A simple method for the synthesis of functionalized 6-aryl-6H-dibenzo[b,d] pyran derivatives from 3-nitro-2H chromenes

Article abstract of DOI:10.1016/j.tet.2010.07.042

The one-pot synthesis of multi-substituted 6-aryl-6H-dibenzo[b,d]pyran derivatives was achieved via vinylogous Michael addition as the key step and domino reactions under mild reaction conditions, employing readily available α,α-dicyanoolefins and 3-nitro-2H-chromenes as substrates.

Full text of DOI:10.1016/j.tet.2010.07.042

Tetrahedron 66 (2010) 7590e7594
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
A simple method for the synthesis of functionalized 6-aryl-6H-dibenzo[b,d]pyran
derivatives from 3-nitro-2H chromenes
*
Ping Li, Ling-Ling Luo, Xin-Sheng Li, Jian-Wu Xie
Zhejiang Key Laboratory for Reactive Chemistry on Solid Surfaces, Department of Chemistry and Life Science, Zhejiang Normal University, Jinhua 321004, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 13 May 2010
Received in revised form 8 July 2010
Accepted 16 July 2010
Available online 22 July 2010
The one-pot synthesis of multi-substituted 6-aryl-6H-dibenzo[b,d]pyran derivatives was achieved via
vinylogous Michael addition as the key step and domino reactions under mild reaction conditions,
employing readily available
a
,a
-dicyanoolefins and 3-nitro-2H-chromenes as substrates.
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
derivatives.12 In this paper, we describe a one-pot synthesis of multi-
substituted 6-aryl-6H-dibenzo[b,d]-pyran derivatives via vinyl-
ogous Michael addition as the key step and domino reactions under
Development of drug-like heterocycle compounds from simple
substrates through domino reactions catalyzed by readily available
small organic molecule is one of the emerging areas in modern
synthetic chemistry, even though there are already many common
synthesis strategies for the construction of CeC, CeN, CeO, CeS and
CeX (X¼halogen) bonds in structurally diverse natural and non-
natural products by conventional methods. The benzopyran unit is
the core structure in a plethora of natural products and synthetic
compounds.1 Among of this class of compounds, the dibenzo[b,d]
pyran nucleus constitutes the skeleton of a number of physiologi-
cally active natural products as well as drugs,2 such as cannabinol,
a constituent of cannabis, which have been characterized to have
this structural unit.3e5 The dibenzo[b,d]pyran and their derivatives
have attracted strong interest due to their useful biological and
pharmacological properties.6 The dibenzo[b,d]pyran ring system
can also afford an interesting photochemical reaction via the pro-
posed o,o0-biphenyl quinone intermediate and will be useful as
photoswitches.7e9 Thus, continuous efforts have been devoted to
the development of more general and versatile synthetic method-
ologies for this class of compounds. Apart from the various classical
approaches towards the synthesis of the dibenzo[b,d]
pyrans,6a,9b,10ej three different strategies developed for their syn-
thesis have been reported recently: Fagnou et al. obtained the
dibenzo[b,d]pyrans by palladium-catalyzed cross-coupling re-
actions catalyzed with Pd(OAc)2 and 2-(diphenylphosphino)-20-(N,
N-dimethylamino) biphenyl at 125e145 ꢀC.11 Wang et al. used a re-
ductive ring opening and cyclization to get the dibenzo[b,d]pyrans
from dibenzofuran.7 The multi-step synthesis by Finet and Fedorov
involved a bismuth-mediated oxidationeortho-arylationecyclisa-
tion sequence for the synthesis of the dibenzo[b,d]pyran
mild reaction conditions, employing readily available
a,a-dicya-
noolefins and 3-nitro-2H-chromenes as substrates.
Recently, we13 and other research groups14 reported that the
electron-deficient a,a-dicyanoolefins could behave as good hydride
acceptors in conjugate reduction reactions and also act as versatile
direct vinylogous donors in asymmetric Michael addition reactions
with excellent chemo- and stereoselectivity. The concept of g-po-
sition activation according to strong electron-withdrawing groups
was expressed adequately. During our ongoing studies of readily
available 3-nitro-2H-chromene derivatives 1 and
fins, we envisaged that tandem reactions would be possible be-
tween the -dicyanoolefins and 3-nitro-2H-chromene derivatives
a,a-dicyanoole-
a,a
1, as outlined in Scheme 1, to provide a straightforward protocol for
the synthesis of the multi-substituted 6-aryl-6H-dibenzo[b,d]-py-
ran derivatives.
Ar2
R2
CN
NC
Ar2
CN
R2
NO2
Ar1
NH2
base
+
O
Ar1
O
R1
R1
1
2
4
(a)
R2
(d)
Ar2
Ar2
Ar2
R2
CN
CN
R2
CN
CN
NH
NO2
(c)
(b)
NO2
Ar1
NH2
O
Ar1
R1
NO2
O
R1
O
Ar1
3
R1
(a) Vinylogous Michael addition; (b) Cyclization;
(c) Rearrangement; (d) elimination of the leave group NO2
* Corresponding author. Fax: þ86 579 82282610; e-mail address: xiejw@zjnu.cn
Scheme 1. The novel method for the synthesis of benzopyran derivatives.
(J.-W. Xie).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.07.042

P. Li et al. / Tetrahedron 66 (2010) 7590e7594
7591
2. Results and discussion
products 4aae4ae and 4ah from 3-nitro-2H-chromenes 1 and a,a-
dicyanoolefins 2 (2g and 2f), the domino reactions were refluxed in
ethanol and catalyzed by 100 mol % NaOAc, however, the reactions
became complicated in many cases. To establish the structure of 3,
single crystal suitable for X-ray crystallographic analysis was for-
tunately obtained from 3df that bears a chlorine atom (Fig. 2).
