Radical functionalization of remote c(sp3)-h bonds mediated by unprotected alcohols and amides

Abstract

Aliphatic alcohols and amides are highly valued, ubiquitous chemicals in synthetic chemistry. Radical-promoted regioselective functionalization of unactivated C(sp3)-H bonds offers an atom and step economic manner for direct transformation of aliphatic alcohols and amides, especially structural elaboration of complex natural products and bioactive molecules without de novo synthesis. Despite the rapid growth of hydrogen atom transfer (HAT) processes mediated by O- or N-centered radicals generated from prefunctionalized precursors of alcohols and amides in the past few years, exploration of remote C(sp3)-H functionalization via HAT mediated by unprotected alcohols or amides lags behind, due to the difficult homolysis of O-H and N-H bonds with high bond-dissociation energies (BDEs). In this minireview, the recent advances in regioselective C(sp3)-H functionalization mediated by unprotected alcohols and amides are summarized.