P-Unsaturated Lactones

Review Problem 7 a-p-Unsaturated lactones are nsefhl intermediates in syntliesis as they take part in Diels-Alder reactions to buhd larger molecules with more complex functionahty. How would you make tliis one ... 

Intramolecular cycloadditions of a,p-unsaturated lactones to alkenes have been used as key step in the synthesis of a precursor of the terpene reserpine 480) (4.68) and of fused cyclooctanes (4.69) 481 ... 

Complete reduction of unsaturated esters to sativated alcohols takes place when the esters are hydrogenated over Raney nickel at 50° and 150-200 atm [44] or over copper chromite at temperatures of 250-300° and pressures of 300-3 50 atm [52,1056] (p. 153). In contrast to most examples in the literature the reduction of ethyl oleate was achieved at atmospheric pressure and 270-280° over copper chromite, giving 80-90% yield of octadecanol [1074]. a.,P-Unsaturated lactones are reduced to saturated ethers or alcohols, depending... 

In the first addition of nitrile ylides to a,P-unsaturated lactones (92), it was found that the reaction of benzonitrilio 4-nitrobenzylide with the lactones 178-180 were strongly regioselective. Compounds 178 and 179 reacted to give [e.g., 181 from 178 (51 %)] and its methyl analogue from 179 (54%). The exocyclic double bond in 180 was, however, the most reactive and gave 182 (69%). The six-membered analogue of 178 was less reactive (34%) and the seven-membered analogue failed to react. 

As seen above with the phosphate receptors, researchers are often not satisfied with only binding their targets, but they also want to mimic enzymes and produce some catalytic activity from their receptors. De Mendoza and collaborators used the bicyclic guanidinium 47 to effect the addition of pyrrolidine to a,p unsaturated lactones [79]. Using a 10% catalyst loading in chloroform, an eightfold reduction in the half-life of the starting materials was observed by... 

To this end, the naphthopyran derivative 44 was our first target, which could be derived from the a,p-unsaturated lactone 40 and the o-methylbenzoate 41 through Michael and Dieckmann reactions. It was expected that the pivotal conversion of a monomer 44 to a dimer 46 could be accomplished by oxidative coupling (Scheme 5). 

On one hand, the a,P-unsaturated lactone 40, which was derived from di-O-acetyl-L-rhamnal (39) according to reported procedures, was submitted to Mitsunobu inversion with HCO2H, followed by hydrolysis and methoxymethylation to afford 40. On the other hand, the o-methylbenzoate 41 was obtained from 3,5-dihydroxytoluene under the protocols described by Solladig. 

After conjugate addition of the hydroperoxide anion to the chelated a,p-unsaturated lactone, the resulting enolate counterattacks the proximal [3-hydroperoxide group to form an epoxide. The latter then ring-expands to create another enolate, which captures a proton from water. The product hemiacetal finally undergoes ring-opening and saponification to produce 9 (Scheme 6.5). 

Reaction of ketones and a,a-dimethoxyketones in the presence of TiCl4-Bu3N led to the formation of a,p-unsaturated lactones, which were converted to 2,3,4-trisubstituted furans. One of the examples is the preparation of menthofuran, the natural mint perfume <02CC2542>. 

Exocyclic a,P-unsaturated lactones (e.g. 137) have been converted to the corresponding spiroaziridines 138 by treatment with ethyl AT- [(4-nitrobenzene)sulfonyl]oxy carbamate (Ns0NHC02Et) in the presence of caleium oxide <03TL4953>. In a similar vein, a novel chiral carbamate 139 based on Helmchen s alcohol has been applied to the same conditions with moderately good diastereoselectivities, as shown in the aziridination of carboethoxy-cyclopentenenone 140 <03TL3031>. 

Reduction has been reported for other hydride reagents, such as diisobutylaluminum hydride aluminum hydride and 9-BBN-H. a,p-Unsaturated lactones are also reduced by DIBAL-H to the corresponding lactols in high yields. ... 

Oxidation of a cyanohydrin derived from a conjugated aldehyde (as the O-TMS derivative) using py-ridinium dichromate (PDC) in DMF gave an a,p-unsaturated lactone (6 -butenolide) as the major product (equation 12). Simple nonconjugated cyanohydrins are not satisfactory substrates for the synthesis of acyl cyanides using PDC, because they seem to add to the initially formed acyl cyanides, leading ultimately to cyanohydrin esters. Oxidation of cyanohydrin to acyl cyanides can be carried out either by means of manganese dioxide, mthenium-catalyzed oxidation with r-butyl hydroperoxide or NBS. ... 

Beecham, A.F. (1972) The CD of a,P-unsaturated lactones. Tetrahedron, 28, 5543-5554. Borsche, W. (1927) Untersuchungen uber die bestandteile der kawawurzel. III. Uber die katalytische hydrierung des methysticins. Chemische Berichte, 60, 982—984. 

Many compounds containing a,P-unsaturated lactones may also give a positive reaction with the following tests. Other reactions for sesquiterpene lactones and cardiac glycosides may be found in the literature (47). 

Heterocycles. Many different heterocycles are synthesized via a carbonylation process hydantoins from aldehydes and urea, flavones from ethynylarenes and o-iodophenol acetates, and a-substituted a,p-unsaturated lactones from iodoalkenols. ... 

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