Lactone and ketone

Both chiral lactones and ketones have been utilized in asymmetric synthesis of bioactive compounds like lipoic acid [175[ and natural products like various insect pheromones [176[. 

Limited progress has been achieved in the enantioselective hydrogenation of a,/ -unsaturated carboxylic acid esters, amides, lactones, and ketones (Scheme 26.10). The Ru-BINAP system is efficient for the hydrogenation of 2-methy-lene-y-butyrolactone, and 2-methylene-cyclopentanone [98]. With a dicationic (S)-di-t-Bu-MeOBIPHEP-Ru complex under a high hydrogen pressure, 3-ethoxy pyr-rolidinone could be hydrogenated in isopropanol to give (R)-4-ethoxy-y-lactam in 98% ee [39]. 

The mixture of optically pure lactone and ketone solution was evaporated by rotary evaporator to dryness. The residue mixture was separated by flash chromatography over silica gel (hexane ethyl acetate 5 1), eluted first as colorless oil (5)-lactone (41 mg, 36 % yield, 99 % ee, [aJo = —16, c = 10, in CH2CI2), followed by (/f)-ketone as colorless oil (19 mg, 19 % yield, 99 % ee). 

The Mo(VI)-peroxide complex, MoOs(Py)(HMPA), has been used424 to hydroxylate selectively enolizable esters, lactones, and ketones, presumably via epoxidation of the enolate ... 

Coupling of lactones and ketones. Sml2 in THF/HMPA effects coupling of a carbohydrate-derived lactone such as 1 and a ketone that involves oxygenation of 1 followed by a carbonyl addition reaction with high diastercosclcctivity. 

In an extension of the methodology described for the preparation of a-methylenebutyrolactones," it has been found that O-silyl enolates of esters, lactones, and ketones can be smoothly monoalkylated by reactive alkyl halides [e.g. benzylic, allylic, MeOCHzCl, PhSCH(Cl)R] in the presence of small amounts of zinc bromide. This approach could find extensive use especially in cases where direct carbanion methods are unsatisfactory. 

Hydroxy-esters.—Enolates derived from esters as well as those from lactones and ketones can be oxidized to the corresponding a-hydroxy-derivatives by the crystalline complex [M0O5,pyridine,HMPA]. Typically, yields are in the range 56—85%. 

Patulin and penicillic acid are unsaturated lactones and are inactivated by cysteine. They are also unsaturated ketones whether they react with cysteine as lactones or as ketones is not known. It has been suggested (48,78) that the unsaturated lactones and ketones that have antibacterial activity react with sulfhydryl and possibly with amino groups of essential enzyme proteins. All of the substances listed above under ketone and lactone, with the possible exception of helvolic acid for which there is no data, are inactivated by cysteine. 

The synthesis of a-methylene lactones and ketones via the elimination of a mesylate has also been reported (eqs 17 and 18). In these cases, the pyridine or triethylamine is sufficiently basic to induce elimination under standard mesylate forming conditions. 

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