Cholestenone reduction

Dihydrocholesterol has been prepared by the reduction of cholestenone with sodium and amyl alcohoP and by the hydrogenation of cholesterol. In the presence of platinum black or platinum oxide, yields varying from 6.5 per cent to 40 per cent have been obtained in ether, acetone, ethyl acetate, and acetic acid. ... 

Reduction of steroid enones like cholestenone 26, with a rigid ring conformation, leads to head-to-head pinacol dimers because of steric hindrance at the alternative dimerization site, and reaction occurs tlnough the a-face of the radical intermediate [101, 102]. The a-face is opposite to the angular methyl substituent... 

Jackson and Zurqiyah129 carried out a study similar to Kupfer s. In their work the reaction mixture was always kept alkaline to avoid the possibility161 of reduction of the double bond by diborane f ormed when solutions of NaBH4 are acidified. The compounds studied were 3-methylcyclohexenone, carvenone and cholestenone, and the solvents used were 2-propanol, diglyme,triglymeand pyridine. Since borohydride does not reduce allylic alcohols, this precludes the possibility that the saturated alcohols are formed from the allylic alcohols. 

Cholestenone, labelled with C , III, 233 Cholesterol, trityl ether, III, 86 Cholic acid, phytochemical reduction of, IV, 92... 

The ease and the stereochemical course of hydrogenation of a,p-unsaturated ketones are particularly influenced by the nature of the solvent and the acidity or basicity of the reaction mixture. Some efforts have been made to rationalize the effect of the various parameters on the relative proportions of 1,2- to 1,4-addition, as well as on the stereochemistry of reduction. For example, the product distribution in -octalone hydrogenation in neutral media is related to the polarity of the solvent if the solvents are divided into aprotic and protic groups. The relative amount of cis- -decalone decreases steadily with decreasing dielectric constant in aprotic solvents, and increases with dielectric constant in protic solvents, as exemplified in Scheme 21 (dielectric constants of the solvents are indicated in parentheses). Similar results were observed in the hydrogenation of cholestenone and of testosterone. In polar aprotic solvents 1,4-addition predominates, whereas in a nonpolar aprotic solvent hydrogenation occurs mainly in the 1,2-addition mode. 

In order to study the factors determining the regioselectivity of sodium borohydride reduction of a, -unsaturated ketones, reactions with 3-methylcyclohexenone, carvone and cholestenone were carried out in 2-propanol, diglyme, triglyme or pyridine. Mixtures of 1,2- and 1,4-reduction products were obtained in the alcoholic and ether solvents, whereas pure 1,4-reduction was observed in pyridine. Addition of triethylamine to NaBH4 in diglyme led to formation of triethylamine borine, EtsN BHs. Similarly, with pyridine, pyridine borine could be isolated, leading to exclusive 1,4-reductions. 

Reductive fission. Use of a mixed hydride was first reported by B. R. Brown, who investigated the action of a 1 1.5 mixture on cholestenone enol acetate (1). The result was a mixture, and the only point of interest is that one product, A -cholestene (2), results from reduction and hydrogenolysis. Reduction of cholestenone... 

After reduction of cholestenone with lithium tri-f-butoxyaluminum hydride, Burgstahler and Nordin hydrolyzed the organometallic complex by treatment with ice, sodium hydroxide, and Rochelle salt. 

Hydride reduction of 3-oxo-A-nor-5jff-cholanoic acid afforded a preponderance of the 3a-hydroxy-compound, although the ratio of 3a 3) alcohols is less than with the normal six-membered homologues. Lithium-ammonia reduction afforded equal amounts of 3a- and 3)5-epimers. AB-Dinor-cholestenone and -testosterone have been prepared by the following sequence ... 

Hydroxy-5-azacholestane (353) has been obtained from B-nor-cholestenone (349) as shown in Scheme 16/ Reduction to the alcohol, acetylation, ozonolysis,... 

Reduction of a unsaturated tosylhydrazones. Hutchins et al. reported briefly that reduction of tosylhydrazones of aliphatic a,/8-unsaturaled ketones produces alkenes resulting from migration of the double bond to the carbon originally bearing the carbonyl group. Taylor and Djerassi have since examined this reduction in detail with steroidal substrates and found that the situation is more complex. Thus reduction of the tosylhydrazone of A -cholestenone gives the four products shown in equation (I). Reduction of the tosylhydrazone of A - -cholestadienone-3 is even more complex (equation II). 

Analogously, the reduction of cholestenone (35) with NaBH4 and NaBH(OMe)3 produces 1,2- and 1,4-reduction products in the ratios of 74 26 and 98 2, respectively. 

---