Enol lactones, hydrogenation

Enol lactones are assumed to form from iV-methylisoquinolinium salts as a result of a Hofmann-type degradation process. This P elimination is a highly stereospecific reaction in which Z isomers are produced from precursors of erythro configuration and isomers from threo diastereomers(5,97). This fact seems to suggest that syn rather than the more usual anti elimination takes place. Examination of models indicates, however, that there is a preferred conformation in which the C-8 hydrogen is in the syn and coplanar position to the quaternary nitrogen. This hypothesis was proved correct in experiments carried out in vitro (5,14,15,91-94). 

Jacobs and Scott studied the hydrogenation of various unsaturated y- and 8-lactones over Adams platinum in ethanol.93 Similar to enol esters, these enol lactones are readily hydrogenolyzed over platinum, as seen in the examples shown in eq. 13.48. In contrast, hydrogenolysis takes place only slightly with an a,P-unsaturated y-lactone 50 (eq. 13.49). The saturated lactones were not reduced at all under the reaction conditions. 

Enol lactones are hydrogenated to the saturated lactone if the bond is not activated to hydrogenolysis by an a-keto or phenyl group . Conversion of a keto-activator to the ketal prevents hydrogenolysis. When bicyclic compounds are involved, e.g., in 4, the cis-trans nature of the hydrogenated product can be reversed according the choice of solvent ... 

The Chemistry of Rii% b.— The 9— 6p lactone (44, R = H) of the 12-methoxy-podocarpa-8,ll,13-triene series was obtained by the successive dehydration of the 7a- and 7)3-hydroxy-lactones with toluene-p-sulphonic acid in acetic anhydride and hydrogenation of the resulting A -enol-lactone over palladium-charcoal. Examination of the width of the C-6 proton resonance led to the... 

As noted in Section 2.5.1.1.1.1.3.2., enol ethers and esters are less reactive than compounds with isolated double bonds. Double bonds in conjugation with an enol ether are also hydrogenated preferentially. Thus, enol lactone 5 is hydrogenated over palladium in a regio- and diastereoselective manner in excellent yield to give the partially saturated enol lactone 67. 

Treatment of abscisic acid with formic acid-hydrogen chloride gave a product which showed an intense violet-red colour with alkali. The product was shown to be the enol-lactone (59), and the colour may be due to the anion (60). The synthesis of or H -labelled abscisic acid is reported, as well as the synthesis of a number of related compounds. " ... 

This oxidative process has been successful with ketones,esters, and lactones. Hydrogen peroxide can also be used as the oxidant, in which case the alcohol is formed directly. The mechanism for the oxidation of enolates by oxygen is a radical-chain autoxidation in which the propagation step involves electron transfer fix)m the carbanion to... 

Cyclic a,/3-unsaturated carbonyl compounds lacking a y-hydrogen can be ozonized to 1,5-dicarbonyl intermediates, but cycUzation to enol lactones is not possible. Reversal... 

In ketones existing largely as the enol, palladium may prove effective in minimizing hydrogenolysis, Hydrogen was added slereoselectively to the least hindered side of L-ascorbic add (3) to give L-gulono-1,4-lactone (4)... 

When a solution of 25 in a 1 1 mixture of methanol and methylene chloride is exposed to periodic acid, the dithiane group is cleaved oxidatively to give, after treatment of the crude product with camphorsulfonic acid (CSA) in methanol, bisacetal 12 as a 2 1 mixture of C-12 anomers in a yield of 80% (Scheme 3). Although the conversion of 12 into 10 could be carried out on the mixture of anomers, it was found to be more convenient to carry each isomer forward separately. When 12 is treated with lithium diethylamide, the methine hydrogen adjacent to the lactone carbonyl is removed as a proton to give an enolate which is then oxidized in a completely diastereoselective fashion with Davis s oxaziridine18 to afford 11. 

In an effort to make productive use of the undesired C-13 epimer, 100-/ , a process was developed to convert it into the desired isomer 100. To this end, reaction of the lactone enolate derived from 100-) with phenylselenenyl bromide produces an a-selenated lactone which can subsequently be converted to a,) -unsaturated lactone 148 through oxidative syn elimination (91 % overall yield). Interestingly, when 148 is treated sequentially with lithium bis(trimethylsilyl)amide and methanol, the double bond of the unsaturated lactone is shifted, the lactone ring is cleaved, and ) ,y-unsaturated methyl ester alcohol 149 is formed in 94% yield. In light of the constitution of compound 149, we were hopeful that a hydroxyl-directed hydrogenation52 of the trisubstituted double bond might proceed diastereoselectively in the desired direction In the event, however, hydrogenation of 149 in the presence of [Ir(COD)(py)P(Cy)3](PF6)53 produces an equimolar mixture of C-13 epimers in 80 % yield. Sequential methyl ester saponification and lactonization reactions then furnish a separable 1 1 mixture of lactones 100 and 100-) (72% overall yield from 149). 

Besides ordinary esters (containing an a hydrogen), the reaction can also be carried out with lactones and, as in 16-38, with the y position of a,p-unsaturated esters (vinylogy). There are also cases, where the enolate anion of an amide was condensed with an aldehyde. ... 

When the enol (XCVII) of 5-keto-4-desoxy-mannosaccharo-3,6-lactone is subjected to ozonolysis, cleavage occurs at the double bond with the formation of oxalic acid and p-erythuronic acid (XCVIII), the latter being identified by the fact that upon oxidation with bromine it yields mcao-tartaric acid (XCIX). The formation of oxalic acid and erythu-ronic acid locates the double bond in XCVII between C4 and C5 and demonstrates that C4 carries a hydrogen atom while C5 has attached to... 

L-dihydroxy-succinic acid (L(dexiro)-tartaric acid, CXIII). This result establishes the position of the double bond between C4 and C5 and demonstrates that C4 carries only one hydrogen atom while C5 has attached to it the enolic hydroxyl group. Treatment of the enol CXI with ethereal diazomethane gives 5-methyl-A4-D-glucosaccharo-3,6-lactone methyl ester (CXIY) which upon further methylation with silver oxide and methyl iodide yields 2,5-dimethyl-A4-D-glucosaccharo-3,6-lactone methyl ester (CXV). When the latter is subjected to ozonolysis there is formed oxalic acid and 3-methyl-L-threuronic acid (CXVI). Oxidation of this aldehydic acid (CXYI) with bromine gives rise to a monomethyl derivative (CXVII) of L-ilireo-dihydroxy-succinic acid. 

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