Oxidation of lactol

PCC very easily oxidizes lactols to lactones.293 However, at the time of writing, the scientific literature does not contain enough data to assess the relative ability of oxidation of lactols versus alcohols with PCC. 

It is important to emphasize that no oxidation of lactol to lactone occurs whenever an easily detectable amount of lactol is present because lactols can react slower than unsaturated alcohols.71... 

Our premise for the selection of a phosphitylation/oxidation sequence derived from its successful application during the course of the Park nucleotide synthesis.14 Hitchcock reported the phosphitylation/oxidation of lactol 17, existing predominantly as the a-anomer, provided the desired a-phosphate, albeit with a modest 2.5 1 preference.15 In related work, the Walker group reported a similar phosphitylation/oxidation sequence applied to lactol 19 provided a-phosphate 20 as the exclusive product in very good chemical yield.16... 

Oxidation Reactions. Hypoiodite intermediates may be generated from the reaction of simple alcohols with NIS. When conducted under photochemical irradiation, the products of Barton-type or fragmentation reactions of alkoxyl radical intermediates may be obtained. Aldehydes are oxidized to methyl esters via hemiacetal intermediates by reaction with NIS in methanol at rt. However, such conditions are not effective for the oxidation of simple alcohols. The combination of NIS and Tetrabutylammonium Iodide in dichloromethane has been developed for the oxidation of a variety of alcohols to the corresponding carbonyl corrpounds (eq 8). This reagent system is most widely used for the oxidation of lactols to lactones, in which near-quantitative yields are generally obtained under mild conditions (eq 9). ... 

Lactols. Oxidations of lactols to lactones are facile and high yielding several examples have been reported in the literature (eq 1) A ... 

A review of oxidations using Ag2C03 on celite includes useful sections on the oxidations of lactols and diols to lactones. 

Robin and Huet have reported a general method for the synthesis of 8-lactones as weU as lactones with several ring sizes via oxidation of the corresponding lactol [87] (Scheme 43). Alkylation of sulfone 211 with bromoacetaldehyde dimethyl acetal, cleavage of the silyl ether, and treatment with acetic acid afforded lactol 212. Oxidation of lactol 212 with PCC furnished the corresponding saturated 8-lactone 213, which underwent elimination of sulfinic acid in the presence of DBU to provide lactone 214. 

Cordova et al. have developed a direct amino acid-catalyzed asymmetric synthesis of 8-lactones by oxidation of lactols [95] (Scheme 51). The strategy involves... 

In view of the biological importance of the 6-lactone moiety, extensive efforts have been devoted for the development of various methods for the synthesis of saturated 8-lactones. Ammig the various methods, the more classical methods include lactonization of the 8-hydroxy acid derivatives, Baeyer-Villiger oxidation of cyclopentanones, and oxidation of lactols. Besides, more challenging and attractive methods such as oxidative lactonization, radical cyclization, and carbonylatimi have also been used efficiently for the synthesis of 8-lactones. The past two decades have witnessed remarkable growth in the development of catalytic and asymmetric methods for the synthesis of 6-lactones in optically pure form. In the next decade, new and more exciting advances in the development of efficient and catalytic enantioselective methods and their application in the synthesis of complex 8-lactone natural products can be expected. 

The slow oxidation of primary alcohols, particularly MeOH, is utilized for the oxidation of allylic or secondary alcohols with allyl methyl carbonate without forming carbonates of the alcohols to be oxidized. Allyl methyl carbonate (564) forms 7r-allylpalladium methoxide, then exchange of the methoxide with a secondary or allylic alcohol 563 present in the reaction medium takes place to form the 7r-allylpalladium alkoxide 565, which undergoes elimination of j3-hydrogen to give the ketone or aldehyde 566. The lactol 567 was oxidized selectively with diallyl carbonate to the lactone 568 without attacking the secondary alcohol in the synthesis of echinosporin[360]. 

The completion of the synthesis of key intermediate 2 requires only a straightforward sequence of functional group manipulations. In the presence of acetone, cupric sulfate, and camphorsulfonic acid (CSA), the lactol and secondary hydroxyl groups in 10 are simultaneously protected as an acetonide (see intermediate 9). The overall yield of 9 is 55 % from 13. Cleavage of the benzyl ether in 9 with lithium metal in liquid ammonia furnishes a diol (98% yield) which is subsequently converted to selenide 20 according to Grie-co s procedure22 (see Scheme 6a). Oxidation of the selenium atom... 

Similarly, (A )-( )-3-(2-methoxymethyl-l-pyrrolidinyl)-l-phenylpropene118 121, after lithia-tion and addition of acetone, acidic hydrolysis and oxidation of the intermediate lactol, gives (5)-dihydro-5,5-dimethyl-4-phenyl-2(3/f)-furanone with 98% ee and 54% overall yield. Thus, these sequences constitute asymmetric homoaldol addition. 

The mechanism of the oxidation of tertiary cyclobutanols with Jones reagent is believed to involve the intermediate lactols (Eq. (18)) and the cleavage of the lactol to ketol and its subsequent oxidation to diketone when R1 = H157). 

Hall and Bischofberger177 found that, when 2,3 5,6-di-0-isopro-pylidene-D-gulono-1,4-lactone was oxidized with ruthenium(VIII) oxide and an excess of sodium periodate, it gave 2,3 5,6-di-0-isopro-pylidene-D-riho-4-hexulosono-l,4-[(R) or (S)]-lactol. Similar results were observed with 2,3 5,6-di-0-isopropylidene-D-mannono-1,4-lactone and 2,3 5,6-di-O-isopropylidene-D-allono-l,4-lactone. This oxidation presumably proceeds by way of lactone cleavage and oxidation of the free 4-hydroxyl group followed, on acidification by relac-tonization, and formation of the new lactol. 

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 transformation of L-arabinose (58) to lactone 57 was based on a route developed by Marquez and Sharma [51] Selective protection of the primary hydroxy group with TBDPSCl and oxidation of the lactol moiety with bromine afforded lactone 59. Subsequent selective deoxygenation a to the carbonyl group proceeded under Barton-McCombie conditions providing lactone 57 in 21% yield (Scheme 14). 

Some lactol-to-lactone oxidations were effected by TPAP/NMO/PMS/CH Clj [498, 499], or TPAP/NMO/PMS/CH3CN [159]. The system RUCI3 or RuO / Na(Br03)/aq. M Na3(C03) generates [RuO ]" in aqueous solution and oxidised secondary alcohols to ketones in high yield (Table 2.2) [213]. Kinetics of the oxidation of benzhydrol and 9-fluorenol by TPAP/NMO/CH3CN/30°C were measured. 

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