A new synthesis of amino acid-based enantiomerically pure substituted 2,3,4,4a,5,6-hexahydro-1H-pyrazino[1,2-a]quinoxalines

Abstract

A new series of enantiomerically pure 2,3,4,4a,5,6-hexahydro-1H-pyrazino[1,2-a]quinoxalines were synthesized for the first time in twelve steps from 1-fluoro-2-nitrobenzene and S-amino acids with 13–20% overall yields. First use of intramolecular Mitsunobu cyclization for 1,2,3,4-tetrahydroquinoxalines followed by PPh₃/I₂/imidazole mediated 6-exo-tet cyclization were the key steps.