The development of practical approaches to the selective functionalization of strong, neutral C(sp3)-H bonds, such as those in petroleum-derived hydrocarbons, is of general interest but remains a remarkable challenge in synthetic chemistry. We here report a photochemical system employing allyl bromides as versatile reagents or pre-catalysts in the presence of sodium uoride. Diverse C(sp3)-H functionalization of alkanes, cycloalkanes and other relatively unreactive substances has been achieved from stoichiometric to catalytic variants ¬(TON up to 3300), furnishing a variety of allylated, heteroarylated, alkylated, hydrazinated and aminated products in good yields and with high chemo-and site-selectivity. Binary NaF-allyl bromide adducts generated in situ appear to play essential roles, in that they can act as visible light-active species, hydrogen atom transfer precursors and potential functionalization reagents. We expect that this transition metal-and photosensitizer-free strategy will provide a general platform for C-H diversi cation of hydrocarbon feedstocks and late-stage modi cation of lead compounds.

Direct and selective C−H methylation is a powerful tool with which to install methyl groups into organic molecules, and is particularly useful in pharmaceutical chemistry. However, practical methods for such modification of biologically interesting targets have been rarely developed. We here report an iron‐catalyzed C(sp3)−H methylation reaction of glycine derivatives, peptides and drug‐like molecules in an alcohol in the presence of di‐tert‐butyl peroxide. A readily available iron catalyst plays multiple roles in the transformation, which accelerates oxidation of C−N bonds to C=N double bonds, activates imine intermediates as Lewis acids by bidentate chelation, and at the same time facilitates cleavage of the peroxide to generate methyl radicals. A variety of methylated N‐aryl glycine derivatives and peptides were obtained in good yield and with excellent chemo‐ and site‐selectivity. This reaction is scalable, easily managed, and can be completed within 1–2 h. It features an economic, bio‐friendly catalyst, a green solvent and low toxic reagents, and will provide effective access to precise C−H modification of biomolecules and natural products.

The development of practical approaches to the selective functionalization of strong, neutral C(sp3)-H bonds, such as those in petroleum-derived hydrocarbons, is of general interest but remains a remarkable challenge in synthetic chemistry. We here report a photochemical system employing allyl bromides as versatile reagents or pre-catalysts in the presence of sodium fluoride. Diverse C(sp3)-H functionalization of alkanes, cycloalkanes and other relatively unreactive substances has been achieved from stoichiometric to catalytic variants ¬(TON up to 3300), furnishing a variety of allylated, heteroarylated, alkylated, hydrazinated and aminated products in good yields and with high chemo- and site-selectivity. Binary NaF-allyl bromide adducts generated in situ appear to play essential roles, in that they can act as visible light-active species, hydrogen atom transfer precursors and potential functionalization reagents. We expect that this transition metal- and photosensitizer-free strategy will provide a general platform for C-H diversification of hydrocarbon feedstocks and late-stage modification of lead compounds.

We have developed an effective photochemical method for site-selective (hetero)arylation of polychlorinated heteroarenes. This approach eliminates the need for transition metal catalysts and photosensitizers by relying on in-situ formation of...