Rhodium-catalyzed oxidative 1:1, 1:2, and 1:4 coupling reactions of phenylazoles with internal alkynes through the regioselective cleavages of multiple C-H bonds

Article abstract of DOI:10.1021/jo1021184

The direct oxidative coupling of phenylazoles with internal alkynes proceeds efficiently in the presence of a rhodium catalyst and a copper oxidant accompanied by double or quadruple C-H bond cleavages. Thus, as a representative example, 4,5-diphenylpyrazolo[1,5-a]quinoline, 1-(1,2,3,4- tetraphenylnaphthalen-5-yl)pyrazole, and 1-(1,2,3,4,5,6,7,8-octaphenylanthracen- 9-yl)pyrazole can be obtained selectively through the coupling of 1-phenylpyrazole and diphenylacetylene in 1:1, 1:2, and 1:4 manners, respectively. The reactions preferentially take place at the electron-deficient sites on the aromatic substrates. A comparison of reactivities of variously substituted and deuterated substrates sheds light on the mechanism of C-H bond cleavage steps. The reaction pathway is highly dependent on reaction conditions employed, especially on the nature of solvent. The influence of solvation of a key rhodacycle intermediate has been investigated computationally. In addition, some of the condensed aromatic products have been found to exhibit intense fluorescence in the solid state.

Full text of DOI:10.1021/jo1021184

pubs.acs.org/joc
Rhodium-Catalyzed Oxidative 1:1, 1:2, and 1:4 Coupling Reactions
of Phenylazoles with Internal Alkynes through the Regioselective
Cleavages of Multiple C-H Bonds
Nobuyoshi Umeda,† Koji Hirano,† Tetsuya Satoh,*,† Naoto Shibata,‡ Hirofumi Sato,*,‡
and Masahiro Miura*,†
†Department of Applied Chemistry, Faculty of Engineering, Osaka University, Suita, Osaka 565-0871,
Japan, and ‡Department of Molecular Engineering, Graduate School of Engineering, Kyoto University,
Nishikyo-ku, Kyoto 615-8510, Japan
satoh@chem.eng.osaka-u.ac.jp; hirofumi@moleng.kyoto-u.ac.jp; miura@chem.eng.osaka-u.ac.jp
Received October 26, 2010
The direct oxidative coupling of phenylazoles with internal alkynes proceeds efficiently in the
presence of a rhodium catalyst and a copper oxidant accompanied by double or quadruple C-H
bond cleavages. Thus, as a representative example, 4,5-diphenylpyrazolo[1,5-a]quinoline, 1-(1,2,3,4-
tetraphenylnaphthalen-5-yl)pyrazole, and 1-(1,2,3,4,5,6,7,8-octaphenylanthracen-9-yl)pyrazole can
be obtained selectively through the coupling of 1-phenylpyrazole and diphenylacetylene in 1:1, 1:2,
and 1:4 manners, respectively. The reactions preferentially take place at the electron-deficient sites on
the aromatic substrates. A comparison of reactivities of variously substituted and deuterated
substrates sheds light on the mechanism of C-H bond cleavage steps. The reaction pathway is
highly dependent on reaction conditions employed, especially on the nature of solvent. The influence
of solvation of a key rhodacycle intermediate has been investigated computationally. In addition,
some of the condensed aromatic products have been found to exhibit intense fluorescence in the solid
state.
Introduction
molecules (eq 1).2 Thus, the catalytic transformations of difunc-
tionalized (X ¼ H, Y ¼ H)2,3 and more readily available
monofunctionalized aromatic substrates (X ¼ H, Y = H)4 have
been developed. While a further straightforward and challenging
Selective syntheses of substituted polycyclic aromatic and
heteroaromatic compounds have become increasingly im-
portant because these reactions have been finding increasing
application as π-conjugated functional materials.1 Among
modern potential strategies to prepare condensed aromatics
is the transition-metal-promoted or -catalyzed homologa-
tion, such as benzene to naphthalene and naphthalene to
anthracene, of a given aromatic substrate with two alkyne
(2) (a) Lin, C.-H.; Lin, K.-H.; Pal, B.; Tsou, L.-D. Chem. Commun. 2009,
803. (b) Takahashi, T.; Li, S.; Huang, W.; Kong, F.; Nakajima, K.; Shen, B.;
Ohe, T.; Kanno, K.-I. J. Org. Chem. 2006, 71, 7967. (c) Takahashi, T.; Li, Y.;
Stepnicka, P.; Kitamura, M.; Liu, Y.; Nakajima, K.; Kotora, M. J. Am.
Chem. Soc. 2002, 124, 576. (d) Takahashi, T.; Kitamura, M.; Shen, B.;
Nakajima, K. J. Am. Chem. Soc. 2000, 122, 12876.
(3) X = Y = halogen: (a) Huang, W.; Zhou, X.; Kanno, K.-I.;
Takahashi, T. Org. Lett. 2004, 6, 2429. X = OTf, Y = SiMe3: (b)
Yoshikawa, E.; Radhakrishnan, K. V.; Yamamoto, Y. J. Am. Chem. Soc.
(1) Selected reviews: (a) Anthony, J. E. Angew. Chem., Int. Ed. 2008, 47,
€
452. (b) Watson, M. D.; Fethtenkotter, A.; Mullen, K. Chem. Rev. 2001, 101,
1267. (c) Mitschke, U.; Bauerle, P. J. Mater. Chem. 2000, 10, 1471. (d)
€
~ ꢀ ꢀ
2000, 122, 7280. (c) Pena, D.; Perez, D.; Guitian, E.; Castedo, L. J. Org.
~ ꢀ ꢀ
Chem. 2000, 65, 6944. (d) Pena, D.; Perez, D.; Guitian, E.; Castedo, L. J. Am.
€
~
ꢀ
Chem. Soc. 1999, 121, 5827. (e) Pena, D.; Escudero, S.; Perez, D.; Guitian, E.;
ꢀ
Harvey, R. G. Polycyclic Aromatic Hydrocarbons; Wiley-VCH: New York,
1996.
Castedo, L. Angew. Chem., Int. Ed. 1998, 37, 2659.
DOI: 10.1021/jo1021184
r
Published on Web 12/08/2010
J. Org. Chem. 2011, 76, 13–24 13
2010 American Chemical Society

Umeda et al.
JOCFeatured Article
strategy may be the coupling via double C-H bond cleavages
(X = Y = H), there has been, to our knowledge, so far no
effective catalytic example of such a homologation.5
SCHEME 1. 1:1, 1:2, and 1:4 Couplings of 1-Phenylpyrazole
with Alkynes
Meanwhile, one of the most promising methods for a
catalytic C-H bond activation is to utilize the proximate
effect by coordination of a functional group in a given
substrate to the metal center of a catalyst.6 As such examples,
we have demonstrated regioselective aromatic C-H aryla-
tion and vinylation directed by hydroxyl,4j,7 carboxyl,4g-i,8
amide,9 and imino functions10 under Pd, Rh, or Ir cata-
lysis. In the course of our further study of the directed
C-H functionalization, it has been found that phenylazoles
regioselectively couple with internal alkynes in a 1:2 manner
via double C-H bond cleavages under rhodium catalysis,
achieving the direct homologation to lead to naphthylazoles.11
Furthermore, under appropriate reaction conditions, these
substrates also underwent 1:1 and 1:4 coupling reactions selec-
tively accompanied by the cleavages of two and four C-H
bonds, respectively, to give condensed (hetero)aromatic pro-
ducts (Scheme 1). The detailed results obtained with respect to
these coupling reactions are described herein.
(4) X = CrPh2, Y = H: (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, Y = H: (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, Y = H:
(f) Yasukawa, T.; Satoh, T.; Miura, M.; Nomura, M. J. Am. Chem. Soc.
2002, 124, 12680. X = CO2H, Y = H: (g) Yamashita, M.; Horiguchi, H.;
Hirano, K.; Satoh, T.; Miura, M. J. Org. Chem. 2009, 74, 7481. (h) Yamashita,
M.; Hirano, K.; Satoh, T.; Miura, M. Org. Lett. 2009, 11, 2337. (i) Ueura, K.;
Satoh, T.; Miura, M. J. Org. Chem. 2007, 72, 5362. X = CR2OH, Y = H:
(j) Uto, T.; Shimizu, M.; Ueura, K.; Tsurugi, H.; Satoh, T.; Miura, M. J. Org.
Chem. 2008, 73, 298. X = B(OH)2, Y = H: (k) Fukutani, T.; Hirano, K.; Satoh,
T.; Miura, M. Org. Lett. 2009, 11, 5198.
Results and Discussion
(5) Coupling of benzene with alkynes using a stoichiometric amount of Pd
was reported. Naphthalene yields based on Pd were less than 20%. See ref 4e.
(6) For selected reviews concerning C-H bond functionalization, see: (a)
Colby, D. A.; Bergman, R. G.; Ellman, J. A. Chem. Rev. 2010, 110, 624. (b)
Sun, C.-L.; Li, B.-J.; Shi, Z.-J. Chem. Commun. 2010, 46, 677. (c) Chen, X.;
Engle, K. M.; Wang, D.-H.; Yu, J.-Q. Angew. Chem., Int. Ed. 2009, 48, 5094.
(d) Kitamura, T. Eur. J. Org. Chem. 2009, 1111. (e) Kakiuchi, F.; Kochi, T.
Synthesis 2008, 3013. (f) Lewis, J. C.; Bergman, R. G.; Ellman, J. A. Acc.
Chem. Res. 2008, 41, 1013. (g) Ferreira, E. M.; Zhang, H.; Stoltz, B. M.
Tetrahedron 2008, 64, 5987. (h) Park, Y. J.; Park, J.-W.; Jun, C.-H. Acc.
Chem. Res. 2008, 41, 222. (i) Herrerias, C. I.; Yao, X.; Li, Z.; Li, C.-J. Chem.
Rev. 2007, 107, 2546. (j) Alberico, D.; Scott, M. E.; Lautens, M. Chem. Rev.
2007, 107, 174. (k) Godula, K.; Sames, D. Science 2006, 312, 67. (l) Satoh, T.;
Miura, M. J. Synth. Org. Chem. 2006, 64, 1199. (m) 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. (n) Kakiuchi, F.; Chatani, N. Adv. Synth. Catal.
2003, 345, 1077. (o) Ritleng, V.; Sirlin, C.; Pfeffer, M. Chem. Rev. 2002, 102,
1731. (p) Kakiuchi, F.; Murai, S. Acc. Chem. Res. 2002, 35, 826. (q) Dyker, G.
Angew. Chem., Int. Ed. 1999, 38, 1698. (r) Kakiuchi, F.; Murai, S. Top.
Organomet. Chem. 1999, 3, 47. (s) Shilov, A. E.; Shul’pin, G. B. Chem. Rev.
1997, 97, 2879.
(7) For example, see: (a) Mochida, S.; Shimizu, M.; Hirano, K.; Satoh,
T.; Miura, M. Chem. Asian J. 2010, 5, 847. (b) Shimizu, M.; Tsurugi, H.;
Satoh, T.; Miura, M. Chem. Asian J. 2008, 3, 881. (c) Nakano, M.; Satoh, T.;
Miura, M. J. Org. Chem. 2006, 71, 8309. (d) Terao, Y.; Wakui, H.; Nomoto,
M.; Satoh, T.; Miura, M.; Nomura, M. J. Org. Chem. 2003, 68, 5236. (e)
Terao, Y.; Wakui, H.; Satoh, T.; Miura, M.; Nomura, M. J. Am. Chem. Soc.
2001, 123, 10407. (f) Nishinaka, Y.; Satoh, T.; Miura, M.; Nomura, M.;
Matsui, H.; Yamaguchi, C. Bull. Chem. Soc. Jpn. 2001, 74, 1727. (g) Satoh,
T.; Inoh, J.-I.; Kawamura, Y.; Kawamura, Y.; Miura, M.; Nomura, M. Bull.
Chem. Soc. Jpn. 1998, 71, 2239.
1:2 Coupling of Phenylazoles with Alkynes. When 1-phenyl-
pyrazole (1a) (0.5 mmol), as a typical azole, was treated with
diphenylacetylene (2a) (1 mmol) in the presence of [Cp*RhCl2]2
(0.01 mmol) and Cu(OAc)2 H2O (1 mmol) in DMF at 80 °C
3
for 6 h under N2,12 1-(1,2,3,4-tetraphenylnaphthalen-5-yl)-
pyrazole (3a) was formed as a 1:2 coupling product in 63%
yield (entry 1, Table 1). The use of an increased amount of 1a
(1 mmol) enhanced the yield to 87% (entry 2). At 60 °C, the
reaction efficiency was somewhat reduced (entry 3). Addition
of C5H2Ph4 (1,2,3,4-tetraphenyl-1,3-cyclopentadiene, 0.04
mmol) as ligand improved the yield up to 93% (entry 4).13
C5H3Ph3 (1,2,4-triphenyl-1,3-cyclopentadiene) and C5HPh5
(1,2,3,4,5-pentaphenyl-1,3-cyclopentadiene) were less effective
than C5H2Ph4 (entries 5 and 6). The reaction using
[RhCl(cod)]2 in place of [Cp*RhCl2]2 was sluggish (entry
7). [Cp*IrCl2]2 did not show any catalytic activity (entry 8).
(11) Preliminary communication: (a) Umeda, N.; Tsurugi, H.; Satoh, T.;
Miura, M. Angew. Chem., Int. Ed. 2008, 47, 4019. Later, a Pd-catalyzed
version without chelation-control was reported: (b) Wu, Y.-T.; Huang,
K.-H.; Shin,; Wu, T.-C. Chem.;Eur. J. 2008, 14, 6697.
(12) The catalyst system of Rh-complex/Cp-ligand/Cu-oxidant has been
developed for related oxidative annulation reactions by our group. See refs
4i-4k, 7a,7b, 8a,8e, 9a, 10a, and 11a. Recently, this system was successfully
employed for the oxidative coupling reactions of 2-phenylpyridines, 2-phe-
nylindoles, amides, and imines with alkynes and alkenes: (a) Hyster, T. K.;
Rovis, T. J. Am. Chem. Soc. 2010, 132, 10565. (b) Patureau, F. W.; Glorius, F.
J. Am. Chem. Soc. 2010, 132, 9982. (c) Rakshit, S.; Patureau, F. W.; Glorius, F.
J. Am. Chem. Soc. 2010, 132, 9585. (d) Morimoto, K.; Hirano, K.; Satoh, T.;
Miura, M. Org. Lett. 2010, 12, 2068. (e) Guimond, N.; Gouliaras, C.; Fagnou, K.
J. Am. Chem. Soc. 2010, 132, 6908. (f) Li, L.; Brennessel, W. W.; Jones, W. D.
Organometallics 2009, 28, 3492. (g) Guimond, N.; Fagnou, K. J. Am. Chem.
Soc. 2009, 131, 12050. (h) Li, L.; Brennessel, W. W.; Jones, W. D. J. Am. Chem.
Soc. 2008, 130, 12414. (i) Stuart, D. R.; Bertrand-Laperle, M.; Burgess, K. M. N.;
Fagnou, K. J. Am. Chem. Soc. 2008, 130, 16474.
(8) (a) Shimizu, M.; Hirano, K.; Satoh, T.; Miura, M. J. Org. Chem. 2009,
74, 3478. (b) Miyasaka, M.; Fukushima, A.; Satoh, T.; Hirano, K.; Miura,
M. Chem.;Eur. J. 2009, 15, 3674. (c) Nakano, M.; Tsurugi, H.; Satoh, T.;
Miura, M. Org. Lett. 2008, 10, 1851. (d) Maehara, A.; Tsurugi, H.; Satoh, T.;
Miura, M. Org. Lett. 2008, 10, 1159. (e) Ueura, K.; Satoh, T.; Miura, M. Org.
Lett. 2007, 9, 1407.
(9) (a) Mochida, S.; Umeda, N.; Hirano, K.; Satoh, T.; Miura, M. Chem.
Lett. 2010, 39, 744. (b) Okazawa, T.; Satoh, T.; Miura, M.; Nomura, M.
J. Am. Chem. Soc. 2002, 124, 5286. (c) Miura, M.; Tsuda, T.; Satoh, T.;
Pivsa-Art, S.; Nomura, M. J. Org. Chem. 1998, 63, 5211.
(10) (a) Fukutani, T.; Umeda, N.; Hirano, K.; Satoh, T.; Miura, M.
Chem. Commun 2009, 5141. (b) Ueura, K.; Satoh, T.; Miura, M. Org. Lett.
2005, 7, 2229.
(13) A similar effect was also observed in the reaction of triarylmethanols
with alkynes. See ref 4j.
14 J. Org. Chem. Vol. 76, No. 1, 2011

