Synthesis of β-Fluoroamines by Lewis Base Catalyzed Hydrofluorination of Aziridines

Abstract

Lewis base catalysis promotes the in situ generation of amine-HF reagents from benzoyl fluoride and a non-nucleophilic alcohol. The hydrofluorination of aziridines to provide β-fluoroamines using this latent HF source is described. This protocol displays a broad scope with respect to aziridine substitution and N-protecting groups. Examples of regio- and diastereoselective ring opening to access medicinally relevant β-fluoroamine building blocks are presented.

A combination of directing groups and chiral anion phase-transfer catalysis for enantioselective fluorination of alkenes

“…Recently reported general methods for the enantioselective synthesis of allylic fluorides include the reaction of allylic chlorides with palladium catalysts (24,25) as well as the fluorination of allylsilanes using cinchona alkaloid catalysis (26,27). Furthermore, we envisioned that, upon removal of the amide directing group, this method would provide access to enantioenriched β-fluoroamines bearing a fluorinated quaternary center, a privileged bioactive motif and longstanding synthetic challenge (28)(29)(30)(31)(32)(33).…”

Achieving regio- and stereo-control in the fluorination of aziridines under acidic conditions

“…Recently, Doyle and co-workers reported opening aziridines with hydrogen fluoride generated in situ from acyl fluoride, but their method only worked with symmetrical cis -2,3-disubsituted aziridines, which also needed expensive hexafluoroisopropanol as reaction medium. 24, 25 …”

A general, enantioselective synthesis of β- and γ-fluoroamines

“…While we and others have made considerable advances in the synthesis of chiral β-fluoroamines, 7–13 the synthesis of γ-congeners still relies on classical DAST approaches which are plagued with rearranged and dehydrated products. 1–6,14 Therefore, new synthetic strategies to access these elusive, chiral γ-fluoroamines were warranted.…”