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Updated: Jun 8, 2026

Optimization of Radiochemical Reactions using Droplet Arrays
Published on: February 12, 2021
Quantitative Evaluation of Fluoroalkyl Anion Donor Abilities of Nucleophilic Fluoroalkylating Reagents
Cui Yu1, Xiaoyu Lai1, Man Li1
1State Key Laboratory of Fluorine and Nitrogen Chemistry and Advanced Materials and Shanghai-Hong Kong Joint Laboratory in Chemical Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Abstract:
A quantitative understanding of the ability of nucleophilic fluoroalkylating reagents to donate fluoroalkyl anions (-CnF2n+1 or -CF2H) remains elusive, limiting predictive reaction design. Here, we report a systematic investigation of fluoroalkyl anion donor ability based on computed X-Rf bond heterolytic dissociation enthalpies via density functional theory (DFT). Across a diverse set of reagents, the intrinsic thermodynamic cost of fluoroalkyl anion release spans a wide range (21.5-221.8 kcal mol- 1), but is dramatically reduced in the presence of activators, with effective donor abilities varying from strongly endergonic to exergonic regimes (-20.1-34.8 kcal mol- 1). This work establishes a quantitative fluoroalkyl anion donor ability scale that correlates well with experimental observations and offers an in-depth mechanistic understanding of the factors regulating fluoroalkyl transfer. The quantitative scale developed herein enables direct comparison across reagent classes and offers a predictive basis for the rational design of nucleophilic fluoroalkylation reactions.
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