Chemo-, Regio-, and Diastereoselective Hydrogenation of Oxopromegestone into Trimegestone over Supported Platinoids: Effects of the Transition Metal, Support Nature, Tin Additives, and Modifiers

The selective hydrogenation of oxopromegestone (17α-methyl-17β-(1,2-dioxopropyl)-estra-4,9-dien-3-one), 1, into Trimegestone (17α-methyl-17β-(2(S)-hydroxy-1-oxopropyl)-estra-4,9-dien-3-one), 2, was carried out on various monometallic catalysts. The order of activity, Pd〉Rh〉Pt〉Ir〉Os, was almost opposite that of the chemoselectivity (selective hydrogenation of the carbonyl versus the internal olefinic double bond), Os〉Ir〉Pt=Pd〉Rh. No metal gave any required diastereoselectivity (selective formation of the 21(S)-OH alcohol). However, silica-supported rhodium, palladium, and platinum exhibited 100% diastereomer excess (d.e.) for the hydrogenation of the C₃ carbonyl group. Pt/SiO₂ catalyst exhibited a low chemoselectivity (24%), but its TON activity was relatively high (42×10^-3 s^-1). Pt_s(Sn)_n/SiO₂ catalysts, prepared by the interaction of Sn(CH₃)₄ with reduced Pt/SiO₂ under H₂ at room temperature, exhibited a significant increase of chemoselectivity compared to Pt/SiO₂, but still a low diastereoselectivity to the desired 21(S)-OH unsaturated ketoalcohol, 2. In parallel, the d.e. for the hydrogenation of the C₃ carbonyl group decreased from 100% to 34%. The addition of (-)cinchonidine and hydrocinchonidine on the platinum-tin catalysts sharply increased the d.e. in favor of the 21(S)-OH unsaturated ketoalcohol to 70% without changing the chemoselectivity.