Efficient methods for the synthesis of benzopyrano[3,4-c]pyrrolidines by catalyzed 1,3-dipolar cycloaddition of azomethine ylides with 3-substituted coumarins

Article abstract of DOI:10.1080/00397911.2010.518273

With triethylamine as a catalyst, the 1,3-dipolar cycloaddition of azomethine ylides with 3-substituted coumarins proceeded smoothly under mild conditions to afford the desired products benzopyrano[3,4-c]pyrrolidines in good to excellent yields.

Full text of DOI:10.1080/00397911.2010.518273

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Efficient Methods for the Synthesis
of Benzopyrano[3,4-c]pyrrolidines by
Catalyzed 1,3-Dipolar Cycloaddition of
Azomethine Ylides with 3-Substituted
Coumarins
Li-Ping Fan a , Wei-Jun Yang a , Dong-Cheng Xu a , Xin-Sheng Li a
Jian-Wu Xie a
&
a Zhejiang Key Laboratory for Reactive Chemistry on Solid Surfaces,
College of Chemistry and Life Sciences, Zhejiang Normal University,
Jinhua, China
Version of record first published: 26 Jul 2011.
To cite this article: Li-Ping Fan , Wei-Jun Yang , Dong-Cheng Xu , Xin-Sheng Li & Jian-Wu Xie (2011):
Efficient Methods for the Synthesis of Benzopyrano[3,4-c]pyrrolidines by Catalyzed 1,3-Dipolar
Cycloaddition of Azomethine Ylides with 3-Substituted Coumarins, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 41:22, 3376-3384
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Synthetic Communications1, 41: 3376–3384, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.518273
EFFICIENT METHODS FOR THE SYNTHESIS OF
BENZOPYRANO[3,4-c]PYRROLIDINES BY CATALYZED
1,3-DIPOLAR CYCLOADDITION OF AZOMETHINE
YLIDES WITH 3-SUBSTITUTED COUMARINS
Li-Ping Fan, Wei-Jun Yang, Dong-Cheng Xu, Xin-Sheng Li,
and Jian-Wu Xie
Zhejiang Key Laboratory for Reactive Chemistry on Solid Surfaces, College
of Chemistry and Life Sciences, Zhejiang Normal University, Jinhua, China
GRAPHICAL ABSTRACT
Abstract With triethylamine as a catalyst, the 1,3-dipolar cycloaddition of azomethine
ylides with 3-substituted coumarins proceeded smoothly under mild conditions to afford
the desired products benzopyrano[3,4-c]pyrrolidines in good to excellent yields.
Keywords Azomethine
dipolar cycloaddition
ylide;
benzopyrano[3,4-c]pyrrolidine;
coumarin;
1,3-
INTRODUCTION
Development of novel synthetic methods for the construction of new analogs
of bioactive heterocyclic compounds is a major challenge in synthetic organic and
medicinal chemistry. The 1,3-dipolar cycloaddition has been employed as one of the
most powerful synthetic tools to provide a variety of five-membered carbocycles as
well as heterocycles.[1] For example, the 1,3-dipolar cycloaddition of azomethine ylides
with olefins affords highly functionalized pyrrolidines, which are structural motifs of
biologically active naturally occurring substances as well as pharmaceuticals.[2] The
ease of generation of 1,3-dipoles, coupled with the olefins to give highly regio- and
stereoselective nature to their cycloaddition reactions, has led to a number of
syntheses.[3] Recently, we have demonstrated the usefulness of the intermolecular
Received July 26, 2009.
Address correspondence to Jian-Wu Xie, Zhejiang Key Laboratory for Reactive Chemistry on
Solid Surfaces, College of Chemistry and Life Sciences, Zhejiang Normal University, Jinhua, 321004,
China. E-mail: xiejw@zjnu.cn
3376

BENZOPYRANO[3,4-c]PYRROLIDINES
3377
=
Figure 1. Reagents and conditions: (i) piperidine or Et2NH=HCl; (ii) PhCH NCH(COOEt)2(2a), base.