Umeda et al.
JOCFeatured Article
TABLE 2. 1:2 Coupling of Phenylazoles 1 with Alkynes 2a
TABLE 1. 1:2 Coupling of 1-Phenylpyrazole (1a) with Diphenylacety-
lene (2a)a
entry
Rh cat.
ligand
temp (°C)
yield of 3ab
1c
2
3
4
5
6
7
8
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[RhCl(cod)]2
[Cp*IrCl2]2
80
80
60
80
80
80
80
80
63
87
41
93 (93)
73
78
37
0
C5H2Ph4
C5H3Ph3
C5HPh5
C5H2Ph4
C5H2Ph4
aReaction conditions: 1a (1 mmol), 2a (1 mmol), Rh cat. (0.01 mmol),
ligand (0.04 mmol), Cu(OAc)2 H2O (1 mmol), DMF (5 mL) under N2
3
for 6 h. bGC yield based on the amount of 2a used. Value in parentheses
indicates yield after purification. c1a (0.5 mmol) was used.
Table 2 summarizes the results for the coupling employing
a number of phenylazoles and internal alkynes in the pre-
sence of the [Cp*RhCl2]2/C5H2Ph4 catalyst system. The
reactions of 1a with diarylacetylenes 2b-d proceeded effi-
ciently to produce the corresponding 1-(1,2,3,4-tetraaryl-
naphthalen-5-yl)pyrazoles 3b-d in good yields (entries 1-3).
In contrast, the reaction with 4-octyne gave only a trace
amount of coupling product. The reaction efficiency could
not be improved by using AgOAc, AgOCOCF3, and Ag2CO3
as oxidants in place of Cu(OAc)2 H2O. Meanwhile, 1-phenyl-
3
1-hexyne (2e) efficiently coupled with 1a to give 1-(1,4-dibutyl-
2,3-diphenylnaphthalen-5-yl)pyrazole (3e) predominantly,
along with a small amount of an unidentified, inseparable
isomer (entry 4). From the reaction of 1-phenyl-1- propyne (2f)
with 1a, 1-(1,4-dimethyl-2,3-diphenylnaphthalen-5-yl)pyrazole
(3f) was obtained in a moderate yield (entry 5). The couplings
of 1-(2-methylphenyl)- (1b) and 1-(3-methylphenyl)pyrazoles
(1c) with 2a took place effectively to afford 1-(6- or 7-methyl-
1,2,3,4-tetraphenylnaphthalen-5-yl)pyrazole 3g and 3h in good
yields (entries 6 and 7). While 1-(4-methylphenyl)pyrazole did
not react at all, which may be due to steric reasons, 1-(4-
fluorophenyl)pyrazole (1d) smoothly coupled with 2a within
45 min to afford product 3i in 97% isolated yield (entry 8).
1-Phenyl-3-methylpyrazole (1e) and 1-phenyl-3,5-dimethylpyr-
azole (1f) also underwent the coupling with 2a to produce the
corresponding 1-naphthylpyrazoles 3j and 3k in good yields
(entries 9 and 10). Not only phenylpyrazoles but also phenyl-
benzimidazole 1g and -pyridine 1h were found to react with2a to
give naphthylbenzimidazole 3l and naphthylpyridine 3m, respec-
tively (entries 11 and 12).
aReaction conditions: 1 (1 mmol), 2 (1 mmol), [Cp*RhCl2]2 (0.01
mmol), C5H2Ph4 (0.04 mmol), Cu(OAc)2 H2O (1 mmol), DMF (5 mL)
3
at 80 °C under N2. bGC yield based on the amount of 2 used. Value in
parentheses indicates yield after purification. cContaminated with an
isomer (3e/isomer = 94:6). d[Cp*RhCl2]2 (0.02 mmol) and C5H2Ph4
(0.08 mmol) were used.
1:4 Coupling of Phenylazoles with Alkynes. Treatment of
1-phenylpyrazoles with an excess amount of diphenylacety-
lene (2a) using the catalyst system of [Cp*RhCl2]2/C5H2Ph4/
Cu(OAc)2 H2O gave the corresponding 1:4 coupling pro-
3
ducts selectively through the cleavages of four C-H bonds.
Thus, 1a (0.125 mmol) reacted with 2a (0.5 mmol) in the
presence of [Cp*RhCl2]2 (0.01 mmol), C5H2Ph4 (0.04 mmol),
underwent the 1:4 coupling with 2a to form the correspond-
ing 1-anthrylpyrazoles 4b and 4c, respectively. Similar
anthracene derivatives were also obtained from 5-aryl-2-
phenyloxazoles 1i-m via the double homologation. Further
reaction on the aryl moiety at their 5-position of the oxazoles
could not be observed at all. Similarly, the reactions of
2-phenylbenzoxazole (1n) and 2-(4-fluorophenyl)benzoxazole
and Cu(OAc)2 H2O (0.5 mmol) at 100 °C in DMF to furnish
3
1-(1,2,3,4,5,6,7,8-octaphenylanthracen-9-yl)pyrazole (4a)
in 74% isolated yield (entry 1, Table 3). 3-Methyl-1-phenyl-
pyrazole (1e) and 3,5-dimethyl-1-phenylpyrazole (1f) also
J. Org. Chem. Vol. 76, No. 1, 2011 15

Umeda et al.
JOCFeatured Article
TABLE 3. 1:4 Coupling of Phenylazoles 1 with Alkynes 2a
aReaction conditions: 1 (0.125 mmol), 2 (0.5 mmol), [Cp*RhCl2]2 (0.01 mmol), C5H2Ph4 (0.04 mmol), Cu(OAc)2 H2O (0.5 mmol), DMF (3 mL) at
3
100 °C under N2 for 6 h. bIsolated yield based on the amount of 1 used.
(1o) with diaryacetylene 2a,d proceeded efficiently to produce
2-(1,2,3,4,5,6,7,8-octaarylanthracen-9-yl)benzoxazole deriva-
tives 4i-k.
(entry 1, Table 4). The yield of 5a decreased in n-octane, 1,4-
dioxane, and acetonitrile (entries 2-4). The desired product
5a could be obtained in a same yield in o-xylene even in the
absence of C5H2Ph4 (entry 5). In these cases, significant
amounts of a nonoxidative 1:1 coupling product, 1-[2-(1,2-
diphenylethenyl)phenyl]pyrazole (6), were also formed in
addition to 3a and 5a.14 Interestingly, addition of K2CO3
suppressed the formation of 3a and 6 completely and
slightly increased the yield of 5a (entry 6). At 150 °C, 5a
was obtained in 34% yield (entry 7). Among bases exam-
ined, Na2CO3 gave the best result to improve the yield of 5a
up to 81% (entry 11).
The thus-obtained anthrylazole derivatives 4 showed
solid-state fluorescence in a range of 470-530 nm (Figure S1,
Supporting Information). Among them, anthryloxazoles
4d-f exhibited a relatively strong emission compared to a
typical emitter, coumarin 153, by a factor of ca. 4. Moreover,
anthrylbenzoxazole 4i was found to exhibit more intense
luminescence (λemis 477 nm), and the intensity is at least
6.5 times stronger than that of coumarin 153. Remarkably,
the solid-state fluorescence quantum efficiency (Φ) of 4i
measured absolutely was 66 ( 2%.
Since nitrogen-containing polycyclic heteroaromatics
such as 5a have attracted considerable attention because
of their photochemical, electrochemical, and biological
1:1 Coupling of 1-Phenylpyrazoles with Alkynes. As de-
scribed above, the aromatic homologation selectively takes
place upon treatment of phenylpyrazoles with alkynes using
the catalyst system of [Cp*RhCl2]2/C5H2Ph4/Cu(OAc)2
(14) For recent examples of hydroarylation of alkynes, see: (a) Schipper,
D. J.; Hutchinson, M.; Fagnou, K. J. Am. Chem. Soc. 2010, 132, 6910 and
references therein. (b) Shibata, Y.; Otake, Y.; Hirano, M.; Tanaka, K. Org.
Lett. 2009, 11, 689. (c) Katagiri, T.; Mukai, T.; Satoh, T.; Hirano, K.; Miura,
M. Chem. Lett. 2009, 38, 118. (d) Mukai, T.; Hirano, K.; Satoh, T.; Miura,
M. J. Org. Chem. 2009, 74, 6410. (e) Cheng, K.; Yao, B.; Zhao, J. Org. Lett.
2008, 10, 5309. (f) Tsuchikama, K.; Kasagawa, M.; Hashimoto, Y.; Endo,
K.; Shibata, T. J. Organomet. Chem. 2008, 693, 3939. (g) Colby, D. A.;
Bergman, R. G.; Ellman, J. A. J. Am. Chem. Soc. 2008, 130, 3645. (h) Nakao,
Y.; Kanyiva, K. S.; Hiyama, T. J. Am. Chem. Soc. 2008, 130, 2448. (i) Lim,
Y.-G.; Lee, K.-H.; Koo, B. T.; Kang, J.-B. Tetrahedron Lett. 2001, 42, 7609.
See also ref 6d,6e,6p.
3
H2O in DMF. It has also been found that the reactions of
these substrates in o-xylene give considerable amounts of
1:1 coupling products, pyrazolo[1,5-a]quinolines 5, in addi-
tion to naphthalenes 3. Thus, 1-phenylpyrazole (1a) reacted
with 2a in the presence of [Cp*RhCl2]2 (0.01 mmol),
C5H2Ph4 (0.04 mmol), and Cu(OAc)2 H2O (1 mmol) at
3
80 °C in o-xylene to give 3a and 4,5-diphenylpyrazolo-
[1,5-a]quinoline (5a) in 19% and 14% yields, respectively
16 J. Org. Chem. Vol. 76, No. 1, 2011

