Triphenylphosphine Oxide-Enabled Nickel-Catalyzed Electrochemical C(sp3)–C(sp2) Cross-Coupling of Challenging Heteroaryl Electrophiles

We report a practical electrochemical decarboxylative cross-coupling enabling direct C(sp3)-C(sp2) bond formation between redox-active esters (RAEs) and recalcitrant (hetero)aryl electrophiles. The transformation is enabled by the use of triphenylphosphine oxide (TPPO) as an additive in the synergistic Ag-Ni electrocatalytic system reported previously. Critically, TPPO acts as a cooperative ligand additive that enables efficient coupling of heteroaryl scaffolds previously inaccessible under state-of-the-art electrochemical cross-electrophile coupling (XEC) conditions. Notably, this strategy accommodates nitrogen-rich heterocycles, including pyrazoles, pyrimidines, quinazolines, and indazoles, despite their frequent failure in existing methodologies and their importance as key medicinal chemistry scaffolds. This advance represents a qualitative expansion of the accessible chemical space, rather than an incremental extension of substrate scope. The protocol operates under mild conditions using an ElectraSyn setup, inexpensive Ni sources, and stoichiometric AgOTf, without strict exclusion of air or moisture, and has been validated at gram scale.