We started our original studies by screening a number of readily
available bases and solvents for the domino reactions of 3-nitro-
2H-chromene 1a with a,a-dicyanoolefin 2a. A few of representative
results are shown in Table 1. To our delight, the domino reactions
proceeded smoothly to provide the desired product 4aa when the
reactions were carried out in the presence of bases (100 mol %) in
THF at room temperature (Table 1, entries 1e5). We got the best
results when the reaction was catalyzed by triethylamine (entry 5).
Somewhat low yields were isolated when the reaction was cata-
lyzed with more strong bases, such as NaOAc, DABCO, DBU and
K2CO3 (Table 1, entries 1e4). Among the solvents examined, use of
DCM gave the best result, affording the desired product 4aa (71%
yield, Table 1, entry 9). Very poor results were observed when the
reaction was carried out in other solvents. (Table 1, entries 6e8). In
the hope of enhancing the yields, the reaction was refluxed in DCM,
unfortunately, the yield was a little decreased (Table 1, entry 10).
NO2
F
NO2
Ph
NO2
Ph
MeO
O
Ph
O
O
1c
1b
1a
NC
CN
Cl
NO2
Ph
NO2 1e Ar = p-CF3C6H4
1f Ar = p-ClC6H4
Ph
1g Ar = p-CH3C6H4
1h Ar = furyl
O
O
Ar
2f
1d
NH2 Ph
NC
CN
NC
NC
CN
O
O
2g
O
4ah
Table 1
2h
Screening studies of one-pot tandem reaction of 3-nitro-2H-chromene 1a and
a,a-
dicyanoolefin 2aa
Figure 1. The structure of 3-nitro-2H-chromenes (1) and
structure of 4ah.
a,a-dicyanoolefins (2) and
Table 2
The one-pot tandem reaction of 3-nitro-2H-chromene 1 and
a
,
a
-dicyanoolefin 2a
R2
R3
CN
Entry
Solvent
Base
Yieldb 4aa
NO2
Ar1
NC
R2
CN
100% mol TEA
+
NH2
1
2
3
4
5
6
7
8
THF
THF
THF
THF
NaOAc
DBU
DABCO
K2CO3
TEA
TEA
TEA
TEA
TEA
51%
44%
53%
37%
59%
31%
49%
46%
71%
53%
DCM, rt, 48h
O
R1
O
4
Ar1
R3
R1
2
1
THF
Entry
1
R2
R3
2
Yieldb (4)
Ethanol
CH3CN
Toluene
DCM
DCM
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
1g
1h
1a
1a
1a
1a
1a
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
H
H
H
H
H
H
H
H
H
H
H
H
2a
2a
2a
2a
2a
2a
2a
2a
2b
2c
2d
2e
2h
71% (4aa)
58% (4ba)
76% (4ca)
72% (4da)
41% (4ea)
73% (4fa)
56% (4ga)
74% (4ha)
62% (4ab)
71% (4ac)
65% (4ad)
52% (4ae)
43% (4ah)
9
10c
TEA
a
Unless otherwise noted, reactions performed with 0.2 mmol of 1a, 0.1 mmol of
2a, 100 mol % catalyst, in 1 mL solvent at 25 ꢀC for 48 h.
b
Isolated yield.
Reflux.
c
9
p-ClC6H4
p-BrC6H4
p-CH3C6H4
10
11
12
13
With the optimal reaction conditions in hand, we then examined
o-CH3OC6H4
a variety of
a,a-dicyanoolefins and 3-nitro-2H-chromene de-
rivatives (Fig. 1) to establish the general utility of this novel trans-
formation (Table 2). The reaction scopes proved to be quite broad
with respect to both a,a-dicyanoolefins and 3-nitro-2H-chromene
a
All the reactions were performed with 0.2 mmol of 1, 0.1 mmol of 2, 100 mol % of
TEA in 1 mL DCM at 25 ꢀC for 48 h.
b
Isolated yield.
derivatives. The domino Michael addition/cyclization was generally
conducted with 100 mol % of TEA in DCM for 48 h. Good yields were
obtained in the domino reactions of 2a and electron-withdrawing
substituent on aryl ring of 3-nitro-2H-chromene derivatives 1ce1d
(entries 3 and 4). On the contrary, an electron-denoting substituent
on aryl ring of 3-nitro-2H-chromene derivative 1b tended to de-
crease the reactivity (entry 2). The substituents on the 2-aryl ring of
3-nitro-2H-chromene derivatives have a little effect on the yield and
good yields were obtained (entries 6e8) except for the substrate 1e
(entry 5). Notably, the high reactivity was observed for the bulkier
nucleophile 2h (Fig. 1), the domino reactions proceeded smoothly
and the product 4ah was isolated in 43% yield under the same re-
R3
R4
CN
NO2
NC
R3
CN
R4
(1)
+
NH2
R1
O
R1
O
4
R2
1
2
R3
1
R2
(
R4
CN
NH
)
)
2
(
NO2
R1
R3
O
action conditions (entry 13). However, reaction of other bulkier a,a-
R2
product 4 yield for two steps
1
R2
2
dicyanoolefins 2f and 2g (Fig.1), we cannot get the desired products
4 but 3 under the above conditions (Scheme 2). Although low re-
activity was observed for the bulkier nucleophile 2f and 2g, the
desired products 4 (4df, 4ff, 4gf and 4ag) were obtained when the
addition products 3 (3df, 3ff, 3gf and 3ag) were refluxed in ethanol
and catalyzed by 100 mol % NaOAc. In order to get the desired
1d C6H5
1f C6H5
1g C6H5
1a Et
CH3 2f
CH3 2f
CH3 2f
CH3 2g
4df
4ff
4gf
63%
61%
68%
38%
4ag
Conditions: (1)Et3N, DCM, rt, 48h; (2) NaAc, TBAB, EtOH
Scheme 2. The domino Michael addition/cyclization catalyzed by NaOAc.

