Synthesis of polycyclic aromatics and heteroaromatics via electrophilic cyclization

Article abstract of DOI:10.1021/jo050104y

(Chemical Equation Presented) A variety of substituted polycyclic aromatics are readily prepared in good to excellent yields under very mild reaction conditions by the reaction of 2-(1-alkynyl)biphenyls with ICl, I₂, NBS, and p-O₂NC<

Full text of DOI:10.1021/jo050104y

Synthesis of Polycyclic Aromatics and Heteroaromatics via
Electrophilic Cyclization
Tuanli Yao, Marino A. Campo, and Richard C. Larock*
Department of Chemistry, Iowa State University, Ames, Iowa 50011
larock@iastate.edu
Received January 18, 2005
A variety of substituted polycyclic aromatics are readily prepared in good to excellent yields
under very mild reaction conditions by the reaction of 2-(1-alkynyl)biphenyls with ICl, I2, NBS,
and p-O2NC6H4SCl. This methodology readily accommodates various functional groups and has
been successfully extended to systems containing a variety of polycyclic and heterocyclic rings.
Introduction
phenylethynyl moiety was apparently critical to the
success of that methodology. No other applications of this
type of carbocyclization have been reported despite its
tremendous synthetic potential.
The electrophilic cyclization of alkenes has been stud-
ied extensively, and utilized as a key step in a variety of
syntheses,1 particularly the biomimic cyclization of poly-
enes.2 Various electrophiles have been reported to effect
C-C bond formation in such ring closures.1-3 Relatively
little attention has been paid to the electrophile-induced
carbocyclization of alkynes. Nevertheless, the electro-
philic addition to carbon-carbon triple bonds can gener-
ate cationic species capable of undergoing intramolecular
cyclization onto an aromatic ring.4 Thus, Barluenga first
used I(py)2BF4, a highly electrophilic source of iodonium
ions, in the presence of a very strong acid to cyclize 1,4-
diphenyl-1-butyne to the corresponding iododihydronaph-
thalene (eq 1).5 Swager employed this same reagent
Polycyclic aromatics are critical to advances in a
number of areas of chemical research. For example, poly-
cyclic aromatic iodides are very useful starting materials
in organic synthetic methodology, particularly palladium-
catalyzed annulation,7 cyclization,8 and carbonylation
system to prepare fused polycyclic aromatics (eq 2).6
Unfortunately, the presence of a p-alkoxy group on the
(3) Sutherland, J. K. Chem. Soc. Rev. 1980, 9, 265.
(4) (a) Kitamura, T.; Takachi, T.; Kawasato, H.; Taniguchi, H. J.
Chem. Soc., Perkin Trans. 1 1992, 1969. (b) For a similar Lewis acid-
promoted cyclization, see: Furstner, A.; Mamane, V. J. Org. Chem.
2002, 67, 6264. (c) Pastine, S. J.; Youn, S. W.; Sames, D. Org. Lett.
2003, 5, 1055. (d) Pastine, S. J.; Youn, S. W.; Sames, D. Tetrahedron
2003, 59, 8859.
(1) (a) Bartlett, P. A. In Asymmetric Synthesis; Morrison, J. D., Ed.;
Academic Press: Orlando, FL, 1984; Vol. 3, p 341. (b) Kitagawa, O.;
Inoue, T.; Taguchi, T. In Reviews on Heteroatom Chemistry; Oae, S.,
Ed.; MYU: Tokyo, Japan, 1996; Vol. 15, p 243. (c) Cardillo, G.; Orena,
M. Tetrahedron 1990, 46, 3321. (d) Frederickson, M.; Grigg, R. Org.
Prep. Proc. Int. 1997, 29, 33.
(5) Barluenga, J.; Gonza´lez, J. M.; Campos, P. J.; Asensio, G. Angew.
Chem., Int. Ed. Engl. 1988, 27, 1546.
(6) (a) Goldfinger, M. B.; Crawford, K. B.; Swager, T. M. J. Am.
Chem. Soc. 1997, 119, 4578. (b) Goldfinger, M. B.; Swager, T. M. J.
Am. Chem. Soc. 1994, 116, 7895.
