Efficient synthesis of furoquinolinones using Hendrickson reagent-initiated cascade annulation

Article abstract of DOI:10.1016/j.tet.2011.05.067

A new synthesis of furo[3,4-b]quinolin-3(1H)-one derivatives has been established in straightforward fashion in high overall yields. An efficient Hendrickson reagent-initiated cascade annulation, which is composed of mild conversion of the stable amide pr

Full text of DOI:10.1016/j.tet.2011.05.067

Tetrahedron 67 (2011) 5455e5460
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Efficient synthesis of furoquinolinones using Hendrickson reagent-initiated
cascade annulation
,
,
*
Peng Xu a b, Guan-Sai Liu a, Jie Xi a, Shaozhong Wang a, Zhu-Jun Yao a
a State Key Laboratory of Coordination Chemistry, Nanjing National Laboratory of Microstructures, School of Chemistry and Chemical Engineering, Nanjing University,
22 Hankou Road, Nanjing, Jiangsu 210093, China
b Laboratory of Green Chemistry, Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 1 April 2011
Received in revised form 11 May 2011
Accepted 17 May 2011
Available online 25 May 2011
A new synthesis of furo[3,4-b]quinolin-3(1H)-one derivatives has been established in straightforward
fashion in high overall yields. An efficient Hendrickson reagent-initiated cascade annulation, which is
composed of mild conversion of the stable amide precursor to the reactive imido-carbonium in-
termediate and subsequent intramolecular aza DielseAlder reaction, successfully serves as the key re-
action in the synthesis. Final oxidative cleavage of the carbonecarbon double bond of representative
tricyclic precursor 8g led to completion of the synthesis of quinoline-lactone 2g in a high yield.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Furo[3,4-b]quinolin-3(1H)-ones
Hendrickson reagent
Carbocation
Aza DielseAlder reaction
Cascade annulation
1. Introduction
As a regioselective oxidation analogue of dihydrofuroquinoline 1
(Fig. 1), furoquinolinones 2 have attracted common interests for the
potentials in their application as synthetic intermediates and their
appearance as the structural cores in some biologically interesting
natural products, such as uncialamycin 3 (Fig. 2).1 In the past several
decades, considerable attentions havebeenpaid in organicsynthesis
to the construction of variously substituted quinoline-lactones.1e5
Among these, two syntheses of quinoline-lactones have been
reported utilizing an intramolecular aza DielseAlder reaction.1,2
However, involvement of unstable intermediates and low overall
yields restrict their further applications in the syntheses of many
useful products bearing multiple functionalities.
BnO
HN
O
O
O
OH
OH
O
MeO
O
N
O
H
uncialamycin 3
Fig. 2. The transformation designed for the synthesis of uncialamycin via a furo-
quinolinone intermediate.1
In our recent work of total syntheses of camptothecin-family
alkaloids,6 Hendrickson reagent7 was successfully employed as
a powerful reagent to convert the stable anilineeamides to the
corresponding highly reactive imidates at ambient temperature.
Such mild procedure enables us to consider a similar strategy in the
synthesis of furoquinolinone derivatives. Herein, an efficient ap-
proach to this class of heterocycles was reported with cascade aza
DielseAlder reaction and eliminative aromatization utilizing Hen-
drickson reagent under mild conditions.
O
O
N
N
O
1
2
,
[
]
quinolin
,
- ( )-
one
3 1H
,
[
- ]
furo
1 3-dihydrofuro 3 4 b quinoline
3 4-b
Fig. 1. Dihydrofuroquinoline (1) and furoquinolinone (2).
According to our proposal (Fig. 3), the in situ generated imido-
carboniums from amides 7 would be able to react with the al-
kyne functionality via an intramolecular aza DielseAlder reaction.
* Corresponding author. Fax: þ86 25 83593732; e-mail address: yaoz@nju.edu.cn
(Z.-J. Yao).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.05.067

5456
P. Xu et al. / Tetrahedron 67 (2011) 5455e5460
effects of substituent group R1 at the aniline phenyl ring A (entries
1e8, Table 1), amides 7aeh were prepared by acylation of the
corresponding anilines with the pre-prepared acid chlorides (Table
1). To examine the substrate scope, additional three representative
amides 7iek bearing different substituent R2 or R3 (entries 9e11,
Table 1) were also prepared.
NC
O
O
R
CN
H
N
Hendrickson
reagent
N
O
CN
DCM
8
0 oC to r.t.
NC
R
7
TfOH
Ph3P=O
& TfOH
Table 1
Synthesis of tricyclic precursors 8aek with a variable substituent R1, R2, and R3
O
R
CN
O
R
R2
CN
N
Ph3P=O
N
IM aza
R2
R3
O
O
Diels-Alder
NC
Ph3P
NC
R3
NC
R1
Ph3PO, Tf2O
O
B
N
A
C
H
CN
O
R
CN
N
DCM, 0 oC to rt
N
A
O
7a-7k
CN
R1
NC
NC
8a-8k
Ph
O
Ph
Ph
P
P
TfO
OTf
Entry
7 (Yield)a,b
8 (Yield)a,d
Ph
Ph
Ph
1
2
3
4
5
6
7a (R1¼R2¼R3¼H, 76%)
8a (90%)
8b (91%)
8c (97%)
8d (93%)
8e (92%)
8f (96%)
8g (95%)
7b (R1¼p-OMe; R2¼R3¼H, 90%)
7c (R1¼p-Br; R2¼R3¼H, 86%)
7d (R1¼p-F; R2¼R3¼H, 78%)
7e (R1¼p-CO2Me; R2¼R3¼H, 80%)
7f (R1¼o-Me; R2¼R3¼H, 91%)
7g (R1¼p-Me; R2¼R3¼H, 78%)
7h (R1¼m-Me; R2¼R3¼H, 84%)
7i (R2¼Et; R1¼R3¼H, 81%)
7j (R2¼Ph; R1¼R3¼H, 75%)
7k (R3¼Me; R1¼R2¼H, 73%)
Hendrickson reagent
Fig. 3. The designed one-step cascade synthesis of dihydrofuroquinoline derivative 8
from amide 7.
7
8c
9
8h (95%; regioselectivity 3:2)c
A subsequent eliminative aromatization would generate the dihy-
drofuroquinoline derivative 8 finally.
8i (93%)
8j (97%)
8k (94%)
10
11
2. Results and discussion
a
Isolated yields.
b
c
Yields from 5 over two steps.
The ratio of 8h was determined by 1H NMR.
Starting from the commercially available 2,6-dicyanotoluene 4,
compounds 5aed were prepared in two steps by condensation of
toluene 4 with diethyl oxalate and Mitsunobu enol ether synthesis
with propargyl alcohol (Scheme 1). It is noteworthy here that
suitable toluene substrate (2,6-dicyanotoluene, selected by the
substrate screening) is not only required by the first step (con-
densation, sufficient acidity of the methyl group of toluene), but
also needed by the second step to favor the formation of enol in-
termediate under Mitsunobu conditions through adequate
electron-withdrawing effects caused by the two cyano groups.
