CATALYTIC BETA-STEREOSPECIFIC EPOXIDATION OF UNSATURATED STEROIDS BY TRANS-DIOXORUTHENIUM(VI)TETRAMESITYLPORPHYRIN - STEREOCHEMICAL GROUNDS FOR THE BETA-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 7-alpha-epimer of the latter, is beta-stereospecific. Substitution by a methyl group on C-6 of pregnenolone acetate results in reduced reactivity towards catalytic epoxidation and lower beta-stereoselectivity. 19-Norsterol esters bearing a double bond at C-8-C-1 4 or C-1 4-C-1 5 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 beta-selectivity of DELTA-5-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 beta-side faces the oxo ligand. On the other hand, reaction on the alpha-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 5,6-beta-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 5,6-beta-epoxide. This change from pseudo-trans- to cis-stereochemistry of the A-B ring junction upon epoxidation is proposed to amplify the beta-diastereofacial selection. Variable temperature H-1 NM R spectra indicate that in CDCl2 solution the 5,6-beta-epoxide (not the 5,6-alpha-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 beta-stereospecificity in Ru(O)2(tmp)-catalysed steroid epoxidations.