Unlocking geminal fluorohaloalkanes in nucleophilic fluoroalkylation chemistry: generation and trapping of lithiumfluorocarbenoids enabled by flow microreactors
Mauro Spennacchio, Marco Colella, Michael Andresini, Roberta Savina Dibenedetto, Elena Graziano, Andrea Aramini, Leonardo Degennaro, Renzo Luisi
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.