7592
P. Li et al. / Tetrahedron 66 (2010) 7590e7594
128.7, 128.6, 127.9, 127.8, 124.0, 122.2, 121.3, 118.4, 117.4, 116.4, 113.7,
74.0; IR (KBr) cmꢁ1 3466, 3359, 3118, 2212, 1718, 1641, 1592, 1555,
1409, 766; ESI-HRMS: calcd for C26H18N2NaO 397.13137, found
397.13113.
4.2.1.2. 3-Methoxyl-7-amino-6,9-diphenyl-6H-dibenzo[b,d]py-
ran-8-carbonitirle (4ba). Yellow solid; mp 195.8e196.9 ꢀC; 1H NMR
(400 MHz, CDCl3)
d (ppm) 7.65e7.61 (m, 3H), 7.54e7.47 (m, 3H),
7.34 (s, 5H), 7.23 (s, 1H), 6.58e6.55 (m, 1H), 6.43 (d, J¼2.5 Hz, 1H),
6.32 (s, 1H), 4.29 (s, 2H), 3.80e3.77 (m, 3H); 13C NMR (100 MHz,
CDCl3)
d (ppm) 129.2, 129.0, 128.6, 128.5, 127.8, 113.0, 109.0, 103.0,
74.3, 55.3; IR (KBr) cmꢁ1 3503, 3310, 3116, 2206, 1709, 1633, 1557,
1411, 743; ESI-HRMS: calcd for C27H20N2NaO2 427.14189, found
427.14170.
Figure 2. Molecular structure of 3df.
4.2.1.3. 2-Fluoro-7-amino-6,9-diphenyl-6H-dibenzo[b,d]pyran-8-
carbonitirle (4ca). Yellow solid; mp 204.5e204.6 ꢀC; 1H NMR
(400 MHz, CDCl3)
7.38e7.35 (m, 1H), 733e7.27 (m, 5H), 7.20 (s, 1H), 6.89e6.81 (m,
2H), 6.30 (s, 1H), 4.35 (s, 2H); 13C NMR (100 MHz, CDCl3)
(ppm)
158.2, 156.8, 146.3, 145.9, 138.5, 136.6, 129.3, 129.0, 128.9, 128.8,
128.7, 128.5, 127.9, 127.8, 119.6, 119.5, 117.7, 117.5, 117.2, 116.6, 113.7,
110.4, 110.2, 74.0; IR (KBr) cmꢁ1 3448, 3109, 2200, 1697, 1650, 1545,
1417, 749; ESI-HRMS: calcd for C26H18FN2O 393.14060, found
393.13977.
d (ppm) 7.63e7.60 (m, 2H), 7.54e7.44 (m, 3H),
3. Conclusion
d
In conclusion, an efficient method for the synthesis of func-
tionalized 6-aryl-6H-dibenzo[b,d]pyran derivatives by domino re-
actions of 3-nitro-2H-chromenes with a,a-dicyanoolefins has been
investigated. The one-pot tandem reaction can proceed smoothly
under mild conditions and provides pure benzopyran derivatives in
moderate to good yield. The reaction’s scope proved to be quite
broad. Notably, this novel methodology provides facile access to
various multifunctional compounds (3df, 3ff, 3gf and 3ag) with
contiguous many chiral centres that might have important bi-
ological and pharmaceutical activities in the future. Current studies
are actively underway to extend this novel and efficient method-
ology to the synthesis of natural products and drugs.
4.2.1.4. 2-Chloro-7-amino-6,9-diphenyl-6H-dibenzo[b,d]pyran-8-
carbonitirle (4da). Yellow solid; mp 207.4e208.0 ꢀC; 1H NMR
(400 MHz, CDCl3)
7.33e7.31 (m, 5H), 729e7.23 (m, 1H), 7.13 (s, 1H), 6.82 (d, J¼8.6 Hz,
1H), 6.31 (s, 1H), 4.33 (s, 2H); 13C NMR (100 MHz, CDCl3)
(ppm)
d (ppm) 7.66e7.61 (m, 3H), 7.52e7.49 (m, 3H),
d
151.1,146.3,146.0,138.5,136.6,133.1,130.7,129.4,129.0,128.9,128.7,
128.5, 127.8, 127.2, 123.8, 122.7, 119.8, 117.1, 116.4, 113.6, 74.2; IR
(KBr) cmꢁ1 3398, 3209, 2117, 1698, 1637, 1547, 1513, 1406, 752; ESI-
HRMS: calcd for C26H17ClN2NaO 431.09254, found 431.09216.
4. Experimental section
4.1. General methods
4.2.1.5. 7-Amino-9-phenyl-6-(4-(trifluoromethyl)phenyl)-6H-di-
benzo[b,d]pyran-8-carbonitirle (4ea). Yellow solid; mp 196.0e
NMR spectra were recorded with tetramethylsilane as the in-
ternal standard. TLC was performed on glass-backed silica plates.
Column chromatography was performed using silica gel (200e300
mesh) eluting with ethyl acetate and petroleum ether. 1H NMR
spectra were recorded at 400 MHz, and 13C NMR spectra were
197.0 ꢀC; 1H NMR (400 MHz, CDCl3)
d (ppm) 7.74e7.70 (m, 2H),
7.66e7.64 (m, 3H), 7.59e7.51 (m, 3H), 747e7.41 (m, 4H), 726e7.22
(m, 1H), 704e7.02 (m, 1H), 6.37 (s, 1H), 4.39 (s, 2H); 13C NMR
(100 MHz, CDCl3)
d (ppm) 152.2, 146.3, 146.2, 138.6, 131.3, 128.9,
recorded at 100 MHz (Bruker Avance). Chemical shifts (
d) are
128.7, 128.6, 128.5, 128.3, 128.1, 127.3, 125.9, 124.1, 123.5, 122.6,
121.2, 118.4, 117.1, 115.5, 113.9, 73.1, 72.9; IR (KBr) cmꢁ1 3471, 3291,
3006, 2206, 1776, 1647, 1555, 1423, 739; ESI-HRMS: calcd for
C27H17F3N2NaO 465.11895, found 465.11852.
reported in parts per million downfield from CDCl3
(
d
¼7.26 ppm)
for 1H NMR and relative to the central CDCl3 resonance
(
d
¼77.0 ppm) for 13C NMR spectroscopy. Coupling constants (J) are
given in hertz. ESI-HRMS spectrometer was measured with a Fin-
nigan LCQDECA ion trap mass spectrometer.