Umeda et al.
JOCFeatured Article
TABLE 5. 1:1 Coupling of 1-Phenylpyrazoles 1 with Alkynes 2a
TABLE 4. Reaction of 1-Phenylpyrazole (1a) with Diphenylacetylene
(2a) in o-Xylenea
yieldb (%)
entry
base
solvent
temp (°C) time (h) 3a
5a
6
1c
2c
3c
4c
5
o-xylene
n-octane
1,4-dioxane
acetonitrile
o-xylene
o-xylene
o-xylene
o-xylene
o-xylene
80
80
6
6
6
6
6
6
2
2
2
2
2
19
21
39
20
11
0
14
tr
36
26
3
80
80
5
0
0
80
80
14
24
34
tr
44
0
6
K2CO3
K2CO3
Cs2CO3
Li2CO3
7
150
150
150
150
150
0
tr
tr
11
tr
tr
8
0
9
tr
6
67
52
10
11
NaHCO3 o-xyIene
Na2CO3 o-xy]ene
tr
81 (78)
aReaction conditions: 1a (1 mmol), 2a (0.5 mmol), [Cp*RhCl2]2 (0.01
mmol), Cu(OAc)2 H2O (1 mmol), base (1 mmol) in o-xylene (3 mL)
3
under N2. bGC yield based on the amount of 2a used. Value in
parentheses indicates yield after purification. c2a (1 mmol) was used in
the presence of C5H2Ph4 (0.04 mmol).
properties,15 the scope of the reaction was next explored.
Table 5 summarizes the results for the 1:1 coupling of substi-
tuted 1-phenylpyrazoles 1 with various internal alkynes 2. The
methyl-, methoxy-, and chloro-substituted diphenylacetylenes
2b-d reacted with 1a to form the corresponding pyrazoloqui-
nolines 5b-d in 56-81% yields (entries 1-3). A dialkylacety-
lene, 4-octyne (2g), also underwent the reaction with 1a to give
4,5-dipropylpyrazolo[1,5-a]quinoline (5e), albeit with a lower
yield (entry 4). From the reactions of unsymmetrical 1-phenyl-1-
hexyne (2e) and 1-phenyl-1-propyne (2f) with 1a, 5-alkyl-4-
phenylpyrazolo[1,5-a]quinolines 5f and 5g were produced pre-
dominantly along with minor amounts of their isomers (entries
5 and 6). While the reaction of 1-(2-methylphenyl)pyrazole
(1b) with 2a was somewhat sluggish (entry 7), those of 1-(3-
methylphenyl)- (1c) and 1-(4-methylphenyl)pyrazoles (1p) pro-
ceeded efficiently even under relatively mild conditions using a
half amount of Na2CO3 (0.5 mmol) at 130 °C to afford the
corresponding pyrazoloquinolines 5i and 5j, respectively
(entries 8 and 9). Under similar conditions, the reactions of
1-(4-substituted phenyl)pyrazoles 1q-s proceeded smoothly to
form 5k-m in 63-88% yields (entries 10-12).
aReaction conditions: 1 (1 mmol), 2 (0.5 mmol), [Cp*RhCl2]2 (0.01
mmol), Cu(OAc)2 H2O (1 mmol), Na2CO3 (1 mmol), o-xylene (3 mL) at
3
150 °C under N2 for 2 h. bGC yield based on the amount of 2 used. Value
in parentheses indicates yield after purification. cContaminated with an
isomer (5f/isomer = 92:8). dContaminated with an isomer (5g/isomer =
81:19). eWith Na2CO3 (0.5 mmol) at 130 °C.
with m-chloro-substituted 1t, the cyclization occurred at the
less hindered ortho-position predominantly (entry 13).
Meanwhile, m-fluoro-substituted 1u reacted at the more
hindered position to form 50o preferentially (entry 14). In
the case of m-methoxy-substituted 1v, comparable amounts
of 5p and 50p were obtained. It was reported that similar
regioselectivity was observed in the palladium-catalyzed
intramolecular arylation16 as well as the ruthenium-
catalyzed ortho-alkylation of ketones.6n,17 The reaction of
In contrast to 1c, other 1-(3-substituted phenyl)pyrazoles
1t-v reacted with 2a to give regioisomeric mixtures of the
corresponding 1:1 coupling products (5 and 50). In the case
~
(15) See, for example: (a) Abet, V.; Nunez, A.; Mendicuti, F.; Burgos, C.;
Alvarez-Builla, J. J. Org. Chem. 2008, 73, 8800. (b) Parenty, A. D. C.; Song,
Y.-F.; Richmond, C. J.; Cronin, L. Org. Lett. 2007, 9, 2253. (c) Gondek, E.;
Kityk, I. V.; Danel, A.; Wisla, A.; Sanetra, J. Synth. Met. 2006, 156, 1348. (d)
Bersuker, I. B.; Bahceci, S.; Boggs, J. E.; Pearlman, R. S. J. Comput.-Aided
Mol. Des. 1999, 13, 419. (e) Tomoda, H.; Hirano, T.; Saito, S.; Mutai, T.;
Araki, K. Bull. Chem. Soc. Jpn. 1999, 72, 1327. (f) Barrio, J. R.; Sattsangi,
P. D.; Gruber, B. A.; Dammann, L. G.; Leonard, N. J. J. Am. Chem. Soc.
1976, 98, 7408.
(16) (a) Garcia-Cuadrado, D.; de Mendoza, P.; Braga, A. A. C.; Maseras,
F.; Echavarren, A. M. J. Am. Chem. Soc. 2007, 129, 6880. (b) Garcia-
Cuadrado, D.; Braga, A. A. C.; Maseras, F.; Echavarren, A. M. J. Am.
Chem. Soc. 2006, 128, 1066.
(17) Sonoda, M.; Kakiuchi, F.; Chatani, N.; Murai, S. Bull. Chem. Soc.
Jpn. 1997, 70, 3117.
J. Org. Chem. Vol. 76, No. 1, 2011 17

Umeda et al.
JOCFeatured Article
SCHEME 2. Plausible Mechanism for the Reaction of 1a with 2
occurs via protonolysis of the C-Rh bond of B by HX to form
6.20 The latter pathway can be eliminated effectively by the
addition of a suitable base such as Na2CO3.
For providing further mechanistic information, competi-
tive reactions of (d0-phenyl)pyrazole (1a-d0) and (d5-phenyl)-
pyrazole (1a-d5) with 2a were conducted under 1:1 and 1:2
coupling conditions (see the Supporting Information). In the
early stage of these reactions, significant primary isotopic
effects of 3.4 and 4.6 were observed for the 1:1 and 1:2 cou-
plings, respectively, which suggests that the rate-determining
step in each case involves C-H(D) bond cleavage.
Jones et al. reported that a trifluoromethyl-substituted
phenylimine underwent cyclometalation by [Cp*RhCl2]2
or [Cp*IrCl2]2 10 times slower than the corresponding
methoxy-substituted one, which is consistent with an elec-
trophilic activation mechanism.12e In our case, however,
such a deactivation effect by electron-withdrawing groups
was not observed (entry 8, Table 2; entry 10, Table 3; and
entries 11-14, Table 5). Actually, the reactions involving the
cleavage of C-H bonds adjacent to a fluoro substituent
took place rather efficiently. Such substituent effects, includ-
ing the regioselectivity in the 1:1 coupling of 1-(3-substituted
phenyl)pyrazoles 1t-v with 2a (entries 13-15, Table 5), appear
to be roughly similar to those observed in cyclopalladation via a
proton-abstraction mechanism,16,21,22 rather than those in elec-
trophilic cyclorhodation and -iridation.12e,g,23
1-phenyl-3-methylpyrazole (1e) with 2a under the standard
conditions gave the corresponding pyrazoloquinoline 5q
(entry 16).
Theoretical Studies of the Metalation. As described above,
the regioselectivity of metalation of the present Rh-catalysis
is highly dependent on the nature of solvent. To shed more
light on the observation, a computational study of the
rhodacycles was carried out using RISM-SCF-SEDD, which
is a hybrid method of quantum chemistry and statistical
mechanics for molecular liquid. The method has been suc-
cessfully applied to a wide range of chemical reactions in
solution. Different from PCM, the method enables us to
explicitly treat solvent molecule. However, highly accurate
quantum chemical computation can be employed with rea-
sonable computational costs because of the analytically
described nature of RISM theory. It is our intent here to
only describe the brief summary of the theory. More lengthy
discussions of the theory can be found in the literature.24
The influence of the rhodacycle was studied with the
model system B (Scheme 2, X = Cp and OAc, R1 = R2 =
H). All of the species have been optimized at the B3LYP level
in the gas phase, and the influence of the solvent (DMF)
was considered through RISM-SCF-SEDD single-point
Reaction Mechanism. A plausible mechanism for the reac-
tion of 1a with alkyne 2, through directed metalation involving
rhodacycle intermediates A-D,18 is illustrated in Scheme 2 as
the representative (neutral ligands are omitted). In the first step,
coordination of the 2-N atom of 1a to a RhIII species appears to
be the key for the regioselective C-H bond cleavage19 to afford
A. Then, alkyne insertion into the C-Rh bond of A may occur
to form a common intermediate B. In the cases using unsym-
metrical alkynes 2e and 2f, Rh tends to add on the sp carbon
bearing a phenyl group, as in other related oxidative couplings
reported previously.4k,7b,8a,9a,10a Interaction between Rh and
the phenyl group may direct the coordination and insertion
steps of such alkynes. In DMF, B undergoes the second
cyclorhodation at the 30-position of 1-phenyl ring (path b) to
form D, and the subsequent second alkyne insertion and
reductive elimination take place to produce a 1:2 coupling
product 3. The resulting RhIX species is oxidized by the added
copper(II) salt to regenerate RhIIIX3. In the 1:4 coupling, the
second homologation may proceed by the same mechanism to
form 4. In o-xylene, on the other hand, there seem to be at least
two additional pathways from B. One of them involves C-H
bond cleavage at the 5-position of the pyrazolyl ring (path a)
forming a seven-membered rhodacycle intermediate C and the
subsequent reductive elimination to give 5. Another route
(20) A similar mechanism has been proposed for the Ru-catalyzed
coupling of 2-phenylpyridine with alkynes (see ref 14e). However, the
participation of another sequence involving oxidative addition of C-H bond
to RhI species followed by alkyne insertion into the formed Rh-H bond
cannot be excluded.
(21) Pascual, S.; de Mendoza, P.; Braga, A. A. C.; Maseras, F.; Echavarren,
A. M. Tetrahedron 2008, 64, 6021.
(18) The stoichiometric reactions of some palladacycles with alkynes to
give naphthalenes were reported: (a) Dupont, J.; Pfeffer, M.; Rotteveel,
M. A. Organometallics 1989, 8, 1116. (b) Dupont, J.; Pfeffer, M.; Daran, J.-C.;
Gouteron, J. J. Chem. Soc., Dalton Trans. 1988, 2421. (c) Reference 4d.
(19) Catalytic functionalizations involving N-directed C-H activation of
1-phenylpyrazoles have been reported. Acylation: (a) Asaumi, T.; Matsuo,
T.; Fukuyama, T.; Ie, Y.; Kakiuchi, F.; Chatani, N. J. Org. Chem. 2004, 69,
4433. (b) Asaumi, T.; Chatani, N.; Matsuo, T.; Kakiuchi, F.; Murai, S.
J. Org. Chem. 2003, 68, 7538. Arylation: (c) Oi, S.; Sakamoto, H.;
Funayama, R.; Inoue, Y. Chem. Lett. 2008, 37, 994. (d) Ackermann, L.;
Althammer, A.; Born, R. Angew. Chem., Int. Ed. 2006, 45, 2619. (e)
Shabashov, D.; Daugulis, O. Org. Lett. 2005, 7, 3657Vinylation: (f) Umeda,
N.; Hirano, K.; Satoh, T.; Miura, M. J. Org. Chem. 2009, 74, 7094.
(22) (a) Lafrance, M.; Lapointe, D.; Fagnou, K. Tetrahedron 2008, 64,
6015. (b) Gorelsky, S. I.; Lapointe, D.; Fagnou, K. J. Am. Chem. Soc. 2008,
130, 10848. (c) Lafrance, M.; Fagnou, K. J. Am. Chem. Soc. 2006, 128, 16496.
(d) Lafrance, M.; Rowley, C. N.; Woo, T. K.; Fagnou, K. J. Am. Chem. Soc.
2006, 128, 8754.
(23) Davies, D. L.; Donald, S. M. A.; Al-Duaij, O.; Macgregor, S. A.;
Polleth, M. J. Am. Chem. Soc. 2006, 128, 4210.
€
(24) (a) Continuum Solvation Models in Chemical Physics; Mennucci, B.,
Cammi, R., Eds.; John Wiley & Sons: Chichester, UK, 2007. (b) Molecular
Theory of Solvation, Understanding Chemical Reactivity; Hirata, F., Ed.:
Kluwer Academic: Dordrecht, Netherlands, 2003. (c) Computational Bio-
chemistry and Biophysics; Becker, O. M., MacKerell, A. D., Jr., Roux, B.,
Watanabe, M., Eds.; Marcel Dekker: New York, 2001.
18 J. Org. Chem. Vol. 76, No. 1, 2011

