C2-Symmetric hemiaminal ethers and diamines: new ligands for copper-catalyzed desymmetrization of meso-1,2-diols and asymmetric Henry reactions

The synthesis of novel, enantiomerically pure C-2-symmetrical hemiaminal ethers and diamines containing piperazine core is presented. The key steps of the synthesis involve the dimerization of an in situ generated a-amino aldehyde into the corresponding cyclic bis-hemiaminal, followed by dehydration in the presence of a base to give a 7-oxa-2,5-diaza-bicyclo[2.2.1]heptane derivative, which can be regarded as a bicyclic bis-hemiaminal inner ether. These compounds represent a new class of molecule, with a structure unambiguously established for the first time. Finally, sodium triacetoxy-borohydride reduction gave the corresponding diamines. Both classes of compounds, new diamines and hemiaminal ethers, were shown to be good ligands for the copper(II)-catalyzed desymmetrization of meso-diols (up to 87% ee) and Henry reactions (up to 84% ee). (C) 2013 Elsevier Ltd. All rights reserved.