Bifunctional primary amine-thiourea-TfOH (BPAT·TfOH) as a chiral phase-transfer catalyst: The asymmetric synthesis of dihydropyrimidines

Article abstract of DOI:10.1039/c0ob01268h

An enantioselective Biginelli reaction has been developed by using a bifunctional primary amine-thiourea-TfOH (BPAT·TfOH) as a chiral phase-transfer catalyst and t-BuNH₂·TFA as an additive in saturated brine at room temperature. The correspondi

Full text of DOI:10.1039/c0ob01268h

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PAPER
Bifunctional primary amine-thiourea–TfOH (BPAT·TfOH) as a chiral
phase-transfer catalyst: the asymmetric synthesis of dihydropyrimidines†
Yangyun Wang, Jipan Yu, Zhiwei Miao* and Ruyu Chen*
Received 30th December 2010, Accepted 10th February 2011
DOI: 10.1039/c0ob01268h
An enantioselective Biginelli reaction has been developed by using a bifunctional primary
amine-thiourea–TfOH (BPAT·TfOH) as a chiral phase-transfer catalyst and t-BuNH2·TFA as an
additive in saturated brine at room temperature. The corresponding dihydropyrimidines were obtained
in moderate-to-good yields with up to 99% ee under mild conditions. A plausible transition state has
been proposed to explain the origin of the activation and the asymmetric induction.
Feng has also reported an enantioselective Biginelli reaction cat-
alyzed by a trans-4-hydroxyproline-derived secondary amine with
Introduction
a Brønsted acid as the combined catalyst.15 Recently, Zhao and
Wang have reported an asymmetric Biginelli reaction catalyzed by
substituted 5-(pyrrolidin-2-yl)tetrazoles.16 In view of these limited
successful examples, it remains desirable to develop other new
organocatalysts for this important transformation. We now wish
to report our efforts in the development of the first enantioselective
phase-transfer-catalyzed Biginelli condensation reactions.
Reactions in water have attracted a great deal of attention.17
Apart from the obvious economic and environmental benefits,
aqueous media might have favorable effects on reaction activity
and selectivity. Recently, the positive benefits of aqueous solu-
tions have also been discovered for organocatalysts.18 In light
of these successes and with the knowledge of the mechanism
of Biginelli reactions, we envisaged that our catalytic system
of a chiral bifunctional primary amine-thiourea and an acid
could promote asymmetric Biginelli reactions in the presence of
water.
Enantioselective reactions that use chiral phase-transfer cata-
lysts provided some of the most useful methods for practical
asymmetric synthesis because of their simple reaction proce-
dures and mild reaction conditions.1,2 In 1984, the first efficient
chiral phase-transfer catalyst, N-(p-(trifluoromethyl)-benzyl) cin-
chonidium bromide, was devised by the Merck group for the
enantioselective synthesis of (+)-Indacrinone with 92% ee in
95% yield.3 In 1989, O’Donnell reported a simple stereoselective
synthesis of a-amino acid derivatives by the enantioselective
alkylation of pro-chiral protected glycine derivatives with a chiral
phase-transfer catalyst derived from a Cinchona alkaloid,4 and
recently, Corey,5 Lygo,6 Na´jera7 and Jew8 have developed more
efficient Cinchona alkaloid-derived chiral catalysts for this system.
Although several efficient chiral phase-transfer catalysts exist,9,10
the further development of efficient chiral phase-transfer catalysts
is of great interest in the field.
The Biginelli reaction, originally described by the Italian
chemist Pietro Biginelli in 1893, is one of the most useful
multicomponent reactions and allows straightforward access
to functionalized 3,4-dihydropyrimidin-2(1H)-ones (DHPMs).11
Compounds containing the DHPM moiety are inherently asym-
metric molecules, and the influence of the absolute configuration
at the stereogenic center at C4 on their biological activity is well
documented.12 Much effort has been directed towards developing
highly efficient asymmetric Biginelli reactions owing to the exhibi-
tion of a wide range of biological activities by DHPMs, such as an-
tiviral, antitumor, antibacterial, and antiflammatory properties.13
In the field of highly enantioselective Biginelli reactions catalyzed
by an organocatalytic methodology, Gong has successfully applied
BINOL-derived phosphoric acids with excellent enantiocontrol.14
Results and discussion
We initially investigated the catalytic asymmetric Biginelli reaction
of urea (5), benzaldehyde (6) and ethyl acetoacetate (7) with the
bifunctional thiourea catalyst BPAT (I)19 (Scheme 1) and 2,4,6-
trichlorbenzonic acid (TCBA) in the presence of water at room
temperature. Based on the previous successful strategy,15 10 mol%
of t-BuNH2·TFA was added as an additive. As shown in Table
1, a series of different amounts of catalyst BPAT (I) was tested.
