Unexpected domino reaction via Pd-catalyzed Sonogashira coupling of benzimidoyl chlorides with 1,6-enynes and cyclization to synthesize quinoline derivatives

Article abstract of DOI:10.1021/jo9026116

(Chemical Equation Presented) A domino reaction via palladium-catalyzed Sonogashira coupling of benzimidoyl chlorides with 1,6-enynes and then cyclization to form quinoline derivatives has been developed. The reaction conditions and the scope of the process are examined, and a plausible mechanism is proposed. The procedure is simple, rapid, and general, and the substrates are readily available. 2010 American Chemical Society.

Full text of DOI:10.1021/jo9026116

pubs.acs.org/joc
5
6
7
€
Miller, the Conrad-Limpach, the Friedlander, the Pfitzin-
ger,8 and other9 reactions have been frequently employed in
the synthesis of quinoline alkaloids. However, some of these
methods usually suffered from relatively low yields, poor
regioselectivity, and rather tedious reaction procedure.
Therefore, the development of mild and simple approaches
to quinoline derivatives is still desired because of their
extreme significance. The cyclization of aryl-substituted
alkynes via intramolecular hydroarylation has proven to be
an efficient method for the construction of carbocycles and
heterocycles.10 Recently, considerable methods have been
directed toward the synthesis of quinolines. For example,
quinolines have been prepared via Rh,11 Ni,10b Ru,12 Au,13
and other metals14 catalyzed reactions. In our ongoing
efforts to explore mild and efficient methodologies for the
synthesis of heterocyclic compounds promoted by transi-
tion-metal catalysts,15 we initially envisioned that reaction of
benzimidoyl chlorides (1a) with (1-(allyloxy)prop-2-ynyl)-
benzene (2a) via palladium-catalyzed Sonogashira coupling
reaction could afford alkynyl amidine (4a). To our delight,
more valuable functionalized quinoline (3a) was obtained
rather than simple coupling product (Scheme 1). Herein, we
wish to report this convenient synthetic approach to substi-
tuted quinolines by utilizing a Pd-catalyzed tandem process.
Our preliminary studies focused on the reaction of N-
phenylbenzimidoyl chloride (1a) with (1-(allyloxy)prop-2-
Unexpected Domino Reaction via Pd-Catalyzed
Sonogashira Coupling of Benzimidoyl Chlorides with
1,6-Enynes and Cyclization To Synthesize Quinoline
Derivatives
Guo-Lin Gao,† Yan-Ning Niu,† Ze-Yi Yan,‡
Hong-Li Wang,† Gang-Wei Wang,† Ali Shaukat,† and
Yong-Min Liang*,†
†State Key Laboratory of Applied Organic Chemistry,
Lanzhou University, Lanzhou 730000, People’s Republic of
China, and ‡Laboratory of Radiochemistry, Lanzhou
University, Lanzhou 730000, People’s Republic of China
liangym@lzu.edu.cn
Received December 9, 2009
A domino reaction via palladium-catalyzed Sonogashira
coupling of benzimidoyl chlorides with 1,6-enynes and
then cyclization to form quinoline derivatives has been
developed. The reaction conditions and the scope of the
process are examined, and a plausible mechanism is
proposed. The procedure is simple, rapid, and general,
and the substrates are readily available.
€
(7) (a) For recent quinoline synthesis via the Friedlander reaction, see:
Marco-Contelles, J.; Perez-Mayoral, E.; Samadi, A.; Carreiras, M. C.;
ꢀ
Soriano, E. Chem. Rev. 2009, 109, 2652. (b) Sridharan, V.; Ribelles, P.;
ꢀ
Ramos, M. T.; Menendez, J. C. J. Org. Chem. 2009, 74, 5715.
(8) (a) Pfitzinger, W. J. Prakt. Chem. 1886, 33, 100.
(9) For selected papers, see: (a) Hosokawa, T.; Matsumura, A.; Katagiri,
T.; Uneyama, K. J. Org. Chem. 2008, 73, 1468. (b) Zhao, Y.-L.; Zhang, W.;
Wang, S.; Liu, Q. J. Org. Chem. 2007, 72, 4985. (c) Zhang, Q.; Zhang, Z.;
Yan, Z.; Liu, Q.; Wang, T. Org. Lett. 2007, 9, 3651. (d) Sandelier, M. J.;
DeShong, P. Org. Lett. 2007, 9, 3209. (e) Tiano, M.; Belmont, P. J. Org.
Chem. 2008, 73, 4101.
(10) For selected papers, see: (a) Shen, R.; Huang, X.; Chen, L. Adv.
Synth. Catal. 2008, 350, 1275. (b) Korivi, R. P.; Cheng, C.-H. J. Org. Chem.
2006, 71, 7079. (c) Sromek, A. W.; Rheingold, A. L.; Wink, D. J.; Gevorgyan,
Quinolines and their derivatives are well-known as imp-
ortant natural alkaloids which often endowed with many
pharmacological properties.1 They also occupied a central
role in many medicinally relevant compounds.2 The synthe-
sis of quinolines and their derivatives has been extensively
developed for more than 100 years since the discovery of
quinoline by Gerhardt in 1842.3 The Skraup,4 the Doebner-
€
V. Synlett 2006, 14, 2325. (d) D’Souza, D. M.; Rominger, F.; Muller, T. J. J.
Angew. Chem., Int. Ed. 2005, 44, 153. (e) Kel’in, A. V.; Sromek, A. W.;
Gevorgyan, V. J. Am. Chem. Soc. 2001, 123, 2074.
(11) For selected papers, see: (a) Berman, A. M.; Lewis, J. C.; Bergman,
R. G.; Ellman, J. A. J. Am. Chem. Soc. 2008, 130, 14926. (b) Horn, J.;
Marsden, S. P.; Nelson, A.; House, D.; Weingarten, G. G. Org. Lett. 2008,
10, 4117.
(12) (a) Arisawa, M.; Nishida, A.; Nakagawa, M. J. Organomet. Chem.
2006, 691, 5109. (b) Movassaghi, M.; Hill, M. D. J. Am. Chem. Soc. 2006,
128, 4592.
(1) For selected papers, see: (a) Natarajan, J. K.; Alumasa, J. N.; Yearick,
K.; Ekoue-Kovi, K. A.; Casabianca, L. B.; de Dios, A. C.; Wolf, C.; Roepe,
P. D. J. Med. Chem. 2008, 51, 3466. (b) Theeraladanon, C.; Arisawa, M.;
Nakagawa, M.; Nisshida, A. Tetrahedron: Asymmetry 2005, 16, 827.
(c) Bray, P. G.; Ward, S. A.; O’Neill, P. M. Curr. Top. Microbiol. 2005,
295, 3. (d) Sawada, Y.; Kayakiri, H.; Abe, Y.; Imai, K.; Katayama, A.; Oku,
T.; Tanaka, H. J. Med. Chem. 2004, 47, 1617. (e) Strekowski, L.; Say, M.;
Henary, M.; Ruiz, P.; Manzel, L.; Macfarlane, D. E.; Bojarski, A. J. J. Med.
Chem. 2003, 46, 1242. (f) Michael, J. P. Nat. Prod. Rep. 2007, 24, 223.
(2) Carey, J. S.; Laffan, D.; Thomson, C.; Williams, M. T. Org. Biomol.
Chem. 2006, 4, 2337.
(13) Liu, X.-Y.; Che, C.-M. Angew. Chem., Int. Ed. 2008, 47, 3805.
(14) For selected papers, see: (a) Zhang, Z.; Tan, J.; Wang, Z. Org. Lett.
2008, 10, 173. (b) Sakai, N.; Annaka, K.; Fujita, A.; Sato, A.; Konakahara,
T. J. Org. Chem. 2008, 73, 4160. (c) Arcadi, A.; Aschi, M.; Marinelli, F.;
Verdecchia, M. Tetrahedron 2008, 64, 5354. (d) Li, L.; Jones, W. D. J. Am.
Chem. Soc. 2007, 129, 10707. (e) Gabriele, B.; Mancuso, R.; Salerno, G.;
Ruffolo, G.; Plastina, P. J. Org. Chem. 2007, 72, 6873. (f) Sakai, N.; Annaka,
K.; Konakahara, T. J. Org. Chem. 2006, 71, 3653. (g) Godet, T.; Belmont, P.
Synlett 2008, 2513.
(3) Manske, R. H. F. Chem. Rev. 1942, 30, 13.
(15) (a) Niu, Y.-N.; Yan, Z.-Y.; Gao, G.-L.; Wang, H.-L.; Shu, X.-Z.; Ji,
K.-G.; Liang, Y.-M. J. Org. Chem. 2009, 74, 2893. (b) Lu, L.; Liu, X.-Y.; Shu,
X.-Z.; Yang, K.; Ji, K.-G.; Liang, Y.-M. J. Org. Chem. 2009, 74, 474. (c) Shu,
X.-Z.; Liu, X.-Y.; Ji, K.-G.; Xiao, H.-Q.; Liang, Y.-M. Chem.;Eur. J. 2008,
14, 5282. (d) Ji, K.-G.; Shen, Y.-W.; Shu, X.-Z.; Xiao, H.-Q.; Bian, Y.-J.;
Liang, Y.-M. Adv. Synth. Catal. 2008, 350, 1275. (e) Zhao, L.-B.; Guan, Z.-
H.; Han, Y.; Xie, Y.-X.; He, S.; Liang, Y.-M. J. Org. Chem. 2007, 72, 10276.
(f) Shu, X.-Z.; Liu, X.-Y.; Xiao, H.-Q.; Ji, K.-G.; Guo, L.-N.; Qi, C.-Z.;
Liang, Y.-M. Adv. Synth. Catal. 2007, 349, 2493.
(4) For selected papers, see: (a) Ranu, B. C.; Hajra, A.; Dey, S. S.; Jana, U.
Tetrahedron2003, 59, 813. (b) Skraup, H. Ber. Dtsch. Chem. Ges. 1880, 13, 2086.
(5) For selected papers, see: (a) Tanaka, S.-Y.; Yasuda, M.; Baba, A. J.
Org. Chem. 2006, 71, 800. (b) Denmark, S. E.; Venkatraman, S. J. Org. Chem.
2006, 71, 1668. (c) Doebner, O.; von Miller, W. Ber. Dtsch. Chem. Ges. 1881,
14, 2812.
(6) Steck, E. A.; Hallock, L. L.; Holland, A. J.; Fletcher, L. T. J. Am.
Chem. Soc. 1948, 70, 1012.
DOI: 10.1021/jo9026116
r
Published on Web 01/20/2010
J. Org. Chem. 2010, 75, 1305–1308 1305
2010 American Chemical Society

Gao et al.
JOCNote
SCHEME 1
TABLE 2. Pd-Catalyzed Synthesis of Substituted of Quinoline 3a
TABLE 1. Optimization of the Reaction Conditions Base on the
Synthesis of 3a from 1a and 2aa
substrate
entry
1
R1
R2
2
R3
yield (%)
1
2
3
4
5
6
7
8
9
1a
1b 4-OMe Ph
H
Ph
2a Ph
85 (3a)
87 (3b)
83 (3c)
76 (3d) b
76 (3e)
70 (3f)
68 (3g) c
80 (3h)
62 (3i)
2a Ph
2a Ph
2a Ph
2a Ph
2a Ph
2a Ph
1c 4-Me
1d 3-Me
1e 2-Me
1f 4-Cl
1g 3-Cl
Ph
Ph
Ph
Ph
Ph
temp time yield
(%)
entry
catalyst
PdCl2, CuI
Pd2(dba)3, CuI
Pd(PPh3)2Cl2, CuI Et3N
Pd(PPh3)4, CuI Et3N
Pd(PPh3)2Cl2, CuI Et2NH
Pd(PPh3)2Cl2, CuI THF
Pd(PPh3)2Cl2, CuI THF
Pd(PPh3)2Cl2, CuI THF
Pd(PPh3)2Cl2, CuI THF
Pd(PPh3)2Cl2, CuI THF
Pd(PPh3)2Cl2, CuI toluene Et3N
Pd(PPh3)2Cl2, CuI CH3CN Et3N
Pd(PPh3)2Cl2, CuI DMF
Pd(PPh3)2Cl2, CuI Et3N
Pd(PPh3)2Cl2, CuI Et3N
Pd(PPh3)2Cl2, CuI Et3N
solvent
base
Et3N
Et3N
Et3N
Et3N
Et2NH
Cs2CO3
NaOAc
Na2CO3
K3PO4
Et3N
(°C)
(h)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
Et3N
Et3N
80
80
80
80
80
80
80
80
80
80
80
80
80
rt
7
7
7
7
7
7
7
7
7
7
7
7
7
10
8
52
63b
85
60
45
49
67
47
70
67
35
52
29
52
73
58
1h
1i
H
H
H
H
H
H
H
H
4-MeC6H4 2a Ph
4-ClC6H4 2a Ph
10 1a
11 1a
12 1a
13 1a
14 1a
15 1a
Ph
Ph
Ph
Ph
Ph
Ph
2b 5-benzo[d] [1,3]dioxole 90 (3j)
2c 4-OMeC6H4
2d 2-OMeC6H4
2e 4-MeC6H4
2f 3-MeC6H4
2g 4-ClC6H4
86 (3k)
70 (3l)
83 (3m)
63 (3n)
mixture
aUnless indicated otherwise, all the reactions were carried out under
Ar atmosphere using 1 (0.30 mmol), 2 (0.33 mmol), Pd(PPh3)Cl2
(0.015 mmol), CuI 0.0075 mmol in 3.0 mL of anhydrous Et3N at
80 °C for 7 h. bOnly one product (5-methyl-2-phenylquinolin-4-yl)-
(phenyl)methanone was isolated. cOnly one product (5-chloro-2-phe-
nylquinolin-4-yl)(phenyl)methanone was isolated.
Et3N
Et3N
Et3N
Et3N
60
100
5
With the optimized conditions in hand, the scope of this
Pd-catalyzed domino reaction was further investigated, and
the results are summarized in Table 2. As depicted in Table 2,
for all the tested substrates, good results have also been
obtained. First of all, using (1-(allyloxy)prop-2-ynyl)benz-
ene (2a), we examined the effect of various substituents on
the N-aryl moiety. In contrast, introducing an electron-
withdrawing -Cl group on the N-aromatic ring apparently
lowered the yield, no matter substituents appeared in para or
meta positions (Table 2, entries 6 and 7). It is noteworthy that
when the imidoyl chloride 1d and 1g bearing meta substitu-
ents on the N-aryl fragment, were used as the starting
substrates, only a unique product was isolated in each case
in moderate yield, which were confirmed as (5-methyl-2-
phenylquinolin-4-yl)(phenyl)methanone (3d) and (5-chloro-
2-phenylquinolin-4-yl)(phenyl)methanone (3g), respectively
(Table 2, entries 4 and 7). The presence of substituents at the
ortho position of the N-aryl fragment did not hinder the
reaction. Thus, quinoline 3e could be synthesized in a
moderate (76%) yield by the coupling and cyclization of
imidoyl chloride 1e with 1,6-enyne 2a (Table 2, entry 5). The
effect of R2 substitution on the CdN double bond has also
been examined. An evident electronic effect was observed.