Umeda et al.
JOCFeatured Article
TABLE 6. Relative Free Energy of Each Species in Scheme 2a
hydrogen bond, but it is relatively weak because the height is
slightly lower than a typical one.25 The RDFs between the solute
Rh and solvent oxygen in B, [CpRhCl]-, and [CpRh(AcOH)]
are shown in Figure 1b. The peaks positioned around 5.5 and
6.8 A are associated to the oxygen atom of DMF. This indicates
that the Rh center of catalysis is not directly coordinated with the
oxygen of DMF in all species against our better instincts.
path a
5 þ [CpRhCl]-
þ
5 þ [CpRh-
media
B þ Cl-
0.0
0.0
AcOH
(AcOH)] þ Cl-
˚
gas (o-xylene)
DMF
-17.1
7.8
-3.3
16.1
path b
Conclusions
media
B þ C2H2 þ
3 þ [CpRhCl]-
þ
3 þ [CpRh-
We have demonstrated that multiply substituted polycyclic
aromatic and heteroaromatic compounds can be constructed
efficiently by the oxidative 1:1, 1:2, and 1:4 coupling reactions
of phenylazoles with internal alkynes in the presence of a
rhodium catalyst and a copper oxidant. Substrates bearing
electron-withdrawing groups underwent the couplings more
smoothly, which is consistent with a proton-abstraction
mechanism for the C-H bond cleavage steps by RhIII species.
A computational study has been carried out to shed further
light on the dependence of the reaction pathway on the nature
of solvent. The present procedure appears to be highly useful
for the straightforward synthesis of various functionalized
π-conjugated molecules. Actually, some of products exhibit
intense fluorescence in the solid state. Studies are underway
toward the further development of this chemistry.
Cl-
AcOH
(AcOH)] þ Cl-
gas (o-xylene)
DMF
0.0
0.0
-53.9
-27.1
-40.2
-18.7
aAll of the energies are given in kcal/mol, and the DMF energies are
obtained by GF methods.
Experimental Section
General Methods. 1H and 13C NMR spectra were recorded at
400 and 100 MHz for CDCl3 solutions. MS data were obtained
by EI. GC analysis was carried out using a silicon OV-17 column
(i.d. 2.6 mm ꢀ 1.5 m). GC-MS analysis was carried out using a
CBP-1 capillary column (i.d. 0.25 mm ꢀ 25 m). The structures
of all products listed below were unambiguously determined by
1H and 13C NMR with the aid of NOE, COSY, HMQC, and
HMBC experiments.
FIGURE 1. Radial distribution functions between (a) the nitrogen
of pyrazole and hydrogen of DMF in B (dashed line), 5 (solid line),
and 3 (dotted line) and (b) the rhodium center and oxygen site
of DMF in B (dashed line), [CpRhCl]- (solid line), and [CpRh-
(AcOH)] (dotted line).
1-Arylpyrazoles 1b-d, 1p-v, 1a-d5,26 1-methyl-2-phenylben-
zimidazole 1g,27 5-aryl-2-phenyloxazoles 1j-m,28,29 2-arylben-
zoxazole 1o,28 and diarylacetylenes 2b-d30 were prepared accor-
ding to published procedures. Other starting materials were
commercially available.
calculations on the gas-phase-optimized geometries. The
standard gas-phase computations are used as a substitute
for the reaction in o-xylene. The reaction mechanisms of
both path a and path b from B were studied. Here we briefly
summarize only the essential part of the computations, and
the full description will be reported elsewhere.
The obtained relative free energy of species B, 5, and 3 are
summarized, Table 6. This shows that both path a and path b
are exothermic in o-xylene (gas phase), but path a is endother-
mic in DMF. This is fully consistent with the experimental
results. The essential difference between the two environments
is attributed to the change in solvation free energy.
The fluorescence analysis of some products was carried out
with the samples recrystallized from hexane-toluene or hexane-
dichloromethane and then crashed.31
General Procedure for 1:2 Coupling of Phenylazoles with
Alkynes. To a 20 mL two-necked flask were added phenylazole 1
(1 mmol), internal alkyne 2 (1 mmol), [Cp*RhCl2]2 (0.01 mmol, 6.2
mg), C5H2Ph4 (0.04 mmol, 14.8 mg), Cu(OAc)2 H2O (1 mmol, 199
3
mg), dibenzyl (ca. 50 mg) as internal standard, and DMF (5 mL).
The resulting mixture was stirred under N2 at 80 °C. GC and
GC-MS analyses of the mixture confirmed formation of 3. After
cooling, the reaction mixture was poured into H2O (100 mL)
containing ethylenediamine (2 mL), extracted with dichloro-
methane (100 mL), washed with H2O (100 mL, three times), and
dried over CaCl2. The product was isolated by column chromatog-
raphy on silica gel using hexane-ethyl acetate as eluant.
In the RISM-SCF-SEDD method, the solvation structure is
described through radial distribution functions (RDFs). We
analyzed the RDFs because the first-solvation-shell effects
between solvent and the nitrogen of pyrazole and the coordina-
tion of solvent to Rh might be responsible for the product
selectivity. Since the essential differences in free energy are seen
in the products, we analyzed the reactant Band the products 5, 3,
[CpRhCl]-, and [CpRh(AcOH)]. The RDFs of species B, 5, and
3 between the solute nitrogen and solvent hydrogen atoms are
(25) Naka, K.; Sato, H.; Morita, A.; Hirata, F.; Kato, S. Theor. Chem.
Acc. 1999, 102, 165.
(26) Cristau, H.-J.; Cellier, P. P.; Spindler, J.-F.; Taillefer, M. Eur. J. Org.
Chem. 2004, 695.
(27) Debdab, M.; Mongin, F.; Bazureau, J. P. Synthesis 2006, 23, 4046.
(28) Yoshizumi, T.; Tsurugi, H.; Satoh, T.; Miura, M. Tetrahedron Lett.
2008, 49, 1598.
(29) Pippel, D. J.; Mapes, C. M.; Mani, N. S. J. Org. Chem. 2007, 72, 5828.
(30) Novak, A.; Nemes, P.; Kotschy, A. Org. Lett. 2004, 6, 4917.
(31) (a) Hirano, K.; Minakata, S.; Komatsu, M. Bull. Chem. Soc. Jpn.
2001, 74, 1567. (b) Hirano, K.; Minakata, S.; Komatsu, M.; Mizuguchi, J.
J. Phys. Chem. A 2002, 106, 4868.
˚
shown in Figure 1a. The sharp peaks around 3.0 A correspond to
hydrogen bonding between the nitrogen of pyrazole and the
˚
DMF hydrogen. The broad peak located around 6.4 A is the
hydrogen atom of DMF distant from nitrogen. This indicates
that the free nitrogen of pyrazole both in 5 and 3 forms a
J. Org. Chem. Vol. 76, No. 1, 2011 19

Umeda et al.
JOCFeatured Article
General Procedure for 1:4 Coupling of Phenylazoles with
Alkynes. To a 20 mL two-necked flask were added phenylazole
1 (0.125 mmol), internal alkyne 2 (0.5 mmol), [Cp*RhCl2]2 (0.01
(0.5 mmol), (d5-phenyl)pyrazole (1a-d5) (0.5 mmol), diphenyla-
cetylene (2a) (0.5 mmol), Cu(OAc)2-H2O (1 mmol), Na2CO3
(0.5 mmol), dibenzyl (ca. 50 mg) as internal standard, and
o-xylene (3 mL) (eq 3). The resulting mixture was stirred under
N2 at 130 °C for 15 min. After cooling, the reaction mixture was
poured into H2O (100 mL) containing ethylenediamine (2 mL),
extracted with Et2O (100 mL), washed with H2O (100 mL, three
times), and dried over Na2SO4. The product was isolated by
column chromatography on silica gel using hexane-ethyl acet-
ate (99:1) as eluant and subsequent Kugelrohr distillation (50
°C, 0.01 mmHg) to remove unreacted phenylpyrazole 1 (56.2
mg, 35%): 1H NMR (400 MHz, CDCl3) δ 6.36 (d, J = 2.2 Hz,
1H), 7.16-7.29 (m, 10H), 7.32 (t, J = 7.3 Hz, 0.77H), 7.49 (d,
J = 8.4 Hz, 0.77H), 7.65 (t, J = 7.3 Hz, 0.77H), 7.99 (d, J = 2.2
Hz, 1H), 8.68 (d, J = 8.4 Hz, 0.80H); kinetic isotope effect
determined by 1H NMR: kH/kD = 0.77/0.23 = 3.35.
mmol, 6.2 mg), C5H2Ph4 (0.04 mmol, 14.8 mg), Cu(OAc)2 H2O
3
(0.5 mmol, 100 mg), and DMF (3 mL). The resulting mixture
was stirred under N2 at 100 °C for 6 h. After cooling, the reaction
mixture was poured into H2O (100 mL) containing ethylenedia-
mine (2 mL), extracted with dichloromethane (100 mL), washed
with H2O (100 mL, three times), and dried over CaCl2. The
product 4 was isolated by thin-layer chromatography on silica
gel using hexane-ethyl acetate as eluant.
General Procedure for 1:1 Coupling of 1-Phenylpyrazoles with
Alkynes. To a 20 mL two-necked flask were added 1-phenylpyr-
azole 1 (1 mmol), internal alkyne 2 (0.5 mmol), [Cp*RhCl2]2 (0.01
mmol, 6.2 mg), Cu(OAc)2 H2O (1 mmol, 199 mg), Na2CO3
3
(1 mmol, 106 mg), dibenzyl (ca. 50 mg) as internal standard, and
o-xylene (3 mL). The resulting mixture was stirred under N2 at 150
°C. GC and GC-MS analyses of the mixture confirmed formation
of 5. After cooling, the reaction mixture was poured into H2O (100
mL) containing ethylenediamine (2 mL), extracted with dichlo-
romethane (100 mL), washed with H2O (100 mL, three times), and
dried over CaCl2. The product was isolated by column chromatog-
raphy on silica gel using hexane-ethyl acetate as eluant and
subsequent Kugelrohr distillation (50 °C, 0.01 mmHg) to remove
unreacted phenylpyrazole 1.
Synthesis of (d5-Phenyl)pyrazole (1a-d5). (d5-Phenyl)pyrazole
(1a-d5) was prepared according to the published procedure.26 To a
20 mL two-necked flask were added pyrazole (3 mmol), d5-bromo-
benzene (2 mmol), Cu2O (0.1 mmol), Cs2CO3 (4 mmol), salicylal-
doxime (0.4 mmol), and CH3CN (1.2 mL). The resulting mixture
was stirred under N2 at 65 °C for 24 h. After cooling, the reaction
mixture was poured into 1 N HCl aq (100 mL), extracted with Et2O
(100 mL), washed with H2O (100 mL), and dried over Na2SO4. The
product 1a-d5 was isolated by column chromatography on silica gel
using hexane-ethyl acetate (99:1) as eluant (179.1 mg, 60%): oil; 1H
NMR (400 MHz, CDCl3) δ 6.46 (dd, J = 1.8, 2.2 Hz, 1H), 7.73 (d,
J = 1.8 Hz, 1H), 7.92 (d, J = 2.2 Hz, 1H).
Competitive Reactions under 1:2 Coupling Conditions. To a
20 mL two-necked flask were added (d0-phenyl)pyrazole (1a-d0) (0.5
mmol), (d5-phenyl)pyrazole (1a-d5) (0.5 mmol), diphenylacetylene
(2a) (1 mmol), Cu(OAc)2-H2O (1 mmol), C5H2Ph4 (0.04 mmol),
dibenzyl (ca. 50 mg) as internal standard, and DMF (5 mL). The
resulting mixture was stirred under N2 at 80 °C for 45 min (eq 2).
After cooling, the reaction mixture was poured into H2O (100 mL)
containing ethylenediamine (2 mL), extracted with CH2Cl2 (100
mL), washed with H2O (100 mL, three times), and dried over CaCl2.
The product was isolated by column chromatography on silica gel
using hexane-ethyl acetate (9:1) as eluant (72.3 mg, 29%): 1HNMR
(400 MHz, CDCl3) δ 5.72 (dd, J = 1.8, 2.2 Hz, 1H), 6.61-6.84 (m,
15H), 7.15 (d, J = 2.2 Hz, 1H), 7.19-7.26 (m, 6H), 7.39-7.44 (m,
1.8H), 7.73-7.77 (m, 0.82H). The kinetic isotope effect was deter-
mined by 1H NMR: kH/kD = 0.82/0.18 = 4.56.
Computational Details. The calculations were performed with
the Gaussian0332 and GAMESS package33 at the B3LYP34
level. Rh was represented by the effective core potential (ECP)
from the Stuttgart group and the associated basis set.35
A
6-31G(d) basis set was used for all the atoms (C,N,O) except
for H for 6-31G basis set and for Cl for 6-31þG(d) basis set.36
The geometry optimizations were performed without any sym-
metry constraint followed by frequency calculations to confirm
that a minimum or a transition state had been reached. The
solvation effect from DMF is treated using the RISM-SCF-
SEDD37 as implemented in GAMESS modified by ourselves.
The geometries obtained in gas phase were used without further
reoptimization within the RISM-SCF-SEDD methodology,
(32) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb,
M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K. N.;
Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J. J.; Barone, V.;
Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakat-
suji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida,
M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox,
J. E.; Hratchian, H. P.; Cross, J. B.; Adamo, C.; Jaramillo, J.; Gomperts, R.;
Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.;
Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, A.; Salvador, P.;
Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain,
M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.;
Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski,
J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.;
Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.;
Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen,
W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian 03, revision D.02;
Gaussian Inc.: Wallingford, CT, 2004.
(33) Schmidt, M. W.; Baldridge, K. K.; Boatz, J. A.; Elbert, S. T.;
Gordon, M. S.; Jensen, J. H.; Koseki, S.; Matsunaga, N.; Nguyen, K. A.;
Su, S. J.; Windus, T. L.; Dupuis, M.; Montgomery, J. A. J. Comput. Chem.
1993, 14, 1347.
(34) Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B 1988, 37, 785.
(35) Andrae, D.; Haussermann, U.; Dolg, M.; Stoll, H.; Preuss, H. Theor.
Chim. Acta 1990, 77, 123.
(36) Hehre, W. J.; Ditchfield, R.; Pople, J. A. J. Chem. Phys. 1972, 56,
2257.
(37) (a) Ten-no, S.; Hirata, F.; Kato, S. J. Chem. Phys. 1994, 100, 7443. (b)
Sato, H.; Hirata, F.; Kato, S. J. Chem. Phys. 1996, 105, 1546. (c) Yokogawa,
D.; Sato, H.; Sakaki, S. J. Chem. Phys. 2007, 126, 244504.
Competitive Reactions under 1:1 Coupling Conditions. To a
20 mL two-necked flask were added (d0-phenyl)pyrazole (1a-d0)
20 J. Org. Chem. Vol. 76, No. 1, 2011

