Waste-free synthesis of condensed heterocyclic compounds by rhodium-catalyzed oxidative coupling of substituted arene or heteroarene carboxylic acids with alkynes

Article abstract of DOI:10.1021/jo900396z

The direct oxidative coupling of 2-amino- and 2-hydroxybenzoic acids with internal alkynes proceeds efficiently in the presence of a rhodium/copper catalyst system under air to afford the corresponding 8-substituted isocoumarin derivatives, some of which

Full text of DOI:10.1021/jo900396z

Waste-Free Synthesis of Condensed Heterocyclic Compounds by
Rhodium-Catalyzed Oxidative Coupling of Substituted Arene or
Heteroarene Carboxylic Acids with Alkynes
Masaki Shimizu, Koji Hirano, Tetsuya Satoh,* and Masahiro Miura*
Department of Applied Chemistry, Faculty of Engineering, Osaka UniVersity, Suita,
Osaka 565-0871, Japan
satoh@chem.eng.osaka-u.ac.jp; miura@chem.eng.osaka-u.ac.jp
ReceiVed February 23, 2009
The direct oxidative coupling of 2-amino- and 2-hydroxybenzoic acids with internal alkynes proceeds efficiently
in the presence of a rhodium/copper catalyst system under air to afford the corresponding 8-substituted
isocoumarin derivatives, some of which exhibit solid-state fluorescence. Depending on conditions, 4-ethenyl-
carbazoles can be synthesized selectively from 2-(arylamino)benzoic acids. The oxidative coupling reactions
of heteroarene carboxylic acids as well as aromatic diacids with an alkyne are also described.
Introduction
stituted ones in eq 2 are readily available. To date, however,
the latter approach has not been extensively explored.5,6
The intermolecular coupling of aromatic substrates with
alkynes by transition-metal catalysis is now recognized to be a
powerful tool to construct π-conjugated molecules.1 Particularly,
the palladium-catalyzed annulation by the coupling of aryl
halides bearing an oxygen or nitrogen nucleophile (-LH in eq
1) with alkynes is a versatile way to produce condensed
heteroaromatics.2 In such processes, however, there is a
substantial problem of forming stoichiometric amounts of salt
wastes (base:HX) as byproducts.
One of the most promising methods to avoid the salt
formation is the aerobic oxidative coupling using nonhaloge-
nated aromatic substrates via C-H bond cleavage, in which no
wastes are formed except for water (eq 2).3,4 The oxygen- or
nitrogen-containing substituent (-LH) can also act as a directing
group in the initial C-H bond cleaving step to result in
regioselective ring construction. Needless to say, compared with
disubstituted aromatic substrates in eq 1, the parent monosub-
As one of the rare examples, we demonstrated that benzoic acids
can directly couple with alkynes under air in the presence of an
Rh/Cu catalyst system to form isocoumarin derivatives (path a in
Scheme 1, Z ) H).5a,b The isocoumarin framework can be found
in various natural products7 and especially 8-amino- and 8-hydroxy
isocoumarins are known to exhibit a broad range of interesting
biological and photochemical properties.7a,8 However, as we
reported previously, the coupling of 2-substituted benzoic acids
with alkynes to produce 8-substituted isocoumarins was sluggish,
and consequently, significant amounts of 1:2 coupling products,
naphthalene derivatives, were also formed as byproducts ac-
companied by decarboxylation.5b During our further study of this
environmentally benign reaction, we have succeeded to conduct
the coupling of 2-substituted benzoic acids such as anthranilic- and
(1) For example, see: (a) Bra¨se, S.; de Meijere, A. In Handbook of
Organopalladium Chemistry for Organic Synthesis; Negishi, E., Ed.; Wiley-
Interscience: New York, 2002; Volume 1, Chapter IV.3, pp 1369-1429. (b)
Tsuji, J. Palladium Reagents and Catalysts, 2nd ed.; John Wiley & Sons:
Chichester, UK, 2004; pp 201-265. (c) Bra¨se, S.; de Meijere, A. In Metal-
Catalyzed Cross-Coupling Reactions; de Meijere, A., Diederich, F., Eds.; Wiley-
VCH: Weinheim, 2004; Volume 1, pp 224-276. (d) Balme, G.; Bouyssi, D.;
Monteiro, N. In Multicomponent Reactions; Zhu, J., Bienayme´, H., Eds.; Wiley-
VCH: Weinheim, 2005; pp 224-276.
