Frontispiece: Flow Technology for the Genesis and Use of (Highly) Reactive Organometallic Reagents

Abstract

In the field of organic synthesis, the advent of flow chemistry and flow microreactor technology represented a tremendous novelty in the way of thinking and performing chemical reactions. Just as the classical flask and glass connectors, are still in use, after centuries, in our synthetic laboratories; flow devices will need to conquer the bench of modern laboratories. For more information, see the Concept article by R. Luisi, A. Nagaki and M. Colella on page 19 ff.

Flow detoxification of a sulfur mustard simulant with organometallic compounds enabled by an optimization algorithm

“…19 Following the pioneer work of Yoshida, [20][21][22][23][24] highly reactive organometallic species (mostly organolithium compounds [25][26][27][28][29][30] and then Grignard reagents [31][32][33] ) were shown to be easily controlled in flow microreactors. [34][35][36] In addition, the fine control brought by miniaturised flow reactors on various parameters (reaction time, temperature) and the spatial resolution of the reaction allowed to obtain the high selectivities required for the effective detoxification of chemical warfare agents. [37][38][39][40][41] Herein, we now report that the yperite simulant CEES can be efficiently detoxified with organometallic reagents (PhMgBr, PhLi) in a flow system with significant acceleration over usual batch conditions (Fig.…”

Organomagnesium Based Flash Chemistry: Continuous Flow Generation and Utilization of Halomethylmagnesium Intermediates

“…The use of continuous flow reactors has introduced robust scale-up strategies for these reactions, facilitating the use of noncryogenic conditions and thus application on industrial scale. 9 Using micromixers, even highly unstable intermediates can be generated and utilized within milliseconds for organic reactions, enabling transformations that are not possible in batch. 10 The term “flash chemistry” was coined by Jun-ichi Yoshida to describe this type of ultrafast reactions.…”

“…The high reactivity of Grignard and especially organolithium reagents frequently requires low temperatures (e.g., −78 °C) to achieve satisfactory selectivities. ,,, Slow addition of the reagent to the reaction is typically required, hampering the scalability of the chemical process. The use of continuous flow reactors has introduced robust scale-up strategies for these reactions, facilitating the use of noncryogenic conditions and thus application on industrial scale . Using micromixers, even highly unstable intermediates can be generated and utilized within milliseconds for organic reactions, enabling transformations that are not possible in batch .…”