Catalyzing Electrosynthesis: A Homogeneous Electrocatalytic Approach to Reaction Discovery

CONSPECTUS: Electrochemistry has been used as a tool to drive chemical reactions for over two centuries. With the help of an electrode and a power source, chemists are bestowed with an imaginary reagent whose potential can be precisely dialed in. The theoretically infinite redox range renders electrochemistry capable of oxidizing or reducing some of the most tenacious compounds (e.g., F- to F-2 and Li+ to Li-0). Meanwhile, a granular level of control over the electrode potential allows for the chemoselective differentiation of functional groups with minute differences in potential. These features make electrochemistry an attractive technique for the discovery of new modes of reactivity and transformations that are not readily accessible with chemical reagents alone. Furthermore, the use of an electrical current in place of chemical redox agents improves the cost-efficiency of chemical processes and reduces byproduct generation. Therefore, electrochemistry represents an attractive approach to meet the prevailing trends in organic synthesis and has seen increasingly broad use in the synthetic community over the past several years. While electrochemical oxidation or reduction can provide access to reactive intermediates, redox-active molecular catalysts (i.e., electrocatalysts) can also enable the generation of these intermediates at reduced potentials with improved chemoselectivity. Moreover, electrocatalysts can impart control over the chemo-, regio-, and stereoselectivities of the chemical processes that take place after electron transfer at electrode surfaces. Thus, electrocatalysis has the potential to significantly broaden the scope of organic electrochemistry and enable a wide range of new transformations. Our initial foray into electrocatalytic synthesis led to the development of two generations of alkene diazidation reactions, using transition-metal and organic catalysis, respectively. In these reactions, the electrocatalysts play two critical roles; they promote the single-electron oxidation of N-3(-) at a reduced potential and complex with the resultant transient N-3(center dot) to form persistent reactive intermediates. The catalysts facilitate the sequential addition of 2 equiv of azide across the alkene substrates, leading to a diverse array of synthetically useful vicinally diaminated products. We further applied this electrocatalytic radical mechanism to the heterodifunctionalization of alkenes. Anodically coupled electrolysis enables the simultaneous anodic generation of two distinct radical intermediates, and the appropriate choice of catalyst allowed the subsequent alkene addition to occur in a chemo- and regioselective fashion. Using this strategy, a variety of difunctionalization reactions, including halotrifluoromethylation, haloalkylation, and azidophosphinoylation, were successfully developed. Importantly, we also demonstrated enantioselective electrocatalysis in the context of Cu-promoted cyanofunctionalization reactions by employing a chiral bisoxazoline ligand. Finally, by introducing a second electrocatalyst that mediates oxidatively induced hydrogen atom transfer, we expanded scope of electrocatalysis to hydrofunctionalization reactions, achieving hydrocyanation of conjugated alkenes in high enantioselectivity. These developments showcase the generality of our electrocatalytic strategy in the context of alkene functionalization reactions. We anticipate that electrocatalysis will play an increasingly important role in the ongoing renaissance of synthetic organic electrochemistry.