(2) For recent reviews, see: (a) Larock, R. C. Top. Organomet. Chem. 2005,
14, 147. (b) Zeni, G.; Larock, R. C. Chem. ReV. 2006, 106, 4644.
3478 J. Org. Chem. 2009, 74, 3478–3483
10.1021/jo900396z CCC: $40.75 2009 American Chemical Society
Published on Web 04/03/2009

Waste-Free Synthesis of Condensed Heterocyclic Compounds
TABLE 1. Reaction of N-Phenylanthranilic Acid (1a) with
SCHEME 1. Coupling of 2-Substituted Benzoic Acids with
Alkynes
Diphenylacetylene (2a)a
% yieldb
temp time
entry
Rh-cat
ligand solvent (°C) (h)
3a
4a
1
2
3
4
5
6
7
8
9
[(Cp*RhCl2)2]
[(Cp*RhCl2)2]
[{RhCl(cod)}2] C5H2Ph4 o-xylene 120
[{RhCl(cod)}2] C5H2Ph4 DMF
[{RhCl(cod)}2] C5H2Ph4 DMF
[{RhCl(cod)}2] C5H2Ph4 DMF
[{RhCl(cod)}2] C5H2Ph4 DMF
-
-
DMF
o-xylene 120
120
4
2
3
2
1
2
8
2
2
41
94 (85)
9
18 (17) 79 (73)
14
5
0
0
53
120
140
100
80
120
120
salicylic acids with alkynes efficiently without decarboxylation
under appropriate conditions to furnish the corresponding 8-amino-
and 8-hydroxyisocoumarin derivatives selectively in good yields
(path a in Scheme 1, Z ) NHR or OH). Actually, most
8-aminoisocoumarins obtained have been found to show solid-
state fluorescence, while the parent 8-unsubstituted ones were not
fluorescent. Furthermore, by using another selected Rh/Cu catalyst
system in the reaction of N-phenylanthranilic acids, 4-ethenylcar-
bazoles can be synthesized predominantly (path b in Scheme 1).9
Carbazoles have been attractive synthesis targets in medicinal
chemistry and materials field, because of their biological activities
80
58
37
0
5
0
6
[{RhCl(cod)}2]
[{RhCl(cod)}2] C5H3Ph3 DMF
-
DMF
67
a Reaction conditions: [1a]:[2a]:[Rh-cat]:[ligand]:[Cu(OAc)2]
)
0.5:0.5:0.005:0.02:0.025 (in mmol), in solvent (2.5 mL) under air. b GC
yield based on the amount of 1a used. Value in parentheses indicates
yield after purification.
as well as photophysical and optoelectronic applications.10 The
results obtained for the reactions of these 2-substituted benzoic acids
as well as heteroarene carboxylic acids and dicarboxylic acids are
described herein.
(3) Pd: (a) Fujiwara, Y.; Moritani, I.; Danno, S.; Teranishi, S. J. Am. Chem.
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Results and Discussion
In an initial attempt to carry out the desired coupling,
N-phenylanthranilic acid (1a, 0.5 mmol) was treated with
diphenylacetylene (2a, 0.5 mmol) under conditions similar to
those employed for the coupling of benzoic acid with 2a.5a,b In
the presence of [{Cp*RhCl2}2] (0.005 mmol) and Cu(OAc)2
(monohydrate, 0.025 mmol) in DMF at 120 °C (bath temper-
ature) under air, 8-(N-phenylamino)-3,4-diphenylisocoumarin
(3a) was formed in 41% yield (entry 1 in Table 1, Cp* ) η5-
pentamethylcyclopentadienyl). In contrast to the case with either
2-methyl- or 2-phenylbenzoic acid,5b no 1:2 coupling product
was detected, and 51% of 2a was recovered. Interestingly, when
the reaction was carried out in o-xylene, 2a was completely
consumed to give 3a in 94% yield (entry 2).
