Divergent Pyridine-to-Pyrazole Conversion via Carbon-Retentive Skeletal Editing.

Regioselective pyrazole synthesis remains a longstanding challenge in medicinal chemistry due to difficulties controlling N-differentiation during ring construction or functionalization. We address this through carbon-retentive skeletal editing that preserves molecular complexity while encoding regioselectivity during framework reorganization. From a single pyridine, mechanistically divergent pathways deliver structurally distinct pyrazoles: photochemical radical deconstruction-rearrangement yields aldehyde- or amine-substituted products; thermal polar reorganization with hydrazines provides orthogonal substitution patterns. Both proceed under mild, one-pot conditions and accommodate complex pharmaceuticals. This divergent platform enables predictable access to complementary pyrazole architectures from common pyridines, circumventing the regioselectivity limitations of peripheral functionalization and expanding accessible chemical space for drug discovery.