Piperidinium borate catalyzed Knoevenagel condensation of carbonyl compounds with active methylenes

A piperidinium borate, an organic conjugate base as a catalyst under mild conditions, effectively pro-motes Knoevenagel condensation between aromatic, heterocyclic, a, b unsaturated aldehydes and alipha-tic, cyclic ketones with active methylenes. Piperidinium borate can be easily prepared from widely available boric acid and piperidine. The present method showed the advantages of mild reaction condi-tions, wide and easy availability of starting materials, and higher product yields. In addition, all the prod-ucts were separated simply by filtering and washing with water. The intermediate of AMG 837, a new GPR40 agonist, was synthesized using the similar reaction conditions used in this protocol. Furthermore, the recyclability and reusability of the catalyst are also excellent.& COPY; 2023 Elsevier Ltd. All rights reserved.

Automated summary

A piperidinium borate, an organic conjugate base, is found to be an effective catalyst for promoting Knoevenagel condensation between aromatic, heterocyclic, a, b unsaturated aldehydes and aliphatic, cyclic ketones with active methylenes under mild conditions. The catalyst can be easily prepared from boric acid and piperidine. The method offers advantages of mild reaction conditions, wide availability of starting materials, higher product yields, and simple separation of products by filtering and washing with water. It has been successfully used for the synthesis of AMG 837, a new GPR40 agonist intermediate, with excellent catalyst recyclability and reusability.