Lactones spirolactones

We have developed a direct synthetic method for the one-pot synthesis of lactones, spirolactones, di-spirolactones, tertiary alcohols, and even 1,2-diols from the corresponding conjugated diene-magnesium reagents mediated by Rieke magnesium [122], The overall lactonization procedure can be considered... 

Butyrolactones can be obtained from carbonyls and the /8-lithiopropionate (58), derived from /3-bromopropionic acid by sequential treatment with n-butyl-lithium and lithium naphthalenide. Although yields are generally less than 50%, the method could find use as a simple route to spirolactones. The spirolac-tone (59), a potential precursor of the trichothecane antibiotic verrucarin A, has been obtained by a Diels-Alder reaction using a-methylenesuccinic anhydride as ene component followed by borohydride reduction to the lactone. Spirolactone... 

Dioxocarboxylic acid 238 upon treatment with HTIB, cyclizes to dioxo-5-lactone 239 by intramolecular participation of the carboxylic group. When cyclic diketo acid 240 is the substrate, spirolactone 241 is obtained (90TL201). 

In 1994, Quayle et al. reported the application of this cyclic Fischer-carbene synthesis from 3-butynols to spirolactone synthesis, although the process was stepwise and a stoichiometric amount of the complex was employed [17]. The key transformation was the chromium or tungsten carbene complex formation followed by the CAN oxidation of the complex to give y-lactone. The reaction was further applied to the synthesis of andirolactone and muricatacin, the former being shown in Scheme 5.14. 

Cyclopentenones. The anion of 1 (LDA, THF, —78") is susceptible to attack by electrophiles at either the a- or /-position. At temperatures of - 78° the reaction occurs at the former position at temperatures near 0" the product is a spirolactone. These lactones are converted into cyclopentenones when heated at 60° with P205 in methanesulfonic acid. 

Spirofuran-2(5H),2 (3 H)furo[2,3-6]furan synthesis, 4, 659 Spirofuranones synthesis, 3, 734 Spiro[3.3]heptane physical properties, 1, 590 Spiroindazoles irradiation, 5, 252 Spiroisoarsindolinium salts, 1, 544 Spiroisoxazolines synthesis, 6, 108 Spirolactones synthesis, 3, 846-847 Spiro-/3-lactones synthesis, 7, 395 Spiro nomenclature, 1, 26 Spirooxadiazoles synthesis, 4, 822 Spirooxaziridines photorearrangement, 7, 541 (8-scission, 7, 211 Spirooxetanes synthesis, 7, 393 Spirooxiranes cleavage... 

Thermal cycloreversion of /3-lactones provides a useful approach to alkenes as illustrated for the conversion of a spirolactone to an exocyclic alkene (Equation 13) <1996J(P1)1287> and several cyclic alkenes (Equations 14 and 15) <2001JOC7818, 2000T3559>. 

Fukuzawa44,45 and Inanaga46 showed that the coupling of ketones and aldehydes with acrylates mediated by Sml2 generally leads to y-lactones due to cyclisation of the intermediate alkoxide produced from the carbon-carbon bond-forming step. This is illustrated by the reaction of cyclooctanone with methyl acrylate to provide the spirolactone 27 in high yield (Scheme 5.22). 

In a second attempt, a whole range of bicyclic 7-spirolactones (synthesized from (+)- and (-)-limonene) as well as tricyclic 7-lactones with a pinane system (from (R)-(-)-myrtenol and (-)-a-pinene) were synthesized. In total, 13 semisynthetic compounds 74-86 were tested for their antifeedant activity against the three storage pests. Antifeedant activities of the semisynthetic compounds were generally not very high when tested against... 

Under similar conditions, reduction of an Qr,)6-unsaturated lactone linked to a linear a,)6-unsaturated ester gave modest yields of two isomeric spirolactones, [Eq. (17)]. CV of simple monofunctional compounds indicates that in this case the a,)6-unsaturated ester function is the electrophore [159]. The regioselective coupling ip to the ester group) and the presence of a proton donor (diethyl malonate) indicate that the probable reaction pathway is a-protonation of the radical anion, further reduction, and Michael addition of the resulting )6-anion to the lactone. 

Similar condensations can be accomplished with other types of stabilized carbanions, e.g. sulfonyl anions, as illustrated by equation (81). The resulting sulfonyl lactone (228) eliminates sulfinic acid on treatment with p-TsOH to furnish the a,3-unsaturated system (229).Spirolactonization is the result of the Reformatsky reaction of ester (231) with cyclic ketones. In equation (82), this reaction is applied to the synthesis of the lysergic acid precursor (232), which is formed stereoselectively from (230). ... 

The common examples are ester (aspirin), thiol ester (spirolactone), amide (chloramphenicol), sulfonamide (sulfapyrazine), imide (phenobarbital), lactam (methicillin), lactone (spiranolactone), and halogenated aliphatic (chlorambucil). 

Other Reactions.—Addition of lithium /3-lithiopropionate to androstenolone leads to the synthesis of the spirolactone (101). Reaction of the lactone (102)... 

Conjugate addition to cyclopropyl lactones and fi-keto esters. (4, 219-220). The reaction of the cyclopropyl lactone (1) with 1.5 eq. of dimethylcopper-lithium at -30 to 0° gives the isomeric spirolactones (2) in high yield. The related cyclopropyl /34ceto ester (3) reacts similarly to give (4). 

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