Synthesis of highly substituted naphthalene and anthracene derivatives by rhodium-catalyzed oxidative coupling of arylboronic acids with alkynes

Article abstract of DOI:10.1021/ol9021172

The rhodium-catalyzed oxidative 1:2 coupling reactions of arylboronic acids with alkynes effectively proceeds in the presence of a copper-air oxidant to produce the corresponding annulated products. Of special note, anthracene derivatives can be obtained

Full text of DOI:10.1021/ol9021172

ORGANIC
LETTERS
2009
Vol. 11, No. 22
5198-5201
Synthesis of Highly Substituted
Naphthalene and Anthracene Derivatives
by Rhodium-Catalyzed Oxidative
Coupling of Arylboronic Acids with
Alkynes
Tatsuya Fukutani, 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 September 13, 2009
ABSTRACT
The rhodium-catalyzed oxidative 1:2 coupling reactions of arylboronic acids with alkynes effectively proceeds in the presence of a copper-air
oxidant to produce the corresponding annulated products. Of special note, anthracene derivatives can be obtained selectively from
2-naphthylboronic acids.
Linearly fused aromatic ring systems can be seen in various
π-conjugated functional materials such as organic semicon-
ductors and luminescent materials.1 Highly substituted
derivatives around fused aromatic cores are of particular
interest because of their stability, solubility, enhanced ability
to transport charge, and fluorescent properties in the solid
state.2 Among modern potential strategies to prepare polysub-
stituted and fused aromatics is transition metal-catalyzed
homologation, such as benzene to naphthalene and naph-
thalene to anthracene, by the coupling of a given aromatic
substrate with two alkyne molecules (Scheme 1).3 Thus, the
Scheme 1
(1) Anthony, J. E. Angew. Chem., Int. Ed. 2008, 47, 452.
(2) For example, see: (a) Kaur, I.; Stein, N. N.; Kopreski, R. P.; Miller,
G. P. J. Am. Chem. Soc. 2009, 131, 3424. (b) Ahmed, E.; Briseno, A. L.;
Xia, Y.; Jenekhe, S. A. J. Am. Chem. Soc. 2008, 130, 1118. (c) Paraskar,
A. S.; Reddy, A. R.; Patra, A.; Wijsboom, Y. H.; Gidron, O.; Shimon,
L. J. W.; Leitus, G.; Bendikov, M. Chem.sEur. J. 2008, 14, 10639. (d)
Cicoira, F.; Santato, C. AdV. Funct. Mater. 2007, 17, 3421. (e) Qiao, X.;
Padula, M. A.; Ho, D. M.; Vogelaar, N. J.; Scutt, C. E.; Pascal, R. A., Jr.
J. Am. Chem. Soc. 1996, 118, 741.
catalytic transformations of various di- (X * H, Y * H)3,4
and monofunctionalized aromatic substrates (X * H, Y )
H)5 have been developed. The latter reaction involving
regioselective C-H bond cleavage is attractive from an atom-
economic point of view.6
10.1021/ol9021172 CCC: $40.75
Published on Web 10/15/2009
 2009 American Chemical Society

