Synthesis of TFA-protected α-Amino Acid Chloride via a Vilsmeier Reagent for Friedel–Crafts Acylation

Abstract

: α-Amino acid chlorides are reactive coupling agents in amide (peptide) formation. The Vilsmeier reagent ((chloromethylene)dimethylammonium chloride) offers a convenient way to prepare α-amino acid chlorides for peptide synthesis. Its use with N-trifluoracetyl (TFA)-protected isoleucine and allo-isoleucine is described. The 1H-NMR of the α-proton signal offers a convenient way to monitor the chirality retention in the acid chloride forming reaction and subsequent Friedel–Crafts acylation of arenes and resulted in α-amino acid aryl-ketone with no loss of chirality.