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Catalyst-free Ullmann coupling in aqueous microdroplets

Ming-Yang Jia, Yue Zhou, Jun-Lei Yang, Qinlei Liu, Zhen‐Feng Cai

2025Nature Communications9 citationsDOIOpen Access PDF

Abstract

Ullmann-type coupling reactions are one of the most important transformations in organic synthesis. Achieving catalyst-free Ullmann couplings under mild conditions is crucial to extending the scope of traditional carbon-carbon and carbon-heteroatom couplings. Herein, we show that Ullmann couplings can be effectively achieved at room temperature without the need for metal catalysts in MeOH/H2O microdroplets. Mechanistic investigations reveal that the Ullmann reaction in microdroplets is driven by •OH radicals and involves a single-electron transfer pathway via nitrogen-centered radicals. This work not only provides fundamental insights into the •OH radical-mediated coupling reactions in microdroplets but also offers a new strategy for catalyst-free Ullmann couplings. Achieving catalyst-free Ullmann couplings under mild conditions is crucial to extending the scope of traditional carbon-carbon and carbon-heteroatom couplings. Here, the authors show that Ullmann couplings can be effectively achieved at room temperature without the need for metal catalysts in MeOH/H2O microdroplets.

Topics & Concepts

Aqueous solutionCoupling (piping)CatalysisChemical physicsChemistryMaterials scienceNanotechnologyChemical engineeringPhysical chemistryOrganic chemistryComposite materialEngineeringInnovative Microfluidic and Catalytic Techniques InnovationMicrofluidic and Capillary Electrophoresis ApplicationsPorphyrin and Phthalocyanine Chemistry