3
CH and NH), 4.13 (d, J = 4.4 Hz, 1H, CH) ppm. C NMR (100
2
1
1
51.2, 142.3, 134.8, 134.6, 130.9, 128.5, 128.4, 128.3, 128.2,
25.8, 122.0, 120.7, 119.5, 110.5, 107.6, 67.9, 67.6, 54.2, 52.1
MHz, CDCl
3
): d = 167.9, 166.5, 166.0, 150.8, 138.0, 134.6, 132.0,
1
1
3
1
9
28.8, 128.5, 128.42, 128.35, 128.11, 128.06, 126.9, 126.3,
ppm. IR (KBr): n 3356, 3143, 3097, 3032, 2952, 1747, 1721,
26.2, 120.3, 120.0, 67.9, 67.6, 57.6, 56.9 ppm. IR (KBr): n 3386,
089, 3060, 3035, 2965, 2929, 1745, 1723, 1594, 1555, 1540,
480, 1446, 1387, 1344, 1306, 1259, 1209, 1157, 1037, 1028,
1
1
7
597, 1564, 1539, 1499, 1484, 1453, 1444, 1382, 1349, 1288,
252, 1237, 1224, 1190, 1174, 1069, 1008, 971, 901, 753, 738,
2
1
2
1
27, 697, 645, 595, 514 cm ; HRMS (ESI): m/z calcd.for
78, 942, 891, 864, 825, 750, 728, 694, 599, 482 cm ; HRMS
+
+
C H N O S [M + H] : 513.1479, found 513.1480.
2
9
25
2
5
(ESI): m/z calcd.for C H ClN O S [M + H] : 557.1296, found
31 26 2 4
Dibenzyl 2-((6-methylbenzo[d]thiazol-2-ylamino)(phenyl)-
methyl)malonate (3ld). Compound 3ld was obtained according
557.1288.
This journal is ß The Royal Society of Chemistry 2013
RSC Adv., 2013, 3, 16349–16358 | 16355

View Article Online
Paper
Dibenzyl 2-((6-methylbenzo[d]thiazol-2-ylamino)(4-nitrophe-
RSC Advances
2
1
+
695 cm ; HRMS (ESI): m/z calcd.for C31
H
25ClN
3
O
6
S [M + H] :
nyl)methyl)malonate (3od). Compound 3od was obtained
according to the general procedure as a yellow solid (115.0
mg, 99% yield); mp 136–137 uC. The enantiomeric excess was
determined by HPLC with a Daicel Chiralpak IA column (n-
602.1147, found 602.1150.
Dibenzyl 2-((5-methylisoxazol-3-ylamino)(phenyl)methyl)-
malonate (3rd). Compound 3rd was obtained according to
the general procedure as a white solid (32.9 mg, 35% yield);
mp 66–67 uC. The enantiomeric excess was determined by
HPLC with a Daicel Chiralpak AD-H column (n-hexane–2-
2
1
hexane–2-propanol 70 : 30 v/v, flow rate 1.0 mL min
,
detection at 254 nm): minor enantiomer t = 47.1 min, major
R
2
D
5
21
enantiomer t = 32.4 min, 96% ee; [a] : +32.7 (c 1.21, CH Cl ).
