Silver(I)-promoted asymmetric halomethoxylation of chiral α,β-unsaturated carboxylic acid derivatives: enantioselective synthesis of N-protected syn-β-methoxy-α-amino acids

Asymmetric halomethoxylation of chiral α,β-unsaturated carboxylic acid derivatives was performed with halogens (Br₂/I₂) promoted by silver(I) salts with high regio- and anti-selectivity and moderate to good diastereoselectivity. Reagent controlled diastereoselectivity was observed for N-cinnamoyl-2-oxazolidinone substrates especially for cinnamoyl and electron-deficient cinnamoyl substrates, when Ag₂O was used as a promoter instead of AgNO₃. Enoyl substrates containing Oppolzer’s sultam chiral auxiliary are independent of the counter ion of the Ag(I) salt. This method was applied to a short synthesis of both enantiomers of N-protected syn-β-methoxyphenylalanine, and N- and O-protected syn-β-methoxytyrosine, unusual amino acid components of biologically active cyclic peptide and depsipeptide antibiotics.