A photochemical strategy for pyrazole to imidazole conversion

Abstract

Heteroaromatic scaffolds are central to modern medicinal chemistry. Methods that can reconfigure the core heterocycle of a molecule while preserving its substitution pattern would greatly streamline analogue synthesis and bioisosteric replacement. Yet, direct heterocycle-to-heterocycle interconversions remain rare. Here we report a photochemical strategy that directly converts pyrazoles into imidazoles with broad functional-group tolerance and full retention of peripheral substitution. The reaction is effective across densely substituted and bicyclic systems and extends to pyrazolo[1,5-a]azines, a class of high-value heteroaromatics that have never previously been reconfigured. This photochemical strategy is readily translated to continuous flow, confirming its potential for scalable applications. Our mechanistic studies support an N–N bond homolysis pathway in which solvent-dependent conformational changes govern the reactivity of the ensuing bi-nitrogen-radical intermediates. Overall, this work establishes a practical platform for direct core reconfiguration, providing modular access to imidazole analogues of pyrazoles that are otherwise difficult to prepare or very expensive.