Synthesis of new triazole substituted pyroaminoadipic and pipecolic acid derivatives

Racemic 5-(4,5-substituted-1H-1,2,3-triazol-1yl)-pyroaminoadipic and pipecolic acid derivatives were synthesized from meso dimethyl-α,α′-dibromoadipate 1 in good yields using mild reaction conditions. The key step of this reaction sequence was the 1,3-dipolar cycloaddition of an acetylenic compound on α-azido-α′-bromoadipate 2. A reactive α-(substituted-1H-1,2,3-triazol-1-yl)-α′- bromoadipate derivative 3a–d was generated and reacted with sodium azide followed by Pd/C-catalyzed hydrogenation to provide lactams 5a–d. The chemoselective reduction of the amide carbonyl group of 5a–d with BH3 followed by acid hydrolysis provided 5-(4,5-substituted-1H-1,2,3-triazol-1-yl) pipecolic acids in racemic form.