Unexpected C2-arylation of 1-(pyridin-2-yl)indole-3-carboxaldehyde mediated by copper

Article abstract of DOI:10.1055/s-0028-1087549

The C2-arylation of 1-(pyridin-2-yl)indole-3-carboxaldehyde with aryl iodides was carried out in the presence of Cu2O in basic medium. This simple and efficient method led to the preparation of 1,2-diarylindole derivatives. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0028-1087549

LETTER
433
Unexpected C2-Arylation of 1-(Pyridin-2-yl)indole-3-carboxaldehyde
Mediated by Copper
C2-Arylation of
1
h
-(Pyridin-2-
a
yl)indole-3
r
-carboxa
l
ldehyd
è
e
ne Sagnes, Guy Fournet, Benoît Joseph*
Laboratoire de Chimie Organique 1, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, UMR-CNRS 5246,
Université Claude Bernard - Lyon 1, Bâtiment Curien, 43 Boulevard du 11 Novembre 1918, 69622 Villeurbanne, France
Fax +33(4)72431214; E-mail: benoit.joseph@univ-lyon1.fr
Received 17 October 2008
20% yield (Scheme 2). The preparation of 3a from 1 was
improved when 0.3 equivalent of Cu2O was used. In this
case, compound 2a and 3a were obtained in 16% and 41%
yield, respectively.
Abstract: The C2-arylation of 1-(pyridin-2-yl)indole-3-carboxalde-
hyde with aryl iodides was carried out in the presence of Cu2O in
basic medium. This simple and efficient method led to the prepara-
tion of 1,2-diarylindole derivatives.
Key words: indole, arylation, copper, pyridine
Similarly, the synthesis of 2a was performed according to
the literature methodology.14 A solution of the indole-3-
carboxaldehyde sodium salt was stirred with 2-fluoro-
pyridine in DMF at 110 °C for 18 hours to afford 2a in
86% yield. Then, compound 2a was engaged in the aryla-
tion reaction (Cu2O: 0.1 equiv, 2-iodopyridine: 2 equiv) to
obtain the C2-arylated product 3a.15 We were pleased to
isolate 3a in 84% yield (Scheme 2).
N-Arylindole derivatives are widely used as
pharmaceuticals1 or agrochimicals.2 The transition-metal-
catalyzed formation (copper or palladium) of C–N bond is
the simplest way to reach these compounds.3,4 Originally,
the classical Ullmann reaction with aromatic amines re-
quired high temperature (140 °C or more) and stoichio-
metric amount of copper in the presence of a base in polar
high-boiling-point solvent.5 Since this time, milder condi-
tions have been reported for the synthesis of N-aryl-
indoles, involving a catalytic amount of copper and a large
scope of ligands such as aliphatic diamines,6 substituted
1,10-phenantroline,7 amino acid (L-proline),8 and differ-
ent oximes or Schiff bases.9 For our part, we became in-
terested in the synthesis of N-arylindole-3-carbox-
aldehydes as starting material of potent serotoninergic
ligands. The N-arylation reaction was performed in the
presence of commercial indole-3-carboxaldehyde (1),
Cu2O (0.1 equiv), aryl iodide (2 equiv), and K2CO3 (2
equiv) in DMF at 153 °C for three days to afford N-arylat-
ed indoles 2 (Scheme 1). These reaction conditions were
chosen in consideration of its advantages.10,11 The method
is easy to handle, the presence of a ligand is not required,
and Cu2O is described as an interesting copper source, due
to its low cost and its insensitivity to light and air.
i
CHO
CHO
4
7
6"
4"
N
5
6
i
5"
1
+
N
N
3"
N
N
3'
4'
6'
5'
2a
3a
Scheme 2 Reagents and conditions: (i) 2-iodopyridine (2 equiv),
Cu2O (0.1 equiv), K2CO3 (2 equiv), DMF, 153 °C, 3 d. From 1: 2a
(65%); 3a (20%). From 2a: 3a (84%).