propanol 80 : 20 v/v, flow rate 1.0 mL min , detection at 254
R
2
2
1
H NMR (400 MHz, CDCl ): d = 7.99 (d, J = 8.4 Hz, 2H, ArH),
nm): minor enantiomer t = 45.8 min, major enantiomer t =
3
R
R
2
5
1
7.46 (d, J = 8.8 Hz, 2H, ArH), 7.35–7.33 (m, 2H, ArH), 7.28–7.16
D
2 2
39.9 min, 25% ee; [a] : +20.3 (c 0.78, CH Cl ). H NMR (400
(m, 7H), 7.12–7.05 (m, 4H, ArH), 5.93 (d, J = 5.2 Hz, 1H, CH),
MHz, CDCl ): d = 7.32–7.23 (m, 13H, ArH), 7.09 (d, J = 7.2 Hz,
3
5
2
1
1
5
2
1
.15–5.02 (m, 5H, CH
2
and NH), 4.14 (d, J = 5.2 Hz, 1H, CH),
2H, ArH), 5.45 (s, 1H, isoxazole-H), 5.37 (d, J = 5.2 Hz, 1H, CH),
1
3
.36 (s, 3H, CH
3
) ppm. C NMR (100 MHz, CDCl
3
): d = 167.4,
5.15–5.02 (m, 5H, CH and NH), 4.04 (d, J = 5.2 Hz, 1H, CH),
2
1
3
66.1, 164.4, 149.6, 147.3, 145.7, 134.4, 131.9, 130.8, 128.6,
28.4, 128.3, 127.5, 127.1, 123.7, 120.8, 119.0, 77.2, 68.0, 67.8,
6.8, 56.4, 21.2 ppm. IR (KBr): n 3367, 3207, 3062, 3033, 2959,
926, 1749, 1738, 1608, 1570, 1540, 1522, 1494, 1455, 1380,
345, 1284, 1257, 1216, 1151, 1014, 907, 855, 813, 732, 696
2.21 (s, 3H, CH ) ppm. C NMR (100 MHz, CDCl ): d = 168.7,
3 3
167.8, 166.8, 163.3, 138.8, 134.9, 134.7, 128.6, 128.4, 128.3,
128.2, 128.0, 127.7, 126.4, 93.2, 67.5, 67.2, 57.5, 56.9, 12.5 ppm.
IR (KBr): n 3384, 3348, 3119, 3090, 3063, 3032, 2945, 1748,
1729, 1626, 1536, 1497, 1485, 1455, 1382, 1348, 1259, 1215,
2
1
+
21
cm ; HRMS (ESI): m/z calcd.for C32
82.1693, found 582.1681.
Dibenzyl 2-((6-methoxybenzo[d]thiazol-2-ylamino)(4-nitro-
H
28
N
3
O
6
S [M + H] :
1152, 1138, 1002, 897, 735, 696, 614 cm ; HRMS (ESI): m/z
+
5
calcd.for C H N O [M + H] : 471.1915, found 471.1925.
2
8
27 2 5
Dibenzyl 2-((5-methyloxazol-2-ylamino)(4-nitrophenyl)-
methyl)malonate (3sd). Compound 3sd was obtained accord-
ing to the general procedure as a white solid (42.2 mg, 41%
yield); mp 120–121 uC. The enantiomeric excess was deter-
mined by HPLC with a Daicel Chiralpak IB column (n-hexane–
phenyl)methyl)malonate (3pd). Compound 3pd was obtained
according to the general procedure as a yellow solid (106.2 mg,
89% yield); mp 151–153 uC. The enantiomeric excess was
determined by HPLC with a Daicel Chiralpak IA column (n-
hexane–2-propanol 70 : 30 v/v, flow rate 1.0 mL min
2
1
21
,
2-propanol 80 : 20 v/v, flow rate 1.0 mL min , detection at
detection at 254 nm): minor enantiomer t = 57.9 min, major
254 nm): minor enantiomer t = 34.6 min, major enantiomer
tR = 22.2 min, 62% ee; [a] : +22.7 (c 0.52, CH Cl ). H NMR
D
2 2
R
R
2
5
25
1
enantiomer t = 33.2 min, 97% ee; [a] : +14.0 (c 1.13, CH Cl ).
