Lewis Acids as Mild and Effective Catalysts for the Synthesis of 3,5‐Bis[(hetero)arylidene]piperidin‐4‐ones

The aldol‐crotonic condensation reactions of N ‐alkyl‐ and N H‐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 N H‐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 O ‐protected piperidin‐4‐one.