Electrophilic amination of amino acids with N-Boc-oxaziridines: efficient preparation of N-orthogonally diprotected hydrazino acids and piperazic acid derivatives.

A general two-step preparation of enantiopure N(alpha),N(beta)-orthogonally diprotected alpha-hydrazino acids 1 is developed on a multigram scale. The key reaction is the efficient electrophilic amination of N-benzyl amino acids 6 with N-Boc-oxaziridine 7 and accommodates various functional groups encountered in side chains of amino acids. The cyclic 2,3,4,5-tetrahydro-3-pyridazine carboxylic acid (piperazic acid) derivatives 2 and 3 or the cyclic 3,4-dihydro-3-pyrazolecarboxylate 4 are conveniently prepared from glutamic acid or aspartic acid via orthogonally diprotected alpha-hydrazino acids 1m and 1n.