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.
Hannachi
Jean-Christophe
JC
Ecole Normale Supérieure de Lyon, Stéréochimie et Interactions Moléculaires, UMR CNRS 5532, 46 Allée d'Italie, F 69364 Lyon Cedex 07, France.
Vidal
Joëlle
J
Mulatier
Jean-Christophe
JC
Collet
André
A
D000586:Amination; D000596:Amino Acids / Q000737:chemistry*; D001224:Aspartic Acid / Q000737:chemistry; D001388:Aziridines / Q000737:chemistry*; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D004563:Electrochemistry / Q000379:methods; D018698:Glutamic Acid / Q000737:chemistry; D006834:Hydrazines / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D015394:Molecular Structure; D011724:Pyridazines / Q000138:chemical synthesis*; D013237:Stereoisomerism
D000596:Amino Acids; D001388:Aziridines; D006834:Hydrazines; D007202:Indicators and Reagents; D011724:Pyridazines; D001224:Aspartic Acid; C014756:piperazic acid; D018698:Glutamic Acid