(2) (a) Van Tamelen, E. E. Acc. Chem. Res. 1975, 8, 152. (b) Johnson,
W. S. Angew. Chem., Int. Ed. Engl. 1976, 15, 9.
10.1021/jo050104y CCC: $30.25 © 2005 American Chemical Society
Published on Web 03/23/2005
J. Org. Chem. 2005, 70, 3511-3517
3511

Yao et al.
processes.9 Polycyclic aromatics can also be used as rigid
molecular platforms in various areas of chemical re-
search, such as host-guest chemistry,10 liquid crystal
chemistry,11 and biochemical studies of synthetic pep-
tides.12 Furthermore, these rigid conjugated materials
can serve as key components in many advanced technolo-
gies utilizing nonlinear optical,13 photo- and electrolu-
minescent,14 and molecule-based sensory devices.15 They
can transfer an applied bias or optical input to a desired
response through their highly conjugated π electron
systems. Polycyclic aromatics obviously possess the de-
gree of conjugation and rigidity necessary to eliminate
conformational disorder, which lowers the effective con-
jugation.16
SCHEME 1
2,3-dihydropyrroles and pyrroles,25 pyrilium salts,26 bi-
cyclic â-lactams,27 isochromenes,28,26a phosphaisocou-
marins,29 and isoindolin-1-ones30 via electrophilic cycliza-
tion of functionally substituted alkynes. This successful
electrophilic cyclization strategy has encouraged us to
develop a more general methodology for the synthesis of
polycyclic aromatics.31 Herein, we report the successful
electrophilic cyclization of arene-containing acetylenes to
polycyclic aromatics. This chemistry generally produces
good to excellent yields of polycyclic aromatics under very
mild reaction conditions, accommodates various func-
tional groups, and has been successfully extended to
systems containing a variety of polycyclic and heterocyclic
rings.
We and others have developed methods for the syn-
thesis of benzo[b]thiophenes,17 isoquinolines and naph-
thyridines,18 isocoumarins and R-pyrones,19 benzofurans,20
furans,21 indoles,22 furopyridines,23 cyclic carbonates,24
(7) For reviews see: (a) Larock, R. C. J. Organomet. Chem. 1999,
576, 111. (b) Larock, R. C. Palladium-Catalyzed Annulation. In
Perspectives in Organopalladium Chemistry for the XXI Century; Tsuji,
J., Ed.; Elsevier Press: Lausanne, Switzerland, 1999; p 111. (c) Larock,
R. C. Pure Appl. Chem. 1999, 71, 1435.
(8) Tsuji, J. Palladium Reagents and Catalysts; John Wiley &
Sons: Chichester, UK, 1999.
(9) (a) Campo, M. A.; Larock, R. C. Org. Lett. 2000, 2, 3675. (b)
Arcadi, A.; Cacchi, S.; Fabrizi, G.; Moro, L. Eur. J. Org. Chem. 1999,
1137. (c) Cacchi, S.; Fabrizi, G.; Pace, P.; Marinelli, F. Synlett 1999, 5,
620. (d) Arcadi, A.; Cacchi, S.; Carnicelli, V.; Marinelli, F. Tetrahedron
1994, 50, 437. (e) Arcadi, A.; Cacchi, S.; Rosario, M. D.; Fabrizi, G.;
Marinelli, F. J. Org. Chem. 1996, 61, 9280. (f) Campo, M. A.; Larock,
R. C. J. Org. Chem. 2002, 67, 5616.
Results and Discussion
A two-step approach to polycyclic aromatics has been
examined involving (i) preparation of 2-(1-alkynyl)biaryls
by the Sonagashira coupling reaction32 and (ii) electro-
philic cyclization (Scheme 1).
(10) (a) Cram, D. J. Nature 1992, 356, 29. (b) Schwartz, E. B.;
Knobler, C. B.; Cram, D. J. J. Am. Chem. Soc. 1992, 114, 10775. (c)
Dijkstra, P. J.; Skowronska-Ptasinska, M.; Reinhoudt, D. N.; Den
Hertog, H. J.; Van Eerden, J.; Harkema, S.; De Zeeuw, D. J. Org. Chem.
1987, 52, 4913.
(11) (a) Chandrasekhar, S. Advances in Liquid Crystals; Academic
Press: New York, 1982; Vol. 5, p 47. (b) Chandrasekhar, S.; Ranganath,
G. S. Rep. Prog. Phys. 1990, 53, 57. (c) Praefcke, K.; Kohne, B.; Singer,
D. Angew Chem., Int. Ed. Engl. 1990, 29, 177.
(12) (a) Veber, D. F.; Strachan, R. G.; Bergstrand, S. J.; Holly, F.
