Rhodium/phosphine/amine-HBr catalyst system for highly selective cross-cyclodimerization of aryl- and alkylalkynes: Efficient access to multisubstituted naphthalene derivatives

Article abstract of DOI:10.1002/chem.200902519

The rhodium/phosphine/amine.HBr catalyst system directed toward the highly chemoselective synthesis of multisubstituted naphthalene derivatives from two different internal alkynes was investigated. Under N₂ atmosphere, [(RhC1(cod)}₂], PPh₃, Py.HBr, 1a, 2a, o-xylene and 1- methylnaphthalene were placed in a 20 mL two-necked reaction flask equipped with a reflux condenser. After the mixture was heated at 160°C for 6 h, the consumption of 1a was checked by GC analysis. The resulting mixture was allowed to cool to room temperature and then concentrated under reduced pressure. The residue obtained was purified by column chromatography on silica gel with hexane as an eluent to give 3-phenyl-1,2-dipropylnaphthalene in 84% yield. The catalyst enabled the use of alkenes as the coupling components, providing the dihydronaphthalenes.

Full text of DOI:10.1002/chem.200902519

COMMUNICATION
DOI: 10.1002/chem.200902519
Rhodium/Phosphine/Amine·HBr Catalyst System for Highly Selective Cross-
Cyclodimerization of Aryl- and AlkylACTHUNTGRNEUNGalkynes: Efficient Access to
Multisubstituted Naphthalene Derivatives
Koichi Sakabe,[a] Hayato Tsurugi,[b] Koji Hirano,[a] Tetsuya Satoh,[a] and
Masahiro Miura*[a]
Various polysubstituted aromatic compounds have long
been of great significance in the chemical and pharmaceuti-
cal industries. In particular, those with polycyclic p-conjugat-
ed structures have recently become increasingly important
in the area of organic electronics.[1] The transition-metal-
mediated annulative benzene ring homologation with al-
kynes or their equivalents[2–6] is one of the modern potential
synthetic strategies to prepare naphthalenes and higher
fused aromatics. As one of the early examples, Sakakibara[2a]
and Heck[2b] independently reported the palladium-catalyzed
annulation reaction of aryl halide with two acetylenedicar-
boxylate or diphenylacetylene molecules to construct the
naphthalene skeletons. Takahashi described the homologa-
tion reaction with o-dihalobenzenes and zirconacyclopenta-
dienes.[3] Our groups also focused on this methodology and
succeeded in the formation of polysubstituted naphthalenes
and anthracenes from internal alkynes and benzoyl chlorides
or benzoic acids accompanied by decarbonylation or decar-
boxylation.[4] In addition, the recent advances of benzyne
chemistry provide an efficient route to fused aromatics in-
volving anthracenes and phenanthrenes by using o-dibromo-
benzene or o-trimethylsilylphenyl triflates as the starting
materials.[5] However, the processes mentioned above re-
quire the leaving groups on the benzene rings so that the in-
evitable wastes, such as the metal salts, are produced simul-
taneously. Recently, we reported the rhodium-catalyzed oxi-
dative homologation of directing-group-containing arenes
[7]
with alkynes through two sp2 C H bond cleavages. Wu
À
also has described the palladium-catalyzed similar type of
transformation with electron-rich arenes, such as p-xylene,
under oxidative conditions.[8] While these procedures are
useful because preactivation of the arene moieties could be
eliminated, a stoichiometric amount of oxidant, CuACHTUNGTRENNUNG(OAc)2
or AgOAc, is required. From the viewpoint of atom econo-
my, further development of different protocols for the syn-
thesis of the multisubstituted aromatics from relatively
simple hydrocarbons is strongly desired.
In 1998, Kisch reported the rhodium-catalyzed cyclodime-
rization of diarylacetylenes to give multisubstituted naphtha-
lenes with the aid of HCl.[9] Although the catalytic dimeriza-
tion is an ideal waste-free process, it is restricted in scope
and generality; one of the possible reasons for this may be
the use of the relatively strong acid. Moreover, the cross-cy-
clodimerization of diaryl- and dialkylacetylenes encounters
difficulty in controlling chemoselectivity of the reaction due
to the competitive homo-cyclodimerization of diaryl-
AHCTUNGTRENNUNG
acetylenes.[10] Nevertheless, the elegant pioneering work ap-
pears to be quite attractive and encourages us to explore a
more efficient rhodium-based catalyst for this type of direct
alkyne coupling. In this communication, we report the rho-
dium/phosphine/amine·HBr catalyst system directed toward
the highly chemoselective synthesis of multisubstituted
naphthalene derivatives from two different internal alkynes.
Under the catalytic conditions, a variety of alkynes are toler-
ant, and the cross-dimerization predominates over the con-
ceivable homo-dimerization. Furthermore, the catalyst
system allows the cross-cyclodimerization event of diaryl-
AHCTUNGTREGaNNNU lkynes with some cyclic alkenes leading to the correspond-
ing dihydronaphthalenes.
We initially investigated the effect of various Brønsted
acids using diphenylacetylene (1a, 0.50 mmol) and 4-octyne
(2a, 1.0 mmol) as model substrates in the presence of
[a] K. Sakabe, Dr. K. Hirano, Prof. Dr. T. Satoh, Prof. Dr. M. Miura
Department of Applied Chemistry
Faculty of Engineering, Osaka University
Suita, Osaka 565-0871 (Japan)
Fax : (+81)6-6879-7362
E-mail: miura@chem.eng.osaka-u.ac.jp
[b] Dr. H. Tsurugi
Department of Chemistry
Faculty of Engineering Science, Osaka University
Toyonaka, Osaka 560-8531 (Japan)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200902519.
Chem. Eur. J. 2010, 16, 445 – 449
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
445

