Recent advances in hydrogen atom transfer induced C(sp3)-H functionalizations initiated by radical addition to alkynes

Direct functionalization of C(sp(3))-H bonds represents a pivotal objective in the realm of synthetic chemistry. However, inherent chemical inertness coupled with low reactivity disparities among these bonds present formidable challenges. The hydrogen atom transfer (HAT)-mediated strategy enables direct and selective C(sp(3))-H functionalization under environmentally benign conditions, exhibiting a wider substrate scope and superior functional group tolerance, and occasionally displaying complementary reactivity to that of transition metal-catalyzed C-H activation. Traditional methods focus on the utilization of heteroatom radicals and necessitate harsh reaction conditions or specific precursors. In contrast, vinyl radical-induced HAT, particularly triggered by radical addition to alkynes, is considered more efficient and eco-friendly, thus facilitating its application in the late-stage modification of complex organic architectures. Over the past decade, significant progress has been made in this area, including switching from the common 5-exo-trig cyclization to uncommon 5-endo-trig, 4-exo-trig, or 6-endo-trig cyclizations, and an extension from traditional intramolecular cyclization to intermolecular C(sp(3))-H functionalization. This review primarily focuses on the advancements made for these new reaction modes since 2013. The reaction mechanisms, merits and limitations, especially the key facts for tuning the reaction pathways, are discussed and may be valuable for the development and application of this methodology.