Efficient Anodic and Direct Phenol-Arene C,C Cross-Coupling: The Benign Role of Water or Methanol

C,C cross-coupling reactions for the synthesis of nonsymmetrical
biaryls represent one of the most significant transformations in contemporary
organic chemistry. A variety of useful synthetic methods have been
developed in recent decades, since nonsymmetrical biaryls play an
evident role in natural product synthesis, as ligand systems in homogeneous
catalysis and materials science. Transformation of simple arenes by
direct C,H activation belongs to the cutting-edge strategies for creating
biaryls; in particular the 2-fold C,H activation is of significant
interest. However, in most examples very costly noble metal catalysts,
ligand systems, and significant amount of waste-producing oxidants
are required. Electrochemical procedures are considered as inherently
“green” methods, because only electrons are required
and therefore, no reagent waste is produced. Here, we report a metal-free
electrochemical method for cross-coupling between phenols and arenes
using boron-doped diamond (BDD) anodes in fluorinated media. Our sustainable
approach requires no leaving functionalities. Employing water or methanol
as mediator represents the key improvement for achieving nonsymmetrical
biaryls with superb selectivity and synthetic attractive yields.