Convenient preparation of diastereomerically pure, diversely substituted pi- perazine-2,5-diones from N-protected -amino acids

Products of the Ugi reaction involving N-Boc--amino acids and t-BuNC, after deprotection, undergo efficient micro- wave-assisted cyclization in acetic acid to give, unexpectedly, diastereomerically pure, racemic piperazine-2,5-dione. The for- mation of a single diastereomer has been rationalized by enoliza- tion equilibrium in acetic acid at high temperatures that enriches the products mixture in only one, more stable diastereomer. The relative stereochemistry of the latter was confirmed by NOESY experiments and is consistent with Molecular Mechanics calcula- tions.