Allyl bromide-enabled diversification of strong C(sp3)-H bonds: From stoichiometric reactions to catalysis

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.