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

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 Pt_xSn_y/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.