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Abstract Electrochemical oxidant regeneration is challenging in reactions that have a slow redox step because the steady‐state concentration of the reduced oxidant is low, causing difficulties in maintaining sufficient current or preventing potential spikes. This work shows that applying an understanding of the relationship between intermediate cation stability, oxidant strength, overpotential, and concentration on reaction kinetics delivers a method for electrochemical oxoammonium ion regeneration in hydride abstraction‐initiated cyclization reactions, resulting in the development of an electrocatalytic variant of a process that has a high oxidation transition state free energy. This approach should be applicable to expanding the scope of electrocatalysis to include additional slow redox processes. 

Abstract Numerous hydride‐abstracting agents generate the same cationic intermediate, but substrate features such as intermediate cation stability, oxidation potential, and steric environment can influence reaction rates in an oxidant‐dependent manner. This manuscript provides experimental data to illustrate the role that structural features play in the kinetics of hydride abstraction reactions with commonly used quinone‐, oxoammonium ion‐, and carbocation‐ based oxidants. Computational studies of the transition state structures and energies explain these results and energy decomposition analysis calculations reveal unique sensitivities to electrostatic attraction and steric repulsions. Rigorous rate studies of select reactions validated the capacity of the calculations to predict reactivity trends. Additionally, kinetics studies demonstrate the potential for product inhibition in DDQ‐mediated reactions. These studies provide a clear guide to select the optimal oxidant for structurally disparate substrates and lead to predictions of reactivity that were validated experimentally. 

Carbon–hydrogen bond functionalizations provide an attractive method for streamlining organic synthesis, and many strategies have been developed for conducting these transformations. Hydride-abstracting reactions have emerged as extremely effective methods for oxidative bond-forming processes due to their mild reaction conditions and high chemoselectivity. This review will predominantly focus on the mechanism, reaction development, natural product synthesis applications, approaches to catalysis, and use in enantioselective processes for hydride abstractions by quinone, oxoammonium ion, and carbocation oxidants. These are the most commonly employed hydride-abstracting agents, but recent efforts illustrate the potential for weaker ketone and triaryl borane oxidants, which will be covered at the end of the review.