Basic hydrolysis of the methyl esters 5aed afforded corresponding
acids 6aed, which were used directly for the next step without
further purification except 6a (isolated for the structure charac-
terizations). Conversion of acids 6aed to the corresponding acid
chlorides followed by acylation with various anilines afforded the
amide precursors 7aek in good yields. In order to investigate the
d
The reactions usually completed in 2 h.
With the anilineeamide substrates in hand, their reactions with
bis(triphenyl)oxodiphosphonium trifluoromethanesulfonate (Hen-
drickson reagent) prepared in situ were examined under the
standard conditions of our previous work (Table 1).6,8 To our de-
light, the expected tricyclic quinoline-lactones 8aek were accord-
ingly afforded in excellent isolated yields. For all the examined
benzamides 7aek, either with or without electron-donating or
electron-withdrawing group(s) in the phenyl ring of aniline moiety,
the reactions completed smoothly and afforded the corresponding
products in high yields (entries 1e11, Table 1).
To confirm the stereochemistry of the exo double bond in the
products, an X-ray single crystal analysis of 8a was carried out. It
revealed that cis configuration was adopted by the double bond
connecting to the 2,6-dicyanophenyl group in its solid state (Fig. 4).
However, the cis isomers are not always stable enough in the so-
lution. Transformation of cis-8 to trans-8 could be detected by 1H
NMR in the CDCl3 solution, and it could be accelerated by the ca-
talysis of trace acid (Scheme 2). Though pure trans-8f was not able
to separate from cis-8f by silica gel chromatography, this
R2
R2
NC
CN
a-b
R2
NC
c
NC
R3
EtO
O
R3
HO
O
O
CN
O
CN
4
5
6
R3
NC
d
O
H
N
R1
CN
O
7
Scheme 1. Synthesis of amide precursors 7aek. Reagents and conditions: (a)
(COOEt)2, t-BuOK; then saturated NaHCO3; (b) prop-2-yn-1-ol, Bu3P, DEAD. 5a (R2¼H,
R3¼H, 62% in two steps), 5b (R2¼Et, R3¼H, 55%), 5c (R2¼Ph, R3¼H, 72%), 5d (R2¼H,
R3¼Me, 47%); (c) LiOH, 6a (94%); (d) (COCl)2, DCM, then aniline, 7a (76% from 5a) (see
Table 1 for the yields of 7aek).
Fig. 4. Single crystal X-ray diffraction structure of 8a.

P. Xu et al. / Tetrahedron 67 (2011) 5455e5460
5457
bicarbonate (2 mL), the reaction mixture was stirred for an addi-
tional hour and yielded a suspension. The resultant precipitate was
filtered and dried, affording a yellowish solid.
O
O
CN
H+
N
NC
N
To the stirred solution of the above solid in THF (25 mL) was
successively added propargyl alcohol (4.2 mmol), n-Bu3P
(5.3 mmol), DEAD (5.3 mmol) at 0 ꢀC under N2 atmosphere. The
reaction was allowed to warm to room temperature and stirred for
additional 3 h. Then, the reaction mixture was quenched by the
addition of H2O, and extracted with CH2Cl2. The combined organic
phases were dried over with anhydrous sodium sulfate, filtered,
and concentrated under reduced pressure. The residue was purified
by silica gel flash column chromatography (ethyl acetate/petroleum
ether¼1:3) to afford 5a (0.61 g, 62% in two steps).
CDCl3
CN
NC
cis
-8f
trans-8f
Scheme 2. Transformation of cis-8f to trans-8f.
transformation could be confirmed by the NMR studies of 8f
through mixing with the two isomers.9 In order to avoid such
isomerization, it is necessary to purify CDCl3 with the basic mate-
rials for NMR measurements, such as K2CO3.
Poor regioselectivity was observed in the reaction of substrate
7h bearing a methyl group at the meta-position of the phenyl ring
(entry 8, Table 1). These two isomers could not be separated by
silica gel flash column chromatography, but their ratio could be
determined by the 1H NMR.
4.2.1. (Z)-Ethyl
3-(2,6-dicyanophenyl)-2-(prop-2-ynyloxy)acrylate
(5a). Yellow solid, 62% yield (two steps), mp 85e86 ꢀC. IR (KBr):
nmax 3276, 3084, 3001, 2904, 2241, 2129, 1721, 1631, 1469, 1446,
1397, 1380, 1335, 1288, 1253, 1234, 1216, 1141, 1108, 1027, 1007, 869,
808, 775, 762, 714, 663, 451 cmꢁ1. 1H NMR (300 MHz, CDCl3):
d 1.41
Conversion of the representative tricyclic precursor 8g to its
corresponding furoquinolinone 2g was finally attempted. Oxidative
cleavage of the carbonecarbon double bond of 8g was smoothly
carried out by NaIO4 oxidation in the presence of catalytic amount
of RuCl3 at room temperature, affording furoquinolinone 2g (40%
overall yield from 2,6-dicyanotoluene 4) (Scheme 3).10 No methyl-
oxidation product was detected in our study. Thus, a short
straightforward synthesis of furoquinolinones has been accom-
plished starting from the commercially available materials.
(3H, t, J¼7.2 Hz), 2.45 (1H, t, J¼2.4 Hz), 4.38 (2H, q, J¼7.2 Hz), 4.85
(2H, d, J¼2.1 Hz), 7.20 (1H, s), 7.55 (1H, t, J¼7.8 Hz), 7.91 (2H, d,
J¼7.5 Hz). Anal. Calcd for C16H12N2O3: C, 68.56; H, 4.32; N, 9.99;
found: C, 68.56; H, 4.58; N, 10.06. ESIMS (m/z): 281(MþNa)þ.
4.2.2. (Z)-Ethyl 3-(2,6-dicyanophenyl)-2-(pent-2-ynyloxy)acrylate
(5b). White solid, 55% yield (two steps), mp 74e76 ꢀC. IR (KBr): nmax
3077, 2984, 2942, 2876, 2233, 1721, 1644, 1452, 1389, 1328, 1288,
1254, 1231, 1169, 1141, 1106, 1023, 1007, 982, 785 cmꢁ1 1H NMR
.
(300 MHz, CDCl3):
d
1.02 (3H, t, J¼7.2 Hz), 1.38 (3H, t, J¼6.9 Hz), 2.11
(2H, m), 4.34 (2H, q, J¼7.2 Hz), 4.77 (2H, s), 7.13 (1H, s), 7.52 (1H, t,
O
.
NaIO4, RuCl3 xH2O
J¼7.5 Hz), 7.88 (2H, d, J¼7.5 Hz). 13C NMR (75 MHz, CDCl3):
d
12.5,
CN
N
O
13.5, 14.2, 60.0, 62.2, 73.6, 91.1, 114.7, 115.6, 116.2, 128.6, 136.5, 141.1,
148.3, 162.1. Anal. Calcd for C18H16N2O3: C, 70.12; H, 5.23; N, 9.09;
found: C, 69.97; H, 5.11; N, 9.07. ESIMS (m/z): 331.08 (MþNa)þ.
N
CCl4-CH3CN-H2O
(v/v=1:1:1.8)
to rt, 88%
O
NC
8g
0 o
C
2g
Scheme 3. Oxidative cleavage of the double bond of 8g.