1.5 mol% of [{RhClACHTNUTRGNEUNG(cod)}2]
(3 mol% Rh) and 6 mol% of
PPh3 in refluxing o-xylene
(Table 1). As shown previous-
ly,[9] no reaction took place
without any acid, and the start-
ing materials were recovered
intact (entry 1). Addition of
PhCOOH or p-TsOH·H2O
(20 mol%) led to the forma-
tion of the desired product
3aa, albeit with low yield and
chemoselectivity (entries 2 and
3). In contrast, use of amine
salts was found to change the
selectivity in the reaction (en-
tries 4–7). Especially, with
Py·HBr (Py=pyridine), the
cross-dimer 3aa was obtained
in
84%
isolated
yield
(entry 7). Although we also
screened other monodentate
triarylphosphine ligands in the
presence of Py·HBr, the effect
on the yield and ratio
(3aa:4aa) was almost negligi-
ble as far as we examined.
However, without PPh3, no
product was formed even in
the presence of Py·HBr.
Scheme 1. The rhodium-catalyzed cross-cyclodimerization of various diarylacetylenes 1 with aliphatic alkynes
2. Reaction conditions: A mixture of [{RhCl(cod)}2] (0.0075 mmol, 3 mol% Rh), PPh3 (0.030 mmol), Py·HBr
(0.10 mmol), 1 (0.50 mmol), and 2 (1.0 mmol) in o-xylene (2.5 mL) was heated at 1608C (bath temp.) for 6 h
under N2. Isolated yields [%] are given and the regioisomeric ratio is given in parentheses where appropriate.
For 3aa a reaction on a five times larger scale in o-xylene (10 mL) led to a yield of 94%.
AHCTUNGTRENNUNG
With the optimized reaction
conditions in hand, the cross-
cyclodimerization of various
diarylacetylenes 1 was carried
out (Scheme 1). Longer alkyl side chains could be intro-
duced to the 1- and 2-positions of naphthalene without any
difficulties (3ab and 3ac): Note that introduction of such
alkyl chains is known to generally improve the solubility of
condensed aromatics. Unsymmetric alkyne 2d also reacted
with diphenylacetylene (1a) to furnish the corresponding
condensed cross-dimer 3ad in 63% yield, although the re-
gioselectivity was moderate. On the other hand, activated al-
kynes such as 3-phenyl-2-propyn-1-ol and ethyl phenylpro-
piolate did not couple with 1a, a large amount of which re-
mained unchanged. Subsequently, the substitution effect on
the benzene ring of diphenylacetylene was examined. The
substrates bearing electron-donating as well as electron-
withdrawing substituents were effectively transformed to the
expected 1,2,3,7-tetrasubstituted naphthalenes in good to
high yields (3ba–ea). Notably, the acid-labile functional
groups CN, Ac, and COOMe were tolerant under the reac-
tion conditions to give rise to 3 fa–ha with substantial yields.
It is worth noting that the reaction of 1a with 2a on a five-
fold larger scale was successfully produced 3aa in a 94%
yield.
Table 1. Effect of various Brønsted acids in rhodium-catalyzed cross-cy-
clodimerization of diphenylacetylene (1a) with 4-octyne (1b).[a]
Entry
Brønsted
acid
Yield [%][b]
3aa
4aa
3aa:4aa
1
2
3
4
5
6
7
none
0
12
2
23
63 (47)
46
0
16
5
5
8
–
PhCOOH
p-TsOH·H2O
Et3N·HCl
Et3N·HBr
Py·HCl
43:57
29:71
82:18
89:11
88:12
97:3
6
3
Py·HBr
93 (84)
[a] A mixture of [RhClACHTNUTRGNEUNG(cod)]2 (0.0075 mmol, 3 mol% Rh), PPh3
Our catalyst system could be applied to the cross-dimeri-
zation with thienylacetylACTHNURGTNEeNUG nes (Scheme 2). Dithienylacety-
lene 5 underwent the cross-dimerization with 4-octyne (2a)
to construct the benzothiophene core 6 in 95% yield (top).
(0.030 mmol), Brønsted acid (0.10 mmol), 1a (0.50 mmol), and 2a
(1.0 mmol) in o-xylene (2.5 mL) was heated at 1608C (bath temp.) for 6 h
under N2. [b] GC yield. Isolated yield is in parentheses. The yield of 4aa
was based on a half amount of 1a employed.
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Chem. Eur. J. 2010, 16, 445 – 449

