Lactones direct olefination

The first direct olefination of carbohydrate lactones was discovered using the tris(dimethylamino)phosphine-carbon tetrachloride couple which reacted at low temperature to yield dichloroolefins in excellent yields (Scheme 1). The reaction was limited to certain lactones in particular those having a dioxolane protecting group at 0-2-0-3. This limitation was later bypassed by using triphenylphosphine which is less reactive but reacts at higher temperature allowing reaction with poorly reactive 8-lactones. ... 

Retrosynthetic cleavage of the A13,14 double bond in 6 significantly simplifies the side-chain appendage attached to C-l2 and affords aldehyde 7 and ketophosphonate 8 as potential precursors. In the synthetic direction, a Homer-Wadsworth-Emmons reaction10 would appear to provide a very simple means of joining intermediates 7 and 8 with concomitant formation of the requisite trans C13-C14 olefin. Retrosynthetic simplification of aldehyde 7 provides intermediate 9, a molecular assembly commonly known as the Corey lactone. 

Like unsaturated ketones, a,0-unsaturated carboxylic acid derivatives, e.g. lactones and anhydrides, undergo cycloadditions to alkenes. As for the preparative conditions (direct irradiation or sensitized experiments) these compounds are situated somewhere in between enones on the one side and olefins on the other. 

Addition of electrophilic carbenes to enamines usually does not proceed with good efficiency, very likely because of the disturbance by the Lewis basic nitrogen 15). If however the less basic enamide derivatives are used as olefins, high conversions to donor-acceptor cyclopropanes are possible. Thus cyclic carbamate 245, which itself originates from an oxycyclopropane, gives the bicyclic compound 246 almost quantitatively. Its cleavage with aqueous base provides lactone 247 that could be coupled with tryptophyl bromide to afford 248, a direct precursor of the alkaloid eburnamoni-ne 105>. 

Some interesting intramolecular variants have been reported. For example, homoallylic alcohols (e.g. 139) can be treated with sulfamoyl chloride to form the corresponding sulfamates (140), which then engage in a direct intramolecular copper-catalyzed aziridination mediated by iodosylbenzene <02OL2481>. A carbamate tether is also effective in delivering the nitrene center to the olefin, as is the case with the cyclohexenyl derivative 142, which spontaneously cyclizes in the presence of iodosylbenzene <02OL2137>. The acetoxy-aminoquinazolinone 144 is converted to the lactone 145 via intramolecular aziridination upon treatment with lead tetraacetate and hexamethyldisilazane (HMDS) <02TL2083>. 

The tandem 0s04-catalyzed oxidative cleavage of olefin 269 with Oxone as the co-oxidant and sequential direct oxidation of intermediate aldehyde in alcoholic media led to cyclic keto lactone 270 in 45% yield (Equation 34) <20030L3089>. Similar oxidative cyclization with KMnCT-GuSITr resulted in 32% yield of 270 <1994T11709>. 

An orf/io-directed lithiation allows the conversion of 25 to aryl iodide 40. Reductive ether formation of aldehyde 40 with crotyl alcohol yields compound 41. Intramolecular Heck reaction of 41 affords a mixture of the olefins 42 and 43. The undesired alkene 42 can be isomer-ized quantitatively to the desired enol ether 43 with Wilkinson s catalyst. Sharpless dihydroxylation ee 94 %) of the enol ether 43 provides lactol 44, which is oxidized directly to lactone 45. Finally, the pyridone-O-methyl ester is cleaved under acid conditions (45 — 7). 

The equilibrium between a hydroxy acid and its lactone is catalyzed by hydrogen ion. This equilibrium favors lactone formation from y- and S-hydroxy acids removal of the water fornied completes the reaction. /S-Lactones are not obtained directly by this method. Under forced conditions y-lactones are formed from certain /S-hydroxy acids, presumably by dehydration of the latter to olefinic acids followed by lactonization according to method 324. Direct lactonization of hydroxy acids having the hydroxyl group in the epsilon or a more remote position in the chain is difficult. Competing interesterification reactions occur which lead to dimers and polyesters.. Under certain conditions, however, e-caprolactone has been obtained in 63% yield. ... 

Lakhrissi, M, Taillefutnier, C, Chaouch, A, Didieijean, C, Aubry, A, Chapleur, Y, Wittig olefination of partially protected sugar lactones a direct entry to dioxabicyclic and trioxatricyclic systems. Tetrahedron Lett., 39, 6457-6460, 1998. 

Wasserman has completed two syntheses of recifeiolide, both employing the use of oxazoles as acetic acid dianion equivalents. The first (Scheme 1.10) utilized a route previously developed by Corey for his synthesis of 1. Cuprate 4 was alkylated and then converted to iodide 38 in a straightforward manner. Alkylation with oxazole anion 39 and removal of the THP with acid then led directly to alcohol 40. Liberation of the carboximide moiety was achieved by treatment with singlet oxygen to afford 41, which led to the isolation of synthetic 1 after an acid-mediated lactonization step, and separation of the olefin isomers. 

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