Synthesis of (±)‐<i>trans</i>‐2,5‐Dialkylpyrrolidines from the <i>Lukes‐Šorm</i> Dilactam: Efficient Preparation of (±)‐<i>trans</i>‐2‐Butyl‐5‐heptylpyrrolidine and Analogs Present in Ant Venoms

Abstract

Abstract A 7‐step synthesis of (±)‐ trans ‐2‐butyl‐5‐heptylpyrrolidine ( 14 ) from the Lukes‐Šorm dilactam 1 was accomplished in 6% overall yield without counting for a reconversion of cis ‐isomer 13 into trans ‐isomer 14 which was also accomplished. Reduction of pyrroline 12 , the precursor of 14 , with NaBH 4 afforded a 1:1 mixture of cis ‐isomer 13 and trans ‐isomer 14 separated by chromatography. Reductive N ‐methylation of 14 afforded the N ‐methyl analog 15 , another ant alkaloid. The synthetic route to 14 was extended to a similar synthesis of analogs 23 – 25 and is representative for the synthesis of trans ‐2,5‐diakyl‐substituted pyrrolidines. Results on the screening of a few compounds for the effect on vascular permeability are reported.