Alcohols, tertiary with lead tetraacetate

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. 

Oxidation of hydrocarbons with a tertiary carbon, e.g. adamantane, with lead tetraacetate in trifluoroacetic acid-dichloromethane solution, in the presence of chloride ion, gave high yields of trifluoroacetate functionahzed bridgehead alcohols [57]. Subsequent hydrolysis yielded the free bridgehead alcohols (Scheme 13.34). Another important advantage of this method is the feasible conversion of the intermediate trifluoroacetate into an amide with acetonitrile. 

Not only 1,2-di-functionalized substrates with heteroatoms but also tertiary alcohols and hemiketals undergo oxidative C-C bond cleavage at the a position on treatment with lead tetraacetate. For example, a y-hydroxy ketone and the corresponding hemiketal have been fragmented by lead tetraacetate into a 9-membered olefinic lactone (Scheme 13.57) [76]. 

Formation and /S-fission of bicyclic tertiary alkoxyl radicals from the corresponding alcohols are well known [38] [40]. The treatment of 5a-cholestane-3/3,5-diol-3-acetate, VII/70, and the 5/3-alcohol, VII/71, respectively (Scheme VII/15), with one molar equivalent of lead tetraacetate in the presence of anhydrous calcium carbonate gives radical fragmentation reactions. The products are the two (E)- and (Z)-3/3-acetoxy-5,10-seco-l(10)-cholesten-5-ones (VII/72 + VII/73) [40]. The ratio of VII/73 VII/72 is 63 10 [41] [42] [43]. 

Barton oxidation was the key to form the 1,2-diketone 341 in surprisingly high yield, in order to close the five-membered ring (Scheme 38). The conditions chosen for the deprotection of the aldehyde, mercuric oxide and boron trifluoride etherate, at room temperature, immediately led to aldol 342. After protection of the newly formed secondary alcohol as a benzoate, the diketone was fragmented quantitatively with excess sodium hypochlorite. Cyclization of the generated diacid 343 to the desired dilactone 344 proved very difficult. After a variety of methods failed, the use of lead tetraacetate (203), precedented by work performed within the stmcmre determination of picrotoxinin (1), was spectacularly successful (204). In 99% yield, the simultaneous formation of both lactones was achieved. EIcb reaction with an excess of tertiary amine removed the benzoate of 344 and the double bond formed was epoxidized with peracid affording p-oxirane 104 stereoselectively. Treatment of... 

Alkoxy radicals for ring expansion can be generated from alcohols by oxidative methods such as hypohalite thermolysis/photolysis [19a] and lead tetraacetate oxidation [19b], or peroxide reduction [19c]. The recent development of the hyper-valent organoiodine reagent (diacetoxyiodo)benzene (DIB) provides another way for efficient generation of alkoxy radicals (Scheme 11) [19d]. Additional oxidative methods to prepare cyclopropyloxy radicals include reaction of tertiary cyclopropanols or their silyl ether derivatives with various reagents such as manganese(III) tris(pyridine-2-carboxylate) [Mn(pic)3] [20a], Fe(III) salts [20b], and vanadyl ace-tylacetate [20c] (Scheme 12). 

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