Lactones, from lactol oxidation

The expected hydroxyaldehyde is obtained accompanied by a lactone, resulting from the oxidation of a lactol equilibrating with the hydroxylaldehyde. 

During selective oxidations of 1,4- and 1,5-diols with active Mn02, sometimes the unreacting alcohol forms a lactol by interaction with the carbonyl group resulting from the oxidation of an unsaturated alcohol. This lactol can be further oxidized to a lactone.70... 

Oxidation. Lactone formation from lactols based on the (PPhjljRuClj-mediated hydrogen transfer to benzalacetone is efficient. The application of this technique to the process of elaborating a dihydropyran unit into two carbon chains played a crucial role in a synthesis of akuammicine. ... 

The more conventional and straightforward way to obtain 8-lactone is through oxidation of the corresponding lactol. For example, a direct synthesis of 8-lactones from 2-(3-lithiopropyl)-l,3-dioxolane and carbonyl compounds has... 

Conjugate addition of methyl magnesium iodide in the presence of cuprous chloride to the enone (91) leads to the la-methyl product mesterolone (92) Although this is the thermodynamically unfavored axially disposed product, no possibility for isomerization exists in this case, since the ketone is once removed from this center. In an interesting synthesis of an oxa steroid, the enone (91) is first oxidized with lead tetraacetate the carbon at the 2 position is lost, affording the acid aldehyde. Reduction of this intermediate, also shown in the lactol form, with sodium borohydride affords the steroid lactone oxandrolone... 

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). 

D-Ribonolactone is a convenient source of chiral cyclopentenones, acyclic structures, and oxacyclic systems, useful intermediates for the synthesis of biologically important molecules. Cyclopentenones derived from ribono-lactone have been employed for the synthesis of prostanoids and carbocyclic nucleosides. The cyclopentenone 280 was synthesized (265) from 2,3-0-cyclohexylidene-D-ribono-1,4-lactone (16b) by a threestep synthesis that involves successive periodate oxidation, glycosylation of the lactol with 2-propanol to give 279, and treatment of 279 with lithium dimethyl methyl-phosphonate. The enantiomer of 280 was prepared from D-mannose by converting it to the corresponding lactone, which was selectively protected at HO-2, HO-3 by acetalization. Likewise, the isopropylidene derivative 282 was obtained (266) via the intermediate unsaturated lactone 281, prepared from 16a. Reduction of 281 with di-tert-butoxy lithium aluminum hydride, followed by mesylation, gave 282. 

Optimum yields of (3-vinyl-y-butyrolactols from the Pd(II) promoted reaction of vinyl triflates with Z-but-2-en-l,4-diol (Scheme 6.33) are attained when tetra-n-butylammonium chloride is added (47]. The lactol is conveniently oxidized to the lactone with celite-supported silver carbonate. The corresponding arylbutyrolactols are obtained in high yield (70-80%) from an analogous reaction of iodoarenes with the enediol. The yields of 2-alkenyl-2,5-dihydrofurans, resulting from the Pd(0) catalysed reaction of cyclic alkynylcarbonates with acrylic esters via tandem C-C and C-0 bond forming reactions, are enhanced by the presence of tetra-n-butyl-ammonium fluoride (e.g. Scheme 6.33) (48]. 

A naive look at the product suggests an oxidation to a ketone followed by a Baeyer-Villiger like reaction. The product is best explained by a fragmentation from an intermediate chromate ester, resulting on an aldehyde and a stabilized tertiary carbocation that is transformed into a tertiary alcohol by reaction with water. The hydroxyaldehyde so obtained may evolve to the final lactone either via a lactol or a hydroxyacid. 

Lactols derived from hydroxyketones cannot be oxidized to lactones. Theoretically, they could be oxidized to dicarbonyl compounds via the minor hydroxyketone equilibrating with the lactol. In practice, this reaction is usually so slow as to allow the selective oxidation of alcohols with PDC, in the presence of lactols derived from hydroxyketones. 

Lactols are easily transformed into lactones in TEMPO-mediated oxidations.49 When the oxidation of a diol leads to a hydroxyaldehyde that is able to equilibrate with a hemiacetal, the latter is further oxidized to a lactone.50 Interestingly, as TEMPO-mediated oxidations can be very selective in favouring oxidations of less hindered alcohols, lactone formation from diols can be very regioselective.500... 

Conclusive proof of the structures of the glycosides B and C was obtained by methylation, hydrolysis, oxidation and comparison of the rates of hydrolysis of the lactones so obtained. From the glycoside B a 1,5-lactone was obtained,141 whereas a 1,4-lactone was derived from C, showing that the glycoside B had a 1,5-pyranose lactol ring and C a 1,4-furanose lactol ring. Since A and B were a- and /3-anomers, it followed that A also had a pyranose structure. 

Conversion of 77 into the O-benzylhydroxamicacid derivative 78 followed by O-desilylation and oxidation of the resulting lactol furnished the lactone 79. The trifluoroacetamide 80 obtained by successive treatment of 79 with samarium (II) iodide and acidic Dowex resin, on exposure to methanolic potassium carbonate generated, (+)-7-deoxypancratistatin (67). The overall yield of the alkaloid starting from D-gulonolactone was 7%. 

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