4.2.1.6. 7-Amino-9-phenyl-6-(4-chlorophenyl)-6H-dibenzo[b,d]-
pyran-8-carbonitirle (4fa). Yellow solid; mp 190.2e191.5 ꢀC; 1H
4.2. General procedure for the one-pot tandem reaction of 3-
NMR (400 MHz, CDCl3) d (ppm) 7.71e7.69 (m,1H), 7.65e7.62 (m, 2H),
nitro-2H-chromenes 1 and
a
,a
-dicyanoolefins 2
7.56e7.42 (m, 5H), 732e7.27 (m, 3H), 724e7.20 (m, 2H), 702e6.98
(m, 1H), 6.90e6.88 (m, 1H), 6.29 (s, 1H), 4.35 (s, 1H); 13C NMR
4.2.1. General procedure. 3-Nitro-2H-chromene
2 equiv) and -dicyanoolefin 2 (0.1 mmol, 1 equiv) were dissolved
in 1 mL CH2Cl2, then 14 L triethylamine (0.1 mmol, 1.0 equiv) was
1
(0.2 mmol,
(100 MHz, CDCl3) d (ppm) 152.2, 146.2, 146.0, 138.6, 135.5, 135.1,
a,
a
134.3,131.2,129.3,129.2,129.1,128.8,128.7,128.6,124.0,122.4,121.2,
118.4, 117.3, 115.9, 113.8, 73.0; IR (KBr) cmꢁ1 3397, 3106, 2184, 1701,
1632, 1581, 1438, 759; ESI-HRMS: calcd for C26H17ClN2NaO
431.09264, found 431.09216.
m
added. The reaction mixture was stirred at 25 ꢀC for 48 h. The end of
reaction was detected by TLC (ethyl acetate/petroleum ether 1:8).
The solvent was removed and flash chromatography on silica gel
(ethyl acetate/petroleum ether 1:10) gave 4 as a yellow solid.
4.2.1.7. 7-Amino-9-phenyl-6-(4-methylphenyl)-6H-dibenzo[b,d]-
pyran-8-carbonitirle (4ga). Yellow solid; mp 199.3e191.1 ꢀC; 1H
4.2.1.1. 7-Amino-6,9-diphenyl-6H-benzo[c]chromene-8-carbon-
NMR (400 MHz, CDCl3)
4H), 7.29 (s, 1H), 721e7.09 (m, 5H), 6.99e6.85 (m, 2H), 6.27 (s, 1H),
4.30 (s, 1H), 2.29 (s, 3H); 13C NMR (100 MHz, CDCl3)
(ppm) 134.1,
d (ppm) 7.70e7.61 (m, 3H), 7.53e7.45 (m,
itrile (4aa). Yellow solid; mp 202.7e204.5 ꢀC; 1H NMR (400 MHz,
CDCl3)
d
(ppm) 7.76e7.73 (m, 1H), 7.69e7.66 (m, 2H), 7.60e7.50 (m,
d
4H), 7.37e7.34 (m, 5H), 7.26e7.22 (m, 1H), 7.04e7.01 (m, 1H), 6.93
131.0, 129.7, 128.7, 128.6, 127.8, 123.9, 122.1, 118.4, 117.4, 113.6, 73.9,
21.19; IR (KBr) cmꢁ1 3517, 3361, 2192, 1751, 1639, 1601, 1555, 1394,
710; ESI-HRMS: calcd for C27H20N2NaO 411.14718, found 411.14678.
(d, J¼8.1 Hz,1H), 6.36 (s,1H) 4.37 (s, 2H); 13C NMR (100 MHz, CDCl3)
d
(ppm) 152.5, 146.3, 145.7, 138.8, 137.0, 134.3, 131.1, 129.2, 128.9,

P. Li et al. / Tetrahedron 66 (2010) 7590e7594
7593
4.2.1.8. 7-Amino-9-phenyl-6-(furan-2-yl)-4-methylphenyl-6H-di-
benzo[b,d]-pyran-8-carbonitirle (4ha). Yellow solid; mp
201.4e202.8 ꢀC; 1H NMR (400 MHz, CDCl3)
(ppm) 7.67e7.64
CDCl3)
d
(ppm), 7.39e6.99 (m, 13H), 5.90 (s, 1H), 5.15 (s, 2H), 4.14
(ppm) 152.4, 136.7, 135.7, 132.9,
(s, 1H); 13C NMR (100 MHz, CDCl3)
d
d
129.7, 129.2, 129.0, 128.5, 128.3, 128.1, 126.6, 122.4, 116.8, 116.2; IR
(KBr) cmꢁ1 3319, 3248, 3027, 2194, 1713, 1651, 1547, 1469, 753; ESI-
HRMS: calcd for C27H20ClN3NaO3 492.10882, found 492.10854.
