Three-component aminofluorination of alkenes with electronically rich amino sources

Summary

The first intermolecular three-component aminofluorination of alkenes with electronically rich amino sources has been developed via an umpolung strategy. In this reaction, electrophilic N-bromodialkylamines are employed as amine electrophiles, whereas multifunctional AgF serves as both a nucleophilic fluoride source and a reductive catalyst, for the first time, to initiate a single-electron transfer with N-bromodialkylamines. The addition of hexafluoroisopropanol as a cosolvent is crucial to promote protonated alkylaminyl radical formation and maintain the nucleophilicity of fluoride ion. This protocol exhibits excellent functional-group tolerance toward various aryl and unactivated alkenes, furnishing the corresponding β-fluoroamines with high regioselectivity. Mechanistic investigation reveals an aziridinium intermediate via a radical pathway. The synthetic utility of this transformation was demonstrated by the aminofluorination of several bioactive molecules, including an efficient route to a Rizatriptan analog. We anticipate that our finding holds promise for new discoveries in medicinal chemistry and the amination reactions.