Rhodium- and iridium-catalyzed oxidative coupling of benzoic acids with alkynes via regioselective C-H bond cleavage

Article abstract of DOI:10.1021/jo070735n

(Chemical Equation Presented) The oxidative coupling of benzoic acids with internal alkynes effectively proceeds in the presence of [Cp*RhCl ₂]₂ and Cu(OAc)₂·H₂O as catalyst and oxidant, respectively, to produce

Full text of DOI:10.1021/jo070735n

Rhodium- and Iridium-Catalyzed Oxidative Coupling of Benzoic
Acids with Alkynes via Regioselective C-H Bond Cleavage
Kenji Ueura, 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 April 9, 2007
The oxidative coupling of benzoic acids with internal alkynes effectively proceeds in the presence of
[Cp*RhCl2]2 and Cu(OAc)2‚H2O as catalyst and oxidant, respectively, to produce the corresponding
isocoumarin derivatives. The copper salt can be reduced to a catalytic quantity under air. Interestingly,
by using [Cp*IrCl2]2 in place of [Cp*RhCl2]2, the substrates undergo 1:2 coupling accompanied by
decarboxylation to afford naphthalene derivatives exclusively. In this case, Ag2CO3 acts as an effective
oxidant.
Introduction
groups2a,3a,4 can also act as good anionic anchors to exhibit the
proximate effect.
Transition-metal-catalyzed organic reactions via C-H bond
cleavage have attracted much attention from the atom-economic
point of view, and various catalytic processes involving different
modes to activate the ubiquitously available bond have been
developed.1 Among the most promising activation strategies is
to utilize the proximate effect by coordination of a functional
group in a given substrate to the metal center of a catalyst that
brings about regioselective C-H bond activation and function-
alization. Several catalytic coupling reactions of aromatic
compounds bearing carbonyl or nitrogen-containing groups with
alkenes or alkynes via such directed C-H bond cleavage have
successfully been developed.1 Besides the functional groups
containing a neutral heteroatom, hydroxyl,2 carboxyl,3 and amide
As such examples, we demonstrated that 2-phenylphenols,2e
N-(arylsulfonyl)-2-phenylanilines,3a and benzoic acids3a undergo
direct oxidative coupling with alkenes under air in the presence
of a Pd/Cu catalyst as depicted in Scheme 1 as a general
sequence (-LH ) 2-hydroxyphenyl, 2-(aminosulfonyl)phenyl,
CO2H). The reaction of the third substrates, benzoic acids, seems
to be of particular interest because of their wide availability as
aryl sources.5 The reactions of benzoic acid with styrene and
an acrylate afford isocoumarin and phthalide derivatives,
respectively, via ortho-vinylation and subsequent oxidative or
nonoxidative cyclization.3a
(2) (a) Nishinaka, Y.; Satoh, T.; Miura, M.; Morisaka, H.; Nomura, M.;
Matsui, H.; Yamaguchi, C. Bull. Chem. Soc. Jpn. 2001, 74, 1727. (b) Satoh,
T.; Nishinaka, Y.; Miura, M.; Nomura, M. Chem. Lett. 1999, 615. (c)
Kokubo, K.; Matsumasa, K.; Nishinaka, Y.; Miura, M.; Nomura, M. Bull.
Chem. Soc. Jpn. 1999, 72, 303. (d) Kokubo, K.; Matsumasa, K.; Miura,
M.; Nomura, M. J. Org. Chem. 1997, 62, 4564. (e) Miura, M.; Tsuda, T.;
Satoh, T.; Nomura, M. Chem. Lett. 1997, 1103.
(3) (a) Miura, M.; Tsuda, T.; Satoh, T.; Pivsa-Art, S.; Nomura, M. J.
Org. Chem. 1998, 63, 5211. For decarboxylative couling, see: (b) Tanaka,
D.; Romeril, S. P.; Myers, A. G. J. Am. Chem. Soc. 2005, 127, 10323. (c)
Tanaka, D.; Myers, A. G. Org. Lett. 2004, 6, 433. (d) Myers, A. G.; Tanaka,
D.; Mannion, M. R. J. Am. Chem. Soc. 2002, 124, 11250. (e) Okazawa, T.;
Satoh, T.; Miura, M.; Nomura, M. J. Am. Chem. Soc. 2002, 124, 5286.
(4) (a) Zaitsev, V. G.; Daugulis, O. J. Am. Chem. Soc. 2005, 127, 4156.
(b) Boele, M. D. K.; van Strijdonck, G. P. F.; de Vries, A. H. M.; Kamer,
P. C. J.; de Vries, J. G.; van Leeuwen, P. W. N. M. J. Am. Chem. Soc.
2002, 124, 1586.
