Selective host amplification from a dynamic combinatorial library of oligoimines for the syntheses of different optically active polyazamacrocycles

Two different macrocyclic hosts are amplified and expressed by metal guests from the same dynamic combinatorial library (DCL) of oligoimines. We studied the thermodynamic template effect and the structure of the final compounds by a combination of ESI-MS, UV and NMR spectroscopy, and Xray crystallography techniques. The use of Ba-II or Cd-II metal salts allows the selective synthesis of dimeric [2+2] or trimeric [3+3] cyclic structures, respectively. We observed a cooperative molding effect for the Cd ion-templated process. A study of the DCL behavior in situ demonstrated a second level of molecular diversity, based on the imine/alpha-methoxy-amine equilibrium. This process is probably promoted by metal ion coordination and shows an interesting diastereoselectivity in the formation of the new chiral centers. Semiempirical (PM3) theoretical calculations also support these experimental observations. Reduction of the imine bonds allows the selective preparation and isolation of each macrocyclic polyamine on a synthetic scale and in a one-pot procedure. (C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.