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. 2024 Mar 22;26(11):2338-2342.
doi: 10.1021/acs.orglett.4c00677. Epub 2024 Mar 8.

FluoroFusion: NHC-Catalyzed Nucleophilic Aromatic Substitution Reaction Unveils Functional Perfluorinated Diarylmethanones

Cheng-Lin Chan  1   2 , Shao-Chi Lee  3   4 , Pei-Shan Lin  1 , Radyn Vanessa Phaz P Tapales  1   2 , Jia-Syuan Li  1 , Chun-An Lai  1 , Jyh-Tsung Lee  1 , Chien-Hung Li  5 , Hsuan-Hung Liao  1   5
Affiliations

FluoroFusion: NHC-Catalyzed Nucleophilic Aromatic Substitution Reaction Unveils Functional Perfluorinated Diarylmethanones

Cheng-Lin Chan et al. Org Lett. .

Abstract

A mild, facile, and metal-free approach via the N-heterocyclic carbene-catalyzed SNAr reaction between aryl aldehydes with perfluoroarenes to obtain the coveted functional perfluorinated diarylmethanones is disclosed. This method accommodates a diverse substrate range and exhibits notable tolerance toward various functional groups. Our success in modifying biologically relevant molecules, crafting a fully fluorinated bioisosteric analogue of drug candidate D1, and highlighting the potential of these ketones as valuable electrolyte additives for lithium-ion batteries (LIBs) underscores the versatility of our methodology.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Synthesis and Application of Perfluorinated Arene
(a) Relevance of perfluorinated diarylmethanones. (b) Approaches to the synthesis of perfluorinated diarylmethanones. (c) Applications of our strategy.
Scheme 2
Scheme 2. Scope Evaluation of the NHC-Catalyzed Synthesis of Perfluorinated Diarylmethanones
Unless otherwise stated, the reaction was conducted with 1 (1.0 equiv, 0.1 mmol), 2 (1.0 equiv, 0.1 mmol), NHC1 precatalyst (0.2 equiv, 0.02 mmol), and Cs2CO3 (1.5 equiv, 0.15 mmol) in anhydrous dichloromethane (1 mL, 0.1 M) under a N2 environment and stirred at room temperature for 18 h. All yields correspond to purified products. Gram-scale synthesis was conducted using 1 (1.0 equiv, 7.0 mmol), 2 (1.1 equiv, 7.7 mmol), NHC1 precatalyst (0.2 equiv, 1.4 mmol), and Cs2CO3 (1.5 equiv, 10.5 mmol) in anhydrous dichloromethane (70 mL, 0.1M) under a N2 environment and stirred at room temperature for 60 h.
Scheme 3
Scheme 3. Application of Our Developed Strategy
(a) Synthesis of a bioisosteric analogue. (b) Evaluation of perfluorinated diarylmethanones as electrolyte additives for Li-ion battery.
See this image and copyright information in PMC

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