The palladium-catalyzed reaction of aryl iodides (X ) I,
Y ) H)5c-e seems to be of considerable synthetic utility
because of the wide availability of simple substrates as aryl
sources. It has been proposed that the reaction involves the
formation of a vinylpalladium intermediate (A) via the
oxidative addition of ArI toward Pd(0) species and sebse-
quent alkyne insertion (Scheme 2).5c Then cyclopalladation,
Table 1. Reaction of Phenylboronic Acid (1a) with
Diphenylacetylene (2a)a
entry
oxidant (mmol)
solvent temp (°C) % yield of 3ab
Scheme 2
1
2
3
4
5
6
7
8
9
Cu(OAc)2·H2O (0.5)
Cu(OAc)2·H2O (0.5)
Cu(OAc)2·H2O (0.5)
Cu(OAc)2·H2O (0.5)
Cu(OAc)2·H2O (0.5)
Cu(OAc)2·H2O (0.5)
Cu(OAc)2·H2O (0.5)
AgOAc (0.5)
DMF
100
100
100
100
100
80
60
100
80
60
rt
100
100
100
56
3
3
DMSO
o-xylene
dioxane
NMP
DMF
DMF
DMF
DMF
DMF
22
50
53
53
74
66
67
67
32
87
86 (78)
AgOAc (0.5)
10 AgOAc (0.5)
11 AgOAc (0.5)
DMF
DMF
DMF
12 Ag2CO3 (0.25)
13 AgOCOCF3 (0.5)
14c Cu(OAc)2·H2O (0.025) DMF
the second alkyne insertion, and final reductive elimination
may occur to form a 1,2,3,4-tetrasubstituted naphthalene.
However, the vinylpalladium intermediate tends to undergo
E/Z isomerization (A to A′).7 Therefore, the reaction of
substituted aryl iodides with diphenylacetylene gives the
corresponding naphthalene as a mixture of its isomers.
a Reaction conditions: 1a (0.5 mmol), 2a (0.5 mmol), [(Cp*RhCl2)2]
(0.005 mmol), solvent (3 mL) under N2 for 2 h. b GC yield based on the
amount of 2a used. Value in parentheses indicate the yield after purification.
c Under air.
Arylboronic acids are also widely used and commercially
available as arylation reagents. The catalytic homologation
of arylboron reagents with alkynes has, however, been less
explored, and only two examples with o-bromophenylboronic
acids (X ) B(OH)2, Y ) Br) have been reported.8 During
our study of the homologations via the rhodium-catalyzed
oxidative coupling of aromatic substrates with alkynes,5g-i
it has been revealed that even ortho-unfunctionalized, simple
phenylboronic acids (X ) B(OH)2, Y ) H) undergo the
coupling effectively to give 1,2,3,4-tetrasubstituted naph-
thalenes selectively.9 Fortunately, the isomer formation has
been found not to occur in this Rh-based system. Further-
more, the reaction of 2-naphthylboronic acids also proceeds
smoothly to afford the desired anthracene derivatives selec-
tively. These new findings are described herein.
In an initial attempt, phenylboronic acid (1a) (0.5 mmol)
was treated with diphenylacetylene (2a) (0.5 mmol) in the
presence of [Cp*RhCl2]2 (0.005 mmol) and Cu(OAc)2·H2O
(0.5 mmol) as catalyst and oxidant, respectively, in DMF (3
mL) at 100 °C under N2 for 2 h. As a result, 1,2,3,4-
tetraphenylnaphthalene (3a) was formed in 56% yield (entry
1 in Table 1, Cp* ) pentamethylcyclopentadienyl). While
the reaction was sluggish in DMSO, o-xylene, and dioxane,
a comparable result was obtained in NMP (entries 2-5). The
reaction was not sensitive to the temperature between 60 and
(3) (a) Lin, C.-H.; Lin, K.-H.; Pal, B.; Tsou, L.-D. Chem. Commun.
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J. Am. Chem. Soc. 2002, 124, 12680. X ) CO2H, Y ) H: (g) Ueura, K.;
Satoh, T.; Miura, M. J. Org. Chem. 2007, 72, 5362. X ) CR2OH, Y ) H:
(h) Uto, T.; Shimizu, M.; Ueura, K.; Tsurugi, H.; Satoh, T.; Miura, M. J.
Org. Chem. 2008, 73, 298. X ) Y ) H: (i) Umeda, N.; Tsurugi, H.; Satoh,
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Chem. ReV. DOI: 10.1021/cr900005n. Published Online: May 12, 2009.
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Chem. Soc. 2001, 123, 9918.
Org. Lett., Vol. 11, No. 22, 2009
5199