Meanwhile, the use of another rhodium catalyst system,
[{RhCl(cod)}2]/C5H2Ph4, which was effective for the oxidative
coupling of salicylaldehydes with alkynes,5d dramatically af-
fected the reaction (C5H2Ph4 ) 1,2,3,4-tetraphenyl-1,3-cyclo-
pentadiene). Thus, the reaction with this catalyst in DMF
proceeded through double C-H bond cleavage and decarboxy-
lation to afford 4-(1,2-diphenylethenyl)-9H-carbazole (4a) in
79% yield along with a minor amount of 3a (18%) (entry 4).
(4) For recent reviews concerning C-H bond functionalization, see: (a)
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Top. Organomet. Chem. 1999, 3, 47. (c) Jia, C.; Kitamura, T.; Fujiwara, Y.
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Ritleng, V.; Sirlin, C.; Pfeffer, M. Chem. ReV. 2002, 102, 1731. (g) Kakiuchi,
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Satoh, T.; Miura, M. J. Org. Chem. 2007, 72, 5362. (c) Uto, T.; Shimizu, M.; Ueura,
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Huang, K.-H.; Shin, C.-C.; Wu, T.-C. Chem.-Eur. J. 2008, 14, 6697. (c) Li, L.;
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71, 5340.
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J. Org. Chem. Vol. 74, No. 9, 2009 3479

Shimizu et al.
TABLE 2. Reaction of N-Phenylanthranilic Acids 1 with Alkynes 2a
entry
1
R1
Cl
R2
H
R3
H
R4
2
R5
R6
conditions
time (h)
product(s), % yieldb
1
2
3
4
5
6
7
8
1b
H
2a
Ph
Ph
Ph
Ph
Pr
Ph
Ph
Ph
Ph
Pr
A
B
A
B
A
B
A
B
A
B
B
A
B
A
B
A
B
C
B
A
B
2
2
2
2
2
4
2
2
2
2
2
2
2
2
2
2
3
2
4
2
2
3b, 75
3b, 8; 4b, 75
3c, 90 (89)
3c, 13; 4c, 66
3d, 87
3d, 15; 4d, 54
3e, 82
3e, 18; 4e, 59
3f, 88
3f, 47; 4f, 35
3g, 40; 4g, 42
3h, 89
3h, 25; 4h, 63
3i, 91
3i, 3; 4i, 76
3j, 77
3j, 2; 4j, 71
3k, 86
1c
1d
1e
1a
H
H
H
H
H
H
Me
OMe
H
2a
2a
2a
2b
H
H
Me
H
Me
H
9
H
10
11
12
13
14
15
16
17
18
19
20
21
1a
1a
H
H
H
H
H
H
H
H
2c
2d
C7H15
4-MeC6H4
C7H15
4-MeC6H4
1a
1a
1a
1a
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
2e
2f
4-MeOC6H4
4-ClC6H4
2-thienyl
Me
4-MeOC6H4
4-ClC6H4
2-thienyl
Ph
2g
2h
3k, 6; 4k, 63
3l, 84c
4l, 46d
a Reaction conditions A: [1]:[2]:[[(Cp*RhCl2)2]]:[Cu(OAc)2] ) 0.5:0.5:0.005:0.025 (in mmol), in o-xylene (2.5 mL) at 120 °C under air; B:
[1]:[2]:[[{RhCl(cod)}2]]:[C5H2Ph4]:[Cu(OAc)2]
)
0.5:0.5:0.005:0.02:0.025 (in mmol), in DMF (2.5 mL) at 120 °C under air; C:
[1]:[2]:[[(Cp*RhCl2)2]]:[Cu(OAc)2] ) 0.5:0.5:0.005:1 (in mmol), in o-xylene (2.5 mL) at 120 °C under N2. b Isolated yield based on the amount of 1
used. c Small amount (6%) of a regioisomer was also formed. d Contaminated with at least two isomers. 3l was also formed in 21% GC yield.