(m, 1H), 7.55e7.52 (m, 2H), 7.45e7.44 (m, 4H), 731e7.30 (m, 2H),
7.02e7.00 (m, 2H), 6.43 (s,1H), 6.28(d, J¼1.4Hz,1H), 6.13 (d, J¼3.3Hz,
1H) 4.50 (s, 1H); 13C NMR (100 MHz, CDCl3)
d (ppm) 152.5, 150.7,
146.3, 145.9, 143.8, 138.7, 134.1, 131.1, 131.0, 128.8, 128.7, 128.6, 128.5,
124.0, 122.4, 121.0, 118.2, 117.3, 114.9, 113.8, 110.5, 110.4, 95.9, 67.4; IR
(KBr) cmꢁ1 3416, 3317, 3106, 2217, 1709, 1603, 1585, 1500, 691; ESI-
HRMS: calcd for C24H16N2NaO2 387.11068, found 387.11040.
4.2.1.15. 7-Imino-10-methyl-6a-nitro-9-phenyl-6-p-tolyl-
6a,7,10,10a-tetrahydro-6H-benzo[c]chromene-8-carbonitrile
(3gf). Pale yellow solid; mp 134.6e136.0 ꢀC; 1H NMR (400 MHz,
CDCl3)
5.24 (s, 2H), 4.12e4.10 (m, 1H), 2.31e2.27 (m, 3H), 1.93 (s, 3H); 13C
NMR (100 MHz, CDCl3) (ppm) 152.8, 147.9, 139.7, 136.8, 131.4,
d (ppm), 7.37e7.26 (m, 4H), 7.17e6.96 (m, 9H), 5.91 (s, 1H),
4.2.1.9. 7-Amino-6-phenyl-9-(4-chlorophenyl)-6H-dibenzo[b,d]-
d
pyran-8-carbonitirle (4ab). Yellow solid; mp 208.6e210.2 ꢀC; 1H
129.6, 129.5, 129.2, 128.4, 128.0, 126.6,126.5, 122.2,117.0, 116.0, 21.2;
IR (KBr) cmꢁ1 3352, 3237, 2916, 2206, 1714, 1647, 1523, 1480, 763;
ESI-HRMS: calcd for C28H23N3NaO3 472.16364, found 472.16316.
NMR (400 MHz, CDCl3)
d (ppm) 7.70e7.68 (m, 1H), 7.57e7.55 (m,
2H), 7.50e7.47 (m, 2H), 733e7.27 (m, 2H), 7.25e7.21 (m, 3H),
701e6.97 (m, 1H), 6.90e6.88 (m, 1H), 6.31 (s, 1H), 4.34 (s, 2H); 13C
NMR (100 MHz, CDCl3)
d
(ppm) 152.5, 146.4, 136.9, 134.4, 131.2,
4.2.1.16. 9-Ethyl-7-imino-10-methyl-6a-nitro-6-phenyl-
6a,7,10,10a-tetrahydro-6H-benzo[c]chromene-8-carbonitrile
(3ag). Pale yellow solid; mp 129.8e130.6 ꢀC; 1H NMR (400 MHz,
129.9, 129.2, 129.0, 128.9, 127.8, 123.9, 122.2, 118.5, 117.2, 113.5, 73.9,
29.7; IR (KBr) cmꢁ1 3451, 3306, 3019, 2101, 1705, 1651, 1570, 1395,
718; ESI-HRMS: calcd for C26H17ClN2NaO 431.09264, found
431.09216.
CDCl3) d (ppm), 7.34e7.25 (m, 4H), 7.22e7.14 (m, 3H), 7.03e6.99 (m,
1H), 6.93 (d, J¼8.2 Hz, 1H), 5.67e5.64 (m, 2H), 4.93 (s, 2H),
4.10e4.09 (m, 1H), 3.41e3.38 (m, 1H), 1.73 (d, J¼7.1 Hz, 3H), 1.14 (d,
4.2.1.10. 7-Amino-6-phenyl-9-(4-bromophenyl)-6H-dibenzo[b,d]-
J¼7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d (ppm) 152.4, 144.9,
pyran-8-carbonitirle (4ac). Yellow solid; mp 204.3e205.7 ꢀC; 1H
134.4, 130.8, 129.5, 128.8, 128.5, 127.6, 127.5, 127.2, 122.2, 121.9,
121.7, 117.3, 116.4, 89.5, 78.4, 40.0, 33.1, 18.8, 13.2; IR (KBr) cmꢁ1
3361, 3272, 2956, 2215,1727,1671,1549,1418, 773; ESI-HRMS: calcd
for C23H21N3NaO3 410.14828, found 410.14751.
NMR (400 MHz, CDCl3)
d
(ppm) 7.70e7.64 (m, 3H), 7.50 (d, J¼8.4 Hz,
3H), 7.31 (s, 5H), 7.21e7.19 (m, 1H), 701e6.97 (m, 1H), 6.89 (d,
J¼8.0 Hz, 1H), 6.31 (s, 1H), 4.34 (s, 2H); 13C NMR (100 MHz, CDCl3)
d
(ppm) 152.5, 146.4, 144.4, 134.4, 131.9, 131.2, 130.2, 129.3, 129.0,
127.8, 123.9, 122.2, 118.5, 117.2, 116.7, 113.4, 73.9, 29.7; IR (KBr) cmꢁ1
3391, 3217, 2209, 1684, 1627, 1527, 1461, 673; ESI-HRMS: calcd for
C26H17BrN2NaO 475.0402, found 475.04166.
4.2.1.17. 14-Amino-1-phenyl-1,7-dihydrobenzo[1,2-c:3,4-c0]di-
chromene-13-carbonitrile (4ah). Yellow solid; mp 231.0e232.1 ꢀC;
1H NMR (400 MHz, CDCl3)
d (ppm), 7.37e7.35 (m, 3H), 7.21e7.18
(m, 4H), 7.10e6.94 (m, 6H), 6.30 (s, 1H), 5.47 (d, J¼12.9 Hz, 1H), 5.09
4.2.1.11. 7-Amino-6-phenyl-9-(4-methylphenyl)-6H-dibenzo[b,d]-
(d, J¼12.9 Hz, 1H), 4.36 (s, 2H); 13C NMR (100 MHz, CDCl3)
d (ppm)
pyran-8-carbonitirle (4ad). Yellow solid; mp 209.1e210.9 ꢀC; 1H
145.8, 135.9, 130.8, 129.2, 128.8, 127.9, 127.8, 125.8, 122.5, 122.0,
119.2, 117.3, 74.7, 66.7, 29.7; IR (KBr) cmꢁ1 3472, 3361, 3104, 2172,
1736, 1607, 1569, 1416, 739; ESI-HRMS: calcd for C27H19N2O2
403.14505, found 403.14410.