Cross-Cyclodimerization
COMMUNICATION
Next, we tried to apply the catalyst system to the cross-di-
merization of diarylacetylenes with alkenes. The preliminary
results are shown in Scheme 4. On exposure of diphenylace-
tylene (1a) and N-methylmaleimide (10) to the Et3N·HBr-
Scheme 2. Reactions of thienylacetylenes 5 and 7.
In this case, the use of Et3N·HBr instead of Py·HBr gave the
better result. It is worth noting that the reaction of 2-(phe-
nylethynyl)thiophene (7) with 2a proceeded regioselectively
to provide 3-thienyl-1,2-dipropylnaphthalene (8) predomi-
nantly (bottom).
Scheme 4. Cross-cyclodimerization with alkenes.
promoted conditions, the corresponding dihydronaphthalene
11a was obtained in 55% yield (top). Methyl-substituted
acetylene 1b was also available for use. It is worth noting
that norbornene (12) coupled with 1a to give the tetracyclic
framework 13a (bottom).
The [{RhCl
proved the efficiency of homo-dimerization with
diarylacetyl
enes (Scheme 3).[9] Not only electron-rich diary-
ACHTUNGTRENNUNG(cod)}2]/PPh3/Py·HBr catalyst system also im-
ACHTUNGTRENNUNG
We are tempted to assume the reaction mechanism of the
cross-cyclodimerization as illustrated in Scheme 5 with di-
phenylacetylene (1a) and 4-octyne (2a) as the representa-
Scheme 3. Products of the rhodium-catalyzed homo-cyclodimerization of
various diarylacetylenes 1 and 5. Reaction conditions: A mixture of
[{RhClACHTUNGTRENNUNG(cod)}2] (0.0075 mmol, 3 mol% Rh), PPh3 (0.030 mmol), Py·HBr
(0.10 mmol), 1 or 5 (0.50 mmol), and 2 (1.0 mmol) in o-xylene (2.5 mL)
was heated at 1608C (bath temp.) for 6 h under N2. The isolated yield
based on the half amount of 1 or 5 employed. In the case of 9 Et3N·HBr
was used in place of Py·HBr.
Scheme 5. Plausible reaction mechanism.
tive substrates.[9] Initial oxidative addition of HX to RhI
gives the rhodium hydride species 14.[11] The subsequent in-
[12]
À
lacetylenes, but also electron-deficient ones readily homo-di-
merized under the standard conditions. In addition,
sertion of 1a to the Rh H bond and geometrical isomeri-
zation via a zwitterionic form[13] would afford the intermedi-
ate 16. The rhodium complex undergoes ortho-metalation[14]
with the liberation of HX to furnish rhodacycle 17, and the
selective insertion of 2a to the rhodium–aryl or –alkenyl
bond followed by productive reductive elimination produces
the cross-dimer 3aa along with the starting RhI complex to
complete the catalytic cycle. Although the reason for the
dithienylacetyl
furnish 9 in excellent yield.[10] In contrast, the dimerization
of aryl(alkyl)acetylene such as 1-phenyl-1-hexyne was un-
ACHTUNGTRENNUNGene 5 could also participate in the reaction to
ACHTUNGTRENNUNG
successful. This is probably due to the diminished reactivity
toward the insertion to the rhodium hydride species in the
catalytic cycle (vide infra).
Chem. Eur. J. 2010, 16, 445 – 449
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
447

