Oxidation of unactivated c-h bonds catalyzed by manganese complexes: control over site-selectivity and enantioselectivity

The oxidation of aliphatic C-H bonds is a very powerful reaction because it allows the functionalization of inert C-H bonds, converting them into a suitable sites for further chemical elaboration. However, it also represents one of the most challenging reactions in modern synthetic organic chemistry because the multitude of aliphatic C-H bonds in a molecule makes site selective oxidation particularly difficult. Moreover, the introduction of chirality represents an unmet but very appealing challenge, because the asymmetric oxidation of hydrocarbons produces chiral compounds of high value in organic synthesis from readily available starting materials. Until now, examples of enantioselective oxidation of nonactivated aliphatic C-H bonds remain exclusive to enzymes. Taking inspiration from the mechanism of action of transition metal dependent oxygenases, such as cytochrome P450, naphthalene 1,2-dioxigenase and proline 4-hydroxylase, this thesis has been devoted to the development of new catalytic systems capable to oxidize nonactivated aliphatic C-H bonds in a site-selective and enantioselective manner. In particularly, chemo- and enantioselective aliphatic C-H oxidation reactions, especially focused in amide containing substrates have been developed. These reactions have been carried out employing bioinspired manganese and iron complexes, bearing N-based tetradentate ligands, hydrogen peroxide as oxidant and carboxylic acids, in short reaction times and under mild conditions. Moreover, well aligns with sustainability criteria, extremely important in today’s society; it is based on first row transition metal catalysts (iron and manganese), less toxic than the noble metals traditionally employed in catalysis, in combination with hydrogen peroxide, an oxidant that exhibits a high atom economy and that only generates water as by-product.