NMR (400 MHz, CDCl3)
d
(ppm) 7.70 (d, J¼7.9 Hz, 2H), 7.54
(d, J¼7.9 Hz, 3H), 7.34e7.30 (m, 9H), 7.01e6.99 (m, 2H), 6.89
(d, J¼7.9 Hz, 1H), 6.32 (s, 1H), 4.34 (s, 2H); 13C NMR (100 MHz,
CDCl3)
d (ppm) 152.5, 138.7, 137.1, 135.9, 134.2, 131.0, 129.4, 129.2,
128.9, 128.4, 127.8, 123.96, 122.1, 118.4, 113.6, 74.0, 31.9, 29.7, 29.6,
21.3; IR (KBr) cmꢁ1 3415, 3292, 3107, 2017, 1691, 1607, 1537, 1402,
692; ESI-HRMS: calcd for C27H20N2NaO 411.14711, found 411.14678.
4.3. Synthesis of 4df, 4ff, 4gf and 4ag catalyzed by NaOAc
4.3.1. General procedure. The reactions performed with
3
(0.1 mmol, 1.0 equiv), NaOAc (0.1 mmol, 1.0 equiv) and TBAB
(0.1 mmol, 1.0 equiv) in 2 mL EtOH. The reaction mixture was
refluxed for 12 h. The end of reaction was detected by TLC (ethyl
acetate/petroleum ether 1:8). The solvent was removed and flash
chromatography on silica gel (ethyl acetate/petroleum ether 1:15)
gave 4 as a yellow solid.
4.2.1.12. 7-Amino-6-phenyl-9-(2-methoxylphenyl)-6H-dibenzo
[b,d]pyran-8-carbonitirle (4ae). Yellow solid; mp 195.6e197.1 ꢀC;
1H NMR (400 MHz, CDCl3)
d
(ppm) 7.63 (d, J¼7.6 Hz, 2H), 7.33e7.31
(m, 9H), 7.21e7.17 (m, 2H), 6.97e6.87 (m, 2H), 6.32 (s, 1H), 4.27 (s,
2H), 2.27 (d, J¼3.8 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d (ppm)
152.5, 145.9, 145.7, 138.6, 134.0, 131.0, 130.4, 129.2, 129.0, 128.7,
127.8, 125.8, 124.0, 122.2, 118.4, 116.8, 114.0, 74.0; IR (KBr) cmꢁ1
3416, 3328, 3105, 2206, 1709, 1637, 1547, 1401, 684; ESI-HRMS:
calcd for C27H20N2NaO2 427.14221, found 427.14170.
4.3.1.1. 2-Chloro-7-amino-6-phenyl-9-(4-chlorophenyl)-6H-di-
benzo[b,d]pyran-8-carbonitirle
(4df). Yellow
solid;
(ppm), 7.64
mp
203.3e204.8 ꢀC; 1H NMR (400 MHz, CDCl3)
d
(d, J¼2.4 Hz, 1H), 7.53e7.50 (m, 3H), 7.44e7.32 (m, 2H), 7.29e7.23
4.2.1.13. 2-Chloro-7-imino-10-methyl-6a-nitro-6,9-diphenyl-
6a,7,10,10a-tetrahydro-6H-benzo[c]chromene-8-carbonitrile
(3df). Pale yellow solid; mp 148.0e149.3 ꢀC; 1H NMR (400 MHz,
(m, 5H), 7.11e7.08 (m, 1H), 6.28 (s, 1H), 4.11 (s, 2H), 2.29 (s, 3H); 13C
NMR (100 MHz, CDCl3)
d (ppm) 152.5, 147.0, 143.1, 138.8, 136.6,
134.3, 129.7, 129.3, 129.0, 128.9, 128.9, 128.9, 128.6, 128.5, 128.1,
128.0, 126.5,125.3,123.1,121.1,120.3,116.9, 98.8, 74.9, 20.5; IR (KBr)
cmꢁ1 3501, 3208, 2092, 1698, 1593, 1537, 1397, 695; ESI-HRMS:
calcd for C27H19ClN2NaO 445.10828, found 445.10781.
CDCl3)
J¼6.8 Hz, 4H), 6.95 (d, J¼8.7 Hz, 1H), 5.93 (s, 1H), 5.18 (s, 2H), 1.92 (s,
3H); 13C NMR (100 MHz, CDCl3)
(ppm) 171.3, 151.4, 136.5, 134.0,
d (ppm), 7.43e7.32 (m, 6H), 7.29e7.23 (m, 3H), 7.16 (d,
d
129.9, 129.8, 129.2, 128.9, 128.5, 128.2, 127.3, 126.6, 117.4, 116.9, 60.5,
21.1, 14.2; IR (KBr) cmꢁ1 3347, 3250, 2959, 2202, 1718, 1663, 1565,
1477, 769; ESI-HRMS: calcd for C27H20ClN3NaO3 492.10917, found
492.10854.
