Chemoselective functionalization of intrinsically less reactive C(sp3)–H bonds of alkyl nitriles are of particular interest to the chemical community in view that these strategies provide opportunities for the introduction of important cyanoalkyl groups onto target frameworks in a step-economic fashion. In recent years, the introduction of nitrile-containing alkyl radicals in tandem radical additions and oxidative couplings inarguably brings chemists a new radical reaction platform for the diverse synthesis of natural products and pharmaceuticals. Compared with the wide applications of various C-centred radicals adjacent to a heteroatom, however, the nitrile-containing alkyl radicals remain largely unexplored. New methods for C(sp3)−H bond oxidative functionalization of alkyl nitriles and new mechanistic manifolds would result in the development of a broad range of novel reactions. Therefore, this review will give an overview of various types of radical cyanoalkylation by using the key alkyl nitrile reactants, which is beyond traditional coupling chemistry.

A novel radical phosphinylation of α,α-diaryl allylic alcohols with arylphosphine oxides was described for the direct preparation of α-aryl-β-phosphinylated carbonyl ketones in medium to good yields via 1,2-aryl migration. In this reaction, formation of new C(Ar)–C(sp³) and C(sp³)–P bonds was observed.

A metal-free method for direct C(sp³)–H bond functionalization of simple ethers with α,α-diaryl allylic alcohols is described. The established protocol provides facile access to α-aryl-β-oxyalkylated carbonyl ketones via radical addition and a 1,2-aryl migration cascade process. An application of the product has been demonstrated in the synthesis of a serotonin antagonist.

Although the demand for privileged (hetero)cyclic molecules continues to grow steadily in organic synthesis, drug discovery, agrochemical chemistry, materials science, etc., the innovative development of incredibly powerful techniques that allow facile (hetero)cycle assembly with structural complexity and diversity from ubiquitous starting materials is hardly keeping pace. Under this context, the straight activation of multiple notorious C–F bonds in poly- or perfluorine-containing compounds (PFCs), which are academically and practically readily accessible by fluorinations or fluorochemical industry, concomitant with further transformations has indeed become an emerging theme for the manufacture of usefully oligofluorinated or nonfluorinated cyclic skeletons. In this review, we highlighted the recent advances in this field by underpinning the cleaved C–F bond number during the defluorinative process, where the distinctive fluorine effects are the synthetic linchpins for tuning the reaction selectivity of PFCs and controlling reaction pathways for the anticipated annulation in a designed sense. Emphasis is placed on the function of fluorine as a detachable “chemical handle”. This review aims to reveal specific research opportunities in the topics of C–F bond activation and heterocyclic chemistry.