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-(Pmethoxy)benzyl-N-chloroacetyl-Phe-O'Bu derivative to the corresponding beta-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. (c) 2005 Elsevier Ltd. All rights reserved.