A Novel Synthesis of Isoquinolines Containing an Electron Withdrawing Substituent

3,4-Dihydroisoquinolines (10, 13) and isoquinolines (1 I), having various electron withdrawing substituent were synthesized in two steps from Nbenzenesulfonyl-or N, N-dimethylsulfamoyl-Pphenethylamines (2 and 5).A novel cyclization method using ethyl chloro(methylthio)acetate (1) in the presence of SnCI, as Lewis acid, followed by acid or base treatment provides the title compounds in good yield.Various substituted isoquinolines have been frequently synthesized and applied to syntheses of natural products as well as in medicinal chemistry.'However, it is well known that the synthesis of isoquinolines containing electron withdrawing substituent by using classical cyclization methodologies, such as Bischler-Napieralski ~eaction,~ Pomeranz-Fritsch rea~tion,~ Pictet-Spengler reaction4 and so on, is difficult.These cyclization reactions occur only when the benzene ring is activated by electron donating suhstituents.Modified methods are reported in which the authors performed cyclizations by increasing the electrophilicity of iminium group by means of an electron withdrawing substituent, such as acy15-' or ~u l f o n ~l ' -~ group on the nitrogen.FPhenethylamines bearing an electron withdrawing substituent on the benezene ring afford 1,2,3,4-tetrahydroisoquinoline derivatives in poor yields or do not give any cyclized product.Previously, we1" reported that the reaction of N-benzenesulfonyl-pphenethylamines (2) with ethyl chloro(methy1thio)acetate (1) in the presence of SnC1, afford the ethyl N-henzenesulfonyl-1.2.3.4tetrahydroisoquinoline-1-carboxylates(3) in good yields.