The reactions of 1a with various internal alkynes 2b-f in
place of 2a were next examined. Under the optimized
conditions in Table 1 (entry 14), methyl- (2b), methoxy- (2c),
and chloro- (2d) substituted diphenylacetylenes underwent
the coupling with 1a to afford the corresponding 1,2,3,4-
tetraarylnaphthalenes 3k-m selectively (entries 1-3 in Table
3). 1-Phenylpropyne (2e) reacted with 1a smoothly to give
1,4-dimethyl-2,3-diphenylnaphthalene (3n) in 70% yield
along with a small amount (7%) of a separable unidentified
isomer (entry 4). In contrast, the reaction of 4-octyne (2f)
was sluggish under the standard aerobic conditions to form
1,2,3,4-tetrapropylnaphthalene (3o) in only 10% yield (entry
5). The reaction efficiency was improved by using a
stoichiometric amount of Cu(OAc)2·H2O (0.5 mmol) at room
temperature (entry 7). 1-Phenyl-2-(trimethylsilyl)acetylene
did not couple with 1a at all under the standard conditions.
A plausible mechanism for the reaction of 1 with 2a is
illustrated in Scheme 3, in which neutral ligands are omitted.
Table 2. Reaction of Arylboronic Acids 1 with
Diphenylacetylene (2a)a
entry
1
R1
Me
R2
R3
product, % yieldb
1
2
1b
1c
1d
1e
1f
H
H
H
H
H
H
H
H
H
H
H
Me
H
H
H
H
H
H
H
H
H
H
H
H
H
Me
3b, 73 (66)
3c, 72 (72)
3d, 89 (83)
3e, 82 (82)
3f, 79 (79)
3g, 22
3g, 82 (82)
3h, 64
3h, 91 (87)
3i, 59
OMe
Cl
3
4
F
5
Br
6
1g
1g
1h
1h
1i
1i
1j
1k
CF3
CF3
CO2Me
CO2Me
CHO
CHO
H
7c
8c
9d
10c
11d
12
13
3i, 79 (79)
3b, 51 (51)
3j, 35 (34)
Scheme 3
H
a Reaction conditions: 1 (0.5 mmol), 2a (0.5 mmol), [(Cp*RhCl2)2]
(0.005 mmol), Cu(OAc)2·H2O (0.025 mmol), DMF (3 mL) at 100 °C under
air for 2 h. b GC yield based on the amount of 2a used. Value in parentheses
indicate the yield after purification. c Cu(OCOCF3)2·nH2O (0.025 mmol)
was used in place of Cu(OAc)2·H2O. d AgOCOCF3 (0.5 mmol) was used
under N2 in place of Cu(OAc)2·H2O.
100 °C (entries 6 and 7). AgOAc could also be used as
oxidant (entires 8-11). Thus, with AgOAc, the reaction
proceeded smoothly even at room temperature to form 3a
in 67% yield within 2 h (entry 11). AgOCOCF3 gave a better
yield (87%, entry 13). To our delight, a comparably good
yield was obtained when the reaction was conducted with a
catalytic amount of Cu(OAc)2·H2O (0.025 mmol) under air
(entry 14). Thus, the aerobic oxidative coupling proceeded
efficiently to give 3a in 86% yield.
Table 2 summarizes the results for the coupling of a series
of substituted phenylboronic acids 1b-k with 2a. 4-Methyl-,
methoxy-, chloro-, fluoro-, and bromophenylboronic acids
1b-f reacted with 2a smoothly under the aerobic conditions
to form 6-substituted 1,2,3,4-tetraphenylnaphthalenes 3b-f
in 72-89% yields (entries 1-5). It was found that electron-
deficient phenylboronic acids were less reactive in the present
reaction. Thus, the reaction of 4-(trifluoromethyl)phenylbo-
ronic acid (1g) with 2a under the standard conditions gave
the corresponding naphthalene 3g in only 22% yield (entry
6). In this case, the use of Cu(OCOCF3)2 (0.025 mmol) in
place of Cu(OAc)2 improved the yield to 82% (entry 7). Even
under the modified condition with Cu(OCOCF3)2, the reac-
tions of 4-(methoxycarbonyl)- (1h) and 4-formyl- (1i)
phenylboronic acids were sluggish (entries 8 and 10). In these
reactions, AgOCOCF3 was found to be more effective as
oxidant. Thus, in the presence of the Ag salt (0.5 mmol)
under N2, naphthalenes 3h and 3i were obtained in 91% and
79% yields, respectively (entries 9 and 11). Treatment of
3-methyl- (1j) and 2-methyl- (1k) phenylboronic acids with
2a under the standard conditions with Cu(OAc)2 gave 3b
and 3j in moderate yields (entries 12 and 13).
Initial transmetalation of the added Rh(III)X3 species with
1 gives an arylrhodium intermediate B. Then, alkyne
insertion occurs to form a vinylrhodium species C. Subse-
quent cyclorhodation, the second alkyne insertion, and
reductive elimination afford naphthalene 3. The resulting
RhX(I) species seems to be oxidized in the presence of the
copper cocatalyst under air to regenerate Rh(III)X3.
The homologation from naphthalene substrates to an-
thracene derivatives could be achieved by the present
procedure (Scheme 4). Thus, treatment of 2-naphthylboronic
acid (1l) with 2a under the standard aerobic conditions gave
Scheme 4
a GC yield based on the amount of 2a used. Value in parentheses indicate
the yield after purification.
5200
Org. Lett., Vol. 11, No. 22, 2009

