Lactone radicals

Second, whereas the cleavage barrier for the dioxetane is reduced on electron transfer (Figure la), for the a-peroxy lactone it disappears completely (Figure lb) presumably, the 0—0 bond is irreversibly cleaved for the a-peroxy-lactone radical anion . This finding is consistent with the experimental observation that the a-peroxy lactones are considerably more efficient in the electron-transfer-induced chemiluminescence than the corresponding dioxetanes . Thus, if persistent a-peroxy lactones were readily accessible, they should be reagents of choice for commercial applications of chemiluminescence. 

Treatment of a-iodo lactone (45) with triethylborane under oxygen atmosphere gives the corresponding a-hydroxy lactone (46), via a-lactone radical species. This reaction comprises of SH2 reaction by Ef on the iodine atom of a-iodo lactones, reaction of the formed a-lactone radical with molecular oxygen, and subsequent hydrogen-atom abstraction from the solvent to form alkyl hydroperoxide (ROOH). Finally, by the addition of dimethyl sulfide for the reduction of the peroxide, the corresponding a-hydroxy lactone is obtained (eq. 2.24) [58]. 

The first catalytic asymmetric radical-mediated allylation was reported in late 1997 by Hoshino and coworkers, who studied the allylation of an a-iodolac-tone substrate, Eq. (19) using trimethylaluminum as Lewis acid and a silylated binaphthol as the chiral catalyst, with triethylborane as radical initiator [62]. Use of one equiv. of diethyl ether was crucial for high enantioselectivity, providing an ee up to 91% in the presence of one equiv. of catalyst, with only a 27% ee in the absence of ether, and poorer ee s when other ethers were employed. In the catalytic version, the ee s dropped off vs. the stoichiometric reaction, with an ee of 81% with 0.5 equiv., and 80% with 0.2 equiv., and 72% with 0.1% catalyst. As in the above example, the presumed chiral intermediate involves complexation of the lactone radical with the Lewis acid-binaphthol complex, with the diethyl ether perhaps as a ligand on the aluminum. 

Exclusive trans addition is observed in reactions of bicyclic lactone radicals, in which the lactone functionality forms the /i.y-substituents43. Acetoxymercurio-, iodo-, and phenylseleno-lactones are used as precursors. The highest yields of addition products arc obtained from thermally initiated reactions of the phenylselenolactone, while the use of the mercury precursor at lower temperature leads to considerable amounts of reduced material. 

Allylic bromination by NBS can be applied with success not only to olefins but also to <%,/ -unsaturated ketones, carboxylic esters, nitriles, and lactones. Radical-formers must be added when NBS is used for allylic bromination of conjugated dienes, for side-chain bromination of aromatic or heterocyclic compounds (see p. 198), or for replacement of tertiary hydrogen atoms next to a C=C bond. 

The resonance stabilized benzofuranyl (lactone) radicals can either reversibly dimerize or react with other free radicals. Model experiments have demonstrated that this class of chemistry behaves as a powerful hydrogen atom donor and are also effective scavengers of carbon-centered and oxygen-centered free radicals (21) (see Fig. 5). 

Fig. 1.40. ESR spectrum of C-centred lactone radical. After Krohnke [823]. Reproduced by permission of the Society of...

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. 

Phthaloyl peroxide, in contrast to diphenoyl peroxide cannot decarboxylate readily to give a stable lactone. The corresponding lactone (25) is unreasonably strained. The as yet unknown phenanthrene dicarboxylic acid and naphthalic peroxides (26) and (27) could form stable lactone radical anions by loss of CO2 on acceptance of an electron from the activator. 

The reaction of perfluoroalkyl iodides with alkenes affords the perfluoro-alkylated alkyl iodides 931. Q.a-Difluoro-functionalized phosphonates are prepared by the addition of the iododifluoromethylphosphonate (932) at room temperature[778], A one-electron transfer-initiated radical mechanism has been proposed for the addition reaction. Addition to alkynes affords 1-perfluoro-alkyl-2-iodoalkenes (933)[779-781]. The fluorine-containing oxirane 934 is obtained by the reaction of allyl aicohol[782]. Under a CO atmosphere, the carbocarbonylation of the alkenol 935 and the alkynol 937 takes place with perfluoroalkyl iodides to give the fluorine-containing lactones 936 and 938[783]. 

