Locating Organocatalysts at Pickering Droplet Interfaces Enables Promotion of Their Catalytic Enantioselectivity

Catalytic reactions at aqueous microdroplet interfaces can be remarkably different from those occurring in bulk water due to the unique interfacial microenvironment that enables possible modification of the transition states. However, current research of microdroplet chemistry is mainly focused on reaction acceleration or future scale-up; the promoted catalytic selectivity, especially stereoselectivity, is still in its infancy. In this work, we present our findings that both the reaction rate and the enantioselectivity of chiral organocatalysts can be drastically promoted by locating them at the water–oil interfaces of Pickering droplets. As impressed by the natural cinchonidine-driven asymmetric Mannich reaction and l-proline-catalyzed Aldol reaction, the Pickering droplet-based interfacial system exhibited 1.94–2.22-fold and 2.37–3.74-fold enhanced catalysis efficiency in comparison to their bulk organic and biphasic counterparts, together with the desired enantioselectivities improved from 26–60 to 94% ee and 64–88 to 99% ee, respectively. Interestingly, the observed activity and chirality enhancement were found to be significantly dependent on droplet size. Insight into the origin of these promoted rates and enantioselectivities at the molecular level was further elucidated by using molecular dynamics simulation and density functional theory calculations. This study highlights a new paradigm of a highly reactive and stereoselective water-medium catalytic system, providing an exemplary pathway to access optically active compounds.