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Volumn 60, Issue 10, 2004, Pages 2283-2291

Synthesis of 5H-pyridazino[4,5-b]indoles and their benzofurane analogues utilizing an intramolecular Heck-type reaction

Author keywords

Aza carboline; Buchwald Hartwig amination; Intramolecular Heck type reaction; Palladium; Pyridazinone

Indexed keywords

2 METHYLBENZO[B]FURO[2,3 D]PYRIDAZIN 1(2H) ONE; BENZOFURAN DERIVATIVE; INDOLE DERIVATIVE; PALLADIUM; PHENOL DERIVATIVE; UNCLASSIFIED DRUG;

EID: 10744229778     PISSN: 00404020     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tet.2004.01.024     Document Type: Article
Times cited : (54)

References (86)
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    • For the synthesis of benzo[b]furo[2,3-d]pyridazines via the reaction of a 2,3-dicarbonylated benzo[b]furane with a hydrazine see: (d) Cugnon de Sevricourt M., Robba M. J. Heterocycl. Chem. 14:1977;777-780.
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    • See Ref. 3a.
    • See Ref. 3a.
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    • For the use of an intramolecular Heck-type reaction for the construction of carbazole, carboline and dibenzofurane skeletons and their aza-analogues see: (a)
    • For the use of an intramolecular Heck-type reaction for the construction of carbazole, carboline and dibenzofurane skeletons and their aza-analogues see: (a) Iida H., Yuasa Y., Kibayashi C. J. Org. Chem. 45:1980;2938-2942.
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    • For a recent review dealing with direct arylation via cleavage of activated and unactivated C-H bonds see: Miura M., Nomura M. Top. Curr. Chem. 219:2002;211-241.
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    • For recent reviews containing a chapter on the Buchwald-Hartwig reaction see: (g)
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    • For the synthesis of 2-substituted 5-alkoxy-4-halopyridazin-3(2H)-ones via selective alkanolysis of 2-substituted 4,5-dihalopyridazin-3(2H)-ones see: (a)
    • For the synthesis of 2-substituted 5-alkoxy-4-halopyridazin-3(2H)-ones via selective alkanolysis of 2-substituted 4,5-dihalopyridazin-3(2H)-ones see: (a) Barlin G.B., Lakshminarayanan P. J. Chem. Soc., Perkin Trans. 1. 1977;1038-1044.
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    • For the synthesis of 2-substituted 5-aryloxy-4-halopyridazin-3(2H)-ones via phenolysis of 2-substituted 4,5-dihalopyridazin-3(2H)-ones see: (f) Kang Y.-J., Chung H.-A., Kweon D.-H., Cho S.-D., Lee S.-G., Kim S.-K., Yoon Y.-J. J. Heterocycl. Chem. 35:1998;595-600.
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    • For general reviews dealing with the synthesis of 2-substituted 4,5-dihalopyridazin-3(2H)-ones and the regioselective nucleophilic substitution of the addition-elimination type on these substrates with O, S and N nucleophiles see: (j) Mátyus P., Czakó K. Trends Heterocycl. Chem. 3:1993;249-264.
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    • See Ref. 9g.
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    • For the related alkanolysis of 4,5-dichloropyridazin-3(2H)-ones with sodium alkanolates in acetonitrile at room temperature a mixture of two alkoxy-chloropyridazin-3(2H)-one isomers was also obtained: see Ref. 9b
    • For the related alkanolysis of 4,5-dichloropyridazin-3(2H)-ones with sodium alkanolates in acetonitrile at room temperature a mixture of two alkoxy-chloropyridazin-3(2H)-one isomers was also obtained: see Ref. 9b.
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    • 3 and NaOAc in DMA are the Spencer's reaction conditions. For intermolecular Heck reactions under 'Spencer's' conditions see: (a) Spencer A. J. Organomet. Chem. 258:1983;101-108.
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    • note
    • The most important side reaction observed in the Pd-catalyzed cyclodehydrohalogenation of 8a and 8b is hydrodehalogenation. The formation of 2-methyl-5-phenoxypyridazin-3(2H)-one has been proven by NMR analysis of the column chromatography fractions that revealed the presence of a compound with a molecular mass of 202.
