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Catalytic S N Ar Hydroxylation and Alkoxylation of Aryl Fluorides
Author(s) -
Kang QiKai,
Lin Yunzhi,
Li Yuntong,
Xu Lun,
Li Ke,
Shi Hang
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202106440
Subject(s) - chemistry , nucleophile , aryl , catalysis , medicinal chemistry , leaving group , hydroxylation , alkyl , heteroatom , rhodium , substitution reaction , organic chemistry , enzyme
Nucleophilic aromatic substitution (S N Ar) is a powerful strategy for incorporating a heteroatom into an aromatic ring by displacement of a leaving group with a nucleophile, but this method is limited to electron‐deficient arenes. We have now established a reliable method for accessing phenols and phenyl alkyl ethers via catalytic S N Ar reactions. The method is applicable to a broad array of electron‐rich and neutral aryl fluorides, which are inert under classical S N Ar conditions. Although the mechanism of S N Ar reactions involving metal arene complexes is hypothesized to involve a stepwise pathway (addition followed by elimination), experimental data that support this hypothesis is still under exploration. Mechanistic studies and DFT calculations suggest either a stepwise or stepwise‐like energy profile. Notably, we isolated a rhodium η 5 ‐cyclohexadienyl complex intermediate with an sp 3 ‐hybridized carbon bearing both a nucleophile and a leaving group.