When benzoic acid (1a, 0.5 mmol) was treated with
diphenylacetylene (2a, 0.6 mmol) in the presence of
Scheme 1
[Cp*RhCl ]
2 2
2 2
(1 mol %) and Cu(OAc) ‚H O (5 mol %) under
air in DMF at 120 °C for 2 h, 3,4-diphenylisocoumarin (3a)
5
was formed in 96% yield (entry 1 in Table 1, Cp* ) η -
Table 1. Reaction of Benzoic Acid (1a) with
Diphenylacetylene (2a)a
approach has not been extensively explored. In some rare
examples, we demonstrated that 2-phenylphenols, N-(aryl-
sulfonyl)-2-phenylanilines, and benzoic acids can directly and
regioselectively couple with alkenes under air in the presence
of a Pd/Cu catalyst.4
The reaction of the third substrates, benzoic acids, seems
to be of particular interest because of their wide availability
as aryl sources, comparable to that of aryl halides. The
entry
1
Rh catalyst
solvent
time (h)
yield of 3ab
5
[Cp*RhCl2]2
RhCl3·H2O
Rh(acac)3
[RhCl(cod)]2
[RhCl(C2H4)2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
DMF
DMF
DMF
DMF
DMF
DMF
DMSO
diglyme
n-nonane
DMF
2
5
5
5
5
5
5
5
5
5
96(93)
0
0
<1
<1
0
2
0
0
41
reactions of benzoic acid with styrene and an acrylate afford
isocoumarin and phthalide derivatives, respectively, via ortho
vinylation and subsequent oxidative or nonoxidative cycli-
c
2
3
c
4
5
6
4
a
zation.
Isocoumarin and phthalide nuclei are found in various
natural products that exhibit a broad range of interesting
d
7
8
9
10e
6
biological properties. Although these reactions have high
potential to provide clean synthetic routes to such hetero-
7
cycles, their efficiency is moderate to low: decomposition
of the homogeneous palladium-based catalyst into inactive
bulk metal seems to be involved. During palladium-catalyzed
oxidation, in general, the regeneration of Pd(II) from Pd(0)
is considered to be the crucial step to determine catalyst
a
Reaction conditions: 1a (0.5 mmol), 2a (0.6 mmol), Rh catalyst (0.005
mmol), Cu(OAc)2‚H2O (0.025 mmol), solvent (2.5 mL) at 120 °C under
air. b GC yield based on the amount of 1a used. Value in parentheses
c
d
indicates yield after purification. Rh catalyst (0.01 mmol) was used.
Without Cu(OAc)2‚H2O. e At 100 °C.
2
c
efficiency. Moreover, the coupling partners are so far
limited to some alkenes, and the reactions with other
unsaturates including alkynes are unexplored. In the context
pentamethylcyclopentadienyl). None or trace amounts of 3a
were obtained in the case using RhCl , Rh(acac) , [RhCl-
in place of [Cp*RhCl (entries
-5, acac ) acetylacetonate, cod ) cyclooctadiene). The
‚H O was crucial for the reaction. Thus,
the reaction did not proceed without the cocatalyst (entry
). DMF was found to be the solvent of choice. In other
8
of our study of catalytic coupling of benzoic acid derivatives,
3
3
(
cod)]
2
, or [RhCl(C
2
4
H )
2
]
2
2 2
]
we have succeeded in finding that the environmentally
benign, direct cyclizative coupling of benzoic acids with
internal alkynes can be realized by using Rh2j,k,9 in place of
Pd as the principal catalyst component to afford isocoumarin
derivatives in good to excellent yields.
2
addition of Cu(OAc)
2
2
6
solvents such as DMSO, diglyme, and n-nonane, the reaction
(
4) (a) Miura, M.; Tsuda, T.; Satoh, T.; Pivsa-Art, S.; Nomura, M. J.
did not proceed catalytically (entries 7-9).
