Endocyclic enol lactones synthesis

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. 

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. 

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... 

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