Mechanisms of C(sp 3 )-H and C = C selective oxidative heterofunctionalizations by non-heme Fe and Mn mimics of oxygenase enzymes

Developing approaches to predictably selective functionalization of aliphatic C-H bonds has long been one of the major challenges ("Holy grails", Bergman, Acc. Chem. Res. 28 (1995) 154) of synthetic chemistry. Transition metal based catalysts offer unsurpassed opportunities for selective transformation of C(sp 3 )-H groups unto novel C-X groups, thus enabling treating "nonfunctional" aliphatic C-H groups as a useful synthetic handle. This is largely achieved via adopting principles of biomimetic control of chemical selectivity (Breslow, Acc. Chem. Res. 13 (1980) 170) for C-H functionalization of complex molecules. Initially, such studies were focused mostly on disclosing the nature of active sites of bioinspired transition metal based catalyst systems, mimicking the catalytic reactivity of naturally occurring metalloenzymes (oxygenases) in aliphatic C-H, as well as in a variety of C=C bond oxygenations. At the current level of knowledge, researchers have the opportunity to apply the established mechanistic principles to develop practical catalyst systems for deliberately chemo- and stereoselective functionalization of complex organic molecules without need for introducing directing groups or redesigning existing multistep synthetic procedures ( late -stage functionalization ). This contribution is aimed at summarizing the state -of -the -art understanding of the molecular mechanisms operating in Fe and Mn based bioinspired catalyst systems for chemo-, regio-, and stereoselective oxidative heterofunctionalization of C(sp 3 )-H and C=C bonds. The discussion focuses around the key high -valent synthetic metal-oxo intermediates exhibiting a rich chemical reactivity palette, which is potentially even broader than that of their metalloenzymic prototypes.