Generation and cyclization of nitrilium ions from amides and synthesis of chiral amines

Abstract

Part I. Cationic cyclization reactions of unsaturated amides were studied. Several different unsaturated amides were prepared and their ability to undergo cyclization in refluxing PPSE was examined. A successful cyclization afforded 5-membered nitrogen heterocycle (pyrroline derivatives). The best results were obtained with unsubstituted amides. The conditions are compatible with esters, halides, and ethers. The cyclization reactions failed when electron withdrawing groups were placed on the $\alpha$-carbon of the amides. Enantiomerically enriched indolizidine ring systems were prepared by asymmetric reduction of pyrroline esters, obtained from cyclizations of amide esters.Part II. trans-1,3-Dibenzyl isoindoline, an amine bearing a C\sb2 axis of symmetry, was prepared using a chiral auxiliary. Use of chiral auxiliaries in asymmetric synthesis of acyclic amines was investigated