R
D
2
2
1
1
H NMR (400 MHz, CDCl ): H NMR (400 MHz, CDCl ): d =
(400 MHz, CDCl ): d = 8.02 (d, J = 8.8 Hz, 2H, ArH), 7.43 (d, J =
3
3
3
8
.00 (d, J = 8.8 Hz, 2H, ArH), 7.46 (d, J = 8.4 Hz, 2H, ArH), 7.35
8.4 Hz, 2H, ArH), 7.30–7.23 (m, 7H, ArH), 7.11 (d, J = 7.2 Hz,
2H, ArH), 5.66 (d, J = 9.6 Hz, 1H, ArH), 5.47 (t, J = 4.6 Hz, 1H,
(d, J = 8.4 Hz, 2H, ArH), 7.28–7.14 (m, 7H, ArH), 7.10–7.05 (m,
3
H, ArH), 6.94 (br s, 1H, ArH), 6.85 (dd, J = 8.4 Hz, J = 2.0, 1H,
CH), 5.45 (s, 1H, isoxazole-H), 5.19–5.02 (m, 5H, CH and NH),
1
2
2
1
3
ArH), 5.92 (br s, 1H, CH), 5.17–5.03 (m, 5H, CH
2
and NH), 4.14
) ppm. C NMR (100
4.01 (d, J = 5.2 Hz, 1H, CH), 2.23 (s, 3H, CH ) ppm. C NMR
3
1
3
(
d, J = 5.2 Hz, 1H, CH), 3.78 (s, 3H, OCH
MHz, CDCl ): d = 167.5, 166.1, 163.3, 155.4, 147.3, 145.9, 145.8,
34.4, 131.7, 128.6, 128.4, 128.3, 127.5, 123.7, 119.8, 113.5,
3
(100 MHz, CDCl ): d = 169.1, 167.5, 166.3, 162.8, 147.3, 146.3,
3
3
134.6, 134.5, 128.6, 128.50, 128.46, 128.36, 128.31, 127.5,
1
1
3
1
1
123.7, 93.2, 67.8, 67.6, 56.7, 56.1, 12.5 ppm. IR (KBr): n 3379,
3112, 3079, 3066, 3033, 2966, 2859, 1755, 1736, 1628, 1608,
1521, 1497, 1455, 1384, 1353, 1301, 1282, 1263, 1229, 1202,
1181, 1156, 1133, 1083, 1031, 978, 902, 888, 859, 822, 782, 746,
05.1, 68.1, 67.8, 56.7, 56.4, 55.8 ppm. IR (KBr): n 3361, 3060,
003, 2957, 2836, 1753, 1728, 1613, 1605, 1580, 1554, 1515,
463, 1437, 1381, 1353, 1306, 1281, 1256, 1216, 1176, 1150,
2
1
21
+
063, 898, 862, 804, 757, 700 cm ; HRMS (ESI): m/z calcd.for
28 26 3 7
736, 698 cm ; HRMS (ESI): m/z calcd.for C H N O [M + H] :
+
C
32
H
28
N
3
O
7
S [M + H] : 598.1643, found 598.1636.
516.1765, found 516.1766.
Dibenzyl 2-((6-chlorobenzo[d]thiazol-2-ylamino)(4-nitrophe-
Dimethyl 2-((benzo[d]thiazol-2-ylamino)(phenyl)methyl)ma-
lonate (3aa). Compound 3aa was obtained according to the
general procedure at room temperature in CH Cl as a white
nyl)methyl)malonate (3qd). Compound 3qd was obtained
according to the general procedure as a yellow solid (119.1
mg, 99% yield); mp 144–146 uC. The enantiomeric excess was
determined by HPLC with a Daicel Chiralpak IA column (n-
2
2
solid (73.2 mg, 99% yield); mp 103–106 uC. The enantiomeric
excess was determined by HPLC with a Daicel Chiralpak IA
column (n-hexane–2-propanol 80 : 20 v/v, flow rate 1.0 mL
2
1
hexane–2-propanol 70 : 30 v/v, flow rate 1.0 mL min
,
2
1
detection at 254 nm): minor enantiomer t = 46.7 min, major
min , detection at 254 nm): minor enantiomer t = 12.7 min,
R
R
2
D
5
25
D
enantiomer t = 26.0 min, 96% ee; [a] : +17.3 (c 1.65, CH Cl ).