Umeda et al.
JOCFeatured Article
and the previously reported Lennard-Jones parameters were
used.38
(dd, J = 7.4, 8.4 Hz, 1H), 7.66 (d, J = 2.2 Hz, 1H), 7.72 (d, J = 1.8
Hz, 1H), 8.29 (d, J = 8.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ
16.7, 17.4, 106.5, 124.5, 125.9, 126.0, 126.9, 127.3 (overlapped),
129.1, 129.6, 130.3 (overlapped), 132.5, 134.1, 138.0, 140.1, 140.2,
141.4, 141.7, 142.6; HRMS m/z calcd for C27H22N2 (Mþ) 374.1783,
found 374.1775.
1-(1,2,3,4-Tetraphenylnaphthalen-5-yl)pyrazole (3a):11a mp
173-174 °C; 1H NMR (400 MHz, CDCl3) δ 5.72 (dd, J =
1.8, 2.2 Hz, 1H), 6.63-6.81 (m, 15H), 7.15 (d, J = 2.2 Hz, 1H),
7.22-7.26 (m, 6H), 7.41-7.42 (m, 2H), 7.74-7.77 (m, 1H); 13
C
NMR (100 MHz, CDCl3) δ 106.0, 124.8, 125.0, 125.1, 125.4,
126.2 (overlapped), 126.5, 126.6, 127.5, 127.6 (overlapped),
128.9, 131.0 (overlapped), 131.1, 131.2, 132.3, 134.3, 136.2,
137.9, 138.7, 139.4, 139.6, 139.7, 139.9, 140.2, 140.3, 142.2;
HRMS m/z calcd for C37H26N2 (Mþ) 498.2096, found
498.2091. Anal. Calcd for C37H26N2: C, 89.13; H, 5.26; N,
5.62. Found: C, 88.91; H, 5.52; N, 5.43.
1-(6-Methyl-1,2,3,4-tetraphenylnaphthalen-5-yl)pyrazole (3g).
1
mp 179 °C; H NMR (400 MHz, CDCl3) δ 1.88 (s, 3H), 5.71
(dd, J = 1.8, 2.2 Hz, 1H), 6.57-6.60 (m, 1H), 6.63-6.83 (m,
14H), 6.99 (d, J = 2.2 Hz, 1H), 7.15-7.25 (m, 6H), 7.28 (d, J =
8.8 Hz, 1H), 7.68 (d, J = 8.8 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 17.4, 105.7, 124.8, 124.9, 125.2, 125.5, 126.0, 126.1,
126.3, 126.4, 126.5 (overlapped), 127.4, 127.6, 128.1, 128.8, 128.9,
130.3, 130.8, 130.97, 130.99, 131.03, 131.06, 131.11, 131.4, 132.4,
133.0, 135.6, 136.0, 137.2, 138.5, 138.7, 139.5, 139.6, 139.8,
140.29, 140.32, 142.4; HRMS m/z calcd for C38H28N2 (Mþ)
512.2252, found 512.2254.
1-[1,2,3,4-Tetrakis-(4-methylphenyl)naphthalen-5-yl]pyrazole
(3b):11a mp 130-132 °C; 1H NMR (400 MHz, CDCl3) δ 2.06 (s,
3H), 2.08 (s, 3H), 2.09 (s, 3H), 2.31(s, 3H), 5.71(t, J = 2.2 Hz,
1H), 6.48-6.65 (m, 12H), 7.05-7.08 (m, 5H), 7.21-7.22 (m,
1H), 7.35-7.36 (m, 2H), 7.69-7.73 (m, 1H); 13C NMR (100
MHz, CDCl3) δ 20.96, 21.00, 21.04, 21.2, 105.6, 124.4, 126.7,
126.9, 127.2, 127.3, 127.7, 128.3, 128.8, 130.8 (overlapped),
131.0, 131.1, 132.3, 134.06, 134.10, 134.4, 134.5, 135.8, 136.1,
136.7, 136.8, 137.3, 137.5, 137.9, 138.5, 139.6, 139.9, 142.3;
HRMS m/z calcd for C41H34N2 (Mþ) 554.2722, found 554.2719.
1-[1,2,3,4-Tetrakis-(4-methoxyphenyl)naphthalen-5-yl]pyrazole
(3c):11a mp 107-110 °C; 1H NMR (400 MHz, CDCl3) δ 3.58 (s,
3H), 3.61 (s, 3H), 3.65 (s, 3H), 3.79 (s, 3H), 5.77 (dd, J = 1.8, 2.2
Hz, 1H), 6.32 (d, J = 8.8 Hz, 2H), 6.34 (d, J = 8.8 Hz, 2H), 6.40
(d, J = 8.8 Hz, 2H), 6.50 (d, J = 8.8 Hz, 2H), 6.63-6.67 (m, 2H),
6.68 (d, J = 8.8 Hz, 2H), 6.79 (d, J = 8.8 Hz, 2H), 7.08-7.10 (m,
2H), 7.12 (d, J = 2.2 Hz, 1H), 7.24 (d, J = 1.8 Hz, 1H), 7.37-7.39
(m, 2H), 7.73-7.76 (m, 1H); 13C NMR(100 MHz, CDCl3) δ54.8,
54.9, 55.09, 55.12, 105.8, 111,85, 111.91, 112.1 (overlapped),
113.1, 124.5, 127.3, 127.6, 128.8, 131.9, 132.06, 132.14, 132.26,
132.30, 132.4, 132.9, 133.1, 134.7, 135.8, 137.8, 138.5, 139.8,
140.0, 142.3, 156.8, 156.9 (overlapped), 158.0; HRMS m/z calcd
for C41H34N2O4 (Mþ) 618.2519, found 618.2516.
1-(7-Methyl-1,2,3,4-tetraphenylnaphthalen-5-yl)pyrazole (3h).
1
mp 227-228 °C; H NMR (400 MHz, CDCl3) δ 2.39 (s, 3H),
5.70 (d, J = 1.8, 2.2 Hz, 1H), 6.61-6.64 (m, 2H), 6.72-6.84 (m,
13H), 7.12 (d, J = 2.2 Hz, 1H), 7.16-7.29 (m, 7H), 7.51 (s, 1H);
13C NMR (100 MHz, CDCl3) δ 21.3, 105.9, 125.0, 125.3, 125.6,
126.2, 126.47, 126.50, 127.6 (overlapped), 127.8, 129.7, 131.0
(overlapped), 131.2, 131.3, 132.3, 134.4, 134.7, 135.9, 137.7,
138.1, 139.5, 139.7, 139.76, 139.79, 140.3, 140.5, 141.2; HRMS
m/z calcd for C38H28N2 (Mþ) 512.2252, found 512.2247.
1-(8-Fluoro-1,2,3,4-tetraphenylnaphthalen-5-yl)pyrazole (3i).
1
mp 123-126 °C; H NMR (400 MHz, CDCl3) δ 5.72 (d, J =
2.2 Hz, 1H), 6.61-6.82 (m, 15H), 7.05-7.19 (m, 7H), 7.22 (d,
J = 1.8 Hz, 1H), 7.34 (m, 1H); 13C NMR (100 MHz, CDCl3) δ
106.2, 110.7 (d, J = 24.5 Hz), 123.7 (d, J = 8.4 Hz), 124.9 (d, J =
9.9 Hz), 125.2, 125.3, 125.4, 126.1, 126.26, 126.30, 126.4, 126.8,
127.6 (d, J = 9.9 Hz), 129.8, 129.9, 130.9, 131.0, 132.3, 134.3,
135.1 (d, J = 2.3 Hz), 136.5 (d, J = 2.3 Hz), 138.9, 139.5, 139.7,
140.0, 141.4, 141.5 (d, J = 22.9 Hz), 143.1 (d, J = 2.3 Hz), 160.5
(d, J = 261 Hz); HRMS m/z calcd for C37H25FN2 (Mþ)
516.2002, found 516.1996.
1-[1,2,3,4-Tetrakis-(4-chlorophenyl)naphthalen-5-yl]pyrazole
1
(3d):11a mp 282-283 °C; H NMR (400 MHz, CDCl3) δ 5.86
3-Methyl-1-(1,2,3,4-tetraphenylnaphthalen-5-yl)pyrazole (3j):11a
mp169-170 °C; 1H NMR (400 MHz, CDCl3) δ 2.05 (s, 3H), 5.46
(d, J = 2.2 Hz, 1H), 6.56-6.81 (m, 15H), 7.09 (d, J = 2.6 Hz, 1H),
7.18-7.24 (m, 5H), 7.38-7.40(m, 2H), 7.70-7.73 (m, 1H); 13C
NMR (100 MHz, CDCl3) δ 13.3, 105.6, 124.7, 124.97, 124.99,
125.3, 125.5, 126.2, 126.5, 126.6, 127.1, 127.6 (overlapped), 127.8,
128.7, 131.0 (overlapped), 131.2, 132.5, 134.4, 136.3, 138.0, 138.6,
139.5, 139.6, 139.7, 140.2, 140.4, 142.0, 148,9; HRMS m/z calcd for
C38H28N2 (Mþ) 512.2252, found 512.2244. Anal. Calcd for
C38H28N2: C, 89.03; H, 5.51; N, 5.46. Found: C, 89.07; H, 5.65;
N, 5.37.
3,5-Dimethyl-1-(1,2,3,4-tetraphenylnaphthalen-5-yl)pyrazole
(3k):11a mp 201 °C; 1H NMR (400 MHz, CDCl3) δ 2.01 (s, 3H),
2.02 (s, 3H), 5.18 (s, 1H), 6.50-6.52 (m, 1H), 6.70-6.86 (m,
14H), 7.20-7.29 (m, 6H), 7.39-7.43 (m, 1H), 7.72-7.74 (m,
1H); 13C NMR (100 MHz, CDCl3) δ 12.1, 13.3, 105.2, 124.7,
125.0, 125.07, 125.10, 125.28, 125.30, 126.1, 126.2, 126.4, 126.5,
126.6, 127.5, 127.6, 128.0, 128.8, 129.5, 130.8, 130.9, 130.98,
131.00, 131.3, 131.4, 131.5, 134.4, 136.4, 138.6, 139.1, 139.60,
139.64, 140.0, 140.3, 140.4, 142.1, 148.1; HRMS m/z calcd for
C39H30N2 (Mþ) 526.2409, found 526.2406. Anal. Calcd for
C39H30N2: C, 88.94; H, 5.74; N, 5.32. Found: C, 88.87; H, 5.98;
N, 4.93.
(dd, J = 1.8, 2.2 Hz, 1H), 6.49-6.56 (m, 2H), 6.65-6.71 (m,
4H), 6.76-6.83 (m, 4H), 6.88-6.90 (m, 2H), 7.09-7.11 (m,
2H), 7.15 (d, J = 1.8 Hz, 1H), 7.25-7.28 (m, 3H), 7.41-7.48
(m, 2H), 7.67-7.69 (m, 1H); 13C NMR (100 MHz, CDCl3) δ
106.3, 125.5, 126.2, 126.6, 127.0, 127.3, 127.8, 128.1, 128.2,
128.7, 131.3, 131.4, 131.7, 131.9 (overlapped), 132.0, 132.1,
132.2, 133.1, 134.2, 135.6, 137.4, 137.8, 137.9, 138.00, 138.03,
138.3, 140.3, 140.6; HRMS m/z calcd for C37H22Cl4N2 (Mþ)
634.0537, found 634.0544. Anal. Calcd for C37H22Cl4N2: C,
69.83; H, 3.48; N, 4.40. Found: C, 69.87; H, 3.57; N, 4.39.
1-(1,4-Dibutyl-2,3-diphenylnaphthalen-5-yl)pyrazole (3e):11a
1
oil; H NMR (400 MHz, CDCl3) δ 0.48 (t, J = 7.3 Hz, 3H),
0.69-0.79 (m, 5H), 1.02-1.10 (m, 2H), 1.20-1.29 (m, 2H),
1.54-1.59 (m, 3H), 1.90 (s, br, 1H), 2.84 (t, J = 8.1 Hz, 2H), 6.44
(t, J = 2.2 Hz, 1H), 6.92-7.12 (m, 10H), 7.40 (d, J = 7.1 Hz,
1H), 7.53 (d, J = 7.3 Hz,1H), 7.72(d, J = 2.2 Hz, 1H), 7.73 (d,
J = 2.2 Hz, 1H), 8.28 (d, J = 8.8 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 13.5, 13.6, 22.6, 23.1, 30.2, 30.4, 33.3, 35.4, 106.4,
124.2, 125.7, 125.9, 126.9, 127.1 (overlapped), 127.2, 128.2,
130.0 (overlapped), 131.9, 133.8, 134.6, 134.7, 137.9, 140.1,
140.2, 141.3, 141.5, 142.3; HRMS m/z calcd for C33H34N2
(Mþ) 458.2722, found.458.2718.
1-(1,4-Dimethyl-2,3-diphenylnaphthalen-5-yl)pyrazole (3f):11a oil;
1H NMR (400 MHz, CDCl3) δ 1.60 (s, 3H), 2.49 (s, 3H), 6.45 (dd,
J= 1.8, 2.2 Hz, 1H), 6.91-7.15 (m, 10H), 7.51 (d, J= 7.4, 1H), 7.58
1-Methyl-2-(1,2,3,4-tetraphenylnaphthalen-5-yl)benzimidazole
(3l):11a mp 198-199 °C; 1H NMR (400 MHz, CDCl3) δ 3.40 (s,
3H), 6.24-6.28 (m, 1H), 6.30-6.34 (m,1H), 6.59-6.63 (m, 2H),
6.68-6.94 (m, 12H), 7.10-7.13 (m, 2H), 7.18-7.22 (m, 2H),
7.24-7.27 (m, 3H), 7.44-7.53 (m, 3H), 7.80-7.83 (m, 1H); 13
C
(38) (a) Jorgenson, W. L.; Swenson, C. J. J. Am. Chem. Soc. 1985, 107,
569. (b) Sato, H.; Hirata, F. J. Phys. Chem. 2002, 106, 2300. (c) Rappe, A. K.;
Casewit, C. J.; Colwell, K. S.; Goddard, W. A., III; Skiff, W. M. J. Am.
Chem. Soc. 1992, 114, 10024.
NMR (100 MHz, CDCl3) δ 30.9, 108.6, 119.2, 121.5, 121.8,
124.5, 124.7, 124.8, 125.1, 125.4, 125.7, 126.1, 126.35, 126.42,
126.57, 126.61, 127.5, 127.7, 128.4, 129.0, 129.8, 130.8, 131.0,
J. Org. Chem. Vol. 76, No. 1, 2011 21

