Buildup and Consumption of Species in Emulsion Droplets during Aqueous Suzuki Coupling Correlate with Yield

Abstract

Fluorescence lifetime imaging microscopy (FLIM) provides spatiotemporal resolution of the changing composition of emulsion droplets during aqueous-surfactant Suzuki coupling. In contrast to previous investigations, the present experiments characterize the full course of a catalytic chemical reaction, addressing key questions about reaction species buildup and correlating these microscale behaviors with bench-scale product yields. At low concentrations of (active) catalyst, droplet environments are stable; however, at higher concentrations, emulsion droplet environments change markedly. These changes are consistent with the buildup and consumption of reaction species inside the droplets. A combination of FLIM and bright-field imaging pinpoints limitations in catalyst solubility as controlling rate and degree of buildup of species in droplets. These solubility limitations are also identified as the cause of a reaction induction period and an origin of the rate-and-reproducibility advantage obtained by adding THF cosolvent. The subsequent mechanistic model from these data led to a bench-scale reaction optimization, wherein premixing the catalyst components bypasses the catalyst induction period, resulting in a faster reaction. The understanding generated by FLIM thus provides an early example of how visualizing changes in droplet compositions on the microscale during ongoing aqueous−organic reactions can be leveraged for enhancing efficiencies in bench-scale reactions.