The loaded amount of catalyst (5 and 10 mol%) could catalyze
this reaction to provide the desired DHPM product in 83 and
State Key Laboratory and Institute of Elemento-Organic Chemistry, Nankai
University, Tianjin, 300071, China. E-mail: miaozhiwei@nankai.edu.cn;
Fax: +86 2350 2351; Tel: +86 2350 4783
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c0ob01268h
Scheme 1 The structures of BPAT (I) and BPAT (II).
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Table 1 Screening the amount of catalyst in an asymmetric Biginelli
Table 3 Optimization of the influence of solvent on an asymmetric
reactiona
Biginelli reactiona
Yield (%)c
ee (%)d
Entry
Load of catalyst BPAT (I) (mol%)
Yield (%)c
ee (%)d
Entry
Concentration of brine (%)
1
2
3
4
5
83
85
88
87
34
36
50
46
1
2
3
4
5
5
10
15
20
82
87
84
80
93
84
83
87
91
10
15
20
26 (saturated)
>99
a The reaction was carried out on a 0.5 mmol scale and the ratio of 5 : 6 : 7
was 1 : 1.5 : 3. b TCBA = 2,4,6-trichlorbenzonic acid. c Isolated yield based
on the urea. d Determined by HPLC (Chiralcel OD-H).
a Reagents and conditions: After stirring a solution of acid (15 mol%)
and catalyst BPAT (I) (15 mol%) in 2 mL of solvent at 25 ◦C for
0.5 h, urea (0.5 mmol), benzaldehyde (0.75 mmol), ethyl acetoacetate
(1.5 mmol) and t-BuNH2·TFA (10 mol%) were added sequentially.
b TfOH = trifluoromethane sulfonic acid. c Isolated yield based on urea.
d Determined by HPLC (Chiralcel OD-H).
Table 2 Investigation of an acid-catalyzed asymmetric Biginelli reactiona
for 36 h when saturated brine was used as the solvent (Table 3, entry
5). Thus, the optimal reaction conditions for this transformation
were determined to be 0.5 mmol urea, 1.5 equivalent aldehyde,
3 equivalent ethyl acetoacetate and 15 mol% catalyst BPAT (I)
combined with 15 mol% of TfOH containing 10 mol% of t-
BuNH2·TFA in saturated brine at room temperature. On the
other hand, when CH2Cl2 was used as the solvent, the reaction
afforded the DHPM product with a lower yield and a decreased
enantioselectivity, accompanied by a longer reaction time (72 h).
Thus, the role of water in the studied reaction is not only via the
reaction medium, but also by its influence on the reaction rate and
stereoselectivity. The beneficial influence of brine over water can
be explained only on the basis of ionic complexation;21 the rate
acceleration may be attributed to hydrogen bonding interactions.
In addition, a temperature investigation of the reaction established
that this reaction is strongly exothermic.22 Because of the large
specific heat capacity of water, it is very efficient for removing the
thermal energy from reaction mixtures.
Based on the above optimized reaction conditions, the substrate
scope of this reaction was investigated (Table 4). In general, all the
examined substrates produced the desired products in good yields.
The scope of the aldehyde was investigated by the reaction with
urea (5a) and ethyl acetoacetate (7). It appears that the electronic
properties and the position of the substituents on the aromatic
aldehyde have a great influence on the enantioselectivity of the
reaction. Both the reactions of benzaldehyde and para-substituted
benzaldehydes with electron-withdrawing groups proceeded in
high yields and excellent enantioselectivities (>99 and 88% ee)
(Table 4, entries 1 and 2). However, p-chlorobenzaldehyde and p-
bromobenzaldehyde gave lower enantioselectivities (55 and 44%
ee) (Table 4, entries 3 and 4), and para-substituted benzaldehydes
with electron-donating groups underwent the Biginelli reaction
with good yields and good enantioselectivities (Table 4, entries
5 and 6). Meta-substituted benzaldehydes with both electron-
withdrawing and electron-donating groups underwent the reaction
with good yields and enantioselectivities (Table 4, entries 7 and 8).
