Construction and Asymmetric Skeletal Rearrangement of Medium-Sized Rings: Divergent Synthesis of Pyrazole/Pyrazolone-Annulated Frameworks

Developing efficient and selective methods for the divergent synthesis of spiro/fused cycles is of great interest yet poses a significant challenge. Herein, we present a distinctive approach for the divergent construction of pyrazole-fused medium-sized rings and pyrazolone spirocyclic frameworks. Unlike previous works that are limited to the construction of medium-sized rings, the presented strategy can achieve fused-to-spirocyclic framework conversion through an unprecedented asymmetric O- to C-acyl rearrangement of medium-sized ring systems. This approach is equally applicable to pharmaceutically relevant molecules, offering a versatile tool for late-stage modifications. Density functional theory calculations provide insights into the explanation for the regioselectivity of [1,4]-acyl transfer, which has previously remained unexplored.