Sequential Knoevenagel condensation/cyclization reaction using Meldrum’s acid

Abstract

Sequential Knoevenagel condensation/cyclization using cyclic active methylene compounds such as Meldrum’s acid have been studied. The reaction of 2-(1-phenylvinyl)benzaldehyde and Meldrum’s acid, dimedone, or 1,3-indandione with piperidine/AcOH or L-proline at room temperature for 17–18 h gave cyclized indene derivatives in 63–80% yield. The reaction of 2-(3,5-dimethoxyphenyl)benzaldehyde and Meldrum’s acid at room temperature for 17 h gave a fluorene derivative in 98% yield. Furthermore, the reaction of 2-(3,5-dimethoxybenzyl)benzaldehyde and Meldrum’s acid with piperidine at room temperature for 18 h gave a dihydroanthracene derivative bearing Meldrum’s acid in 83% yield. The reaction of 2-(3,5-dimethoxybenzyl)benzaldehyde and Meldrum’s acid with piperidine at 110 °C for 2 h gave Meldrum’s acid fragmentated dihydroanthracene derivative in 48% yield. The reaction mechanisms of the cyclization steps and Meldrum’s acid fragmentation have been examined by the DFT calculations.