Continuous, stable, and safe organometallic reactions in flow at room temperature assisted by deep eutectic solvents

Abstract

This work demonstrates the first continuous, stable, and safe operation of organometallic reactions in flow under ambient conditions with high moisture tolerance and clogging resistance. The addition of deep eutectic solvents (DESs), such as glyceline (choline chloride/glycerol) and reline (choline chloride/urea), overcomes the previous limitations associated with the need for cryogenic conditions (long residence times and high energy requirements) and clogging. The immiscibility of the different solvents leads to a segmented flow where the reactive organic substrates are dispersed in a continuous DES-containing carrier phase. This system provides intimate contact between solvents, favoring the dissolution of lithium species (by-product) into the DES phase, avoiding the clogging under a wide range of conditions. In addition, the microfluidic scale provides excellent heat management (recirculation flow patterns) and a high surface area/volume ratio, enabling safe operation. The benefits of DESs were studied with a selection of two organolithiums and two organomagnesium reagents, and different imine/ketone substrates.