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

研究成果: Article

141 引用 (Scopus)

抄録

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).

元の言語English
ページ(範囲)10113-10122
ページ数10
ジャーナルChemistry - A European Journal
17
発行部数36
DOI
出版物ステータスPublished - 2011 8 29
外部発表Yes

Fingerprint

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

ASJC Scopus subject areas

  • Chemistry(all)

これを引用

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.

:: Chemistry - A European Journal, 巻 17, 番号 36, 29.08.2011, p. 10113-10122.

研究成果: Article

@article{3817d88cfa8440ba9719e537edf7e989,
title = "Nickel-catalyzed C-H arylation of azoles with haloarenes: Scope, mechanism, and applications to the synthesis of bioactive molecules",
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).",
keywords = "C-H functionalization, cross-coupling, drug discovery, heterocycles, natural products, nickel",
author = "Takuya Yamamoto and Kei Muto and Masato Komiyama and J{\'e}r{\^o}me Canivet and Junichiro Yamaguchi and Kenichiro Itami",
year = "2011",
month = "8",
day = "29",
doi = "10.1002/chem.201101091",
language = "English",
volume = "17",
pages = "10113--10122",
journal = "Chemistry - A European Journal",
issn = "0947-6539",
publisher = "Wiley-VCH Verlag",
number = "36",

}

TY - JOUR

T1 - Nickel-catalyzed C-H arylation of azoles with haloarenes

T2 - Scope, mechanism, and applications to the synthesis of bioactive molecules

AU - Yamamoto, Takuya

AU - Muto, Kei

AU - Komiyama, Masato

AU - Canivet, Jérôme

AU - Yamaguchi, Junichiro

AU - Itami, Kenichiro

PY - 2011/8/29

Y1 - 2011/8/29

N2 - 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).

AB - 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).

KW - C-H functionalization

KW - cross-coupling

KW - drug discovery

KW - heterocycles

KW - natural products

KW - nickel

UR - http://www.scopus.com/inward/record.url?scp=80052020935&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052020935&partnerID=8YFLogxK

U2 - 10.1002/chem.201101091

DO - 10.1002/chem.201101091

M3 - Article

VL - 17

SP - 10113

EP - 10122

JO - Chemistry - A European Journal

JF - Chemistry - A European Journal

SN - 0947-6539

IS - 36

ER -