Unlocking geminal fluorohaloalkanes in nucleophilic fluoroalkylation chemistry: generation and trapping of lithiumfluorocarbenoids enabled by flow microreactors
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Updated: Aug 14, 2025

A Scalable Balz-Schiemann Reaction Protocol in a Continuous Flow Reactor
Published on: February 10, 2023
Mauro Spennacchio1, Marco Colella1, Michael Andresini1
1Flow Chemistry and Microreactor Technology FLAME-Lab, Department of Pharmacy - Drug Sciences, University of Bari "A. Moro", Bari, 70125, Italy. renzo.luisi@uniba.it.
Abstract:
A direct nucleophilic monofluoroalkylation strategy leveraging on lithium fluorocarbenoids has been developed. Flow microreactor technology allows capitalization of the synthetic potential of these scarcely explored short-lived intermediates - namely 1-fluoro-2-phenylethyllithium, 1-fluoro-3-phenylpropyllithium, and 1-fluorononyllithium - generated through lithium/iodine exchange reaction. This robust protocol was employed to prepare new fluorinated products, adopting various classes of electrophiles. The inherent advantages of microreactor technology contribute to rendering this approach a new valuable tool for direct fluoroalkylation chemistry.