major enantiomer t = 15.0 min, 92% ee; [a] : 28.7 (c 1.75,
CH Cl ). H NMR (400 MHz, CDCl ): d = 7.52 (t, J = 7.8 Hz, 2H,
2 2 3
R
2
2
R
1
1
H NMR (400 MHz, CDCl ): d = 8.02 (d, J = 8.8 Hz, 1H, ArH),
3
7.49–7.45 (m, 3H, ArH), 7.33 (d, J = 8.4 Hz, 1H, ArH), 7.29–7.09
ArH), 7.40 (d, J = 7.6 Hz, 2H, ArH), 7.33–7.24 (m, 4H, ArH), 7.06
(
m, 11H, ArH), 5.95 (br s, 1H, CH), 5.19–5.03 (m, 5H, CH and
(t, J = 7.6 Hz, 1H, ArH), 5.68 (d, J = 5.2 Hz, 1H, CH), 4.05 (d, J =
2
1
3
13
NH), 4.13 (d, J = 4.8 Hz, 1H, CH) ppm. C NMR (100 MHz,
CDCl ): d = 167.5, 166.0, 165.1, 150.4, 147.4, 145.4, 134.3,
31.9, 128.6, 128.5, 128.4, 128.3, 127.4, 127.3, 126.3, 123.8,
5.6 Hz, 1H, CH), 3.68 (s, 3H, CH3), 3.66 (s, 3H, CH ) ppm.
C
3
3
NMR (100 MHz, CDCl ): d = 168.2, 167.1, 166.3, 151.7, 138.2,
3
1
1
3
1
130.5, 128.7, 128.1, 126.4, 125.8, 121.8, 120.7, 119.1, 77.2, 58.0,
56.9, 53.0, 52.8 ppm. IR (KBr): n 3376, 3027, 3003, 2953, 2845,
1739, 1600, 1563, 1543, 1488, 1457, 1444, 1434, 1359, 1344,
1298, 1262, 1236, 1188, 1164, 1128, 1072, 1039, 1007, 970, 939,
20.4, 120.1, 68.1, 67.8, 56.7, 56.3 ppm. IR (KBr): n 3362, 3066,
033, 2960, 1743, 1729, 1596, 1560, 1538, 1497, 1447, 1401,
383, 1348, 1304, 1289, 1272, 1221, 1155, 907, 854, 749, 733,
1
6356 | RSC Adv., 2013, 3, 16349–16358
This journal is ß The Royal Society of Chemistry 2013

View Article Online
RSC Advances
05, 887, 857, 818, 787, 752, 728, 699, 607, 581, 530, 502 cm
HRMS (ESI): m/z calcd.for C19H N O S [M + H] : 371.1060,
19 2 4
found 371.1055.
Paper
2
1
9
;
120.6, 119.0, 70.2, 62.9, 62.6, 61.4, 13.9 ppm. IR (KBr): n 3384,
3352, 3063, 3024, 2985, 2940, 1747, 1716, 1597, 1541, 1492,
1466, 1453, 1442, 1388, 1369, 1326, 1293, 1280, 1250, 1211,
1174, 1126, 1094, 1070, 1024, 1005, 971, 885, 859, 848, 804,
759, 728, 705, 678, 643, 613, 576, 551, 532, 488 cm ; HRMS
24 3 4
(ESI): m/z calcd.for C21H N O S [M + H] : 414.1482, found
+
Diethyl 2-((benzo[d]thiazol-2-ylamino)(phenyl)methyl)malo-
nate (3ab). Compound 3ab was obtained according to the
2
1
+
procedure at room temperature in CH Cl2 as a white solid
2
(72.7 mg, 91% yield); mp 76–78 uC. The enantiomeric excess
414.1480.
was determined by HPLC with a Daicel Chiralpak IB column
Diethyl 2-((benzo[d]thiazol-2-ylamino)(phenyl)methyl)-2-
ethylmalonate. Compound 3af was obtained according to the
general procedure at room temperature in CH Cl as a white
2
1
(n-hexane–2-propanol 97 : 3 v/v, flow rate 1.0 mL min
,
detection at 254 nm): minor enantiomer t
R
= 13.0 min, major
Cl ).
3
): d = 7.52 (t, J = 8.6 Hz, 2H, ArH),
2
2
2
5
enantiomer t
R
= 11.2 min, 92% ee; [a] : 213.2 (c 0.50, CH
2
2
solid (21.3 mg, 25% yield); mp 35–37 uC. The enantiomeric
excess was determined by HPLC with a Daicel Chiralpak AS-H
column (n-hexane–2-propanol 95 : 5 v/v, flow rate 0.8 mL
D
1
H NMR (400 MHz, CDCl
7
7
.41 (d, J = 7.2 Hz, 2H, ArH), 7.32 (t, J = 7.4 Hz, 2H, ArH), 7.27–
.23 (m, 2H, ArH), 7.06 (t, J = 7.8 Hz, 1H, ArH), 5.70 (d, J = 5.2
2
1
min , detection at 254 nm): minor enantiomer t = 6.7 min,
R
2
5
Hz, 1H, CH), 4.20–4.07 (m, 4H, CH ), 4.03 (d, J = 5.2 Hz, 1H,
R
D
major enantiomer t = 7.3 min, 20% ee; [a] : +44.9 (c 0.37,
CH Cl ). H NMR (400 MHz, CDCl ): d = 7.71 (br s, 1H, NH),
2 2 3
2
3
1
1
CH), 1.17–1.11 (m, 6H, CH
d = 167.8, 166.7, 166.3, 151.6, 138.2, 130.4, 128.6, 127.9, 126.5,
25.8, 121.7, 120.7, 119.0, 77.2, 62.1, 61.8, 58.0, 57.1, 13.8 ppm.
