Application of Organometallic Chemistry on Metal Surfaces to Fine Chemicals: A New Access to Trimegestone by Chemo-, Regio-, and Diastereoselective Hydrogenation of Cetaloxopromegestone on Pt/Sn/SiO2 Catalysts

Abstract

The selective hydrogenation of cetaloxopromegestone (17α-methyl-17β-(1,2-dioxopropyl)-estra-5,9-dien-3-ketal) to the ketal precursor of Trimegestone (17α-methyl-17β-(2(S)-hydroxy-1-oxopropyl)-estra-5,9-dien-3-ketal) was carried out on various silica-supported monometallic catalysts and on bimetallic platinum–tin catalysts prepared by the interaction of Sn(CH3)4 with reduced Pt/SiO2 under H2 at room temperature. The selective hydrogenation must occur stereoselectively at the C21 ketone of cetaloxopromegestone, which possesses another ketone at C20 and two conjugated olefinic double bonds at C5–C10 and C9–C11. Of the various supported metals (Pd, Ru, Rh, Pt), the Pt/SiO2 catalyst exhibited low chemoselectivity (52%), but the diastereoselectivity at C21 reached 70%. The chemoselectivity of PtxSny/SiO2 catalysts increased from 52 to 100%. At the same time, however, the d.e. at C21 decreased from 70 to 30%. This inverse tendency of chemo- and diastereoselectivity upon the addition of tin can be explained by the fact that the multifunctional molecule can be coordinated to the surface either by its C21 carbonyl (which leads to high chemoselectivity) or simultaneously by its C=C bonds and C21 carbonyl (which leads to high diastereoselectivity). This substrate–catalyst binding, governed by the amount of tin that is added, controls the chemo- and diastereoselectivity via the coordination mode of the chiral cetaloxopromegestone.