2a smoothly under both conditions A and B to produce the
corresponding 3b-e and 4b-e, respectively (entries 1-8). Di-
alkylacetylenes such as 4-octyne (2b) underwent the coupling with
1a under conditions A efficiently to give 3 (entry 9). Under
conditions B, however, separable mixtures of 3 and 4 were obtained
in comparable amounts (entries 10 and 11). The reactions of 1a
with substituted diphenylacetylenes 2d-f effectively took place
to afford 3h-j or 4h-j selectively in good yields, depending on
the conditions (entries 12-17). The aerobic oxidative coupling of
1a with bis(2-thienyl)acetylene (2g) was found to be sluggish under
conditions A, the yield of 8-(N-phenylamino)-3,4-bis(2-thienyl)-
isocoumarin (3k) being 46% even after 4 h. However, when the
reaction was conducted in the presence of a stoichiometric amount
of Cu(OAc)2 (1 mmol) under N2 (conditions C), 3k was obtained
in 92% yield (entry 18). 1-Phenylpropyne (2h) reacted with 1a
under conditions A to give 8-(N-phenylamino)-4-methyl-3-phe-
nylisocoumarin (3l) in 89% yield, along with a small amount (6%)
of an unidentified isomer (entry 20). The corresponding carbazole
FIGURE 1. Fluorescence spectra of 3a (A), 4i (B), and Coumarin 153
(C) in the solid state upon excitation at 421 nm.
4l formed in the reaction of these substrates under conditions B
was also contaminated with at least two isomers, detected by GC
and GC-MS (entry 21).
At 140 °C, a comparable result was obtained, while the yield
of 4a decreased at 100 or 80 °C (entries 5-7). Without C5H2Ph4,
the reaction did not proceed at all (entry 8). C5H3Ph3 was
somewhat less effective than C5H2Ph4 (entry 9, C5H3Ph3 ) 1,2,4-
triphenyl-1,3-cyclopentadiene).
Table 2 summarizes the results for the synthesis of a series of
8-(arylamino)isocoumarins 3 and 4-ethenylcarbazoles 4 via the
aerobic oxidative coupling of various anthranilic acids 1 and
alkynes 2 in the presence of [{Cp*RhCl2}2] (conditions A) or
[{RhCl(cod)}2]/C5H2Ph4 (conditions B). Chloro-, methyl- and
methoxy- substituted N-phenylanthranilic acids 1b-e reacted with
Expectedly, most 8-(arylamino)isocoumarins 3 obtained above
showed solid-state fluorescence in a range of 450-500 nm (see
the Supporting Information). In contrast, the parent 3,4-diphenyl-
isocoumarin did not show fluorescence at all, confirming that the
substitution of the isocoumarin core with an amino group at the
8-position is essential for the fluorescence properties. Notably, 3a
exhibited a relatively strong emission compared to a typical emitter,
Coumarin 153 (2,3,6,7-tetrahydro-9-(trifluoromethyl)-1H,5H,11H-1
benzopyrano[6,7,8-ij]quinolizin-11-one), by a factor of 2.0 (λemis
473 nm, A versus C in Figure 1). Meanwhile, among 4-ethenyl-
3480 J. Org. Chem. Vol. 74, No. 9, 2009

Waste-Free Synthesis of Condensed Heterocyclic Compounds
SCHEME 2. Plausible Mechanism for the Coupling of N-Phenylanthranilic Acid (1a) with Alkynes 2
SCHEME 3. Reaction of o-Substituted Benzoic Acids with
Diphenylacetylene (2a), in DMF (2.5 mL) under Air at
120 °C for 2 ha
zoylbenzoic acid (7) underwent the coupling with 2a to form
isocoumarin 8.
It has also been found that the present procedure is applicable
to the synthesis of not only isocoumarins but also their heteroaryl
analogs.13 Thus, treatment of 1-methyl-1H-indole-2-carboxylic
acid (9a) with 2a under conditions A′ (similar to conditions A
in Table 2 but in DMF) for 2 h gave 9-methyl-3,4-diphen-
ylpyrano[3,4-b]indol-1(9H)-one (10a) in 96% yield (entry 1 in
Table 3). Meanwhile, other heteroarene carboxylic acids con-
taining an indole, pyrrole, benzothiophene, thiophene, or furan
ring underwent the oxidative coupling with 2a more smoothly
under the conditions using a stoichiometric amount of Cu(OAc)2
in DMF (conditions C′). In the reaction of benzofuran-2-
carboxylic acid (9h) with 2a, comparable amounts of product
10h were obtained under both conditions A’ and C’ (entries 14
and 15).
a Reaction conditions: [ArCO2H]:[2a]:[[(Cp*RhCl2)2]]:[Cu(OAc)2] ) 0.5:
0.5:0.005:0.025 (in mmol). b GC yield. Value in parentheses indicates yield
after purification.
