Lactones by oxidation

In the aldopentose series, 2,3,4-tri-O-acetyl-a-D-xylopyranose afforded the corresponding unsaturated 1,5-lactone by oxidation - elimination. Likewise, hepta-O-acetylcellobiose gave, upon oxidation (184), the product of -elimination at the reducing end. 2,3,4,6-Tetra-O-benzoyl-D-gluco- and D-mannopyranoses were not oxidized by the same reagents. 

A diol was converted to a lactone by oxidation with stoich. RuOyCCl as part of the total synthesis of the quassinoid ( )-amaroMe [355] stoich. (PPh )[Ru(0)2Cl3]/... 

Oxidation of oleic acid to 10-hydroxyoctadecanoic acid by a gram-positive bacterium was described with a transformation yield of 65% at a concentration of 50 g oleic acid after 72 h in a medium containing Tween 80 [232]. The hydroxy fatty acid can be converted to 4-dodecanolide, an important coconut-fruity like lactone, by -oxidation with yeasts, affording a total lactone yield of about 20% from oleic acid [222, 232]. 

For examples of the preparation of lactones by oxidation of diols, sec Doyle Bagheri J. Org. Chem. 1981, 46, 4806 Ishii Suzuki Ikariya Saburi Yoshikawa J. Org. Chem. 1986, 51, 2822 Jefford Wang J. Chem. Soc., Chem. Commun. 1988, 634 Jones Jakovac Org. Synth. VII, 406. For a list of reagents used to effect this conversion, with references, see Ref. 21. pp. 837-838. 

E. Ayadi, S. Czemecki, and J. Xie, Convenient preparation of perbenzylated 2-azido and 2-iV-acetylamino-2-deoxy-D-hexono-1,5-lactones by oxidation of the corresponding lactols,. /. Carbohydr. Chem., 15 (1996) 191-199. 

Isbell and Hudson identified lactones as the oxidation products of aldoses in buffered solution. The conditions were such that any free aldonic acid formed would be converted into the salt. Hence, lactones are the initial oxidation products and it was concluded that cyclic sugars give 5-lactones by oxidation with bromine water. The reactions were carried out in a solution buffered with barium carbonate and carbon dioxide. In the slightly acidic medium employed, the oxidation was rapid and interconversion between the anomeric forms of the sugars was relatively slow. In some cases the oxidation was 95% complete in five minutes. The extent of the reactions can be seen in Table X. 

A similar case of a stereoselective radical-induced lactonization is the cyclization of 4-substitut-ed homoallylic xanthates25. The 5-exo cyclization proceeds with high diastereoselectivity. The thionolactone is easily converted to the corresponding lactone by oxidation with 3-chloroper-oxybenzoic acid to give 2,3-disubstituled dihydro-2(3//)-furanones. 

Scheme 12. Formation of oxadiazoles and hydrazono lactones by oxidation of benzoylhy-drazones.

The synthesis of 7-lactones by oxidative addition of acetic acid to alkenes in the presence of Mn(0Ac)2 has been documented for some... 

M.C. Bagley, Z. lin, D.J. Philips, A.E. Craham, Barium manganate in microwave-assisted oxidation reactions synthesis of lactones by oxidative cyctization of diols. Tetrahedron Lett. 50 (2009) 6823-6825. 

Scheme 28 Enantiospecific preparation of lactones by oxidative lactonization of primary meso-diols. " ...

Aye KT, Colpitts D, Ferguson G, Puddephatt RJ. Activation of -lactone by oxidative addition and the structure of a platina(IV)lactone. Organometallics. 1988 7 1454-1456. 

Similarly, Schlecht and Kim have reported a substituent-directed oxidation method for the synthesis of 8-lactones by oxidative cyclization of hydroxyalkenes [80] (Scheme 36). Addition of alkenyl Grignard reagent to ketones 184 afforded hydroxyalkene 185, which upon treatment with chromium trioxide in acetic acid and acetic anhydride provided spiro-8-lactone 186. 

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... 

Alkynes undergo stoichiometric oxidative reactions with Pd(II). A useful reaction is oxidative carboiiyiation. Two types of the oxidative carbonyla-tion of alkynes are known. The first is a synthesis of the alkynic carbox-ylates 524 by oxidative carbonylation of terminal alkynes using PdCN and CuCh in the presence of a base[469], Dropwise addition of alkynes is recommended as a preparative-scale procedure of this reation in order to minimize the oxidative dimerization of alkynes as a competitive reaction[470]. Also efficient carbonylation of terminal alkynes using PdCU, CuCI and LiCi under CO-O2 (1 I) was reported[471]. The reaction has been applied to the synthesis of the carbapenem intermediate 525[472], The steroidal acetylenic ester 526 formed by this reaction undergoes the hydroarylalion of the triple bond (see Chapter 4, Section 1) with aryl iodide and formic acid to give the lactone 527(473],... 