(1) Reviews: (a) Alberico, D.; Scott, M. E.; Lautens, M. Chem. ReV.
2007, 107, 174. (b) Satoh, T.; Miura, M. Chem. Lett. 2007, 36, 200. (c)
Satoh, T.; Miura, M. J. Synth. Org. Chem. 2006, 64, 1199. (d) Conley, B.
L.; Tenn, W. J., III; Young, K. J. H.; Ganesh, S. K.; Meier, S. K.; Ziatdinov,
V. R.; Mironov, O.; Oxgaard, J.; Gonzales, J.; Goddard, W. A., III; Periana,
R. A. J. Mol. Catal. A 2006, 251, 8. (e) Miura, M.; Satoh, T. In Handbook
of C-H Transformations; Dyker, G., Ed.; Wiley-VCH: Weinheim, Germany,
2005; Vol. 1, p 223. (f) Miura, M.; Satoh, T. Top. Organomet. Chem. 2005,
14, 55. (g) Kakiuchi, F.; Chatani, N. AdV. Synth. Catal. 2003, 345, 1077.
(h) Jun, C.-H.; Moon, C. W.; Lee, D.-Y. Chem. Eur. J. 2002, 8, 2622. (i)
Ritleng, V.; Sirlin, C.; Pfeffer, M. Chem. ReV. 2002, 102, 1731. (j) Miura,
M.; Nomura, M. Top. Curr. Chem. 2002, 219, 211. (k) Kakiuchi, F.; Murai,
S. Acc. Chem. Res. 2002, 35, 826. (l) Dyker, G. Angew. Chem., Int. Ed.
1999, 38, 1698. (m) Kakiuchi, F.; Murai, S. Top. Organomet. Chem. 1999,
3, 47. (n) Shilov, A. E.; Shul’pin, G. B. Chem. ReV. 1997, 97, 2879.
10.1021/jo070735n CCC: $37.00 © 2007 American Chemical Society
Published on Web 06/06/2007
5362
J. Org. Chem. 2007, 72, 5362-5367

Rhodium- and Iridium-Catalyzed OxidatiVe Coupling
TABLE 1. Dehydrogenative Coupling of Benzoic Acid (1a) with
Diphenylacetylene (2a)a
SCHEME 1. Transition-Metal-Catalyzed Oxidative
Coupling of Functionalized Aromatic Substrates with
Unsaturated Compounds
% yieldb
entry Cu(OAc)2‚H2O (mmol) solvent temp (°C) time (h) 3a
4a
1c
2c
3c
4d
5d
6d
7d
8d
9d
4
4
2
o-xylene
o-xylene
o-xylene
o-xylene
DMF
DMSO
diglyme
n-nonane
DMF
120
100
100
120
120
120
120
120
100
6
9
10
5
2
5
5
5
5
95
94
90 (81)
25
96 (93)
2
0
0
41
5
2
3
32
3
<1
4
<1
17
Isocoumarin and phthalide nuclei are found in various natural
products that exhibit a broad range of interesting biological
properties.6 Although these reactions have high potential to
provide atom-economic routes to such heterocycles,7,8 their
efficiency is moderate to low: decomposition of the homoge-
neous 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 efficiency.9 Moreover, the
coupling partners are so far limited to some alkenes, and the
reactions with other unsaturated substrates including alkynes
are unexplored. In the context of our study of catalytic coupling
of benzoic acid derivatives,10 we have succeeded in finding that
the direct oxidative coupling of benzoic acids with internal
alkynes can be realized by using Rh11,12 in place of Pd as the
principal catalyst component to afford isocoumarin derivatives
in good to excellent yields.13 Furthermore, by using an iridium
catalyst, the corresponding naphthalene derivatives can be
produced selectively from the same combination of substrates
0.025
0.025
0.025
0.025
0.025
0.025
a Reaction conditions: [1a]/[2a]/[[Cp*RhCl2]2] ) 0.5:0.6:0.005 (in
mmol), under N2. b GC yield based on the amount of 1a used. Value in
parentheses indicates yield after purification. c [1a]/[2a] ) 1:1.2 (in mmol).
d Under air.
accompanied by decarboxylation. This represents a new example
of aromatic homologation by the coupling of ArX and two
alkyne molecules.14 The results obtained with respect to the
scope and limitations for these reactions are described herein.
