D-Homo-steroids. Part 7. Further studies on the mechanism of D-homoannulation of 17α-hydroxypregnan-20-ones with Lewis acids

Abstract

The role of boron trifluoride in the D-homoannulation of a 17α-hydroxypregnan-20-one (1) is truly catalytic: kinetic and ¹⁹F n.m.r. data for the rearrangements of suitable derivatives show that boron trifluoride is not consumed. Rates of reaction, however, approximate to a second-order dependence on the concentration of boron trifluoride. The thermal rearrangement of 3β,17α-dihydroxy-5α-pregnan-20-one (9) leads initially to a preponderance of the same D-homo-ketol as that which results from the Lewis-acid-catalysed reaction, although prolonged thermal rearrangement leads to an equilibrated mixture of isomeric ketols. Use of magnesium ethoxide as a catalyst with both Lewis-acidic and -basic characteristics, gives a mixture of D-homo-ketols even under conditions of kinetic control. A new structure (13) is proposed for the transition state in the Lewis-acid-catalysed rearrangement: the novel features are a proton as the species responsible for holding the two oxygen atoms of the ketol in a syn-orientation, and catalysis by co-ordination of each oxygen atom with a molecule of Lewis acid. Selection of C-16 as the migrating centre is attributed to steric effects associated with the conformational rigidity of the hydrogen bridged transition state (13).