Periodic Reporting for period 2 - ElectroFun (Electrochemical Bond Functionalization)
Berichtszeitraum: 2023-02-01 bis 2024-07-31
The tremendous advances in molecular synthesis over the past decades advanced this discipline to its central position in the natural sciences. Thus, modern organic synthesis stands out as the key enabling technology in applied areas, including drug discovery, crop protection, and material sciences among others. Today, compounds of remarkable structural complexity can be prepared. However, despite enormous progress, established molecular syntheses for molecular assembly continue to be inefficient. For instance, the development of powerful metal-catalyzed transformations, including the Nobel-prize winning palladium-catalyzed cross-couplings, have revolutionized the toolbox of molecular syntheses. While indisputable advances have been realized, these approaches largely fall short in addressing central criteria of sustainability. Thus, resource-economical syntheses should ideally avoid pre-functionalizations, undesired waste generation, harsh reaction conditions, and precious metal catalysts. In this context, direct C–H activation has surfaced as an increasingly viable tool to minimize waste generation, and improve the step- and atom-economy. Oxidative C–H transformations are particularly attractive, because they are operative without any elements of pre-functionalization. However, these oxidative functionalizations feature an additional level of complexity in terms of oxidant economy. Unfortunately, this strategy primarily relies on often toxic chemical oxidants. This directly translates into the generation of stoichiometric amounts of undesired waste, which contradicts the sustainable nature of the approach. The direct use of electric current for organic electrosynthesis sets the stage for exploiting the complete array of available renewable energy resources, including the predominant wind and solar energy. Importantly, in the scenario of electrooxidations protons and electrons serve as the terminal oxidant and generates molecular hydrogen as the sole byproduct through cathodic proton reduction. Hence, electrooxidative C–H activation has been recognized as an environmentally-sound strategy towards an ideal oxidant economy. In addition to molecular syntheses, the synergistic combination of synthetically useful anodic organic oxidations with the hydrogen evolution reaction is highly desirable with regard to a sustainable future hydrogen economy.
During the first phase of the ERC Advanced Grant Electrochemical Bond Activation, we succeeded in the development of sustainable electrochemical direct functionalizations with excellent resource-economy for a sustainable organic synthesis. Specifically, we addressed major challenges in enantioselective metallaelectro-catalysis and made possible enantioselective rhodaelectro-catalyzed spiroannulations (W. Wei, A. Scheremetjew, L. Ackermann, Chem. Sci. 2022, 13, 2783-2788.). We could directly exploit natural sunlight as sustainable power source for atropoenantioselective palladaelectro-catalysis with molecular hydrogen as the only stoichiometric by-product (J. Frey, X. Hou, L. Ackermann, Chem. Sci. 2022, 13, 2729-2734). Furthermore, we harvested machine learning approaches based on transition state knowledge to predict enantioselectivities in pallada-electrocatalyzed C–H activation (L.-C. Xu, J. Frey, X. Hou, S.-Q. Zhang, Y.-Y. Li, J. C. A. Oliveira, S.-W. Li, L. Ackermann, X. Hong, Nature Synthesis 2023, 2, 321–330, see also Z-J. Zhang, S.-W. L, J. C. A. Oliveira, Y. Li, X. Chen, S.-Q. Zhang, L.-C. Xu, T. Rogge, X. Hong, L. Ackermann, Nature Commun. 2023, 14, 3149). Utilizing cost-efficient and less toxic 3d transition metals in contrast to precious 4d and 5d transition metals continues to be challenging. Here, we devised the first cobaltaelectro-catalyzed enantioselective C–H activation (T. von Münchow, S. Dana, Y. Xu, B. Yuan, L. Ackermann, Science 2023, 379, 1036–1042.). Thereby, a variety of complex molecular motifs were accessible with a chiral carbon or phosphorus centers, as well as axially chiral polycyclic compounds. The sole byproduct of the resource-economic transformation is molecular hydrogen. Given the planets limited resources and the damage caused by plastic waste, closing the loop on plastics is of great importance for our society to enable a circular economy. Thus, manganaelectrocatalysis was developed for polymer up-cycling and to enable plastic waste to reenter the carbon cycle (I. Maksso, R. C. Samanta, Y. Zhan, K. Zhang, S. Warratz, L. Ackermann, Chem. Sci. 2023, 14, 8109-8118). Thus far, the potential of merging electrocatalysis and photocatalysis is still largely untapped. Therefore, we developed photoelectrochemical iron-catalyzed direct alkane borylation in a position-selective manner without the need for directing groups (W. Wei, B. Wang, S. L. Homölle, J. Zhu, Y. Li, T. von Münchow, I. Maksso, L. Ackermann, CCS Chem. 2024, doi: 10.31635/ccschem.024.202403894). Importantly, our strategy proved complementary to strategies utilizing precious iridium borylation catalyst.
The program enables the first asymmetric electrocatalysis with earth-abundant transition metals. This approach merges the beneficial features of non-toxic metal catalysts with asymmetric electrooxidation, employing protons and electrons as user-friendly redox agents. Thereby, electrocatalysis with full selectivity control sets the stage for the formation of compounds with axial chirality, stereogenic center or spirocyclic compounds. Also, double enantioinduction will be made viable by asymmetric cobaltaelectrocatalysis. Likewise, the gained mechanistic insights are and will be exploited for efficient polymer functionalizations and degradations of post-consumer polymers for a circular economy. Importantly, electrooxidative polymer functionalizations are not limited to polystyrene. Indeed, even unactivated polyethylene could be functionalized as well. In contrast to the vast majority of electrochemical approaches, we will harness the unique power of combining photochemistry and electrooxidation for the resource-economical molecular assembly line synthesis.