SupraPhoCat · Supramolecular photocatalytic late-stage C-H functionalization

Supramolecular photocatalytic late-stage C-H functionalization

Organic synthesis is still one of the main limiting factors in drug-discovery projects in spite of all the astonishing breakthroughs that have been achieved in the last decades. Both academia and industry keep looking for new reactions and synthetic strategies to speed up the generation of compounds libraries. Traditionally, the generation of these libraries requires tedious synthetic routes to introduce modifications into the lead compound, thus the implementation of new methodologies to modify drugs in a selective way in the late stages of their synthesis is highly attractive. LSF of C-H bonds in drugs has recently emerged as a new strategy for the fast generation of drug derivatives and quick diversification of biologically relevant molecules, without the need to start the synthesis de novo every time a derivative needs to be synthesized. In order to get selectivity, most of the C-H activation protocols described in literature require the covalently introduction of a directing group in the substrate (“directed” C-H bond functionalization), which then needs to be removed. From a synthetic point of view, it is much more attractive to place the directing group in the catalyst rather than the substrate to avoid its introduction and subsequent removal. Nature already uses this approach in enzymes by burying the catalytic center in a binding pocket where the substrate must fit in. Alternatively, it is possible to target specific C-H bonds using molecular recognition, however the examples are much scarcer. Recently, Hydrogen Atom Transfer (HAT) reactions have emerged as a new strategy to tackle selective C-H bond activation in combination with photoredox catalysis. In SupraPhoCat , several supramolecular receptors will be provided with catalytic activity and combined with photoredox catalysis to achieve unprecedent asymmetric C-H funtionalization reactions with exquisite selectivity. This ambitious project will establish new methodologies for C-H Late-Stage Functionalization of drugs, which is a key point towards the development of libraries of compounds according to EU green chemistry insights. This Fellowship proposes supramolecular receptors with Hydrogen Atom Transfer (HAT) activity which will be combined with photoredox catalysis to achieve unprecedent asymmetric C-H functionalization in molecules, merging photoredox catalysis, supramolecular chemistry, and C-H bond activation reactions. The Marie Sklodowska Curie action merges the expertise of the host group (Prof. Luca Dell’Amico from University of Padova) in photoredox catalysis with the expertise of the fellow on supramolecular chemistry, molecular recognition and organocatalysis. This process will rely on a photochemical Hydrogen Atom Transfer reaction controlled by a supramolecular receptor which governs the process. The objectives of this proposal include to design and synthesize supramolecular receptors with HAT groups and the selective C-H abstraction in a model substrate. Moreover, asymmetric version of these processes will be evaluated.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз