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Volumn 350, Issue 16, 2008, Pages 2653-2660

Synthesis of α-carbolines starting from 2,3-dichloropyridines and substituted anilines

Author keywords

carbolines; C H activation; Direct arylation; Malaria; Microwave heating; Palladium

Indexed keywords


EID: 56649114523     PISSN: 16154150     EISSN: 15213897     Source Type: Journal    
DOI: 10.1002/adsc.200800077     Document Type: Article
Times cited : (79)

References (79)
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    • For recent reviews and accounts on the Buchwald-Hartwig reaction, see: a
    • For recent reviews and accounts on the Buchwald-Hartwig reaction, see: a) A. R. Muci, S. L. Buchwald, Top. Curr. Chem. 2002, 219, 131-209;
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    • For recent reviews dealing with intramolecular direct arylation reactions, see: a
    • For recent reviews dealing with intramolecular direct arylation reactions, see: a) L. C. Campeau, K. Fagnou, Chem. Commun. 2006, 1253-1264;
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    • For general reviews dealing with a-carbolines, see: a
    • For general reviews dealing with a-carbolines, see: a) R. A. Abramovitch, I. D. Spenser, Adv. Heterocycl. Chem. 1964, 3, 79-207;
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    • For recent procedures, see: a
    • For recent procedures, see: a) A. Abouabdellah, R. H. Dodd, Tetrahedron Lett. 1998, 39, 2119-2122;
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    • 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;
    • 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;
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    • 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-methylpyridinium iodide; for a report on halogen exchanage reactions on 2-halopyridines, see: H. L. Bradlow, C. A. Vanderwerf, J. Org. Chem. 1951, 16, 1143-1152. The presence 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-methylpyridinium iodide is then formed by methylation of 3-chloro-2-iodopyridine with iodomethane.
    • 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-methylpyridinium iodide; for a report on halogen exchanage reactions on 2-halopyridines, see: H. L. Bradlow, C. A. Vanderwerf, J. Org. Chem. 1951, 16, 1143-1152. The presence 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-methylpyridinium iodide is then formed by methylation of 3-chloro-2-iodopyridine with iodomethane.
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    • It is very likely that a halogen exchange reaction between iodide and chloride anions occurs on substrate 8 whereby a more reactive pyridinium salt is formed. Initially, inspired by a literature report, we found that addition 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
    • 3 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.
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    • For examples of the use of DBU in Pd-catalyzed intramolecular direct arylation reactions, see ref.[6b] and references cited therein
    • [6b] and references cited therein.
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    • 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.
    • 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.
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    • French Patent, FR 28976377, 390900;
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    • B. U. W. Maes, K. T. J. Loones, G. L. F. Lemière, R. A. Dommisse, Synlett 2003, 1822-1825. In this paper the synthesis of the structurally related N-methyl-N-phenylpyridin-2-amine starting from 2-chloropyridine and N-methylaniline was described
    • B. U. W. Maes, K. T. J. Loones, G. L. F. Lemière, R. A. Dommisse, Synlett 2003, 1822-1825. In this paper the synthesis of the structurally related N-methyl-N-phenylpyridin-2-amine starting from 2-chloropyridine and N-methylaniline was described.
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    • +: 197.0715.
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    • For recent procedures for the synthesis of neocryptolepine or its 6H-indolo[2,3-b]quinoline skeleton, see: a M. Schmittel, J.-P. Steffen, B. Engels, C. Lennartz, M. Hanrath, Angew. Chem. Int. Ed. 1998, 37, 2371-2373;
    • For recent procedures for the synthesis of neocryptolepine or its 6H-indolo[2,3-b]quinoline skeleton, see: a) M. Schmittel, J.-P. Steffen, B. Engels, C. Lennartz, M. Hanrath, Angew. Chem. Int. Ed. 1998, 37, 2371-2373;
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    • DBU has been used previously in microwave-assisted Pd-catalyzed aminations involving nonaflates, see
    • DBU has been used previously in microwave-assisted Pd-catalyzed aminations involving nonaflates, see: R. E. Tundel, K. W. Anderson, S. L. Buchwald, J. Org. Chem. 2006, 71, 430-433.
    • (2006) J. Org. Chem , vol.71 , pp. 430-433
    • Tundel, R.E.1    Anderson, K.W.2    Buchwald, S.L.3


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.