Alcohols axial

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

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

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Bu3Sn)20, toluene, reflux BnBr, A-methylimidazole, 95% yield." Equatorial alcohols are benzylated in preference to axial alcohols in diol-con-taining substrates. 

The 2-nitrobenzylidene acetal has been used to protect carbohydrates. It can be cleaved by photolysis (45 min, MeOH CF3CO3H, CH2CI2, 0°, 95% yield) to form primarily axial 2-nitrobenzoates from diols containing at least one axial alcohol. ... 

With this ortho ester good selectivity for the axial alcohol is achieved in the acidic hydrolysis of a pyranoside derivative." ... 

The reduction of an asymmetric cyclohexanone (e.g. a steroidal ketone) can lead to two epimeric alcohols. Usually one of these products predominates. The experimental results for the reduction of steroidal ketones with metal hydrides have been well summarized by Barton and are discussed in some detail in a later section (page 76) unhindered ketones are reduced by hydrides to give mainly equatorial alcohols hindered ketones (more accurately ketones for which axial approach of the reagent is hindered " ) are reduced to give mainly axial alcohols. 

In reductions with NaBH4 the proportions of epimers are generally of the same order as with Li AIH4, but usually more of the axial alcohol is produced. This is especially true of reductions done in methanol. " A summary of the... 

The reduction of keto steroids by treatment with chloroiridic acid, or sodium chloroiridate, and trimethyl phosphite has been studied in some detail.Ketones at the 2- and 3-positions are reduced predominantly to the corresponding axial alcohols, while ketones at 4,6,7,11,12,17 and 20 are not affected. The rate of reaction is increased by addition of aqueous sodium hydroxide. Replacement of sodium chloroiridate by tris(triphenylphos-phine)rhodium chloride gives a system which reduces a 3-keto steroid to the... 

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). 

Axial alcohols e.g. 60) are formed predominantly when platinum is used in moderately acidic media. The use of acetic acid alone as solvent affords the equatorial alcohol as the main product from both and 7-keto compounds. Addition of 2-10% of a strong acid e.g. hydrochloric acid) to this solvent leads to the axial alcohol as the primary, if not the exclusive, product. Primary and secondary alcohols may be converted in part to the corresponding acetates under these conditions. 

Dehydration occurs readily with the axial alcohol (100), whereas the equatorial isomer (101) forms an ester which does not eliminate. This difficulty is not experienced with 1 la-alcohols. 

A recently discovered reduction procedure provides a convenient route to axial alcohols in cyclohexyl derivatives (5). The detailed mechanism of the reaction remains to be elucidated, but undoubtedly the reducing agent is an iridium species containing one or more phosphate groups as ligands. In any case, it is clear that the steric demands of the reducing agent must be extraordinary since the stereochemical outcome of the reaction is so specific. The procedure below is for the preparation of a pure axial alcohol from the ketone. 

In conformationally fixed irons- and cts-4-f-buiylcyclohexene epoxides, ihe direction of ring opening is such as to give the axial alcohol, regardless of solvent (/). 

As a rule, axial alcohols oxidize somewhat faster than equatorial alcohols. Which would you expect to oxidize faster, ch-4-te/t-butylcyclohexanol or t/m/.v-4-teh-buiylcyclohexanol Draw the more stable chair conformation of each molecule. 

As a general rule, equatorial alcohols are esterified more readily than axial alcohols. What product would you expect to obtain from reaction of the following two compounds with 1 equivalent of acetic anhydride ... 

The stereochemical outcome of nucleophilic addition reactions to cyclic ketones is the subject of numerous experimental and theoretical studies, with substituted cyclohexanones and cy-clopcntanones having been intensively studied. In addition reactions to substituted cyclohexanones 1 the problem of simple diastereoselectivity is manifested in the predominance of cither axial attack of a nucleophile, leading to the equatorial alcohol 2 A. or equatorial attack of the nucleophile which leads to the axial alcohol 2B. 

The 1H NMR spectra of the epimeric cyclohexanols in DMSO reveal that the hydroxyl proton in the axial alcohol shows a resonance absorption at a higher field than in the equatorial one, indicating that the conformational effect of the hydrogen bond influences the XH NMR chemical shifts128. 

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