Electrocatalytic Cross-Coupling Reactions Assisted By Redox-Active Mediators

Abstract

The seminar will detail electrocatalytic C–C and C–N bond-forming methodologies enabled by redox-active mediators and shuttles. Here, we will demonstrate a symbiotic relationship between energy storage and metal-catalyzed organic synthesis. Two research initiatives will be discussed that highlight the use of a mediator to (i) protect a coupling catalyst from overreduction through a degenerate shuttling of electrons and (ii) assist in oxidation of complexes with slow ET kinetics under electrochemical conditions.The concept of protecting catalyst from degradation using shuttles will be discussed in the context of cross-electrophile coupling (XEC). Couplings of alkyl and aryl halides promoted by electrochemistry represents an attractive alternative to conventional methods that require stoichiometric quantities of high-energy reductants. Most importantly, electroreduction can readily exceed the reducing potentials of chemical reductants to activate catalysts with improved reactivities and selectivities that are otherwise incompatible with conventional reductants. This work details the mechanistically-driven development of an electrochemical methodology for XEC that utilizes redox-active shuttles developed by the energy-storage community to protect reactive coupling catalysts from overreduction. The resulting electrocatalytic system is practical, scalable, and broadly applicable to the reductive coupling of a wide range of aryl, heteroaryl, or vinyl bromides with primary or secondary alkyl bromides. The impact of overcharge protection as a strategy for electrosynthetic methodologies is underscored by the dramatic differences in yields from coupling reactions with added redox shuttles (generally >80%) and those without (generally <20%). In addition to excellent yields for a wide range of substrates, reactions protected from overreduction can be performed at high currents and on multigram scalesThe second half of the talk will demonstrate the use of mediators to protect ligandless complexes that are susceptible to electroplating on a cathode and to facilitate oxidation of the electrochemically-inactive catalysts to the active form. This strategy is applied to an electrochemically driven, scalable Chan-Lam-Evans reaction that utilizes simple copper salts to promote C-N bond formation under an inert atmosphere. This work represents a rare example of air-free CLE coupling. This oxidative reaction is performed in an undivided cell with a simple Cu salt that would otherwise rapidly plate out of solution. Mediator-assisted CLE coupling provides access to a broad range of amine products that are otherwise challenging to form even in air. The methodology seeks to eliminate the need for O2 on scale and provide an attractive alternative for process groups in industry.