1,3-dipolar cycloaddition of azomethine ylides in the synthesis of highly functionalized
pyrrolidines with high diastereo- and enantioselectivities.[4] This method gives rapid
access to the pyrrolidine ring system.
To the best of our knowledge, coumarins have never been used as 2p components
in cycloaddition reactions, although they were promising starting materials for the
synthesis of functionalized heterocyclic frameworks. We considered that the incorpor-
ation of a pyrrolidine heterocyclic unit into coumarins might provide new compouds
that had important biological and pharmaceutical activities. During our ongoing
studies of 3-carbethoxycoumarin 1a, we envisaged that 1,3-dipolar cycloaddition
would be possible between the azomethine ylides and 3-carbethoxycoumarin 1a, which
was conveniently prepared from salicylaldehyde in a single step, to provide a straight-
forward protocol for the synthesis of benzopyrano[3,4-c]pyrrolidine 3a with a highly
functionalized pyrrolidine ring (Fig. 1).
In an initial study, we investigated 1,3-dipolar cycloaddition reaction between
1a and 2a in a series of organic solvents and bases (Table 1). First, we tested several
Table 1. Screening studies of 1,3-dipolar cycloaddition of a-amino malonate imine 2a to 3-carbethoxy-
coumarin 1aa
Entry
Base
Solvent
Yield (%)c
1
N(C2H5)3
DABCO
DBU
EtOH
EtOH
EtOH
EtOH
H2O
96
92
2
3
88
4
CH3COONa
N(C2H5)3
N(C2H5)3
N(C2H5)3
NRd
NRd
NRd
Mixture
5
6b
7b,e
EtOH
Toluene
aReactions performed with 0.3 mmol 1a and 0.6 mmol 2a, 0.06 mmol base, in 2.5 ml solvent at room
temperature.
b
=
Reactions performed with PhCH NCH2COOEt (2b).
cIsolated yield.
dNo reaction.
eReflux.

3378
L.-P. FAN ET AL.
bases for their application in the 1,3-dipolar cycloadditions. To our delight, when the
reaction was carried out in the presence of triethylamine (20 mol%) in ethanol at
room temperature, [3 þ 2] cycloadduct was isolated with good yield (96% yield, entry
1). Somewhat poor yields were isolated when the reaction was catalyzed with more
strong bases, such as 1,4-diazabicyclo[2.2.2]octane (DABCO) or 1,8-diazabicy-
clo[5.4.0]undec-7-ene (DBU) (92% yield and 88% yield, Table 1, entries 2 and 3).
Among the solvents examined, use of ethanol gave the best results, affording the
[3 þ 2] cycloadduct 3a (96% yield, Table 1, entry 1). No cycloadduct 3a was observed
when the reaction was carried out in water. 1,3-Dipolar cycloadditions of azo-
methine ylides derived from glycine ethyl ester were also investigated, but unfortu-
nately, no product was observed when the reaction was carried out in ethanol
(Table 1, entry 6). By increasing the temperature in toluene, no main product was
observed (Table 1, entry 7).
Having established the optimal reaction conditions for the 1,3-dipolar cycload-
dition between 1a and 2a, we investigated a series of analogs that bear various substi-
tuents on the phenyl group and 3-position of coumarin. The 1,3-dipolar cycloaddition
was generally conducted with 20 mol% of triethyamine in ethanol at 25 ꢀC (Table 2).
