Straightforward synthesis of fluorinated amino acids by Michael addition of ethyl bromodifluoroacetate to α,β-unsaturated α-amino acid derivatives

Abstract

Copper-mediated Michael addition of ethyl bromodifluoroacetate to N-protected α,β-unsaturated α-amino acid esters was applied for straightforward synthesis of γ,γ-difluorinated analogues of glutamic acid (compound 1) and glutamine (compound 10). Moreover, a proline-based, sterically constrained analog of γ,γ-difluoroglutamic acid (compound 24) was prepared.