Results and Discussion
When benzoic acid (1a) was treated with diphenylacetylene
(2a, 1.2 equiv) in the presence of [Cp*RhCl2]2 (1 mol %) and
Cu(OAc)2‚H2O (4 equiv) in o-xylene at 120 °C for 6 h under
N2, 3,4-diphenylisocoumarin (3a) was formed in 95% yield,
along with a small amount of 1,2,3,4-tetraphenylnaphthalene
(4a, 5%) (entry 1 in Table 1, Cp* ) η5-pentamethylcyclopen-
tadienyl). No amount of 3a or trace amounts of 3a were obtained
in the case using RhCl3‚H2O, Rh(acac)3, [RhCl(cod)]2, or [RhCl-
(C2H4)2]2 in place of [Cp*RhCl2]2 (acac ) acetylacetonate, cod
) cyclooctadiene). Although the reaction was somewhat
retarded, 3a was obtained in 90% yield even using a reduced
amount of Cu(OAc)2‚H2O (2 equiv) at 100 °C (entry 3). The
amount of the copper salt could be reduced to 5 mol % when
the reaction was conducted under air. Thus, the aerobic oxidative
coupling of 1a with 2a using a catalyst system of [Cp*RhCl2]2/
Cu(OAc)2‚H2O proceeded efficiently in DMF at 120 °C to afford
3a in 96% yield (entry 5). DMF was found to be the solvent of
choice. Thus, a significant amount of 4a (32%) was formed
accompanied by a decrease of the yield of 3a in o-xylene (entry
4). The reaction did not proceed catalytically in other solvents
(5) Recently, palladium-catalyzed ipso-decarboxylative arylation and
ortho-arylation of arene and heteroarene carboxylic acids were reported.
ipso-Arylation: (a) Gooâen, L. J.; Deng, G.; Levy, L. M. Science 2006,
313, 662. (b) Forgione, P.; Brochu, M.-C.; St-Onge, M.; Thesen, K. H.;
Bailey, M. D.; Bilodeau, F. J. Am. Chem. Soc. 2006, 128, 11350. ortho-
Arylation: Giri, R.; Maugel, N.; Li, J.-J.; Wang, D.-H.; Breazzano, S. P.;
Saunders, L. B.; Yu, J.-Q. J. Am. Chem. Soc. 2007, 129, 3510.
(6) For example, see: (a) Rossi, R.; Carpita, A.; Bellina, F.; Stabile, P.;
Mannina, L. Tetrahedron 2003, 59, 2067. (b) Yao, T.; Larock, R. C. J.
Org. Chem. 2003, 68, 5936. (c) Mali, R. S.; Babu, K. N. J. Org. Chem.
1998, 63, 2488 and references cited therein.
(7) Pt-catalyzed lactone synthesis via C-H bond activation directed by a
carboxyl group and oxidative cyclization has been reported: (a) Lee, J.
M.; Chang, S. Tetrahedron Lett. 2006, 47, 1375. (b) Dangel, B. D.; Johnson,
J. A.; Sames, D. J. Am. Chem. Soc. 2001, 123, 8149.
(8) For recent reports concerning Pd-catalyzed synthesis of isocoumarins
and phthalides, see: (a) Mereyala, H. B.; Pathuri, G. Synthesis 2006, 2944.
(b) Subramanian, V.; Rao Batchu, V.; Barange, D.; Pal, M. J. Org. Chem.
2005, 70, 4778. (c) Wu, X.; Mahalingam, A. K.; Wan, Y.; Alterman, M.
Tetrahedron Lett. 2004, 45, 4635. (d) Lee, Y.; Fujiwara, Y.; Ujita, K.;
Nagamoto, M.; Ohta, H.; Shimizu, I. Bull. Chem. Soc. Jpn. 2001, 74, 1437.
(e) Larock, R. C.; Doty, M. J.; Han, X. J. Org. Chem. 1999, 64, 8770. (f)
Orito, K.; Miyazawa, M.; Kanbayashi, R.; Tokuda, M.; Suginome, H. J.
Org. Chem. 1999, 64, 6583. (g) Liao, H.-Y.; Cheng, C.-H. J. Org. Chem.
1995, 60, 3711. (h) Larock, R. C.; Yum, E. K.; Doty, M. J.; Sham, K. K.
C. J. Org. Chem. 1995, 60, 3270.
(9) Stahl, S. S. Angew. Chem., Int. Ed. 2004, 43, 3400 and references
therein.
(12) 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.; Se´re´e de Roch, I. J. Am.
Chem. Soc. 1978, 100, 5437.
(10) (a) Sugihara, T.; Satoh, T.; Miura, M. Tetrahedron Lett. 2005, 46,
8269. (b) Sugihara, T.; Satoh, T.; Miura, M.; Nomura, M. AdV. Synth. Catal.