4.2.3. (Z)-Ethyl 3-(2,6-dicyanophenyl)-2-(3-phenylprop-2-ynyloxy)
acrylate (5c). White solid, 72% yield (two steps), mp 107e109 ꢀC. IR
(KBr): nmax 3076, 2971, 2926, 2871, 2232, 1727, 1638, 1445, 1379,
3. Conclusion
1261, 1092, 1050, 882, 802 cmꢁ1. 1H NMR (300 MHz, CDCl3):
d 1.38
In summary, a new efficient approach has been developed for
the synthesis of variously substituted furoquinolinones utilizing
Hendrickson reagent-initiated cascade annulation and oxidative
cleavage of exo carbonecarbon double bond. The short route and
mild conditions used in this newly developed synthesis enable the
tolerance of some common functional groups and thus facilitate
future applications in preparation of medicinal and biologically
interesting compounds.
(3H, t, J¼7.2 Hz), 4.36 (2H, q, J¼7.2 Hz), 5.03 (2H, s), 7.20 (1H, s),
7.27e7.32 (5H, m), 7.43 (1H, t, J¼7.8 Hz), 7. 78 (2H, d, J¼8.1 Hz). 13C
NMR (75 MHz, CDCl3):
d
¼14.2, 60.2, 62.3, 83.3, 88.3, 114.6, 116.1,
116.3, 121.9, 128.2, 128.6, 128.9, 131.9, 136.5, 140.8, 148.3, 162.1. Anal.
Calcd for C22H16N2O3: C, 74.15; H, 4.53; N, 7.86; found: C, 74.21; H,
4.47; N, 7.81. ESIMS (m/z): 357.25 (MþH)þ, 379.25 (MþNa)þ
4.2.4. (Z)-Ethyl 2-(but-3-yn-2-yloxy)-3-(2,6-dicyanophenyl)acrylate
(5d). White solid, 47% yield (two steps), mp 95e96 ꢀC. IR (KBr):
nmax 3079, 2961, 2924, 2854, 2230, 1727, 1639, 1532, 1459, 1375,
4. Experimental section
4.1. General
1261, 1098, 1020, 864, 801, 696 cmꢁ1 1H NMR (300 MHz, CDCl3):
.
d
1.38(3H, t, J¼7.2 Hz), 1.44 (3H, d, J¼6.6 Hz), 2.31 (1H, d, J¼2.1 Hz),
4.28e4.39 (2H, m), 5.15 (1H, qd, J¼6.6 , 2.1 Hz), 7.28 (1H, s), 7.54
14.2, 21.9,
Unless stated otherwise, all reactions were carried out in dried
glassware under nitrogen atmosphere. All solvents were purified
and dried prior to use. Flash chromatographies were performed on
silica gel H (400 mesh). Elemental analyses were carried out at the
Analytical Center of Nanjing University.
(1H, t, J¼7.8 Hz), 7.91 (2H, d, J¼7.8 Hz). (75 MHz, CDCl3):
d
62.2, 67.7, 75.1, 81.6, 115.0, 116.2, 117.4, 128.7, 136.4, 141.1, 147.8,
162.2. Anal. Calcd for C17H14N2O3: C, 69.38; H, 4.79; N, 9.52; found:
C, 69.17; H, 4.75; N, 9.52. ESIMS (m/z): 317.17 (MþNa)þ.
4.3. Typical procedures for the preparation of substituted (Z)-
3-(2,6-dicyanophenyl)-2-(prop-2-ynyloxy)acrylic acids (6aed)
4.2. Typical procedures for the preparation of substituted (Z)-
ethyl 3-(2,6-dicyanophenyl)-2-(prop-2-ynyloxy)acrylates
(5aed)
To a solution of ester 5a (1.2 mmol) in THF (3 mL) and water
(1 mL) was added lithium hydroxide monohydrate (1.8 mmol) at
To a solution of the 2-methylisophthalonitrile 4 (3.5 mmol) in
diethyl oxalate (4 mL) was added potassium tert-butoxide
(7.4 mmol) under N2 atmosphere. The reaction mixture was stirred
for 6 h at room temperature. After addition of saturated sodium
0
ꢀC. The reaction was allowed to warm to room temperature and
stirred for additional 2 h. When the substrate was consumed, THF
was removed in vacuo and the pH of the residue was adjusted to
4e5 by addition of 1 N HCl. The resultant precipitation was filtrated

5458
P. Xu et al. / Tetrahedron 67 (2011) 5455e5460
and dried, giving acid 6a (0.28 g). White solid, 94% yield. Mp
160e162 ꢀC (dec). IR (KBr): nmax 3262, 3082, 2120, 1739, 1715, 1654,
1642, 1574, 1450, 1434, 1388, 1322, 1307, 1288, 1269, 1174, 1108,
1019, 1002, 933, 918, 860, 804, 798, 754, 737, 691, 678, 652,
(KBr): nmax 3337, 3289, 3074, 3011, 2935, 2880, 2243, 2235, 2121,
1689, 1669, 1646, 1608, 1532, 1509, 1450, 1408, 1381, 1318, 1301,
1227, 1213, 1159, 1098, 1002, 836, 809, 714, 681, 648, 520, 446 cmꢁ1
.
1H NMR (300 MHz, CDCl3):
d
2.57 (1H, t, J¼2.4 Hz), 4.41 (2H, d,
466 cmꢁ1
.
1H NMR (300 MHz, DMSO-d6):
d
3.44 (1H, t, J¼2.4 Hz),
J¼2.4 Hz), 7.07 (2H, m), 7.42 (1H, s), 7.57e7.65 (3H, m), 7.95 (2H, d,
4.71 (2H, d, J¼2.4 Hz), 7.23 (1H, s), 7.72 (1H, t, J¼7.8 Hz), 8.22 (2H, d,
J¼8.1 Hz). Anal. Calcd for C14H8N2O3: C, 66.67; H, 3.20; N, 11.11;
found: C, 66.87; H, 3.47; N, 11.37. ESIMS (m/z): 251 (MꢁHþ).
Compound 6bed was prepared by a similar procedure as that
for compound 6a, and they were used directly for the next steps.
J¼7.8 Hz), 8.47 (1H, s). 13C NMR (75 MHz, acetone-d6):
d 60.7, 78.1,
2
78.6, 112.9, 115.4, 116.1 (d, JCF¼22.7 Hz), 117.0, 123.2 (d,
3JCF¼8.9 Hz), 130.3, 135.4 (d, JCF¼2.9 Hz), 137.8, 141.7, 152.3, 160.2
4
1
(d, JCF¼240 Hz), 160.7. Anal. Calcd for C20H12FN3O2: C, 69.56; H,
3.50; N, 12.17; found: C, 69.49; H, 3.57; N, 12.11. ESIMS (m/z): 346.17
(MþH)þ, 368.17 (MþNa)þ.
4.4. Typical procedures for the preparation of substituted (Z)-
3-(2,6-dicyanophenyl)-N-phenyl-2-(prop-2-ynyloxy)
acrylamides (7aek)
4.4.5. (Z)-Methyl 4-(3-(2,6-dicyanophenyl)-2-(prop-2-ynyloxy)acryl-
amido)benzoate (7e). White solid, 80% yield, mp 157e158 ꢀC. IR
(KBr): nmax 3310, 3267, 3085, 3049, 2994, 2952, 2242, 2231, 2125,
1708, 1681, 1641, 1603, 1529, 1513, 1435, 1394, 1370, 1285, 1249, 1194,
1177, 1130, 1116, 1013, 997, 860, 837, 804, 770, 759, 715, 699, 674, 518,
To a solution of acid 6a (4.0 mmol) in CH2Cl2 (35 mL) was added
(COCl)2 (12.0 mmol) and a catalytic amount of DMF at 0 ꢀC. After gas
evolution ceased, the reaction mixture was concentrated in vacuo.
