A Facile Synthesis of 1-Substituted 3-Alkoxy-1H-isoindoles Based on the Reaction of 2-(Dialkoxymethyl)phenyllithiums with Nitriles, Followed by Acid-Catalyzed Cyclization

作者：Kuroda Minami; Kobayashi Kazuhiro^*

来源：Helvetica Chimica Acta, 2015, 98(3): 279-286.

DOI：10.1002/hlca.201400333

• 1H-Isoindoles
• 3-alkoxy-
• Phenyllithium
• 2-(dialkoxymethyl)-

A two-step synthesis of 1-substituted 3-alkoxy-1H-isoindoles 4 has been developed. Thus, the reaction of 2-(dialkoxymethyl)phenyllithium compounds, which are easily generated in situ by Br/Li exchange between 1-bromo-2-(dialkoxymethyl)benzenes 1 and BuLi in THF at -78 degrees, with nitriles afforded [2-(dialkoxymethyl)phenyl]methanimines 2, which were treated with a catalytic amount of TsOHH2O in refluxing CHCl3 to give the desired products in reasonable yields. Similarly, 3-aryl-1-ethoxy-1-methyl-1H-isoindoles 7 have been prepared starting from 1-bromo-2-(1,1-diethoxyethyl)benzenes 5.

• 出版日期2015-3