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. 

The proposed mechanism for the conversion of the furanone 118 to the spiro-cyclic lactones 119 and 120 involves electron transfer to the a -unsaturated methyl ester electrophore to generate an anion radical 118 which cyclizes on the /3-carbon of the furanone. The resulting radical anion 121 acquires a proton, giving rise to the neutral radical 122, which undergoes successive electron transfer and protonation to afford the lactones 119 and 120 (Scheme 38) (91T383). 

As early as 1940 it has been established9 that diketene does not polymerize by a radical mechanism. It has, however, been shown later10 that it undergoes reactions of radical copolymerization with many vinyl monomers11. In this reaction the double bond is involved and the lactone ring is preserved in the copolymer. 

From a study of the decompositions of several rhodium(II) carboxylates, Kitchen and Bear [1111] conclude that in alkanoates (e.g. acetates) the a-carbon—H bond is weakest and that, on reaction, this proton is transferred to an oxygen atom of another carboxylate group. Reduction of the metal ion is followed by decomposition of the a-lactone to CO and an aldehyde which, in turn, can further reduce metal ions and also protonate two carboxyl groups. Thus reaction yields the metal and an acid as products. In aromatic carboxylates (e.g. benzoates), the bond between the carboxyl group and the aromatic ring is the weakest. The phenyl radical formed on rupture of this linkage is capable of proton abstraction from water so that no acid product is given and the solid product is an oxide. 

The paraffin wax is oxidized by air in a liquid phase process at 110-130°C. Catalysts for this radical reaction are cobalt or manganese salts [54]. The quality of the obtained mixture of homologous carboxylic acids is impaired by numerous byproducts such as aldehydes, ketones, lactones, esters, dicarboxylic acids, and other compounds. These are formed despite a partial conversion of the paraffin and necessitate an expensive workup of the reaction product [50,55]. 

An efficient two-step annelation of functionalized orthoesters with trimethyl-silyloxyfuran derivatives has been reported that produces bicyclo[3. .0]lactones. ° The reaction in Scheme 7 shows an example in which the initial condensation between silyl enol ether and orthoester is followed by the radical cyclization reaction under standard conditions. It is worth underlining the complete diastereocontrol in which three contiguous stereocenters are generated in one step with >95% stereoselectivity. 

Treatment of bicyclic lactones 66, derived from Diels-Alder reaction of 3-carboxy-2-pyrone under standard radical conditions using (TMSlsSiH, leads to bridged lactones 67, which can smoothly be converted to bicyclo[3.3.0]-lactones 68 (Scheme 10). For X = CHaOMe, this cascade of rearrangements took place in a 78% overall yield, providing 68 in diastereomerically pure form. Three additional steps provided a novel route toward Corey s lactone 69. 

As the mechanism, a radical and a cationic pathway are conceivable (Eq. 31). The stereochemical results with rac- or mcjo-1,2-diphenyl succinic acid, both yield only trans-stilbene [321], and the formation of a tricyclic lactone 51 in the decarboxylation of norbornene dicarboxylic acid 50 (Eq. 32) [309] support a cation (path b, Eq. 31) rather than a biradical as intermediate (path a). 

In carboxylic acids with an aromatic group or a double bond the ii-systems can be oxidized to radical cations that react with the carboxyl group to lactones (Eqs. 7, 42) [142, 351]. 

Radical cyclization is compatible with the presence of other functional groups. Treatment of XCH2CON(R)-C(R )=CH2 derivatives (X = Cl, Br, 1) with Ph3SnH and AIBN led to formation of a lactam via radical cyclization. " Cyclization of N-iodoethyl-5-vinyl-2-pyrrolidinone led to the corresponding bicyclic lactam, " and there are other examples of radical cyclization with molecules containing a lactam unit " or an amide unit. Radical cyclization occurs with enamines as well. Photochemical irradiation of A,A-dialIyl acrylamide leads to formation of a lactam ring, and in this case thiophenol was added to generate the phenylthio derivative. Phenylseleno N-allylamines lead to cyclic amines. co-Iodo acrylate esters cyclize to form lactones. " ... 

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