Manganese catalyzed direct regio- and stereoselective hydroxylation of 5α- and 5β-androstane derivatives.

[Display omitted] • Late-stage C(sp3)–H oxyfunctionalization of saturated 5 α - and 5 β -steroids with gonane core. • Synthetic access to 20 oxidized metabolites, using H 2 O 2 as oxidant. • Preferential C–H hydroxylation of methylenic groups. • The oxidation regioselectivity is governed by steric effects. Herewith we report late-stage catalytic selective oxidative functionalization of several steroids with a common gonane core, namely androstane derivatives 5 α -androsterone-3-acetate, 5 β -androstan-17 β -ol-3-one (etiocholan-17 β -ol-3-one), 17 β -acetoxy-5 β -androstan-3-one, and 5 β -pregnane-3,20-dione, at C–H groups in the presence of chiral bis -amino- bis -pyridylmethyl and structurally related Mn complexes, using H 2 O 2 as terminal oxidant. Depending on the steric demand and absolute chirality of the catalyst, mono-hydroxylation at A, B, or C rings is achieved in up to 58% isolated yield. Strongly hydrogen-bond donating solvent hexafluoroisopropanol (HFIP) effectively protects the C17–OH group in etiocholan-17 β -ol-3-one from ketonization, thus providing an opportunity to obtain 6,17- and 12,17-dihydroxy androstane derivatives without using protecting groups. [ABSTRACT FROM AUTHOR]