A platform for automated nanomole-scale reaction screening and micromole-scale synthesis in flow

TLDR

Continuous flow techniques are increasingly used by pharmaceutical chemists to improve reaction screening efficiency. They adapted an HPLC system to rapidly screen solvent, ligand, and base combinations for carbon‑carbon bond formation, injecting catalyst and reactant aliquots into a carrier solvent stream to vary conditions and scale up the optimal protocol. The platform demonstrates that flow apparatuses can accelerate reaction optimization early in drug discovery. Perera et al., Science, this issue p.

Abstract

A reaction screen in flowing solvent Chemists charged with manufacturing pharmaceuticals have recently been exploring the efficiency advantages of continuous flow techniques. Perera et al. now show that a flow apparatus can also accelerate reaction optimization earlier in the drug discovery process. They modified a high-performance liquid chromatography system to screen a wide variety of solvent, ligand, and base combinations to optimize carbon-carbon bond formation. Injecting stock solution aliquots of the catalyst and reactants into a carrier solvent stream let the authors vary the main solvent efficiently and scale up the optimal conditions for product isolation. Science , this issue p. 429