Photochemical Skeletal Editing of Pyridines to Bicyclic Pyrazolines and Pyrazoles

We present an efficient one-pot photochemical skeletal editing protocol for the transformation of pyridines into diverse bicyclic pyrazolines and pyrazoles under mild conditions. The method requires no metals, photocatalysts, or additives and allows for the selective removal of specific carbon atoms from pyridines, allowing for unprecedented versatility. Our approach offers a convenient and efficient means for the late-stage modification of complex drug molecules by replacing the core pyridine skeleton. Moreover, we have successfully scaled up this procedure in stop-flow and flow-chemistry systems, showcasing its applicability to intricate transformations such as the Diels–Alder reaction, hydrogenation, 3 + 2 cycloaddition, and Heck reaction. Through control experiments and DFT calculations, we provide insights into the mechanistic underpinnings of this skeletal editing protocol.