Chromium-mediated synthesis of polycyclic aromatic compounds from halobiaryls

Article abstract of DOI:10.1021/ol052214x

(Chemical Equation Presented) Reaction of 2,2′-dihalobiphenyl with butyllithium followed by the addition of chromium(III) chloride and alkynes afforded the corresponding phenanthrene derivatives via formal [4 + 2] cycloaddition. A variety of alkynes could be used for this reaction, such as alkyl, aryl, silyl, and alkoxycarbonyl alkynes. Repetitive process of the reaction gave more extended polycyclic compounds such as benzo[g]chrysene and azacyclopentaphenalene derivatives.

Full text of DOI:10.1021/ol052214x

ORGANIC
LETTERS
2005
Vol. 7, No. 24
5453-5456
Chromium-Mediated Synthesis of
Polycyclic Aromatic Compounds from
Halobiaryls
Ken-ichiro Kanno, Yuanhong Liu, Atsushi Iesato, Kiyohiko Nakajima,† and
Tamotsu Takahashi*
Catalysis Research Center, and Graduate School of Pharmaceutical Sciences,
Hokkaido UniVersity, and SORST, Japan Science and Technology Agency (JST),
Sapporo 001-0021, Japan, and Department of Chemistry, Aichi UniVersity of
Education, Igaya, Kariya, Aichi 448-8542, Japan
tamotsu@cat.hokudai.ac.jp
Received September 14, 2005
ABSTRACT
Reaction of 2,2
phenanthrene derivatives via formal [4
′
-dihalobiphenyl with butyllithium followed by the addition of chromium(III) chloride and alkynes afforded the corresponding
2] cycloaddition. A variety of alkynes could be used for this reaction, such as alkyl, aryl, silyl, and
+
alkoxycarbonyl alkynes. Repetitive process of the reaction gave more extended polycyclic compounds such as benzo[g]chrysene and
azacyclopentaphenalene derivatives.
Construction of polycyclic aromatic ring skeletons has
attracted considerable attention in recent years due to their
increasing importance in organic material science.1 Among
several synthetic methods for polycyclic aromatics,2,3 inter-
molecular [4 + 2] cycloadditions between functionalized
biaryls and alkynes seem the simplest and straightforward
for the formation of phenanthrene derivatives. Although
several examples of such strategy with a series of late
transition metals are known,4 there are still some limitations
for availability of substituents of alkynes. In this paper we
would like to report chromium-mediated phenanthrene
formation from 2,2′-dihalobiphenyl and various alkynes and
its application to synthesis of polycyclic aromatic com-
pounds.
In the late of 1950s, Zeiss and co-workers reported that
triphenylchromium(III) could catalyze the cyclization of
2-butyne or diphenylacetylene to afford the corresponding
hexasubstituted benzene along with 1,2,3,4-tetrasubstituted
naphthalene.5 Later, Ehmann and co-workers investigated that
the reaction of 2-biphenylylmagnesium halide with chro-
† Aichi University of Education.
(4) (a) Edelbach, B. L. Lachicotte R. J.; Jones, W. D. Organometallics
1999, 18, 4040. (b) Edelbach, B. L. Lachicotte R. J.; Jones, W. D.
Organometallics 1999, 18, 4660. (c) Mu¨ller, C.; Lachicotte, R. J.; Jones,
W. D. Organometallics 2002, 21, 1975. (d) Iverson, C. N.; Jones, W. D.
Organometallics 2001, 20, 5745. (e) Larock, R. C.; Dory, M. J.; Tian, Q.;
Zenner, J. M. J. Org. Chem. 1997, 62, 7536. (f) Campo M. A.; Larock, R.
C. J. Am. Chem. Soc. 2002, 124, 14326. (g) Campo, M. A.; Huang, Q.;
Yao, T.; Tian, Q.; Larock, R. C. J. Am. Chem. Soc. 2003, 125, 11506. (h)
Dyker, G.; Kellner, A. Tetrahedron Lett. 1994, 35, 7633. (i) Wu, G.;
Rheingold, A.; Geib, S. J.; Heck, R. F. Organometallics 1987, 6, 1941. (j)
Dougherty, T. K.; Lau, K. S. Y.; Hedberg, F. L. J. Org. Chem. 1983, 48,
5273. (k) Mandal, A. B.; Lee, G.-H.; Liu, Y.-H.; Peng, S.-M.; Leung M.-k.
J. Org. Chem. 2000, 65, 332.
(1) (a) Katz, H. E.; Bao, Z.; Gilat, S. L. Acc. Chem. Res. 2001, 34, 359.
(b) Dimitrakopoulos, C. D.; Malenfant, P. R. L. AdV. Mater. 2002, 14, 99.
(2) (a) Watson, M. D.; Fechtenko¨tter, A.; Mu¨llen, K. Chem. ReV. 2001,
101, 1267. (b) Harvey, R. G.; Fu, P. P. Chem. ReV. 1978, 78, 317. (c) Floyd,
A. J.; Dyke, S. F.; Ward, S. E. Chem. ReV. 1976, 76, 6, 509.
(3) Selected examples of intramolecular cyclizations: (a) Tovar, J. D.;
Swager, T. M. J. Organomet. Chem. 2002, 653, 215. (b) Yamaguchi, S.;
Swager, T. M. J. Am. Chem. Soc. 2001, 123, 12087. (c) Goldfinger, M. B.;
Crawford, K. B.; Swager, T. M. J. Am. Chem. Soc. 1997, 119, 4578. (d)
Fu¨rstner, A.; Mamane, V. Chem. Commun. 2003, 2112. (e) Fu¨rstner, A.;
Mamane, V. J. Org. Chem. 2002, 67, 6264. (f) Yao, T.; Campo, M. A.;
Larock, R. C. Org. Lett. 2004, 6, 2677.
10.1021/ol052214x CCC: $30.25
© 2005 American Chemical Society
Published on Web 10/27/2005

