The allenic carbocyclization reaction of allene-ynes: Progress towards the syntheses of fumagillol and ovalicin

The Rh(I)-catalyzed allenic carbocyclization reaction is a powerful strategy for the assembly of densely functionalized cyclic cross-conjugated trienes. This methodology exhibits excellent functional group compatibility, and allows for the construction of five-, six-, and seven-membered rings in high yields from allene-yne precursors. In this thesis, progress towards the total synthesis of (--)-fumagillol and (--)-ovalicin is reported. The entire carbocyclic skeleton of both structurally related natural products has been synthesized in a single synthetic transformation via an allenic carbocyclization reaction. It is anticipated that the allylic hydroxyl group of the functionalized cross-conjugated can be used for the chemo- and stereoselective installation of epoxides and hydroxyl groups incorporated in both sesquiterpenes.;The constitutional group selectivity of the beta-hydride elimination step in the allenic carbocyclization reaction has been investigated. We found that TMS-alkynyl allenes with an appending isobutylene group can be reacted under Rh(I)-catalyzed allenic carbocyclization reaction conditions to afford regioisomerically pure cross-conjugated trienes in good yields. The examples within, indicate that a coordinating alkene can be incorporated into the allene-yne substrate to control the beta-hydride elimination step of the cyclization reaction to yield trienes with a 1,1-disubstituted alkene side chain.