IR (KBr): n 3369, 3194, 3062, 2981, 2936, 1737, 1599, 1540,
3
) ppm. C NMR (100 MHz, CDCl
3
):
7.52–7.49 (m, 2H, ArH), 7.36–7.23 (m, 6H, ArH), 7.04 (t, J = 7.6
1
Hz, 1H, ArH), 5.24 (s, 1H, CH), 4.32–4.14 (m, 4H, CH ), 1.91–
2
1.72 (m, 2H, CH ), 1.27 (t, J = 7.0 Hz, 3H, CH ), 1.20 (t, J = 7.2
2
3
1
3
1
9
495, 1455, 1444, 1370, 1290, 1259, 1174, 1155, 1095, 1030,
3 3
Hz, 3H, CH ), 0.99 (t, J = 7.4 Hz, 3H, CH ) ppm. C NMR (100
2
1
09, 862, 754, 726, 699, 591 cm ; HRMS (ESI): m/z calcd.for
MHz, CDCl ): d = 170.0, 169.7, 166.2, 136.7, 128.4, 128.1, 125.9,
3
+
C H N O S [M + H] : 399.1373, found 399.1380.
121.7, 120.7, 118.8, 63.5, 63.2, 61.9, 27.6, 14.0, 13.9, 9.8 ppm.
2
1
23 2 4
Diisopropyl 2-((benzo[d]thiazol-2-ylamino)(phenyl)methyl)-
malonate (3ac). Compound 3ac was obtained according to
the general procedure at room temperature in CH Cl as a
2 2
IR (KBr): n 3397, 3063, 3028, 2980, 2937, 2888, 1774, 1750,
1705, 1619, 1597, 1564, 1476, 1443, 1393, 1368, 1313, 1272,
1236, 1206, 1115, 1094, 1026, 965, 924, 868, 760, 725, 706, 603
cm ; HRMS (ESI): m/z calcd.for C23H N O S [M + H] :
27 2 4
427.1686, found 427.1691.
2
1
+
white solid (50.3 mg, 59% yield); mp 118–121 uC. The
enantiomeric excess was determined by HPLC with a Daicel
Chiralpak IA column (n-hexane–2-propanol 80 : 20 v/v, flow
2
1
rate 1.0 mL min , detection at 254 nm): minor enantiomer t
R
5
2
=
+
=
15.3 min, major enantiomer t = 12.4 min, 89% ee; [a] :
R
D
Acknowledgements
1
16.0 (c 0.50, CH
2
Cl
2
). H NMR (400 MHz, CDCl
3
): d = 7.52 (t, J
We are grateful for financial support from the National Natural
Science Foundation of China (Grant No. 21272024), the
Science and Technology Innovation Program of Beijing
Institute of Technology (Grant No. 2011CX01008) and the
Development Program for Distinguished Young and Middle-
aged Teachers of Beijing Institute of Technology.
8.4 Hz, 2H, ArH), 7.41 (d, J = 7.6 Hz, 2H, ArH), 7.31 (t, J = 7.6
Hz, 2H, ArH), 7.27–7.22 (m, 2H, ArH), 7.05 (t, J = 7.2 Hz, 1H,
ArH), 5.69 (d, J = 5.2 Hz, 1H, CH), 5.04–4.96 (m, 2H, CH), 3.97
(
=
d, J = 5.2 Hz, 1H, CH), 1.195 (d, J = 6.0 Hz, 3H, CH
6.0 Hz, 3H, CH ), 1.09 (d, J = 6.4 Hz, 3H, CH ), 1.05 (d, J = 6.0
Hz, 3H, CH ) ppm. C NMR (100 MHz, CDCl ): d = 167.5,
3
), 1.192 (d, J
3
3
1
3
3
3
1
1
66.3, 166.2, 151.8, 138.4, 130.5, 128.6, 127.8, 126.5, 125.8,
21.7, 120.7, 119.1, 69.9, 69.5, 57.9, 57.3, 21.5, 21.4, 21.3 ppm.
