New Synthesis of Isoquinoline and 3,4-Dihydroisoquinoline Derivatives

A simple and efficient synthesis of isoquinoline and 3,4-dihydroisoquinoline derivatives is described. 1-Alkyl(or aryl)isoquinoline and 1-isoquinolinamine derivatives were obtained by intramolecular cyclization of 2-(2-methoxyethenyl)benzonitriles initiated by the addition of alkyl(or aryl)lithiums and lithium dialkylamides to the nitrile carbons, respectively. Synthesis of 4-aryl-3,4-dihydroisoquinolines was achieved by reactions of 2-(1-arylethenyl)benzonitriles with organolithiums, followed by aqueous workup. Treatment of the reaction mixtures with electrophiles prior to aqueous workup allowed the synthesis of 4,4-disubstituted 3,4-dihydroisoquinolines.