Synthesis of N,N-bis[2-(2-pyridyl)ethyl]amino steroids and related compounds intended as chiral ligands for copper ions

Compounds with the N,N-bis2-(2-pyridyl)ethyl]amino structure (RPY2) are useful tridentate ligands for copper(I) ions, which can bind and activate oxygen from the atmosphere. For diastereoselective and enantioselective oxidation reactions, hitherto unknown chiral ligands possessing tripodal structures have been synthesized starting from homochiral steroids. The double Michael addition of primary steroidal amines and aminoalcohols to 2-vinyl pyridine was not very succesful. However, homochiral bidentate ligands with N-2-(2-pyridyl)ethyl]amino steroid structure could be obtained by this procedure in most cases. New routes (acylation of the bidentate ligands with 2-pyridylacetic acid followed by BH₃·THF reduction, or reductive amination of steroidal ketones, acylation and borane reduction) to the desired tridentate RPY2, also at sterically hindered positions, are described. In the last reaction sequence, ‘mixed’ tridentate ligands can also be obtained. Copper complexation and oxygen activation with these ligands are briefly discussed.