Hydrogenation to the axial alcohol

On the other hand, 50-cholestan-3-one was hydrogenated to the axial alcohol, 50-cholestan-30-ol, in 99% yield (GC) over Urushibara cobalt A (U-Co-A) in methanol as solvent (eq. 5.45) and in 72% yield (GC) over U-Ni-A.170 In these cases the yields decreased in less polar solvents over both catalysts. 

Cholestan-3-one was also stereoselectively hydrogenated to the axial alcohol in 98.5% yield (GC) over a palladium black in isopropyl alcohol at 25°C and atmospheric pressure (see Fig. 5.1 and Section 5.4.2).153d Accompanying formation of the isopropyl ether was not observed in the case of the steroid ketone, whereas a large amount (55%) of the ether and an almost 1 1 mixture of cis and trans alcohols were produced in the hydrogenation of 4-f-butylcyclohexanone under the same conditions. 

These mechanistic interpretations can also be applied to the hydrogenation of cyclohexanones. In acid, the carbonium ion (19) is formed and adsorbed on the catalyst from the least hindered side. Hydride ion transfer from the catalyst gives the axial alcohol (20). " In base, the enolate anion (21) is also adsorbed from the least hindered side. Hydride ion transfer from the catalyst followed by protonation from the solution gives the equatorial alcohol (22). 

The addition of hydrogen to hindered ketones usually occurs preferentially from a less hindered side and the stereochemistry is less influenced by the nature of solvents than in the cases of unhindered ketones, as generalized in ASB rules 1 and 2. According to these rules, the axial alcohols are formed predominantly in the hydrogenation of hindered cyclohexanones under both acidic and neutral (or alkaline) conditions. The ABS rule, however, is oversimplified, as pointed out by Dauben et al.,180 since the addition of hydrogen from a less hindered side does not always give axial alcohols as in the cases of 5a-cholestan-l-one (28)181 and the 12-oxo steroid 29 (hecogenin),182 where... 

Accrombessi et al. studied the hydrogenolysis of various epoxycyclohexanes over 10% Pd-C in different solvents at 20° and 1 atm H2.25 The hydrogenolysis of both trans- and cA-l,2-epoxy-4-f-butylcyclohexanes (13 and 14) occurs to give preferentially the axial alcohols by apparent trans addition of hydrogen (eq. 13.8), as evidenced by deuterolysis. 

There are two possible modes of delivery of the hydride to the carbonyl carbon of cyclohexanone (1) axial attack with formation of the equatorial alcohol and (2) equatorial attack with formation of the axial alcohol. Two factors are competing with each other (1) steric interaction of the incoming hydride with the 3,5-diaxial hydrogens in the axial attack and (2) torsional strain of the incoming hydride with the 2,6-diaxial hydrogens in the equatorial attack. 

The reduction of a number of steroids at a Hg cathode was found to yield the corresponding equatorial alcohols with a high degree of stereoselectivity. Conversely the catalytic hydrogenation of steroids mainly yields the axial alcohols... 

---