The enantioselectivity was improved from 51 to 81% ee when 2
equivalents of TfOH were employed in the Biginelli reaction with
o-chlorobenzaldehyde (Table 4, entries 9 and 10). Simultaneously,
Entry
Acid
Yield (%)b
ee (%)c
1
2
3
4
5
6
HAc
HCl
Benzoic acid
p-TSA
TFA
16
41
33
58
72
90
60
54
65
61
22
77
TfOH
a The reaction was carried out on a 0.5 mmol scale and the ratio of 5 : 6 : 7
was 1 : 1.5 : 3. b Isolated yield based on the urea. c Determined by HPLC
(Chiralcel OD-H).
85% yields respectively, but the enantioselectivities were rather
poor (Table 1, entries 1 and 2). Next, we explored catalyst BPAT
(I) (15 mol%) and found that this reaction worked effectively
to provide the DHPM in 88% yield and 50% ee. Furthermore,
increasing the loaded amount of catalyst from 15 to 20 mol% did
not affect the yield, but resulted in a lower ee (Table 1, entry 4).
The acid additive was found to play another important role in
Biginelli reactions.20 In order to improve the efficiency, various
acids combined with catalyst BPAT (I) were then employed to
catalyze this reaction. Compared to TCBA, other organic and
inorganic acids catalyzed the reaction smoothly. For example,
acetic acid, hydrochloric acid, benzoic acid, p-toluenesulfonic acid,
TFA and trifluoromethane sulfonic acid (TfOH) combined with
catalyst BPAT (I) and 10 mol% of t-BuNH2·TFA as an additive
were employed to catalyze the reaction, and DHPMs in moderate
ee were obtained (Table 2, entries 1–5). Within the acids examined,
TfOH was found to be the most effective, and the reaction achieved
90% yield with 77% ee (Table 2, entry 6).
In order to clarify the effect of water on this reaction, the
Biginelli reaction was further undertaken in unsaturated and
saturated NaCl aqueous solutions in the presence of catalyst BPAT
(I) combined TfOH and t-BuNH2·TFA as an additive (Table 3).
Reactions in 5, 10, 15 and 20% NaCl aqueous solutions gave
similar stereochemical results and yields. The best result, with a
93% yield and a greater than 99% ee, was obtained after a reaction
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Table 4 Enantioselective Biginelli reactions catalyzed by chiral bifunc-
the neighbouring primary amine activated ethyl acetoacetate (7)
forms an enamine intermediate, as shown in transition state I
(TS I). The obtained absolute configuration (S) of the DHPMs
is explained by TS I, in which the Re-face of the imine is
predominantly approached by the enamine intermediate. The
approach of the enamine to the Si-face of the benzylideneurea
is restricted by the cyclohexyl scaffold of the catalyst. The fact
that brine significantly enhances the catalytic performance of the
Biginelli reaction suggests that, besides the salt effect, brine could
stabilize TS I through a hydrogen bonding interaction with the aid
of TfOH and promote the hydrolysis step to complete the catalytic
cycle.
tional primary amine-thiourea phase-transfer catalysts in brinea
Entry
8
R
Yield (%)b ee (%)c
Configurationd
1
2
3
4
5
6
7
8
8a
8b
8c
8d
8e
8f
8g
8h
8i
C6H5
93
86
77
74
89
66
84
82
62
72
90
>99
88
55
44
82
89
87
80
51
S
S
S
S
S
S
S
S
S
S
R
4-(F)-C6H4
4-(Cl)-C6H4
4-(Br)-C6H4
4-(Me)-C6H4
4-(OMe)-C6H4
3-(F)-C6H4
3-(Me)-C6H4
2-(Cl)-C6H4
2-(Cl)-C6H4
C6H5
Conclusions
9
In summary, we have developed an enantioselective multi-
component Biginelli reaction catalyzed by a bifunctional primary
amine-thiourea–TfOH (BPAT·TfOH) as a chiral phase-transfer
catalyst and t-BuNH2·TFA as an additive. The catalyst worked
efficiently in aqueous media and offered high yields and moderate
enantioselectivities. The configuration of the products have been
rationalized on the basis of a proposed transition state. Most
importantly, saturated brine significantly promoted the reaction’s
performance. Further studies on the catalytic system in other
reactions are now under way.