As illustrated in Table 2, 3-carbmethoxycoumarin cleanly underwent 1,3-dipolar
cycloaddition with a-amino malonate imines, and the electronic effect on the phenyl
ring of a-amino malonate imines was very marginal (Table 2, entries 1–4). Entries 6
Table 2. 1,3-Dipolar cycloaddition of various a-amino malonate imine 2a to 3-substituted coumarins 1a
Entry
R1
R2 (1)
Ar
C6H5
(2)
Products 3
Yields (%)b
1
2
H
H
H
H
COOMe (1a)
COOMe (1a)
COOMe (1a)
COOMe (1a)
COOEt (1b)
COOEt (1c)
COOEt (1d)
NO2 (1e)
(2a)
(2b)
(2c)
(2d)
(2a)
(2a)
(2a)
(2a)
(2c)
(2e)
(2b)
(2d)
(2a)
3a
3b
3c
3d
3e
3f
96
92
p-BrC6H4
p-CH3C6H4
2-Furanyl
C6H5
3
90
4
73
5
4-CH3O
NRc
94
6
5-F
5-Cl
H
C6H5
C6H5
C6H5
7
3g
3h
3i
96
97
8
9
H
NO2 (1e)
NO2 (1e)
p-CH3C6H4
p-ClC6H4
p-BrC6H4
2-Furanyl
C6H5
84
87
10
11
12
13
H
3j
H
NO2 (1e)
NO2(1e)
COMe (1f)
3k
3l
88
91
H
H
3m
90
aReactions performed with 0.3 mmol 1a and 0.6 mmol 2a, 0.06 mmol triethylamine, in 2.5 mL ethanol at
room temperature for 12 h.
bIsolated yield.
cNo reaction.

BENZOPYRANO[3,4-c]PYRROLIDINES
3379
Figure 2. Molecular structure of 3g.
and 7 (Table 2) show that 3-carbmethoxycoumarin with electron-withdrawing substi-
tuents provided the cycloadducts 3f–g in excellent yields. In conrast, 3-carbmethoxy-
coumarin with electron-donating substituents gave no cycloadduct (Table 2, entry 5).
Various electron-withdrawing substituents on the 3-position of coumarin underwent
reaction smoothly as well and furnished the desired adducts with excellent yields
(Table 2, entries 8–13).
To determine the configuration of benzopyrano[3,4-c]pyrrolidines, single crystals
suitable for x-ray crystallographic analysis were fortunately obtained from racemic 3g,
which bears a chlorine atom. As shown in Fig. 2, the x-ray structure of 3g confirmed
the cis stereochemistry at the ring junction.
In conclusion, we have successfully demonstrated the 1,3-dipolar cycloaddition
of a variety of 3-substituted coumarins to various a-amino malonate imines with
excellent diastereoselectivity, employing readily available Et3N as catalyst. The
1,3-dipolar cycloaddition can proceed smoothly at room temperature and provides
pure benzopyrano[3,4-c]pyrrolidines in good to excellent yields. This novel method-
ology should be of great interest for natural product synthesis and pharmaceutical
synthesis.
EXPERIMENTAL
1H NMR (400-MHz) spectra were recorded on a Bruker AV400 NMR instru-
ment as CDCl3 solutions using tetramethylsilane (TMS) as internal standard.
Chemical shifts (d) are reported in parts per million (ppm) and coupling constants
J are given in hertz (Hz). Infrared (IR) spectra were recorded in film or using KBr
disks with a Nexus 670 Fourier transform (FT)–IR spectrometer. Mass spectra were
recorded on an HP 5989B MS spectrometer. Elemental analyses were performed on
a Vario-EL III instrument. Electrospray ionization–high-resolution mass spec-
trometry (ESI-HRMS) was measured with a Finnigan LCQDECA ion trap mass spec-
trometer. Compounds 1a–1d, 1f,[5] and 1e[6] were prepared according to literature
procedures.

3380
L.-P. FAN ET AL.
General Procedure for the 1,3-Dipolar Cycloaddition of Various
a-Amino Malonate Imines to 3-Substituted Coumarins
Compounds 1a (0.3 mmol) and 2a (0.6 mmol) and 0.06 mmol triethylamine
were stirred in ethanol (2.5 mL) at 25 ꢀC for 12 h. Then 1 ml petroleum ether was
added to the solution. The product crystallized; the mixture was stirred from time
to time as crystallization proceeded. The crystalline product was collected by
filtration and washed with a solution (10% ethyl acetate=petroleum ether) to give
3a as a white solid. Product 3a was also obtained by flash chromatography on silica
gel (15% ethyl acetate=petroleum ether).