IR (KBr): n 3375, 3062, 3029, 2981, 2938, 2876, 1738, 1706,
References
1
1
602, 1546, 1498, 1453, 1443, 1367, 1284, 1240, 1213, 1180,
2
1
1 For reviews, see: (a) M. Arend, B. Westermann and
N. Risch, Angew. Chem., 1998, 110, 1096, (Angew. Chem.,
Int. Ed., 1998, 37, 1044); (b) S. Kobayashi and H. Ishitani,
Chem. Rev., 1999, 99, 1069.
103, 1033, 999, 916, 839, 808, 751, 726, 699, 582, 490 cm
;
+
27 2 4
HRMS (ESI): m/z calcd.for C23H N O S [M + H] : 427.1686,
found 427.1693.
Diethyl 2-amino-2-((benzo[d]thiazol-2-ylamino)(phenyl)-
methyl)malonate (3ae). Compound 3ae was obtained accord-
2
For selected recent reviews, see: (a) B. Han, J.-L. Li, Y.-
C. Xiao, S.-L. Zhou and Y.-C. Chen, Curr. Org. Chem., 2011,
2 2
ing to the general procedure at room temperature in CH Cl as
15, 4128; (b) L. Bernardi, A. Ricci and M. C. Franchini, Curr.
a white solid (74.2 mg, 90% yield); mp 113–115 uC. The
enantiomeric excess was determined by HPLC with a Daicel
Chiralpak IA column (n-hexane–2-propanol 80 : 20 v/v, flow
Org. Chem., 2011, 15, 2210; (c) R. Gomez Arrayas and J.
C. Carretero, Chem. Soc. Rev., 2009, 38, 1940; (d) A. Ting
and S. E. Schaus, Eur. J. Org. Chem., 2007, 5797; (e) J. M.
M. Verkade, L. J. C. van Hemert, P. J. L. M. Quaedflieg and
F. P. J. T. Rutjes, Chem. Soc. Rev., 2008, 37, 29; (f) P.
M. Pihko and H. Rahaman, in Enantioselective
Organocatalyzed Reactions (Ed.: R. Mahrwald), Springer,
Heidelberg, 2011, p. 185.
2
1
rate 1.0 mL min , detection at 254 nm): minor enantiomer t
R
5
2
=
+
7
4
4
6
1
R
D
12.8 min, major enantiomer t = 17.6 min, 95% ee; [a] :
14.4 (c 0.75, CH Cl ). H NMR (400 MHz, CDCl ): d = 7.52–
.49 (m, 2H, ArH), 7.44 (d, J = 7.2 Hz, 2H, ArH), 7.31–7.22 (m,
H, ArH), 7.03 (t, J = 7.6 Hz, 1H, ArH), 5.65 (s, 1H, CH), 4.32–
1
2
2
3
.22 (m, 2H, CH), 4.18–4.03 (m, 4H, CH
2
), 1.22 (t, J = 7.0 Hz,
) ppm. C NMR (100 MHz, CDCl ): d = 169.0, 168.2,
66.0, 151.8, 136.3, 130.5, 128.5, 128.3, 128.0, 125.8, 121.5,
3 For selected organocatalysed examples, see: (a) T. Kano,
S. Song, Y. Kubota and K. Maruoka, Angew. Chem., Int. Ed.,
2012, 51, 1191; (b) N. Nicolas, A. Madarasz, A. Valkonen,
1
3
H, CH
3
3
This journal is ß The Royal Society of Chemistry 2013
RSC Adv., 2013, 3, 16349–16358 | 16357

View Article Online
Paper
I. Papai, K. Rissanen, A. Neuvonen and P. M. Pihko, Angew.
RSC Advances
A. Song, P. S. Bhadury, L. Li, Z. Wang, X. Zhang, D. Y. Hu,
Z. Chen, Y. Zhang, S. Bai, J. Wu and S. Yang, Chirality,
2012, 24, 223.
