Total synthesis of natural bicyclic lactones (+)-dihydrocanadensolide, (+/-)-avenociolide, and (+/-)-isoavenociolide via tungsten-pi-allyl complexes

A synthetic method using tungsten-pi-allyl compounds is developed for total syntheses of natural bislactones including (+)-dihydrocanadensaolide (2), (+/-)-avenociolide (3), and (+/-)-isoavenociolide (4). Syntheses of these n atural compounds are based on a common intermediate, trans-alpha-methylene butyrolactones bearing an anti-homoallylic alcohol. The kep steps in the sy ntheses involve an intramolecular alkoxycarbonylation of propargyltungsten complexes to yield tungsten-pi,gamma-lactonyl species, followed by condensa tion of their CpW(NO)I(pi-allyl) derivatives with suitable aldehydes. This new method is very efficient for the synthesis of(+/-)-avenociolide (3) and (+/-)-isoavenociolide (4). Total syntheses of compounds 3 and 4 require on ly six and three steps, respectively, on the basis of chloropropargyl deriv atives.