Synthesis of novel tridentate N,O,S and N,N,O ligands of the tripod type in racemic and enantiomerically pure form

Article abstract of DOI:10.1002/cber.19961290113

A series of seven chiral, tripoda: N,O,S and N,N,O ligands were prepared in which N stands for a secondary amine or imidazole donor, O for a phenol, arid S for a thioether or thiol metal-binding group. Key steps are (1) the construction of ortfzo-hydroxyacetophenones bearing the phenolic binding group and either a thioether, a protected thiol or an imidazole substituent in the a-position, and (2) subsequent reductive animation with a primary amine. The modular synthesis allows a rapid construction of a variety of structurally related ligands. In three cases, the enantiomers of the racemic products could be separated after condensation with (R)-glyceraldehyde acetonide as chiral auxiliary. The relative configurations of the cyclic N,O- and N,N-acetals thus obtained were established by NOE spectroscopy. X-ray structural analysis of two crystalline N,O- and N.N-acetals allowed the assignment of absolute configurations. Hydrolysis of the diastereomencally pure acetals afforded the enantiomerically pure ligands in high yield. By comparison of their CD spectra, absolute configuration could also be assigned to the third pair of enantiomerically pure ligands.