4.3.1.2. 7-Amino-6-(4-chlorophenyl)-9-phenyl-6H-benzo[c]-chro-
mene-8-carbonitrile (4ff). Yellow solid; mp 198.3e199.5 ꢀC; 1H
NMR (400 MHz, CDCl3)
(m, 5H), 7.33e7.14 (m, 5H), 6.97e6.89 (m, 2H), 6.23 (s, 1H), 4.11
(s, 2H), 2.28 (s, 3H); 13C NMR (100 MHz, CDCl3)
(ppm) 153.6, 147.0,
d
(ppm) 7.65 (d, J¼7.8 Hz, 1H), 7.50e7.39
4.2.1.14. 6-(4-Chlorophenyl)-7-imino-10-methyl-6a-nitro-9-phe-
nyl-6a,7,10,10a-tetrahydro-6H-benzo[c]chromene-8-carbonitrile
(3ff). Pale yellow solid; mp 149.3e150.7 ꢀC; 1H NMR (400 MHz,
d
143.0, 139.0, 135.4, 135.0, 134.7, 130.2, 129.5, 129.1, 129.0, 128.9,
128.6, 128.5, 128.5, 128.4, 123.9, 123.2, 121.8, 120.6, 119.0, 117.1, 98.3,

7594
P. Li et al. / Tetrahedron 66 (2010) 7590e7594
73.8, 29.7, 20.6; IR (KBr) cmꢁ1 3442, 3279, 3100, 2237, 1697, 1603,
1536, 1412, 697; ESI-HRMS: calcd for C27H19ClN2NaO 445.10809,
found 445.10781.
Supplementary data
Supplementary data associated with this article can be found in
the online version at doi:10.1016/j.tet.2010.07.042. These data in-
clude MOL files and InChIKeys of the most important compounds
described in this article.
4.3.1.3. 7-Amino-9-phenyl-6-p-tolyl-6H-benzo[c]chromene-8-
carbonitrile (4gf). Yellow solid; mp 205.2e206.7 ꢀC; 1H NMR
(400 MHz, CDCl3)
d
(ppm) 7.66 (d, J¼7.9 Hz, 1H), 7.52e7.42 (m, 5H),
7.17e7.14 (m, 3H), 7.08e6.98 (m, 2H), 6.96e6.90 (m, 2H), 6.25 (s,
References and notes
1H), 4.10 (s, 2H), 2.30 (s, 3H), 2.23 (s, 3H); 13C NMR (100 MHz,
CDCl3)
d (ppm) 154.0, 146.6, 143.1, 139.1, 139.0, 135.4, 133.1, 130.0,
1. Curini, M.; Cravotto, G.; Epifano, F.; Giannone, G. Curr. Med. Chem. 2006, 13,
199e222.
129.6, 129.4, 129.1, 128.6, 128.4, 128.3, 128.1, 124.0, 123.0, 121.6,
121.6, 121.5, 119.1, 117.3, 98.1, 74.5, 21.2, 20.6; IR (KBr) cmꢁ1 3387,
3176, 3108, 2217, 1770, 1614, 1541, 1410, 686; ESI-HRMS: calcd for
C28H22N2NaO 425.16271, found 425.16243.
2. (a) Majumder, P. L.; Banerjee, S.; Maiti, D. C.; Sen, S. Phytochemistry 1995, 39,
649e653; (b) Majumder, P. L.; Banerjee, D. C.; Sen, S. Phytochemistry 1996, 42,
847e852; (c) Majumder, P. L.; Guha, S.; Sen, S. Phytochemistry 1999, 52,
1365e1369; (d) Anuradha, V.; Rao, N. S. P. Phytochemistry 1998, 48 181e182;
183e184; 185e186; (e) Zhang, G.-L.; Ruecker, G.; Breitmaier, E.; Mayer, R.;
Steinbeck, C. Planta Med. 1998, 64, 165e171.
3. Gaoni, Y.; Mechoulam, R. J. Am. Chem. Soc. 1971, 93, 217e224.
4. Bowd, A.; Swann, D. A.; Turnbull, J. H. J. Chem. Soc., Chem. Commun. 1975,
797e798.
5. Kogan, N. M.; Rabinowitz, R.; Levi, P.; Gibson, D.; Sandor, P.; Schlesinger, M.;
Mechoulam, R. J. Med. Chem. 2004, 47, 3800e3806.
6. (a) Devlin, J. P. Can. J. Chem. 1975, 53, 343e345; (b) Devlin, J. P. Can. J. Chem.
1975, 53, 350e354; (c) Stewart, P. B.; Devlin, J. P.; Freter, K. R. Fed. Proc. 1974, 33,
762e773.
7. Wang, B.; Li, M.; Xu, S.; Song, H.; Wang, B. J. Org. Chem. 2006, 71, 8291e8293.
8. Huang, C.-G.; Beveridge, K. A.; Wan, P. J. Am. Chem. Soc. 1991, 113, 7676e7684.
9. (a) Shi, Y.; Wan, P. J. Chem. Soc., Chem. Commun. 1995, 1217e1218; (b) Shi, Y.;
Wan, P. Chem. Commun. 1997, 273e274.
10. (a) Wan, P.; Huang, C.-G. J. Chem. Soc., Chem. Commun. 1988, 1193e1195; (b)
Ames, D. E.; Opalko, A. Tetrahedron 1984, 40, 1919e1925; (c) Rosa, A. M.; Lobo,
A. M.; Branco, P. S.; Prabhakar, S. Tetrahedron 1997, 53, 285e298; (e) Bowman,
W. R.; Mann, E.; Parr, J. J. Chem. Soc., Perkin Trans. 1 2000, 2991e2999; (f)
Harrowven, D. C.; Nunn, M. I. T.; Newman, N. A.; Fenwick, D. R. Tetrahedron Lett.
2001, 42, 961e964; (g) Hennings, D. D.; Iwasa, S.; Rawal, V. H. J. Org. Chem. 1997,
62, 2e3; (h) Grigg, R.; Savic, V.; Tambyrajah, V. Tetrahedron Lett. 2000, 41,
3003e3006; (i) Beletskaya, I. P.; Cheprakov, A. V. Chem. Rev. 2000, 100,
3009e3066; (j) Yoshid, H.; Tanino, K.; Ohshit, J.; Kunai, A. Chem. Commun. 2005,
5678e5680.
