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
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Article de revue
Este ítem está publicado en
European Journal of Organic Chemistry. 2023-03-07, vol. 26, n° 10
Resumen en inglés
We report the direct incorporation of the 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-h ...Leer más >
We report the direct incorporation of the 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 the enolate through a tandem allylic shift/hydrofluorination process. We showed that the use of neutral organic base DBU generates in situ an original DBU⋅HF salt, which preserves the fluoride nucleophilicity and acts as a fluorinating agent. This fluoride salt promotes the hydrofluorination of the pentafluorinated alkene overcoming the usual fluoride β-elimination observed with α-CF3-vinyl reagents. With alkali metal bases, by contrast, the hydrofluorination is disfavored and the pentafluorinated alkene intermediate is obtained predominantly. This study highlights the critical role of the fluoride counter ion to preserve its nucleophilicity. The protocol is amenable to multidecagram scale synthesis of enantiopure (S)- and (R)-5,5,5,5’,5’,5’-hexafluoroleucine and their N-Fmoc or N-Boc derivatives in good overall yield.< Leer menos
Palabras clave en inglés
Fluoroalkylation
Fluorination
Amino acids
Stereoselective synthesis
Synthetic methods
Proyecto ANR
Interactions supramoléculaires sélectives et directionnelles à base de synthons fluorés hautement polaires - ANR-20-CE06-0008
Centros de investigación