Lactones, hydrolysis ketones

A dihydro version of the pyranoindoI-3-one has also been used as a precursor of an indole quinodimethane, as the result of thermal loss of carbon dioxide <89TL7289, 93T439>. The dihydro compounds can be prepared effectively from the pyranoindolones by a sequence of lactone hydrolysis, carbonyl reduction and relactonization. They can then be decomposed thermally in the presence of suitable dienophiles such as maleimides, quinones, or unsaturated ketones or esters. For example, the dihydroindolone (309) in its thermal reaction with iV-phenylmaleimide gives the tetracyclic adduct (310) (Scheme 93). 

One of the many useful applications of anions of vinyl cyanohydrins, derived from a.jS-unsaturated aldehydes, is in the spiro-lactonization of cyclic ketones for example, cyclohexanone can be converted into (71) in 60% isolated yield. The a-aminonitrile analogues of the cyanohydrins can be used in much the same way. The same spiro-lactonization of ketones can also be carried out using trimethylsilylallylzinc chloride followed by Sharpless epoxidation, hydrolysis, and oxidation, or by using dianions derived from phosphorodiamidates. ... 

When the compound for identification fails to respond to test 4 (aldehyde or ketone), the next class reactions to apply are the hydroxatnic acid teat and saponification, i.e., hydrolysis in alkaline solution. These are the class reactions for esters and anhydrides the rarely-encountered lactones react similarly. 

Reaction of (T)-(-)-2-acetoxysuccinyl chloride (78), prepared from (5)-mahc acid, using the magnesiobromide salt of monomethyl malonate afforded the dioxosuberate (79) which was cyclized with magnesium carbonate to a 4 1 mixture of cyclopentenone (80) and the 5-acetoxy isomer. Catalytic hydrogenation of (80) gave (81) having the thermodynamically favored aH-trans stereochemistry. Ketone reduction and hydrolysis produced the bicycHc lactone acid (82) which was converted to the Corey aldehyde equivalent (83). A number of other approaches have been described (108). 

The third synthetic scheme is employed when the phenylthio substituent is in the a-position of the lactone function, which interferes with the cyclization (90JOC5894). Acetylenic ketone 194 (95% yield) is readily transformed to the acetal 195 (with potassium carbonate in methanol) however, under the above conditions neither its hydrolysis nor cyclization to the spiroketal occurs. The spirocyclic pyrone 197 is formed in quantitative yield on treatment of 195 with p-toluenesulfonic acid in a 4 1 THF-H2O mixture at reflux for 12 h. 

The action of aqueous potassium hydroxide on chloronitrile 14 in DMSO at 25-30°C accomplishes the hydrolysis of the chloronitrile moiety and furnishes ketone 13 in a yield of 80%. Treatment of a solution of ketone 13 in CH2CI2 with mCPBA and sodium bicarbonate results in a selective Baeyer-Villiger oxidation to give bicyclic lactone 12 in >95% yield. It is noteworthy that the Baeyer-Villiger oxidation is completely regioselective and that the... 

As might be expected, a complex mixture of lactones corresponding to abstraction of a hydrogen atom from various sites along the methylene chain was obtained from the photolysis. The mixture of lactones was converted by dehydration, ozonolysis, and hydrolysis to a mixture of ketones. It was found that no functionalization occurs with ester side chains of less than nine carbon atoms. This is probably due to the inability of the carbonyl to approach any methylene closely enough to abstract a hydrogen. The data for side chains of nine carbons or greater is presented in Table 3.11. 

Carbohydrate lactones have been used as the carbonyl reagent in the Reformatsky reaction. Thus, 2,3 5,6-di-O-cyclohexylidene-D-mannono-1,4-lactone [44, obtained by oxidation of the mannofuranose derivative (49)] reacted with ethyl bromoacetate and zinc to give the protected 2-deoxy-3-octulosonic acid ethyl ester (45a) in 69% yield (50). Ketonic hydrolysis with potassium hydroxide in aqueous methanol, followed by acidification and heating, afforded the 1-deoxyheptulose derivative 45b. Similarly, starting from compound 44, the 1-C-substituted allyl and propar-gyl lactols were prepared on reaction with allyl or propaigyl bromides in the presence of zinc (51). 

The reagent most commonly used for oxidation of ethers is RuO. The subject is well summarized in an early review by Gore [75], Primary methyl ethers RCHjOCHj are oxidised to esters RCOOCH, and secondary methyl ethers R R CjHjOCHj to ketones R COR while with benzyl ethers PhCH OR the esters PhCOOR are formed. For cyclic ethers, the carbon atoms adjacent to the O atom are oxidised, and if there are two secondary carbon atoms the main products are lactones, sometimes with partial hydrolysis to carboxylic acids [75], There is a short review on oxidation of ethers by RuO, principally on the mechanisms involved [76],... 

As will be seen in the following section the most widespread use of the alkylation of lactones is that of y-lactones. Clearly the need for a-substitution of y-lactones was present before the advent of Creger s non-nucleophilic base. The most versatile method was the reaction of a-substitutcd malonic or acetoacetic esters with epoxyethane or 2-chloroethanol, followed by hydrolysis and decarboxylation or ketonic cleavage5. Another common approach was the condensation of butyrolactones (y-lactones) with aldehydes and subsequent hydrogenation5,s. It should be mentioned at this point that these older methods still have their merits, especially for large scale production. 

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