Substrates with an electron-donating R2 group showed
better results than those with an electron-withdrawing R2
group (1h vs 1i) (Table 2, entries 8 and 9).
aUnless otherwise specified, the reaction was carried out in Ar atmo-
sphere using 1a (0.30 mmol), 2a (0.33 mmol), Pd catalysts (0.015 mmol),
and CuI (0.0075 mmol). If the base is a solid, 0.9 mmol of the base and
3.0 mL of the solvent were added. If a liquid base is used, 1.0 mL of base and
2.0 mL of the solvents were added. DMF = dimethylformamide. dba =
1,5-diphenylpenta-1E,4E-dien-3-one. b0.0075 mmol of Pd2(dba)3 was used.
ynyl)benzene (2a) in the presence of 5 mol % of PdCl2 and
2.5 mol % of CuI in Et3N at 80 °C. The unexpected quinoline
product 3a was isolated in 52% yield after 7 h (Table 1, entry
1). This inspirited us to examine optimal reaction conditions
for the coupling and cyclization of 1a with 2a in order to
obtain more satisfied results. Subsequently, different palla-
dium species such as Pd2(dba)3, Pd(PPh3)2Cl2, and Pd(PPh3)4
were also tested (Table1, entries 2-4). Pd(PPh3)2Cl2
proved to be the more efficient catalyst in this reaction.
Other common bases used in this reaction such as Et2NH,
Cs2CO3, NaOAc, Na2CO3, and K3PO4 were effective as well,
although lower yields were obtained (Table 1, entries 5-9).
This indicated that base played an important role in this
process. The effect of the solvent was also investigated.
Changing the solvent to THF, toluene, CH3CN, and DMF
failed to improve the yield of the product 3a (Table 1, entries
10-13). Further investigation revealed that temperature was
also a key factor in this domino reaction. When the reaction
was run at room temperature, the product 3a was obtained in
52% yield even though the reaction was prolonged to 10 h
(Table 1, entry 14). When the temperature was increased to
60 °C, more satisfied result was obtained (Table 1, entry 15).
Further increasing the temperature to 100 °C, a lower yield of
58% was observed (Table 1, entry 16). Thus, we chose the
following reaction conditions as optimum for all subsequent
cyclization: 0.3 mmol of 1a, 0.33 mmol of 2a, 0.015 mmol
Pd(PPh3)2Cl2, and 0.0075 mmol of CuI in 3.0 mL of Et3N
were stirred at 80 °C for 7 h.
We continued to elucidate the scope of the reaction by
examining the effect of various R3 substituents. When the
phenyl is replaced with benzo[d][1,3]dioxole at the R3 posi-
tion, the reaction proceeds smoothly to give the correspond-
ing products in excellent yield (Table 2, entry 10). When there
is only one electron-donating substituent attached to the
phenyl ring at the para position, the cyclization affords the
corresponding quinoline derivatives in similar yields
1306 J. Org. Chem. Vol. 75, No. 4, 2010

Gao et al.
JOCNote
TABLE 3. Pd-Catalyzed Coupling of 1a with Other 1,6-Enynesa
SCHEME 2
aAll of the reactions were carried out in Ar atmosphere using 1
(0.30 mmol), 2 (0.33 mmol), Pd(PPh3)Cl2 (0.015 mmol), and CuI
(0.0075 mmol) in 3.0 mL of anhydrous Et3N at 80 °C for 7 h. Flash
chromatography was carried out on Al2O3.
SCHEME 3. Plausible Mechanism for the Formation of Qui-
nolines
(Table 2, entries 11 and 13). However, the presence of
substituents at both the meta and ortho positions of the
phenyl ring clearly hampered the reaction (Table 2, entries 12
and 14). Further, when R3 was phenyl with an electron-
withdrawing group, a rather intractable complex reaction
mixture was detected (Table 2, entry 15). The structures of all
these products (3) were confirmed with the help of spectral
and analytical data, and the structure of 3c was further
established by X-ray diffraction analysis (see the Supporting
Information).
by a 6π-electrocyclization18 to form quinoline intermediate
B; (iv) subsequently, activation of the allyl moiety of quino-
line B by Pd species generates intermediate C; (v) and
removal of an allyl palladium complex D from C form the
final product 3 and the complex D lost a molecule of
propylene and regenerate the Pd(0) catalyst.19 However, at
lower temperature, we observed that the intermediate B
underwent a [1, 3]-H shift to form the product 5, which
was in good agreement with the previous result.10c We
assumed that at low temperature Pd species did not effec-
tively activate allyl moiety of quinoline B. Because the allyl
palladium intermediate was an excellent leaving group at
moderate temperature, enol activated by Pd species lost an
allyl group from the proposed intermediate B and conse-
quently converted into the ketones 3.