The residue was re-dissolved in dry CH2Cl2 (45 mL) and then was
introduced into a suspension of corresponding aniline (4.0 mmol)
in the presence of NaHCO3 (12.0 mmol) in CH2Cl2 (10 mL). After 1 h,
H2O was added to quench the reaction and the aqueous layer was
extracted with CH2Cl2. The combined organic layers were washed
with brine, dried over Na2SO4, filtered, and concentrated. The crude
product was purified by flash chromatography on silica gel (ethyl
acetate/petroleum ether¼1:3 to 2:3).
483 cmꢁ1. 1H NMR (300 MHz, acetone-d6):
d
3.05 (1H, t, J¼2.4 Hz),
3.87 (3H, s), 4.61 (2H, d, J¼2.4 Hz), 7.38 (1H, s), 7.80 (1H, t, J¼7.8 Hz),
8.00 (4H, m), 8.17 (2H, d, J¼7.8 Hz). 13C NMR (75 MHz, acetone-d6):
d
52.2, 60.7, 78.0, 78.7, 113.4, 115.4, 117.0, 120.6, 126.7, 130.4, 131.1,
137.9, 141.6, 143.2, 152.0, 161.2, 166.8. Anal. Calcd for C22H15N3O4: C,
68.57; H, 3.92; N, 10.90; found: C, 68.47; H, 3.97; N, 10.87. ESIMS (m/
z): 386.33 (MþH)þ, 408.50 (MþNa)þ.
4.4.6. (Z)-3-(2,6-Dicyanophenyl)-2-(prop-2-ynyloxy)-N-o-tolylacry-
lamide (7f). Yellowish solid, 91% yield, mp 167e170 ꢀC. IR (KBr):
nmax 3420, 3265, 3074, 3014, 2986, 2235, 2123, 1687, 1652, 1589,
1532, 1457, 1383, 1328, 1305, 1265, 1251, 1216, 1127, 1105, 1003, 829,
4.4.1. (Z)-3-(2,6-Dicyanophenyl)-N-phenyl-2-(prop-2-ynyloxy)acryl-
amide (7a). Yield: 76%, mp 144e146 ꢀC. IR (KBr): nmax 3318, 3273,
3074, 3052, 3016, 2927, 2235, 2120, 1675, 1649, 1598, 1575, 1526,
1494, 1456, 1442, 1374, 1323, 1296, 1241, 1178, 1102, 1077, 1008, 935,
810, 762, 699, 655, 633, 447 cmꢁ1. 1H NMR (300 MHz, CDCl3):
d 2.35
(3H, s), 2.57 (1H, t, J¼2.4 Hz), 4.41 (2H, d, J¼2.7 Hz), 7.14 (1H, m), 7.
24 (2H, m), 7.41 (1H, s), 7.60 (1H, t, J¼7.8 Hz), 7.95 (2H, d, J¼7.8 Hz),
8.10 (1H, d, J¼8.1 Hz), 8.42 (1H, br s). 13C NMR (75 MHz, CDCl3):
.
913, 808, 780, 759, 725, 694, 654, 574 cmꢁ1 1H NMR (300 MHz,
DMSO-d6):
d
3.49 (1H, t, J¼2.4 Hz), 4.59 (2H, d, J¼2.1 Hz), 7.15 (2H,
m), 7.38 (2H, t, J¼8.0 Hz), 7.75 (1H, t, J¼8.0 Hz), 7.80 (2H, d,
J¼8.1 Hz), 8.25 (2H, d, J¼8.1 Hz), 10.41 (1H, s). Anal. Calcd for
C20H13N3O2: C, 73.38; H, 4.00; N, 12.84; found: C, 73.33; H, 4.08; N,
12.76. ESIMS (m/z): 328 (MþH)þ.
d 17.8, 60.8, 76.6, 78.1, 111.3, 114.9, 115.9, 122.3, 125.6, 127.1, 128.7,
129.2, 130.6, 135.0, 136.9, 141.1, 151.9, 159.2. Anal. Calcd for
C21H15N3O2: C, 73.89; H, 4.43; N, 12.31; found: C, 73.78; H, 4.41; N,
12.34. ESIMS (m/z): 342.08 (MþH)þ, 364.08 (MþNa)þ.
4.4.2. (Z)-3-(2,6-Dicyanophenyl)-N-(4-methoxyphenyl)-2-(prop-2-
ynyloxy)acrylamide (7b). White solid, 90% yield, mp 133e136 ꢀC. IR
(KBr): nmax 3313, 3252, 3049, 3014, 2961, 2931, 2839, 2242, 2230,
2122, 1669, 1642, 1595, 1520, 1444, 1415, 1373, 1314, 1297, 1267,
4.4.7. (Z)-3-(2,6-Dicyanophenyl)-2-(prop-2-ynyloxy)-N-p-tolylacry-
lamide (7g). White solid, 78% yield, mp 136e137 ꢀC. IR (KBr): nmax
3314, 3246, 3077, 3053, 3031, 2939, 2921, 2870, 2242, 2230, 2121,
1669, 1645, 1594,1521, 1448,1404, 1375, 1317, 1242,1099, 1004, 805,
1234, 1184, 1110, 1098, 1031, 996, 942, 829, 806, 740, 705, 438 cmꢁ1
.
746, 706, 455 cmꢁ1. 1H NMR (300 MHz, CDCl3):
d 2.34 (3H, s), 2.56
1H NMR (300 MHz, acetone-d6):
d
3.02 (1H, t, J¼2.4 Hz), 3.80 (3H, s),
(1H, s), 4.42 (2H, d, J¼1.8 Hz), 7.18 (2H, d, J¼8.1 Hz), 7.40 (1H, s),
4.59 (2H, d, J¼2.4 Hz), 6.93 (2H, m), 7.34 (1H, s), 7.77 (3H, m), 8.15
7.52e7.61 (3H, m), 7.94 (2H, d, J¼8.1 Hz), 8.43 (1H, s). 13C NMR
(2H, d, J¼7.5 Hz), 9.61 (1H, s). 13C NMR (75 MHz, acetone-d6):
d
55.7,
(75 MHz, acetone-d6): d 20.9, 60.7, 78.1, 78.5, 112.5, 115.4, 117.0,
60.6, 78.2, 78.5, 112.4, 114.6, 115.4, 117.0, 122.8, 130.2, 132.1, 137.8,
141.9, 152.7, 157.5, 160.3. Anal. Calcd for C21H15N3O3: C, 70.58; H,
4.23; N, 11.76; found: C, 70.47; H, 4.34; N, 11.63. ESIMS (m/z):
358.17(MþH)þ, 380.17(MþNa)þ.
