Towards an approach to small-scale aryllithium flash flow chemistry using low-cost, low volume reactors

Abstract

Two low-cost reactors for aryllithium generation and trapping with an electrophile in flow have been developed for use with small quantities of limiting reagent (600 \(\upmu \)mol) using reductions in flow rates as the approach to miniaturisation. To this end, a number of inexpensive, commercially available mixing elements were characterised via model lithium-halogen exchange reactions to determine their performance at low (< 5 mL min^-1) flow rates. From these studies, a glass chip mixer, and 250 \(\upmu \)m tee-pieces were identified for use at low flow rates and therefore incorporated into the aforementioned reactors. These reactors were demonstrated to be suitable for the successful lithiation and trapping of a selection of ArX substrates. Impact of flow: Organolithium chemistry greatly benefits from translation to flow. Increased heat transfer means that reactions may be run at higher temperatures than in batch, with drastically reduced reaction times. Moreover, the precise control of stoichiometry via flow rates, coupled with the improved mixing in flow leads to improved functional group tolerance and selectivity.