Lactones elimination reactions

Because of the activating effect of the carbonyl group, aldonolactone derivatives readily undergo -elimination reactions to yield unsaturated lactones. 

Benzoylation of D-g/ycero-D-gw/o-heptono-1,4-lactone with an excess of benzoyl chloride and pyridine afforded the hept-2-enono-1,4-lactone as the main product (198). The di- and triunsaturated compounds were isolated in very low yield from the mother liquors (199). Higher yields of the di- and triunsaturated derivatives 153 and 154 were obtained when the /5-elimination reaction was performed with triethylamine on the previously synthesized per-O-benzoyl D-g/ycero-D-gw/o-heptono-1,4-lactone. Employing 10% triethylamine in chloroform, the lactone 153 was obtained as an E, Z dias-tereomeric mixture in 9 11 ratio as determined by H n.m.r. When 20% triethylamine was used, the furanone 154 was obtained in 59% yield (200). Its structure was assigned, on the basis of H and 13C n.m.r. spectra, as 3 -benzoyloxy - (5Z)-[(Z)-3 - benzoyloxy - 2 - propenyliden] -2(5 H)- furanone. The stereochemistry of the exocyclic double bonds was established (201) by nuclear Overhauser effect spectroscopy (NOESY). 

The lactonization-elimination step was investigated independently with a broad array of A,A-disubstituted 2-(hydroxymethyl)benzamides. The rate of this reaction was highly sensitive to the nature of the /V-subslilucnls and to pH (minimum at pH 5 - 6). Above pH 6, general base catalysis occurred. 

An unexpected result was obtained when DTBB-catalyzed lithiation was applied to the vinyl-oxetane 313 . After work-up, lactone 314 was isolated, the process being explained by an elimination reaction via a radical pathway more than by reduction of the benzyl radical into the anion. Thus, this hypothetical intennediate reacted with the lithium enolate of acetaldehyde, generated in situ by reductive decomposition of THF (Scheme 92). 

A novel one-pot synthesis of various fused lactones has been achieved via a domino sequence of Knoevenagel/ hetero-Diels-Alder/elimination reactions of N- and 0-prenyl aryl aldehyde derivatives with Meldrum s acid in the presence of D- or L-proline with high diastereoselectivity (Scheme 68) <2005MI1353>. 

A straightforward explanation for the unexpected stability of / -lactone enolate 2 has been put forward, a stereoelectronic reason in the rigid system 2 the essential orbitals are held orthogonal to each other as in 2 thus, an elimination reaction has a much higher activation energy than in an open system49. 

Starting from L-rhamnono-1,4- or 1,5-lactone, via p-elimination reactions, 3,5,6-trideoxy-a-DL-t/zra -hexose276 or 3,4,6-trideoxy-DL-t/zreo-hexose has been obtained.277... 

The / -elimination reaction has been used as the first step for the enantioselective synthesis of 1,3-polyols, starting from per-O-benzoyl-D-g/ycero-D-gM/o-heptono-1,4-lactone.101... 

Deoxy- and dideoxy-aldonolactones have also been prepared via the bromo derivatives, which on hydrogenolysis yield the corresponding deoxyaldonolactones.293 3-Deoxyaldonolactones have been obtained via /1-elimination reactions on aldonolactones and catalytic hydrogenation of the intermediate 2-enonolactone derivatives.37 The synthetic potential of this reaction was used for the synthesis of 3-deoxyaldonolactones by combining the base-catalyzed elimination of peracylated lactones with the in situ reduction.294... 

In a third general approach, 2-keto-3-deoxyaldonic acids are prepared from 2-enonolactones. These precursors are readily prepared in good yield by /1-elimination reactions on the protected lactones.37 Starting from... 

Starting from D-galactono-1,4-lactone, 2-keto-3-deoxy-D-hexonic acids with either the D-erythro (119) or D-threo configuration (120) were obtained in only three steps.318 Epimerization at C-4 occurred during the base-catalyzed /1-elimination reaction on the galactonolactone derivative 136. 

Quite recently, Tiecco [46a, 128] reported the asymmetric version of the one-pot conversion of, y-unsaturated esters and nitriles 261 (Scheme 42) into the enantiomerically enriched allylic ethers and alcohols 276 (Scheme 45). The reactions were effected with the selenenyl sulfate produced from the camphor diselenide 26. Unfortunately, in the present case, this diselenide must be employed in stoichiometric amounts. However, it can be partially recovered at the end of the reaction. Good chemical yields and enantiomeric excesses (up to 86%) were obtained in the methoxyselenenylation-elimination reactions. Lower ee was observed when the reactions were run in ethylene glycol or in water. In the case of the hydroxyselenenylations, reaction yields were low because the addition products 275 gave rise to the lactones, which were then deselenenylated to the butenolides. These were isolated in about 30% yield. 

The same method was applied to the synthesis of biologically active nucleosides ( )-2 -deoxy-2 -(carboxymethylene)-5 -0-trityluridine-3, 2 -)/-lactone 158 (O Scheme 42). Exposure of 2, 5 -cyclouridine derivative to the House-Blankey protocol afforded the corresponding diazo compound 156, which could be converted to the y-butyrolactone of uridine 157 in 65% yield via [1,5]-C,// insertion. Lactone 158 could be smoothly obtained by an elimination reaction with sodium hydride in 85% yield. 

The thermal decarboxylation of a P-lactone has been widely used for preparation of an olefin. See [51, 52]. Recent examples of the thermal decarboxylation of P-lactones are described in [53-57], 301efins have been prepared by elimination reactions, in which oxazolidinone functioned as a leaving group. See [59-61],... 

Either photolysis or flash-vacuum pyrolysis of a y-sultine B may result in the elimination of sulfur dioxide and the formation of the corresponding cyclopropane. As in the case of y-lactones, the reaction is promoted by substituents on the y-carbon atom that promote the initial C-0 bond homolysis and reactions are rarely successful in unactivated systems. ... 

In connection with a synthesis of the hydroazulenic sesquiterpene kessanol (304), Knoevenagel condensation of photocitral-A (302) with ethyl cyanoacetate was found to give (303) as a single isomer. The following sequence includes an intramolecular Prins reaction initiated with SnCU. In Isobe s synthesis of vemolepin (307) the two carbons of the -y-iactone are introduced by a Knoevenagei condensation. Reaction of ketone (305) with di-f-butyl maionate followed by treatment with DBU affords (306), which is transformed to the a,a -dihydroxy compound (308). Hydrolysis of the esters foliowed by decarboxy-iation, formation of the y-lactone, Mannich reaction and elimination yields vemolepin (307 Scheme 58).3"... 

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