In summary, we have described a mild and efficient
approach for the synthesis of substituted quinoline via Pd-
catalyzed reaction of benzimidoyl chlorides with 1,6-enynes.
This Pd-catalyzed reaction is simple, and the reaction pro-
ceeds smoothly in moderate to good yields. Further applica-
tion of the methodology to synthesize some natural alkaloids
and pharmaceutical compounds is in progress in our labora-
tory.
Furthermore, to expand the scope of this reaction, we also
introduced hydrogen atom or alkyl group at the R3 position
(2h-j); no expected quinoline product was formed under the
optimized conditions, and only the Sonogashira coupling
product was isolated (Table 3, entries 1-3).
To have a more insight into the reaction, we also per-
formed the following reactions as shown in Scheme 2. The
reaction of 1a with 2c at room temperature gave 5a in 85%
yield. When 5a was treated with 5 mol % of Pd(PPh3)Cl2 and
2.5 mol % of CuI in 3.0 mL of Et3N at 80 °C, no desired
product 3l was observed. When the reaction temperature was
further increased to 100 °C, the compound 5a could be still
recovered. We reasoned that the allyl in product 5a is not a
good leaving group in palladium-catalyzed allylations; thus,
5a could not be transformed into 3l. On the other hand, when
1a and 2k were also treated under the optimized conditions,
no 3a was observed, and only 5b was isolated in 87% yield.
When 1-phenylprop-2-yn-1-ol was used as substrate, neither
quinoline nor Sonogashira coupling product was isolated,
and the reaction led to a mixture. This revealed that allyl and
the aryl as R3 substituents on alkynes 2 played a vital role and
are indispensable for the present method. Hence, based on
the above results, we propose the following plausible me-
chanism for this reaction (Scheme 3): (i) benzimidoyl chlor-
ides (1) and 1,6-enynes (2) react via Sonogashira coupling to
afford intermediate alkynyl imine 4;16 (ii) the intermediate 4
undergoes a base-assisted propargyl-allenyl isomerization
to form allene intermediate A;17 (iii) that reaction is followed
Experimental Section
General Proceduce for the preparation of Quinolines. An oven-
dried Schlenk tube containing a Teflon-coated stir bar was cha-
rged with CuI (1.4 mg, 0.0075 mmol), Pd(PPh3)2Cl2 (10.5 mg,
0.015 mmol), and 1 (0.30 mmol). The Schlenk tube was sealed
and then evacuated and backfilled with argon (three cycles).
(16) (a) Likhar, P. R.; Subhas, M. S.; Roy, S.; Kantam, M. L.; Sridhar, B.;
Seth, R. K.; Biswas, S. Org. Biomol. Chem. 2009, 7, 85. (b) Van den Hoven, B.
G.; Alper, H. J. Am. Chem. Soc. 2001, 123, 10214. (c) Uneyama, K.;
Watanabe, H. Tetrahedron Lett. 1991, 32, 1459. (d) Ito, Y.; Inouye, M.;
Murakami, M. Chem. Lett. 1989, 1261.
ꢀ
(18) (a) Garcıa-Rubın, S.; Varela, J. A.; Castedo, L.; Saa, C. Org. Lett.
´ ´
(17) For selected papers, see: (a) Shen, R.; Zhu, S.; Huang, X. J. Org.
Chem. 2009, 74, 4118. (b) Sha, F.; Huang, X. Angew. Chem., Int. Ed. 2009, 48,
3458. (c) Chernyak, D.; Gadamsetty, S. B.; Gevorgyan, V. Org. Lett. 2008,
10, 2307. (d) Schwier, T.; Sromek, A. W.; Yap, D. M. L.; Chernyak, D.;
Gevorgyan, V. J. Am. Chem. Soc. 2007, 129, 9868.
