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

✍ Scribed by Evgeniya Leonova; Mihail Makarov; Zinaida Klemenkova; Irina Odinets

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: German
• Weight: 197 KB
• Volume: 93
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.201000005

✦ Synopsis

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. 19 F-NMR data) already after 4 h. a ) Yield of isolated 3a (the yield according to the 19 F-NMR data is shown in parentheses). b ) The product 3a was isolated as HBF 4 salt. c ) At 808.