A New Synthesis of N-Hydroxyamides Using Trimethylsilyl Protection

Abstract

The concept of transient hydroxylamine oxygen protection for the unambiguous synthesis of N-hydroxyamides has been applied in the amino acid field. First, hydroxylamines 1 were silylated in pyridine with chlorotrimethylsilane; then 2 was immediately N-acylated with mixed anhydride 3 of a protected amino acid or peptide; and finally, the O-trimethylsilyl protection was removed during the isolation procedure giving pure N-hydroxyamides 5.