Alkylations of isoquinoline via lithium aluminium hydride

Abstract

Lithium aluminium hydride (LAH) in tetrahydrofuran (THF) reacted rapidly with isoquinoline to give lithium tetrakis dihydroisoquinoline aluminate (LTDA). Proton and ('13)C NMR spectra indicated the presence of only 1,2- but not 1,4-dihydro isomer. Unlike isoquinoline, pyridine or quinoline was less reactive and gave the corresponding 1,2- as well as 1,4-dihydro ligands. In THF, the isoquinoline-LAH intermediate (LTDA) reacted with methyl iodide, ethyl bromide, n-propyl bromide, allyl bromide, n-butyl bromide and benzyl chloride but not sec- and tert-butyl bromides to give the corresponding 4-substituted isoquinolines. In diethyl ether (Et(,2)O), all of these alkyl halides reacted. The yields of products ranged from 25 to 64% in THF, and 43 to 61% in Et(,2)O. For most reactions, yields of alkylated products were substantially higher in Et(,2)O than in THF: a one-electron transfer mechanism was proposed. ('1)H NMR and mass spectra for the 4-substituted isoquinolines were reported. These reactions also gave other minor products including 1,2,3,4-tetrahydroisoquinoline, monoalkylated tetrahydroisoquinolines and dialkylated tetrahydroisoquinolines.