LETTER
Synthesis of a-Carbolines
175
(9) (a) Kaczmarek, L.; Peczynka-Czoch, W.; Osiadacz, J.;
Mordarski, M.; Sokalski, W. A.; Boratynski, J.;
ed materials helped in the characterization of the com-
pounds (the N-deprotected compounds have very low
solubility). In conclusion, we have reported a novel and
efficient method for the synthesis of functionalised a-car-
bolines and their annelated derivatives from oxindole uti-
lizing the ‘tertiary amino effect’ strategy. Most of the
reactions were carried out at room temperature. The elet-
rocyclization step which is usually carried out at very high
temperature could be carried out at moderate temperature
by using an electron-withdrawing Boc substituent on the
nitrogen atom of the indole. The formation of the products
is explained by a proposed mechanism. This reaction
which can be further utilized in the synthesis of many oth-
er heterocyclic compounds of biological importance is a
valuable addition to the chemistry of a-carbolines in par-
ticular and heterocyclic compounds as a whole. Further
study of the reaction is in progress.
Marcinkovska, E.; Glazman-Kusnierczyk, H.; Radzikowski,
C. Bioorg. Med. Chem. Lett. 1999, 7, 22457. (b) Laurson,
W.; Perkin, W. H.; Robinson, R. J. Chem. Soc. 1924, 125,
626. (c) Kaczmarek, L.; Balicki, R.; Nantka-Namirski, P.;
Peczynska-Czoch, W.; Mordarski, M. Arch. Pharm.
(Weinheim, Ger.) 1988, 321, 463. (d) Mehta, L. K.; Parrick,
J.; Payne, F. J. Chem. Soc., Perkin. Trans. 1 1993, 1261.
(10) (a) Okuda, S.; Robinson, M. M. J. Am. Chem. Soc. 1959, 81,
740. (b) Yamazaki, T.; Matoba, K.; Imoto, S.; Terashima,
M. Chem. Pharm. Bull. 1976, 24, 3011.
(11) (a) Tahri, A.; Buysens, K. J.; Van der Eycken, E. V.;
Vanderberghe, D. M.; Hoornaert, G. J. Tetrahedron 1998,
54, 13211. (b) Molina, P.; Alajarín, M.; Vidal, A.; Sánchez-
Aranda, P. J. Org. Chem. 1992, 57, 929. (c) Forbes, I. T.;
Johnson, C. N.; Thompson, M. Synth. Commun. 1993, 23,
715.
(12) Rocca, P.; Marsais, F.; Godard, A.; Queguiner, G.
Tetrahedron 1993, 49, 49.
(13) Vera-Luque, P.; Alajarin, R.; Alvarez-Builla, J.; Vaquero,
J. J. Org. Lett. 2006, 8, 415.
(14) Meth-Cohn, O.; Suschitzky, H. Adv. Heterocycl. Chem.
Acknowledgment
The authors thank DST, New Delhi for financial support and Dr.
P. G. Rao, the Director, NEIST, Jorhat for providing the facilities to
perform the work. Mr. S. Majumder thanks CSIR for a research
fellowship.
1972, 14, 211.
(15) (a) Verboom, W.; Reinhoudt, D. N. Recl. Trav. Chim. Pays-
Bas 1990, 109, 311. (b) Verboom, W.; Reinhoudt, D. N.;
Visser, R.; Harkema, S. J. Org. Chem. 1984, 49, 269.
(16) (a) Tverdokhlebov, A. V.; Gorulya, A. P.; Tolmachev, A. A.;
Kostyuk, A. N.; Chernega, A. N.; Rusanov, E. B.
Tetrahedron 2006, 62, 9146. (b) Rabong, C.; Hametner, C.;
Mereiter, K.; Kartsev, V. G.; Jordis, U. Heterocycles 2008,
75, 799. (c) Ryabukhin, S. V.; Plaskon, A. S.; Volochnyuk,
D. M.; Pipko, S. E.; Tolmachev, A. A. Synth. Commun.
2008, 38, 3032.
(17) (a) Ojea, V.; Maestro, M. A.; Quintela, J. M. Tetrahedron
1993, 49, 2691. (b) Ojea, V.; Muinelo, I.; Figueroa, M. C.;
Ruiz, M.; Quintela, J. M. Synlett 1995, 622. (c) Ojea, V.;
Muinelo, I.; Quintela, J. M. Tetrahedron 1998, 54, 927.
(d) Devi, I.; Baruah, B.; Bhuyan, P. J. Synlett 2006, 2593.
(18) Vlaskina, N. M.; Suzdalev, K. F.; Babakova, M. N.;
Mezheritskii, V. V.; Kartsev, V. G. Russ. Chem. Bull. 2006,
55, 384.
References and Notes
(1) (a) Venkat, R. G.; Qi, L.; Pierce, M.; Robbins, P. B.;
Sahasrabudhe, S. R.; Selliah, R. WO 2007076085, 2007.