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    • 2 or Pd(BINAP) catalyst is ArI>ArBr≫ArCl. However, the presence of electron withdrawing groups on, as well as the incorporation of nitrogen atoms in the benzene ring of the aryl chloride makes oxidative addition of aryl chlorides to palladium catalysts with traditional triarylphosphane ligands possible: (a)
    • 2 or Pd(BINAP) catalyst is ArI>ArBr≫ArCl. However, the presence of electron withdrawing groups on, as well as the incorporation of nitrogen atoms in the benzene ring of the aryl chloride makes oxidative addition of aryl chlorides to palladium catalysts with traditional triarylphosphane ligands possible: (a) Fitton P., Rick E.A. J. Organomet. Chem. 28:1971;287-291.
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    • See Ref. 8g.
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    • note
    • 4NBr (1 equiv.): no reaction.
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    • 4NY in DMF are the Jefferey's reaction conditions. For intermolecular Heck reactions under Jefferey's conditions see:
    • 4NY in DMF are the Jefferey's reaction conditions. For intermolecular Heck reactions under Jefferey's conditions see: Jefferey T. Tetrahedron. 52:1996;10113-10130.
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    • It is often considered that the Pd-catalyzed cyclodehydrohalogenation involving C-H bond activation, occurs via the intramolecular electrophilic attack of the oxidative addition complex on the π system: (a) See Ref. 8.
    • It is often considered that the Pd-catalyzed cyclodehydrohalogenation involving C-H bond activation, occurs via the intramolecular electrophilic attack of the oxidative addition complex on the π system: (a) See Ref. 8.
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    • If one accepts this model the Pd-catalyzed cyclodehydrohalogenation involving the cleavage of a vinylic C-H bond (e.g., in
    • Echavarren A.M., Gómez-Lor B., González J.J., de Frutos Ó. Synlett. 2003;585-597. If one accepts this model the Pd-catalyzed cyclodehydrohalogenation involving the cleavage of a vinylic C-H bond (e.g., in 10 ) should occur more readily than when an aromatic C-H bond is involved (e.g., in 8 ) since the mechanistic pathway does not include loss of aromaticity. This is in accordance with the results we obtained when comparing the Pd-catalyzed cyclization of 8a with 10.
    • (2003) Synlett , pp. 585-597
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    • For publications dealing with the rate accelerating effect of large excesses of carbonate bases on Pd-catalyzed aminations see: (a)
    • For publications dealing with the rate accelerating effect of large excesses of carbonate bases on Pd-catalyzed aminations see: (a) Watanabe M., Nishiyama M., Yamamoto T., Koie Y. Tetrahedron Lett. 41:2000;481-483.
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    • note
    • 3 were used 40% of 5-[(2-bromophenyl)amino]-2-methylpyridazin-3(2H)-one ( 15 ) and a recovery of 52% of 5-iodo-2-methylpyridazin-3(2H)-one ( 1 ) were obtained after refluxing for 3 h, whereas the use of 1 equiv. of the same base under the same reaction conditions gave a yield of 30% of 15 and a recovery of 63% of 1 in the same reaction time.
  • 86
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    • A similar selective behaviour has recently been reported by us for the Suzuki reaction of
    • A similar selective behaviour has recently been reported by us for the Suzuki reaction of 11 with 2-bromophenylboronic acid. In this case the conjugate base of 2-bromophenylboronic acid probably sterically and electronically retards oxidative addition of the ortho C-Br bond to the Pd(0) catalyst: see Ref. 2e. Interestingly, also Armin de Meijere's group reported selectivity when using 2-bromophenylboronic acid in the Suzuki cross-coupling reaction with 1-bromonaphthalene: Wegner H.A., Scott L.T., de Meijere A. J. Org. Chem. 68:2003;883-887.
    • (2003) J. Org. Chem. , vol.68 , pp. 883-887
    • Wegner, H.A.1    Scott, L.T.2    De Meijere, A.3


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