HAT-TRICK · Flow Photoelectrocatalysis via Hydrogen-Atom Transfer: net-oxidative C-H to C-C bond conversion

Flow Photoelectrocatalysis via Hydrogen-Atom Transfer: net-oxidative C-H to C-C bond conversion

Currently, direct functionalization of C-H bonds via photocatalyzed Hydrogen Atom Transfer is mainly limited to redox neutral transformations, where the electrons in the reagents are preserved in the product of interest. The few non-redox neutral approaches reported are oxidative processes that require aggressive oxidants or fragile dual-catalytic systems to remove the extra electrons. HAT-TRICK combines photocatalyzed Hydrogen Atom Transfer (p-HAT), electrochemistry (e-chem) and flow chemistry (flow-chem) to deliver a game-changing and easy-to-use technology to drive these net-oxidative transformations sustainably. On one side, p-HAT will be used as the substrate activation manifold because it consists in the direct activation of a C-H bond in the substrate by the excited state of a photocatalyst to deliver an organoradical to be exploited for synthetic purposes. This methodology shows unrivalled atom-efficiency, step-economy and sustainability and waives chemists from installing activating groups in the molecule. On the other side, e-chem stands as a unique way to remove extra electrons from the reaction mixture, since an anode works as a recyclable, bottomless sink of electrons. This strategy outperforms those based on chemical oxidants as it allows to have absolute control on the applied potential, which is vital in the presence of the fleeting reactive intermediates that will be generated via p-HAT. Finally, flow-chem constitutes a godsend for this project: in a flow electrochemical cell the interelectrode distance can be reduced to micrometers, ensuring that radical intermediates are generated next to the anode to encourage the needed oxidation. On top of that, flow-chem innate modularity enables the possibility of performing tandem reactions. Besides the intrinsic synthetic benefits, the approach proposed herein has important implications for society as it proves that complex organic synthesis can be carried out without environmentally harmful, explosive and flammable chemicals. Instead, photons and electrons will be used to achieve the desired transformation; our Star, the Sun, is an inexhaustible source of photons, while electrons can be easily produced from renewable sources. On top of that, one should not forget that the chemistry carried out during the project will benefit from the flow technology: this technique allows for the smooth scaling of chemical reactions, with the same reactor being used for both discovery and process chemistry. This means that the same reactor can produce a few milligrams of desired product, as well as larger quantities (up to several kilograms of material!). This approach is not only technically superior, but also provides a more sustainable and scalable solution for organic synthesis, benefiting both the scientific community and society at large. In summary, the implications of this approach are significant, as it paves the way for a more sustainable synthesis and demonstrates that complex organic synthesis can be achieved without compromising the environment.

Data: CORDIS, © European Union