W.; Homnick, C. F.; Hirschmann, R.; Torchiana, M. L.; Saperstein, R.
J. Am. Chem. Soc. 1976, 98, 2367. (b) Tsang, K. Y.; Diaz, H.; Graciani,
N.; Kelly, J. W. J. Am. Chem. Soc. 1994, 116, 3988.
(13) (a) Munn, R. W.; Ironside, C. N. Principles and Application of
Nonlinear Optical Materials; Chapman & Hall: London, UK, 1993.
(b) Nie, W. Adv. Mater. 1993, 5, 520. (c) Prasad, P. N.; Williams, D. J.
Introduction to Nonlinear Optical Effects in Molecules and Polymers;
Wiley: New York, 1991.
The 2-(1-alkynyl)biaryls required for our approach are
readily prepared by Sonogashira coupling32 of the corre-
sponding 2-iodobiaryls with terminal alkynes by using
2% PdCl2(PPh3)2 and 1% CuI in Et3N solvent at 55 °C.
The yields of this process range from 55% to 99% and
this procedure readily accommodates considerable func-
tionality.
To explore the scope of our electrophilic cyclization
strategy, the reactions of alkynyl biphenyl 1 with various
electrophiles (ICl, I2, NBS, p-O2NC6H4SCl, and PhSeCl)
(21) (a) Bew, S. P.; Knight, D. W. J. Chem. Soc., Chem. Commun.
1996, 1007. (b) Djuardi, E.; McNelis, E. Tetrahedron Lett. 1999, 40,
7193. (c) El-Taeb, G. M. M.; Evans, A. B.; Jones, S.; Knight, D. W.
Tetrahedron Lett. 2001, 42, 5945. (d) Rao, M. S.; Esho, N.; Sergeant,
C.; Dembinski, R. J. Org. Chem. 2003, 68, 6788.
(14) (a) Greenham, N. C.; Moratti, S. C.; Bradley, D. D. C.; Friend,
R. H.; Holmes, A. B. Nature 1993, 365, 628. (b) Schwoerer, M. Phys.
Bull. 1994, 50, 52. (c) Gru¨ner, J. F.; Hamer, P.; Friend, R. H.; Huber,
J.; Scherf, U.; Holmes, A. B. Adv. Mater. 1994, 6, 748. (d) Braun, D.;
Heeger, A. J. Appl. Phys. Lett. 1991, 58, 1982.
(22) (a) Barluenga, J.; Trincado, M.; Rubio, E.; Gonzalez, J. M.
Angew. Chem., Int. Ed. 2003, 42, 2406. (b) Yue, D.; Larock, R. C. Org.
Lett. 2004, 6, 1037.
(15) (a) Swager, T. M.; Marsella, M. J. Adv. Mater. 1994, 6, 595. (b)
Marsella, M. J.; Swager, T. M. J. Am. Chem. Soc. 1993, 115, 12214.
(c) Marsella, M. J.; Carroll, P. J.; Swager, T. M. J. Am. Chem. Soc.
1994, 116, 9347. (d) McCullough, R. D.; Williams, S. P. J. Am. Chem.
Soc. 1993, 115, 11608. (e) Youssoufi, H. K.; Hmyene, M.; Garnier, F.;
Delabouglise, D. J. Chem. Soc., Chem. Commun. 1993, 1550. (f)
Schuhmann, W.; Huber, J.; Mirlach, A.; Daub, J. Adv. Mater. 1993, 5,
124.
(23) Arcadi, A.; Cacchi, S.; Di Giuseppe, S.; Fabrizi, G.; Marinelli,
F. Org. Lett. 2002, 4, 2409.
(24) Marshall, J. A.; Yanik, M. M. J. Org. Chem. 1999, 64, 3798.
(25) Knight, D. W.; Redfern, A. L.; Gilmore, J. J. Chem. Soc., Chem.
Commun. 1998, 2207.
(26) (a) Barluenga, J.; Vazque-Villa, H.; Ballesteros, A.; Gonzalez,
J. M. J. Am. Chem. Soc. 2003, 125, 9028. (b) Barluenga, J.; Vazque-
Villa, H.; Ballesteros, A.; Gonzalez, J. M. Org. Lett. 2003, 5, 4121.
(27) Ren, X.-F.; Konaklieva, M. I.; Shi, H.; Dickey, S.; Lim, D. V.;
Gonzalez, J.; Turos, E. J. Org. Chem. 1998, 63, 8898.
