STEREOCONTROLLED SYNTHESIS OF N-METHYL-1,2,3,4-TETRAHYDROISOQUINOLINE DERIVATIVES VIA CHROMIUM TRICARBONYL METHODOLOGIES

Two chromium tricarbonyl based methods are described for the stereocontrolled synthesis of N-methyl-1,2,3,4-tetrahydroisoquinoline derivatives. Sequential deprotonation-alkylation reactions introduce substituents completely stereoselectively onto the 1- and 4-positions of N-methyl tetrahydroisoquinolines. Acid promoted cyclisations of (N-3,4-dimethoxybenzyl)N-methyl-2-amino-1-aryl ethanol chromium tricarbonyl complexes produce, stereospecifically with retention of configuration, the corresponding 4-phenyl-N-methyl tetrahydroisoquinolines. These cyclisations stereochemically complement those observed for the uncomplexed series. In all cases oxidative decomplexation efficiently releases the free elaborated N-methyl tetrahydroisoquinoline derivatives.