Large-Scale Synthesis of Symmetric Tetramine Ligands by Using a Modular Double Reductive Amination Approach

Tetramine ligands play an important role in a broad range of transition metal catalyzed transformations. We here present a flexible and modular approach to this class of ligands using a double reductive amination strategy. Thus, the target molecules were prepared in a highly efficient manner in only three steps, from commercially available starting materials. Excellent overall yields, of up to 96 % were reached. Notably, chiral C₂-symmetric ligands are available using this procedure. All reactions are easily scalable and the tetramine ligands were obtained in excellent purity, while only a single chromatographic purification is required at the end of the three step sequence.