Such an approach has been successfully implemented in a wide range of catalytic asymmetric transformations, accelerating reaction optimization while meticulously designing new improved catalytic performers through predictive modeling. We envision that the use of these in silico modeling tools can overcome the limitations of traditional optimization methods so far employed in C-H oxidation catalyst development, and thus may grow the potential of this reaction by unraveling the key parameters impacting yield and selectivity. In this context, we recently reported the site-and enantioselective oxidation of methylenic C-H bonds in monosubstituted cyclohexanes with H2O2 catalyzed by chiral manganese complexes. One interesting facet of the reaction is the furnishing of the corresponding ketoamides derived from the oxidation at C3 of the cyclohexane ring, producing a desymmetrized product with high enantioselectivity (Figure ). Besides being a rare case of site-selective and enantioselective oxidation of strong C-H bonds, the resulting enantioenriched ketoamides have several diversification handles and are important building blocks for the synthesis of bioactive compounds. For example, product 1 is a valuable intermediate en route to the synthesis of the anticancer agent EPZ-719, a potent SET domain-containing protein 2 (SETD2) inhibitor (Figure ). Enantioselectivities and product yields were found to be quite sensitive to apparently modest changes in catalyst structure, substrate, and carboxylic acid co-catalyst, with the best results in terms of enantioselectivity being obtained with N-cyclohexylalkanamides, a sterically encumbered manganese catalyst ([Mn(OTf)2( TIPS ecp)]) (ecp = N,N′-diethyl N,N′-bis(2pyridylmethyl)-1,2-transdiamino cyclohexane) and cyclopropanecarboxylic acid. The proposed reaction mechanism for this class of catalysts entails heterolytic cleavage of H2O2 in a [Mn III (OOH)(OCOR)(N4L)] 2+ intermediate (where N4L stands for a tetradentate ligand such as TIPS ecp) facilitated by the carboxylic acid, to generate an electrophilic high-valent manganese oxo carboxylato species, [Mn V O(OCOR)(N4L)] 2+ , that has been shown to execute C3-H hydroxylation via a hydrogen atom transfer (HAT)/rebound mechanism as exhibited by heme and non-heme iron-dependent hydroxylases. Overoxidation of the first formed alcohol moiety to the corresponding ketone eliminates the stereocenter at C3, but the product remains chiral because of the initial desymmetrization that uncovers a remote chiral center at C1 (Figure ).