2004, 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,
297. (g) Kametani, Y.; Satoh, T.; Miura, M.; Nomura, M. Tetrahedron Lett.
2000, 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.
(13) Preliminary communication: Ueura, K.; Satoh, T.; Miura, M. Org.
Lett. 2007, 9, 1407.
(14) Related naphthalene synthesis by the 1:2 coupling of ArX with
internal alkynes: X ) CrPh2: (a) Whitesides, G. M.; Ehmann, W. J. J.
Am. Chem. Soc. 1970, 92, 5625. (b) Herwig, W.; Metlesics, W.; Zeiss, H.
J. Am. Chem. Soc. 1959, 81, 6203. X ) I: (c) Kawasaki, S.; Satoh, T.;
Miura, M.; Nomura, M. J. Org. Chem. 2003, 68, 6836. (d) Wu, G.;
Rheingold, A. L.; Feib, S. L.; Heck, R. F. Organometallics 1987, 6, 1941.
(e) Sakakibara, T.; Tanaka, Y.; Yamasaki, T.-I. Chem. Lett. 1986, 797. X
) COCl: see ref 7d. o-Dihalobenzenes: Huang, W.; Zhou, X.; Kanno,
K.-I.; Takahashi, T. Org. Lett. 2004, 6, 2429.
(11) Rh-Catalyzed oxidative coupling of unactivated aromatic compounds
with alkenes has been reported: (a) Matsumoto, T.; Periana, R. A.; Taube,
D. J.; Yoshida, H. J. Catal. 2002, 206, 272. (b) Matsumoto, T.; Yoshida,
H. Chem. Lett. 2000, 1064.
J. Org. Chem, Vol. 72, No. 14, 2007 5363

Ueura et al.
TABLE 2. Dehydrogenative Coupling of Benzoic Acids 1a-i with Alkynes 2a-ea
entry
1
R1
H
R2
R3
R4
2
R5
Prn
R6
Prn
conditions
time (h)
products, % yieldb
3b, 96 (86)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
1a
H
H
H
2b
A
B
A
B
A
B
A
B
9
2
9
2
6
2
6
2
8
2
10
8
2
10
2
9
2
5
2
3b, 83 (77)
3c, 96 (90)
3c, 97 (94)
3d, 89 (86)c
3d, 84 (79)c
3e, 86 (81)c
3e, 88 (84)c
3f, 92 (82); 4b, 6 (6)
3f, 94 (84); 4b, 6 (6)
3g, (63)
3h, 82 (74); 4c, 16 (12)
3h, 84 (76); 4c, 16 (13)
3i, 73 (65); 4d, 12 (10)
3i, 59; 4d, 16
3j, 97 (92); 4b, 3 (3)
3j, 81 (75); 4b, 2 (2)
3k, 99 (89)
n
n
1a
1a
1a
1b
H
H
H
H
H
H
H
H
H
H
H
H
H
2c
2d
2e
2a
C7H15
Me
C7H15
Ph
H
H
Bun
Ph
Ph
Me
Ph
A
B
1c
1d
H
H
H
H
OH
Cl
H
H
2a
2a
Ph
Ph
Ph
Ph
A
A
Bd
A
Bd
A
Bd
A
Bd
A
Bd
Af
1e
1f
H
H
CF3
H
H
2a
2a
2a
2a
2a
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
H
Me
OMe
H
H
1g
1h
1i
H
H
OMe
H
3k, 97 (92)
Me
H
10
2
4
3l, 67 (57); 4′e ()4b), 17 (14)e
3l, 91 (83); 4′e ()4b), 7 (7)e
3m, 42 (30); 4′f, 53 (43)g
Ph
H
H
H
a Reaction conditions A: [1]/[2]/[[Cp*RhCl2]2]/[Cu(OAc)2‚H2O] ) 1:1.2:0.005:2 (in mmol), in o-xylene at 120 °C under N2; B: [1]/[2]/[[Cp*RhCl2]2]/
Cu(OAc)2‚H2O) ) 0.5:0.6:0.005:0.025 (in mmol), in DMF at 120 °C under air. b GC yield based on the amount of 1 used. Value in parentheses indicates
yield after purification. c A minor amount of 3-alkyl-4-phenyl isomer was formed (see text). d At 140 °C. e 6-Methyl-1,2,3,4-tetraphenylnaphthalene (4′e )
4b) was formed in place of 5-methyl-1,2,3,4-tetrahenylnaphthalene (4: R1 ) Me, R2 ) R3 ) R4 ) H, R5 ) R6 ) Ph). f With 2a (2 mmol) at 160 °C.
g 1,2,3,4,6-Pentaphenylnaphthalene (4′f) was formed in place of 1,2,3,4,5-pentaphenylnaphthalene (4: R1 ) R5 ) R6 ) Ph, R2 ) R3 ) R4 ) H).
