Facile synthesis of substituted isoquinolines

A facile three-step protocol toward methoxy isoquinolines 7 starting with substituted 2-allylbenzaldehydes 9 was described. The overall synthetic process of skeleton 7 was carried out using the Grignard addition, PCC-oxidation, and one-pot oxidative cleavage of the olefinic group of skeleton 9 with OsO4–NaIO4 followed by the condensation of the resulting 1,5-dicarbonyl compounds with NH4OAc. Skeleton 9 was prepared in high yield via the known Claisen rearrangement of skeleton 8 and O-methylation. Papaverine 2 is also synthesized via the simple three-step synthetic protocol.