(16) Schlu¨ter, A. Adv. Mater. 1991, 3, 282.
(17) (a) Larock, R. C.; Yue, D. Tetrahedron Lett. 2001, 42, 6011. (b)
Yue, D.; Larock, R. C. J. Org. Chem. 2002, 67, 1905. (c) Flynn, B. L.;
Verdier-Pinard, P.; Hamel, E. Org. Lett. 2001, 3, 651.
(28) (a) Asao, N.; Nogami, T.; Takahashi, K.; Yamamoto, Y. J. Am.
Chem. Soc. 2002, 124, 764. (b) Nakamura, H.; Ohtaka, M.; Yamamoto,
Y. Tetrahedron Lett. 2002, 43, 7631.
(18) (a) Huang, Q.; Hunter, J. A.; Larock, R. C. Org. Lett. 2001, 3,
2973. (b) Huang, Q.; Hunter, J. A.; Larock, R. C. J. Org. Chem. 2002,
67, 3437.
(29) Peng, A.-Y.; Ding, Y.-X. Org. Lett. 2004, 6, 1119.
(30) Yao, T.; Larock, R. C. J. Org. Chem. 2005, 70, 1232.
(31) For a previous communication, see: Yao, T.; Campo, M. A.;
Larock, R. C. Org. Lett. 2004, 6, 2677.
(19) (a) Yao, T.; Larock, R. C. Tetrahedron Lett. 2002, 43, 7401. (b)
Yao, T.; Larock, R. C. J. Org. Chem. 2003, 68, 5936. (c) Oliver, M. A.;
Gandour, R. D. J. Org. Chem. 1984, 49, 558. (d) Biagetti, M.; Bellina,
F.; Carpita, A.; Stabile, P.; Rossi, R. Tetrahedron 2002, 58, 5023. (e)
Rossi, R.; Carpita, A.; Bellina, F.; Stabile, P.; Mannina, L. Tetrahedron
2003, 59, 2067.
(32) For reviews, see: (a) Campbell, I. B. The Sonogashira Cu-Pd-
Catalyzed Alkyne Coupling Reaction. Organocopper Reagents; Taylor,
R. J. K., Ed.; IRL Press: Oxford, UK, 1994; pp 217-235. (b) Sono-
gashira, K.; Takahashi, S. Yuki Gosei Kagaku Kyokaishi 1993, 51,
1053. (c) Sonogashira, K. In Comprehensive Organic Synthesis; Trost,
B. M., Ed.; Pergamon: Oxford, UK, 1991; Vol. 3, pp 521-549.
(20) Arcadi, A.; Cacchi, S.; Fabrizi, G.; Marinelli, F.; Moro, L. Synlett
1999, 1432.
3512 J. Org. Chem., Vol. 70, No. 9, 2005

Synthesis of Polycyclic Aromatics and Heteroaromatics
in CH2Cl2 at room temperature have been studied (Table
1, entries 1-5). Excellent 99% and 92% yields of the
expected iodo- and sulfur-containing phenanthrenes
have been obtained in only 30 min when ICl and
p-O2NC6H4SCl were used as electrophiles, respectively
(entries 1 and 4). I2 can also be employed as the electro-
phile, but the reaction took 24 h at room temperature to
afford the corresponding product in only an 80% yield
(entry 2). It should be noted that NaHCO3 is indispen-
sable in this reaction. Otherwise, an inseparable mixture
of unidentified products was obtained. The structure of
compound 2 was confirmed by comparison with 9-iodo-
10-phenylphenanthrene prepared by the palladium-
catalyzed annulation of (phenylacetylenyl)trimethylsilane
by 2-iodobiphenyl, followed by subsequent iododesilyla-
tion by ICl.9a NBS itself did not react with 2-(1-phenyl-
ethynyl)biphenyl (1). Interestingly, a mixture of NBS and
silica gel provided the cyclized bromine-containing prod-
uct 3 in an 86% yield after 6 d. Unfortunately, none of
the desired selenium-containing product was observed
when using PhSeCl. Only 1,2-adducts formed by PhSeCl
addition to the carbon-carbon triple bond were obtained.
