Generation of Lithium Ethenolate by Lithiation of Tetrahydrofuran in Flow Mode

The development of a continuous flow process facilitating the lithiation of THF is presented. After in situ fragmentation of the lithiated THF species into ethylene gas and lithium ethenolate, the latter is trapped with TIPSOTf (triisopropylsilyl triflate), providing the corresponding silylenol ether as a versatile building block whose use in various cycloaddition reactions is discussed. Importantly, the initial flow process can be run at elevated temperatures using n-hexyllithium in combination with commercially available flow reactor systems, and the resulting process is stable over several hours. This study thus highlights the potential exploitation of continuous processing for lithiation reactions to optimize the generation of valuable building blocks in a safe and scalable manner.