mium(III) chloride followed by 2-butyne produced 9,10-
dimethyl-phenanthrene via dibenzochromacyclopentadiene as
an intermediate.6 Although these results have suggested the
usefulness of organochromium complex for construction of
polycyclic aromatic compounds with alkynes, their investiga-
tions were concentrated on the mechanism of these reactions,
and efficiency and applicability of the reactions had not been
examined sufficiently.7
Table 1. Synthesis of Phenanthrenes Using CrCl3
Until now our group has reported zirconium-mediated
synthesis of highly substituted polycyclic aromatic com-
pounds.8 Furthermore, we found that the combination of these
zirconium-mediated reactions with chromium(III) chloride
have shown unique reactivity toward a series of unsaturated
compounds.9 During the course of our investigation in such
direction, we found efficient synthesis of polycyclic com-
pounds from halobiaryls and alkynes mediated by chromium
as described below.
A typical experimental procedure is as follows (Scheme
1). To a THF solution of 2,2′-dibromobiphenyl 1 was added
Scheme 1
n-butyllithium at -78 °C, and the mixture was stirred for 1
h. After addition of 1 equiv of chromium(III) chloride, the
mixture was warmed to room temperature. After stirring for
1 h, 2 equiv of an alkyne was added, and the mixture was
heated to 50 °C for 6-12 h to afford the corresponding
phenanthrene derivatives 2 in good to excellent yields.10
As summarized in Table 1, the chromium-mediated
reaction was applicable for a wider variety of alkynes
compared with the precedent methods,4 and the desired
phenanthrenes were obtained in good to excellent yields.
Arylalkynes can be used for this benzannulation as well as
aliphatic alkynes (entries 2 and 3). With terminal alkynes,
the desired phenanthrenes were formed without significant
loss of efficiency (entries 4 and 5). When conjugated diynes
were subjected to the reaction, the corresponding alky-
a GC yields. Isolated yields are shown in parentheses. b The reaction was
carried out in the presence of 2 equiv of TMEDA.
nylphenanthrenes were formed, and no biphenanthryl deriva-
tives, the doubly annulated products, were obtained (entries
6 and 7). As functionalized alkynes, silylated alkynes and
alkynes with one or two ester groups can be used for this
reaction to produce the corresponding phenanthrene deriva-
tives 2h-j in good yields. For the reactions using alkynes
with ethoxy- or methoxycarbonyl groups (entries 9 and 10),
addition of TMEDA was effective to increase the product
yields by ca. 10%.
(5) (a) Zeiss, H. H.; Herwig, W. J. Am. Chem. Soc. 1958, 80, 2913. (b)
Zeiss, H. H.; Tsutsui, M. J. Am. Chem. Soc. 1959, 81, 6090. (c) Herwig,
W.; Metlesics, W.; Zeiss, H. H. J. Am. Chem. Soc. 1959, 81, 6203.
(6) (a) Whitesides, G. M.; Ehmann, W. J. J. Am. Chem. Soc. 1968, 90,
804. (b) Whitesides, G. M.; Ehmann, W. J. J. Am. Chem. Soc. 1970, 92,
5625.
(7) Recent example of chromium-mediated cyclization: Nishikawa, T.;
Kakiya, H.; Shinokubo, H.; Oshima, K. J. Am. Chem. Soc. 2001, 123, 4629.
(8) (a) Takahashi, T.; Li, Y.; Stepnicka, P.; Kitamura, M.; Liu, Y.;
Nakajima, K.; Kotora, M. J. Am. Chem. Soc. 2002, 124, 576. (b) Takahashi,
T.; Kitamura, M.; Shen, B.; Nakajima, K. J. Am. Chem. Soc. 2000, 122,
12876. (c) Takahashi, T.; Hara, R.; Nishihara, Y.; Kotora, M. J. Am. Chem.
Soc. 1996, 118, 5154.
The chromium-mediated reaction can be applied for the
other dilithium compounds. As shown in Scheme 2, it is well-
known that a reaction of diphenylacetylene with 2 equiv of
butyllithium affords dilithiated stilbene derivative in high
yield.11 When the dilithiated stilbene derivative was treated
with chromium(III) chloride followed by the addition of
(9) Takahashi, T.; Liu, Y.; Iesato, A.; Chaki, S.; Nakajima, K.; Kanno,
K. J. Am. Chem. Soc. 2005, 127, 11928.
(10) Although the reaction mechanism is still unclear yet, it seems to
proceed Via formation of dibenzochromacyclopentadiene as key intermediate
followed by cycloaddition with alkynes.
5454
Org. Lett., Vol. 7, No. 24, 2005

