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). Pts{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.