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Volumn 72, Issue 14, 2007, Pages 5113-5118

Regioselective synthesis of 4- and 7-alkoxyindoles from 2,3-dihalophenols: Application to the preparation of indole inhibitors of phospholipase A 2

Author keywords

[No Author keywords available]

Indexed keywords

7-ALKOXYINDOLES; ORTHO-METALATION; PHOSPHOLIPASE;

EID: 34447337739     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo070643y     Document Type: Article
Times cited : (83)

References (53)
  • 9
    • 34447326317 scopus 로고    scopus 로고
    • Functionalization at the 1-, 2-, and 3-positions of the indole ring can be effected easily by conventional methods: Sundberg, R. J. Indoles; Academic Press, London, 1996.
    • Functionalization at the 1-, 2-, and 3-positions of the indole ring can be effected easily by conventional methods: Sundberg, R. J. Indoles; Academic Press, London, 1996.
  • 10
    • 34447322695 scopus 로고    scopus 로고
    • Although 4-hydroxyindole is commercially available, it is quite expensive to be used as starting material in multigram preparations
    • Although 4-hydroxyindole is commercially available, it is quite expensive to be used as starting material in multigram preparations.
  • 14
    • 34447305631 scopus 로고    scopus 로고
    • 4-Alkoxy-3-formylindoles have been prepared by a one-pot thallation-iodination-alkoxylation reaction sequence from 3-formylindole; see Somei, M.; Yamada, F.; Kunimoto, M.; Kaneko, C. Heterocycles 1984, 22, 797-801.
    • 4-Alkoxy-3-formylindoles have been prepared by a one-pot thallation-iodination-alkoxylation reaction sequence from 3-formylindole; see Somei, M.; Yamada, F.; Kunimoto, M.; Kaneko, C. Heterocycles 1984, 22, 797-801.
  • 19
    • 34447343472 scopus 로고    scopus 로고
    • We have optimized the conditions for the ortho-lithiation of 1a by using LDA instead of our initially reported conditions s-BuLi/TMEDA
    • We have optimized the conditions for the ortho-lithiation of 1a by using LDA instead of our initially reported conditions (s-BuLi/TMEDA).
  • 20
    • 34447335488 scopus 로고    scopus 로고
    • The protection of the hydroxy group of 2,3-dihalophenols turns out to be necessary because coupling of 3-halo-2-iodophenols with terminal alkynes under copper-palladium-catalyzed conditions afforded benzo[b]-furan derivatives. See ref 10
    • The protection of the hydroxy group of 2,3-dihalophenols turns out to be necessary because coupling of 3-halo-2-iodophenols with terminal alkynes under copper-palladium-catalyzed conditions afforded benzo[b]-furan derivatives. See ref 10.
  • 21
    • 0033553109 scopus 로고    scopus 로고
    • Developed by Kondo and Uchiyama for the chemoselective deprotonative zincation of functionalized aromatic compounds: (a) Kondo, Y, Shilai, M, Uchiyama, M, Sakamoto, T. J. Am. Chem. Soc. 1999, 121, 3539-3540
    • Developed by Kondo and Uchiyama for the chemoselective deprotonative zincation of functionalized aromatic compounds: (a) Kondo, Y.; Shilai, M.; Uchiyama, M.; Sakamoto, T. J. Am. Chem. Soc. 1999, 121, 3539-3540.
  • 24
    • 0347985383 scopus 로고    scopus 로고
    • Buchwald and Gelman have indeed found that CuI has a deleterious effect on Sonogashira couplings: Gelman, D.; Buchwald, S. L. Angew. Chem., Int. Ed. 2003, 42, 5993-5996.
    • (b) Buchwald and Gelman have indeed found that CuI has a deleterious effect on Sonogashira couplings: Gelman, D.; Buchwald, S. L. Angew. Chem., Int. Ed. 2003, 42, 5993-5996.
  • 31
    • 34447300074 scopus 로고    scopus 로고
    • We have observed that the reaction of 3-bromo-2-iodoanisole 3e with phenylacetylene (2 equiv) gave rise to a small amount of 2,3-bis(phenylethynyl)anisole. Formation of this side product could be inhibited by using only a slight excess of the alkyne 1.2 equiv
    • We have observed that the reaction of 3-bromo-2-iodoanisole 3e with phenylacetylene (2 equiv) gave rise to a small amount of 2,3-bis(phenylethynyl)anisole. Formation of this side product could be inhibited by using only a slight excess of the alkyne (1.2 equiv).
  • 33
    • 0004136578 scopus 로고    scopus 로고
    • Ricci, A, Ed, Wiley-VCH: Weinheim, Germany
    • (b) Hartwig, J. F. In Modern Amination Methods; Ricci, A., Ed.; Wiley-VCH: Weinheim, Germany, 2000; pp 195-262.
    • (2000) Modern Amination Methods , pp. 195-262
    • Hartwig, J.F.1
  • 37
    • 0042808535 scopus 로고    scopus 로고
    • An alternative approach consisting of a hydroamination and a subsequent intramolecular Pd-catalyzed amination reaction has also been reported: Siebeneicher, H, Bytschkov, I, Doye, S. Angew. Chem, Int. Ed. 2003, 42, 3042-3044
    • An alternative approach consisting of a hydroamination and a subsequent intramolecular Pd-catalyzed amination reaction has also been reported: Siebeneicher, H.; Bytschkov, I.; Doye, S. Angew. Chem., Int. Ed. 2003, 42, 3042-3044.
  • 41
    • 34447344651 scopus 로고    scopus 로고
    • 3. However, when we tried this one-pot approach using 3b and phenylacetylene as starting materials, the reaction did not work, probably due to the presence of the Cu(I) salt, which favours the oxidative homocoupling of the alkyne.
    • 3. However, when we tried this one-pot approach using 3b and phenylacetylene as starting materials, the reaction did not work, probably due to the presence of the Cu(I) salt, which favours the oxidative homocoupling of the alkyne.


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