Synthesis of a-Carbolines Starting from 2,3-Dichloropyridines and Substituted Anilines
UPDATE
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[16] For procedures for the construction of 1-methyl-1H-a-
carboline, see: a) see ref.[10b]; b) see ref.[11a]; c) see
´
ref.[11b]
; d) W. Peczynska-Czoch, M. Mordarski, L.
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[17] a) these reaction conditions were developed for the
synthesis of 2-iodo-1-methylpyridinium iodide starting
from 2-chloropyridine, see: Y. Takahashi, S. Otsuka, H.
Masuda, M. Hirota, Y. Ito, Y. Hamada, Bull. Chem.
Soc. Jpn. 1976, 49, 2770–2774; b) the formation of 3-
chloro-2-iodo-1-methylpyridinium iodide instead of 2,3-
dichloro-1-methylpyridinium iodide can be explained
by a nucleophilic substitution of the 2-Cl by the iodide
anion in the initially formed 2,3-dichloro-1-methylpyri-
dinium iodide; for a report on halogen exchanage reac-
tions on 2-halopyridines, see: H. L. Bradlow, C. A. Van-
derwerf, J. Org. Chem. 1951, 16, 1143–1152. The pres-
ence of small amounts of 3-chloro-2-iodopyridine in
the reaction mixture suggests that 3-chloro-2-iodo-1-
methylpyridinium chloride is demethylated in the
course of the reaction. 3-Chloro-2-iodo-1-methylpyridi-
nium iodide is then formed by methylation of 3-chloro-
2-iodopyridine with iodomethane.
[18] It is very likely that a halogen exchange reaction be-
tween iodide and chloride anions occurs on substrate 8
whereby a more reactive pyridinium salt is formed. Ini-
tially, inspired by a literature report, we found that ad-
dition of POCl3 to the reaction mixture of 8 and 5d was
crucial to obtain 9d, see: C. T. Brain, S. A. Brunton,
Tetrahedron Lett. 2002, 43, 1893–1895. Later we found
that LiCl, which is readily soluble in THF, had a similar
effect.
[19] a) For the use of triethylamine in Pd-catalyzed intramo-
lecular direct arylations, see ref.[6b] and references cited
therein. b) For the use of N,N-dicyclohexylmethylamine
in Pd-catalyzed intramolecular direct arylations, see
ref.[9].
[13] For recent procedures, see: a) A. Abouabdellah, R. H.
Dodd, Tetrahedron Lett. 1998, 39, 2119–2122; b) P.
Molina, P. M. Fresneda, M. A. Sanz, C. Foces-Foces,
M. C. Ramirez de Arellano, Tetrahedron 1998, 54,
9623–9638; c) A. Tahri, K. J. Buysens, E. V. Van der
Eycken, D. M. Vandenberghe, G. J. Hoornaert, Tetrahe-
dron 1998, 54, 13211–13226; d) O. Barun, P. K. Patra,
H. Ila, H. Junjappa, Tetrahedron Lett. 1999, 40, 3797–
3800; e) B. Joseph, H. Da Costa, J.-Y. Mꢁrour, S.
[20] a) For examples of the use of DBU in Pd-catalyzed in-
tramolecular direct arylation reactions, see ref.[6b] and
references cited therein. b) Recently, Echavarren and
co-workers found the use of DBU in the intramolecular
direct arylation reaction on substituted 1-bromo-2-(2,2-
diphenylethyl)benzenes to be ineffective; see: D.
Garcia-Cuadrado, P. de Mendoza, A. A. C. Braga, F.
Maseras, A. M. Echavarren, J. Am. Chem. Soc. 2007,
129, 6880–6886.
Adv. Synth. Catal. 2008, 350, 2653 – 2660
ꢂ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2659