10e
11f
8i
81
>99
8j
a Reagents and conditions: After stirring a solution of TfOH (15 mol%) and
catalyst BPAT (I) (15 mol%) in 2 mL of saturated brine at 25 ◦C for 0.5 h,
urea (0.5 mmol), benzaldehyde (0.75 mmol), ethyl acetoacetate (1.5 mmol)
and t-BuNH2·TFA (10 mol%) were added sequentially. b Isolated yield
based on urea. c Determined by HPLC (Chiralcel OD-H). d The absolute
configuration was determined by comparison of the optical rotation with
literature data.23 e 2 equivalents of TfOH were employed. f Catalyst BPAT
(II) (15 mol%) was employed in the reaction.
chiral catalyst BPAT (II) exhibited a similar level of stereoselectiv-
ity with an opposite mode of asymmetric induction, and up to 99%
ee could be obtained. This result indicates that both the (R,R) and
(S,S)-configurations of 1,2-diaminocyclohexane matched the b-D-
glucopyranose and enhanced the stereochemical control (Table 4,
entry 11).
A possible mechanism for the reaction is shown in Fig. 1.
When the reaction is carried out in an aqueous medium, the water
molecules hydrogen bond with the thiourea moiety of bifunctional
catalyst BPAT (I) and the acyl group of the benzylideneurea, while
Experimental
General remarks
All reactions were performed under air. Unless otherwise indi-
cated, all materials were obtained from commercial sources and
used as purchased without dehydration. Element analyses were
carried out on a Yanaco CHN Corder MT-3 automatic analyzer
in the Analysis Center of Nankai University. H NMR and 13C
NMR spectra were recorded in CDCl3 or d6-DMSO using Bruker
1
Fig. 1 A plausible reaction mechanism.
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400 MHz spectrometers. TMS served as the internal standard (d =
0) for H NMR and DMSO was used as the internal standard
(S)-(+)-5-Ethoxycarbonyl-6-methyl-4-(4-methylphenyl)-3,4-
dihydropyrimidin-2(1H)-one (8e). White solid; mp 213–214 ◦C;
1
[a]2D0 = 56◦ (c = 0.5, MeOH); H NMR (400 MHz, CDCl3): d
1
(d = 42.4) for 13C NMR; coupling constants, J, are given in Hz.
HPLC analyses were recorded on a chiral column (Daicel Chiralcel
OD-H column at 254 nm). Melting points were determined on a
T-4 melting point apparatus. Optical rotations were recorded on a
Perkin-Elmer 241 polarimeter.
3
1.17 (t, JH,H = 7.2 Hz, 3H, OCH2CH3), 2.30 (s, 3H, CH3), 2.31
3
(s, 3H, CH3), 4.07 (q, JH,H = 7.2 Hz, 2H, OCH2CH3), 5.35 (d,
3JH,H = 2.8 Hz, 1H, CH), 6.16 (s, 1H, NH), 7.09–7.26 (m, 4H, Ph),
8.73 (s, 1H, NH); 13C NMR (75 MHz, CDCl3): d 14.17, 18.54,
21.12, 55.23, 59.93, 101.36, 126.47, 129.31, 137.59, 140.90, 146.39,
153.90, 165.74; ESI-MS: 273.07 ([M - H]-).
General procedure for the Biginelli reaction
To a suspension of catalyst BPAT (I) (0.039 g, 0.075 mmol)
in saturated brine (2 mL) was added TfOH (0.011 g, 0.075
mmol). After stirring for 30 min, aldehyde 6 (0.75 mmol), urea
5 (0.030 g, 0.5 mmol), ethyl acetoacetate 7 (0.195 g, 1.5 mmol)
and t-BuNH2·TFA (0.009 g, 0.05 mmol) were added sequentially.
The reaction mixture was stirred at room temperature for 36
h. After completion of the reaction, the resulting mixture was
extracted with AcOEt and dried using anhydrous sodium sulfate.
After concentration, the residue was purified by CC (silica gel,
AcOEt/petroleum ether (b.p. 60–90 ◦C) 3 : 2) to afford the DHPM
as a white solid.
(S)-(+)-5-Ethoxycarbonyl-6-methyl-4-(4-methoxyphenyl)-3,4-
dihydropyrimidin-2(1H)-one (8f). White solid; mp 202–205 ◦C;
[a]2D0 = 53◦ (c = 0.5, MeOH); H NMR (400 MHz, CDCl3): d
1
3
1.17 (t, JH,H = 7.2 Hz, 3H, OCH2CH3), 2.30 (s, 3H, CH3), 3.77
3
(s, 3H, OCH3), 4.07 (q, JH,H = 7.2 Hz, 2H, OCH2CH3), 5.33 (d,
3JH,H = 2.4 Hz, 1H, CH), 6.24 (s, 1H, NH), 6.81–7.23 (m, 4H, Ph),
8.77 (s, 1H, NH); 13C NMR (75 MHz, CDCl3): d 14.20, 18.53,
54.96, 55.25, 59.98, 101.47, 101.47, 113.94, 127.81, 136.20, 146.26,
153.95, 159.16, 165.78; ESI-MS: 289.07 ([M - H]-).
