Synthesis of 3-substituted tetrahydroisoquinolines by acid-catalyzed cyclization of p-toluenesulfonamides of N-benzyl aminoacetaldehyde derivatives

The acid-catalyzed cyclization of p-toluenesulfonamides of N-benzyl aminoacetaldehyde, or their acetalic counterparts, usually yields 1,2-dihydroisoquinolines. However, cyclization of intermediates bearing a substituent α to the carbonyl group affords 3-substituted 2-p-toluenesulfonyl tetrahydroisoquinolin-4-ol derivatives, capable of further transformation into the related 1,2,3,4-tetrahydroisoquinolines.