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.

Automated summary

Radical-mediated sp(3) C-H functionalization has wide applications in synthesis and derivatization. The site-selectivity of a reaction is determined by bond strength, polarity, steric accessibility, and acceptor properties. Activating primary C-H bonds selectively has been a difficult task, but recent attempts focus on exploring the steric effects of acceptors.