Synthesis of Fluorinated Aromatic Compounds by One-Pot Benzyne Generation and Nucleophilic Fluorination

Takashi Ikawa; Shigeaki Masuda; Tsuyoshi Nishiyama; Akira Takagi; Shuji Akai

doi:10.1071/CH13548

RESEARCH ARTICLE

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Synthesis of Fluorinated Aromatic Compounds by One-Pot Benzyne Generation and Nucleophilic Fluorination

Takashi Ikawa ^A ^B ^C , Shigeaki Masuda ^B , Tsuyoshi Nishiyama ^B , Akira Takagi ^B and Shuji Akai ^A ^B ^C

+ Author Affiliations

- Author Affiliations

^A Graduate School of Pharmaceutical Sciences, Osaka University, Yamadaoka, Suita, Osaka 565-0871, Japan.

^B School of Pharmaceutical Sciences, University of Shizuoka, Yada, Suruga-ku, Shizuoka, Shizuoka 422-8526, Japan.

^C Corresponding authors. Email: ikawa@phs.osaka-u.ac.jp; akai@phs.osaka-u.ac.jp

Australian Journal of Chemistry 67(3) 475-480 https://doi.org/10.1071/CH13548
Submitted: 10 October 2013 Accepted: 21 November 2013 Published: 24 December 2013

Abstract

The fluorination of substituted benzenes using fluoride ions under mild reaction conditions has been one of the most important challenges for the synthesis of biologically active fluorinated aromatic compounds; however, only a few synthetically useful methods are known. In this paper, it is reported that the nucleophilic fluorination of benzynes, generated from either 2-(trialkylsilyl)phenyl nonafluorobutanesulfonates or 2-(trialkylsilyl)phenols, meets this challenge. In particular, the fluorination starting from 2-(trialkylsilyl)phenols for fabricating aryl fluorides involves three sequential reactions in one-pot: the nonaflylation of phenols, benzyne generation, and nucleophilic fluorination of the benzynes. The regioselectivities of these reactions are controlled by the substituents at the C3-position of the benzynes.

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Synthesis of Fluorinated Aromatic Compounds by One-Pot Benzyne Generation and Nucleophilic Fluorination

Abstract

References

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