Direct Skeletal Modification of Bioactive N -Fused Heterocycles via Transmutation

Abstract Advancements in pharmaceutical and agricultural lead discovery and optimization have been significantly enhanced through the precise editing of organic molecules at the atomic level, eliminating the need for prefunctionalization. Although many atom insertion and deletion reactions have been documented recently, instances of single-atom swaps are still limited, primarily due to the complexities involved in selectively cleaving and forming multiple chemical bonds surrounding the same atom. On the other hand, several natural products, dyes, and medications contain N-fused heterocycles that display a wide array of biological and photophysical activities. This situation presents an unexplored frontier for the skeleton editing of N-fused heterocycles. Herein, we disclose the straightforward single-atom editing of N-fused bioactive molecules by carbon-to-nitrogen transmutation. The reaction exhibits remarkable versatility and is capable of transforming a diverse array of functional groups containing heterocycles, including compounds with pharmaceutical relevance, thereby rendering it appropriate for a multitude of discovery initiatives.