Umeda et al.
JOCFeatured Article
131.08, 131.11, 131.2, 131.25, 131.33, 131.5, 132.5, 133.4, 134.9,
137.7, 138.7, 138.9, 139.6, 139.6, 140.3, 140.4, 141.7, 142.8, 154.2;
HRMS m/z calcd for C42H30N2 (Mþ) 562.2409, found 562.2407.
2-(1,2,3,4-Tetraphenylnaphthalen-5-yl)pyridine (3m): mp 107-
109 °C; 1H NMR (400 MHz, CDCl3) δ 6.62-6.80 (m, 16H), 6.93
(d, J = 7.7 Hz, 1H), 7.14-7.23 (m, 6H), 7.39 (d, J = 5.5 Hz, 2H),
7.70 (dd, J = 4.8, 5.2Hz, 1H), 8.23 (d, J =4.8 Hz, 1H); 13C NMR
(100 MHz, CDCl3) δ 120.1, 124.7, 124.9, 125.1, 125.2 (over-
lapped), 126.1, 126.35, 126.42, 127.43, 128.0, 130.0, 130.7, 131.0
(overlapped), 131.4, 131.9, 132.9, 133.7, 134.9, 137.8, 138.6,
139.1, 139.9, 140.1, 140.5, 140.6, 140.8, 141.1, 148.1, 161.8;
HRMS m/z calcd for C39H27N (Mþ) 509.2143, found 509.2148.
1-(1,2,3,4,5,6,7,8-Octaphenylanthlacen-9-yl)pyrazole (4a):
mp >300 °C; 1H NMR (400 MHz, CDCl3) δ 4.64 (t, J = 1.8 Hz,
1H), 6.46-6.54 (m, 4H), 6.55-6.65 (m, 8H), 6.66-6.86 (m, 20H),
125.0, 125.1, 125.3, 125.5, 125.6, 125.65, 125.69, 125.9, 126.0,
126.1, 126.3, 126.5, 127.2, 128.1, 128.6, 128.8, 130.2, 130.3,
130.8, 131.0, 131.1, 131.3, 131.9, 132.0, 133.9, 136.9, 138.4,
138.5, 139.0, 139.2, 140.4, 140.6, 142.6, 149.6, 158.9; HRMS
m/z calcd for C75H49NO (Mþ) 979.3814, found 979.3808.
5-(4-Methoxyphenyl)-2-(1,2,3,4,5,6,7,8-octaphenylanthracen-
9-yl)oxazole (4g): mp 199-200 °C; 1H NMR (400 MHz, CDCl3)
δ 3.83 (s, 3H), 5.95 (s, 1H), 6.47 (t, J = 7.0 Hz, 3H), 6.52-6.59
(m, 6H), 6.63-6.72 (m, 10H), 6.74-6.85 (m, 13H), 6.98-7.07
(m, 12H), 8.07 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 55.2,
113.7, 121.7, 122.2, 124.6, 124.8, 125.3, 125.80, 125.83, 126.1,
126.2, 126.5, 127.2, 130.2, 130.5, 130.9, 131.0, 131.1, 131.2,
131.98, 132.02, 137.0, 138.3, 138.5, 139.0, 139.1, 140.4, 140.7,
142.5, 150.7, 158.1, 158.8; HRMS m/z calcd for C72H49NO2
(Mþ) 959.3763, found 959.3773.
2-(1,2,3,4,5,6,7,8-Octaphenylanthracen-9-yl)-5-(4-trifluoro-
methylphenyl)oxazole (4h): mp >300 °C; 1H NMR (400 MHz,
CDCl3) δ 6.20 (s, 1H), 6.45 (t, J = 7.0 Hz, 3H), 6.50-6.60 (m,
6H), 6.62-6.72 (m, 10H), 6.75-6.83 (m, 11H), 6.98-7.07 (m,
10H), 7.17 (d, J = 8.1 Hz, 2H), 7.54 (d, J = 8.1 Hz, 2H), 8.10
(s, 1H); 13C NMR (100 MHz, CDCl3) δ 121.7, 124.1 (d, J =
270 Hz), 124.2, 124.7, 124.9, 125.2, 125.3 (d, J = 3.8 Hz),
125.4, 125.8, 126.2, 126.3, 126.5, 127.2, 128.9 (d, J = 32.6 Hz),
130.6, 130.8, 131.0, 131.1, 131.2, 131.87, 131.92, 132.0, 136.7,
138.4, 138.6, 138.9, 139.2, 140.3, 140.5, 142.8, 149.3, 160.0;
HRMS m/z calcd for C72H46F3NO (Mþ) 997.3531, found
997.3557.
6.94-7.06 (m, 8H), 7.09 (d, J = 7.4 Hz, 2H), 8.03 (s, 1H); 13
C
NMR (100 MHz, CDCl3) δ 105.2, 124.6, 124.8, 124.9, 125.3,
126.0, 126.1, 126.15, 126.20, 126.5, 127.1, 127.3, 129.0, 129.1,
130.7, 130.8, 130.9, 131.0, 131.1, 131.2, 131.7, 133.2, 135.6, 135.8,
138.4, 139.0, 139.3, 140.3, 140.49, 140.52, 142.7; HRMSm/z calcd
for C65H44N2 (Mþ)852.3504, found 852.3520.
3-Methyl-1-(1,2,3,4,5,6,7,8-octaphenylanthlacen-9-yl)pyrazole
(4b): mp >300 °C; 1H NMR (400 MHz, CDCl3) δ 1.78 (s, 3H),
4.34 (d, J = 2.2 Hz, 1H), 6.50-6.60 (m, 7H), 6.61-6.84 (m,
24H), 6.95-7.04 (m, 8H), 7.07 (d, J = 7.3 Hz, 2H), 7.98 (s, 1H);
13C NMR (100 MHz, CDCl3) δ 13.2, 105.2, 124.5, 124.78,
124.80, 125.1, 125.3, 126.0, 126.16, 126.19, 126.5 (overlapped),
127.1, 127.2, 128.7, 129.0, 130.8, 130.96, 130.98, 131.2 131.5,
131.8, 133.3, 135.8, 136.5, 138.3, 139.0, 139.2, 140.4, 140.6, 142.5,
149.0; HRMS m/z calcd for C66H46N2 (Mþ)866.3661, found
866.3649. Anal. Calcd for C66H46N2: C, 91.42; H, 5.35; N, 3.23.
Found: C, 91.33; H, 5.38; N, 3.32.
2-(1,2,3,4,5,6,7,8-Octaphenylanthlacen-9-yl)benzoxazole (4i):11a
mp >300 °C; 1H NMR (400 MHz, CDCl3) δ 6.11 (t, J = 7.7 Hz,
2H), 6.28 (dd, J = 7.7, 8.0 Hz, 4H), 6.54-6.56 (m, 4H), 6.63 (d,
J = 8.4 Hz, 4H), 6.67-6.68 (m, 6H), 6.73-6.82 (m, 11H),
6.89-6.94 (m, 2H), 6.97-7.06 (m, 11H), 8.11 (s, 1H); 13C NMR
(100 MHz, CDCl3) δ 110.6, 119.7, 121.8, 122.9, 123.7, 124.1, 125.0,
125.1, 125.4, 126.2, 126.3, 126.6, 127.3, 130.6, 131.0, 131.1, 131.2,
131.3, 131.7, 131.8, 136.9, 138.51, 138.53, 138.6, 139.0, 140.4, 140.6,
141.4, 142.9, 149.8, 161.3; HRMS m/z calcd for C69H45NO (Mþ)
903.3501, found 903.3499.
2-(10-Fluoro-1,2,3,4,5,6,7,8-octaphenylanthracen-9-yl)benzo-
xazole (4j): mp >300 °C; 1H NMR (400 MHz, CDCl3) δ 6.16 (t,
J = 7.3 Hz, 2H), 6.30 (dd, J = 7.7, 8.0 Hz, 4H), 6.49 (d, J = 7.7
Hz, 4H), 6.59-6.70 (m, 14H), 6.79-6.83 (m, 7H), 6.92-7.04 (m,
13H); 13C NMR (100 MHz, CDCl3) δ 110.5, 117.6 (d, J = 6.9
Hz), 119.7, 119.9 (d, J = 9.2 Hz), 123.1, 124.0, 124.5, 125.1,
125.27, 125.34, 125.8, 126.3, 126.5, 126.8, 129.8, 129.9, 130.7,
131.1, 131.8, 133.48, 133.51, 134.6, 136.6, 138,3, 139.7, 140.1,
140.3, 141.37, 141.40 (d, J = 5.4 Hz), 142.9, 149.8, 158.0 (d, J =
276 Hz), 161.1; HRMS m/z calcd for C69H44FNO (Mþ)
921.3407, found 921.3431.
3,5-Dimethyl-1-(1,2,3,4,5,6,7,8-octaphenylanthlacen-9-yl)-
1
pyrazole (4c): mp >300 °C; H NMR (400 MHz, CDCl3) δ
1.64 (s, 3H), 1.83 (s, 3H), 4.16 (s, 1H), 6.46-6.84 (m, 30H),
6.93-7.03 (m, 8H), 7.04-7.09 (m, 2H), 7.97 (s, 1H); 13C NMR
(100 MHz, CDCl3) δ 22.6, 31.6, 106.2, 124.5, 124.6, 124.8, 124.9,
125.3, 126.0, 126.2, 126.5, 127.1, 127.2, 128.4, 129.1, 129.9,
130.95, 130.96, 130.98, 131.2, 131.5, 131.8, 131.9, 135.7, 138.3,
138.35, 138.37, 139.0, 140.4, 140.6, 142.1, 142.7, 148.6; HRMS
m/z calcd for C67H48N2 (Mþ) 880.3817, found 880.3824.
2-(1,2,3,4,5,6,7,8-Octaphenylanthracen-9-yl)-5-phenyloxazole
(4d): mp >300 °C; 1H NMR (400 MHz, CDCl3) δ 6.16 (s, 1H),
6.45-6.48 (m, 2H), 6.51-6.56 (m, 6H), 6.62-6.70 (m, 10H),
6.75-6.81 (m, 11H), 6.98-7.10 (m, 13H), 7.18-7.22 (m, 1H),
7.24-7.29 (m, 2H), 8.08 (s, 1H); 13C NMR (100 MHz, CDCl3) δ
122.20, 122.22, 123.5, 124.3, 124.6, 124.8, 125.3, 125.8, 126.1,
126.2, 126.5, 127.16, 127.21, 128.2, 128.7, 130.3, 130.9, 131.0,
131.1, 131.2, 131.97, 131.99, 137.0 (overlapped), 138.3, 138.5,
139.0, 139.1, 140.4, 140.6, 142.6, 150.7, 158.8; ESI-MS m/z calcd
for C71H47NO (M þ H) 930.3736, found 930.3703.
2-[1,2,3,4,5,6,7,8-Octakis-(4-chlorophenyl)anthracen-9-yl]benzo-
xazole (4k): mp >300 °C; 1H NMR (400 MHz, CDCl3) δ 6.34 (d,
J = 8.1 Hz, 4H), 6.45 (d, J= 8.4 Hz, 4H), 6.51 (d, J= 8.4 Hz, 4H),
6.66 (d, J = 8.4 Hz, 4H), 6.75 (d, J = 8.4 Hz, 4H), 6.88 (d, J = 8.4
5-(2-Methylphenyl)-2-(1,2,3,4,5,6,7,8-octaphenylanthracen-9-
1
yl)oxazole (4e): mp >300 °C; H NMR (400 MHz, CDCl3) δ
Hz, 4H), 6.92-6.94 (m, 5H), 7.10-7.18 (m, 7H), 7.89 (s, 1H); 13
C
2.08 (s, 3H), 6.08 (s, 1H), 6.41 (t, J = 7.3 Hz, 2H), 6.48-6.58 (m,
7H), 6.64-6.72 (m, 10H), 6.75-6.83 (m, 11H), 6.98-7.07 (m,
10H), 7.10-7.13 (m, 2H), 7.14-7.19 (m, 1H), 7.35 (d, J = 7.7
Hz, 1H), 8.08 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 22.2,
122.2, 124.7, 124.8, 125.3, 125.5, 125.8, 126.1, 126.2, 126.3,
126.5, 126.79, 126.82, 127.2, 127.6, 130.3, 130.6, 130.9, 131.0,
131.1, 131.2, 131.9, 132.0, 133.7, 137.0, 138.3, 138.5, 139.0,
139.1, 140.4, 140.6, 142.6, 149.9, 158.1; HRMS m/z calcd for
C72H49NO (Mþ) 943.3814, found 943.3820.
5-(Naphthalen-1-yl)-2-(1,2,3,4,5,6,7,8-octaphenylanthracen-
9-yl)oxazole (4f:). mp >300 °C; 1H NMR (400 MHz, CDCl3) δ
6.35 (s, 1H), 6.40 (t, J = 7.3 Hz, 2H), 6.47-6.57 (m, 7H),
6.65-6.84 (m, 21H), 6.98-7.09 (m, 10H), 7.39 (d, J = 6.2 Hz,
2H), 7.43-7.49 (m, 3H), 7.82-7.86 (m, 1H), 7.89-7.94 (m,
1H), 8.10 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 122.0, 124.8,
NMR (100 MHz, CDCl3) δ110.3, 119.5, 122.2, 124.3, 125.5, 125.9,
127.1, 127.5, 127.9, 130.4, 131.1, 131.45, 131.54, 131.7, 131.82,
131.84, 132.1, 132.3, 132.4, 133.4, 136.28, 136.33, 136.5, 137.5,
137.8, 137.9, 138.0, 140.7, 141.8, 149.5, 160.4; ESI-MS m/z calcd
for C69H37Cl8NO (M þ H) 1176.0461, found 1176.0431. Anal.
Calcd for C69H37Cl8NO: C, 70.25; H, 3.16; N, 1.19. Found: C,
69.86; H, 3.35; N, 1.37.
4,5-Diphenylpyrazolo[1,5-a]quinoline (5a): mp 214 °C; 1H NMR
(400 MHz, CDCl3) δ 6.37 (d, J = 2.2 Hz, 1H), 7.17-7.30 (m,
10H), 7.34 (t, J = 7.5, 8.0 Hz,1H), 7.50 (d, J = 8.0 Hz, 1H), 7.67
(dd, J = 7.5, 8.0 Hz, 1H), 8.00 (d, J = 2.2 Hz, 1H), 8.69 (d, J = 8.4
Hz, 1H); 13C NMR (100 MHz, CDCl3) δ101.0, 115.4, 124.1, 124.6,
127.3, 127.4, 127.9, 128.0 (overlapped), 129.00, 129.03, 130.0,
131.1, 134.0, 134.2, 136.8, 137.0, 139.2, 141.2; HRMS m/z calcd
for C23H16N2 (Mþ) 320.1313, found 320.1311. Anal. Calcd for
22 J. Org. Chem. Vol. 76, No. 1, 2011

