Palladium-catalyzed tandem reactions to form 1-vinyl-1H-isochromene derivatives

The palladium-catalyzed reaction of pinacolone with tert-butyldimethyl(3-(2 -bromophenyl)allyloxy)-silane results in direct formation of 1-vinyl-3-tert -butyl-1H-isochromene. This is the result of a ketone arylation followed by an intramolecular cyclization of the enolate with the allylic system. The use of a lithium diamide base appears to be essential for success. The tert -butyldimethylsilyl protecting group is also an essential choice as it furn ishes the appropriate reactivity to promote allylic substitution after the aryl coupling process. The use of more effective leaving groups, such as ac etate, results in reaction of the allylic group, and no aryl coupling is ob served. Through the appropriate selection of phosphine ligand and solvent, either the cyclized isochromene product or the noncyclized intermediate may be formed selectively. A short combinatorial study of the scope and limita tions of the reaction, involving 24 ketones, is described.