Lactones oxidative lactonization

Colourless crystals m.p. I25°C, soluble in water and alcohol. In aqueous solution forms equilibrium with its lactones. Gluconic acid is made by the oxidation of glucose by halogens, by electrolysis, by various moulds or by bacteria of the Acetobacter groups. 

C (rapid heating). Manufactured by the oxidation of lactose or the galactans from wood with nitric acid. When heated with water it forms a soluble lactone. Converted to furoic... 

By saccharic acid is usually meant D-gluco-saccharic acid, m.p. 125-126°C, obtained by the oxidation of glucose or starch. This exists in water solution in equilibrium with its two y lactones, both of which can be obtained crystalline, though the acid itself does not crystallize readily. 

Cyclic compounds capable of undergoing ring opening (alkylene oxides, lactones, lactams, anhydrides, etc.). 

Baeyer-Villiger Oxidation- oxidation of ketones to esters and lactones via oxygen insertion... 

The y-lactone problem is made easier because the FGs are all based on oxygen. The molecule can therefore be disconnected without FGl except for oxidation or reduction. Let s now look at the synthesis of a molecule with a difficult FG the muscle relaxant baclofen TM 349. What is the difficult FG ... 

Synthesis of (A) started with the combination of 2,4,6-trimethylphenol and allyl bromide to give the or/Ao-allyl dienone. Acid-catalyzed rearrangement and oxidative bydroboration yielded the dienone with a propanol group in porlactone ring were irons in the product as expected (see p. 275). Treatment with aqueous potassium hydroxide gave the epoxy acid, which formed a crystalline salt with (R)-l-(or-naphthyl)ethylamine. This was recrystallized to constant rotation. 

The (partial) description of the synthesis and coupling of the five fragments starts with the cyclohexyl moiety C —C. The first step involved the enantio- and diastereoselective harpless epoxidation of l,4-pentadien-3-ol described on p. 126f. The epoxide was converted in four steps to a d-vinyl d-lactone which gave a 3-cyclohexenecarboxylate via Ireland-CIaisen rearrangement (cf. p. 87). Uncatalysed hydroboration and oxidation (cf. p. 131) yielded the desired trans-2-methoxycyclohexanol which was protected as a silyl ether. The methyl car-... 

The furo- and pyranobenzopyranones 114 and 115 are prepared by the reaction of 0-enolate of i(-keto lactone 113[132], The isoxazolc 117 is obtained by the oxidation of the oxime 116 of a, /3- or, d, 7-unsaturated ketones with PdCh and Na2C03 in dichloromethane[l 33], but the pyridine 118 is formed with PdCl2(Ph3P)2 and sodium phenoxide[134]. 

The intramolecular oxidative earbonylation has wide synthetie applieation. The 7-lactone 247 is prepared by intramolecular oxycarbonylation of the alke-nediol 244 with a stoichiometric amount of Pd(OAc)2 under atmospheric pres-sure[223]. The intermediate 245 is formed by oxypalladation, and subsequent CO insertion gives the acylpalladium 246. The oxycarbonylation of alkenols and alkanediols can be carried out with a catalytic amount of PdCl2 and a stoichiometric amount of CuCb, and has been applied to the synthesis of frenolicin(224] and frendicin B (249) from 248[225]. The carbonylation of the 4-penten-l,3-diol 250, catalyzed by PdCl2 and CuCl2, afforded in the c -3-hydroxytetrahydrofuran-2-aeetie acid lactone 251[226J. The cyclic acetal 253 is prepared from the dienone 252 in the presence of trimethyl orthoformate as an accepter of water formed by the oxidative reaction[227]. 

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],... 

Carbonylation of the complex 548 proceeds in ethanol gives ethyl 3-chloro-3-butenoate (554), The lactone 555 and the two esters 556 and 557 are obtained by carbonylation of the dimeric complex 549. The oxidative carbonylation of allene in ethanol with PdCl2 gives ethyl itacoante (558), although the yield is low[498]. 

