Radical-Mediated Selective Functionalization of Unactivated Primary C-H Bonds

Radical-mediated sp^(3)C—H functionalization has found broad applications in synthesis and late-stage derivatization of complex molecules.The site-selectivity of a given reaction is mainly dictated by the bond strength,polarity and steric accessibility of diverse C—H bonds as well as the characters of hydrogen atom acceptors.Unactivated sp^(3)C—H bonds usually follow the relative reactivity sequence of tertiary>secondary>primary,which is even recognized as the innate preferences of certain substrates.The development of innovative methods capable of overriding the“inherent”site-selectivity is exceedingly attractive.Although it has been demonstrated that secondary C—H bonds could be selectively converted in the presence of weaker tertiary C—H bonds by tuning the steric and electronic properties of hydrogen atom acceptors,the selective activation of primary C—H bonds remains a daunting challenge.Herein,we highlight the recently emerging attempts towards this goal by interrogating the steric effect of hydrogen atom acceptors.