David N. Kirk

Reactions of epoxides—XVII: “Backbone rearrangements” of cholest-5-ene and 5,6α-epoxy-5α-cholestane

Abstract The “backbone rearrangement” leading to 13(17)-enes (e.g. III) occurs when cholest-5-ene is heated with toluene-p-sulphonic acid in acetic acid, and also when 5,6α-epoxy-5α-cholestane (VII) is treated with boron trifluoride.

Tetrahedron report number 22 : An empirical analysis of the circular dichroism of chiral olefins☆☆☆

Abstract CD data between 185 and 230 nm for 228 chiral olefins have been analysed empirically in order to determine the main features of the relationships between molecular structure and chiroptical properties. Most of the compounds examined are cyclohexene or methylene-cyclohexane derivatives: they include many compounds of steroid type. The regular and generally unstrained structures of such compounds are particularly favourable for initial studies on olefins, as they were earlier for carbonyl compounds. Cyclopentene and methylene-cyclopentane analogues are included for comparison, but are not discussed in detail because of their relatively limited number and less-clearly defined conformations. Olefinic compounds are divided into four classes (A–D), according to their substitution patterns when considered as alkylated ethylene derivatives. In the first stage of the analysis, characteristic wavelengths ar recognised for the two (or three) electronic transitions detectable from the CD curves for each class of olefine. Some of the tetrasubstituted-ethylene analogues have optically-active transitions in the regions ca. 220 nm and ca. 202 nm, but one or other of these transitions may be undetectable from CD surveys for some structural types, a feature not appreciated in earlier discussions of olefin CD. In the second stage of the analysis, the CD curves are studied by the usual empirical method of pairwise comparisons, in order to evaluate the contributions (δΔϵ) of structural features to the observed CD at each of the absorption bands. Each of the four substituted-ethylene classes shows its own characteristic behaviour, confirming that no one symmetry rule can be applicable to all chiral olefins. The main conclusions for the lowest-energy CD band (⩾ 200 nm) are: Class A 1,1- Disubstituted ethylenes . Exocyclic methylene compounds for the most part follow a carbonyl-like “Octant Rule”, the main point of difference being a large consignate (“octant”) contribution from a “β”-axial methyl group, which can outweigh effects of carbocyclic rings; Class B Cis-1,2- disubstituted ethylenes . Cyclohexene analogues give a CD band with sign corresponding to a cosignate effect of allylic axial CH bonds; Class C Trisubstituted ethylenes . Compounds of the “1-methylcyclohexene” type follow those of class (B) fairly closely, but “trisubstituted ethylene” fragments of the ethylidenecyclohexane type, including “Δ” 1(19) -octalin “analogues, give strong CD bonds with signs determined by the chirality of the ethylidenecyclohexane unit; an additional feature of “Δ 1(19) -octalin” analogues is a very large dissignate effect accompanying axial alkyl substitution at the allylic carbon atom trans to the olefinic CH bond: alkyl substitution at the other allylic centres has relatively little effect; Class D Tetrasubstituted ethylenes . These compounds generally show rather weak CD curves, but axial-allylic methyl substituents produce dissignate effects. The CD characteristics associated with the second (higher energy) absorption band ( quasi-equatorial alkyl substituents are present.

Chiroptical studies-part 991: The circular dichroism of seven-membered lactams and lactones

Abstract This empirical analysis of CD data for 7-membered lactams includes examples of all twelve possible structural types in which the lactam is fused to a cyclohexane ring as part of a polycyclic compound. The CD behaviour of several classes of lactams shows ‘dOguras sign rule’ to be an over-simplification. The signs and values of Δϵ for lactams in which the second ring is fused at the 3,4- or 6,7-positions of the lactam ring show considerable deviations from the “normal’ values for 4,5- or 5,6-fused lactams. No simple pattern of group contributions emerged from this analysis, but a correlation of CD behaviour with the torsion angle in the C-CO-NH-C structural component is suggested, on the basis of a study of Dreiding models, and is supported by the result of an X-ray crystallographic analysis of one of the lactams.This study of CD data is extended to a smaller group of lactones with a seven-membered ring, most of which show Cotton effects opposite in sign and of smaller magnitude than those of the corresponding lactams.

Improved preparation of pregn-5-ene-3β, 16α, 20-triols and 5α-Pregnane-3α, 16α, 20-triols

Abstract The compounds named in the title were prepared by routes which included the reduction of suitable 16α,17-epoxypregnan-20-ones with aluminium amalgam to give 16α-hydroxypregnan-20-ones, and reduction of the 20-oxo function either with sodium borohydride to obtain the 3, 16α, 20β-triols or with lithium-liquid ammonia to obtain the 3, 16α, 20α-triols.

