Competition between C–C and C–H Bond Fluorination: A Continuum of Electron Transfer and Hydrogen Atom Transfer Mechanisms

Abstract

In 2015, we reported a photochemical method for directed C–C bond cleavage/radical fluorination of relatively unstrained cyclic acetals using Selectfluor and catalytic 9-fluorenone. Herein, we provide a detailed mechanistic study of this reaction, during which it was discovered that the key electron transfer step proceeds through substrate oxidation from a Selectfluor-derived N -centered radical intermediate (rather than through initially suspected photoinduced electron transfer). This finding led to proof of concept for two new methodologies, demonstrating that unstrained C–C bond fluorination can also be achieved under chemical and electrochemical conditions. Moreover, as C–C and C–H bond fluorination reactions are both theoretically possible on 2-aryl-cycloalkanone acetals and would involve the same reactive intermediate, we studied the competition between single-electron transfer (SET) and apparent hydrogen-atom transfer (HAT) pathways in acetal fluorination reactions using density functional theory. Finally, these analyses were applied more broadly to other classes of C–H and C–C bond fluorination reactions developed over the past decade, addressing the feasibility of SET processes masquerading as HAT in C–H fluorination literature.