Ferraz, RicardoGomes, José R. B.Oliveira, Eliandre deMoreira, RuiGomes, Paula2021-10-202021-10-202007-05-03Ferraz, R., Gomes, J. R. B., de Oliveira, E., Moreira, R., & Gomes, P. (2007). Unanticipated Stereoselectivity in the Reaction of Primaquine α-Aminoamides with Substituted Benzaldehydes:  A Computational and Experimental Study. The Journal of Organic Chemistry, 72(11), 4189-4197. https://doi.org/10.1021/jo0703202http://hdl.handle.net/10400.22/18746Imidazolidin-4-ones are commonly employed as skeletal modifications in bioactive oligopeptides, either as proline surrogates or for protection of the N-terminal amino acid against aminopeptidase- and endopeptidase-catalyzed hydrolysis. Imidazolidin-4-one synthesis usually involves the reaction of an α-aminoamide moiety with a ketone or an aldehyde to yield an imine, followed by intramolecular cyclization. We have unexpectedly found that imidazolidin-4-one formation is stereoselective when benzaldehydes containing o-carboxyl or o-methoxycarbonyl substituents are reacted with α-aminoamide derivatives of the antimalarial drug primaquine. A systematic computational and experimental study on the stereoselectivity of imidazolidin-4-one formation from primaquine α-aminoamides and various substituted benzaldehydes has been carried out, and they have allowed us to conclude that intramolecular hydrogen-bonds involving the CO oxygen of the o-substituent play a crucial role.engImidazolidin-4-onesN-terminal aminoacidα-aminoamide moietyjournal article10.1021/jo07032021520-6904