Org. Chem. 1998, 63, 5211. (b) Miura, M.; Tsuda, T.; Satoh, T.; Nomura,
M. Chem. Lett. 1997, 1103.
Table 2 summarizes the results for the coupling employing
a series of benzoic acids and alkynes under the optimized
conditions. The reaction of 1a with dialkylacetylenes 2b and
(
5) Recently, palladium-catalyzed decarboxylative arylation and viny-
lation of arene and heteroarene carboxylic acids were reported. Arylation:
a) Gooâen, L. J.; Deng, G.; Levy, L. M. Science 2006, 313, 662. (b)
(
2
c proceeded efficiently, as did that with diphenylacetylene,
to produce 3,4-dialkylisocoumarins 3b and 3c in good yields
entries 1 and 2). From unsymmetrical alkylphenylacetylenes,
Forgione, P.; Brochu, M.-C.; St-Onge, M.; Thesen, K. H.; Bailey, M. D.;
Bilodeau, F. J. Am. Chem. Soc. 2006, 128, 11350. Vinylation: (c) Tanaka,
D.; Romeril, S. P.; Myers, A. G. J. Am. Chem. Soc. 2005, 127, 10323. (d)
Tanaka, D.; Myers, A. G. Org. Lett. 2004, 6, 433. (e) Myers, A. G.; Tanaka,
D.; Mannion, M. R. J. Am. Chem. Soc. 2002, 124, 11250.
(
2d and 2e, 4-alkyl-3-phenylisocoumarins 3d and 3e were
predominantly formed in 84 and 88% yields, along with
minor amounts (5 and 10%, respectively) of their regioiso-
mers, 3-alkyl-4-phenylisocoumarins (entries 3 and 4). In
contrast, 1-phenyl-2-(trimethylsilyl)acetylene did not couple
with 1a at all: only a desilylative homocoupling product
was detected by GC-MS. Electron-rich (entries 5, 7 and 8),
(6) For example, see: (a) Subramanian, V.; Rao Batchu, V.; Barange,
D.; Pal, M. J. Org. Chem. 2005, 70, 4778. (b) Mali, R. S.; Babu, K. N. J.
Org. Chem. 1998, 63, 2488 and references therein.
(
7) Pt-catalyzed oxidative cyclization of amino acids: Dangel, B. D.;
Johnson, J. A.; Sames, D. J. Am. Chem. Soc. 2001, 123, 8149.
8) (a) Sugihara, T.; Satoh, T.; Miura, M. Tetrahedron Lett. 2005, 46,
(
8
2
269. (b) Sugihara, T.; Satoh, T.; Miura, M.; Nomura, M. AdV. Synth. Catal.
004, 346, 1765. (c) Sugihara, T.; Satoh, T.; Miura, M.; Nomura, M. Angew.
Chem., Int. Ed. 2003, 42, 4672. (d) Yasukawa, T.; Satoh, T.; Miura, M.;
Nomura, M. J. Am. Chem. Soc. 2002, 124, 12680. (e) Okazawa, T.; Satoh,
T.; Miura, M.; Nomura, M. J. Am. Chem. Soc. 2002, 124, 5286. (f) Oguma,
K.; Miura, M.; Satoh, T.; Nomura, M. J. Organomet. Chem. 2002, 648,
97. (g) Kametani, Y.; Satoh, T.; Miura, M.; Nomura, M. Tetrahedron Lett.
000, 41, 2655. (h) Kokubo, K.; Matsumasa, K.; Miura, M.; Nomura, M.
J. Org. Chem. 1996, 61, 6941. (i) Kokubo, K.; Miura, M.; Nomura, M.
Organometallics 1995, 14, 4521.
(9) For examples of rhodium-catalyzed aerobic oxidation, see: (a) Fazlur-
Rahman, A. K.; Tsai, J.-C.; Nicholas, K. M. J. Chem. Soc., Chem. Commun.
1992, 1334. (b) Bressan, M.; Morvillo, A. Inorg. Chim. Acta 1989, 166,
177. (c) Mimoun, H. Angew. Chem., Int. Ed. Engl. 1982, 21, 734. (d)
Mimoun, H.; Perez-Machirant, M. M.; S e´ r e´ e de Roch, I. J. Am. Chem. Soc.
1978, 100, 5437.
2
2
1408
Org. Lett., Vol. 9, No. 7, 2007