Application of organometallic chemistry on metal surfaces to fine chemicals: A new access to trimegestane by chemo-, regio-, and diastereoselective hydrogenation of cetaloxopromegestone on Pt/Sn/SiO2 catalysts

The selective hydrogenation of cetaloxopromegestone (17 alpha -methyl-17 be ta-(1,2-dioxopropyl)-estra-5,9-dien-3-ketal) to the ketal precursor of Trim egestone (17 alpha -methyl-17 beta-(2(S)-hydroxy-1-oxopropyl)-estra-5,9-die n-3-ketal) was carried out on various silicasupported monometallic catalyst s and on bimetallic platinum-tin catalysts prepared by the interaction of S n(CH3)(4) with reduced Pt/SiO2 under H-2 at room temperature. The selective hydrogenation must occur stereoselectively at the C-21 ketone of cetaloxop romegestone, which possesses another ketone at C-20 and two conjugated olef inic double bands at C-5-C-10 and C-9-C-11. Of the various supported metals (Pd, Ru, Rh, Pt), the Pt/SiO2 catalyst exhibited low chemoselectivity (52% ), but the diastereoselectivity at C-21 reached 70%. The chemoselectivity o f PtxSny/SiO2 catalysts increased from 52 to 100%. At the same time, howeve r, the d.e. at C-21 decreased from 70 to 30%. This inverse tendency of chem o- and diastereoselectivity upon the addition of tin can be explained by th e fact that the multifunctional molecule can be coordinated to the surface either by its C-21 carbonyl (which leads to high chemoselectivity) or simul taneously by its C=C bonds and C-21 carbonyl (which leads to high diastereo selectivity). This substrate-catalyst binding, governed by the amount of ti n that is added, controls the chemo- and diastereoselectivity via the coord ination mode of the chiral cetaloxopromegestone. (C) 2001 Academic Press.