For the synthesis of further complicated heterocyclic systems,
the reactions of aromatic diacids were next examined. Diphenic
acid (11) and terephthalic acid (13) efficiently reacted with 2b
to selectively produce 1:2 coupling products, 3,3′,4,4′-tetrapro-
pyl[8,8′-bi-1H-2-benzopyran]-1,1′-dione (12) and 3,4,8,9-tetra-
propylbenzo[1,2-c:4,5-c′]dipyran-1,6-dione (14),14 respectively,
in good yields (Scheme 4). In these cases, the use of stoichio-
metric amounts of Ag2CO3 as the oxidant was essential for the
efficient coupling. In the cases using Cu(OAc)2, no desired
products were detected.
In summary, we have demonstrated that highly substituted
isocoumarins and their heteroaryl analogs, 4-ethenylcarbazoles,
and benzodipyrandione frameworks can be constructed ef-
ficiently by the direct coupling of (hetero)arene carboxylic acids
with internal alkynes in the presence of a rhodium catalyst and
an appropriate oxidant. Some of the condensed heterocyclic
products exhibit intense fluorescence in the solid state.
carbazoles obtained, 4i was found to be more luminescent (λemis
480 nm) than Coumarin 153 by a factor of 1.3 (B versus C).
A plausible mechanism for the reaction of N-phenylanthranilic
acid (1a) with alkynes 2 is illustrated in Scheme 2, in which
neutral ligands are omitted for clarity. Coordination of the
carboxylic oxygen atom to an RhIIIX3 species gives a rhod-
ium(III) benzoate A. In the case using [{Cp*RhCl2}2] as catalyst,
subsequent ortho- rhodation to form a rhodacycle intermediate
B,11 alkyne insertion, and reductive elimination from C occur
to produce 3. On the other hand, in the reaction employing
[{RhCl(cod)}2]/C5H2Ph4, the intermediate C may undergo
decarboxylation and protonation to form ortho-ethenylated
arylrhodium intermediate D, which then followed by cyclo-
rhodation on its aminophenyl group and reductive elimination
to construct the carbazole framework of 4.12 However, the origin
of the ligand effect, which determines the preferable pathway
from the intermediate C to 3 or 4, is not clear at the present
stage. In both cases, the resulting RhIX species may be oxidized
by a copper(II) salt to regenerate RhIIIX3. Under air, CuI species
may also be reoxidized to CuII.
Experimental Section
General Procedure for Aerobic Oxidative Coupling of
2-Substituted Benzoic Acids with Internal Alkynes under
Conditions A. To a 20 mL two-necked flask were added benzoic
N-Methyl- (1f) and N-acetylanthranilic acids (1g) reacted with
2a to afford the corresponding 8-aminoisocoumarins 3m and
3n, respectively, in good yields (Scheme 3). These reactions
proceeded smoothly in DMF rather than in o-xylene, which is
preferable solvent for the reaction of N-arylanthranilic acids as
described above. From salicylic acid (5), 8-hydroxy-3,4-
diphenylisocoumarin (6) was produced in 87% yield. 2-Ben-
(13) (a) Freter, K. J. Org. Chem. 1972, 37, 2010. (b) Kita, Y.; Mohri, S.-I.;
Tsugoshi, T.; Maeda, H.; Tamaru, Y. J. Org. Chem. 1985, 33, 4723. (c) Ram,
V. J.; Goel, A.; Shukla, P. K.; Kapil, A. Bioorg. Med. Chem. Lett. 1997, 7,
3101. (d) Calvo, L.; Gonza´lez-Ortega, A.; Navarro, R.; Pe´rez, M.; San˜udo, M. C.
Synthesis 2005, 3152. (e) Raju, S.; Batchu, V. R.; Swamy, N. K.; Dev, R. V.;
Sreekanth, B. R.; Babu, J. M.; Vyas, K.; Kumar, P. R.; Mukkanti, K.; Annamalai,
P.; Pal, M. Tetrahedron 2006, 62, 9554. (f) Hellal, M.; Bourguignon, J.-J.; Bihel,
F. J.-J. Tetrahedron Lett. 2008, 49, 62. (g) Patankar, J. A.; Khombare, R. T.;
Khanwelkar, R. R.; Shet, J. B. J. Chem. Res. 2008, 129.
