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9095
3-carbamoylindole-2-carboxylic acid (3a) was not
References and notes
isolated (entry 1). The treatment of 2a with N-methyl-
aniline in CH2Cl2 afforded a mixture of the indole-2-
carboxylic acid (3b) and indole-3-carboxylic acid (4b)
in 39% and 60% yields, respectively, but in aceto-
nitrile, 3b was isolated in 73% yield as the major prod-
uct along with 4b (22%) (entries 2 and 3). Compound
2a was also reacted with N-methyl-2-iodoaniline at
room temperature for 72 h to provide a mixture of the
indole-2-carboxylic acid (3c) and indole-3-carboxylic
acid (4c) in 77% and 9% yields, respectively (entry
4). The reaction of 1-benzylindole-2,3-dicarboxylic
anhydride (2b) with N-methylaniline in acetonitrile
gave the corresponding indole-2-carboxylic acid (3d) in
78% yield as the major product (Scheme 1, Table 1,
entry 5).
1. Sharaf, M. H. M.; Schiff, P. L.; Tackie, A. N.; Phoebe, C.
H.; Martin, G. E. J. Heterocycl. Chem. 1996, 33, 239–
243.
2. Fresneda, P. M.; Molina, P. M.; Delgado Tetrahedron
Lett. 1999, 40, 7275–7278; Fresneda, P. M.; Molina, P.
M.; Delgado Tetrahedron 2001, 57, 6197–6702.
´
´
´
3. Timari, G.; Soos, T.; Hajos, G. Synlett 1997, 1067–1068.
`
4. Jonckers, T. H. H.; Maes, B. U. W.; Lemiere, G. L. F.;
Rombouts, G.; Pieters, L.; Haemers, A.; Dommisse, R. A.
Synlett 2003, 615–618.
5. Dhanabal, T.; Sangeetha, R.; Mohan, P. S. Tetrahedron
2006, 62, 6258–6263; Dhanabal, T.; Sangeetha, R.;
Mohan, P. S. Tetrahedron Lett. 2005, 46, 4509–4510;
Kumar, R. N.; Suresh, T.; Mohan, P. S. Tetrahedron Lett.
2002, 43, 3327–3328.
´
6. Mouladdib, A.; Joseph, B.; Hasnaoui, A.; Merour, J.
Synthesis 2000, 549–556.
The decarboxylative Heck-type cyclization of 1-benzene-
sulfonylindole-2-carboxylic acid (3b) was performed by
treatment with Pd(OCOCF3)2 (20 mmol %)7 and
Ag2CO3 in DMSO and DMF at 80 °C to give a mixture
of the 11-benzenesulfonyl-5-methylindolo[3,2-c]quino-
line (5)11 and decarboxylation product (6) in 45% and
24% yields, respectively, but from the 2-iodo derivative
(3c), 5 was isolated in a low yield (13%) along with the
decarboxylation product (7) (37%) (entries 1 and 2).
However, several efforts (Pd(PPh3)4 or Pd(OAc)2,
Ag2O, AgO, or Cs2CO3) were made to obtain the
cyclization product (8) and (9) from the 1-benzylindole
compound (3d) and NH compound (3e), but the results
were less than satisfactory (entries 3 and 4). Finally, 5
was obtained in fairly good yield (71%) at 50 °C for
48 h (entry 5, Table 2). The 11-benzenesulfonyl-5-
methylindolo[3,2-c]quinoline (5) could be converted to
cryptosanguinolentine (1)12 by treatment with tetra-
butylammomium fluoride (rt, 6 h in THF, 80%)
followed by treatment with Red-Al (110 °C, 32 h in
toluene, 53%),2 but the reduction of 5 with LiAlH4 in
hot dioxane produced 1 in 98% yield (Scheme 2).
7. Tanaka, D.; Romeril, S. P.; Myers, A. G. J. Am. Chem. Soc.
2005, 127, 10323–10333; Tanaka, D.; Myers, G. Org. Lett.
2004, 6, 433–436; Myers, A. G.; Tanaka, D.; Mannion, M.
R. J. Am. Chem. Soc. 2002, 124, 11250–11251.
8. Forgione, P.; Brochu, M.-C.; St-Onge, M.; Thesen, K. H.;
Bailey, M. D.; Bilodeau, F. J. Am. Chem. Soc. 2006, 128,
11350–11351.
9. Miki, Y.; Tsuzaki, Y.; Hibino, H.; Aoki, Y. Synlett 2004,
2206–2208.
10. Miki, Y.; Aoki, Y.; Miyatake, H.; Minematsu, T.; Hibino,
H. Tetrahedron Lett. 2006, 47, 5215–5218.
11. 11-Benzenesulfonyl-5-methylindolo[3,2-c]-quinoline (5):
mp 212–214 °C (MeOH). IR (Nujol) cmÀ1: 1645. 1H
NMR (CDCl3) d: 3.84 (3H, s, Me), 7.08–7.18 (2H, m,
arom), 7.20–7.28 (2H, m, arom), 7.30–7.56 (5H, m, arom),
7.65 (1H, ddd, J = 8.5, 8.0, 2.0 Hz, arom), 8.24–8.35 (2H,
m, arom), 8.82 (1H, dd, J = 8.0, 2.0 Hz, arom). HRMS
(EI) m/z: calcd for C23H18O5N2S, 388.0881; found,
388.0872. Anal. Calcd for C23H18O5N2S: C, 68.02; H,
4.15; N, 7.21. Found: C, 68.15; H, 4.12; N, 7.33.
12. Cryptosanguinolentine: mp 134–135 °C (CH3CN) (lit.,3
132–133 °C). IR (Nujol) cmÀ1: 1636, 1612, 1596, 1455,
1
1225, 746, 736. H NMR (DMSO-d6) d: 4.32 (3H, s, Me),
7.29 (H, br t, J = 7.5 Hz, H-8), 7.47 (1H, dt, J = 7.5,
1.0 Hz, H-9), 7.77 (1H, br t, J = 8.0 Hz, H-2), 7.80 (1H, br
d, J = 7.5 Hz, H-10), 7.90 (1H, dt, J = 8.0, 1.0 Hz, H-3),
8.13 (1H, br d, J = 8.0 Hz, H-4), 8.16 (1H, br d, J = 7.5 Hz,
H-7), 8.78 (1H, dd, J = 8.0, 1.0 Hz, H-1), 9.51 (1H, s, H-6).
13C NMR (DMSO-d6) d: 151.49, 150.74, 139.63, 135.78,
130.16, 126.21, 126.05, 124.95, 124.21, 120.72, 120.16,
119.99, 118.14, 117.47, 115.77, 42.81. HRMS m/z (M+)
calcd for C16H12N2, 232.1000; found, 232.0986.
Acknowledgments
This work was supported by ‘High-Tech Research
Center Project’ for Private Universities and matching
fund subsidy from MEXT (2007) and Kinki University.