Ligand- and Bronsted acid/base-switchable reaction pathways in gold(I)-catalyzed cycloisomerizations of allenoic acids

Gold-promoted cyclizations of 2,2-diaryl substituted gamma-allenoic acids were found to give three isomeric lactone products, each of which could be obtained selectively by exploiting Bronsted acid/base and ligand effects. Simple 5-exo-trig cyclization products were favored by strong donor ligands or base additives, whereas weak donor ligands and a Bronsted acid additive gave isomeric enelactones resulting from double bond migration. Further optimization afforded a class of medicinally relevant bridged tricyclic lactones via a tandem hydroacyloxylation/hydroarylation process. Kinetic studies and control experiments indicated that the initial 5-exo-trig cyclization product serves as a branch point for further isomerization to the other lactone products via cooperative gold(I)/Bronsted acid catalysis.