Over the past few years, intermolecular direct C2-aryla-
tion of indoles via cross-coupling of C2–H bond with aryl
halide in the presence palladium16 and rhodium17 catalysts
has received considerable attention. To our knowledge,
one example of C2-arylation of indole with diarylio-
dine(III) reagents mediated by Cu(OTf)2 was reported in
a recent work.18 For our part, we next explored the scope
of this coupling reaction.
When 2-iodopyridine was used as the aryl halide, 1-(pyri-
din-2-yl)indole-3-carboxaldehyde (2a)12 was obtained in
65% yield but biarylated product 3a13 was also isolated in
CHO
CHO
We investigated a first set of experiments using various
indole-3-carboxaldehyde derivatives [1-methylindole-3-
carboxaldehyde, 1-phenylindole-3-carboxaldehyde, 1-
(pyridin-3-yl)indole-3-carboxaldehyde, and 1-(methyl-
sulfonyl)indole-3-carboxaldehyde] in the presence of 0.1
equivalent of Cu2O and 2 equivalents of 2-iodopyridine.
The C2-arylated derivatives were isolated in low yield
(11–23%). Thus, the presence of the 2-pyridinyl group at
the N-position is crucial to promote the C2-arylation in
fair yield.
i
N
N
H
Ar
2
1
Scheme 1 Reagents and conditions: (i) ArI (2 equiv), Cu2O (0.1
equiv), K2CO3 (2 equiv), DMF, 153 °C, 3 d; Ar: Ph (74%), 3-pyridi-
nyl (70%), 4-MeC6H4 (64%), 2-MeC6H4 (26%).
SYNLETT 2009, No. 3, pp 0433–0436
Advanced online publication: 21.01.2009
x
x.
x
x.
2
0
0
9
DOI: 10.1055/s-0028-1087549; Art ID: G33408ST
© Georg Thieme Verlag Stuttgart · New York

434
C. Sagnes et al.
LETTER
The model compound 2a was then treated with various the reaction. In this last example, compound 3k was iso-
substituted aromatic halides to afford 2-aryl-1-(pyridin-2- lated in 35% yield.
yl)indole-3-carboxaldehydes 3b–k in 4–88% yield
(Scheme 3, Table 1).
In a second time, different functional groups at the C3-
position of indole were tested (Scheme 4). N-arylation of
indoles 10a–e was first performed to give derivatives
CHO
CHO
11a–e in good yield (Table 2).14,21,22 The C2-arylation for
11a–c did not occurr in the presence of Cu2O and 2-iodo-
pyridine in basic medium. For compounds 11d and 11e,23
the same reaction afforded the compounds 12d and 12e24
in 11–87% yield (Table 2). The arylation conditions re-
quire an aldehyde or nitrile group at the C3-position of in-
dole.
i
Ar
N
N
N
N
3b–k
2a
Scheme 3 Reagents and conditions: (i) ArX (2 equiv), Cu2O (0.1
equiv), K2CO3 (2 equiv), DMF, 153 °C, 3 d (see Table 1).
R
R
N
ii
i
10a–e
Table 1 C2-Arylation of 2a
N
N
Entry
1
ArX
Compd
Yield (%)
79
N
N
3b19
I
11a–e
12a–e
Scheme 4 Reagents and conditions: (i) NaH (1.5 equiv), 2-fluoro-
pyridine (2 equiv), DMF, 110 °C, 18 h; (ii) 2-iodopyridine (2 equiv),
Cu2O (0.1 equiv), K2CO3 (2 equiv), DMF, 153 °C, 3 d (see Table 2).