We next examined the reaction of 2-(p-methoxyphen-
ylethynyl)biphenyl (6) and ICl (Table 1, entry 6). We first
examined the reaction of 6 with 1.2 equiv of ICl in
CH2Cl2 at room temperature. This reaction afforded a
mixture of the corresponding iodocyclization product 7
and a side-product, which is believed to be 10-iodo-9-(3-
iodo-4-methoxyphenyl)phenanthrene. Fortunately, when
the same reaction was carried out at -78 °C, the desired
10-iodo-9-(p-methoxyphenyl)phenanthrene (7) was the
only product formed in a 99% yield. Thus, our standard
reaction conditions employ 0.30 mmol of acetylene, 1.2
equiv of ICl in CH2Cl2 at -78 °C.
By employing this standard protocol, the reaction of
2-(p-tolylethynyl)biphenyl (8) with ICl afforded the de-
sired 10-iodophenanthrene 9 in a 98% yield (entry 7). The
presence of a modest electron-withdrawing group, like a
p-CO2Et group, on the phenylethynyl moiety, as in 10,
still provided the cyclization product 11 in a quantitative
yield (entry 8). Surprisingly, even the presence of a strong
electron-withdrawing p-NO2 group on the phenylethynyl
moiety (12) afforded the corresponding cyclization prod-
uct 13 in a 57% yield, along with a 42% combined yield
of side-products presumed to be 1,2-adducts formed by
ICl addition to the carbon-carbon triple bond (entry 9).
Thus, the p-alkoxy group on the phenylethynyl moiety,
which was critical to the success of Swager’s cyclization
methodology, is obviously not necessary in our chemistry.
A notable feature in this chemistry is the preference for
the 6-endo-dig cyclization to give phenanthrenes over the
alternative 5-exo mode of cyclization.
in which the aromatic ring undergoing cyclization is
electron-poor is consistent with our proposed mechanism
(see the later mechanistic discussion). Substrate 18,
which also contains a nitro group, undergoes cyclization
smoothly to produce the desired product 19 in an 88%
yield (compare entries 11 and 12). Obviously, moving the
nitro group from the ring undergoing substitution to the
central arene facilitates electrophilic aromatic substitu-
tion.
To further investigate the scope of this methodology,
we have examined the effect of various substituents on
the remote end of the alkyne moiety. An olefin-substi-
tuted alkyne 20 is readily accommodated (entries 13).
However, the reaction of alkynes bearing a saturated
alkyl or TMS group with ICl under our standard reaction
conditions failed to produce the desired phenanthrene
products (entries 14 and 15). Interestingly, the (trimeth-
ylsilyl)methyl-substituted alkyne 26 underwent smooth
iodocyclization to afford the desired phenanthrene 27 in
a 50% yield. This favorable result can be attributed to
the fact that a silyl group can stabilize a carbocation
located in the â position,33 which favors cyclization onto
the neighboring phenyl group (see the later mechanistic
discussion). The desilylation of product 27 will afford a
9-alkyl-substituted phenanthrene, which means that
9-alkyl phenanthrenes can be prepared by this electro-
philic cyclization method in two steps.
This cyclization chemistry has been successfully ex-
tended to other biaryl systems. For instance, 1-phenyl-
2-(phenylethynyl)naphthalene (28) afforded the cycliza-
tion product 29 in a 48% yield (entry 17). Changing the
phenyl group of the phenylethynyl moiety to a p-meth-
oxyphenyl group dramatically increased the yield to 97%
(compare entries 17 and 18). The thiophene-containing
acetylene 32 afforded the expected cyclization product 33
in a 96% yield (entry19), despite our concern that
electrophilic substitution in the very reactive thiophene
ring might prove competitive. Obviously it is not. In a
similar manner, the isocoumarin-containing alkyne 34
provided a 65% yield of the corresponding polycycle 35.
Treatment of the benzofuran-containing acetylene 36
with ICl afforded the cyclization product 37 in a 91% yield
(entry 21). Again, direct substitution of the electron-rich
benzofuran does not appear to be competitive with
iodocyclization. However, the benzofuran-containing acety-
lene 38 failed to afford the desired product (entry 22).
This may be the result of inductive electron-withdrawal
by the oxygen moiety disfavoring cation formation or it
may be the unfavorable geometry present when the
alkyne and arene undergoing substitution are placed on
an unsaturated five-membered ring, rather than the
more usual six-membered benzene ring. Treatment of the
benzothiophene-containing acetylene 40 with NBS and
p-O2NC6H4SCl afforded the anticipated cyclization prod-
ucts 41 and 42 in 88% and 91% yields, respectively, with
no indication of any products being formed by direct
substitution of the benzothiophene (entries 23 and 24).