(11) For stoichiometric ortho-rhodation of a Cp*Rh benzoate, see: Kisenyi,
J. M.; Sunley, G. J.; Cabeza, J. A.; Smith, A. J.; Adams, H.; Salt, N. J.; Maitlis,
P. M. J. Chem. Soc., Dalton Trans. 1987, 2459.
(12) A similar mechanism involving metal migration on diphenylamine
systems was reported. See ref 9.
(14) This is a partial structure of ladder-type conjugated polymers: Kim, I;
Kim, T.-H.; Kang, Y; Lim, Y.-B Tetrahedron Lett. 2006, 47, 8689.
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Shimizu et al.
TABLE 3. Reaction of Heteroarene Carboxylic Acids 9 with Diphenylacetylene (2a)a
a Reaction conditions A′: [9]:[2a]:[[(Cp*RhCl2)2]]:[Cu(OAc)2] ) 0.5:0.5:0.005:0.025 (in mmol), in DMF (2.5 mL) at 120 °C for 2 h under air; C′:
[9]:[2a]:[[(Cp*RhCl2)2]]:[Cu(OAc)2] ) 0.5:0.5:0.005:1 (in mmol), in DMF (2.5 mL) at 120 °C for 2 h under N2. b GC yield based on the amount of 2a
used. Value in parentheses indicates yield after purification. c 9 (0.6 mmol) was used. d At 140 °C.
SCHEME 4. Reaction of Aromatic Diacids with 4-Octyne
extracted with EtOAc (100 mL). Then the organic layer was washed
by water (100 mL, twice) and dried over sodium sulfate. After
evaporation of the solvents under vacuum, the residue was washed
by hexane (10 mL, three times) to give crystals of the isocoumarin
product.
(2b), in DMF (3 mL) under N2 at 140 °C for 2 ha
8-(N-Phenylamino)-3,4-diphenylisocoumarin (3a) (entry 4
in Table 1). mp 196-200 °C; 1H NMR (400 MHz, CDCl3) δ 6.36
(d, J ) 7.7 Hz, 1H), 7.13-7.41 (m, 17H), 10.25 (s, 1H); 13C NMR
(100 MHz, CDCl3) δ 104.1, 111.0, 113.8, 117.8, 123.8, 124.6,
127.8, 127.9, 128.8, 128.9, 129.1, 129.5, 131.3, 132.9, 135.0, 135.5,
140.1, 140.8, 149.4, 150.1, 164.1; MS m/z 389 (M+). Anal. Calcd
for C27H19NO2: C, 83.27; H, 4.92; N, 3.60. Found: C, 83.09; H,
4.96; N, 3.68.
General Procedure for Aerobic Oxidative Coupling of
N-Arylanthranilic Acids with Internal Alkynes under Con-
ditions B. To a 20 mL two-necked flask were added N-arylanthra-
nilic acid 1 (0.5 mmol), alkyne 2 (0.5 mmol), [RhCl(cod)]2 (0.005
mmol, 3 mg), C5H2Ph4 (0.02 mmol, 7 mg), Cu(OAc)2 (0.025 mmol,
5 mg), 1-methylnaphthalene (ca. 50 mg) as internal standard, and
DMF (2.5 mL). The resulting mixture was stirred under air at
120 °C. GC and GC-MS analyses of the mixtures confirmed
formation of 4-ethenylcarbazole 4 and 3. Then, the mixture was
cooled to room temperature and Et2O (100 mL) and diluted
hydrochloric acid (ca. 20 wt%, 100 mL) were added. The color of
the organic layer turned from green to yellow during the extraction
a Reaction conditions: [diacid]:[2b]:[[(Cp*RhCl2)2]]:[Ag2CO2] ) 0.5:1:
0.005:1 (in mmol). b GC yield. Value in parentheses indicates yield after
purification.
acid 1, 5, or 7 (0.5 mmol), alkyne 2 (0.5 mmol), (Cp*RhCl2)2 (0.005
mmol, 3 mg), Cu(OAc)2 (0.025 mmol, 5 mg), 1-methylnaphthalene
(ca. 50 mg) as internal standard, and o-xylene (2.5 mL). The
resulting mixture was stirred under air at 120 °C. GC and GC-MS
analyses of the mixtures confirmed formation of isocoumarin 3, 6,
or 8. Then, the mixture was cooled to room temperature and
3482 J. Org. Chem. Vol. 74, No. 9, 2009

Waste-Free Synthesis of Condensed Heterocyclic Compounds
process. After it was washed by water (100 mL, twice) and dried
over sodium sulfate, the solvents were evaporated under vacuum.