2
3
3c
4
Br
I
3d
65
Table 2 Arylation of 10 and 11
10
Yield (%) of 11
Yield (%) of 12
I
4
5
3e
84
77
a
11a21 94
–
N
H
3f20
I
10a
Me
a
11b22 96
11c 60
11d 93
11e 98
–
6
3g
80
I
I
N
H
10b
10c
10d
10e
CO2Me
7
8
3h
3i
71
88
a
–
OMe
N
H
I
COMe
MeO
MeO
12d 11
12e 87
9
3j
60
35
I
N
H
10
3k
O2N
I
CN
N
As shown in Table 1, higher yield was obtained when aryl
iodide was used (compare entries 1 and 2). In our hands,
bromobenzene gave poor yield. Electron-donating groups
on ortho-, meta-, or para-position of the aryl iodide gave
fair yields (entries 3–5 and 7–9). The use of bulky 2-iodo-
1,3-dimethylbenzene (entry 6) led also to the desired with
80% yield. The presence of an electron-withdrawing
group (entry 10) had a dramatic effect on the efficiency of
H
a No reaction.
In a last part, we applied this arylation reaction under
microwave dielectric heating as an alternative to the clas-
sical conductive heating. The reaction was first performed
Synlett 2009, No. 3, 433–436 © Thieme Stuttgart · New York

LETTER
C2-Arylation of 1-(Pyridin-2-yl)indole-3-carboxaldehyde
435
(2) (a) Pallos, F. M.; Mathews, C. J. WO 9315049, 1993; Chem.
Abstr. 1993, 120, 8470. (b) (Novartis AG) EP 1783114,
2007; Chem. Abstr. 2007, 146, 500886.
with 1, 2-iodopyridine (1 or 3 equiv), and Cu2O (0.1 or 0.3
equiv) in DMF at 153 °C or 240 °C for 1–2 hours
(Table 3).25 At 153 °C, compound 2a was the lone deriv-
ative observed and was isolated in 94% yield. In the pres-
ence of 3 equivalents of 2-iodopyridine and 0.3 equivalent
of Cu2O at 240 °C for 2 hours, 1,2-diaryl compound 3a
was obtained in 70% yield. The same reaction conditions
were applied to 2a and 10e (Table 3). Again, the best
yields were obtained when 0.3 equivalent of Cu2O were
used (2 equiv of 2-iodopyridine at 240 °C for 1 h).
(3) Ley, S. V.; Thomas, A. W. Angew. Chem. Int. Ed. 2003, 42,
5400.
(4) Old, D. W.; Harris, M. C.; Buchwald, S. L. Org. Lett. 2000,
2, 1403.
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I. P.; Cheparov, A. V. Coord. Chem. Rev. 2004, 248, 2337.
(6) Antilla, J. C.; Klapars, A.; Buchwald, S. L. J. Am. Chem.
Soc. 2002, 124, 11684.
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Lett. 2001, 3, 4315. (b) Van Allen, D.; Venkataraman, D.
J. Org. Chem. 2003, 68, 4590. (c) Tang, B.-X.; Guo, S.-M.;
Zhang, M.-B.; Li, J.-H. Synthesis 2008, 1707.
(8) (a) Ma, D.; Cai, Q. Synlett 2004, 128. (b) Cai, Q.; Zhu, W.;
Zhang, H.; Zhang, Y.; Ma, D. Synthesis 2005, 496.
(9) Cristau, H.-J.; Cellier, P. P.; Spindler, J.-F.; Taillefer, M.
Chem. Eur. J. 2004, 10, 5607.
Table 3 Arylation of 1, 2a, and 10e under Microwave Conditions
Compd Cu2O 2-Iodopyridine Temp
(equiv) (equiv)
Time Compd, yield
(°C)
153
240
240
240
240
240
240
240
240
240
240
240
(h)
(%)
1
0.1
0.1
0.1
0.3
0.3
0.3
0.1
0.1
0.3
0.1
0.1
0.3
2
2
2
2
2
3
1
2
2
2
2
2
1
2a, 94
1
1
2a, 58; 3a, 36
2a, 47; 3a, 37
2a, 40; 3a, 47
2a, 31; 3a, 57
2a, 17; 3a, 70
3a, 28
(10) Huang, Y.-Z.; Miao, H.; Zhang, Q.-H.; Chen, C.; Xu, J.
