Direct regio- and stereoselective mono- and polyoxyfunctionalization of estrone derivatives at C(sp³)-H bonds

Late-stage catalytic selective oxidative C-H functionalization at B and C rings of estrone 3-acetate, 17α- and 17β-estradiol 3-acetates with H₂O₂ in the presence of bioinspired nonheme Mn complexes with N₄-donor ligands has been developed. Depending on the ligand architecture and absolute chirality, products of α-hydroxylation or ketonization at C6, or α-hydroxylation at C9, or 9,11-desaturation/C12α-hydroxylation can be obtained in synthetically useful yields; the resulting monooxygenated derivatives can be involved in further selective oxidative transformations to yield polyoxygenated metabolites. The aromatic A ring remains intact under the conditions, and ketonization of the hydroxo groups at C17 is effectively prevented by using hexafluoroisopropanol as strong hydrogen bond donor reaction solvent.