The regioselectivity in this electrophilic cyclization
chemistry has also been investigated. The iodocyclization
of biphenyl 43 afforded approximately a 3:1 regiochemical
Encouraged by our success with the above substrates,
we next investigated the cyclization of analogous acety-
lenes in which various substituents have been attached
to the arene undergoing substitution. Treatment of p-[2-
(phenylethynyl)phenyl]benzaldehyde (14) with ICl under
our standard reaction conditions afforded cyclization
product 15 in a 71% yield. A 17% yield of products from
ICl addition to the alkyne was also obtained (entry 10).
Substrate 16 containing a strong electron-withdrawing
p-NO2 group afforded the desired iodophenanthrene 17
in a 55% yield, along with a 31% yield of ICl alkyne
adducts (entry 11). The lower yields for these substrates
(33) For reviews, see: (a) Lambert, J. B. Tetrahedron 1988, 46, 2677.
(b) Apeloig, Y. In The Chemistry of Organic Silicon Compounds; Patai,
S., Rappoport, Z., Eds.; Wiley-Interscience: New York, 1989; pp 57-
225. (c) Fleming, I. CHEMTRACTS Org. Chem. 1993, 6, 113.
J. Org. Chem, Vol. 70, No. 9, 2005 3513

Yao et al.
TABLE 1. Synthesis of Polycyclic Aromatics via Electrophilic Cyclizationa
3514 J. Org. Chem., Vol. 70, No. 9, 2005

Synthesis of Polycyclic Aromatics and Heteroaromatics
Table 1 (Continued)
a All reactions were run under the following conditions, unless otherwise specified: 0.30 mmol of the acetylene in 3 mL of CH2Cl2 was
placed in a 4-dram vial under N2 and 1.2 equiv of electrophile was added at -78 °C. b The reaction was run at room temperature. c 3.0
equiv of electrophile and 3.0 equiv of NaHCO3 were used. d Silica gel (50 mg) was added. e Contains a 42% yield of addition products.
f Contains a 17% yield of alkyne addition products. g Contains a 31% yield of alkyne addition products. h Only alkyne addition products
were obtained.
mixture of 44 and 45, with cyclization to the less hindered
position being favored (entry 25). In the cyclization of
thiophene 46, electronic effects control the regioselectiv-
ity, affording product 47 as the major isomer by cycliza-
J. Org. Chem, Vol. 70, No. 9, 2005 3515

Yao et al.
SCHEME 2
SCHEME 3
tion to the more electron-rich R-position of the thiophene
(entry 26). However, substantial amounts of the product
of substitution in the 4-position are also observed. The
iodocyclization of the naphthalene-containing acetylene
49 afforded approximately a 5:1 regiochemical mixture
of 50 and 51 in an excellent overall yield (entry 27). The
predominant isomer is 50, which arises by cyclization
onto the 1-position of the naphthalene moiety. Clearly,
electronic effects favor cyclization to 50 over cyclization
to the less hindered 3-position of the naphthalene, which
affords 51.
In conclusion, an efficient synthesis of polycyclic aro-
matics under very mild reaction conditions has been
developed. This methodology accommodates various func-
tional groups and affords the anticipated substituted
polycyclic aromatics in good to excellent yields. It can be
applied to the synthesis of simple polycyclic aromatic
hydrocarbons and heterocyclic systems. Finally, the
resulting iodine-containing products can be readily elabo-
rated to more complex products by using known organo-
palladium chemistry.
The facility with which this carbocyclization process
occurs encouraged us to attempt a double cyclization. The
double cyclization of diyne 52 afforded the desired
product 53 in a 90% yield (entry 28).
We propose a mechanism for this electrophilic cycliza-
tion chemistry that involves (1) formation of an electro-
phile acetylene complex, (2) electrophilic attack of this
intermediate on the neighboring aromatic ring of the
biaryl moiety, and (3) deprotonation to generate the
desired polycyclic aromatic (Scheme 2).
An interesting feature of this chemistry is the fact that
the polycyclic aromatic iodides produced can be further
elaborated by using a variety of palladium-catalyzed
processes. For example, palladium-catalyzed Sonogashira
coupling,32 alkyne annulation,7 cyclocarbonylation,9 and
the Heck reaction34 have afforded the corresponding
products 54-57 in 53%, 83%, 98%, and 98% yields,
respectively (Scheme 3). The Sonogashira reaction nicely
provides products which can again be subjected to elec-
trophilic cyclization to generate still further aromatic
rings in an iterative process.