2009, 11, 983. (b) Menz, H.; Kirsch, S. F. Org. Lett. 2006, 8, 4795. (c) Kleinke,
A. S.; Li, C.; Rabasso, N.; Porco, J. A. Jr. Org. Lett. 2006, 8, 2847. (d)
Tambar, U. K.; Kano, T.; Zepernick, J. F.; Stoltz, B. M. J. Org. Chem. 2006,
´
71, 8357. (e) Rodrıguez-Otero, J. J. Org. Chem. 1999, 64, 6842.
(19) Tsuji, J.; Minami, I.; Shimizu, I. Tetrahedron Lett. 1984, 25, 2791.
J. Org. Chem. Vol. 75, No. 4, 2010 1307

Gao et al.
JOCNote
A solution of 2 (0.33 mmol) in 3.0 mL of anhydrous Et3N was
subsequently added to the reaction system. The reaction was
stirred at 80 °C for 7 h. After the reaction was completed
(monitored by TCL), the reaction mixture was cooled to room
temperature and extracted with ethyl acetate (3 ꢀ 5 mL), and the
organic layers were combined, washed with saturated NaCl
solution (2 ꢀ 5 mL), and dried over anhydrous Na2SO4. After
the solvent was evaporated in vacuo, the residues were purified
by column chromatography, eluting with hexanes/EtOAc (15:1)
to afford pure 3.
(6-Methoxy-2-phenylquinolin-4-yl)(phenyl)methanone (3b).
Yield: 89 mg (87%). Yellowish solid: mp 140-142 °C. 1H
NMR (400 MHz, CDCl3) δ: 3.80 (s, 3 H), 7.22 (d, J = 2.8 Hz,
1 H), 7.41-7.45 (m, 2 H), 7.48-7.52 (m, 4 H), 7.65 (t, J =
7.6 Hz, 1 H), 7.84 (s, 1 H), 7.92 (d, J = 7.2 Hz, 2 H), 8.11-8.14
(m, 2 H), 8.16 (s, 1 H). 13C NMR (100 MHz, CDCl3) δ: 55.5,
102.8, 118.3, 123.1, 125.0, 127.2, 128.8, 128.9, 129.3, 130.4,
131.7, 134.0, 136.9, 139.0, 143.1, 145.2, 153.9, 158.5, 196.6. IR
(KBr): 740, 1264, 1455, 2925 cm-1. HRMS (ESI): calcd for
C23H18NO2þ (MHþ) 340.1332, found 340.1328.
Phenyl(2-phenylquinolin-4-yl)methanone (3a). Yield: 79 mg
(85%). Yellowish solid: mp 102-104 °C. 1H NMR (400 MHz,
CDCl3) δ: 7.46-7.53 (m, 6 H), 7.63 (t, J = 7.6 Hz, 1 H),
7.74-7.78 (m, 1 H), 7.84-7.91 (m, 4 H), 8.15-8.17 (m, 2 H),
8.26 (d, J = 8.4 Hz, 1 H). 13C NMR (100 MHz, CDCl3) δ: 117.5,
123.9, 125.1, 127.2, 127.5, 128.8, 128.9, 129.7, 130.2, 130.2,
130.3, 134.2, 136.6, 138.9, 145.2, 148.7, 156.4, 196.3. IR (KBr):
Acknowledgment. We thank the National Science Foun-
dation (NSF-20732002, NSF-20090443, and NSF-20872052)
for financial support. We also thank our reviewers for sugges-
tions about the mechanism of the reaction.
Supporting Information Available: Experimental proce-
695, 737, 767, 1070, 1252, 1347, 1449, 1592, 1668, 2924 cm-1
.
dure, characterization details, and copies of 1H NMR and 13
C
HRMS (ESI): calcd for C22H16NOþ (MHþ) 310.1226, found
310.1222.
NMR spectra of all compounds. This material is available free
of charge via the Internet at http://pubs.acs.org.
1308 J. Org. Chem. Vol. 75, No. 4, 2010