Environmental-friendly one-pot cascade synthesis of 3-cyanopiperidin-2,6-diones

Abstract

3-Cyanopiperidin-2,6-diones are key intermediates in the synthesis of several drugs and natural products. We developed one-pot synthesis of 3-cyanopiperidin-2,6-diones by Knoevenagel condensation of cyanoacetic acid and aldehydes, followed by addition of cyanoacetic acid, Achmatowicz reaction and decarboxylation. We tested a wide range of aliphatic and aromatic aldehydes. Products were obtained under simple, environmentally friendly conditions and in yields up to 99%. Substrates were stirred in toluene at reflux, and filtered through short pad of silica gel, and the product was purified by recrystallization.