Halofluorination of N-protected α,β-dehydro-α-amino acid esters—A convenient synthesis of α-fluoro-α-amino acid derivatives

• Halofluorination reactions of N-protected α,β-dehydro-α-amino acid esters proceed regioselectively.
• Most of the formed α-fluoro-β-halo-α-amino acid derivatives are stable until their melting point.
• Reduction of the β-halogen substituent is possible.
• Nucleophilic substitution reactions of the β-halogen as well as deprotection reactions failed so far.

N-protected dehydroamino acid methyl esters have been converted to α-fluoro-β-halo amino acid derivatives under halofluorination reaction conditions. The influences of the nitrogen protecting group of the substrates and of the halonium electrophile on the reaction outcome and the stability of the obtained products have been studied. Furthermore, reduction of the halogen substituent (Cl or Br) under radical conditions provided a possibility for follow-up reactions. Nucleophilic substitution reactions, however, failed.

Regioselective halofluorinations of aliphatic and cyclic N-protected α,β-dehydro-α-amino acid esters lead to α-fluoro-α-amino acid derivatives bearing a reactive β-halogen.Figure optionsDownload as PowerPoint slide