121.2, 130.0, 130.2, 134.7, 136.5, 137.8, 141.8, 152.6, 160.5. Anal. Calcd
for C21H15N3O2: C, 73.89; H, 4.43; N, 12.31; found: C, 73.84; H, 4.41;
N, 12.22. ESIMS (m/z): 342.17 (MþH)þ, 364.17 (MþNa)þ.
4.4.8. (Z)-3-(2,6-Dicyanophenyl)-2-(prop-2-ynyloxy)-N-m-tolyl-
acrylamide (7h). White solid, 84% yield, mp 145e147 ꢀC. IR (KBr):
nmax 3324, 3256, 3080, 3020, 2924, 2876, 2237, 2119, 1680, 1649,
1595, 1577, 1536, 1489, 1455, 1430, 1368, 1313, 1293, 1234, 1104,
1002, 936, 793, 772, 705, 576, 437 cmꢁ1. 1H NMR (300 MHz, CDCl3):
4.4.3. (Z)-N-(4-Bromophenyl)-3-(2,6-dicyanophenyl)-2-(prop-2-
ynyloxy)acrylamide (7c). Yellowish solid, 86% yield, mp
158e160 ꢀC. IR (KBr): nmax 3309, 3263, 3082, 3037, 2901, 2855,
2239, 2111, 1679, 1645, 1591, 1525, 1488, 1450, 1395, 1315, 1233,
1093, 1070, 1003, 833, 665, 446 cmꢁ1
.
1H NMR (300 MHz, CDCl3):
d
2.36 (3H, s), 2.56 (1H, t, J¼2.4 Hz), 4.42 (2H, d, J¼2.7 Hz), 6.98 (1H,
d
2.57 (1H, t, J¼2.4 Hz), 4.40 (2H, d, J¼2.4 Hz), 7.42 (1H, s), 7.49 (2H,
d, J¼7.5 Hz), 7.22e7.27 (1H, m), 7.42 (2H, m), 7.50 (1H, s), 7.58 (1H, t,
m), 7.55e7.62 (3H, m), 7.94 (2H, d, J¼7.8 Hz), 8.51 (1H, s). 13C NMR
J¼7.8 Hz), 7.93 (2H, d, J¼7.8 Hz), 8.46 (1H, s). 13C NMR (75 MHz,
(75 MHz, acetone-d6):
d
60.8, 78.0, 78.6, 113.2, 115.4, 116.9, 117.4,
CDCl3): d 21.6, 60.7, 76.5, 78.1, 111.7, 114.8, 116.0, 117.3, 120.9, 126.0,
123.1, 130.3, 132.5, 137.8, 138.4, 141.6, 152.1, 160.8. Anal. Calcd for
C20H12BrN3O2: C, 59.13; H, 2.98; N,10.34; found: C, 59.11; H, 2.97; N,
10.29. ESIMS (m/z): 428.08 (C20H1279BrN3O2þNa)þ; 430.00
(C20H1281BrN3O2þNa)þ.
129.0, 129.2, 136.8, 136.9, 139.2, 141.0, 151.7, 159.2. Anal. Calcd for
C21H15N3O2: C, 73.89; H, 4.43; N, 12.31; found: C, 73.92; H, 4.37; N,
12.29. ESIMS (m/z): 342.08 (MþH)þ, 364.08 (MþNa)þ.
4.4.9. (Z)-3-(2,6-Dicyanophenyl)-2-(pent-2-ynyloxy)-N-phenyl-
acrylamide (7i). White solid, 81% yield, mp 143e145 ꢀC. IR (KBr):
nmax 3229, 3076, 3041, 2974, 2935, 2233, 1667, 1641, 1596, 1523,
4.4.4. (Z)-3-(2,6-Dicyanophenyl)-N-(4-fluorophenyl)-2-(prop-2-
ynyloxy)acrylamide (7d). White solid, 78% yield, mp 145e148 ꢀC. IR

P. Xu et al. / Tetrahedron 67 (2011) 5455e5460
5459
1442, 1373, 1323, 1299, 1141, 1098, 974, 804, 771, 754, 697 cmꢁ1. 1H
NMR (300 MHz, CDCl3):
(KBr): nmax 3075, 2927, 2831, 2230, 1659, 1624, 1502, 1454, 1386,
1369, 1251, 1225, 1142, 1124, 1073, 1026 cmꢁ1 1H NMR (300 MHz,
CDCl3): 3.94 (3H, s), 5.66 (2H, s), 6.86 (1H, s), 7.07 (1H, d,
d
1.01 (3H, t, J¼7.5 Hz), 2.09e2.16 (2H, m),
.
4.36 (2H, s), 7.14 (1H, t, J¼7.5 Hz), 7.33e7.40 (3H, m), 7.56 (1H, t,
J¼7.8 Hz), 7.65 (2H, d, J¼7.5 Hz), 7.91 (2H, d, J¼7.5 Hz), 8.61 (1H, s).
d
J¼2.7 Hz), 7.36e7.43 (2H, m), 7.86 (2H, d, J¼7.8 Hz), 8.98 (1H, s),
13C NMR (75 MHz, CDCl3):
d
12.4, 13.3, 61.6, 72.4, 92.5, 111.2, 114.6,
8.06 (1H, d, J¼9.3 Hz). 13C NMR (75 MHz, CDCl3):
d 55.8, 72.7, 90.7,
115.9, 120.0, 125.0, 129.0, 129.1, 136.7, 137.1, 141.2, 151.6, 159.5. Anal.
Calcd for C22H17N3O2: C, 74.35; H, 4.82; N, 11.82; found: C, 74.25; H,
4.82; N, 11.79. ESIMS (m/z): 356.00 (MþH)þ, 378.08 (MþNa)þ.
105.4, 114.1, 117.2, 123.5, 126.7, 127.5, 129.6, 131.3, 131.5, 137.0, 143.4,
145.3, 149.9, 158.8. Anal. Calcd for C21H13N3O2: C, 74.33; H, 3.86; N,
12.38; found: C, 74.37; H, 3.97; N, 12.34. ESIMS (m/z): 340.33
(MþH)þ, 362.42 (MþNa)þ.
4.4.10. (Z)-3-(2,6-Dicyanophenyl)-N-phenyl-2-(3-phenylprop-2-
ynyloxy)acrylamide (7j). Yellow solid, 75% yield, mp 109e111 ꢀC. IR
(KBr): nmax 3383, 3328, 3051, 2924, 2857, 2233, 1670, 1643, 1597,
4.5.3. (Z)-2-((7-Bromofuro[3,4-b]quinolin-3(1H)-ylidene)methyl)iso-
phthalonitrile (8c). Yellow solid, 97% yield, mp 276 ꢀC (dec). IR
(KBr): nmax 3077, 2926, 2869, 2851, 2229, 1663, 1603, 1487, 1457,
1387, 1359, 1239, 1141, 1060, 1040, 1004, 913, 823, 796, 780 cmꢁ1. 1H
1527, 1490, 1442, 1320, 1234, 1099, 1073, 985, 959, 756, 690 cmꢁ1
.