Experimental Section
General Procedure for Preparation of the 2-(1-Alky-
nyl)biphenyls. To a solution of the corresponding aryl iodide
(1.0 mmol) and the terminal alkyne (1.2 mmol, 1.2 equiv) in
Et3N (4 mL) were added PdCl2(PPh3)2 (14 mg, 2 mol %) and
CuI (2 mg, 1 mol %). The resulting mixture was then heated
under a N2 atmosphere at 55 °C for 3 h. The mixture was
allowed to cool to room temperature, and the ammonium salt
was removed by filtration. The solvent was removed under
reduced pressure and the residue was purified by column
chromatography on silica gel to afford the corresponding
product.
2-[(4-Methoxyphenyl)ethynyl]biphenyl (6). 2-Ethynyl-
biphenyl and 4-iodoanisole were employed. Purification by
flash chromatography (30:1 hexane/EtOAc) afforded 211 mg
(74%) of the product as a clear liquid: 1H NMR (CDCl3) δ 3.80
(s, 3H), 6.84 (dd, J ) 2.4, 6.9 Hz, 2H), 7.30 (dd, J ) 2.1, 6.9
Hz, 2H), 7.34-7.50 (m, 6H), 7.64-7.73 (m, 3H); 13C NMR
(CDCl3) δ 55.5, 88.4, 92.5, 114.2, 115.9, 122.2, 127.3, 127.6,
128.1, 128.4, 129.6, 129.7, 132.9, 133.1, 140.9, 143.9, 159.8;
IR (neat, cm-1) 3059, 3017, 2214, 1605; HRMS calcd for
C21H16O 284.1201, found 284.1205.
General Procedure for the Electrophilic Cyclization
of 2-(1-Alkynyl)biphenyls by ICl. To a solution of 2-(1-
alkynyl)biphenyl (0.30 mmol) in CH2Cl2 (3 mL) under N2 was
added ICl (1.2 equiv) in CH2Cl2 (0.5 mL) at -78 °C. The
reaction mixture was stirred at -78 °C for 0.5 h unless
otherwise indicated. The reaction mixture was then diluted
with diethyl ether (50 mL), washed with satd aq Na2S2O3 (25
(34) For leading reviews of the Heck reaction, see: (a) de Meijere,
A.; Meyer, F. E. Angew. Chem., Int. Ed. Engl. 1994, 33, 2379. (b)
Shibasaki, M.; Boden, C. D. J.; Kojima, A. Tetrahedron 1997, 53, 7371.
(c) Cabri, W.; Candiani, I. Acc. Chem. Res. 1995, 28, 2. (d) Overman,
L. E. Pure Appl. Chem. 1994, 66, 1423.
3516 J. Org. Chem., Vol. 70, No. 9, 2005

Synthesis of Polycyclic Aromatics and Heteroaromatics
mL), dried (MgSO4), and filtered. The solvent was evaporated
under reduced pressure and the product was purified by
chromatography on a silica gel column.
2H); 13C NMR (CDCl3) δ 122.9, 123.8, 127.1, 127.3, 127.7,
127.9, 128.0, 128.2, 128.7, 129.2, 129.3, 130.2, 130.7, 131.2,
132.9, 139.9, 141.3; IR (neat, cm-1) 3071, 3058, 3026, 1583,
1567, 1484; HRMS calcd for C20H15Br 332.0201, found 332.0209.
General Procedure for the Electrophilic Cyclization
of 2-(1-Alkynyl)biphenyls by p-O2NC6H4SCl. To a solution
of 2-(1-alkynyl)biphenyl (0.30 mmol) in CH2Cl2 (3 mL) was
added p-O2NC6H4SCl (1.2 equiv) at room temperature. The
reaction mixture was stirred for 0.5 h unless otherwise
indicated. The reaction mixture was then diluted with diethyl
ether (50 mL), washed with satd aq NH4Cl (25 mL), dried
(MgSO4), and filtered. The solvent was evaporated under
reduced pressure and the product was purified by chromatog-
raphy on a silica gel column.
9-(4-Nitrophenylsulfenyl)-10-phenylphenanthrene (4).
