Versatile synthesis of (Z)-1-alkylidene-1,3-dihydroisobenzofurans and 1H-isochromenes by palladium-catalyzed cycloisomerization of 2-alkynylbenzyl alcohols

An easy synthesis of (Z)-1-alkylidene-1,3-dihydroisobenzofurans and 1H-isochromenes by palladium-catalyzed cyclo-isomerization of readily available 2-alkynylbenzyl alcohols under neutral conditions is reported. Reactions were carried out at 70-100degreesC in the presence of catalytic amounts (1-2%) of PdI2 in conjunction with 2 equiv. of KI for 1.5-24 h. The preference towards the 5-exo-dig cyclization mode (leading to 1,3-dihydroisobenzofurans) or the 6-endo-dig cyclization mode (leading to isochromenes) turned out to be dependent on the substitution pattern of the substrate as well as reaction conditions. In several cases, by properly adjusting the reaction conditions. the same substrate could be selectively converted into either the dihydroisobenzofuran or the 1H-isochromene derivative. (C) 2003 Elsevier Ltd. All rights reserved.