In Situ Generated DBU⋅HF Acts as a Fluorinating Agent in a Hexafluoroisobutylation Tandem Reaction: An Effective Route to 5,5,5,5’,5’,5’‐Hexafluoroleucine

We report the direct incorporation of hexafluoroisobutyl group on a chiral glycine Schiff base complex mediated by 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). The fluoroalkylation involves 2-(bromomethyl)-1,1,1,3,3,3-hexafluoropropane reagent, which generates in situ hexafluoroisobutylene (HFIB), and reacts then with enolate through tandem allylic shift/hydrofluorination process. showed that use neutral organic DBU an original DBU⋅HF salt, preserves fluoride nucleophilicity acts as fluorinating agent. This salt promotes hydrofluorination pentafluorinated alkene overcoming usual β-elimination observed α-CF3-vinyl reagents. With alkali metal bases, contrast, is disfavored intermediate obtained predominantly. study highlights critical role counter ion to preserve its nucleophilicity. protocol amenable multidecagram scale synthesis enantiopure (S)- (R)-5,5,5,5’,5’,5’-hexafluoroleucine their N-Fmoc or N-Boc derivatives good overall yield.