Ortho-Lithiation/functionalization of diaryltetrahydrofurans proceeds well with t-BuLi both in Et₂O and cyclopentyl methyl ether and, remarkably, also in protic eutectic mixtures.

This Frontier highlights and analyses, from the authors’ perspective, some recent selected contributions from the organolithium field with an eye towards new challenging research directions.

o-Tolyl-substituted tetrahydrofurans undergo highly regioselective ring opening with the concomitant formation of new C–C bonds as the result of a lateral lithiation reaction. This reaction provides a new method for the synthesis of functionalised primary alcohols and can be run directly in protic eutectic mixtures as benign reaction media at 0 °C and under air, competitively with protonolysis.

A Pd-catalysed aminocarbonylation of aryl iodides has been first achieved in environmentally responsible and recyclable deep eutectic solvents.

A valuable and direct method to access 2-substituted-2-phenyloxetanes by electrophilic quenching of the corresponding 2-lithiated derivative has, for the first time, been described. 2-Lithiated-2-phenyloxetane was found to be configurationally unstable. Evidence is presented to show that electron-transfer processes are also operative in the coupling reactions with electrophiles.