Synthesis of dihydrobenzofurans via palladium-catalyzed heteroannulations

Abstract

<p>Dihydrobenzofurans, dihydrofurocoumarins and dihydrofuroflavonoids occur commonly in plants and fruits and are very important because of their pronounced biological properties. Existing methodology for the synthesis of these classes of natural products suffer from low yields and limited scope. In this dissertation a new efficient heteroannulation approach to various natural products via palladium-catalyzed annulation of 1,3-dienes by 3-iodo-2-alkenols, 2-iodo-2-alkenols, and acylated o-iodophenols is presented. Preliminary studies using o-iodophenols revealed a major problem with rapid dehalogenation. To solve this problem, we have developed "optimal" reaction conditions using acetoxy derivatives. The presence of the acetyl group on the phenolic oxygen and the use of silver carbonate as a base are crucial for this process. This reaction is very general, regio- and stereoselective, and a wide variety of terminal, cyclic and internal 1,3-dienes can be utilized. This new methodology can be utilized for the synthesis of various substituted dihydrofuroumarins, dihydrofuroflavones, and dihydrobenzofurans.</p>