Reactions of epoxides—XIII : The backbone rearrangement of 3α-acetoxy-4α,5-epoxy-5α-cholestanes with lewis acid

Abstract 3α-Acetoxy-4α,5-epoxy-4β-methyl-5α-cholestane (Ia) undergoes a “backbone rearrangement” with BF3etherate to give the (enantio) 5β,14β-dimethyl-18,19-bisnorcholest-13(17)-ene derivative (IIa). One of the products obtained from reaction of 3α-acetoxy-4α,5-epoxy-5α-cholestane (Ib) with a Grignard reagent is now shown to be the related 13(17)-olefin (IIb). The epoxide Ib also undergoes a backbone rearrangement on treatment with BF3-etherate.

A study of the rearrangement of hecogenin derivatives into C-nor-D-homo steroids

Abstract Base-catalysed decomposition of the 12-tosylhydrazone (II) of hecogenin acetate under aprotic conditions occurs without rearrangement, to give the Δ 11 -olefin (III). Hydroxylic solvents favour the formation of the C-nor-D-homo-Δ 13(17a) -olefin (VI). The tosylate (Ia) of the 12β-alcohol derived from hecogenin acetate undergoes solvolysis to give mixtures containing varying proportions of the C-nor-D-homo-Δ 13(17a) -olefin (VI) and the Δ 7a(18) -isomer (IV), depending upon the reaction conditions. Polar solvents and elevated temperatures favour the endocyclic (Δ 13(17a) -olefin, but the exocyclic (Δ 17a(18) -olefinpredominates in solvents of lo NMR evidence is presented in support of the Δ 13(17a) -structure for the endocyclic olefin. Rearrangements of the 12-tosylhydrazone (XVIb) and 12β-tosyloxy (XVIa) derivatives in the pregnane series gave only the endocyclic Δ 13(17a) - and Δ 17(17a) -olefins.

Some observations on the preparation of 2-hydroxy-steroid 4-En-3-ones

Improved experimental conditions are described for the preparation of 2β, 17β- and 2α,17β-dihydroxyestr-4-en-3-one diacetates and 2β-acetoxyandrost-4-ene-3,17-dione. 6β-Acetoxyandrost-4-ene-3,17-dione has been obtained, together with the 2-acetoxy-derivatives, by acetolysis of 6β-bromoandrost-4-ene-3,17-dione. N.m.r. and c.d. data for the 2-hydroxy-compounds and their acetates are interpreted in terms of alternative conformations for ring A.

18-Substituted steroids. Part 12. Synthesis of aldosterone 21-sulphate, and an improved general procedure for preparing steroid sulphates

Treatment of aldosterone with triethylamine–sulphur trioxide in pyridine followed by a convenient purification procedure involved absorption on a C18‘Sep-pak’ was found to give aldosterone 21-sulphate. The product was characterised by its 400 MHz 1H n.m.r. spectrum, which showed the presence of four isomeric forms. The improved sulphation and purification procedure has been extended to the preparation of some other steroid sulphates.

Optical rotatory dispersion and circular dichroism. Part LXXXII. An empirical analysis of the circular dichroism of decalones and their analogues

An empirical analysis of c.d. data (n→π*; ca. 290 nm) for a wide variety of ketones of the ‘extended decalone’ class has led to sets of numerical contributions for ring systems (Figure 8; Tables 9 and 14) and alkyl substituents (Table 3). These contributions can be summed to give ΔIµ values corresponding very closely to those observed (usually within ±0·2 units, although a few exceptions are noted and discussed). This is the first such analysis to embrace, within a single scheme, compounds of both the trans- and cis-decalone types, as well as their polycyclic analogues. The treatment covers data obtained for solutions in four types of solvent: hexane, dioxan, aceto-nitrile, and methanol (or ethanol).Further analysis of c.d. data for extended decalones indicates that certain coplanar zig-zag arrangements of C–C bonds (termed ‘primary zig-zags’: Figure 3) are probably responsible in many cases for a major part of the observed c.d., although other significant contributions may come from alkyl substituents in the vicinity of the carbonyl group. Atoms or bonds which form part of the alicyclic framework but do not lie on or adjacent to a primary zig-zag generally make little or no contribution to the value of ΔIµ; structural features lying very close to the carbonyl group and in a ‘front’ octant are the main exceptions. Methyl substituents at the β-axial positions fall into the two distinct classes, having consignate or dissignate c.d. effects, respectively, according to the number of bonds comprising the primary zig-zag which passes through the particular β-carbon atom.The scope and significance of these conclusions are discussed, and attention is drawn to some apparent correlations between c.d. and 13C n.m.r. data.

5α-Androst-6-ene derivatives as intermediates for labelling with isotopic hydrogen

5α-Androst-6-ene-3β,17β-diol, 17β-hydroxy-5α-androst-6-en-3-one, and 3α-hydroxy-5α-androst-6-en-17-one have been prepared, and have been reduced with deuterium to give [6,7-2H2]-5α-androstane derivatives.