The products of the Ugi reaction of various N-tert-but­oxy­carbonyl-protected α-amino acids, aldehydes, amines and tert-butyl isocyanide, after tert-butoxycarbonyl deprotection, undergo efficient microwave-assisted cyclization in acetic acid to give dia­stereomerically pure, racemic piperazine-2,5-diones. The formation of a single diastereomer is rationalized via an enolization equilibration process in acetic acid at high temperature which enriches the product mixture in the more stable diastereomer. The relative ste­reo­chemistry of the products are confirmed by NOESY experiments and are consistent with molecular mechanics calculations.