BifurCAT · Artificial Catalysts for Endergonic Reduction by Electron Bifurcation

Endergonic catalysis converts low-energy substrates into high-energy products. Such reactions are highly desirable in academia and industry as they allow the transformation of abundant starting materials into complex products. However, endergonic reactions are impossible by classical catalysis, since the reverse reaction to the starting materials always dominates. Nature found an amazing way to drive endergonic reduction reactions catalytically by coupling an energetically uphill reduction to a separate, energetically downhill reduction. This strategy is called electron bifurcation and has been discovered with quinone- and flavin-dependent enzymes. No artificial catalysts capable of electron bifurcation have been realised to date. In BifurCAT, I propose the design, realisation, and application of molecular electron bifurcation catalysts. The key to achieving this goal is the precise localisation of two designed, organic redox sites in close proximity. This mimics the enzymatic strategy of splitting two electrons of a medium-potential reductant into a strongly reducing electron at the expense of a second, weakly reducing electron at separate redox sites. Electron bifurcation allows using environmentally benign, abundant, organic reductants such as formic acid or ascorbic acid to drive energetically uphill one-electron reductions at the strongly reducing redox site. Currently, these reactions require super-stoichiometric, rare-earth metal reductants or constant irradiation. I propose to demonstrate the utility of this new approach by applications in reductive incorporation of carbon dioxide into organic substrates and challenging dearomatisation reactions, which both lead to highly sought-after compounds for the preparation of pharmaceuticals, agrochemicals, and precursors to organic materials. BifurCAT has the aim to change our view on energetically “impossible” reactions and to provide a resource- and energy-conserving, alternative strategy inspired by nature.