The a-bromo-7-lactone 901 undergoes smooth coupling with the acetonyltin reagent 902 to afford the o-acetonyl-7-butyrolactone 903[763j. The o-chloro ether 904, which has no possibility of //-elimination after oxidative addition, reacts with vinylstannane to give the allyl ether 905, The o -bromo ether 906 is also used for the intramolecular alkyne insertion and transmetallation with allylstannane to give 907[764],... 

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 product (6 hexanohde) is a cyclic ester or lactone (Section 19 15) Like the Baeyer-Vilhger oxidation an oxygen atom is inserted between the carbonyl group and a carbon attached to it But peroxy acids are not involved m any way the oxidation of cyclohexanone is catalyzed by an enzyme called cyclohexanone monooxygenase with the aid of certain coenzymes... 

Compounds known as lactones which are cyclic esters are formed on Baeyer—Vilhger oxi dation of cyclic ketones Suggest a mechanism for the Baeyer—Vilhger oxidation shown... 

The use of epoxides as alkylating agents for diethyl malonate provides a useful route to y lactones Wnte equations illustrating such a sequence for styrene oxide as the starting epoxide Is the lactone formed by this reaction 3 phenylbutanohde or is it 4 phenylbutanohde ... 

When a preparative method for an aldonic acid is re quired bromine oxidation is used The aldonic acid is formed as its lactone More properly described as a reaction of the anomeric hy droxyl group than of a free aldehyde... 

Tetrahydrofurfuryl alcohol is oxidized to 2-tetrahydrofurfural [7681-84-7] in good yield by passage, with oxygen, over silver gauze at 500°C (123—124). With chromate oxidizing agents, lactones are also formed (124,125). 

Alkoxide-Type Initiators. Using the guide that an appropriate initiator should have approximately the same stmcture and reactivity as the propagating anionic species (see Table 1), alkoxide, thioalkoxide, carboxylate, and sUanolate salts would be expected to be usehil initiators for the anionic polymeri2ation of epoxides, thikanes, lactones, and sUoxanes, respectively (106—108). Thus low molecular weight poly(ethylene oxide) can be prepared... 

The chemical properties of cycHc ketones also vary with ring size. Lower members (addition reactions, than corresponding acycHc ketones. The Cg—C 2 ketones are unreactive, reflecting the strain and high enol content of medium-sized ring systems. Lactones are prepared from cycHc ketones by the Bayer-ViUiger oxidation reaction with peracids. S-Caprolactone is manufactured from cyclohexane by this process ... 

Carbonyl Compounds. Cychc ketals and acetals (dioxolanes) are produced from reaction of propylene oxide with ketones and aldehydes, respectively. Suitable catalysts iaclude stannic chloride, quaternary ammonium salts, glycol sulphites, and molybdenum acetyl acetonate or naphthenate (89—91). Lactones come from Ph4Sbl-cataly2ed reaction with ketenes (92). 

The most significant chemical characteristic of L-ascorbic acid (1) is its oxidation to dehydro-L-ascorbic acid (L-// fi (9-2,3-hexodiulosonic acid y-lactone) (3) (Fig. 1). Vitamin C is a redox system containing at least three substances L-ascorbic acid, monodehydro-L-ascorbic acid, and dehydro-L-ascorbic acid. Dehydro-L-ascorbic acid and the intermediate product of the oxidation, the monodehydro-L-ascorbic acid free radical (2), have antiscorbutic activity equal to L-ascorbic acid. 

This synthesis was the first step toward industrial vitamin production, which began in 1936. The synthetic product was shown to have the same biological activity as the natural substance. It is reversibly oxidized in the body to dehydro-L-ascorbic acid (3) (L-// fi (9-2,3-hexodiulosonic acid y-lactone), a potent antiscorbutic agent with hiU vitamin activity. In 1937, Haworth and Szent-Gyn rgyi received the Nobel Prize for their work on vitamin C. 

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