Catal. Lett. 2008, 122, 344.
(11) Correa, A.; Bolm, C. Adv. Synth. Catal. 2007, 349, 2673.
(12) Analytical Data of 1-(Pyridin-2-yl)-1H-indole-3-
carboxaldehyde (2a)
1
2
1
1
Mp 114–115 °C (MeOH). IR (KBr): 3101, 3050, 2821,
1667, 1649, 1593, 1579, 1539, 1471, 1455, 1444, 1224,
1128, 1083, 739 cm–1. 1H NMR (300 MHz, CDCl3):
d = 7.33–7.43 (m, 3 H, H-5, H-5¢, H-6), 7.64 (d, 1 H, J = 8.3
Hz, H-3¢), 7.95 (td, 1 H, J = 1.9, 7.7 Hz, H-4¢), 8.02–8.05 (m,
1 H, H-4 or H-7), 8.38 (s, 1 H, H-2), 8.38–8.41 (m, 1 H, H-4
or H-7), 8.64 (dd, 1 H, J = 1.3, 4.7 Hz, H-6¢), 10.16 (s, 1 H,
CHO). 13C NMR (75 MHz, CDCl3): d = 112.8 (CH), 115.7
(CH), 120.5 (C), 122.2 (CH), 122.3 (CH), 123.8 (CH), 125.1
(CH), 126.3 (C), 136.2 (C), 137.0 (CH), 139.0 (CH), 149.4
(CH), 150.9 (C), 185.4 (CO). ESI-MS: m/z = 223 [M + H]+.
Anal. Calcd for C14H10N2O: C, 75.66; H, 4.54; N, 12.60.
Found: C, 75.99; H, 4.32; N, 12.55.
1
2
1
2
2a
2a
2a
10e
10e
10e
1
1
3a, 61
1
3a, 81
1
11e, 45; 12e, 42
11e, 29; 12e, 55
11e, 17; 12e, 71
2
1
(13) Analytical Data of 1,2-Di(pyridin-2-yl)-1H-indole-3-
carboxaldehyde (3a)
Mp 127–128 °C (EtOAc–PE). IR (KBr): 3051, 3012, 2831,
1648, 1443, 1387, 1050, 754, 741 cm–1. 1H NMR (300 MHz,
CDCl3): d = 7.19 (d, 1 H, J = 7.9 Hz, H-3¢ or H-3¢¢), 7.27–
7.44 (m, 5 H, H-3¢ or H-3¢¢, H-5, H-5¢, H-5¢¢, H-6), 7.54 (d,
1 H, J = 7,4 Hz, H-4 or H-7), 7.67–7.79 (m, 2 H, H-4¢, H-4¢¢),
8.53–8.60 (m, 3 H, H-4 or H-7, H-6¢, H-6¢¢), 10.18 (s, 1 H,
CHO). 13C NMR (75 MHz, CDCl3): d = 111.4 (CH), 117.7
(C), 122.1 (CH), 122.7 (CH), 123.1 (CH), 123.6 (CH), 124.0
(CH), 125.3 (CH), 125.4 (C), 126.8 (CH), 136.3 (CH), 137.4
(C), 138.4 (CH), 147.3 (C), 148.8 (C), 149.6 (CH), 149.9
(CH), 150.4 (C), 187.8 (CO). ESI-MS: m/z = 300 [M + H]+.
Anal. Calcd for C19H13N3O: C, 76.24; H, 4.38; N, 14.04.
Found: C, 76.34; H, 4.43; N, 13.96.
In conclusion, the outcome of the C2-arylation of the
indole core depends of the presence of a 2-pyridinyl group
at the N-position and an aldehyde (or nitrile) group at C3.
By this route, 1,2-diaryl-3-formylindoles have been pre-
pared in one or two steps in good yields. Further applica-
tions are now under investigation.
