Tetrahydroisoquinolines. Part 2. Synthesis of 4-substituted N-methyl-1,2,3,4-tetrahydroisoquinolines via regio- and stereo-selective elaboration of tricarbonyl(N-methyl-1,2,3,4-tetrahydroisoqumoline)chromium

Abstract

Thermolysis of hexacarbonylchromium with N-methyltetrahydroisoquinoline generates the tricarbonyl-(N-methyltetrahydroisoquinoline)chromium complex (4). The 4-exo proton of complex (4) can be regio- and stereo-selectively removed with butyl-lithium and replaced stereoselectivity with retention of configuration by a variety of electrophiles [Mel, Etl, PhCH₂Br, CD₃OD, Cr(CO)₃(PhF), MoOPH, Me₂CO]. Oxidative decomplexation generates quantitatively the corresponding 4-methyl, ethyl, benzyl, deuterio, phenyl, hydroxy, and (1-hydroxy-1-methylethyl)-N-methyltetrahydroisoquinolines.