Weinreb amide based synthetic equivalents for convenient access to 4-aryl-1,2,3,4-tetrahydroisoquinolines

New synthetic equivalents. N-methoxy-N-methyl-N'-phenylsulfonyl glycinamide and N-methoxy-N-methyl-N'-benzyl-N'-tert-butyloxy carbonyl glycinamide based on WA functionality were developed for the convenient synthesis of 4-aryl-1,2,3,4-tetrahydroisoquinoline framework. Two simple reactions. N-benzylation and addition of arylmagnesium halide on the WA functionality of the former afforded the key intermediate for convenient synthesis of N-phenylsulfonyl protected 4-aryl-1,2,3,4-tetrahydroisoquinoline, through reduction and acid promoted cyclization. With the latter, the addition of arylmagnesium halide on the WA functionality followed by the same protocol afforded the direct synthesis of 4-aryl-1,2,3,4-tetrahydroisoquinolines in good yields. The acid promoted cyclization step enabled concomitant removal of N-Boc protection. (C) 2010 Elsevier Ltd. All rights reserved.