Po adrninistered nifedipine is almost completely absorbed. The onset of action is 20 min and peak effects occur at 1—2 h. The principal route of elimination is through hepatic metaboHsm by oxidation to hydroxycarboxyHc acid and the corresponding lactone. These metaboHtes are pharmacologically inactive. Almost 70—80% of dmg is eliminated in the urine during the first 24 h. About 15% is excreted in the feces. The elimination half-life of nifedipine is about 1—2.5 h (1,98,99). Frequency of occurrence of side effects in patients is about 17% with about 5% requiring discontinuation of therapy (1,98,99). 

Transformation of cyclic ketones into lactones by Baeyer-Villiger oxidation 99EJ0737. 

By analogy, thermal cyclization was described also for 6-nitro-2 -hydroxy-biphenyl-2-carboxylic acids, e.g. 14, obtained by other methods. The same product 15 was also formed from lactone 17, prepared by oxidation of fluorenone 16 (Scheme 2). If the reaction was performed in DMF, the corresponding dimethylamide was isolated (82KGS703, 86KGS852, 87KGS314, 89MI1). 

It has been reported that concentrated H2SO4 (98%) promotes conversion of 3,5-dibromolevulinic acid 47 into 4-bromo-5-(bromomethylene)-2(5// )-furanones 48 (R = Br R = H) along with minor products, while similar treatment using 20% oleum gives the isomeric 5-(dibromomethylene)-2(5// )-furanone 49 (R = H R = Br) as the major product (63AJC165). Spectroscopic data and chemical structures were not provided for the minor substances, but the formation of the major product was explained on the basis of the enol-lactonization process followed by oxidation (63AJC165). 

As inert as the C-25 lactone carbonyl has been during the course of this synthesis, it can serve the role of electrophile in a reaction with a nucleophile. For example, addition of benzyloxymethyl-lithium29 to a cold (-78 °C) solution of 41 in THF, followed by treatment of the intermediate hemiketal with methyl orthoformate under acidic conditions, provides intermediate 42 in 80% overall yield. Reduction of the carbon-bromine bond in 42 with concomitant -elimination of the C-9 ether oxygen is achieved with Zn-Cu couple and sodium iodide at 60 °C in DMF. Under these reaction conditions, it is conceivable that the bromine substituent in 42 is replaced by iodine, after which event reductive elimination occurs. Silylation of the newly formed tertiary hydroxyl group at C-12 with triethylsilyl perchlorate, followed by oxidative cleavage of the olefin with ozone, results in the formation of key intermediate 3 in 85 % yield from 42. 

THF/liq. NH3, followed sequentially by oxidation and base-induced double bond isomerization, provides butenolide 33, a compound that possesses the lactone system of the steroidal cardiac aglycones. 

The next key step, the second dihydroxylation, was deferred until the lactone 82 had been formed from compound 80 (Scheme 20). This tactic would alleviate some of the steric hindrance around the C3-C4 double bond, and would create a cyclic molecule which was predicted to have a greater diastereofacial bias. The lactone can be made by first protecting the diol 80 as the acetonide 81 (88 % yield), followed by oxidative cleavage of the two PMB groups with DDQ (86% yield).43 Dihydroxylation of 82 with the standard Upjohn conditions17 furnishes, not unexpectedly, a quantitative yield of the triol 84 as a single diastereoisomer. The triol 84 is presumably fashioned from the initially formed triol 83 by a spontaneous translactonization (see Scheme 20), an event which proved to be a substantial piece of luck, as it simultaneously freed the C-8 hydroxyl from the lactone and protected the C-3 hydroxyl in the alcohol oxidation state. 

The surface of carbonaceous materials contains numerous chemical complexes that are formed during the manufacturing step by oxidation or introduced during post-treatment. The surface complexes are typically chemisorbed oxygen groups such as carbonyl, carboxyl, lactone, quinone, and phenol (see Fig. 3). 

The acid 19 has been dimerized, although in low yield, in the course of a perhydro-phenanthrene synthesis [141]. When the oxidation potential of the double bond is sufficiently lowered by alkyl substituents, lactone formation by oxidation of the couble bond rather than of the carboxyl group occurs (Eq. 7) [142] (see also chap. 15). 

Scheme 13.17 depicts a synthesis based on enantioselective reduction of bicyclo[2.2.2]octane-2,6-dione by Baker s yeast.21 This is an example of desym-metrization (see Part A, Topic 2.2). The unreduced carbonyl group was converted to an alkene by the Shapiro reaction. The alcohol was then reoxidized to a ketone. The enantiomerically pure intermediate was converted to the lactone by Baeyer-Villiger oxidation and an allylic rearrangement. The methyl group was introduced stereoselec-tively from the exo face of the bicyclic lactone by an enolate alkylation in Step C-l. 

The structure of narlumidine (119) was established by Dasgupta et al. (117,119) on the basis of spectral data, particularly by comparison with spectra of bicucullinine (108), and also on chemical grounds. On hydrolysis followed by oxidation-methylation, narlumidine (119) was converted to ester 147, which was also obtained from 108 by N.O-methylation. Sodium borohydride reduction gave lactone 145, identical to the lactone obtained from 108. 

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