1H NMR (300 MHz, CDCl3):
d
4.65 (2H, s), 7.14 (1H, t, J¼7.2 Hz),
7.22e7.36 (7H, m), 7.47 (2H, m), 7.64 (2H, d, J¼7.8 Hz), 7.83 (2H, d,
NMR (300 MHz, CDCl3): d 5.71 (2H, s), 6.97 (1H, s), 7.44 (1H, t,
J¼8.1 Hz), 8.65 (1H, s). 13C NMR (75 MHz, CDCl3):
d
61.9, 82.0, 89.4,
3J¼8.1 Hz), 7.85 (1H, dd, 3J¼9.0 Hz, 4J¼2.1 Hz), 7.90 (2H, d,
112.1,114.6,116.0,120.2,121.2,125.0,128.3,129.0, 129.1,129.2, 132.0,
136.7,137.0, 141.0, 152.0, 159.5. Anal. Calcd for C26H17N3O2: C, 77. 41;
H, 4.25; N, 10.42; found: C, 77.23; H, 4.21; N, 10.34. ESIMS (m/z):
404.17 (MþH)þ, 426.33 (MþNa)þ.
3J¼7.8 Hz), 8.03 (1H, d, 4J¼2.1 Hz), 8.06 (1H, s), 8.09 (1H, d,
3J¼9.0 Hz). 13C NMR (75 MHz, pyridine-d5):
d 73.6, 92.4, 114.6, 118.1,
122.0, 128.1, 129.3, 130.2, 131.1, 132.2, 132.9, 134.2, 137.8, 143.3,
148.3, 153.5, 159.1. Anal. Calcd for C20H10BrN3O: C, 61.88; H, 2.60; N,
10.82; found: C, 61.73; H, 2.81; N, 10.64. ESIMS (m/z): 388.08
(C20H1079BrN3OþH)þ; 390.17 (C20H1081BrN3OþH)þ.
4.4.11. (Z)-2-(But-3-yn-2-yloxy)-3-(2,6-dicyanophenyl)-N-phenyl-
acrylamide (7k). White solid, 73% yield, mp 126e127 ꢀC. IR (KBr):
nmax 3324, 3259, 3077, 2989, 2936, 2898, 2237, 1678, 1645, 1599,
1533, 1441, 1317, 1242, 1102, 1018, 957, 802, 754, 689 cmꢁ1. 1H NMR
4.5.4. (Z)-2-((7-Fluorofuro[3,4-b]quinolin-3(1H)-ylidene)methyl)iso-
phthalonitrile (8d). Yellowsolid, 93% yield, mp 254e257 ꢀC. IR (KBr):
nmax 3079, 2951, 2933, 2922, 2882, 2230, 1665, 1631, 1505, 1458,
1359,1207,1142,1043,1006, 904, 830, 796 cmꢁ1. 1H NMR (300 MHz,
(300 MHz, CDCl3):
d
1.50 (3H, d, J¼6.6 Hz), 2.52 (1H, d, J¼2.1 Hz),
4.38 (1H, qd, J¼6.6 Hz, J¼2.1 Hz), 7.17 (1H, t, J¼7.2 Hz), 7.38 (2H, t,
J¼7.5 Hz), 7.50 (1H, s), 7.59 (1H, t, J¼8.4 Hz), 7.65 (2H, m), 7.93 (2H,
CDCl3): d 5.69 (2H, s), 6.91 (1H, s), 7.40e7.49 (2H, m), 7.52e7.59 (1H,
d, J¼7.8 Hz), 8.49 (1H, s). 13C NMR (75 MHz, CDCl3):
d
22.5, 69.7,
m), 7.89 (2H, d, J¼7.8 Hz), 8.08 (1H, s), 8.19 (1H, dd, J¼9.3 , 5.4 Hz).13C
2
76.6, 80.5, 113.1, 114.9, 116.0, 120.2, 125.2, 129.2, 129.3, 136.8, 137.1,
141.3, 151.4, 159.6. Anal. Calcd for C21H15N3O2: C, 73.89; H, 4.43; N,
12.31; found: C, 73.74; H, 4.41; N, 12.34. ESIMS (m/z): 342.08
(MþH)þ, 364.17 (MþNa)þ.
NMR (75 MHz, CDCl3):
d
72.6, 91.7, 111.2 (d, JCF¼22.7 Hz), 114.2,
117.2, 120.9 (d, 2JCF¼24.9 Hz), 127.0, 128.4 (d, 4JCF¼5.9 Hz), 129.0 (d,
3JCF¼10.1 Hz), 131.9, 132.5 (d, 3JCF¼9.2 Hz), 137.0, 143.1, 146.3, 152.0
4
1
(d, JCF¼2.9 Hz), 158.3, 161.3 (d, JCF¼248.6 Hz). Anal. Calcd for
C21H10FN3O: C, 73.39; H, 3.08; N, 12.84; found: C, 73.41; H, 3.18; N,
12.83. ESIMS (m/z): 328.17 (MþH)þ.
4.5. General procedure for the cascade reactions and
characterizations for the tricyclic products 8aek
4.5.5. (Z)-Methyl 3-(2,6-dicyanobenzylidene)-1,3-dihydrofuro[3,4-b]
quinoline-7-carboxylate (8e). Yellow solid, 92% yield, mp
234e237 ꢀC. IR (KBr): nmax 3072, 3004, 2954, 2877, 2232, 1725,
1665, 1621, 1458, 1267, 1171, 1102, 1041, 1000, 919, 805, 783 cmꢁ1. 1H
To a solution of triphenylphosphine oxide (1.87 g, 6.72 mmol) in
dry CH2Cl2 (30 mL) was added trifluoromethanesulfonic anhydride
(0.57 mL, 3.36 mmol) slowly at 0 ꢀC under N2 atmosphere. After the
mixture was stirred at 0 ꢀC for 30 min, the solution of substrate 7a
(0.73 g, 2.23 mmol) in dry CH2Cl2 (10 mL) was then added at the
same temperature. The reaction was allowed to warm to room
temperature and monitored by TLC (the reaction usually completed
after 2 h). The reaction mixture was quenched by adding saturated
aqueous NaHCO3 solution. The aqueous layer was extracted with
CH2Cl2, and the combined organic layers were dried over Na2SO4 or
K2CO3, filtered, and concentrated. The crude product was purified
by flash chromatography on silica gel (dichloromethane/meth-
anol¼200:1e100:1) to afford pure 8a (0.62 g, 90% yield).