1,1-Diethyl 3a-Methyl 4-Oxo-3-phenyl-2,3,3a,4-tetrahydrochromeno-
[3,4-c]-pyrrole-1,1,3a(9bH)-tricarboxylate (3a)
1H NMR (400 MHz, CDCl3) d (ppm) 7.71 (d, J ¼ 7.6 Hz, 1H), 7.43
(d, J ¼ 6.6 Hz, 2H), 7.35–7.13 (m, 5H), 7.01 (d, J ¼ 8.1 Hz, 1H), 5.85 (d, J ¼ 6.4 Hz,
1H), 5.06 (s, 1H), 4.45–4.31 (m, 2H), 3.97–3.78 (m, 2H), 3.44 (d, J ¼ 6.5 Hz, 1H), 3.18
(s, 3H), 1.32 (t, J ¼ 7.0 Hz, 3H), 0.83 (t, J ¼ 7.1 Hz, 3H); 13C NMR (100 MHz,
CDCl3) d (ppm) 170.5, 167.1, 165.6, 164.7, 150.6, 139.7, 131.0, 129.6, 129.2, 128.2,
127.7, 127.5, 124.8, 124.7, 117.5, 116.6, 75.7, 66.5, 63.7, 62.5, 62.4, 53.1, 46.8, 14.0,
13.4; nmax(KBr)=cmꢁ1 3341, 2980, 1703, 1718, 1600, 1470, 1434, 756, 712, 656;
ESI-HRMS: calcd. for C25H25NO8þNa 490.1473; found 490.1471.
1,1-Diethyl 3a-Methyl 3-(4-Bromophenyl)-4-oxo-2,3,3a,4-tetrahydro-
chromeno-[3,4-c]pyrrole-1,1,3a(9bH)-tricarboxylate (3b)
1H NMR (400 MHz, CDCl3) d (ppm) 7.71 (d, J ¼ 7.4 Hz, 1H), 7.46–7.14
(m, 6H), 7.01 (d, J ¼ 8.1 Hz, 1H), 5.00 (d, J ¼ 6.4 Hz, 1H), 5.01 (s, 1H), 4.42–4.31
(m, 2H), 3.91–3.80 (m, 2H), 3.39 (d, J ¼ 6.4 Hz, 1H), 3.23 (s, 3H), 1.31 (t, J ¼ 7.0 Hz,
3H), 0.88–0.80 (m, 3H); 13C NMR (100 MHz, CDCl3) d (ppm) 170.4, 168.8, 165.6,
164.6, 150.5, 139.8, 131.2, 131.2, 131.0, 129.7, 129.5, 129.3, 124.9, 122.1, 117.2,
116.6, 77.5, 65.8, 63.4, 62.6, 62.4, 53.3, 46.9, 14.0, 13.3; nmax(KBr)=cmꢁ1 3310,
2970, 1746, 1713, 1600, 1479, 1407, 735, 645; ESI-HRMS: calcd. for C25H24
BrNO8þNa 568.0578; found 568.0578.
1,1-Diethyl 3a-Methyl 4-Oxo-3-(p-tolyl)-2,3,3a,4-tetrahydrochromeno-
[3,4-c]-pyrrole-1,1,3a(9bH)-tricarboxylate (3c)
1H NMR (400 MHz, CDCl3) d (ppm) 7.73 (d, J ¼ 16.4 Hz, 1H), 7.38–7.13
(m, 6H), 7.01 (d, J ¼ 8.1 Hz, 1H), 5.81 (d, J ¼ 6.5 Hz, H), 5.10 (s, 1H), 4.45–4.27
(m, 2H), 3.97–3.62 (m, 2H), 3.42 (d, J ¼ 6.5 Hz, 1H), 3.22 (s, 3H), 2.32 (s, 3H),
1.32 (t, J ¼ 7.1 Hz, 3H), 0.84 (t, J ¼ 8.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) d
(ppm) 170.5, 169.2, 165.6, 164.7, 150.7, 137.8, 136.6, 131.0, 129.6, 128.9, 128.9,
127.4, 127.4, 124.8, 117.6, 116.6, 75.7, 66.4, 63.6, 62.5, 62.4, 53.2, 46.8, 21.2, 14.0;
n
max(KBr)=cmꢁ1 3323, 2974, 1753, 1725, 1643, 1489, 1423, 750, 710, 630;
ESI-HRMS: calcd. for C26H27NO8þNa 504.1629; found 504.1631.