11. (a) Campeau, L.-C.; Thansandote, P.; Fagnou, K. Org. Lett. 2005, 7, 1857e1860; (b)
Campeau, L.-C.; Parisien, M.; Leblanc, M.; Fagnou, K. J. Am. Chem. Soc. 2004, 126,
9186e9187; (c) Parisien, M.; Valette, D.; Fagnou, K. J. Org. Chem. 2005, 70,
7578e7584; (d) Campeau, L.-C.; Parisien, M.; Jean, A.; Fagnou, K. J. Am. Chem.
Soc. 2006, 128, 581e590.
12. (a) Fedorov, A. Y.; Carrara, F.; Finet, J.-P. Tetrahedron Lett. 2001, 42, 5875e5877;
(b) Bolshakov, A. V.; Ganina, O. G.; Shavirin, A. S.; Kurskii, Y. A.; Finet, J.-P.;
Fedorov, A. Y. Tetrahedron Lett. 2002, 43, 8245e8248.
13. (a) Xie, J.-W.; Yue, L.; Xue, D.; Ma, X.-L.; Chen, Y.-C.; Wu, Y.; Zhu, J.; Deng, J.-G.
Chem. Commun. 2006, 1563e1565; (b) Xie, J.-W.; Chen, W.; Li, R.; Zeng, M.; Du,
W.; Yue, L.; Chen, Y.-C.; Wu, Y.; Zhu, J.; Deng, J.-G. Angew. Chem., Int. Ed. 2007,
46, 389e392; (c) Kang, T.-R.; Xie, J.-W.; Du, W.; Feng, X.; Chen, Y.-C. Org. Biomol.
Chem. 2008, 6, 2673e2675; (d) Wu, Z.-J.; Luo, S.-W.; Xie, J.-W.; Xu, X.-Y.; Fang,
D.-M.; Zhang, G.-L. J. Am. Soc. Mass Spectrom. 2007, 18, 2074e2080.
14. (a) Chen, Y.-C.; Xue, D.; Deng, J.-G.; Cui, X.; Zhu, J.; Jiang, Y.-Z. Tetrahedron Lett.
2004, 45, 1555e1558; (b) Xue, D.; Chen, Y.-C.; Cui, X.; Wang, Q.-W.; Zhu, J.;
Deng, J.-G. J. Org. Chem. 2005, 70, 3584e3591; (c) Poulsen, T. B.; Alemparte, C.;
Jørgensen, K. A. J. Am. Chem. Soc. 2005, 127, 11614e11615; (d) Poulsen, T. B.; Bell,
M.; Jørgensen, K. A. Org. Biomol. Chem. 2006, 4, 63e70; (e) Xue, D.; Chen, Y.-C.;
Cun, L.-F.; Wang, Q.-W.; Zhu, J.; Deng, J.-G. Org. Lett. 2005, 7, 5293e5296; (f) Liu,
T.-Y.; Cui, H.-L.; Long, J.; Li, B.-J.; Wu, Y.; Ding, L.-S.; Chen, Y.-C. J. Am. Chem. Soc.
2007, 129, 1878e1879; (g) Cui, H.-L.; Chen, Y.-C. Chem. Commun. 2009,
4479e4486.
4.3.1.4. 7-Amino-9-ethyl-10-methyl-6-phenyl-6H-benzo[c]-chro-
mene-8-carbonitrile (4ag). Yellow solid; mp 198.1e199.6 ꢀC; 1H
NMR (400 MHz, CDCl3)
d
(ppm) 7.59 (d, J¼7.8 Hz, 1H), 7.24e7.20 (m,
5H), 7.13e7.09 (m, 1H), 6.97e6.93 (m, 1H), 6.87 (d, J¼8.0 Hz, 1H),
6.19 (s, 1H), 4.01 (s, 2H), 2.97e2.91 (m, 2H), 2.51 (s, 3H), 1.27 (t,
J¼7.3 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d (ppm) 153.9,147.2,143.1,
136.2, 135.4, 129.8, 129.0, 128.7, 128.6, 128.0, 124.2, 122.6, 121.5,
120.1, 119.1, 117.4, 97.6, 74.8, 26.6, 17.9, 14.2; IR (KBr) cmꢁ1 3297,
3169, 3112, 2009, 1756, 1651, 1532, 1421, 656; ESI-HRMS: calcd for
C23H20N2NaO 363.14706, found 363.14678.
5. Crystallographic data
Crystallographic Data Crystal data for 3df C27H19ClN3O3
(468.90), space group monoclinic, C2/2, a¼32.1978(16), b¼9.3776
(4), c¼20.6161(9) Å, U¼6210.4(5) Å3, Z¼8, specimen 0.215ꢂ
0.183ꢂ0.094 mm3, T¼296(2) K, SIEMENS P4 diffractometer, ab-
sorption coefficient 0.149 mmꢁ1, reflections collected 46,321/7116
[R(int)¼0.0763], refinement by Full-matrix least-squares on F2,
data/restraints/parameters
7116/1/310,
goodness-of-fit
on
F2¼1.041, final R indices [I>2
s
(I)] R1¼0.1842, wR2¼0.4711, R indices
(all data) R1¼0.2453, wR2¼0.5447, largest diff. peak and hole 3.065
and ꢁ0.530 e Åꢁ3. Crystallographic data for the structure 3df have
been deposited with the Cambridge Crystallographic Data Centre as
supplementary publication no. CCDC-761098.
Acknowledgements
We are grateful for the financial support from the National
Natural Science Foundation of China (20902083), Province Natural
Science Foundation of Zhejiang (Y4090082) and Zhejiang Normal
University.