(S)-(+)-5-Ethoxycarbonyl-6-methyl-4-(3-fluorophenyl)-3,4-
◦
dihydropyrimidin-2(1H)-one (8g). White solid; mp 212–213 C;
(S)-(+)-5-Ethoxycarbonyl-6-methyl-4-phenyl-3,4-dihydropyri-
[a]2D0 = 58◦ (c = 0.5, MeOH); 1H NMR (400 MHz, CDCl3): d 1.18 (t,
◦
midin-2(1H)-one (8a). White solid; mp 206–207 C; [a]2D0 = 65◦
3JH,H = 7.2 Hz, 3H, OCH2CH3), 2.37 (s, 3H, CH3), 4.10 (q, 3JH,H
=
(c = 0.5, MeOH); 1H NMR (400 MHz, CDCl3): d 1.16 (t, 3JH,H
=
6.8 Hz, 3H, OCH2CH3), 2.34 (s, 3H, CH3), 4.08 (q, 3JH,H = 6.8 Hz,
2H, OCH2CH3), 5.40 (d, 3JH,H = 2.4 Hz, 1H, CH), 5.79 (s, 1H, NH),
7.27–7.32 (m, 5H, Ph), 8.25 (s, 1H, NH); 13C NMR (75 MHz,
CDCl3): d 14.14, 18.67, 55.72, 60.03, 101.32, 126..60, 127.99,
128.71, 143.09, 146.33, 153.35, 165.63; ESI-MS: 259.07 ([M - H]-).
7.2 Hz, 2H, OCH2CH3), 5.41 (s, 1H, CH), 5.53 (s, 1H, NH), 6.95–
7.27 (m, 4H, Ph), 7.34(s, 1H, NH); 13C NMR (75 MHz, CDCl3): d
14.17, 18.77, 55.28, 60.20, 100.96, 113.61, 114.92, 122.19, 130.30,
146.09, 146.67, 153.10, 161.72, 165.45; ESI-MS: 277.07 ([M - H]-).
(S)-(+)-5-Ethoxycarbonyl-6-methyl-4-(3-methylphenyl)-3,4-
◦
(S)-(+)-5-Ethoxycarbonyl-6-methyl-4-(4-fluorophenyl)-3,4-dihy-
dropyrim◦idin-2(1H)-one (8b). White solid; mp 191–192 ◦C;
[a]2D0 = 65 (c = 0.5, MeOH); 1H NMR (400 MHz, CDCl3): d 1.16 (t,
dihydropyrimidin-2(1H)-one (8h). White solid; mp 209–210 C;
[a]2D0 = 56◦ (c = 0.5, MeOH); 1H NMR (400 MHz, CDCl3): d 1.17
3
(t, JH,H = 6.8 Hz, 3H, OCH2CH3), 2.33 (s, 3H, CH3), 2.34 (s,
3JH,H = 6.8 Hz, 3H, OCH2CH3), 2.32 (s, 3H, CH3), 4.07 (q, 3JH,H
=
3
3H, CH3), 4.07 (q, JH,H = 6.8 Hz, 2H, OCH2CH3), 5.36 (s, 1H,
3
6.8 Hz, 2H, OCH2CH3), 5.39 (d, JH,H = 2.4 Hz, 1H, CH), 6.29
(s, 1H, NH), 6.99–7.29 (m, 4H, Ph), 8.69 (s, 1H, NH); 13C NMR
(75 MHz, CDCl3): d 14.16, 18.57, 54.92, 60.11, 101.22, 115.52,
128.30, 139.65, 146.44, 153.74, 161.07, 163.52, 165.55; ESI-MS:
277.07 ([M - H]-).
NH), 5.72 (s, 1H, CH), 7.06–7.26 (m, 4H, Ph), 8.25 (s, 1H, NH);
13C NMR (75 MHz, DMSO): d 14.15, 18.70, 21.51, 55.75, 60.01,
101.34, 123.71, 127. 28, 128.58, 128.74, 138.39, 143.66, 146.24,
153.39, 165.70; ESI-MS: 273.13 ([M - H]-).
