Three-Component Synthesis of 1,2-Dihydroisoquinolines

Significance

Reported is a very mild procedure for the synthesis of 1,2-dihydroisoquinolines by the one-pot reaction of o-alkynylbenzaldehydes, primary amines, and pronucleophiles in generally excellent yields. The reaction shows good scope, requires no catalysis, and utilizes alkyl, aryl, and allyl primary amines, and several pronucleophiles. Sluggish reactivity of substituted alkynyl derivatives is combated by increased reaction temperature in 1,2-dichloroethane. Facile reduction to tetrahydroisoquinoline derivatives may be achieved. A mechanism involving an intermediate zwitterionic species and excluding the involvement of the amine as catalyst is suggested and supported by deuterium labeling experiments.