BENZOPYRANO[3,4-c]PYRROLIDINES
3381
1,1-Diethyl 3a-Methyl 3-(Furan-2-yl)-4-oxo-2,3,3a,4-tetrahydrochro-
meno[3,4-c]-pyrrole-1,1,3a(9bH)-tricarboxylate (3d)
1H NMR (400 MHz, CDCl3) d (ppm) 7.69 (d, J ¼ 7.0, 1H), 7.34–7.13 (m, 3H),
7.00 (d, J ¼ 8.1 Hz, 1H), 6.31–6.24 (m, 2H), 5.71 (d, J ¼ 4.72 Hz, 1H), 5.23 (s, 1H),
4.44–4.28 (m, 2H), 3.79–3.68 (m, 2H), 3.62 (d, J ¼ 4.7 Hz, 1H), 3.51 (s, 3H),
1.37–1.29 (m, 3H), 0.83 (t, J ¼ 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) d (ppm)
170.2, 169.8, 165.0, 163.4, 152.1, 150.8, 142.8, 131.1, 129.6, 124.8, 117.7, 116.7,
110.5, 108.4, 76.2, 63.2, 62.7, 62.6, 61.0, 53.6, 47.1, 14.1, 13.2; nmax(KBr)=cmꢁ1
3168, 2921, 1770, 1734, 1612, 1435, 1410, 756, 715; ESI-HRMS: calcd. for
C23H23NO9þNa 480.1265; found 480.1261.
Triethyl 8-Fluoro-4-oxo-3-phenyl-2,3,3a,4-tetrahydrochromeno[3,4-c]-
pyrrole-1,1,3a(9bH)-tricarboxylate (3f)
1H NMR (400 MHz, CDCl3) d (ppm) 7.72–7.24 (m, 8H), 5.63 (s, 1H), 5.29
(s, 1H), 4.45–4.25 (m, 2H), 4.00–3.50 (m, 6H), 1.29 (t, J ¼ 7.1 Hz, 3H), 1.12 (t,
J ¼ 7.1 Hz, 3H), 1.05 (t, J ¼ 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) d (ppm)
169.6, 169.6, 168.3, 166.8, 166.6, 138.9, 138.0, 129.3, 128.6, 128.6, 128.5, 128.5,
128.5, 128.0, 127.8, 127.8, 76.7, 67.7, 62.2, 62.2, 62.1, 61.1, 61.1, 14.0, 13.3;
n
max(KBr)=cmꢁ1 3100, 2923, 1731, 1715, 1623, 1431, 1407, 715, 663; ESI-HRMS:
calcd. for C25H24FNO8þNa 522.1538; found 522.1531.
Triethyl 8-Chloro-4-oxo-3-phenyl-2,3,3a,4-tetrahydrochromeno[3,4-c]-
pyrrole-1,1,3a(9bH)-tricarboxylate (3g)
1H NMR (400 MHz, CDCl3) d (ppm) 7.72–7.24 (m, 8H), 5.63 (s, 1H), 5.29
(s, 1H), 4.44–4.25 (m, 2H), 4.86–3.66 (m, 6H), 1.29 (t, J ¼ 7.1 Hz, 3H), 1.12
(t, J ¼ 7.1 Hz, 3H), 1.05 (t, J ¼ 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) d (ppm)
169.6, 169.6, 168.3, 166.8, 166.6, 138.9, 138.0, 129.3, 128.6, 128.6, 128.5, 128.5,
128.5, 128.0, 127.8, 127.8, 76.7, 67.7, 62.2, 62.2, 62.1, 61.1, 61.1, 14.0, 13.3;
n
max(KBr)=cmꢁ1 3301, 2914, 1743, 1710, 1643, 1423, 1406, 712, 705, 653;
ESI-HRMS: calcd. for C25H24ClNO8þNa 538.1240; found 538.1229.
