Coacervate Droplets Drive Organocatalyzed Aqueous C–C Bond Formation via Interfacial Activation
Kevin Peyraud-Vicré, C Dechamps, Nicolas Martin, Valérie Desvergnes
Abstract
Compartmentalization is central to the regulation of biochemical reactions in living systems, with membraneless organelles formed by liquid-liquid phase separation (LLPS) offering dynamic environments that influence biochemical reactivity. Inspired by this principle, coacervate microdroplets have emerged as promising synthetic analogues for modulating both enzymatic and nonenzymatic reactions in water. Here, we report that coacervates can actively promote aqueous N-heterocyclic carbene (NHC) organocatalysis, enabling base-free carbon-carbon (C-C) bond formation via the Stetter reaction. Using a newly designed amphiphilic thiazolium precatalyst, we show that model polyelectrolyte coacervates not only sequester organic droplets containing the Stetter reactants, creating a unique coacervate/organic droplet interface, but also directly facilitate carbene generation. Remarkably, this activation arises from a strong electrostatic interaction between the thiazolium salt and the polyanion, which spontaneously coacervate together to form catalytically active droplets. These coacervates act as sacrificial reaction compartments, dissolving upon carbene formation while driving C-C bond formation in the absence of added base, highlighting the capacity of coacervates to restructure and respond dynamically during catalysis. Together, our results uncover a previously unrecognized mode of organocatalyst activation within LLPS-based materials, expanding the functional scope of phase-separated systems and suggesting broader potential for leveraging multiphase systems to modulate reactivity through emergent interfacial phenomena in water.