The product was isolated by column chromatography on silica gel
using hexane-ethyl acetate (90:10, v/v) as eluant.
0.97 (t, J ) 7.3 Hz, 6H), 1.06 (t, J ) 7.3 Hz, 6H), 1.60-1.74 (m,
8H), 2.50-2.54 (m, 4H), 2.60-2.66 (m, 4H), 7.14 (d, J ) 7.3 Hz,
2H), 7.54 (d, J ) 8.4 Hz, 2H), 7.69 (t, J ) 7.9 Hz, 2H); 13C NMR
(100 MHz, CDCl3) δ 13.9, 14.2, 21.0, 22.8, 28.6, 32.6, 112.1, 118.6,
121.9, 127.7, 133.2, 138.7, 146.1, 154.0, 161.4; MS m/z 458 (M+).
Anal. Calcd for C30H34O4: C, 78.57; H, 7.47. Found: C, 78.29; H,
7.31.
3,4,8,9-Tetrapropylbenzo[1,2-c:4,5-c′]dipyran-1,6-dione
(14) (Scheme 4). mp 161-168 °C; 1H NMR (400 MHz, CDCl3) δ
1.00-1.08 (m, 12H), 1.58-1.68 (m, 4H), 1.72-1.82 (m, 4H), 2.60
(t, J ) 7.7 Hz, 4H), 2.68 (t, J ) 7.9 Hz, 4H), 8.47 (s, 2H); 13C
NMR (100 MHz, CDCl3) δ 13.8, 14.1, 21.1, 22.9, 28.1, 32.7, 112.2,
124.8, 125.5, 135.7, 154.5, 162.1; MS m/z 382 (M+). Anal. Calcd
for C24H30O4: C, 75.36; H, 7.91. Found: C, 75.09; H, 7.78.
4-(1,2-Diphenylethenyl)-9H-carbazole (4a) (entry
4 in
Table 1).9 mp 121-126 °C; 1H NMR (400 MHz, CDCl3) δ
6.95-7.06 (m, 3H), 7.16-7.37 (m, 14H), 8.02 (s, 1H), 8.29 (d, J
) 8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 104.4, 110.4, 119.3,
121.1, 121.5, 122.7, 123.1, 125.4, 125.6, 126.9, 127.3, 128.2, 128.3,
129.5, 129.9, 130.8, 137.4, 139.8, 140.0, 140.1, 140.4, 141.0; HRMS
m/z Calcd for C26H19N (M+) 345.1517, found 345.1534.
General Procedure for Oxidative Coupling of Aromatic
Diacids with Internal Alkynes. To a 20 mL two-necked flask were
added diacid 11 or 13 (0.5 mmol), 4-octyne (2b) (1 mmol, 110
mg), (Cp*RhCl2)2 (0.005 mmol, 3 mg), Ag2CO3 (1 mmol, 275 mg),
1-methylnaphthalene (ca. 50 mg) as internal standard, and DMF
(3 mL). The resulting mixture was stirred under N2 at 140 °C. GC
and GC-MS analyses of the mixtures confirmed formation of 12
or 14. Then, the mixture was cooled to room temperature and
extracted with EtOAc (100 mL). Then the organic layer was washed
by water (100 mL, twice) and dried over sodium sulfate. After
evaporation of the solvents under vacuum, the residue was washed
by hexane (10 mL, three times) to give crystals of the product.
3,3′,4,4′-Tetrapropyl[8,8′-bi-1H-2-benzopyran]-1,1′-dione
(12) (Scheme 4). mp 181-186 °C; 1H NMR (400 MHz, CDCl3) δ
Acknowledgment. This work was partly supported by a
Grant-in-Aid from the Ministry of Education, Culture, Sports,
Science and Technology, Japan and the General Sekiyu Research
Foundation.
Supporting Information Available: Characterization data
of products. This material is available free of charge via the
Internet at http://pubs.acs.org.
JO900396Z
J. Org. Chem. Vol. 74, No. 9, 2009 3483