Synthesis of New Tetrazole-Substituted Pyroaminoadipic and Pipecolic Acid Derivatives

Racemic 5‐aryl‐ and 5‐(arylmethyl)tetrazolyl‐substituted pyroaminoadipic and pipecolic acid derivatives were diastereoselectively synthesized from dimethyl meso‐2,5‐dibromoadipate (1) in good yields under mild reaction conditions. The key step of this reaction sequence is the selective N2‐alkylation of 5‐substituted tetrazoles with 1. The reactive 2‐bromo‐5‐tetrazolyladipate derivatives 2a−g were generated and treated with sodium azide, followed by Pd/C‐catalyzed hydrogenation, to provide lactams 4a−g. The chemoselective reduction of the amide carbonyl group of 4a−g with BH3, followed by acid hydrolysis, provided 5‐tetrazolylpipecolic acids in racemic form. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)