Steroidal alcohols, selective oxidation

When used at room temperature in the presence of an active platinum catalyst in an inert solvent, e.g., acetone or ethyl acetate, oxygen will oxidize nonhindered, saturated hydroxyl groups and exposed allylic alcohols. This reagent has found extensive use in sugar chemistry and is particularly suited for the selective oxidation of either 3a- or 3j -alcohols of steroids. Other hydroxyl groups on the steroid skeleton are much less sensitive to oxidation. As a result, this reaction has been used extensively in research on polyhydroxy cardiac-active principles, e.g., the cardenolides and bufadienolides, where the 3-hydroxyl group is easily oxidized without extensive oxidation or dehydration of other hydroxyl groups. The ordinarily difficult selective oxidation of the... 

The facile and selective oxidation of both primary and secondary hydroxy groups with certain nucleotides led Pfitzner and Moffatt (48) to explore the scope of the carbodiimide-methyl sulfoxide reagent with steroid and alkaloid alcohols. Relatively minor differences were apparent in the rate of oxidation of epimeric pairs of 3- and 17- hydroxy steroids whereas the equatorial lLx-hydroxyl group in several steroids was readily oxidized under conditions where the axial epimer was unreactive [cf. chromic oxide oxidation (51)]. 

The nickel hydroxide electrode resembles in its applications and selectivity the chemical oxidant nickel peroxide. The nickel hydroxide electrode is, however, cheaper, easy to use and in scale-up, and produces no second streams/ waste- and by-products [196], Nickelhydroxide electrode has been applied to the oxidation of primary alcohols to acids or aldehydes, of secondary alcohols to ketones, as well as in the selective oxidation of steroid alcohols, cleavage of vicinal diols, in the oxidation of y-ketocarboxylic acids, of primary amines to nitriles, of 2,6-di-tert-butylphenol to 2,2, 6,6 -tetra-rert-butyldiphenoquinone, of 2-(benzylideneamino)-phenols to 2-phenyloxazols, of 1,1-dialkylhydrazines to tetraalkyltetrazenes. For details the reader is referred to Ref. [195]. 

The oxidation of alcohols to carbonyl compounds has been studied by several authors and a variety of methods have been used. Papers concerned vith such oxidations are illustrated (Scheme 3.26). Good results have been obtained using pyridinium chlor-ochromate (PCC) adsorbed onto silica gel for the selective oxidation of unsaturated substrates e.g. terpene [135] and furanyl derivatives [136]. Steroidal homoallylic alcohols can be converted to the corresponding 4-ene-3,6-diones using tetrapropylammo-nium per-ruthenate (TPAP) in catalytic amounts [137]. In this case, the oxidising agent is N-methyl morpholine N-oxide (NMO). 

In steroidal alcohols the 3a- or 3P-hydroxy group (18, Table 10) is selectively oxidized in the presence of the 17P-hydroxy group. The yield obtained corresponds to that of the Oppenauer-oxidation which is the most selective oxidation method for the 3-OH group. 

Selective oxidation of allylic alcohols.2 PCC in CH2C12 containing pyridine (2%) selectively oxidizes steroidal equatorial allylic hydroxyl groups. PCC buffered with... 

The regioselectivity of the C-H insertion is mainly controlled by the reactivity of the C-H bonds. For example, in the DMD oxidation of trans-dimethylcyclohex-ane [24] the tertiary C-H bond is selectively oxidized rather than the secondary bonds (Scheme 1). Similarly, when methylcyclohexane (1) is oxidized by TFD, the alcohol 2 (oxidation at the tertiary C-H bond) prevails, as shown in Scheme 2. When the reactivity is similar, the regioselectivity is governed by steric factors. This is well illustrated in Scheme 3 for the steroid pregnane (4), which, for steric reasons, is selectively hydroxylated at the C14 position in the presence of other tertiary C-H bonds (C5, C8, C9 C17, C20) [25]. Similarly, in the TFD oxidation of brassi-nolide (6), only the tertiary C-H bond of the side-chain (position 25) is hydroxylated (Scheme 3) [26],... 

PCC can be modified to show selectivity for the oxidation of allylic alcohols in steroidal systems. A solution of PCC in dichloromethane with 2% pyridine at ca. 2 C was found to be an effective and selective oxidant (Table 6). In contrast to chromate oxidations of saturated alcohols in rigid systems. Parish and coworicers found that quasiequatorial allylic alcohols were oxidized faster than axial ones. Similar prcperties were also found for solutions of PCC and 3,5-dimethylpyrazole (2%) in dichloromethane. In adtUtion, Parish and coworicers also examined several other aromatic amines for the ability to promote allylic selectivity. 2,2 -Bipyridine, pyrazine, pyridazine, j-triazine and 2,4,6-triphenylpyridine all had some effect, but their efficacy appear to be substrate dependent. Most recently the combination of PCC... 

Steroidal alcohols have been oxidised with a variety of other reagents. Sources of positive" halogen, such as N-bromoamides [30-32], isocyanuric chloride [33], and tert-butyl hypochlorite [34], readily convert many alcohols into ketones. Axial alc idls are again the most probably for reasons similar to those discussed above [31]. This reactivity difference has been exploited, for example, in the selective oxidation of 5a-cholestane-3j5,5a,6jS"triol (5) to give the 3 S,3a"dihydroxy-6-ketone (6) [35]. Equatorial alcohols display differences in rates of oxidation the more... 

A similar two-phase procedure involves addition over 15 min. of the theoretical quantity of chromic acid (from Na2Cr207-2 HjO, H2SO4, and water) to a solution of the alcohol in ether. After 2 hrs. at 25-30° the ether layer is separated and the product isolated. Oxidation of (-menthol gave (-menthone in 97% yield with only a trace of d-isomenthone, whereas 3-4% of this isomer was present on oxidation with aqueous chromic acid (50-55°), H2Cr04 in 90% acetic acid (25°), or HjCrO,-acetone (5-10°), and the yields in these oxidations were 90, 71, and 86%. This procedure has been used for Ihc selective oxidation of steroidal l6/l,2()o-diols to l6-keto-20 -ols. ... 

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