Simple, efficient copper-free Sonogashira coupling of haloaryl carboxylic acids or unactivated aryl bromides with terminal alkynes

In the absence of Cu(I), the catalytic coupling of haloaryl carboxylic acids or unactivated aryl bromides with terminal alkynes are shown to occur in the presence of 10 equiv. piperidine at 85 °C within 20 min using PdCl2(PPh3)2 as catalyst in good to excellent yields. This procedure avoids the carboxy group protection/deprotection steps and enhances the total yield to simplify the synthesis of acetylenic retinoids. It is noteworthy that this protocol employs direct, mild and efficient copper-free reaction conditions.