Umeda et al.
JOCFeatured Article
C23H16N2: C, 86.22; H, 5.03; N, 8.74. Found: C, 86.04; H, 4.99;
N, 8.79.
7.98 (d, J = 2.2 Hz, 1H), 8.51 (s, 1H); 13C NMR (100 MHz,
CDCl3) δ 21.7, 100.7, 115.3, 121.8, 126.1, 127.17, 127.23, 127.8,
127.88, 127.90, 127.91, 130.1, 131.1, 133.9, 134.0, 136.9, 137.1,
139.3, 139.7, 141.1; HRMS m/z calcd for C24H18N2 (Mþ)
334.1470, found 334.1475.
4,5-Bis(4-methylphenyl)pyrazolo[1,5-a]quinoline (5b): mp 141
°C; 1H NMR (400 MHz, CDCl3) δ 2.31 (s, 3H), 2.35 (s, 3H), 6.36
(d, J = 1.8 Hz, 1H), 7.04-7.13 (m, 8H), 7.32 (dd, J = 7.0, 8,4
Hz, 1H), 7.49 (d, J = 8.1 Hz, 1H), 7.64 (dd, J = 6.4, 7.0 Hz, 1H),
7.98 (d, J = 2.2 Hz, 1H), 8.66 (d, J = 8.4 Hz, 1H); 13C NMR
(100 MHz, CDCl3) δ 21.2, 21.3, 100.9, 115.4, 124.42, 124.44,
128.0, 128.7 (overlapped), 128.8, 129.0, 129.9, 131.0, 133.8,
133.9, 134.1, 134.2, 136.8, 136.9, 139.5, 141.1; HRMS m/z calcd
for C25H20N2 (Mþ) 348.1626, found 348.1628.
4,5-Bis(4-methoxyphenyl)pyrazolo[1,5-a]quinoline (5c): mp
163-165 °C; 1H NMR (400 MHz, CDCl3) δ 3.78 (s, 3H), 3.81 (s,
3H), 6.38 (d, J= 1.8 Hz, 1H), 6.79 (d, J= 8.8 Hz, 2H), 6.84 (d, J=
8.8 Hz, 2H), 7.09 (d, J= 8.8 Hz, 2H), 7.15 (d, J= 8.8 Hz, 2H), 7.33
(dd, J = 7.0, 8.4 Hz, 1H), 7.53 (d, J = 8.1 Hz, 1H), 7.64 (dd, J =
7.0, 7.9 Hz, 1H), 7.99 (d, J = 1.8 Hz, 1H), 8.66 (d, J = 8.4 Hz,
1H); 13C NMR (100 MHz, CDCl3) δ 55.1, 55.2, 100.9, 113.47,
113.51, 115.4, 124.46, 124.52, 127.9, 128.75, 128.81, 129.1, 129.5,
131.2, 132.2 (overlapped), 133.6, 134.1, 139.6, 141.1, 158.7;
HRMS m/z calcd for C25H20N2O2 (Mþ) 380.1525, found
380.1534.
4,5-Diphenyl-7-methylpyrazolo[1,5-a]quinoline (5j): mp 219
1
°C; H NMR (400 MHz, CDCl3) δ 2.38 (s, 3H), 6.34 (d, J =
2.2 Hz, 1H), 7.15-7.31 (m, 11H), 7.49 (dd, J = 1.8, 8.4 Hz, 1H),
7.97 (d, J = 2.2 Hz, 1H), 8.57 (d, J = 8.4 Hz, 1H); 13C NMR
(100 MHz, CDCl3) δ 21.4, 100.7, 115.3, 124.1, 127.2, 127.3,
127.4, 127.90, 127.91, 129.0, 130.0, 130.4, 131.1, 132.3, 133.8,
134.2, 136.9, 137.1, 138.9, 140.9; HRMS m/z calcd for C24H18N2
(Mþ) 334.1470, found 334.1464.
4,5-Diphenyl-7-methoxypyrazolo[1,5-a]quinoline (5k): mp
199-201 °C; 1H NMR (400 MHz, CDCl3) δ 3.73 (s, 3H), 6.34
(d, J = 2.2 Hz, 1H), 6.92 (d, J = 2.9 Hz, 1H), 7.17-7.31 (m,
11H), 7.95 (d, J = 2.2 Hz, 1H), 8.61 (d, J = 9.5 Hz, 1H); 13C NMR
(100 MHz, CDCl3) δ 55.5, 100.7, 110.1, 116.8, 117.4, 125.3, 127.32,
127.33, 127.9, 128.0, 129.1, 129.5, 130.0, 131.0, 133.6, 136.8, 137.1,
138.5, 140.6, 156.5; HRMS m/z calcd for C24H18N2O (Mþ)
350.1419, found 350.1423. Anal. Calcd for C24H18N2O: C, 82.26;
H, 5.18; N, 7.99. Found: C, 82.04; H, 5.14; N, 7.93.
7-Chloro-4,5-diphenylpyrazolo[1,5-a]quinoline (5l): mp 205-206
4,5-Bis(4-chlorophenyl)pyrazolo[1,5-a]quinoline (5d): mp 160
1
1
°C; H NMR (400 MHz, CDCl3) δ 6.38 (d, J = 2.2 Hz, 1H),
°C; H NMR (400 MHz, CDCl3) δ 6.34 (d, J = 2.2 Hz, 1H),
7.15-7.18 (m, 2H), 7.19-7.27 (m, 5H), 7.28-7.34 (m, 3H), 7.46
(d, J = 2.2 Hz, 1H), 7.61 (dd, J = 2.2, 9.2 Hz, 1H), 7.99 (d, J = 2.2
Hz, 1H), 8.63 (d, J = 8.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ
101.4, 117.0, 125.4, 127.1, 127.58, 127.61, 128.0, 128.2, 129.2, 129.9,
130.26, 130.32, 131.0, 132.6, 133.1, 136.0, 136.6, 139.1, 141.5;
HRMS m/z calcd for C23H15ClN2 (Mþ) 354.0924, found 354.0920.
4,5-Diphenyl-7-trifluoromethylpyrazolo[1,5-a]quinoline (5m):
mp 171 °C; 1H NMR (400 MHz, CDCl3) δ 6.42 (d, J = 2.2 Hz,
1H), 7.16-7.19 (m, 2H), 7.20-7.28 (m, 5H), 7.29-7.35 (m, 3H),
7.79 (d, J = 2.2 Hz, 1H), 7.89 (dd, J = 2.2, 8.8 Hz, 1H), 8.05 (d,
J = 2.2 Hz, 1H), 8.79 (d, J = 8.8 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 101.8, 116.3, 123.9, 124.1 (q, J = 273 Hz), 125.3 (q, J =
4.6 Hz), 125.4 (q, J = 1.5 Hz), 126.7 (q, J = 33 Hz), 127.7, 127.8,
128.1, 128.3, 129.8, 130.5, 131.0, 133.7, 135.72 (q, J = 4.6 Hz),
135.73 (q, J = 1.5 Hz), 136.5, 139.7, 142.2; HRMS m/z calcd for
C24H15F3N2 (Mþ) 388.1187, found 388.1190. Anal. Calcd for
C24H15F3N2: C, 74.22; H, 3.89; N, 7.21. Found: C, 74.03; H,
3.81; N, 7.12.
8-Chloro-4,5-diphenylpyrazolo[1,5-a]quinoline (5n): mp 184-
186 °C; 1H NMR (400 MHz, CDCl3) δ 6.37 (d, J = 2.2 Hz, 1H),
7.13-7.31 (m, 11H), 7.41 (d, J = 8.8 Hz, 1H), 7.99 (d, J = 2.2 Hz,
1H), 8.69 (d, J = 2.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ
101.3, 115.4, 122.6, 125.1, 127.47, 127.50, 128.0, 128.1, 129.2, 129.3,
129.9, 131.0, 133.5, 134.5, 135.1, 136.3, 136.6, 139.4, 141.7; HRMS
m/z calcd for C23H15ClN2 (Mþ) 354.0924, found 354.0922.
4,5-Diphenyl-6-fluoropyrazolo[1,5-a]quinoline (50o): mp 165-
167 °C; 1H NMR (400 MHz, CDCl3) δ 6.27 (d, J = 2.2 Hz, 1H),
7.00 (dd, J = 8.1, 12.4 Hz, 1H), 7.13-7.23 (m, 10H), 7.58 (dt,
J = 5.1, 8.1 Hz, 1H), 7.97 (d, J = 2.2 Hz, 1H), 8.52 (d, J = 8.8
Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 101.5, 111.6 (d, J = 22.9
Hz), 111.7 (d, J = 3.8 Hz), 113.5 (d, J = 11.5 Hz), 126.8, 127.2,
127.3, 127.8, 129.6 (d, J = 10.0 Hz), 129.8, 129.85, 120.91, 130.3,
130.5 (d, J = 26.7 Hz), 135.4 (d, J = 26.7 Hz), 136.4, 138.6 (d, J =
4.6 Hz), 139.2, 141.7, 150.8 (d, J = 257 Hz); HRMS m/z calcd for
C23H15FN2 (Mþ) 338.1219, found 338.1222.
7.10-7.17 (m, 4H), 7.24-7.28 (m, 2H), 7.29-7.33 (m, 2H), 7.36
(d, J = 7.5, 7.7 Hz, 1H), 7.44 (d, J = 8.0 Hz, 1H), 7.69 (t, J = 7.7
Hz, 1H), 8.01 (d, J = 2.2 Hz, 1H), 8.68 (d, J = 8.4 Hz, 1H); 13
C
NMR (100 MHz, CDCl3) δ 101.0, 115.6, 123.7, 124.8, 127.6,
128.0, 128.51, 128.53, 129.4, 131.3, 132.3, 133.0, 133.6, 133.7,
134.2, 135.0, 135.2, 138.7, 141.4; HRMS m/z calcd for
C23H14Cl2N2 (Mþ) 388.0534, found 388.0529.
4,5-Dipropylpyrazolo[1,5-a]quinoline (5e): oil; 1H NMR (400
MHz, CDCl3) δ 1.05-1.12 (m, 6H), 1.66-1.74 (m, 4H), 2.85 (t,
J = 6.1 Hz, 2H), 2.95 (t, J = 6.1 Hz, 2H), 6.54 (d, J = 2.2 Hz,
1H), 7.44 (t, J = 7.0 Hz, 1H), 7.60 (t, J = 7.0 Hz, 1H), 7.88 (d,
J = 8.4 Hz, 1H), 7.96 (d, J = 2.2 Hz, 1H), 8.59 (d, J = 8.4 Hz,
1H); 13C NMR (100 MHz, CDCl3) δ 14.50, 14.52, 23.0, 23.9,
29.8, 32.1, 98.2, 115.8, 123.5, 124.4, 124.9, 127.4, 127.9, 131.3,
134.0, 139.4, 140.9; HRMS m/z calcd for C17H20N2 (Mþ)
252.1626, found 252.1621.
5-Butyl-4-phenylpyrazolo[1,5-a]quinoline (5f): oil; 1H NMR
(400 MHz, CDCl3) δ 0.82 (t, J = 7.9 Hz, 3H), 1.23-1.34 (m,
2H), 1.54-1.63 (m, 2H), 2.81 (t, J = 8.3 Hz, 2H), 6.07 (d, J = 2.2
Hz, 1H), 7.36-7.39 (m, 2H), 7.42-7.53 (m, 4H), 7.67 (t, J = 7.4
Hz, 1H), 7.89 (d, J = 1.8 Hz, 1H), 7.96 (d, J = 8.4 Hz, 1H), 8.66
(d, J = 8.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 13.7, 22.9,
28.4, 33.0, 100.1, 115.9, 123.2, 124.6, 125.6, 127.8, 128.6, 128.7,
128.8, 129.4, 132.5, 134.5, 137.6, 139.7, 140.9; HRMS m/z calcd
for C21H20N2 (Mþ) 300.1626, found 300.1636.
5-Methyl-4-phenylpyrazolo[1,5-a]quinoline (5g): oil; 1H NMR
(400 MHz, CDCl3) δ 2.33 (s, 3H), 6.06 (d, J = 2.2 Hz, 1H),
7.29-7.43 (m, 6H), 7.56-7.60 (m, 1H), 7.81 (d, J = 1.8 Hz, 1H),
7.85 (d, J = 8.1 Hz, 1H), 8.55 (d, J = 8.4 Hz, 1H); 13C NMR (100
MHz, CDCl3) δ15.4, 100.0, 115.6, 124.2, 124.6, 125.4, 127.5, 127.7,
127.9, 128.5, 128.8, 129.7, 134.1, 137.6, 139.5, 140.9; HRMS m/z
calcd for C18H14N2 (Mþ) 258.1157, found 258.1147.
4,5-Diphenyl-9-methylpyrazolo[1,5-a]quinoline (5h): mp 174-
175 °C; 1H NMR (400 MHz, CDCl3) δ 3.24 (s, 3H), 6.32 (d, J =
2.2 Hz, 1H), 7.13-7.30 (m, 11H), 7.33 (d, J = 8.0 Hz, 1H), 7.44
(d, J = 7.3 Hz, 1H), 7.98 (d, J = 2.2 Hz, 1H); 13C NMR (100
MHz, CDCl3) δ 25.1, 100.0, 123.8, 125.8, 126.1, 127.1, 127.2,
127.88, 127.91, 128.3, 129.0, 130.0, 131.0, 132.5, 133.6, 134.4,
137.2, 137.5, 140.1, 140.5; HRMS m/z calcd for C24H18N2 (Mþ)
334.1470, found 334.1467. Anal. Calcd for C24H18N2: C, 86.20;
H, 5.43; N, 8.38. Found: C, 86.06; H, 5.45; N, 8.30.
4,5-Diphenyl-8-methoxypyrazolo[1,5-a]quinoline (5p): mp
1
195 °C; H NMR (400 MHz, CDCl3) δ 4.02 (s, 3H), 6.36 (d,
J = 2.2 Hz, 1H), 6.94 (dd, J = 2.6, 9.2 Hz, 1H), 7.15-7.19
(m, 2H), 7.20-7.24 (m, 5H), 7.25-7.29 (m, 3H), 7.40 (d, J = 9.2
Hz, 1H), 8.00 (d, J = 2.2 Hz, 1H), 8.12 (d, J = 2.6 Hz, 1H);
13C NMR (100 MHz, CDCl3) δ 55.8, 97.1, 100.5, 114.7, 117.9,
126.3, 127.15, 127.20, 127.88, 127.90, 129.4, 130.2, 131.1, 134.0,
135.3, 136.9, 137.1, 139.7, 141.3, 160.6; HRMS m/z calcd for
C24H18N2O (Mþ) 350.1419, found 350.1418.
4,5-Diphenyl-8-methylpyrazolo[1,5-a]quinoline (5i): mp 190-
1
192 °C; H NMR (400 MHz, CDCl3) δ 2.57 (s, 3H), 6.35 (d,
J = 2.2 Hz, 1H), 7.13-7.30 (m, 11H), 7.38 (d, J = 8.4 Hz, 1H),
J. Org. Chem. Vol. 76, No. 1, 2011 23

