Recent advances in transition-metal-free deconstructive functionalization of saturated N-, O-, P-, and S-heterocycles

Saturated heterocycles containing oxygen, nitrogen, sulfur, and phosphorus are prevalent structural motifs in natural products, pharmaceuticals, and functional materials. Although significant progress has been made in the direct functionalization of their peripheral C-H bonds, the deconstructive modification of the core heterocyclic skeletons through carbon-heteroatom bond cleavage remains a substantial synthetic challenge, especially for the less strained five- and six-membered ring frameworks. A key strategy to overcome the inherent stability of carbon-heteroatom linkage involves activation of the heteroatom, forming reactive onium species to increase ring electrophilicity, thereby facilitating the following nucleophilic ring-opening. In alignment with the principles of sustainable chemistry, there has been a notable shift from expensive and toxic transition-metal (TM) dependent traditional methodologies toward TM-free approaches for these transformations in recent years. This feature article reviews the major advances in TM-free ring-opening reactions of saturated N-, O-, P-, and S-containing heterocycles over the past five years (2020-2025), while also acknowledging notable earlier studies that have shaped the field.