During the synthesis of the new antimalarial drug candidate NITD609, a high degree of diastereoselectivity was observed in the Pictet-Spengler reaction. By isolating both the <strong>4<em>E</em></strong> and <strong>4<em>Z</em></strong> imine intermediates, a systematic mechanistic study of the reaction under both kinetic and thermodynamic conditions was conducted. This study provides insight into the source of the diastereoselectivity for this important class of compounds.