It should be noted that the corresponding phenanthrenes
were not formed at all, while the mixtures of anthracene and
phenanthrene derivatives were usually formed in the previous
homologations of iodides5c and acid chlorides.5f Various
arylboron compounds,10 including 2-naphthylboronates,11 are
now preparable via the direct borylation of their parent arenes
under Ir-catalysis. Combining our homologation with bory-
lation, a wide range of fused aromatic compounds including
acenes appear to be readily available.
Table 3. Reaction of Phenylboronic Acid (1a) with Alkynes 2a
In summary, we have demonstrated that the rhodium-
catalyzed oxidative coupling of substituted phenyl- and
naphthylboronic acids with alkynes proceeds efficiently to
give the corresponding 1,2,3,4-tetrasubstituted naphthalene
and anthracene derivatives, respectively. Particularly, the
latter is the first example, to our knowledge, of the selective
construction of anthracene frameworks by homologations
with monofunctionalized naphthyl substrates (X * H, Y )
H in Scheme 1). Work is underway toward further develop-
ment of the synthetic methods.
Acknowledgment. This work was partly supported by
Grants-in-Aid from the Ministry of Education, Culture,
Sports, Science and Technology, Japan and the Kurata
Memorial Hitachi Science and Technology Foundation.
Supporting Information Available: Standard experimen-
tal procedure and characterization data of products. This
material is available free of charge via the Internet at
http://pubs.acs.org.
a Reaction conditions: 1a (0.5 mmol), 2 (0.5 mmol), [(Cp*RhCl2)2]
(0.005 mmol), Cu(OAc)2·H2O (0.025 mmol), DMF (3 mL) under air for
2 h. b GC yield based on the amount of 2 used. Value in parentheses indicate
the yield after purification. c A small amount (7%) of a regioisomer was
also formed. d Cu(OAc)2·H2O (0.5 mmol) was used under N2.
OL9021172
(10) For example, see: (a) Cho, J.-Y.; Tse, M. K.; Holmes, D.; Maleczka,
R. E., Jr.; Smith, M. R., III Science 2002, 295, 305. (b) Ishiyama, T.; Takagi,
J.; Ishida, K.; Miyaura, N.; Anastasi, N. R.; Hartwig, J. F. J. Am. Chem.
Soc. 2002, 124, 390. (c) Iverson, C. N.; Smith, M. R., III J. Am. Chem.
Soc. 1999, 121, 7696. For a review, see: (d) Ishiyama, T.; Miyaura, N. J.
Organomet. Chem. 2003, 680, 3.
1,2,3,4-tetraphenylanthracene (4a) in 77% yield as a single
coupling product. 6-Methoxy-2-naphthylboronic acid (1m)
also underwent the reaction in a similar manner to afford
the corresponding anthracene 4b.
(11) Coventry, D. N.; Batsanov, A. S.; Goeta, A. E.; Howard, J. A. K.;
Marder, T. B.; Perutz, R. N. Chem. Commun. 2005, 2172.
Org. Lett., Vol. 11, No. 22, 2009
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