Steroids allylic oxidation

Scheme 16 Allylic oxidation of A5-steroids catalyzed by Bi(III) salts, using r-BuOOH...

SCHEME 125. Metal-catalyzed allylic oxidation of steroids with THBP... 

The above criteria apply in the case of isolated hydroxyl groups but when additional polar substituents are placed in the vicinity of the substrate hydroxyl the oxidation rate can be expected to change. Allylic hydroxyls are generally oxidized more rapidly than their saturated counterparts. Burstein and Rin-gold have studied the chromic acid oxidation of steroidal allylic alcohols in some detail and have found that the quasi-equatorial 3)3-isomer is oxidized more... 

Intramolecular interception of the Criegee carbonyl/carbonyl oxide intermediate was observed in the ozonolysis of steroidal allylic alcohols at — 70 °C. In hexane, the 1,2,4-trioxolane 132 (a mixture of ( Vcpimers) was isolated in 26% yield. Reductive workup afforded the hemiacetal of the dioxolane 133 which could be oxidized to the dioxolane-lactone the hydroperoxide 134 can be isolated in other solvents. When the ozonolysis was carried out in ethyl acetate at —78°C, the yield of the dioxolane-hemiacetal 133 was 95% (Scheme 51) <1990J(P1)1220>. 

There are few examples of synthetically useful allylic hydroxylations except in the steroidal field (Section 1.4.4.2), although some others are shown in Sections 1.4.3.3 and 1.4.1. Previous reviews on microbial oxidation have also included some examples of allylic oxidations. 

Allylic oxidation of steroids, particularly at the 7-position, has evoked interest over many years. For example, chromium trioxide-acetic acid," sodium dichromate,and r-butyl chromate have all been used in the oxidation of the 5-a-pregnane series e.g. equation 26). 

Indeed, Parish claims that PCC is the reagent of choice in the allylic oxidation of A -steroids (e.g. equation 32). The reactions were carried out using PDC in pyridine solution at 100 C, PCC in refluxing benzene solution, and PCC in DMSO solution at 100 °C. lliese solvent systems are claimed to be superior to the more usual methylene chloride. 

In contrast to lead tetraacetate, simple addition to the double bond does not occur as a side re-action. While allylic rearrangement is common and mixtures of products are frequently obtained, the reaction often proceeds in very high yield and is simple to carry out the alkene is simply heated in an appropriate solvent with mercury(II) acetate until reaction is complete. Mercury(II) acetate has also been us for dehydrogenation, particularly in the steroid field. One interesting example incorporating simultaneous dehydrogenation and allylic oxidative rearrangement is seen in the reaction of abietic acid (37 equation 16). ... 

A number of other chromium-based reagents have been developed for allylic oxidation for example that of steroids by r-butyl hydroperoxide in the presence of a catalytic amount (0.05-0.5 mol equiv.) of chromium trioxidein dichloromethane solution at room temperature (equation 39). Yields vary from 32 to 69%. This modification is useful in terms of cost, ( rational simplicity and yields. 

Clearly, regio- and chemo-selectivities of this reagent are highly dependent on the substrate structure. Allylic oxidation to give enones has also been reported at the 11-position of steroids upon treatment with nitrosyl fluoride solutions. °°... 

Selenium dioxide dehydrogenated the 3)8-fluoro-oestra-5(10)-ene (155) to give the 5(10),9(ll)-diene (156). Allylic oxidation of a 3) -fluoro-A -steroid (157) with selenium dioxide gives the 4)5-hydroxy-derivative (160). A similar oxidation is well known in 3) -hydroxy-A -steroids, where the 3/i-hydroxy-group... 

Most allylic oxidations of methylene to carbonyl groups are carried out by chromic oxide [552, 555] or its complexes with pyridine [593, 606] and performed on steroidal esters [552, 593, 606] and ketones [61, 552] (equation 130). 

Allylic alcohols in steroids are oxidized by 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ), either alone (equation 258) [975] or as a catalyst with periodic acid as a reoxidant [974]. Saturated alcohols and other func-... 

Nickon noted that in the activated-MnOa oxidation of steroid allylic alcohols (A -3-ols and A -T-ols) the quasi-equatorial isomer is oxidized in one tenth to one third the time required for the quasi-axial isomer. 

A key step in the partial synthesis of the steroidal insect hormone ecdysone is introduction of a 14a-hydroxyl group. Three groups [Schering (Berlin)-Hoffmann La Roche (Basel)18d and Syntex18 ] achieved this end by allylic oxidation of A7-6-keto-stcroids, both 5a and 5/3, by selenium dioxide in dioxane. Yields are high. 

Oxidation of allylic alcohols. Steroidal allylic alcohols are oxidized to the corresponding a,/3-unsaturated ketones in high yield by chromic anhydride in HMPT.2 The reaction is rapid in the case of equatorial alcohols but requires some weeks in the case of axial alcohols. Nonallylic hydroxyl groups are not affected. If the alcohol is only slightly soluble in HMPT, purified acetone is used as cosolvent. The reaction, if slow, can be carried out at 50°. Benzyl alcohol is oxidized, but in low yield (30%). 

Allylic oxidation. A6-Steroids (cholesteryl acetate and diosgenyl acetate) undergo allylic acetoxylation at C7 when oxidized with lead tetraacetate in benzene or glacial acetic acid solution. 7/3-Acetoxy and 7 -acetoxy derivatives are formed in a ratio of 3 2.10... 

Secondary alcohols have been oxidized to ketones with excess ferf-butylhydroperoxide in up to 93-99% yields using a zirconium catalyst.250 Zirconium catalysts have also been used with ferf-butylhydroperoxide in the oxidation of aromatic amines to nitro compounds and of phenols to quinones. Allylic oxidation of steroids in 75-84% yields has been performed with ferf-butylhydroperoxide and cop-... 

N-Substituted 3)5-acetoxy-6/ -amino-5a-androstanes bearing histidine and related imidazole and triazole derivatives have been prepared. Allylic oxidation with selenium dioxide of 3a- and 3)8-dimethylamino-5-enes, c.g. (498) and similar steroids, gave 4/ -hydroxy-5-ene and the allylic rearrangement product... 

Oxo-steroids, which are not usually very accessible, may be prepared by the allylic oxidation of 8(14)-enes with potassium chromate. Yields, which vary between 20—60%, are highest when a 12-oxo-group is present." ... 

Solasodine (1) and related Solanum alkaloids are useful starting materials for the commercial preparation of steroid hormones." In particular the pregnane derivative (6) was prepared from solasodine in 65% overall yield via the intermediates (2), (3), and (4). The oxidative cleavage of the 20(22) double bond of pseudosolasodine diacetate (3), which is the least efficient step in this synthesis, has been investigated in more detail With sodium dichromate in acetic acid compound (3) gave the hydroxyester (5) and the hydroxylactone (7), in addition to the ester (4). Results of a kinetic study of this reaction were interpreted in terms of formation of hydroxyester (5) via allylic oxidation of pseudosolasodine diacetate prior to cleavage of the 20(22) double bond. ... 

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