Stereoselective synthesis of amino acid-derived β-lactams. Experimental evidence for TADDOL as a memory of chirality enhancer

In model experiments, concerning the modulation of memory of chirality during the intramolecular alkylation of N-(p-methoxy)benzyl-N-chloroacetyl-Phe-OtBu derivative to the corresponding β-lactam, TADDOL was selected from a panel of different phase-transfer catalysts as the best chiral additive (ee up to 82%). We have demonstrated here that the degree and sign of the cyclization selectivity was virtually independent on TADDOL configuration, providing experimental proof that in this reaction this additive works as a memory of chirality enhancer and not as a real catalyst. The effect of TADDOL is strongly dependent on the starting amino acid derivative, the increase of selectivity being only observed for those with aromatic side chains.