A concise synthesis of piperazine-2-carboxylic acids via β-lactam-derived α-amino acid N-carboxy anhydrides

Abstract

A route to piperazine-fused 3-hydroxy β-lactams was accomplished via [2+2] cycloaddition of alkoxyketenes with imines derived from chiral α-amino aldehydes and chiral β-aminoalcohols. The resulting β-lactams on exposure to 0.55M NaOCl and a catalytic amount of 2,2,6,6-tetramethylpiperidinyl-1-oxyl (TEMPO) afforded α-amino acid N-carboxy anhydrides formally derived from piperazine-2-carboxylic acids.