Enantioselective addition of vinylzinc reagents to isoquinoline nitrones and the synthetic approach to D/L-tetrahydroisoquinoline amino acid derivatives

ORGN 115

Sa Wang and Christopher T. Seto. Department of Chemistry, Brown University, 324 Brook St. Box H, Providence, RI 02912
A convenient method to access enantiomerically enriched tetrahydroisoquinoline 1-carboxylic acid (Tiq) derivatives was reported. Highly enantioselective addition of vinylzinc reagents to 3,4-dihydroisoquinoline N-oxide in the presence of N-acylethylenediamine ligands gave the chiral allylic hydroxyamines with up to 95% ee. The enantiomeric excess was further increased by recrystallization in hexanes and the ally adduct thus obtained was transformed to the unnatural Tiq amino acids in a two-step process. These types of isoquinoline structures with a chiral center at their C-1 position have appeared very useful in various biologically active natural alkaloids and as a scaffold in drug discovery.