Chem., Int. Ed., 2012, 51, 8496; (c) J. W. Yang, M. Stadler
and B. List, Angew. Chem., Int. Ed., 2007, 46, 609; (d)
A. Ricci, D. Pettersen, L. Bernardi, F. Fini, M. Fochi, R.
P. Herrera and V. Sgarzani, Adv. Synth. Catal., 2007, 349,
11 S. Bai, X. P. Liang, B.-A. Song, P. S. Bhadury, D. Y. Hu and
S. Yang, Tetrahedron: Asymmetry, 2011, 22, 518.
1
2
037; (e) D. Uraguchi and M. Terada, J. Am. Chem. Soc.,
004, 126, 5356; (f) W. Zhuang, S. Saaby and K.
12 During the preparation of this manuscript, Hu and
coworker reported one-pot Mannich reaction catalyzed by
squaramide: (a) K. K. Zhang, X. P. Liang, M. He, J. Wu, Y.
P. Zhang, W. Xue, L. H. Jin, S. Yang and D. Y. Hu,
Molecules, 2013, 18, 6142.
13 For reviews of squaramides, see: (a) J. Aleman, A. Parra,
H. Jiang and K. A. Jørgensen, Chem.–Eur. J., 2011, 17, 6890;
(b) R. I. Storer, C. Aciro and L. H. Jones, Chem. Soc. Rev.,
2011, 40, 2330.
14 For selected examples of asymmetric reactions using
squaramides, see: (a) J. P. Malerich, K. Hagihara and V.
H. Rawal, J. Am. Chem. Soc., 2008, 130, 14416; (b) Y. Zhu, J.
P. Malerich and V. H. Rawal, Angew. Chem., Int. Ed., 2010,
49, 153; (c) H. Konishi, T. Y. Lam, J. P. Malerich and V.
H. Rawal, Org. Lett., 2010, 12, 2028; (d) W. Yang and D.-
M. Du, Org. Lett., 2010, 12, 5450; (e) H. Y. Bae, S. Some, J.
H. Lee, J.-Y. Kim, M. J. Song, S. Lee, Y. J. Zhang and C.
E. Song, Adv. Synth. Catal., 2011, 353, 3196; (f) C. Min,
X. Han, Z. Q. Liao, X. F. Wu, H.-B. Zhou and C. Dong, Adv.
Synth. Catal., 2011, 353, 2715; (g) D. Q. Xu, Y.-F. Wang,
W. Zhang, S.-P. Luo, A.-G. Zhong, A.-B. Xia and Z.-Y. Xu,
Chem.–Eur. J., 2010, 16, 4177; (h) Y. Qian, G. Ma, A. Lv, H.-
L. Zhu, J. Zhao and V. H. Rawal, Chem. Commun., 2010, 46,
3004; (i) W. Yang and D.-M. Du, Chem. Commun., 2011, 47,
12706; (j) W. Yang and D.-M. Du, Adv. Synth. Catal., 2011,
353, 1241; (k) S. V. Pansare and E. K. Paul, Chem. Commun.,
2011, 47, 1027; (l) W. Yang, Y. Jia and D.-M. Du, Org.
Biomol. Chem., 2012, 10, 332; (m) X. Fang, Q.-H. Li, H.-
Y. Tao and C.-J. Wang, Adv. Synth. Catal., 2013, 355, 327.
15 H.-X. He, W. Yang and D.-M. Du, Adv. Synth. Catal., 2013,
355, 1137.
A. Jørgensen, Angew. Chem., Int. Ed., 2004, 43, 4476; (g)
W. Notz, S. I. Watanabe, N. S. Chowdari, G. Zhong, J.
M. Betancort, F. Tanaka and C. F. Barbas III, Adv. Synth.
Catal., 2004, 346, 1131; (h) A. C ´o rdova, Chem.–Eur. J., 2004,
1
0, 1987; (i) Y. Hayashi, W. Tsuboi, I. Ashimine,
T. Urushima, M. Shoji and K. Sakai, Angew. Chem., Int.
Ed., 2003, 42, 3677; (j) A. G. Wenzel and E. N. Jacobsen, J.
Am. Chem. Soc., 2002, 124, 12964; (k) B. List, P. Pojarliev, W.
