Covalent anchorage of a metallic co-factor to a DNA-based architecture is merely the only way to ensure an accurate positioning of a catalytic site within the chiral micro-environment offered by the DNA double helix. Ultimately, it also allows a fine-tuning of the catalytic pocket through simple synthetic modifications of the DNA sequence. Here, we report highly selective copper(II)-catalysed asymmetric Friedel-Crafts conjugate addition/ enantioselective protonation, which is due to a careful positioning of a bipyridine ligand within a DNA framework. Most importantly, this study unveils specific structural features that account for an optimal chirality transfer from the duplex to the Friedel-Crafts adducts.