Catalytic β-stereospecific epoxidation of unsaturated steroids by trans-dioxoruthenium(VI)tetramesitylporphyrin. Stereochemical grounds for the β-diastereofacial selection

The catalytic epoxidation by dioxygen with trans-dioxoruthenium(VI)tetramesitylporphyrin [Ru(O)2(tmp)] of the acetic esters of cholesterol, 3-epicholesterol and isocholesterol,† as well as of the 7α-epimer of the latter, is β-stereospecific. Substitution by a methyl group on C-6 of pregnenolone acetate results in reduced reactivity towards catalytic epoxidation and lower β-stereoselectivity. 19-Norsterol esters bearing a double bond at C-8–C-14 or C-14–C-15 are inert towards O2–RU(O)2(tmp) epoxidation. The variable reactivity of these sterol ester substrates is explained by a transition state in which the steroid nucleus approaches the ruthenium–oxo bond approximately perpendicular to the porphyrin ring. The β-selectivity of Δ5-sterol ester epoxidation is accounted for in terms of this transition state geometry which provides a good fit between the porphyrin catalyst and the steroid substrate when the β-side faces the oxo ligand. On the other hand, reaction on the α-side involves unfavourable steric interactions between axial hydrogen atoms on C-3 and C-7 of the substrate and the porphyrin ring and a mesityl substituent of the catalyst, respectively. The crystal and molecular structures of cholesteryl ethyl carbonate and of its 5,6β-epoxide have been determined by single-crystal X-ray diffraction. The overall conformation of the steroid nucleus is nearly planar in the cholesteryl ester, while it is bent at the junction between rings A and B in the 5,6β-epoxide. This change from pseudo-trans- to cis-stereochemistry of the A–B ring junction upon epoxidation is proposed to amplify the β-diastereofacial selection. Variable temperature 1H NMR spectra indicate that in CD2Cl2 solution the 5,6β-epoxide (not the 5,6α-epoxide) of the cholesteryl acetate coordinates the ruthenium atom of Ru(CO)(tmp) with a nearly perpendicular geometry. These results corroborate the orthogonal substrate approach and the steric origin of the β-stereospecificity in Ru(O)2(tmp)-catalysed steroid epoxidations.