Alcohols with lead tetraacetate

The radical X is formed by homolysis of the X—R bond either thermally or photolytically. In the reactions of alcohols with lead tetraacetate evidence suggests that the X—R bond (X = 0, R = Pb(OAc)3) has ionic character. In this case the oxy radical is formed by a one electron transfer (thermally or photochemically induced) from oxygen to lead. 

The oxidation of alcohols with lead tetraacetate was the first reaction used for oxygenation of an angular methyl group in steroids. It is a simple and efficient method and produces tetrahydrofuran derivatives directly from alcohols. 

Cyclization of alcohols with lead tetraacetate (tetrahydrofurans)... 

For the substitution of the angular methyl groups in steroids five methods are known (a) homolysis of N-chloramines [Loffier-Freytag reaction (only C-18)] (b) oxidation of alcohols with lead tetraacetate (c) photolysis of nitrite esters (d) homolysis of hypochlorites (e) the hypoiodite reaction. ... 

Since in the reaction of 20a- and 200-alcohols with lead tetraacetate somewhat similar relative reactivity has been reoorded (L. Velluz, G. Muller, R. Bardoneschi, and A. Poittevin, Cornpt. Rend., 1960, 725), this strongly suggests that the conformational requirements in the transition state of the lead tetraacetate reaction are comparable with those of the Barton reaction. Also see ref. 6 and G. Cainelli, B. Kamber, J. Keller, M. Lj. Mihailovic, D. Arigoni, and O. Jeger, Helv. Chim. Acta, 44, 518 (1961). 

A number of skeletal fragmentation reactions resulting from treating steroid alcohols with lead tetraacetate require comment. These reactions occur as the alternative to cyclic ether... 

Ceric ammonium nitrate in water or in 50% acetic acid oxidizes ben-zylic alcohols at 90 °C in very good yields [420]. Only catalytic amounts of the reagent and sodium bromate as a reoxidant are needed to convert benzyl alcohol into benzaldehyde in 90% yield on heating in acetonitrile at 80 °C [421]. A similar result is obtained on treatment of benzyl alcohol with lead tetraacetate in pyridine at room temperature for a few hours (yield 85%) [442]. 

Table 6.7 Oxidation of Alcohols With Lead Tetraacetate —cont d...

The application of hypoiodite photolysis for remote functionalization has been mostly in the steroid field. There has been, however, a resurgence of appHcations in the field of spiroacetal-type compounds. The reaction was originally found in 1966 by Mihailovic and collaborators, who described remote functionalization by a thermal reaction of alcohols with lead tetraacetate. ... 

A method for oxidative cleavage of cyclic ketones involves a four-stage process. First, the ketone is converted to an a-phenylthio derivative (see Section 4.7). The ketone is then converted to an alcohol, either by reduction or addition of an organolithium reagent. This compound is then treated with lead tetraacetate to give an oxidation... 

A similar reaction can be effected by the treatment of amides with lead tetraacetate.2 4 In this case the initial isocyanate and the amine formed from it react with the acetic acid liberated from the lead tetraacetate to give, respectively, ureas and amides. If the reaction is carried out in the presence of an alcohol, carbamates are formed (6-8). 

The 40-alcohols of the type 2159 with lead tetraacetate and iodine gave, after oxidation of the photolysis mixture, the corresponding lactones (22) as the major product. As illustrated in structure 23, the steric locations of the 40-oxygen atom and the iodomethyl group in this molecule are similar to those in the case of 200-alcohols thus favoring an intramolecular hydrogen abstraction (conversion 11 — 13) over the cycli-zation reaction (conversion 11 —> 12). 

Pinocarveol has been prepared by the autoxidation of a-pinene,5 by the oxidation of /S-pinene with lead tetraacetate,6 and by isomerization of a-pinene oxide with diisobutylalumi-num,7 lithium aluminum hydride,8 activated alumina,9 potassium ferf-butoxide in dimethylsulfoxide,10 and lithium diethylamide.11 The present method is preferred for the preparation of pinocarveol, since the others give mixtures of products. It also illustrates a general method for converting 1-methylcy-cloalkene oxides into the corresponding exocyclic methylene alcohols.11 The reaction is easy to perform, and the yields are generally high. 

The diterpenoid 1 from the heartwood of Callitris macleayana is the Diels-Alder dimer of the dienone 2a. The acetate 2b of the alcohol 2a is readily available by oxidation of 5-isopropyl-2-methylphenol with lead tetraacetate, but all attempts to hydrolyse 2b to 2a failed. "Dimeric indans" were obtained under acidic conditions, while use of potassium hydroxide in methanol at room temperature for 15 minutes followed by acidification with 1M hydrochloric acid, extraction and repeated chromatography over silica gave the three products 3, 4 and 5 in the relative distribution 11.7, 63.7 and 24.7%. The same products were formed in similar proportions when the reaction temperature was varied from 0°C to 64°C treatment of any of the products 3, 4 or 5 with potassium hydroxide in methanol also gave a mixture of 3,4 and 5. 

Monohydric alcohols react rapidly with lead tetraacetate to form alkoxy lead (IV) intermediates. These intermediates decompose thermally or photolytically in a variety of ways to produce ketones, esters, and cyclic ethers (62), as can be seen below (Reaction XXXVII). 

The starting material for the present synthesis was Wieland-Miescher ketone (24), which was converted to the known alcohol (25) by the published procedure [10], Tetrahydropyranylation of alcohol (25) followed by hydroboration-oxidation afforded the alcohol (26), which on oxidation produced ketone (27). Reduction of (27) with metal hydride gave the alcohol (28) (56%). This in cyclohexane solution on irradiation with lead tetraacetate and iodine produced the cyclic ether that was oxidized to obtain the keto-ether (29). Subjection of the keto-ether (29) to three sequential reactions (formylation, Michael addition with methyl vinyl ketone and intramolecular aldol condensation) provided tricyclic ether (30) whose NMR spectrum showed it to be a mixture of C-10 epimers. The completion of the synthesis of pisiferic acid (1) did not require the separation of epimers and thus the tricyclic ether (30) was used for the next step. The conversion of (30) to tricyclic phenol (31) was... 

Some interesting intramolecular variants have been reported. For example, homoallylic alcohols (e.g. 139) can be treated with sulfamoyl chloride to form the corresponding sulfamates (140), which then engage in a direct intramolecular copper-catalyzed aziridination mediated by iodosylbenzene <02OL2481>. A carbamate tether is also effective in delivering the nitrene center to the olefin, as is the case with the cyclohexenyl derivative 142, which spontaneously cyclizes in the presence of iodosylbenzene <02OL2137>. The acetoxy-aminoquinazolinone 144 is converted to the lactone 145 via intramolecular aziridination upon treatment with lead tetraacetate and hexamethyldisilazane (HMDS) <02TL2083>. 

The rest of the synthesis (Scheme 13) is completely stereospecific and most of the steps are known (20). The bicyclic acid was oxidatively decarboxylated with lead tetraacetate and copper acetate (21). The resulting enone was alkylated with methyllithium giving a single crystalline allylic tertiary alcohol. This compound was cleaved with osmium tetroxide and sodium periodate. Inverse addition of the Wittig reagent effected methylenation in 85% yield. Finally, the acid was reduced with lithium aluminum hydride to grandisol. 

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