Acknowledgment
The financial support and the grant to C.S. from the ‘Cluster de
recherche Chimie de la Région Rhône-Alpes’ are duly acknowled-
ged.
(14) Seki, K.; Ohkura, K.; Terashima, M.; Kanaoka, Y.
Heterocycles 1994, 37, 993.
(15) Typical Procedure
References and Notes
In a sealed tube, a solution of 2a (100 mg, 0.45 mmol, 1
equiv), Cu2O (6.5 mg, 0.045 mmol, 0.1 equiv), 2-iodo-
pyridine (101 mL, 0.90 mmol, 2 equiv), and K2CO3 (124 mg,
0.90 mmol, 2 equiv) in anhyd DMF (0.9 mL) was stirred at
153 °C for 3 d. The reaction was cooled to r.t., filtered
through Celite, and the filtrate was concentrated in vacuo.
The residue was diluted in EtOAc (20 mL). The organic
layer was washed with a solution of 2.5% aq NH4OH (2 × 20
mL) and brine (20 mL). The organic phase was dried over
MgSO4, filtered, and concentrated in vacuo. The crude
(1) (a) Perregaard, J.; Andersen, K.; Hyttel, J.; Sánchez, C.
J. Med. Chem. 1992, 35, 4813. (b) Zhang, H.-C.; Derian,
C. K.; McComsey, D. F.; White, K. B.; Ye, H.; Hecker,
L. R.; Li, J.; Addo, M. F.; Croll, D.; Eckardt, A. J.; Smith,
C. E.; Li, Q.; Cheung, W.-M.; Conway, B. R.; Emanuel, S.;
Demarest, K. T.; Andrade-Gordon, P.; Damiano, B. P.;
Maryanoff, B. E. J. Med. Chem. 2005, 48, 1725. (c) Xu, H.;
Liu, W.-Q.; Fan, L.-L.; Chen, Y.; Yang, L.-M.; Lv, L.;
Zheng, Y.-T. Chem. Pharm. Bull. 2008, 56, 720.
Synlett 2009, No. 3, 433–436 © Thieme Stuttgart · New York

436
C. Sagnes et al.
LETTER
(22) Seki, K.; Ohkura, K.; Terashima, M.; Kanaoka, Y.
product was purified by flash column chromatography (PE–
EtOAc, 2:8 to 1:1) to provide 3a (110 mg, 84%).
Heterocycles 1987, 26, 3101.
(23) Analytical Data of 1-(Pyridin-2-yl)-1H-indole-3-
carbonitrile (11e)
(16) (a) Lane, S. S.; Sames, D. Org. Lett. 2004, 6, 2897.
(b) Lane, B. S.; Brown, M. A.; Sames, D. J. Am. Chem. Soc.
2005, 127, 8050. (c) Toure, B. B.; Lane, B. S.; Sames, D.
Org. Lett. 2006, 8, 1979. (d) Bellina, F.; Cauteruccio, S.;
Rossi, R. Eur. J. Org. Chem. 2006, 1379. (e) Bellina, F.;
Calandri, C.; Cauteruccio, S.; Rossi, R. Tetrahedron 2007,
63, 1970. (f) Wang, X.; Gribkov, D. V.; Sames, D. J. Org.
Chem. 2007, 72, 1476. (g) Lebrasseur, N.; Larrosa, I. J. Am.
Chem. Soc. 2008, 130, 2926. (h) Alberico, D.; Scott, M. E.;
Lautens, M. Chem. Rev. 2007, 107, 174.