T. Biller and H. J. Martin, J. Am. Chem. Soc., 2002, 124, 827.
For selected matal complexes-catalysed examples, see: (a)
M. Marigo, A. Kjærsgaard, K. Juhl, N. Gathergood and K.
A. Jørgensen, Chem.–Eur. J., 2003, 9, 2359; (b) N.
S. Josephsohn, M. L. Snapper and A. H. Hoveyda, J. Am.
Chem. Soc., 2004, 126, 3734; (c) S. Kobayashi, M. Ueno,
S. Saito, Y. Mizuki, H. Ishitani and Y. Yamashita, Proc. Natl.
Acad. Sci. U. S. A., 2004, 101, 5476; (d) Y. Ihori,
Y. Yamashita, H. Ishitani and S. Kobayashi, J. Am. Chem.
Soc., 2005, 127, 15528; (e) Y. Hamashima, N. Sasamoto,
D. Hotta, H. Somei, N. Umebayashi and M. Sodeoka,
Angew. Chem., Int. Ed., 2005, 44, 1525; (f) S. Harada,
S. Handa, S. Matsunaga and M. Shibasaki, Angew. Chem.,
Int. Ed., 2005, 44, 4365; (g) T. Akiyama, J. Itoh, K. Yokota
and K. Fuchibe, Angew. Chem., Int. Ed., 2004, 43, 1566; (h)
B. M. Trost, J. Jaratjaroonphong and V. Reutrakul, J. Am.
Chem. Soc., 2006, 128, 2778; (i) N. Sasamoto, C. Dubs,
Y. Hamashima and M. Sodeoka, J. Am. Chem. Soc., 2006,
4
1
28, 14010; (j) Z. Chen, H. Morimoto, S. Matsunaga and
M. Shibasaki, J. Am. Chem. Soc., 2008, 130, 2170; (k)
A. Yamaguchi and S. Matsunaga, Org. Lett., 2008, 10, 2319;
(
l) G. Lu, T. Yoshino, H. Morimoto, S. Matsunaga and
16 (a) P. C. Sharma, A. Sinhmar, A. Sharma, H. Rajak and D.
P. Pathak, J. Enzyme Inhib. Med. Chem., 2013, 28, 240; (b) R.
M. Kumbhare, U. B. Kosurkar, M. J. Ramaiah, T.
L. Dadmal, S. N. C. V. L. Pushpavalli and M. Pal-Bhadra,
M. Shibasaki, Angew. Chem., Int. Ed., 2011, 50, 4382.
J. Song, Y. Wang and L. Deng, J. Am. Chem. Soc., 2006, 128,
6
J. Song, H. W. Shih and L. Deng, Org. Lett., 2007, 9, 603.
O. Marianacci, L. Micheletti, F. Bernardi, M. Fini, M. Fochi,
D. Pettersen, V. Sgarzani and A. Ricci, Chem.–Eur. J., 2007,
5
048.
´
6
7
Bioorg. Med. Chem. Lett., 2012, 22, 5424; (c) I. Caleta,
M. Kralj, M. Marjanovi ´c , B. Berto ˇs a, S. Tomi ´c , G. Pavlovi ´c ,
K. Paveli ´c and G. Karminski-Zamola, J. Med. Chem., 2009,
52, 1744; (d) S. Aiello, G. Wells, E. L. Stone, H. Kadri,
R. Bazzi, D. R. Bell, M. F. G. Stevens, C. S. Matthews, T.
D. Bradshaw and A. D. Westwell, J. Med. Chem., 2008, 51,
5135; (e) Y. Cho, T. R. Ioerger and J. C. Sacchettini, J. Med.
Chem., 2008, 51, 5984.
1
3, 8338.
8
9
X. Han, K. Kwiatkowski, F. Xue, K.-W. Huang and Y. X. Lu,
Angew. Chem., Int. Ed., 2009, 48, 7604.
Y. Sohtome, S. Tanaka, K. Takada, T. Yamaguchi and
K. Nagasawa, Angew. Chem., Int. Ed., 2010, 49, 9254.
1
0 (a) L. Li, B.-A. Song, P. S. Bhadury, Y.-P. Zhang, D.-Y. Hu
and S. Yang, Eur. J. Org. Chem., 2011, 4743; (b) W. H. Li, B.
17 J. W. Lee, T. H. Ryu, J. S. Oh, H. Y. Bae, H. B. Jang and C.
E. Song, Chem. Commun., 2009, 7224.
1
6358 | RSC Adv., 2013, 3, 16349–16358
This journal is ß The Royal Society of Chemistry 2013