(S)-(+)-5-Ethoxycarbonyl-6-methyl-4-(2-chlorophenyl)-3,4-
dihydropy◦rimidin-2(1H)-one (8i). White solid; mp 228–230 ◦C;
(S)-(+)-5-Ethoxycarbonyl-6-methyl-4-(4-chlorophenyl)-3,4-dih-
ydropyrimidin-2(1H)-one (8c). White solid; mp 210–212 ◦C;
1
[a]2D0 = 46 (c = 0.5, MeOH); H NMR (400 MHz, [D6]DMSO):
[a]2D0 = 37◦ (c = 0.5, MeOH); H NMR (400 MHz, CDCl3): d
1
3
d 1.06 (t, JH,H = 6.8 Hz, 3H, OCH2CH3), 2.45 (s, 3H, CH3),
3
1.17 (t, JH,H = 6.8 Hz, 3H, OCH2CH3), 2.31 (s, 3H, CH3), 4.09
3
4.01 (q, JH,H = 6.8 Hz, 2H, OCH2CH3), 5.73 (s, 1H, CH), 5.89
3
(q, JH,H = 6.8 Hz, 2H, OCH2CH3), 5.36 (s, 1H, CH), 6.32 (s,
(s, 1H, NH), 7.21–7.39 (m, 4H, Ph), 8.36 (s, 1H, NH); 13C NMR
(75 MHz, [D6]DMSO): d 13.99, 18.43, 52.15, 60.02, 98. 94, 127.56,
127.98,129.32, 129.82, 132. 58, 139.43, 148.33, 152.84, 165.30; ESI-
MS: 293.00 ([M + H]+).
1H, NH), 7.22–7.30 (m, 4H, Ph), 8.64 (s, 1H, NH); 13C NMR
(75 MHz, CDCl3): d 14.19, 18. 62, 54.98, 60.19, 101.10, 128.01,
128.87, 133.70, 142.24, 146.65, 153.72, 165.51; ESI-MS: 293.00
([M - H]-).
(S)-(+)-5-Ethoxycarbonyl-6-methyl-4-(4-bromophenyl)-3,4-dih-
ydropyrimidin-2(1H)-one (8d). White solid; mp 209–210 ◦C;
[a]2D0 = 38◦ (c = 0.5, MeOH); 1H NMR (400 MHz, CDCl3): d 1.17 (t,
(R)-(-)-5-Ethoxycarbonyl-6-methyl-4-phenyl-3,4-dihydropyri-
midin-2(1H)-one (8j). White solid; mp 202–204 ◦C; [a]D20 = -64◦
(c = 0.5, MeOH); 1H NMR (400 MHz, CDCl3): d 1.16 (t, 3JH,H
=
=
3
3JH,H = 7.2 Hz, 3H, OCH2CH3), 2.33 (s, 3H, CH3), 4.09 (q, 3JH,H
=
6.8 Hz, 3H, OCH2CH3), 2.32 (s, 3H, CH3), 4.07 (q, JH,H
3
7.2 Hz, 2H, OCH2CH3), 5.35 (d, JH,H = 2.8 Hz, 1H, CH), 6.15
(s, 1H, NH), 7.18–7.44 (m, 4H, Ph), 8.46 (s, 1H, NH); 13C NMR
(75 MHz, CDCl3): d 14.19, 18.69, 55.12, 60.19, 100.99, 121.88,
128.38, 131.83, 142.72, 146.58, 153.42, 153.48, 165.47; ESI-MS:
336.93 ([M - H]-).
6.8 Hz, 2H, OCH2CH3), 5.39(d, 3JH,H = 2.4 Hz, 1H, CH), 6.11(s,
1H, NH), 7.26–7.31 (m, 5H, Ph), 8.64 (s, 1H, NH); 13C NMR
(75 MHz, CDCl3): d 14.16, 18.70, 55.73, 60.05, 101.35, 126.62,
127.98, 128.73, 143.71, 145.33, 153.33, 165.66. ESI-MS: 259.07
([M - H]-).
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Acknowledgements
We thank the National Natural Science Foundation of China
(21072102), the Committee of Science and Technology of Tianjin,
and the State Key Laboratory of Elemento-Organic Chemistry of
Nankai University for financial support.
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3054 | Org. Biomol. Chem., 2011, 9, 3050–3054
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