Methane Manifesto: A Theorist’s Perspective on Catalytic Light Alkane Functionalization

The catalytic functionalization of light alkanes, particularly methane, has attracted considerable attention from the inorganic and organic research communities for nearly five decades. The literature mechanisms for C—H activation may be divided into three broad categories: metal directed, ligand directed, or metal-ligand directed. The advantages for metal-ligand directed pathways have both steric and electronic origins. Furthermore, computations suggest that the stereoelectronic requirements for the activation and functionalization component reactions can be diametrically opposed. From this research, several questions emerge for theorists that would aid in the hunt for synthesizable complexes for efficient catalytic functionalization of light alkanes. First, is there a happy medium by which a complex is nucleophilic enough to activate a alkane C—H bond with a reasonable rate, but that is not so basic as to thwart the subsequent C—O,N bond-forming step? Second, what are the energetic consequences of moving along the “ide”/“yl” continuum? Third, how can the electronic coupling among the three main catalyst components—metal, actor ligand, and spectator ligand—be modulated to permit the use of Earth-abundant catalysts to effect catalytic functionalization of light alkanes?