NMR (300 MHz, CDCl3): d 4.02 (3H, s), 5.74 (2H, s), 7.02 (1H, s), 7.46
(1H, t, J¼7.8 Hz), 7.91 (2H, d, J¼7.8 Hz), 8.26 (2H, m), 8.36 (1H, dd,
J¼9.0 , 1.8 Hz), 8.65 (1H, d, J¼1.8 Hz). 13C NMR (75 MHz, CDCl3):
d
52.7, 72.6, 92.7, 114.4, 117.1, 127.2, 127.5, 129.2, 129.9, 130.4, 131.1,
131.8, 136.0, 137.1, 143.0, 151.2, 154.6, 158.2, 166.5. Anal. Calcd for
C22H13N3O3: C, 71.93; H, 3.57; N, 11.44; found: C, 71.67; H, 3.74; N,
11.61. ESIMS (m/z): 368.25 (MþH)þ.
4.5.6. (Z)-2-((5-Methylfuro[3,4-b]quinolin-3(1H)-ylidene)methyl)
isophthalonitrile (cis-8f). Compound cis-8f was prepared according
to the general procedure, except K2CO3 was used as the dehydrating
agent in workup. Yellow solid, 96% yield, mp 249e250 ꢀC. IR (KBr):
nmax 3082, 2919, 2878, 2852, 2231, 1661, 1578, 1501, 1455, 1441,
4.5.1. (Z)-2-(Furo[3,4-b]quinolin-3(1H)-ylidenemethyl)iso-
phthalonitrile (8a). Mp 252e254 ꢀC. IR (KBr): nmax 3070, 2239,
2228, 1688, 1662, 1621, 1615, 1572, 1502, 1458, 1446, 1359, 1349,
1245, 1162, 1038, 1002, 905, 899, 808, 773, 757, 706, 608 cmꢁ1. 1H
1378, 1161, 1150, 998 cmꢁ1. 1H NMR (300 MHz, CDCl3):
d 2.89 (3H,
s), 5.72 (2H, s), 6.96 (1H, s), 7.42 (1H, t, J¼7.8 Hz), 7.47e7.52 (1H, m),
NMR (300 MHz, CDCl3):
d 5.73 (2H, s), 6.95 (1H, s), 7.44 (1H, t,
7.62 (1H, d, J¼6.9 Hz), 7.70 (1H, d, J¼8.1 Hz), 7.89 (2H, d, J¼7.5 Hz),
J¼7.7 Hz), 7.62 (1H, t, J¼7.5 Hz), 7.83e7.78 (1H, m), 7.92e7.87 (3H,
8.11 (1H, s). 13C NMR (75 MHz, CDCl3):
d 18.2, 72.8, 91.1, 114.1, 117.3,
m), 8.16 (1H, s), 8.22 (1H, d, J¼8.4 Hz), 7.96 (2H, d, J¼7.8 Hz), 8.50
126.0, 126.8, 127.6, 128.3, 129.2, 130.4, 136.1, 137.0, 138.3, 143.4,
148.4, 151.1, 159.0. Anal. Calcd for C21H13N3O: C, 78.00; H, 4.05; N,
13.00; found: C, 77.97; H, 4.11; N, 13.00. ESIMS (m/z): 324.25
(MþH)þ; 362.33 (MþK)þ.
(1H, s). 13C NMR (75 MHz, CDCl3):
d 21.5, 68.7, 75.6, 79.5,112.1,113.9,
115.0, 119.2, 124.2, 128.2, 128.3, 135.8, 136.1, 140.3, 150.4, 158.6. Anal.
Calcd for C20H11N3O: C, 77.66; H, 3.58; N, 13.58; found: C, 77.75; H,
3.34; N, 13.54. HRMS (MALDI, m/z) calcd for C20H11N3O (MþH)þ:
310.0975; found: 310.0969.
4.5.7. (Z)-2-((7-Methylfuro[3,4-b]quinolin-3(1H)-ylidene)methyl)
isophthalonitrile (8g). Yellow solid, 95% yield, mp 203e206 ꢀC. IR
(KBr): nmax 3081, 2919, 2872, 2854, 2228, 1657, 1570, 1502, 1447,
1356, 1245, 1136, 1040, 999, 916, 824, 800 cmꢁ1. 1H NMR (300 MHz,
4.5.2. (Z)-2-((7-Methoxyfuro[3,4-b]quinolin-3(1H)-ylidene)methyl)
isophthalonitrile (8b). Yellowish solid, 91% yield, mp 247e250 ꢀC. IR

5460
P. Xu et al. / Tetrahedron 67 (2011) 5455e5460
CDCl3):
d
2.55 (3H, s), 5.66 (2H, s), 6.89 (1H, s), 7.39 (1H, t, J¼8.1 Hz),
J¼8.1 Hz), 7.78 (1H, t, J¼8.4 Hz), 7.85e7.89 (3H, m), 8.06 (1H, s), 8.21
7.60 (2H, m), 7.86 (2H, d, J¼7.8 Hz), 8.01 (1H, s), 8.07 (1H, d,
(1H, d, J¼8.7 Hz). 13C NMR (125 MHz, CDCl3):
d 21.9, 81.2, 91.1, 114.3,
J¼9.3 Hz). 13C NMR (75 MHz, CDCl3):
d
21.8, 72.7, 91.2, 114.1, 117.2,
117.2, 126.8, 127.7, 128.1, 128.4, 128.8, 130.0, 130.4, 135.7, 137.0, 143.3,
149.3, 152.4, 158.0. Anal. Calcd for C21H13N3O: C, 78.00; H, 4.05; N,
13.00; found: C, 78.01; H, 4.23; N, 12.95. ESIMS (m/z): 324.25
(MþH)þ; 346.25 (MþNa)þ.
126.8, 126.9, 128.27, 128.32, 129.6, 131.0, 132.8, 137.0, 138.0, 143.3,
147.8, 151.4, 158.7. Anal. Calcd for C21H13N3O: C, 78.00; H, 4.05; N,
13.00; found: C, 77.94; H, 4.21; N, 12.82. ESIMS (m/z): 324.33
(MþH)þ; 346.25 (MþNa)þ.
4.6. Preparation of furo[3,4-b]quinolin-3(1H)-one 2g
4.5.8. (Z)-2-((6-Methylfuro[3,4-b]quinolin-3(1H)-ylidene)methyl)
isophthalonitrile and (Z)-2-((8-methylfuro[3,4-b]quinolin-3(1H)-yli-
dene)methyl)isophthalonitrile (8h). Yellow solid, 95% combined
yield, mp 231e234 ꢀC. IR (KBr): nmax 3068, 2926, 2871, 2852, 2230,
1727, 1660, 1625, 1576, 1502, 1458, 1445, 1381, 1348, 1286, 1243,
To a stirred solution of 8g (70 mg, 0.22 mmol) in CCl4 (1 mL),
CH3CN (1 mL) and water (1.8 mL) was successively added NaIO4
(232 mg, 1.1 mmol), RuCl3$xH2O (1.2 mg) at 0 ꢀC. The reaction was
allowed to warm to room temperature and stirred for 3 h. Saturated
aqueous Na2S2O3 solution was added to quench the reaction and
the aqueous layer was extracted with ethyl acetate. The combined
organic layers were dried over Na2SO4, filtered, and concentrated.
The residue was purified by flash chromatography on silica gel
(dichloromethane/methanol¼70:1), affording 7-methylfuro[3,4-b]
quinolin-3(1H)-one (2g) as a white solid (38 mg, 88% yield). Mp
252e253 ꢀC. IR (KBr): nmax 3045, 2981, 2955, 2923, 2852, 1773,
1616, 1568, 1499, 1465, 1376, 1341, 1303, 1234, 1143, 1054, 995, 913,
1161, 1126, 1074, 1037, 1001 cmꢁ1. 1H NMR (300 MHz, CDCl3):
d 2.59
(1.8H, s), 2.69 (1.2H, s), 5.66 (1.2H, s), 5.70 (0.8H, s), 6.91 (1H, s),
7.38e7.43 (2H, m), 7.65 (0.4H, t, J¼7.7 Hz), 7.73 (0.6H, d, J¼8.1 Hz),
7.87 (2H, d, J¼7.8 Hz), 7.96 (0.6H, s), 8.04 (1H, m), 8.27 (0.4H, s). 13C
NMR (75 MHz, CDCl3): d 19.1, 22.0, 72.7, 72.9, 91.3, 91.4, 114.2, 117.2,
125.5, 126.4, 126.79, 126.83, 127.6, 127.7, 128.3, 128.4, 128.7, 129.0,
130.0, 130.1, 130.2, 130.7, 134.7, 136.0, 137.0, 140.9, 143.28, 143.32,
149.6, 152.2, 158.9. Anal. Calcd for C21H13N3O: C, 78.00; H, 4.05; N,
13.00; found: C, 77.93; H, 4.13; N, 13.12. ESIMS (m/z): 324.17
(MþH)þ.
