The aldol-crotonic condensation reactions of N-alkyl-and NH-piperidin-4-one derivatives with (hetero)aromatic aldehydes promoted by Lewis acids or bases were examined. This comparative study has revealed three effective catalytic systems based on Lewis acids, i.e., LiClO 4 and MgBr 2 (in the presence of tertiary amine), and BF 3 · Et 2 O, for the synthesis of N-alkyl-substituted 3,5-bis(heteroarylidene)piperidin-4-ones, including those bearing acid-or base-labile groups both in the (hetero)aromatic groups and in the alkyl substituent at the N-atom. The highest reaction rate was observed for LiClO 4 -mediated synthesis. Both MgBr 2 -and LiClO 4 -mediated syntheses were inefficient in the case of NH-piperidin-4-one, while BF 3 · Et 2 O provided the final compounds in high yields. This catalyst is especially advantageous as it allows simultaneous condensation and deprotection in the case of Oprotected piperidin-4-one.