Purification by flash chromatography (30:1 hexane/EtOAc)
afforded 112 mg (92%) of the product as a yellow solid: mp
192-193 °C; 1H NMR (CDCl3) δ 6.94-6.98 (m, 2H), 7.20-7.24
(m, 2H), 7.39-7.47 (m, 3H), 7.50-7.54 (m, 2H), 7.71-7.64 (m,
1H), 7.72-7.79 (m, 2H), 7.93 (dt, J ) 9.3, 2.1 Hz, 2H), 8.46
(dd, J ) 8.4, 0.9 Hz, 1H), 8.83 (d, J ) 8.4 Hz, 2H); 13C NMR
(CDCl3) δ 123.0, 123.4, 124.1, 125.0, 125.9, 127.3, 127.4, 127.8,
128.1, 128.3, 128.4, 128.6, 129.2, 129.4, 131.3, 131.6, 131.7,
132.3, 139.9, 145.1, 148.0, 149.2; IR (neat, cm-1) 3066, 3024,
2834, 1610; HRMS calcd for C26H7NO2S 407.0980, found
407.0989.
9-Iodo-10-(4-methoxyphenyl)phenanthrene (7). Puri-
fication by flash chromatography (30:1 hexane/EtOAc) afforded
122 mg (99%) of the product as a white solid: mp 170-171
1
°C; H NMR (CDCl3) δ 3.94 (s, 3H), 7.09 (dd, J ) 2.1, 6.6 Hz,
2H), 7.21 (dd, J ) 2.1, 6.6 Hz, 2H), 7.40-7.49 (m, 2H), 7.64-
7.72 (m, 3H), 8.45-8.49 (m, 1H), 8.67-8.78 (m, 2H); 13C NMR
(CDCl3) δ 55.6, 107.7, 114.0, 122.8, 122.9, 127.2, 127.3, 127.7,
128.3, 129.0, 130.5, 130.8, 131.3, 132.7, 132.9, 135.0, 138.2,
145.3, 159.4; IR (neat, cm-1) 3066, 3024, 2834, 1610; HRMS
calcd for C21H15IO 410.0168, found 410.0172.
General Procedure for the Electrophilic Cyclization
of 2-(1-Alkynyl)biphenyls by I2. To a solution of 2-(1-
alkynyl)biphenyl (0.30 mmol) in CH2Cl2 (3 mL) was added I2
(3.0 equiv) and NaHCO3 (3.0 equiv) at room temperature. The
reaction mixture was stirred at room temperature for 24 h
unless otherwise indicated. The reaction mixture was then
diluted with diethyl ether (50 mL), washed with satd aq
Na2S2O3 (25 mL), dried (MgSO4), and filtered. The solvent was
evaporated under reduced pressure and the product was
purified by chromatography on a silica gel column.
9-Iodo-10-phenylphenanthrene (2). Purification by flash
chromatography (50:1 hexane/EtOAc) afforded 92 mg (80%)
of the product as a white solid with a melting point and
spectral properties identical with those previously reported.9a
General Procedure for the Electrophilic Cyclization
of 2-(1-Alkynyl)biphenyls by NBS. To a solution of 2-(1-
alkynyl)biphenyl (0.30 mmol) in CH2Cl2 (3 mL) was added NBS
(1.2 equiv) and silica gel (50 mg) at room temperature. The
reaction mixture was stirred at room tempature for 144 h
unless otherwise indicated. The reaction mixture was then
diluted with diethyl ether (50 mL), washed with satd aq
Na2S2O3 (25 mL), dried (MgSO4), and filtered. The solvent was
evaporated under reduced pressure and the product was
purified by chromatography on a silica gel column.
Acknowledgment. We gratefully acknowledge the
donors of the Petroleum Research Fund, administered
by the American Chemical Society, the National Science
Foundation, and the National Institute of General
Medical Sciences (GM070620) for partial support of this
research, and Johnson Matthey, Inc. and Kawaken Fine
Chemicals Co., Ltd. for donations of palladium catalysts.
Supporting Information Available: Characterization
data for the compounds listed in Table 1 and experimental
procedures and characterization data for the reactions sum-
marized in Scheme 3. This material is available free of charge
via the Internet at http://pubs.acs.org.
9-Bromo-10-phenylphenanthrene (3). Purification by
flash chromatography (40:1 hexane/EtOAc) afforded 86 mg
(86%) of the product as a white solid: mp 108-109 °C; 1H NMR
(CDCl3) δ 7.34-7.38 (m, 2H), 7.41-7.47 (m, 2H), 7.50-7.60
(m, 3H), 7.64-7.77 (m, 3H), 8.53-8.57 (m, 1H), 8.72-8.77 (m,
JO050104Y
J. Org. Chem, Vol. 70, No. 9, 2005 3517