<p>In the realm of molecular construction, the skeletal editing techniques of heterocyclic compounds demonstrate unique efficiency, particularly in synthesizing molecular structures that are challenging to obtain through traditional synthetic methods. Compared to the ring-contraction reaction of saturated nitrogen heterocycles and aryl rings, the site selectivity and stereoselective skeletal editing of pyrimidine fused heterocycles remain relatively underdeveloped. Here we report a chiral hypervalent iodine(III)-catalyzed skeletal editing of pyrimidine moieties within polynitrogen heterocycles, which efficiently produces optically pure multi-substituted imidazoline rings. The reaction demonstrates exceptional functional group tolerance, as shown by the ring contraction of diverse polynitrogen heterocycles and the late-stage functionalization of M₁G-<i>d</i>R and its analogues, including nucleosides, nucleotides, and oligonucleotides. Density functional theory calculations explore the details of the mechanism and the factors that determine the reaction’s stereoselectivity.</p>