Diethyl 3a-Nitro-4-oxo-3-phenyl-2,3,3a,4-tetrahydrochromeno[3,4-c]-
pyrrole-1,1(9bH)-dicarboxylate (3h)
1H NMR (400 MHz, CDCl3) d (ppm) 7.71 (d, J ¼ 7.6 Hz, 1H), 7.51–7.17
(m, 7H), 7.08 (d, J ¼ 8.2 Hz, 1H), 5.97 (d, J ¼ 6.4 Hz, 1H), 5.32 (s, 1H), 4.48–4.35
(m, 2H), 3.96–3.85 (m, 2H), 3.41 (d, J ¼ 6.4 Hz, 1H), 1.34 (t, J ¼ 7.1 Hz, 3H), 0.87
(t, J ¼ 14.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) d (ppm) 169.7, 168.1, 159.3,
150.1, 136.6, 131.0, 130.5, 129.1, 128.5, 128.5, 127.4, 125.4, 125.4, 117.1, 114.9,
96.0, 74.6, 65.6, 62.9, 62.8, 49.0, 14.1, 13.4; nmax(KBr)=cmꢁ1 3307, 2914, 1727,
1705, 1639, 1422, 1408, 712, 709, 643; ESI-HRMS: calcd. for C23H22N2O8þNa
477.1268; found 477.1262.

3382
L.-P. FAN ET AL.
Diethyl 3a-Nitro-4-oxo-3-(p-tolyl)-2,3,3a,4-tetrahydrochromeno[3,4-c]-
pyrrole-1,1(9bH)-dicarboxylate (3i)
1H NMR (400 MHz, CDCl3) d (ppm) 7.70 (d, J ¼ 7.7 Hz, 1H), 7.38–7.14
(m, 6H), 7.07 (d, J ¼ 8.2 Hz, 1H), 5.92 (d, J ¼ 6.4 Hz, 1H), 5.31 (s, 1H), 4.43–4.40
(m, 2H), 3.94–3.87 (m, 2H), 3.39 (d, J ¼ 6.3 Hz, 1H), 2.33 (s, 3H), 1.35 (t, J ¼ 7.1 Hz,
3H), 0.86 (t, J ¼ 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) d (ppm) 168.7, 168.2,
159.3, 150.2, 138.9, 133.5, 131.0, 130.4, 129.2, 129.2, 127.3, 125.4, 117.1, 117.1,
115.0, 96.0, 74.6, 65.6, 62.9, 62.8, 49.0, 21.2, 14.0, 13.3, nmax(KBr)=cmꢁ1 3109,
2924, 1778, 1759, 1615, 1456, 1431, 718, 709, 632; ESI-HRMS: calcd. for
C24H24N2O8þNa 491.1425; found 491.1423.
Diethyl 3-(4-Chlorophenyl)-3a-nitro-4-oxo-2,3,3a,4-tetrahydrochro-
meno[3,4-c]-pyrrole-1,1(9bH)-dicarboxylate (3j)
1H NMR (400 MHz, CDCl3) d (ppm) 7.73–7.07 (m, 8H), 5.94 (d, J ¼ 6.38 Hz,
1H), 5.28 (s, 1H), 4.43–4.39 (m, 2H), 3.93–3.90 (m, 6H), 3.35 (d, J ¼ 6.4 Hz, 1H),
1.37–1.31 (m, 3H), 0.86 (t, J ¼ 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) d (ppm)
169.6, 169.6, 168.3, 166.8, 166.6, 138.9, 138.0, 129.3, 128.6, 128.6, 128.5, 128.5,
128.5, 128.0, 127.8, 127.8, 76.7, 67.7, 62.2, 62.2, 62.1, 61.1, 61.1, 14.0, 13.3;
n
max(KBr)=cmꢁ1 3309, 2967, 1712, 1675, 1412, 760, 712, 610; ESI-HRMS: calcd.
for C23H21ClN2O8þNa 511.0879; found 511.0877.
