FLOW MICROREATOR TECHONOLOGY AS UNIQUE TOOL FOR THE GENERATION AND USE OF (HIGHLY) REACTIVE ORGANOLITHIUM REAGENTS

The advent of flow chemistry represented a tremendous novelty in the way of thinking and performing transformations in organic synthesis. Flow microreactor technology allowed the refining of various synthetic methodologies offering the possibility to explore transformations impossible to run using batch methods. In this contribution, our recent efforts on the use of flow microreactor technology for the genesis and use of short-lived organometallic intermediates will be described. Specific attention will be attributed to the development of new fluoroalkylation strategies exploiting fluorinated lithium carbenoids. Indeed, we, recently, merged our long-lasting interests in fluorine chemistry and flow microreactor technology reporting an external quenching method based on flow microreactors which allows the generation and use of short-lived fluoro-substituted methyllithium species, such as fluoromethyllithium, fluoroiodomethyllithium, and fluoroiodostannylmethyllithium. In this report, we further demonstrated the potential of flow microreactor technology in fluoroalkylation chemistry by reporting the generation and use of secondary Li/F carbenoids. A detailed study on the stability and reactivity of these unprecedented highly reactive intermediates will be reported. Furthermore, the advantages of flow microreactor technology in taming other lithiated short-lived intermediates will be reported.