SCHEME 2. Dehydrogenative Coupling of Benzoic Acids
1h, i with Diphenylacetylene (2a)
such as DMSO, diglyme, and n-nonane (entries 6-8). Even in
DMF, the reaction efficiency was low at 100 °C (entry 9). Again,
RhCl3‚H2O, Rh(acac)3, [RhCl(cod)]2, and [RhCl(C2H4)2]2 showed
no catalytic activity, as they showed none in the reaction using
a stoichiometric amount of Cu(OAc)2‚H2O. The addition of the
copper cocatalyst was crucial for the reaction. Thus, the reaction
did not proceed without it.
Table 2 summarizes the results for the coupling employing a
series of benzoic acids and alkynes in the presence of a
conditions A to give the corresponding substituted isocoumarins
stoichiometric (conditions A) or catalytic amount of Cu(OAc)2‚
3f-k in 63-99% yields (entries 9, 11, 12, 14, 16, and 18). On
H2O (conditions B). The reaction of 1a with dialkylacetylenes
the other hand, the oxidative coupling under conditions B also
2b and 2c proceeded efficiently, as that with diphenylacetylene,
proceeded similarly (entries 10, 13, 15, 17, and 19), except that
to produce 3,4-dialkylisocoumarins 3b and 3c in good yields
the reaction of 4-hydroxybenzoic acid (1c) with 2a did not give
under both conditions A and B (entries 1-4). From unsym-
3g at all under air. The reaction of 3-toluic acid (1f) exclusively
metrical alkylphenylacetylenes, 2d and 2e, 4-alkyl-3-phenyl-
gave a single regioisomer, 7-methyl-3,4-diphenylisocoumarin
isocoumarins 3d and 3e were predominantly formed in 84-
(3j) (entries 16 and 17). This indicates that the C-H bond
89% yields, along with minor amounts of their regioisomers,
cleavage only occurs at the sterically less hindered 6-position
3-alkyl-4-phenylisocoumarins (9, 5, 14, and 10% for entries 5,
regioselectively. In most cases, minor amounts of 4 were also
6, 7, and 8, respectively). In these reactions of 1a with 2b-e,
in contrast to the case using 1a with 2a, naphthalene derivatives
as byproducts were not detected by gas chromatography-mass
spectrometry (GC-MS). 1-Phenyl-2-(trimethylsilyl)acetylene and
formed as separable byproducts. Although the reactions of
sterically hindered benzoic acids 1h and 1i with 2a proceeded
under conditions A, considerable amounts of naphthalenes 4′
were formed with decrease of yields of 3 (entries 20 and 22).
phenylacetylene did not couple with 1a at all, and only a
They were identified to be 6-substituted naphthalenes, 6-methyl-
desilylative or dehydrogenative homocoupling product, diphen-
ylbutadiyne, was detected by GC-MS. Bis(trimethylsilyl)-
acetylene and diethyl acetylenedicarboxylate could not be used
for the reaction; they were consumed by unidentified reactions
other than the desired coupling in treatment with 1a under
conditions A. Electron-rich (1b, c, f, g) and -deficient (1d, e)
benzoic acids were found to react with 2a smoothly under
1,2,3,4-tetraphenylnaphthalene (4′e ) 4b) and 1,2,3,4,6-pen-
taphenylnaphthalene (4′f), and not the expected 5-substituted
naphthalenes (Scheme 2). The 6-substituted naphthalenes were
obtained similarly under iridium catalysis (vide infra).
Under similar conditions to those for the reaction of 1i with
2a (Table 2, entry 22), 1-naphthoic acid (5) efficiently underwent
5364 J. Org. Chem., Vol. 72, No. 14, 2007

Rhodium- and Iridium-Catalyzed OxidatiVe Coupling
SCHEME 3. Dehydrogenative Coupling of 1-Naphthoic
Acid (5) with Diphenylacetylene (2a)
proceeded efficiently in o-xylene to give the corresponding
phthalide 8b in 76% yield.
In this reaction, a rhodacycle intermediate, generated in a
similar manner to that in the reaction with alkynes (B in Scheme
4), may undergo alkene insertion and successive â-hydride
elimination to form the ortho-monovinylated benzoic acid. Prior
to the nucleophilic cyclization, the second vinylation takes place
to lead to the divinylated product 8 along with 9.
