Catalyst-free Ullmann coupling in aqueous microdroplets.

Jia, Ming-Yang; Zhou, Yue-Wen; Yang, Jun-Lei; Liu, Qinlei; Cai, Zhen-Feng · Nat Commun · 2025

basic_science · Level V

Where this comes from

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/H<sub>2</sub>O 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.