Regioselective Ring-Opening of Amino Acid-Derived Chiral Aziridines: an Easy Access to cis-2,5-Disubstituted Chiral Piperazines

An efficient four-step synthetic strategy for cis-2,5-disubstituted chiral piperazines derived from amino-acid-based aziridines is described. The key steps in this strategy are the highly regioselective boron trifluoride diethyl etherate (BF3 center dot OEt2)-mediated ring-opening of less-reactive N-Ts chiral aziridines by alpha-amino acid methyl ester hydrochloride followed by Mitsunobu cyclization. This protocol has been used in an attempt to construct the piperazine core framework of natural product (+)-piperazinomycin.