Enantioselective Synthesis of N-Protected α-Amino Acid Hydrazides

A new, mild general, and efficient synthesis of N-protected a-amino acid hydrazides is described. This two-step preparation uses N-aminophthalimide as protected hydrazine to prepare N-protected alpha-amino acid hydrazide precursors, and subsequent dephthaloylation with an aminomethyl polystyrene resin yields N-protected alpha-amino acid hydrazides. It has the advantages of avoiding the use of the toxic hydrazine reagent and being compatible with the most commonly used N-protecting groups. This strategy is particularly interesting in the case of N-(9-fluorenylmethoxycarbonyl)protected amino acids. Within the limits of chiral HPLC detection, no epimerization is apparent.