Scheme 2
Scheme 4
diphenylacetylene, 1-butyl-2,3,4-triphenylnaphthalene 3 was
obtained in 87% isolated yield.
afforded 9-phenyl-10-trimethylsilylphenanthrene 2h, which
could be converted into 9-iodo-10-phenylphenanthrene 8 by
the treatment with iodine monochloride in high yield.12 When
the iodophenanthrene 8 was subjected again to the chromium-
mediated reaction with 3-hexyne, the corresponding benzo-
[g]chrysene 9 was obtained.
1-Phenylpyrrole 10 was dilithiated by the addition of 2
equiv of n-butyllithium in hexane in the presence of
TMEDA.13 This dilithiated 1-phenylpyrrole was converted
to the pyrroloquinoline derivative 11 by the same way as
above in good yield (Scheme 5). Moreover, the bay region
2,2′-Dilithiobiphenyl derivatives were prepared from not
only 2,2′-dihalogenated biphenyls but 2-monohalogenated
ones. When 2 equiv of n-butyllithium was added to 2-bro-
mobiphenyl 4a, the same dilithiated biphenyl was generated
as that from dibromobiphenyl. After treatment with chro-
mium(III) chloride and 3-hexyne, 9,10-diethylphenanthrene
2a was obtained in a comparable yield. Similarly, 2-iodo-
4′-methylbiphenyl 4b was converted into the corresponding
phenanthrene 5a in the same way in 58% yield (Scheme 3).
Scheme 3
Scheme 5
of the pyrroloquinoline 11 could also be dilithiated and
transformed into the corresponding 9b-azacyclopenta[cd]-
phenalenes 12 (Scheme 5 and Table 2). It is worth noting
The use of monohalogenated biaryl enabled us to produce
more extended polycyclic aromatic compounds. As shown
in Scheme 3, 1-(2-lithiophenyl)-2-lithionaphthalene was
generated by the addition of 2 equiv of n-butyllithium into
the THF solution of 1-(2-iodophenyl)naphthalene 6. After
the reaction with chromium(III) chloride and an alkyne, the
corresponding benzo[c]phenanthrenes 7 were formed.
Furthermore, stepwise benzannulation is also possible by
appropriate selection of the substituents on the starting
alkynes as shown in Scheme 4. The reaction with 2,2′-
dibromobiphenyl 1 and 1-phenyl-2-trimethylsilylacetylene
Table 2. Synthesis of Azacyclopentaphenalene 12
entry
R
time/h
product
yield/%
1
2
3
4
Et
Ph
p-tol
2-thienyl
12
3
12
24
12a
12b
12c
12d
39
55
49
38
(11) (a) Mulvaney, J. E.; Carr, L. J. J. Org. Chem. 1968, 33, 3286. (b)
Mulvaney, J. E.; Garlund, Z. G.; Garlund, S. L.; Newton, D. J. J. Am. Chem.
Soc. 1966, 88, 476.
that the chromium-mediated reaction enables us to construct
these polycyclic systems in short steps.
Org. Lett., Vol. 7, No. 24, 2005
5455

highly planar structure in the solid state. All of the atoms
that constitute the fused polycyclic skeleton are located on
the same plane.
In summary, the chromium-mediated benzannulation reac-
tion allows us to construct a variety of polycyclic aromatic
compounds starting from halogenated biaryls and a series
of alkynes. A wide availability of alkynes is the most
remarkable advantage of this benzannulation reaction com-
pared to the palladium-catalyzed ones. Also, the present
reaction provides a convenient method to build up the
complex polycyclic skeletons compared with the known
methods. Further investigation especially for the synthesis
of heterocyclic compounds is now in progress.
Supporting Information Available: Experimental details
and spectroscopic characterization of new compounds and
X-ray crystallographical data of 12b in CIF format. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL052214X
Figure 1. Molecular structure of 9b-azacyclopentaphenalene 12b.
(12) (a) Campo, M. A.; Larock, R. C. Org. Lett. 2000, 23, 3675-3677.
(b) Miller, R. B.; McGarvey, G. Synth. Commun. 1978, 8, 291.
(13) Faigl, F.; Schlosser, M. Tetrahedron 1993, 49, 10271.
Azacyclopentaphenalene 12b was characterized by X-ray
crystallographical analysis (Figure 1), which shows 12b has
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Org. Lett., Vol. 7, No. 24, 2005