(b) Arakawa, H.; Monden, Y.; Nakatsuru, Y.; Kodera, T.
WO 2003080077, 2003. (c) Burstein, H. J.; Overmoyer, B.;
Gelman, R.; Silverman, P.; Savoie, J.; Clarke, K.; Dumadag,
L.; Younger, J.; Ivy, P.; Winer, E. P. Invest. New Drugs
2007, 25, 161.
(2) (a) Li, X.; Vince, R. Bioorg. Med. Chem. 2006, 14, 2942.
(b) Zhao, G.; Wang, C.; Liu, C.; Lou, H. Mini-Rev. Med.
Chem. 2007, 7, 707.
(3) (a) Gelbard, H. A.; Maggirwar, S. B.; Dewhurst, S.;
Schifitto, G. P. WO 2007076372, 2007. (b) Mellman, I.;
Jiang, A. WO 2007075911, 2007.
(4) (a) Paolini, L. Sci. Rep. Ist. Super. Sanita 1961, 1, 86.
(b) Okamoto, T.; Akase, T.; Izumi, S.; Inaba, S.; Yamamoto,
H. JP 7220196, 1972; Chem. Abstr. 1972, 77, 152142.
(c) Winter, J.; Di Mola, N. West German Patent 2442513,
1975; Chem. Abstr. 1975, 82, 156255.
(5) (a) Stubbs, M. C.; Armstrong, S. A. Curr. Drug Targets
2007, 8, 703. (b) Shenoy, S.; Vasania, V. S.; Gopal, M.;
Mehta, A. Toxicol. Appl. Pharmacol. 2007, 222, 80.
(c) Seedhouse, C. H.; Hunter, H. M.; Lloyd-Lewis, B.;
Massip, A.-M.; Pallis, M.; Carter, G. I.; Grundy, M.; Shang,
S.; Russel, N. H. Leukemia 2006, 20, 2130.
(6) (a) Joseph, J.; Meijer, L.; Liger, F. FR2876377, 2006.
(b) Das, S.; Brown, J. W.; Dong, Q.; Gong, X.; Kaldor, S.
W.; Liu, Y.; Paraselli, B. R.; Scorah, N.; Stafford, J. A.;
Wallace, M. B. WO 2007044779, 2007.
(7) Fong, T. M.; Erondu, N. E.; Macneil, D. J.; Mcintyre, J. H.;
Vander Pleog, L. H. T. WO 2004110368, 2004.
(8) (a) Molina, P.; Fresneda, P. M. Synthesis 1989, 878.
(b) Beccalli, E. M.; Clerici, F.; Marchesini, A. Tetrahedron
2001, 57, 4787. (c) Erba, E.; Gelmi, M. L.; Pocar, D.
Tetrahedron 2000, 56, 9991. (d) Ono, A.; Narasaka, K.
Chem. Lett. 2001, 146. (e) Achab, S.; Guyor, M.; Potier, P.
Tetrahedron Lett. 1995, 36, 2615.
(19) Sandip Murarka, S.; Zhang, C.; Konieczynska, M. D.;
Seidel, D. Org. Lett. 2009, 11, 129.
(20) (a) Baruah, B.; Bhuyan, P. J. Tetrahedron 2009, 65, 7099.
(b) Deb, M. L.; Majumder, S.; Baruah, B.; Bhuyan, P. J.
Synthesis 2010, 929. (c) Deb, M. L.; Bhuyan, P. J. Synlett
2008, 325. (d) Deb, M. L.; Bhuyan, P. J. Synthesis 2008,
2891. (e) Deb, M. L.; Baruah, B.; Bhuyan, P. J. Synthesis
2007, 28.
(21) Synthesis of 2-Chloro-3-formylindole (2)
To a mixture of anhyd DMF (10 mL) and anhyd CHCl3 (10
mL) was added phosphorous oxychloride (10 mL) over 15
min. To this a solution of oxindole 1 (3.2 g, 24 mmol) and
pyridine (5 mL), both in anhyd CHCl3 (25mL), was slowly
added. The reaction mixture was kept for 48 h at r.t. and then
poured into ice-cold H2O (100 mL). The solid compound 2
formed was filtered and dried. Yield 2.48 g (80%); mp 167–
168 °C. 1H NMR (300 MHz, CDCl3): d = 7.22–7.38 (m, 2
H), 7.95–7.99 (m, 1 H), 8.15–8.18 (m, 1 H), 9.61 (s, 1 H),
10.10 (s, 1 H).
Synthesis of 1-(tert-Butoxycarbonyl)-2-chloro-3-
formylindole (3)
Equimolar amounts of 2-chloro-3-formylindole (2; 10
mmol, 1.79 g) and Boc2O (10 mmol, 2.18 g) were stirred in
the presence of catalytic amount of DMAP (0.12 g) and Et3N
(0.10 g) at 0–5 °C for 1 h using CH2Cl2 (15 mL) as solvent.
Synlett 2011, No. 2, 173–176 © Thieme Stuttgart · New York