Conversion to lactones

Scheme 8 Alcohol (94), prepared from (72, was converted to hydroxy hemiacetal (95) upon treatment with potassium carbonate in aqueous isopropanol. Selective oxidation and acetylation yielded ester (96), whose conversion to lactone (97) was achieved without dificulty. Dehydration of (97), followed by cuprate addition, provided (98), whose conversion to phytuberin has already been accomplished.

SCHEME 1.6 ProUne-catalyzed assembly of propionaldehyde and conversion to lactone. 

Figure 3.11 shows the relative reactivity as a function of ring size for two other intramolecular displacement reactions, namely, conversion of ethers from ca-bromoalkyl monoethers of 1,2-dihydroxyben-zene. 

The transformation of an ester carbonyl group to a difluoromethylene group, which IS usually difficult to perform, can be accomplished by conversion to the thiaesier followed by treatment with diethylaminosulfur trifluoride (DAST). A vanety of ester types react efficiently, although the reaction fails with lactones. Remarkably, trimethylsilylmethyl esters carry through the proeedure with the silyl group intact [13] (equation 17). 

The reaction of peracids with ketones proceeds relatively slowly but allows for the conversion of ketones to esters in good yield. In particular, the conversion of cyclic ketones to lactones is synthetically useful because only a single product is to be expected. The reaction has been carried out with both percarboxylic acids and Caro s acid (formed by the combination of potassium persulfate with sulfuric acid). Examples of both procedures are given. 

When the lactone silyl ketene acetal 18-1 is heated to 135° C a mixture of four stereoisomers is obtained. Although the maj or one is the expected [3,3] -sigmatropic rearrangement product, lesser amounts of other possible C(4a) and C(5) epimers are also formed. When the reaction mixture is heated to 100° C, partial conversion to the same mixture of stereoisomers is observed, but most of the product at this temperature is an acyclic triene ester. Suggest a structure for the triene ester and show how it can be formed. Discuss the significance of the observation of the triene ester for the lack of complete stereospecificity in the rearrangement. 

Methylation of X with silver oxide and methyl iodide gave the lactone of methyl 2,5-dimethyl-j8-D-glucofururonoside (XIII) which was characterized by its conversion to the crystalline amide (XIV). Further methylation of XIII, form, with methyl sulfate and sodium hydroxide gave methyl 2,3,5-trimethyl-/3-D-glucofururonoside (XVI) from which by hydrolysis of the glycosidic methyl group and subsequent oxidation with bromine, there was obtained 2,3,5-trimethyl-D-glucosaccharolactone (XVII) characterized by the formation of its crystalline methyl ester. 

It has been shown that Lewis acid catalyzed isomerization of thionolactones provides access to thiolactones. For example, exposure of the substrate 22 to catalytic amounts of BF3 OEt2 led to efficient conversion to the thiolactone 23. Such transformations were also found to give minor amounts of lactone or dithiolactone side products <06TL6067>. Substituted tetrahydrothiophene derivatives have also been obtained from 1,4-dithiane-2,5-diol and 2-nitroethyl acetate derivatives by a base induced sequence featuring a Michael addition and a Henry reaction <06TL8087>. 

Somewhat better results were obtained by the use of (Ph3P)2PtI2 in a polar solvent such as dimethylformamide (122). At 180°C and 250 atm H2/CO, an 89% conversion to aldehydes with an isomer ratio of 4.3 1 was obtained in 1 hour. Relatively high concentrations of catalyst (2500 ppm as Pt metal) were required. Palladium, as (Ph3P)2PdI2, was less effective and also produced considerable amounts of lactones. 

Substituted benzo[b]furan can be oxidatively converted to the lactone 57 in 81% yield, which is allowed to react with chloroformate containing a chiral trans-( R,2R)-2-phenylcyclohexyl group (R ) to give the benzo[ft]furan-based enol carbonate. When the carbonate is treated with DMAP, nearly complete conversion to the new benzo-fused y-lactone 58 is observed in dichloromethane or in THF with a diastereomeric ratio of 3 1 <00OL1031>. 

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