Hydrogenation axial alcohols from

A useful method for the synthesis of axial alcohols from unhindered cyclohexanones is by hydrogenation over rhodium in THF-HCl, Reduction... 

Catalytic hydrogenation in neutral medium gives an axial alcohol from sterically hindered ketone and an equatorial alcohol from sterically unhindered ketones. 

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). 

Iridium-catalyzed hydrogen transfer from aqueous phosphite esters or phosphorous acid is an effective way of producing axial alcohols (77,25,J4,46,57). 

Therefore we used 4-androsten-3,17-dione 1 and 5a-androstan-3,17-dione 2 as model substrates to investigate the chemo- regio- and stereoselectivity of hydrogen transfer from different secondary alcohols, 2-propanol, 2-octanol, cyclohexanol, 1-phenyl-ethanol and diphenylmethanol in the presence of CU/AI2O3. In particular, hydrogenation of 1 allowed to determine the selectivity towards 5p isomers, whereas the percent of axial alcohol was derived from the hydrogenation of 2. These results can be compared with those obtained with the same catalyst in the presence of molecular hydrogen. 

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... 

Hydrogenations of cyclohexanones in basic media leads to the formation of the more stable, equatorial alcohol, 18, as the primary product (Eqns. 18.18-19). With basic Raney nickel catalysts, the predominance of equatorial alcohol has been shown to arise from the isomerization of the initially produced axial alcohol under hydrogenation conditions. The use of platinum oxide with its alkaline impurity also leads to extensive equatorial alcohol formation unless acetic acid is used as the solvent. This basic impurity was shown to be... 

Tris(triphenylphosphine)RhCl associated with trimethyl phosphite in isopropanol gives even greater selectivity (100%) of the axial alcohol. Reductions are conveniently effected (24 h at 82°C) in a sealed tube. The reducing agent approaches from the less hindered side of the carbonyl and the mechanism does not proceed via the hydrogenation of an enol. 

Two novel complex hydrides are likely to find applications in steroid chemistry lithium perhydro-9b-boraphen yl hydride affords unusually high proportions of axial alcohols in model compounds sodium bis(methoxyethoxy)aluminium dihydride, Na (MeOCH2CH20)JAlH2, a very safe and convenient substitute for lithium aluminium hydride, readily reduces not only ketones but also acids, nitro-compounds, oximes, amides, lactones, etc. An improved procedure for Clemmensen reduction of steroid ketones involves saturating an ethereal solution with hydrogen chloride while stirring with zinc. 5a-Cholestane was obtained from the 3-one in 89% yield. ... 

When we compare the rates of reaction of axial and equatorial hydroxyl groups in six-membered rings, we find that the reactions of the axial alcohols are faster than those of equatorial alcohols. This tells us that it is the second step, the elimination process, that is rate determining the hydrogen to be removed from the axial alcohol is in the equatorial position and hence more accessible (Figure 10.41). 

The geometry of the cis-alkylcyclohexanol is favorable for trans elimination since the hydroxyl and the neighboring trans hydrogen are coplanar, but this is not true for the l,i-trans isomer hence the molecular conformation has to flip over, to set the hydroxyl group in the axial position for the trans elimination to occur. This would require a few kilocalories of energy and for frans-lert-butylcyclohexanol it would be more difficult to achieve than for IroMs-methylcyclohexanol. It is, therefore, possible that the trans elimination from a boat conformation, or possibly even an epimerization from the trans to the cis isomer which then undergoes a trans elimination reaction. Such an epimerization was found to occur under conditions of dehydration of certain alcohols over alumina, as will be seen under 1,4-cyclohexanediol. The more facile elimination of the cis-i-tert-butylcyclohexanol system as compared with the trans system in solution was also reported in the literature 63). 

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