Functionalization of indole at C-5 or C-7 via palladium-catalysed double carbonylation. A facile synthesis of indole ketocarboxamides and carboxamide dimers

Attila Takács, Diána Marosvölgyi-Haskó, Zsuzsanna Kabak-Solt, Liliana Damas, Fábio M S Rodrigues, Rui M B Carrilho, Marta Pineiro, Mariette M. Pereira, L. Kollár

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Palladium-catalysed aminocarbonylation of 7-iodoindole derivatives (the parent compound and 5-bromo-7-iodoindole), as well as 5-iodoindole with various primary and secondary amines, including amino acid esters and chiral diamines, was carried out. In this way, a highly selective double carbonylation reaction at the C-7 was performed resulting in the formation of the corresponding indol-7-ylglyoxylamides when monoamines were used. The bromoarene moiety remained intact, so bromo-substituted glyoxylamides of practical importance have been synthesised in moderate to high yields. The use of chiral alkyl and aryl diamines as nucheophiles allowed the synthesis of a new family of dimeric 7-indole derivatives under moderate reaction conditions (10 bar, 100 °C). The aminocarbonylation at the C-5 position led to much lower chemoselectivities toward indol-5-ylglyoxylamides under similar conditions (40 bar CO, 50 °C). The aminocarbonylation of iodoindoles shows a strikingly different chemoselectivity depending on the basicity of the amine while primary and secondary amines of high basicity gave 2-ketocarboxamides in up to 98% chemoselectivity, aniline resulted in almost exclusive formation of the corresponding carboxamide product.

Original languageEnglish
Pages (from-to)247-256
Number of pages10
JournalTetrahedron
Volume72
Issue number2
DOIs
Publication statusPublished - Jan 14 2016

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Carbonylation
Palladium
Dimers
Amines
Diamines
Alkalinity
Derivatives
Carbon Monoxide
Esters
Amino Acids
indole

Keywords

  • 2-Ketocarboxamide
  • Carbon monoxide
  • Carbonylation
  • Iodoindole
  • Palladium

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Drug Discovery

Cite this

Functionalization of indole at C-5 or C-7 via palladium-catalysed double carbonylation. A facile synthesis of indole ketocarboxamides and carboxamide dimers. / Takács, Attila; Marosvölgyi-Haskó, Diána; Kabak-Solt, Zsuzsanna; Damas, Liliana; Rodrigues, Fábio M S; Carrilho, Rui M B; Pineiro, Marta; Pereira, Mariette M.; Kollár, L.

In: Tetrahedron, Vol. 72, No. 2, 14.01.2016, p. 247-256.

Research output: Contribution to journalArticle

Takács, A, Marosvölgyi-Haskó, D, Kabak-Solt, Z, Damas, L, Rodrigues, FMS, Carrilho, RMB, Pineiro, M, Pereira, MM & Kollár, L 2016, 'Functionalization of indole at C-5 or C-7 via palladium-catalysed double carbonylation. A facile synthesis of indole ketocarboxamides and carboxamide dimers', Tetrahedron, vol. 72, no. 2, pp. 247-256. https://doi.org/10.1016/j.tet.2015.11.007
Takács, Attila ; Marosvölgyi-Haskó, Diána ; Kabak-Solt, Zsuzsanna ; Damas, Liliana ; Rodrigues, Fábio M S ; Carrilho, Rui M B ; Pineiro, Marta ; Pereira, Mariette M. ; Kollár, L. / Functionalization of indole at C-5 or C-7 via palladium-catalysed double carbonylation. A facile synthesis of indole ketocarboxamides and carboxamide dimers. In: Tetrahedron. 2016 ; Vol. 72, No. 2. pp. 247-256.
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