Bio-inspired manganese-catalyzed asymmetric C-H oxidation: chiral pool expansion and predictive data analysis

Palone, Andrea
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ENG- The strategic, site, and enantioselective C-H oxygenation of aliphatic fragments holds significant appeal in organic chemistry due to the versatility of oxygen functionalities, which serve as valuable synthetic intermediates and key components in natural products and pharmaceuticals. Despite their potential utility, these transformations remain notably underdeveloped. However, several classes of oxygenase enzymes catalyze selective oxidation of strong C-H bonds using high-valent metal−oxo species, which are formed upon the reductive activation of O2 or H2O2 at metal centers. Drawing inspiration from the reaction mechanism of these enzymes, the development of bio-inspired iron and manganese catalysts has emerged as an efficient strategy for enantioselective C-H bond oxidation In this Thesis, general and straightforward catalytic synthetic methodologies have been developed to expand the chiral pool with optically active oxygenated structures through site-selective and enantioselective C(sp3)-H bond oxygenation, via powerful, bio-inspired metal-oxo species. These methodologies are especially focused on substrates containing non-activated C-H bonds and C-H bonds adjacent to methoxy groups. Furthermore, the implementation of predictive data science tools for identifying the key molecular parameters affecting stereoselectivity in manganese-catalyzed C-H oxidation was explored. Moreover, key aspects of bio-mimetic C-H oxidation catalysis include the use of bench-stable first-row transition metal catalysts that operate in short reaction times, under mild conditions, employing waste-free H2O2 as the oxidant, making these reactions environmentally friendly ​
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