Diethyl 3-(4-Bromophenyl)-3a-nitro-4-oxo-2,3,3a,4-tetrahydrochro-
meno[3,4-c]-pyrrole-1,1(9bH)-dicarboxylate (3k)
1H NMR (400 MHz, CDCl3) d (ppm) 7.72 (d, J ¼ 7.3 Hz, 1H), 7.49–7.33
(m, 5H), 7.22–7.18 (m, 1H), 7.08 (d, J ¼ 7.1 Hz, 1H), 5.93 (d, J ¼ 6.4 Hz, 1H), 5.28
(s, 1H), 4.46–4.36 (m, 2H), 3.94–3.88 (m, 2H), 3.36 (d, J ¼ 7.2 Hz, 1H), 1.35
(t, J ¼ 7.1 Hz, 3H), 0.85 (t, J ¼ 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) d (ppm)
169.7, 167.9, 159.2, 150.0, 135.7, 131.7, 131.0, 131.0, 130.6, 129.2, 129.2, 125.5,
123.3, 117.1, 114.6, 95.9, 74.5, 65.1, 63.0, 62.9, 49.2, 14.0, 13.3; nmax(KBr)=cmꢁ1
3209, 2912, 1732, 1729, 1409, 1432, 734, 701, 632; ESI-HRMS: calcd. for C23H21
BrN2O8þNa 555.0373; found 555.0367.
Diethyl 3-(Furan-2-yl)-3a-nitro-4-oxo-2,3,3a,4-tetrahydrochromeno[3,
4-c]pyrrole-1,1(9bH)-dicarboxylate (3l)
1H NMR (400 MHz, CDCl3) d (ppm) 7.52 (dd, J ¼ 7.7, 1.2 Hz, 1H), 7.48–7.18
(m, 4H), 7.07 (d, J ¼ 8.2 Hz, 1H), 6.37–6.34 (m, 2H), 5.83 (s, 1H), 5.57 (s, 1H),
4.47–4.37 (m, 2H), 3.83–3.69 (m, 2H), 1.37 (t, J ¼ 7.1 Hz, 3H), 0.85 (t, J ¼ 7.1 Hz,
3H); 13C NMR (100 MHz, CDCl3) 169.4, 169.0, 158.0, 154.9, 150.4, 149.1, 143.7,
131.1, 130.5, 126.0, 125.5, 117.1, 115.6, 110.8, 110.4, 75.0, 63.2, 63.0, 48.0, 14.1,
13.2, nmax(KBr)=cmꢁ1 3312, 2904, 1725, 1722, 1479, 1453, 763, 625; ESI-HRMS:
calcd. for C21H20N2O9þNa 467.1061; found 467.1053.

BENZOPYRANO[3,4-c]PYRROLIDINES
3383
Diethyl 3a-Acetyl-4-oxo-3-phenyl-2,3,3a,4-tetrahydrochromeno[3,4-c]-
pyrrole-1,1(9bH)-dicarboxylate (3m)
1H NMR (400 MHz, CDCl3) d (ppm) 7.73 (d, J ¼ 7.7 Hz, 1H), 7.45–7.13
(m, 7H), 6.98 (d, J ¼ 8.1 Hz, 1H), 5.82 (d, J ¼ 6.1 Hz, 1H), 5.12 (s, 1H), 4.40–4.28
(m, 2H), 3.92–3.68 (m, 2H), 3.38 (d, J ¼ 6.2 Hz, 1H), 1.71 (s, 3H), 1.34–1.21 (m,
3H), 0.87 (t, J ¼ 7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) d (ppm) 170.6, 169.1,
166.9, 166.9, 150.4, 139.3, 134.5, 131.0, 130.3, 129.5, 128.6, 128.5, 128.1, 125.0,
117.7, 116.4, 75.6, 69.9, 67.3, 62.4, 62.4, 46.0, 27.7, 14.1, 13.3, nmax(KBr)=cmꢁ1
3123, 2912, 1773, 1749, 1665, 1467, 1412, 767, 720, 675; ESI-HRMS: calcd. for
C25H25NO7þNa 474.1524; found 474.1519.
ACKNOWLEDGMENTS
We are grateful for the financial support from the National Natural Science
Foundation of China (20902083), the Province Natural Science Foundation of
Zhejiang (Y4090082), and Zhejiang Normal University.
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