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The conformations of (Z)- and (E)-5-oxo-B-nor-5,10-secocholest-1(10)-en-3β-yl acetates (2 and 3, resp.) were examined by a combination of X-ray crystallographic analysis and NMR spectroscopy, with emphasis on the geometry of the cyclononenone moiety. The 1H- and 13C-NMR spectra showed that the unsaturated nine-membered ring of (E)-isomer 3 in C6D6 and (D6)acetone solution exists in a sole conformation of type 4;B1, which is similar to its solid-state conformation. The (Z)-isomer 2 in C6D6, CDCl3, and (D6)acetone solution, however, exists in two conformational forms of different families, with different orientation of the carbonyl group, the predominant form (85%) corresponding to the conformation of type 4;A1 and the minor (15%) to the conformation A2 present also in the crystalline state. In this solid-state conformations of the nine-membered ring of both compounds, the 19-Me and 5-oxo groups are ‘β’-oriented. The NMR analysis suggests that the nine-membered ring of 4 has a conformation of type 4;C1 in CDCl3 solution.

Oxidations of 5α-hydroxy-B-norcholestan-3β-yl acetate (8) with Pb(OAc)4 under thermal or photolytic conditions or in the presence of iodine afforded only complex mixtures of compounds. However, the HgO/I2 version of the hypoiodite reaction gave as the primary products the stereoisomeric (Z)- and (E)-1(10)-unsaturated 5,10-seco B-nor-derivatives 10 and 11, and the stereoisomeric (5R,10R)- and (5S,10S)-acetals 14 and 15 (Scheme 4). Further reaction of these compounds under conditions of their formation afforded, in addition, the A-nor 1,5-cyclization products 13 and 16 (from 10) and 12 (from 11) (see also Scheme 6) and the 6-iodo-5,6-secolactones 17 and 19 (from 14 and 15, resp.) and 4-iodo-4,5-secolactone 18 (from 15) (see also Scheme 7). Oxidations of 5β-hydroxy-B-norcholestan-3β-yl acetate (9) with both hypoiodite-forming reagents (Pb(OAc)4/I2 and HgO/I2) proceeded similarly to the HgO/I2 reaction of the corresponding 5α-hydroxy analogue 8. Photolytic Pb(OAc)4 oxidation of 9 afforded, in addition to the (Z)- and (E)-5,10-seco 1(10)-unsaturated ketones 10 and 11, their isomeric 5,10-seco 10(19)-unsaturated ketone 22, the acetal 5-acetate 21, and 5β,19-epoxy derivative 23 (Scheme 9). Exceptionally, in the thermal Pb(OAc)4 oxidation of 9, the 5,10-seco ketones 10, 11, and 22 were not formed, the only reaction being the stereoselective formation of the 5,10-ethers with the β-oriented epoxy bridge, i.e. the (10R)-enol ether 20 and (5S,10R)-acetal 5-acetate 21 (Scheme 8). Possible mechanistic interpretations of the above transformations are discussed.

Oxidations of 14α-hydroxy-5α-cholestan-3β-yl acetate (5) with lead tetraacetate under thermal or photolytic conditions or in the presence of iodine proceed mainly by fragmentation of the C(13)−C(14) bond to give as the primary products the 13,18-didehydro-13,14-seco derivative 6 and the (E )-Δ¹²-13,14-seco ketone 11, respectively. Further transformations of these compounds under conditions of their formation afforded, in addition, the acetoxy derivatives 7 – 9 (from 6), and the D-homo-C-nor compound 12 and (12R,13R)-epoxide 13 (from 11). Unexpectedly, the photolytic lead-tetraacetate oxidation of 5 resulted partly (to ca. 20%) in a reversible fragmentation involving scission and recombination of the C(8)−C(14) bond followed by formation of the 14β,22-ether 10. Possible mechanisms for the observed transformations are discussed.