Annulative Skeletal Diversification of Pyrimidines to Expanded Heteroaromatic Space

Single-atom skeletal editing has recently emerged as a powerful strategy for the direct diversification of the heterocyclic cores of various compounds. Yet, methods that enable monocycle-to-bicycle transformations that involve core atom changes remain scarce. Herein, we report a two-step, one-pot protocol that converts pyrimidines into 7-azaindazoles and pyrazolo[1,5-a]pyrimidines, two privileged scaffolds in medicinal chemistry. Fine-tuning the reaction parameters enables chemodivergent control, allowing selective access to either framework, with the pyrimidine scope including pharmaceutical drug molecules. Moreover, the strategy has been extended to afford differently substituted pyrimidines, partially saturated fused skeletons, and quinoline derivatives. Access to this broad, expanded, heteroaromatic space underscores the potential for heterocyclic diversification using this approach.