HETEROATOM-DIRECTED LATERAL LITHIATION - SYNTHESIS OF ISOQUINOLINE DERIVATIVES FROM N-(TERT-BUTOXYCARBONYL)-2-METHYLBENZYLAMINES

Methodology for the preparation of isoquinoline derivatives from N-(tert-butoxycarbonyl)-2-methylbenzylamines (1) was developed. Conversion of 1 to the dilithio species followed by condensation with DMF afforded Boc-3-hydroxy-1,2-3,4-tetrahydroisoquinolines 3, which could be dehydrated to 1,2-dihydroisoquinolines 4. Hydrogenation of dihydro compounds 4 afforded the corresponding tetrahydroisoquinolines 5. Treatment of the dilithio species from 1 with N-methoxy-N-methylamides afforded ketones 15, which were converted to 3-substituted dihydro-isoquinoline 15, tetrahydroisoquinolines (16,17), or isoquinolines (20).