Investigating the stereochemical outcome of a tandem cyclization - coupling reaction leading to a 3-arylmethylideneisobenzofuran-1-one

A palladium-catalyzed tandem cyclization-coupling reaction of o-ethynylbenzoic acids with p-iodoanisole led to a stereochemical mixture of 3-arylmethylideneisobenzofuran-1-ones. The major product resulted from an unexpected syn addition of the aryl group and carboxylic acid across the alkyne. Treatment of the major product with the hypervalent iodine reagent (bis(trifluoroacetoxy)iodo)benzene (phenyliodine bis(trifluoacetate)) (PIFA) led to an alkene isomerization that produced the minor tandem product. The structure and stereochemistry of the major and minor tandem reaction products were confirmed by independent syntheses. This work provides access to both the (E) and (Z) stereoisomers of arylmethylideneisobenzofuran-1-ones (phthalides). [GRAPHICS] .