Synthesis of Polysubstituted 3-Methylisoquinolines through the 6π-Electron Cyclization/Elimination of 1-Azatrienes derived from 1,1-Dimethylhydrazine

Abstract

A convenient one pot microwave-assisted 6π-electron cyclization/aromatization approach toward 3-methylisoquinolines is reported. The starting 1-azatriene derivatives were prepared in situ by reaction of 2-propenylbenzaldehydes with 1,1-dimethylhydrazine, which exhibited superior performance when compared with other hydrazine derivatives. Minor amounts of the related 3,4-dihydro isoquinolines were formed concomitantly with the isoquinolines, and a mechanism for their generation was proposed. The reaction conditions were optimized, and its scope and limitations were explored. In general, the transformation proceeded in moderate to good yields.