Mp 150–151 °C (MeOH). IR (KBr): 3135, 3050, 2222,
1592, 1540, 1473, 1455, 1434, 1229, 1095, 735 cm–1. 1H
NMR (300 MHz, CDCl3): d = 7.32–7.45 (m, 3 H, H-5, H-5¢,
H-6), 7.56 (d, 1 H, J = 8.1 Hz, H-3¢), 7.83 (br d, 1 H, J = 7.5
Hz, H-4 or H-7), 7.93 (td, 1 H, J = 1.9, 7.5 Hz, H-4¢), 8.10
(br d, 1 H, J = 7.1 Hz, H-4 or H-7), 8.23 (s, 1 H, H-2), 8.63
(dd, 1 H, J = 1.1, 4.9 Hz, H-6¢). 13C NMR (75 MHz, CDCl3):
d = 89.8 (C), 113.4 (CH), 115.3 (C), 115.6 (CH), 120.0
(CH), 122.3 (CH), 123.4 (CH), 125.2 (CH), 128.7 (C), 133.3
(CH), 134.4 (C), 139.1 (CH), 149.5 (CH), 150.7 (C). ESI-
MS: m/z = 220 [M + H]+. Anal. Calcd for C14H9N3: C, 76.70,
H, 4.14, N, 19.17. Found: C, 76.72; H, 4.08; N, 19.25.
(24) Analytical Data of 1,2-Di(pyridin-2-yl)-1H-indole-3-
carbonitrile (11d)
(17) Wang, X.; Lane, B. S.; Sames, D. J. Am. Chem. Soc. 2005,
127, 4996.
(18) Phipps, R. J.; Grimster, N. P.; Gaunt, M. J. J. Am. Chem. Soc.
2008, 130, 8172.
(19) Analytical Data of 2-Phenyl-1-(pyridin-2-yl)-1H-indole-
3-carboxaldehyde (3b)26
Mp 171–172 °C (EtOAc–PE). IR (KBr): 3065, 3043, 2836,
1652, 1466, 1454, 1384, 1225, 1082, 756 cm–1. 1H NMR
(300 MHz, CDCl3): d = 6.94 (d, 1 H, J = 7.9 Hz, H-3¢), 7.30–
7.43 (m, 8 H, H-5, H-5¢, H-6, Harom), 7.51 (d, 1 H, J = 7.5 Hz,
H-4 or H-7), 7.68 (td, 1 H, J = 1.9, 8.0 Hz, H-4¢), 8.50 (br d,
1 H, J = 6.9 Hz, H-4 or H-7), 8.65 (dd, 1 H, J = 1.3, 4.9 Hz,
H-6¢), 9.97 (s, 1 H, CHO). 13C NMR (75 MHz, CDCl3):
d = 111.6 (CH), 116.9 (C), 122.2 (CH), 122.4 (CH), 123.2
(CH), 123.9 (CH), 124.8 (CH), 125.5 (C), 128.5 (2 CH),
128.8 (C), 129.5 (CH), 131.1 (2 CH), 137.5 (C), 138.3 (CH),
149.6 (CH), 149.9 (C), 150.2 (C), 187.6 (CO). ESI-MS: m/z
= 299 [M + H]+. Anal. Calcd for C20H14N2O: C 80.52; H,
4.73; N, 9.39. Found: C, 80.83; H, 4.85; N, 9.27.
Mp 128–129 °C (CH2Cl2–PE). IR (KBr): 3065, 2213, 1589,
1569, 1467, 1448, 1435, 1393, 1225, 738 cm–1. 1H NMR
(300 MHz, CDCl3): d = 7.24–7.41 (m, 5 H, H-3¢ or H-3¢¢,
H-5, H-5¢, H-5¢¢, H-6), 7.50–7.53 (m, 1 H, H-4 or H-7), 7.82–
7.89 (m, 4 H, H-3¢ or H-3¢¢, H-4 or H-7, H-4¢, H-4¢¢), 8.44 (br
d, 1 H, J = 4.1 Hz, H-6¢or H-6¢¢), 8.51 (dd, 1 H, J = 1.1, 4.7,
H-6¢ or H-6¢¢). 13C NMR (75 MHz, CDCl3): d = 89.3 (C),
112.1 (CH), 116.1 (C), 120.0 (CH), 122.0 (CH), 123.1 (CH),
123.4 (CH), 123.5 (CH), 124.9 (CH), 125.5 (CH), 127.6 (C),
136.8 (CH), 137.2 (C), 138.4 (CH), 144.8 (C), 148.2 (C),
149.5 (CH), 149.6 (CH), 150.7 (C). ESI-MS: m/z = 297 [M
+ H]+. Anal. Calcd for C19H12N4: C, 77.01, H, 4.08, N, 18.91.
