Synthesis of 15N-Labeled Complex Saturated N -Heterocycles via Late-Stage Carbonyl-to-Nitrogen Swap

Efficient construction of 15N-labeled complex saturated N-heterocycles remains a substantial challenge. Here we report a late-stage carbonyl-to-15N skeletal modification strategy that converts complex cyclic ketones directly into 15N-enriched saturated heterocycles. This transformation is enabled by a methylsulfonyl-based 15N-labeled azonation reagent that suppresses unwanted overoxidation without compromising the desired C–C bond cleavage pathway. The reaction exhibits a broad substrate scope and tolerates a wide range of functional groups, serving as an effective tool for late-stage skeletal modifications of complex natural products and drug-like molecules. Mechanistic insights on the sequential double C–C activation events have been elucidated by preliminary computational studies.