Abstract
The lithiation of N-tert-butoxycarbonyl (N-Boc)-1,2,3,4-tetrahydroisoquinoline was optimized by in situ IR (ReactIR) spectroscopy. Optimum conditions were found by using n-butyllithium in THF at -50 degrees C for less than 5min. The intermediate organolithium was quenched with electrophiles to give 1-substituted 1,2,3,4-tetrahydroisoquinolines. Monitoring the lithiation by IR or NMR spectroscopy showed that one rotamer reacts quickly and the barrier to rotation of the Boc group was determined by variable-temperature NMR spectroscopy and found to be about 60.8kJmol-1, equating to a half-life for rotation of approximately 30s at -50 degrees C. The use of (-)-sparteine as a ligand led to low levels of enantioselectivity after electrophilic quenching and the poor man's Hoffmann test indicated that the organolithium was configurationally unstable. The chemistry was applied to N-Boc-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline and led to the efficient synthesis of the racemic alkaloids salsolidine, carnegine, norlaudanosine and laudanosine.