In contrast to the acrylates, N,N-dimethylacrylamide (7c) and
acrylonitrile (7d) reacted with 1a in a 1:1 ratio under similar
conditions to afford 10c and 10d (Scheme 6). In these cases,
the cyclization exclusively occurs after the first vinylation (see
Scheme 5), as occurs in the palladium-catalyzed reaction.3a
SCHEME 4. A Plausible Mechanism for the
Rhodium-Catalyzed Reaction of 1a with 2
The synthesis of naphthalene derivatives by the 1:2 coupling
of benzoic acids 1 with alkynes 2 was next examined aiming at
developing a new method for aromatic homologation. Treatment
of 1a with 2a (2 equiv) in the presence of [Cp*RhCl2]2 (1 mol
%) and Cu(OAc)2‚H2O (4 equiv) in mesitylene at 180 °C for 2
h gave a mixture of 3a and 4a in 81% and 19% yields,
respectively (Table 3, entry 1). The naphthalene 4a became a
predominant product (3a:4a ) 40:60) when the reaction was
conducted using AgOAc (4 equiv) in place of the copper salt
as an oxidant (entry 2). Ag2CO3 (2 equiv) could be used as
well as AgOAc (entry 4). Interestingly, it was found that 4a
can be obtained exclusively under iridium catalysis. Thus, the
reaction in the presence of [Cp*IrCl2]2 (2 mol %) and AgOAc
(2 equiv) in o-xylene at 160 °C for 6 h afforded 4a in 73%
yield and did not give 3a (entry 6). Ag2CO3 (1 equiv) was as
effective as AgOAc (entry 7). The reactions in polar solvents
such as DMAc, DMSO, and diglyme were sluggish (entries
8-10). When [IrCl(cod)]2, [IrCl(coe)2]2, and IrCl(CO)(PPh3)2
were used in place of [Cp*IrCl2]2, the reaction did not proceed
catalytically (entries 11-13). Increasing the amount of Ag2CO3
to 2 equiv enhanced the yield of 4a up to 88% (entry 15).
Decreasing the amount of catalyst to 1 mol % still gave 60%
yield of 4a (entry 16).
coupling with 2a to give 6 exclusively in 93% yield (Scheme
3).
A plausible mechanism for the reaction of benzoic acid (1a)
with alkyne 2 is illustrated in Scheme 4, in which neutral ligands
are omitted. Coordination of the carboxylate oxygen to
Cp*RhX2(III) gives a rhodium(III) benzoate A. Subsequent
ortho-rhodation to form a rhodacycle intermediate B,15 alkyne
insertion, and reductive elimination occur to produce isocou-
marin 3. The resulting Cp*Rh(I) species may be oxidized in
the presence of a copper(II) salt to regenerate Cp*RhX2(III).
Under air (conditions B), Cu(I) formed in the last step may also
be reoxidized to Cu(II). No deposition of deactivated bulk metal
is observed during the reaction, while this often occurs in Pd/
Cu-catalyzed reactions.9 The minor products, naphthalene 4 and
4′, may be produced via decarboxylation of C, the second
insertion of 2, and reductive elimination, as proposed for the
iridium catalysis (vide infra, Scheme 8).
Table 4 summarizes the results for the reactions of substituted
benzoic acids 1 with 2 equiv of diarylacetylenes 2 in the
presence of [Cp*IrCl2]2 and Ag2CO3. Bis(4-methoxyphenyl)-
(2f) and bis(4-chlorophenyl)acetylene (2g) reacted with 1a
efficiently to give the corresponding 1,2,3,4-tetraarylnaphtha-
lenes 4g and 4h in 64% and 91% yields, respectively (entries 1
and 2). In contrast to the rhodium-catalyzed reactions (Table
2), the iridium-catalyzed reactions with dialkylacetylenes were
found to be sluggish. Thus, treatment of 1a with 2b and 2c
Benzoic acid (1a) also reacted with n-butyl acrylate (9a)
smoothly under conditions B using a less polar solvent such as
o-xylene (Scheme 5). Interestingly, disubstitution at both the
ortho-positions occurred to afford 7-vinylphthalide 8a as a 1:2
coupling product in 66% isolated yield along with a minor
amount of its dehydrogenated separable derivative 9a. In DMF,
which is the solvent of choice for the isocoumarin synthesis
(Table 1), the reaction was sluggish to give 8a in a poor yield
(ca. 10%). The reaction of 1a with ethyl acrylate (7b) also
SCHEME 5. Dehydrogenative Coupling of Benzoic Acid (1a) with Acrylates 7a, b
J. Org. Chem, Vol. 72, No. 14, 2007 5365

Ueura et al.
