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

Herewith we report late-stage catalytic selective oxidative functionalization of several steroids with a common gonane core, namely androstane derivatives 5α-androsterone-3-acetate, 5β-androstan-17β-ol-3-one (etiocholan-17β-ol-3-one), 17β-acetoxy-5β-androstan-3-one, and 5β-pregnane-3,20-dione, at C–H groups in the presence of chiral bis-amino-bis-pyridylmethyl and structurally related Mn complexes, using H2O2 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-17β-ol-3-one from ketonization, thus providing an opportunity to obtain 6,17- and 12,17-dihydroxy androstane derivatives without using protecting groups.