Development of Dual Cooperative Multi-Urea Catalysts for Henry Reaction

A dual cooperative multi-urea catalyst for Henry reaction was developed in which four urea groups were introduced into a rigid and rotatable framework. The tetraurea catalyst 1 showed higher activity for Henry reaction than its analogues, close-bisurea 2 or distal-bisurea 3 with two urea units, demonstrating additional cooperativity between the two substrate-pinching catalytic sites of tetraurea 1. Addition of the reaction product to the reaction system resulted in a small amount of further activation. This work would provide a basis for new cooperative molecular catalysts, leading to a high degree of regulation based on allosteric cooperativity, e.g. with a distinct ON/OFF threshold for reactivity, or feedback activation by using the product as a reaction template.