Umeda et al.
6.93-6.96 (m, 2H), 7.01-7.13 (m, 8H), 7.38-7.48 (m, 6H); 13
NMR (100 MHz, CDCl3) δ 106.2, 126.7, 126.9, 127.1, 127.8,
127.9, 128.1, 128.4, 129.3, 129.5, 130.7, 130.8, 131.6, 137.1,
139.0, 139.2, 139.95, 139.99, 140.1; HRMS m/z calcd for
C23H18N2 (Mþ) 322.1470, found 322.1464.
JOCFeatured Article
4,5-Diphenyl-6-methoxypyrazolo[1,5-a]quinoline (50p): mp
C
1
181 °C; H NMR (400 MHz, CDCl3) δ 3.38 (s, 3H), 6.20 (d,
J = 2.2 Hz, 1H), 6.81 (d, J = 8.4 Hz, 1H), 7.05-7.20 (m, 10H),
7.61 (t, J = 8.4 Hz, 1H), 7.96 (d, J = 2.2 Hz, 1H), 8.36 (d,
J = 8.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 55.8, 100.6,
107.2, 108.5, 114.3, 125.7, 126.5, 127.0, 127.7, 129.4, 129.7,
129.8, 130.2, 132.6, 135.6, 137.2, 139.2, 140.9, 141.4, 158.0;
HRMS m/z calcd for C24H18N2O (Mþ) 350.1419, found
350.1417.
Acknowledgment. We thank Prof. Dr. N. Tohnai, Osaka
University, for measurement of fluorescence quantum effi-
ciency. N.S. and H.S. are grateful to Prof. Shigeyoshi Sakaki,
Drs. Daisuke Yokogawa, and Yu-ya Onishi for helpful
discussions. 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.
2-Methyl-4,5-diphenylpyrazolo[1,5-a]quinoline (5q): mp 168-
169 °C; 1H NMR (400 MHz, CDCl3) δ 2.52 (s, 3H), 6.15 (s, 1H),
7.16-7.31 (m, 11H), 7.47 (d, J = 8.4 Hz,1H), 7.63 (t, J = 7.7 Hz,
1H), 8.61 (d, J = 8.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ
14.1, 100.6, 115.2, 123.7, 124.0, 127.2, 127.3, 127.87, 127.90,
127.91, 128.6, 128.9, 130.0, 131.1, 133.9, 134.0, 136.9, 137.2,
140.1, 151.2; HRMS m/z calcd for C24H18N2 (Mþ) 334.1470,
found 334.1480.
Supporting Information Available: Characterization data of
products. This material is available free of charge via the
Internet at http://pubs.acs.org.
1-[2-(1,2-Diphenylvinyl)phenyl]pyrazole (6): oil; 1H NMR
(400 MHz, CDCl3) δ 6.11 (t, J = 2.2 Hz, 1H), 6.65 (s, 1H),
24 J. Org. Chem. Vol. 76, No. 1, 2011