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.