836 cmꢁ1
.
1H NMR (300 MHz, CDCl3):
d
2.59 (3H, s), 5.53 (2H, s),
22.0, 68.1,
7.69 (2H, m), 8.24 (2H, m). 13C NMR (75 MHz, CDCl3):
d
126.8, 129.4, 129.7, 130.8, 133.6, 134.1, 140.1, 143.8, 148.8, 168.7. Anal.
Calcd for C12H9NO2: C, 72.35; H, 4.55; N, 7.03; found: C, 72.31; H,
4.57; N, 7.17. ESIMS (m/z): 200.17 (MþH)þ; 222.17 (MþNa)þ.
4.5.9. (Z)-2-((9-Ethylfuro[3,4-b]quinolin-3(1H)-ylidene)methyl)iso-
phthalonitrile (8i). Yellow solid, 93% yield, mp 230e233 ꢀC. IR
(KBr): nmax 3071, 2969, 2932, 2874, 2232, 1660, 1614, 1577, 1510,
1444, 1388, 1360, 1343, 1228, 1130, 1057, 1025, 991, 798, 760,
711 cmꢁ1. 1H NMR (300 MHz, CDCl3):
d
1.35 (3H, t, J¼7.8 Hz), 3.04
Acknowledgements
(2H, q, J¼7.8 Hz), 5.68 (2H, s), 6.92 (1H, s), 7.41 (1H, t, J¼7.8 Hz), 7.62
(1H, t, J¼8.4 Hz), 7.76 (1H, t, J¼8.4 Hz), 7.88 (2H, d, J¼8.1 Hz), 8.06
(1H, d, J¼8.4 Hz), 8.21 (1H, d, J¼8.4 Hz). 13C NMR (75 MHz, CDCl3):
This project is financially supported by NSFC (21032002), MOST
973 project (2010CB833200) MOH (2009ZX09501-001, 2009Z
X09501), and 985-III program of MOE at NJU.
d
14.1, 23.2, 72.3, 91.4, 114.1, 117.2, 123.3, 126.8, 127.1, 127.5, 129.2,
129.9, 130.9, 137.1, 143.3, 143.9, 149.7, 151.7, 159.3 ppm. Anal. Calcd
for C22H15N3O: C, 78.32; H, 4.48; N, 12.46; found: C, 78.17; H, 4.41;
N, 12.27. ESIMS (m/z): 338.08 (MþH)þ; 360.08 (MþNa)þ.
Supplementary data
Supplementary data of NMR spectra of new compounds are
available. Supplementary data related to this article can be found
online at doi:10.1016/j.tet.2011.05.067.
4.5.10. (Z)-2-((9-Phenylfuro[3,4-b]quinolin-3(1H)-ylidene)methyl)
isophthalonitrile (8j). Yellow solid, 97% yield, mp 248e251 ꢀC. IR
(KBr): nmax 3056, 2929, 2869, 2230, 1659, 1609, 1573, 1493, 1443,
1384, 1344, 1228, 1144, 1026, 798, 765, 703 cmꢁ1 1H NMR
.
References and notes
(300 MHz, CDCl3):
d 5.55 (2H, s), 6.97 (1H, s), 7.39e7.44 (3H, m),
7.51e7.59 (4H, m), 7.76e7.82 (2H, m), 7.88 (2H, d, J¼8.1 Hz), 8.26
1. Desrat, S.; van de Weghe, P. J. Org. Chem. 2009, 74, 6728e6734.
2. Sagi, M.; Sato, O.; Konno, S. Heterocycles 1989, 29, 2253e2256.
3. Townsend, N. O.; Jackson, Y. A.; Yamanaka, H. Heterocycles 2007, 71, 669e675.
4. Haddadin, M. J.; Zahr, G. E.; Rawdah, T. N.; Chelhot, N. C.; Issidorides, C. H.
Tetrahedron 1974, 30, 659e666.
(1H, d, J¼8.1 Hz) ppm. 13C NMR (75 MHz, CDCl3):
d 72.8, 91.6, 114.1,
117.2, 120.2, 125.7, 126.8, 127.1, 127.7, 128.9, 129.2, 129.6, 130.1, 130.3,
134.9, 137.0, 142.4, 143.2, 150.0, 151.8, 159.2 ppm. Anal. Calcd for
C26H15N3O: C, 81.02; H, 3.92; N, 10.90; found: C, 81.01; H, 3.90; N,
10.94. ESIMS (m/z): 386.17 (MþH)þ.
5. Anzini, M.; Cappelli, A.; Vomero, S. Heterocycles 1994, 38, 103e111.
6. (a) Liu, G.-S.; Dong, Q.-L.; Yao, Y.-S.; Yao, Z.-J. Org. Lett. 2008, 10, 5393e5396; (b)
Zhou, H.-B.; Liu, G.-S.; Yao, Z.-J. J. Org. Chem. 2007, 72, 6270e6272; (c) Liu, G.-S.;
Yao, Y.-S.; Xu, P.; Wang, S.-Z.; Yao, Z.-J. Chem.dAsian J. 2010, 5, 1382e1388.
7. Hendrickson, J. B.; Schwartzman, S. M. Tetrahedron Lett. 1975, 16, 277e280.
8. (a) Dong, Q.-L.; Liu, G.-S.; Zhou, H.-B.; Chen, L.; Yao, Z.-J. Tetrahedron Lett. 2008,
49, 1636e1640; (b) Xi, J.; Dong, Q.-L.; Liu, G.-S.; Wang, S.; Chen, L.; Yao, Z.-J.
Synlett 2010, 1674e1678.
4.5.11. (Z)-2-((1-Methylfuro[3,4-b]quinolin-3(1H)-ylidene)methyl)
isophthalonitrile (8k). Yellowish solid, 94% yield, mp 229e231 ꢀC. IR
(KBr): nmax 3065, 2974, 2921, 2849, 2229, 1661, 1616, 1569, 1501,
1448, 1407, 1385, 1244, 1162, 1073, 1050, 945, 908, 809, 770,
9. The Z/E isomerization was supported by the 1H NMR and 13C NMR experiments
by mixing with cis-8f and trans-8f.
10. Takano, S.; Kamikubo, T.; Moriya, M.; Ogasawara, K. Synthesis 1994, 6, 601e604.
758 cmꢁ1. 1H NMR (300 MHz, CDCl3):
(1H, q, J¼6.6 Hz), 6.92 (1H, s), 7.41 (1H, t, J¼8.1 Hz), 7.60 (1H, t,
d
1.78 (3H, d, J¼6.6 Hz), 5.96