Leveraging ligand-based proton and electron transfer for aerobic reactivity and catalysis

While O2 is an abundant, benign, and thermodynamically potent oxidant, it is also kinetically inert. This frequently limits its use in synthetic transformations. Correspondingly, direct aerobic reactivity with O2 often requires comparatively harsh or forcing conditions to overcome this kinetic barrier. Forcing conditions limit product selectivity and can lead to over oxidation. Alternatively, O2 can be activated by a catalyst to facilitate oxidative reactivity, and there are a variety of sophisticated examples where transition metal catalysts facilitate aerobic reactivity. Many efforts have focused on using metal-ligand cooperativity to facilitate the movement of protons and electrons for O2 activation. This approach is inspired by enzyme active sites, which frequently use the secondary sphere to facilitate both the activation of O2 and the oxidation of substrates. However, there has only recently been a focus on harnessing metal-ligand cooperativity for aerobic reactivity and, especially, catalysis. This perspective will discuss recent efforts to channel metal-ligand cooperativity for the activation of O2, the generation and stabilization of reactive metal-oxygen intermediates, and oxidative reactivity and catalysis. While significant progress has been made in this area, there are still challenges to overcome and opportunities for the development of efficient catalysts which leverage this biomimetic strategy. O2 is an attractive oxidant but it is also kinetically inert which limits its use in synthetic transformations. Metal-ligand cooperativity is a promising biomimetic strategy to activate O2 for oxidative reactivity and catalysis.