1-Methoxyisobenzofuran from Base-Induced and Acid-Catalyzed Reactions of 1,3-Dihydro-1,3-dimethoxyisobenzofuran

Article abstract of DOI:10.1021/jo00381a015

The title bis acetal (1) has been used in both acid-catalyzed and strong base induced procedures to generate 1-methoxyisobenzofuran (2).The acid-catalyzed reaction is not synthetically useful, since it requires forcing conditions and gives cycloadduct only with very reactive dienophiles (e.g., maleic anhydride).However, the LiNR2-induced 1,4-elimination reaction of 1 yields isolable solutions of 2.This process is strongly solvent-dependent, being more rapid in THF than in diethyl ether, and very slow in hexane.The elimination exhibits syn selectivity in ether solvent, allowing the recovery of unreacted 1 enriched in the cis isomer.However, cis 1 also undergoes base-induced elimination to form 2, showing that an anti elimination pathway, although not favored, is energetically accessible.The utility of the base-induced method was demonstrated by the formation of the 3-lithiated derivative of 2, which was in turn converted to 1-methoxy-3-(trimethylsilyl)isobenzofuran.This derivative gave cycloadducts upon treatment with the dienophiles N-methylmaleimide and benzyne, the latter generated by dehydrohalogenation of bromobenzene.