The development of practical approaches for 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 convenient approach that employs allyl bromides as the reagents and sodium fluoride as an activator in photochemical processes. Diverse C(sp3)–H functionalizations of alkanes, cycloalkanes and other relatively unreactive substances were enabled by using a stoichiometric or catalytic amount of allyl bromides as initiators in the presence of NaF, which furnished various allylated, heteroarylated, alkylated, hydrazinated and aminated products in good yields with high chemoselectivity and site selectivity. Binary NaF–allyl bromide adducts generated in situ appear to play essential roles in the reaction as light-active species, initiators for radical-mediated C–H cleavage and potential functionalization reagents. We expect that this transition-metal- and photosensitizer-free strategy will offer new opportunities for the C–H diversification of hydrocarbon feedstocks and the late-stage modification of lead compounds. The selective functionalization of strong, neutral C(sp3)–H bonds, such as in alkanes, is synthetically challenging. Now, a transition-metal- and photosensitizer-free strategy employing allyl bromides as reagents and sodium fluoride as an activator has been developed for the selective C(sp3)–H functionalization of alkanes, cycloalkanes and other relatively unreactive molecules.

Abstract 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.

Transition metal- and photosensitizer-free C(sp3)-H (sulfonyl)amidation reactions have been realized by employing Selectfluor® as a versatile reagent, functioning as a photoactive component, a HAT precursor and an oxidant. Various toluene derivatives, cycloalkanes, natural products and bioactive molecules can be converted into N-containing products under mild conditions in good yield and with high chemo- and site-selectivity.

Regiodivergent asymmetric cycloadditions from the same set of starting materials offer interesting oppor-tunities for rapid construction of optically active cyclic molecules with structural diversity. However, this remains a challenging task due to the difficulty of simultaneously controlling the regio-, diastereo-, and enantioselectivity in the ring formation processes. To address this long-standing problem, we have developed a convenient strategy relying on the differ-ent reactivity of nickel-activated alpha,beta-unsaturated car-bonyl compounds under photochemical or thermal conditions, as well as their ability to react with electron-donating alkenes in an inverse-electron -demand manner. Through switching the reaction con-ditions from light irradiation to darkness, or adjusting the electronic features of the reaction partners, regio-diverse diastereo-and enantioselective [2+2], [2+4], and [4+2] cycloadditions have been accessed using the same chiral nickel catalyst. Of them, the photo-chemical [2+2] reaction does not require the addition of other photosensitizers, since the nickel intermediate complexes upon exposure to visible light can serve as the active components. A wide variety of chiral cyclic products have been obtained in good yields, with high diastereo-and enantioselectivity (51 examples, 48-92% yield, up to >20:1 dr, 50-97% ee), including syn-thetically and biologically interesting cyclobutanes, cyclohexenes, and dihydropyrane derivatives as well as bicyclic and spirocyclic compounds. [GRAPHICS]