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Selective C-F Functionalization of Unactivated Trifluoromethylarenes.

ABSTRACT: Fluorinated organic molecules are pervasive within the pharmaceutical and agrochemical industries due to the range of structural and physicochemical properties that fluorine imparts. Currently, the most abundant methods for the synthesis of the aryl-CF2 functionality have relied on the deoxyfluorination of ketones and aldehydes using expensive and poorly atom economical reagents. Here, we report a general method for the synthesis of aryl-CF2R and aryl-CF2H compounds through activation of the corresponding trifluoromethyl arene precursors. This strategy is enabled by an endergonic electron transfer event that provides access to arene radical anions that lie outside of the catalyst reduction potential. Fragmentation of these reactive intermediates delivers difluorobenzylic radicals that can be intercepted by abundant alkene feedstocks or a hydrogen atom to provide a diverse array of difluoalkylaromatics.

SUBMITTER: Vogt DB

PROVIDER: S-EPMC6703934 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Selective C-F Functionalization of Unactivated Trifluoromethylarenes.

Vogt David B DB Seath Ciaran P CP Wang Hengbin H Jui Nathan T NT

Journal of the American Chemical Society 20190809 33

Fluorinated organic molecules are pervasive within the pharmaceutical and agrochemical industries due to the range of structural and physicochemical properties that fluorine imparts. Currently, the most abundant methods for the synthesis of the aryl-CF2 functionality have relied on the deoxyfluorination of ketones and aldehydes using expensive and poorly atom economical reagents. Here, we report a general method for the synthesis of aryl-CF2R and aryl-CF2H compou ...[more]

PMID: 31369264

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