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Cation Sampling Enables Regiodivergent Distal Functionalization of Ketones
Philipp Spieß1, Miloš Vavrík1, Jakob Frey1
1Institute of Organic Chemistry, University of Vienna, Währinger Straße 38, 1090 Vienna, Austria.
None:
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.
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