Review and Theoretical Analysis of Fluorinated Radicals in Direct CAr−H Functionalization of (Hetero)arenes

Direct installation of fluorinated motifs onto (hetero)arenes has seen widespread application in recent years. A general strategy relies on the generation of fluorinated radicals from Functional Group Transfer Reagents. This Review highlights recent contributions in this field while discussing mechanisms and providing key DFT-based parameters and a computed reactivity scale to enhance the understanding of the chemical behaviour of these radicals.

Abstract

We highlight key contributions in the field of direct radical C_Ar− H (hetero)aromatic functionalization involving fluorinated radicals. A compilation of Functional Group Transfer Reagents and their diverse activation mechanisms leading to the release of radicals are discussed. The substrate scope for each radical is analyzed and classified into three categories according to the electronic properties of the substrates. Density functional theory computational analysis provides insights into the chemical reactivity of several fluorinated radicals through their electrophilicity and nucleophilicity parameters. Theoretical analysis of their reduction potentials also highlights the remarkable correlation between electrophilicity and oxidizing ability. It is also established that highly fluorinated radicals (e.g. ⋅OCF₃) are capable of engaging in single-electron transfer (SET) processes rather than radical addition, which is in good agreement with experimental literature data. A reactivity scale, based on activation barrier of addition of these radicals to benzene is also elaborated using the high accuracy DLPNO-(U)CCSD(T) method.

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