• DNA-based asymmetric catalysis
• iminium catalysis
• synergistic catalysis
• supramolecular anchoring

DNA-based asymmetric catalysis has emerged as a powerful approach for enantioselective synthesis. DNA-based hybrid catalysts, which are assembled from DNA and a metal complex with a specific ligand through covalent or supramolecular anchoring strategies, have demonstrated high enantioselectivity in multiple C-C bond forming reactions. Up to date, only DNA-based hybrid catalysts functioning as Lewis acid catalysts has been developed. This project elaborates on this approach by introducing iminium ion activation into DNA-based catalysis. This activation mode can be applied in a wide variety of reactions. Therefore, the design of DNA-binding ligands herein proposed includes both a transition metal binding motive and an amine residue, represented in the same structure in order to perform a reaction in close proximity to DNA. Two catalytic sites with two different activation modes (Cu(II) by Lewis acid activation and aniline residues by iminium ion activation), are combined to act synergistically.
The project involves the synthesis of two novel ligands 8 and 9, based on the design of second-generation ligands used in DNA-based asymmetric catalysis. Compound 20, which is ligand 8 with Boc protected amine functionalities, was obtained, but purification remained challenging. Phenanthroline ligand 9 was successfully synthesized in good purity and low synthetic effort. However, the synthesis of its complex 11 was challenging due to solubility issues of ligand 9. Afterwards, a DNA-based synergistic Michael addition reaction was explored using crotonaldehyde 13 (as the Michael acceptor), p-methoxy-substituted 2-acyl imidazole 12 (as the Michael donor) and different catalysts. The DNA-based catalysis using ligand 9 and complex 11 did not show any enantioselectivity in the Michael reaction. However, the inherent properties of the BiPy-based ligand might be more suitable for this application. Overall, this research indicated directions to potentially achieve synergistic DNA-based catalysis.