Cation Sampling Enables Regiodivergent Distal Functionalization of Ketones.

Despite notable progress in catalytic olefin isomerization processes enabling distal Csp3-H functionalization, most methods depend on complex metal-based catalytic systems and face inherent challenges in achieving regiodivergent outcomes. Herein, we present a conceptually distinct approach in which we leverage cationic olefin isomerization for regiodivergent Csp3-H functionalization, wherein the selectivity results from a ketone-assisted process we term cation sampling. This method enables site-selective regiodivergent functionalization of sp3-hybridized carbons, allowing the formation of C-heteroatom bonds in challenging positions and unlocking access to products previously unattainable through metal-based methodologies. Detailed mechanistic studies support the proposed reaction pathway, which involves the engagement of two key oxocarbenium species that govern the regioselectivity of this process.