A Chemoselective α-Oxytriflation Enables the Direct Asymmetric Arylation of Amides

Jing Li, Martin Berger, Wojciech Zawodny, Marwan Simaan, Nuno Maulide

研究成果: Article査読

10 被引用数 (Scopus)

抄録

Until recently, the direct oxidative oxysulfonylation of carbonyl compounds was limited to ketones. Here, we report the first direct oxytriflation of simple, non-activated amides. Amide umpolung with triflic anhydride and pyridine-N-oxide in the absence of external nucleophiles directly leads to the formation of reactive α-triflates in a single step, which provides a platform for the deployment of valuable downstream α-functionalization reactions. The utility of this method was demonstrated by in situ clean conversion to their corresponding bromides, as desirable starting materials for nickel-catalyzed deracemizing enantioselective arylation. This approach not only enables a telescoped asymmetric arylation of unsubstituted amides but also extends its scope because of the broad chemoselectivity and functional group tolerance of the method. Amides bearing a functional group in α-position are found in many natural products and drugs. The direct α-functionalization of amides is one of the most popular approaches to access these moieties. Classically, the α-functionalization of amides has been dominated by enolate chemistry; however, carboxamides are among the least C-H acidic carbonyl derivatives, and the presence of further carbonyl or carboxyl groups (such as esters and ketones) is therefore not usually tolerated. Here, we report the first direct α-oxytriflation of simple, non-activated amides using triflic anhydride and pyridine-N-oxide in the absence of external nucleophiles, which provides a platform for the deployment of valuable downstream α-functionalization reactions. The utility of this method was demonstrated by in situ clean conversion to the corresponding bromides, which are valuable starting materials for nickel-catalyzed deracemizing enantioselective arylation. A direct and chemoselective α-oxytriflation of simple and non-activated amides has been developed. This approach provides a platform for the development of valuable downstream α-functionalization reactions of amides. Furthermore, the combination of α-oxytriflation of amides and nickel-catalyzed Suzuki reaction provides an efficient approach for direct asymmetric α-arylation of simple amides.

本文言語English
ページ(範囲)1883-1891
ページ数9
ジャーナルChem
5
7
DOI
出版ステータスPublished - 2019 7 11
外部発表はい

ASJC Scopus subject areas

  • 化学 (全般)
  • 生化学
  • 環境化学
  • 化学工学(全般)
  • 生化学、医学
  • 材料化学

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