Synthesis of Dihydrobenzofurans via Palladium-Catalyzed Annulation of 1,3-Dienes by o-Iodoaryl Acetates

Abstract

The palladium-catalyzed annulation of 1,3-dienes by o-iodoaryl acetates provides an efficient approach to biologically interesting dihydrobenzofurans. The annulation is believed to proceed via (1) oxidative addition of the aryl iodide to Pd(0), (2) syn-addition of the resulting arylpalladium complex to the 1,3-diene, (3) intramolecular coordination of the phenolic oxygen to the Pd center, (4) hydrolysis of the acetyl group, and (5) reductive elimination of Pd(0), which regenerates the catalyst. This reaction is quite general, regioselective, and stereoselective, and a wide variety of terminal, cyclic, and internal 1,3-dienes, as well as electron-rich and electron-deficient o-iodoaryl acetates, can be utilized.

A Facile and Efficient Synthesis of Dronedarone Hydrochloride

“…The iodination of 4-nitrophenol gave 2-iodo-4-nitrophenol (3), 26 which was subjected to esterification with acetic anhydride to afford phenyl acetate 4 in almost quantitative yield. The Sonogashira coupling of 4 and 1-hexyne worked well at 25 o C for 7 h in anhydrous THF in the presence of Pd(PPh 3 ) 4 /CuI/Et 3 N in 81% yield.…”

Palladium‐Catalyzed Heterocyclization: A Carbon‐Centered Approach

“…After oxidative addition, carbopalladation generates the first new bond; this intermediate can then react with a second part of the arene to form the new heterocycle. Rozhkov and Larock showed how acetylated phenols could be used in the second step to generate a selection of dihydrobenzofurans (Scheme a), whilst Kadnikov and Larock also showed how CO could be incorporated during this step, thereby creating a range of quinolones (Scheme b) …”

Strategies for the Synthesis of 2,3-Dihydrobenzofurans

“…An improved procedure was recently reported for the Pdcatalysed reaction of 2-iodophenyl acetates 92 with dienes 93 to give DHBs 94 (Scheme 20). 72 A range of 2,2-disubstituted DHBs (e.g. 95) could be accessed in good yield, although the effect of substituents at all positions on the diene was not investigated simultaneously.…”