Photochemical diversification of strong C(sp3)–H bonds enabled by allyl bromide and sodium fluoride

Abstract

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.