M. Miura et al.
preferable insertion of 4-octyne (2a) rather than diphenyl-
acetylene (1a) to the rhodacycle 17 is not clear at this stage,
Acknowledgements
ACHTUNGTRENNUNG
This work was partly supported by Grants-in-Aid from the Ministry of
Education, Culture, Sports, Science, and Technology, Japan.
the free pyridine generated in situ may coordinate to the
rhodium center of 17 to cause the unusual chemoselectivi-
ty.[15] Moreover, the possibility that the bromide ligand on
Rh of 17 enhances the selectivity could not be excluded
(Table 1, entry 4 vs. 5 and 6 vs. 7).
Keywords: alkynes
·
cross-cyclodimerization
·
dihydronaphthalenes · naphthalenes · rhodium
Finally, in order to demonstrate the synthetic utility of the
catalytic reaction, we performed the derivatization of the
cross-dimer 6 (Scheme 6). The regioselective mono-bromi-
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In summary, we have developed the efficient rhodium/
phosphine/amine·HBr catalyst system for highly selective
cross-cyclodimerization as well as homo-dimerization of di-
ACHTUNGTRENNUNGarylacetylenes leading to the multisubstituted naphthalenes.
In addition, the catalyst enabled the use of alkenes as the
coupling components, providing the dihydronaphthalenes.
Thus, the catalytic reactions appear to be powerful synthetic
tools for the construction of naphthalene core from the
simple and readily accessible unsaturated molecules.
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Experimental Section
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(89 mg, 0.50 mmol), 2a (110 mg, 1.0 mmol), o-xylene (2.5 mL), and 1-
methylnaphthalene (ca. 50 mg, internal standard) were placed in a 20 mL
two-necked reaction flask equipped with a reflux condenser. After the
mixture was heated at 1608C for 6 h, the consumption of 1a was checked
by GC analysis. The resulting mixture was allowed to cool to room tem-
perature and then concentrated under reduced pressure. The residue ob-
tained was purified by column chromatography on silica gel with hexane
as an eluent to give 3-phenyl-1,2-dipropylnaphthalene (3aa, 121 mg,
0.42 mmol) in 84% yield.
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[16] M. Kuroboshi, Y. Waki, H. Tanaka, Synlett 2002, 0637.
448
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Chem. Eur. J. 2010, 16, 445 – 449

Cross-Cyclodimerization
COMMUNICATION
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Received: September 12, 2009
Published online: November 24, 2009
Chem. Eur. J. 2010, 16, 445 – 449
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www.chemeurj.org
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