Endocyclic enol lactones

Up to now no reversible photorearrangement of a nonenolizable jS-diketone to an endocyclic enol lactone is known, but several examples of photo-stationary equilibria between j8-diketones and exocyclic enol lactones have been established. After irradiation of either 175 or 176 in benzene a photoequilibrium mixture containing 175 + 176 + 177 is formed with a product ratio 3 95 2.109 With 2-mono- or disubstituted 1.3-indanediones and cis- and frans-alkylidenenaphthalides 43 44,16 it was shown that the ratio of enol... 

Epoxidation of exocyclic enol lactones. Peracids, even under buffered conditions, are not useful for this epoxidation because of rearrangement and decomposition. Dimethyldioxirane effects epoxidation of y-methylene-y-butyrolactones (1) in 94-96% yield in 2-3.5 hours. It is also effective for epoxidation of endocyclic enol lactones such as 3. 

The regioselective anti-Markovnikov addition of benzoic acid to phenylacetylene has also been carried out successfully at 111 °C in the presence of mthenium complexes containing a tris(pyrazolyl)borate (Tp) ligand, (RuCl(Tp)(cod), RuCl(Tp)(pyridine), RuCl(Tp)(tmeda)) with a stereoselectivity in favor of the ( )-enol ester isomer [17]. The cr-enynyl complex Ru(Tp)[PhC=C(Ph)C=CPh)](PMe-i-Pr2) efficiently catalyzes the regioselective cyclization of a,alkynoic acids to give endocyclic enol lactones (Scheme 8.18) [68]. 

The CT-enynyl complex [Ru C(Ph)=C(Ph)C CPh (Tp)(PMeiPr2)] is able to catalyze the regioselective cyclization of a,co-alkynoic acids to yield endocyclic enol lactones.75... 

Finally, Tenorio et al showed that the (7-enynyl complex TpRu(CPh = CPhC = CPh)(PMeTr2) efficiently catalyses the regioselective cyclization of a,co-alkynoic acids to yield predominantly endocyclic enol lactones having ring size up to 12 atoms [Eq. (11)]. 

Alper and Yu in 2007 developed the palladium-catalyzed highly substituted endocyclic enol lactone synthesis via the carbonylation of terminal alkyne and 1,3-diketones in an ionic hquid system (Table 15.21) [29]. Thirteen examples have been isolated under this process. It should be noted that this catalytic system can be recycled five times with only modest loss of its catalytic activity. 

S Palladium-Catalyzed Heterocyclic Synthesis via Carbonylative C-H Activation 489 Table 15.21 Carbonylation for the highly substituted endocyclic enol lactone synthesisl l. 

XLIV) centers about elaboration of hydroxymethylene ketone (574) into the tricyclic diketone (578). Alkylation of keto nitrile 575 proceeds exclusively cis to the angular methyl groups as does the subsequent reductive methylation. These authors were not able to achieve aldol cycUzation of keto aldehyde 576 and consequently proceeded to enol lactone 577 The addition of a methyl group to 578 could be achieved regioselectively. Subsequently dehydration gave 579 and its endocyclic isomer which were separated chromatographically. 

Enol lactones of carboxylic acids [X = —COR— (to C2) with exocyclic and X = —COR— (to C3) with endocyclic lactones Section VIII]. 

In recent work Coates, Mason and Shah have successfully achieved the synthesis of gymnomitrol (29Ja).280) Since intramolecular aldol condensation of the aldehyde obtained by hydrolysis of 291 (Scheme 45) was unfavorable, conversion to enol lactone 292 was effected. Dibal-H reduction of 292 resulted directly in aldoli-zation of the intermediate lactol, oxidation of which afforded 293. The latter was converted successfully to keto alcohol 294 by capitalizing on the different steric environments about the carbonyl groups. Sequential dehydration and hydride reduction of 294 gave a 45 55 mixture of exo and endocyclic isomers 295a and295 b which were separated by TLC. 

Cl 1-25 of the milbemycins. The intramolecular spiroketalization theme was slightly altered to feature an endocyclic enol ether [86] by condensation of a lithio-2-benzenesulfonyl-tetrahydropyran with a suitable epoxide. An alternative but not enantiospecific approach from lactone B 3 comes from a double Baeyer-Villiger oxidation of bicyclo[2.2.1]heptane-2,5-dione to control [107] the relative stereochemistry in the B ring. The acetylenic partner was in turn derived from two different routes, the more selective being an anti hydroxyl group directed alkylation of a homopropargylic alcohol. 

The a-methylene-) -butyrolactone grouping is incorporated in a large number of sesquiterpenoids, many of which have significant biological activity. A number of routes have been devised for the synthesis of this moiety but recently an important contribution from Ourisson s laboratory has demonstrated that the more accessible a-methyl-y-lactones can be converted in two steps into the a-methylene analogues.This is achieved by reaction of the lactone (263 R = H) with triphenylmethyl-lithium and quenching the resultant enolate with 1,2-dibromoethane. Dehydrobromination of the derived bromide (263 R = Br) with diazabicyclononene gives exclusively the exocyclic methylene lactone (264). This method is only suitable for c/s-y-lactones since the trans-lactone yields exclusively the endocyclic isomer. To illustrate this method Ourisson et at. have converted dihydro-6-epi-santonin (265) into (- )-frullanolide (266). More recently the same authors have developed a method which is applicable to... 

Deoxo-l,2-dihydro-6-episantonin treated at 5° with excess triphenylmethyl-lithium in dimethoxyethane in the presence of tetramethylethylenediamine, and the resulting enolate quendied with 1,2-dibromoethane at the same temp. -> a-bromolactone (Y ca. 50%) refluxed 1 hr. with excess diazabicyclononene in toluene (-)-frullanolide (Y 80%). F. e. s. A. E. Greene, J.-C. Muller, and G. Ourisson, Tetrah. Let. 1972, 2489 f. method, also endocyclic a,j -ethylene-y-lactones, cf. ibid. 1972, 3375. 

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