Found: C, 76.88; H, 4.27; N, 19.01.
(20) Analytical Data of 1-(Pyridin-2-yl)-2-(4-methylphenyl)-
1H-indole-3-carboxaldehyde (3f)
(25) Typical Procedure
In a microwave vial with a magnetic stir bar was introduced
indole-3-carboxaldehyde (100 mg, 0.68 mmol, 1 equiv),
Cu2O (10 mg, 0.07 mmol, 0.1 equiv), and K2CO3 (189 mg,
1.36 mmol, 2 equiv) in anhyd DMF (1.4 mL). After a purge
with argon, 2-iodopyridine (153 mL, 1.36 mmol, 2 equiv)
was added. The vial was sealed and heated at 240 °C under
microwave irradiation (Biotage Initiator) for 1 h. The
mixture was filtered through Celite, and the filtrate was
concentrated in vacuo. The residue was diluted in EtOAc (20
mL). The organic layer was washed with a solution of 2.5%
aq NH4OH (2 × 20 mL) and brine (20 mL). The organic
phase was dried over MgSO4, filtered, and concentrated in
vacuo. The crude residue was purified by flash
Mp 206–207 °C (EtOAc–PE). IR (KBr): 3048, 2916, 2836,
1642, 1435, 1081, 747, 737 cm–1. 1H NMR (300 MHz,
CDCl3): d = 2.37 (s, 3 H, CH3), 6.92 (d, 1 H, J = 6.9 Hz,
H-3¢), 7.15 (d, 2 H, J = 8.0 Hz, Harom), 7.26 (d, 2 H, J = 8.0
Hz, Harom), 7.29–7.41 (m, 3 H, H-5, H-5¢, H-6), 7.50 (dd, 1
H, J = 0.9, 7.4 Hz, H-4 or H-7), 7.68 (td, 1 H, J = 1.9, 7.7 Hz,
H-4¢), 8.48 (dd, 1 H, J = 1.1, 7.3 Hz, H-4 or H-7), 8.65 (dd,
1 H, J = 1.1, 4.9 Hz, H-6¢), 9.95 (s, 1 H, CHO). 13C NMR (75
MHz, CDCl3): d = 21.4 (CH3), 111.5 (CH), 116.7 (C), 122.1
(CH), 122.5 (CH), 123.1 (CH), 123.8 (CH), 124.7 (CH),
125.5 (C), 125.8 (C), 129.2 (2 CH), 131.0 (2 CH), 137.5 (C),
138.3 (CH), 139.7 (C), 149.6 (CH), 150.2 (C), 150.3 (C),
187.6 (CO). ESI-MS: m/z = 313 [M + H]+. Anal. Calcd for
C21H16N2O: C, 80.75, H, 5.16; N, 8.97. Found: C, 8.48; H,
4.97; N, 9.03.
chromatography (PE–EtOAc, 2:8 to 1:1) to provide 2a (88
mg, 58%) and 3a (73 mg, 36%).
(26) (a) Fernandez, I.; Galvez, C.; Urpi, L. An. Quim. 1991, 87,
936. (b) Maassarani, F.; Pfeffer, M.; Spencer, J.; Wehman,
E. J. Organomet. Chem. 1994, 466, 265.
(21) Kantam, M. L.; Yadav, J.; Laha, S.; Sreedhar, B.; Jha, S.
Adv. Synth. Catal. 2007, 349, 1938.
Synlett 2009, No. 3, 433–436 © Thieme Stuttgart · New York

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