Equatorial secondary alcohol

In another study (93), cyclization of optically active substrate 244 gave optically active tetracyclic product 245 with the same optical purity. Since, 245 was converted into Ua-hydroxyprogesterone (246), this work constitutes a total asymmetric synthesis of that steroid. This remarkable asymmetric control is due to the chiral center at C-10 of 244 the relative orientation of the hydroxyl group in the transition state of the cyclization process, controlled by stereoelectronic factors, is such that it yields a product (245) having an equatorial secondary alcohol. 

Curiously, tertiary propargylic alcohols may be alkylated in preference to either axial or equatorial secondary alcohols, using sodium hydride in DMF (eq 3). ... 

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. 

The reactivity of various steroid alcohols decreases in the order primary > secondary (equatorial) > secondary (axial) > tertiary. The only systematic investigation relating to the selective protection of steroidal hydroxyl functions has been carried out with the cathylate (ethyl carbonate) group. Since only equatorial hydroxyl groups form cathylates this ester has been used as a diagnostic tool to elucidate the configuration of secondary alcohols. 

This procedure illustrates a general method for the selective splitting of a carbomethoxy group in the presence of easily hydrolyzed esters of other alcohols, such as the easily hydrolyzed equatorial acetoxy group. The specificity of the reaction is not affected by steric hindrance, and a highly hindered methyl ester can be split in the presence of other less hindered esters of secondary alcohols. Normal alkaline saponification goes in exactly the opposite way. 

Oxidation of primary, secondary and benzylic alcohols with TBHP or CHP, mainly catalyzed by Mo and Zr derivatives, were performed by different authors. As an example, Ishii, Ogawa and coworkers reported the conversion of secondary alcohols such as 2-octanol to ketones mediated by catalyst 39 and TBHP. The oxidation of cyclic alcohols depended on steric factors. Zirconium alkoxides may act as catalysts in the conversion of different alcohol typologies with alkyl hydroperoxides . Secondary alcohols, if not severely hindered, are quantitatively converted to the corresponding ketones. The selectivity for equatorial alcohols is a general feature of the system, as confirmed by the oxidation of the sole cis isomer 103 of a mixture 103-bl04 (equation 68). Esters and acids could be the by-products in the oxidation of primary alcohols. 

It is well established that oxygen in the presence of platinum (Adams catalyst) can achieve specific oxidation of secondary alcohols by a preferential attack upon hydrogen in an equatorial position (25). Catalytic oxidation of methyl a- and /3-D-galactopyranoside (26), fallowed by catalytic reduction with hydrogen, led to the formation of methyl a- and /3-6-deoxy-D-galactopyranoside (D-fuco-pyranoside) in 15% and 35% yield, respectively. This oxidation-reduction sequence with selective oxidation at carbon 4 as the initial step is structurally closely related to the above described pathway for TDPG-oxidoreductase. 

Secondary alcohols give good yields of ketones, but the foremost use of die Joies oxidation has been for the conversion of saturated primary alcohols to the corresponding acid. In direct contrast, primary allylic and benzylic alcohols can be selectively oxidized to aldehydes acids are obtained only after prolonged exposure to the oxidant. In rigid systems it has been found that axial alcohols are oxidized faster than equatorial alcohols. ... 

Further consequences of the distinction between axial and equatorial bonds lie in different rates of acylation of steroid alcohols, hydrolysis of esters, and oxidation of secondary alcohols, which were among the earliest steroid reactions to be interpreted in conformational terms. These reactions are discussed in Chapter 2. 

Nucleophilic substitution of toluene- -sulphonates (tosy-lates) and other sulphonic esters of secondary steroidal alcohols has received much attention, both in studies of reaction mechanisms, and also as a route for the conversion of alcohols into their epimers. One of the most important practical objectives has been the synthesis of 3a-hydroxy-5a-steroids, which include androsterone and a wide variety of metabolites of the steroid hormones, Tosylates of equatorial 3jS-alcohols (15) give 3a-alcohols or their derivatives (16) in acceptable... 

The platinum-catalyzed oxidation with oxygen can also be applied for selective oxidation of secondary alcohols if no primary alcohol is present [73]. Like the tin-bromine method, axial secondary hydroxy groups will undergo preferential oxidation over equatorial hydroxy groups. However, as described above large amounts of platinum metal are required for these oxidations. Some improvement in catalyst activity has been achieved by promotion of platinum with bismuth or lead [76]. This also causes a change in selectivity and makes it possible in... 

Occasionally, it is possible to glycosylate one secondary alcohol over another, and the most common examples include preferential glycosylation of equatorial hydroxyl groups over their axial counterparts.119 187,192 196 Among many applications, acceptor polyols are commonly used for the introduction of bulky... 

BzCl or BZ2O, Pyr, 0 C. Benzoyl chloride is the most common reagent for the introduction of the benzoate group. Reaction conditions vary, depending on the nature of the alcohol to be protected. Cosolvents such as CH2CI2 are often used with pyridine. Benzoylation in a polyhydroxylated system is much more selective than acetylation. A primary alcohol is selectively protected over a secondary allylic alcohol, and an equatorial alcohol can be selectively protected in preference to an axial alcohol," but this has been shown to be solvent dependant in some cases." A cyclic secondary alcohol was selectively protected in the presence of a secondary acyclic alcohol. ... 

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