TABLE 3. Dehydrogenative, Decarboxylative Coupling of Benzoic Acid (1a) with Diphenylacetylene (2a)a
% yieldb
entry
catalyst
oxidant (mmol)
solvent
temp (°C)
time (h)
3a
81
40 (43)
39
4a
19
60 (57)
61
1c
2c
3
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*IrCl2]2
[Cp*IrCl2]2
[Cp*IrCl2]2
[Cp*IrCl2]2
[Cp*IrCl2]2
[Cp*IrCl2]2
[IrCl(cod)]2
[IrCl(coe)2]2
IrCl(CO)(PPh3)2
[Cp*IrCl2]2
[Cp*IrCl2]2
[Cp*IrCl2]2
Cu(OAc)2‚H2O (1)
AgOAc (1)
AgOAc (1)
Ag2CO3 (0.5)
Cu(OAc)2‚H2O (0.5)
AgOAc (0.5)
Ag2CO3 (0.25)
Ag2CO3 (0.25)
Ag2CO3 (0.25)
Ag2CO3 (0.25)
Ag2CO3 (0.25)
Ag2CO3 (0.25)
Ag2CO3 (0.25)
Ag2CO3 (0.25)
Ag2CO3 (0.5)
Ag2CO3 (0.5)
mesitylene
mesitylene
mesitylene
mesitylene
o-xylene
o-xylene
o-xylene
DMAc
180
180
180
180
160
160
160
160
160
160
160
160
160
120
160
160
2
2
2
2
6
6
6
6
6
6
6
6
6
10
6
6
4c
5
41
59
18
73
75
12
2
31
2
6
7
8
9
10
11
12
13
14
15
16c
DMSO
diglyme
o-xylene
o-xylene
o-xylene
o-xylene
o-xylene
o-xylene
<1
<1
70
88 (79)
60
a Reaction conditions: [1a]/[2a]/[catalyst] ) 0.25:0.5:0.005 (in mmol), under N2. b GC yield based on the amount of 1a used. Value in parentheses
indicates yield after purification. c [catalyst] ) 0.0025 (in mmol).
TABLE 4. Reaction of Benzoic Acids 1 with Diarylacetylenes 2 Accompanied by Dehydrogenation and Decarboxylationa
entry
1
R1
R2
R3
R4
2
Ar
time (h)
products, % yieldb
4g, 64 (53)
4h, 91 (89)
4b, 95 (86)
1
2
3
4
5
6
7c
8
1a
1a
1b
1j
1k
1h
1l
H
H
H
H
Cl
Me
Cy
O(i-Pr)
H
H
H
Me
H
H
H
H
H
H
Me
H
H
H
H
H
H
H
H
Me
H
H
H
H
2f
4-MeOC6H4
4-ClC6H4
3
2
2
2
10
6
2g
2a
2a
2a
2a
2a
2a
Ph
Ph
Ph
Ph
Ph
Ph
4i, 93 (85)
4j and 4′k ()4c) (3:1), 63 (63)
4′e () 4b), 88(81)
4′l, 60 (60)
10
2
1m
4′m, 80 (76)
a Reaction conditions: [1]/[2]/[[Cp*IrCl2]2]/[Ag2CO3] ) 0.25:0.5:0.005:0.5 (in mmol), in o-xylene at 160 °C under N2. b GC yield based on the amount
of 1 used. Value in parentheses indicates yield after purification. c R1 ) Cy ) cyclohexyl.
SCHEME 6. Dehydrogenative Coupling of Benzoic Acid
(1a) with Alkenes 7c, d
SCHEME 7. Reaction of Benzoic Acid (1a) with Diethyl
Acetylenedicarboxylate (2h)
O-H adduct, diethyl (Z)-(benzoyloxy)fumarate, in 78% yield
(Scheme 7). The reactions of 1b and 3,5-dimethylbenzoic acid
(1j) with 2a proceeded smoothly to give naphthalenes 4b and
4i in 95 and 93% yields, respectively (entries 3 and 4). The
reaction of 2-chlorobenzoic acid (1k) with 2a gave not only an
expected naphthalene, 5-chloro-1,2,3,4-tetraphenylnaphthalene
a The reaction was conducted at 160 °C.
