Angle-Strained Cycloalkyne-Mediated Carbonyl 1,2-Transposition

Carbonyl 1,2-transposition represents a powerful yet challenging transformation in molecular editing, enabling the precise repositioning of ketone functionalities within carbocyclic frameworks. While this approach holds significant promise for streamlining synthetic routes and tailoring molecular properties, efficient methods for relocating carbonyls in ubiquitous cyclopentanones remain underdeveloped. Herein, we report a strain-release-driven strategy for the one-step translocation of carbonyl moieties within prevalent cyclic ketones. This method exploits the pronounced reactivity of angle-strained cycloalkynes, generated in situ directly from accessible cyclic ketones, which then undergo regioselective 1,2-addition followed by hydrolysis to yield the desired carbonyl-migrated products. By harnessing the intrinsic strain energy of small-ring cycloalkynes to facilitate a fundamental skeletal rearrangement, this work provides rapid access to complex structures and natural product analogs through late-stage functionalization.