Potassamide induced in situ alkylation of 5,6-dihydroisoquinolines: Structure of products

Article abstract of DOI:10.1016/S0040-4020(01)80377-X

Potassamide induced in situ alkylation of 1-alkyl- 4-cyano-3-methoxy-5,6-dihydroisoquinolines (2a & 2b) with alkyl iodides (CH₃I, CH₃CH₂I & cyclohexyl iodide) gave the 5-alkyl- and 5,9-dialkyl-5,6-dihydroisoquinolines (4-ad & 3a-e), isoquinoline derivatives, (5a-b) and diastereomeric mixture of 4- alkyl-1,2,3,4-tetrahydroisoquinolin-3(2H)-ones (6a-e & 6′a-e). Structures were assigned on the basis of spectral data [Mass, ¹H & ¹³C NMR, 2D NOESY & HC-COLOC]. Amide induced in situ alkylation of compounds 3a and 4a with CH₃I gave in almost quantitative yield the dimethylated compounds 3d and 3a respectively. While KNH₂/liq.NH₃ methylation of 1,2-dihydroisoquinoline, 1 with CH₃I gave the mixture of compounds, 6a & 6′a and the isoquinoline derivative 5a, NaH/benzene reaction of 1 with CH₃I gave exclusively 5a. N-methylation of the mixture of compounds 6a & 6′a with NaH/CH₃I gave the methylated derivatives, 7 & 8. A suitable mechanism has been proposed for the formation of products.