gave the corresponding tetraalkylnaphthalenes in low yields
(10-20%, by GC-MS). Diethyl acetylenedicarboxylate (2h)
reacted with 1a to afford not the desired naphthalene but an
5366 J. Org. Chem., Vol. 72, No. 14, 2007

Rhodium- and Iridium-Catalyzed OxidatiVe Coupling
SCHEME 8. A Plausible Mechanism for the Iridium-Catalyzed Reaction of 1 with 2
(4j), but also its isomer, 6-chloro-1,2,3,4-tetraphenylnaphthalene
(4′k ) 4c). The possible pathway toward the latter unexpected
naphthalene via isomerization will be discussed below (Scheme
8). Furthermore, the reactions of other 2-substituted benzoic
acids 1h-m with 2a proceeded involving the isomerization to
exclusively form 6-substituted 1,2,3,4-tetraphenylnaphthalenes
4′e ()4b), 4′l, and 4′m in 60-88% yields (entries 6-8).
A plausible mechanism for the reaction of benzoic acids 1
with diarylacetylenes 2 by the iridium catalysis is illustrated in
Scheme 8, in which neutral ligands are omitted. A seven-
membered iridacycle intermediate D appears to be generated
in a manner similar to that to a rhodacycle C in Scheme 4.
Then, D undergoes decarboxylation to form a key, five-
membered iridacycle intermediate E rather than reductive
elimination that is a preferable pathway in the rhodium catalysis.
Subsequently, the second alkyne insertion and reductive elimi-
nation occur to produce naphthalene 4. The resulting Ir(I)X
species may be oxidized in the presence of the silver salt to
regenerate Ir(III)X3. In the cases with 2-substituted benzoic
acids, the key intermediate E may undergo rearrangement driven
by steric reasons through protonation and cycloiridation to form
an isomeric iridacycle F, which reacts with alkyne to afford
6-substituted naphthalene 4′.
produce naphthalene derivatives exclusively accompanied by
decarboxylation. Rh- and Ir-catalyst systems for oxidative
C-C coupling reactions have been less explored than those with
Pd. The present catalyst systems and related ones are expected
to be applicable to other coupling reactions. Work is underway
toward further development of the catalysis.
Experimental Section
Rh/Cu-Catalyzed Reaction of Benzoic Acid (1a) with Diphen-
ylacetylene (2a) (Entry 5 in Table 1). To a 20 mL two-necked
flask were added benzoic acid (1a) (0.5 mmol, 61 mg), diphenyl-
acetylene (2a) (0.6 mmol, 107 mg), [Cp*RhCl2]2 (0.005 mmol, 3.1
mg), Cu(OAc)2‚H2O (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 (with a calcium chloride tube) at 120
°C (bath temperature) for 2 h. After cooling, analysis of the mixture
by GC confirmed formation of compounds 3a and 4a in 96 and
3% yields, respectively. The product 3a (139 mg, 93%) was also
isolated by evaporation of DMF in vacuo and chromatography on
silica gel using hexane-ethyl acetate (98:2, v/v). Compound 3a:
1
mp 172-174 °C (lit.16 170 °C); H NMR (400 MHz, CDCl3): δ
7.16-7.27 (m, 6H), 7.33 (d, J ) 8.3 Hz, 2H), 7.39-7.44 (m, 3H),
7.52 (dd, J ) 7.6, 7.6 Hz, 1H), 7.64 (ddd, J ) 7.6, 7.6, 1.5 Hz,
1H), 8.41 (d, J ) 8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ
116.9, 120.4, 125.3, 127.8 (2C), 128.06, 128.09, 128.9, 129.0 (2C),
129.2 (2C), 129.5, 131.2 (2C), 132.9, 134.3, 134.6, 138.8, 150.9,
162.2; HRMS m/z (M+) calcd for C21H14O2: 298.0994. Found
298.0998.
In summary, we have demonstrated that the oxidative
coupling reaction of benzoic acids with internal alkynes can be
performed in the presence of a rhodium catalyst and a copper
oxidant to selectively give the corresponding 1:1 coupling
products, isocoumarin derivatives. The reaction proceeds cata-
lytically with respect to both metals under air. Under the aerobic
conditions, the coupling of benzoic acids with acrylates takes
place efficiently. On the other hand, the acids and alkynes have
been found to react in a ratio of 1:2 under iridium catalysis to
Acknowledgment. This work was partly supported by a
Grant-in-Aid from the Ministry of Education, Culture, Sports,
Science, and Technology, Japan.
Supporting Information Available: Standard experimental
procedure and characterization data of products. This material is
available free of charge via the Internet at http://www.pubs.acs.org.
JO070735N
(15) 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.
(16) Delaunay, J.; Simonet, J. Tetrahedron Lett. 1988, 29, 543.
J. Org. Chem, Vol. 72, No. 14, 2007 5367