Transformable Imidates Enabled Regiodivergent and Redox-Neutral C–H Amination That Tolerated Strongly Coordinating Heterocycles

Abstract The translation of C–H activation into practical platforms for bioactive molecule discovery remains constrained by poor functional group compatibility, limited scalability, and inefficient downstream diversification. Here we present a robust and scalable, redox-neutral C–H amination strategy that overcomes these challenges through the synergistic use of readily installed and traceless imidates with internal oxidizing N–OPiv reagents. This redox-neutral C–H amination features unprecedented tolerance across 12 classes of strongly coordinating heterocycles, including the notoriously challenging pyridines and azole. The resulting imidate products serve as versatile linchpins for direct transformation into nitriles, carboxylic acids, tetrazoles, and amines, enabling rapid molecular diversification. This methodology facilitates regiospecific late-stage modification of pharmaceuticals, such as celecoxib and letrozole analogues, and expedites the construction of a celecoxib-focused molecular library, from which novel antibacterial derivatives active against Staphylococcus aureus were identified.