Work

Deacylative Polyfluoroarylation via C–C Cleavage of Alkyl Ketones

Year: 2025

Type: article

Abstract: Polyfluoroarenes often exist in functional molecules; however, construction of alkyl-polyfluoroaryl bonds remains nontrivial, and the current approaches exhibit various limitations. Here we report the first deacylative polyfluoroarylation of readily available methyl ketones, enabled by aromatization-driven C-C bond cleavage. This method allows efficient synthesis of both primary and secondary alkyl-substituted polyfluoroarenes under simple and convenient conditions, demonstrating excellent functional group tolerance and generality. The preliminary mechanistic study suggests the involvement of direct addition of the alkyl radical intermediate, generated after the C-C bond cleavage, to the polyfluoroarene, followed by either a single-electron transfer (SET) or hydrogen-atom transfer (HAT) process with the prearomatic intermediate (PAI).

Source: Organic Letters

DOI: 10.1021/acs.orglett.5c03436

Authors: Sohee Kim, Ching-Nung Chen, Scott A. Snyder, Guangbin Dong

Institution: University of Chicago

Language: English

Topic: Fluorine in Organic Chemistry

Subfield: Pharmaceutical Science

Field: Pharmacology, Toxicology and Pharmaceutics

Domain: Life Sciences

Open Access status: green

Funders: University of Chicago, National Institute of General Medical Sciences

Award: Catalytic C−C Activation/Functionalization of Ketones and Amides