Nickel-catalyzed C-H arylation of azoles with haloarenes

Scope, mechanism, and applications to the synthesis of bioactive molecules

Takuya Yamamoto, Kei Muto, Masato Komiyama, Jérôme Canivet, Junichiro Yamaguchi, Kenichiro Itami

Research output: Contribution to journalArticle

140 Citations (Scopus)

Abstract

Novel nickel-based catalytic systems for the C-H arylation of azoles with haloarenes and aryl triflates have been developed. We have established that Ni(OAc) 2/bipy/LiOtBu serves as a general catalytic system for the coupling with aryl bromides and iodides as aryl electrophiles. For couplings with more challenging electrophiles, such as aryl chlorides and triflates, the Ni(OAc) 2/dppf (dppf=1,1′-bis(diphenylphosphino)ferrocene) system was found to be effective. Thiazoles, benzothiazoles, oxazoles, benzoxazoles, and benzimidazoles can be used as the heteroarene coupling partner. Upon further investigation, we discovered a new protocol for the present coupling using Mg(OtBu) 2 as a milder and less expensive alternative to LiOtBu. Attempts to reveal the mechanism of this nickel-catalyzed heterobiaryl coupling are also described. This newly developed methodology has been successfully applied to the syntheses of febuxostat (a xanthine oxidase inhibitor that is effective for the treatment of gout and hyperuricemia), tafamidis (effective for the treatment of TTR amyloid polyneuropathy), and texaline (a natural product having antitubercular activity).

Original languageEnglish
Pages (from-to)10113-10122
Number of pages10
JournalChemistry - A European Journal
Volume17
Issue number36
DOIs
Publication statusPublished - 2011 Aug 29
Externally publishedYes

Fingerprint

Azoles
Nickel
Benzothiazoles
Benzoxazoles
Oxazoles
Benzimidazoles
Thiazoles
Molecules
Xanthine Oxidase
Iodides
Biological Products
Bromides
Amyloid
Chlorides
Febuxostat
texaline
tafamidis
ferrocene
Oxidoreductases

Keywords

  • C-H functionalization
  • cross-coupling
  • drug discovery
  • heterocycles
  • natural products
  • nickel

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Nickel-catalyzed C-H arylation of azoles with haloarenes : Scope, mechanism, and applications to the synthesis of bioactive molecules. / Yamamoto, Takuya; Muto, Kei; Komiyama, Masato; Canivet, Jérôme; Yamaguchi, Junichiro; Itami, Kenichiro.

In: Chemistry - A European Journal, Vol. 17, No. 36, 29.08.2011, p. 10113-10122.

Research output: Contribution to journalArticle

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