D. Neville Jones

Stereochemistry of formation and reduction of π-allyl palladium chloride complexes from steroidal olefins

The regioselectivity and stereoselectivity of palladium π-allyl chloride complex formation from steroidal olefins was apparently controlled by steric effects, and both cholest-4-ene and cholest-5-ene gave diastereoisomeric complexes; two of the complexes were reduced to olefins by lithium aluminium hydride stereo-specifically with retention of configuration.

Regioselective and stereoselective oxidation of steroidal palladium π-allyl complexes to allylic alcohols

Steroidal palladium π-allyl complexes are oxidised regiospecifically and with high stereoselectivity to allylic alcohols by 3-chloroperbenzoic acid in light petroleum containing pyridine, the hydroxy-group being delivered preferentially to the same diastereotopic face of the π-allyl system as that originally occupied by palladium.

Steroidal sulphur compounds. Part XI. 4-Thia-5α- and 5β-cholestane and their oxides and dioxides

Cholesterol was converted in nine steps into 4-thia-5β-cholestane in 36% overall yield. The final step involved the intramolecular addition of a thio-radical, generated photocatalytically from A-nor-3,5-secocholest-5-ene-3-thiol, to the double bond to give 4-thia-5β-cholestane stereospecifically. Another approach involved the intramolecular addition of a sulphenic acid, generated by pyrolysis of 3-t-butylsulphinyl-A-nor-3,5-secocholest-5-ene, to the double bond to give 4-thia-5β-cholestane 4α-oxide stereospecifically. Base-catalysed isomerisation of 4-thia-5β-cholestane 4,4-dioxide and 4-thia-5β-cholestane 4α-oxide gave 4-thia-5α-cholestane 4,4-dioxide and 4-thia-5α-cholestane 4α-oxide quantitatively, whereas 4-thia-5β-cholestane 4β-oxide gave a ca. 56 : 44 mixture of starting material and 4-thia-5α-cholestane 4β-oxide. Reduction of 4-thia-5α-cholestane 4β-oxide gave 4-thia-5α-cholestane. The oxides were configurationally stable at 190°, but underwent photocatalysed stereomutation at sulphur without concomitant isomerisation at C-5.

Steroidal sulphur compounds. Part IX. 6α- and 6β-Methylsulphinylcholest-4-ene and related compounds; stereochemical aspects of the allyl sulphoxide–sulphenate rearrangement

The rates of several [2,3] sigmatropic allyl sulphoxide–sulphenate rearrangements in the steroidal system have been shown to be influenced by chirality at sulphur. The configuration of the alcohols formed by trapping the sulphenates with piperidine showed that the rearrangements were cleanly suprafaciat with respect to the allyl system. The results of kinetic investigations and equilibration studies suggested that the rate differences were attributable mainly to differences in free energy of the transition states, and consideration of the relative steric compressions in model transition states led to allocations of configuration at sulphur in the sulphoxides. N.m.r. data were in accord with the configurational assignments, and enabled tentative conformational assignments to four of the sulphoxides to be made.

General synthesis of homochiral trisubstituted γ-butyrolactones

The synthetically useful keto ester methyl 2-deoxy-2-(2-ethoxy-2-oxoethyl)-4,6-O-(phenylmethylene)-α-D-ribo-hexopyranosid-3-ulose can be prepared exclusively by reaction of the potassium enolate of methyl 2-deoxy-4,5-O-(phenylmethylene)-α-D-erythro-hexopyranosid-3-ulose and ethyl iodoacetate in toluene in 74% yield. Reduction of methyl 2-deoxy-2-(2-ethoxy-2-oxoethyl)-4,6-O-(phenylmethylene)-α-D-ribo-hexopyranosid-3-ulose and subsequent cyclisation led to methyl 2-deoxy-2-(2-oxoethyl)-4,6-O-(phenylmethylene)-α-D-allopyranoside 2′,3 lactone, whose lithium enolate reacted with high stereoselectivity to give exclusively (>95% d.r.) methyl 5′-(R)-2-deoxy-5′-methyl-2-(2-oxoethyl)-4,6-O-(phenylmethylene)-α-D-allopyranoside 2′,3 lactone, methyl 5′-(R)-2-deoxy-5′-(1-hexyl)-2-(2-oxoethyl)-4,6-O-(phenylmethylene)-α-D-allopyranoside 2′,3 lactone and methyl 5′-(R)-2-deoxy-2-(2-oxoethyl)-4,6-O-(phenylmethylene)-5′-(2-propenyl)-α-D-allopyranos-ide 2′,3 lactone derivatives. This method provides a convenient and high-yielding route to homo-chiral γ-butyrolactones, thereby offering an opening into a wide range of enantiomerically pure γ-lactones. The work described provides another solution to the ‘off-template’ problem.

Steroidal selenoxides diastereoisomeric at selenium; syn-elimination, absolute configuration, and optical rotatory dispersion characteristics

Steroidal selenoxides have been separated chromatographically into diastereoisomers at selenium, and their mode of elimination permitted allocations of configuration at selenium; their chiroptical properties were similar to those of related sulphoxides.

Steroidal sulphur compounds. Part XII. Regiospecific formation of steroidal olefins by thermolysis of sulphoxides.

The first examples of the regiospecific generation of isomeric olefins from two sulphoxides diastereoisomeric at sulphur are reported. Thermolysis of (R)- and (S)-3α-(1-adamantylsulphinyl)-5α-cholestane at 110 °C gave respectively 5α-cholest-3-ene and 5α-cholest-2-ene; (S)-3β-(1-adamantylsulphinyl)-5β-cholestane gave 5β-cholest-3-ene at a rate much greater than that at which the diastereoisomeric (R)-sulphoxide decomposed to 5β-cholest-2-ene, so providing a convenient preparation of these erstwhile rather inaccessible olefins. In contrast, thermolysis of 3α-(1-naphthyl)- and 3α-(anthracen-9-yl)-5α-cholestanes was not highly regioselective, and the corresponding steroidal diphenyl sulphoxides underwent stereomutation at sulphur more readily than elimination to give olefins.

Steroidal sulphur compounds. Part X. Chiroptical properties of steroidal allyl sulphoxides

The chiroptical properties of eight steroidal allyl sulphoxides were markedly influenced by the relative spatial orientation of the olefinic double bond and the sulphoxide group, and chirality at sulphur did not necessarily play a predominant role. The influence of solvent upon the chiroptical spectra of some of the sulphoxides depended upon chirality at sulphur.

Stereospecific synthesis of thiolan 1-oxide derivatives by intramolecular addition of sulphenic acids to olefins

Pyrolysis of derivatives of 5-t-butylsulphinylpentene, which may be prepared by reaction of t-butylsulphenic acid with 1,5-dienes, provides a method for the stereospecific synthesis of thiolan 1-oxide derivatives.

Chiroptical properties of steroidal βγ-unsaturated sulphoxides

The chiroptical properties of steroidal βγ-unsaturated sulphoxides are determined by the relative spatial orientation of the olefinic double bond and the lone electron pair on sulphur, and chirality at sulphur does not necessarily play a predominant role.