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The Combination of Electrochemistry and Nickel Catalysis: New Bond-Forming Reactions on a Sustainable Platform

Periodic Reporting for period 2 - ElectroNick (The Combination of Electrochemistry and Nickel Catalysis: New Bond-Forming Reactions on a Sustainable Platform)

Reporting period: 2020-05-01 to 2021-04-30

Throughout the design of new molecules for pharmaceutical and agrochemical applications to benefit society, the formation of carbon–carbon bonds represents a key strategy to combine chemical groups together. However, many of these methods use metal atoms, which become waste at the end of the reaction. To overcome this, chemists use catalysts which can produce multiple equivalents of the new carbon–carbon bond for every molecule of metal catalyst, improving the efficiency and sustainability of the reaction. In particular, electrocatalysts have recently become an important tool towards sustainability in organic chemistry reaction design, using a cheap and efficient supply of electricity to drive the reaction and limit waste.

To this end, ElectroNick aims at establishing a suite of new electrocatalytic carbon–carbon bond formation reactions using nickel complexes as efficient catalysts for synthesis. Reactive intermediates can be forged within the reaction mixture, limiting the waste of metals such as zinc and cobalt. Not only will these reactions improve sustainability in organic synthesis, they will provide the possibility of designing the synthesis of new carbon–carbon bonds with high efficiency and selectivity. However, in order to design these new catalytic systems, it is important to build a deep understanding of the multiple steps within each catalytic cycle, and how subtle changes in the metal complex or substrates that form the new carbon–carbon bond affect overall reactivity. ElectroNick has utilized cutting-edge techniques in electroanalysis and ‘big data’ science to understand these intricate effects, and employed the knowledge gained through these processes in developing new reactions for carbon–carbon and carbon–heteroatom bond formation.
ElectroNick commenced with a study into using cobalt electrocatalysts to create cobalt–carbon bonds, which could then transfer the organic group onto a nickel catalyst that would be key to forging novel carbon–carbon bonds. However, when we reduced the Co(II) species, adding an electron from the electrical curcuit to generate a Co(I) intermediate, we found these new Co(I) compounds were very unstable to decomposition, which would not be productive in our desired transformation. To understand this decomposition event, we used advanced electronalytical techniques to study the rate of the reaction. Changing the ligand bound to Co(I), we surveyed how small differences affected this decomposition rate, collecting large data sets to correlate with structural features of the ligand. In doing so, we developed a mechanism for the undesired decomposition pathway, and gained insight in how to avoid it.
With that in hand, we used the same toolkit to understand how the Co(I) would react productively with organic molecules, developing understanding on how, of many possibilities, the Co(I) would add into a carbon–bromine bond (oxidative addition). This strategy of combining electroanalytical techniques with statistical modeling to understand these processes represents a significant advance in building methods to interrogate reactivity, and we have expanded its use to investigating reactivity with alternative substrates and nickel complexes. Finally, the statisical modeling techniques were utilized to understand intricate interactions which drive selectivity in a new palladium catalyzed transformation, forging new carbon–nitrogen and carbon–oxygen bonds towards pharmaceutical targets.

In the outgoing phase of ElectroNick, the project developed new tools combining electroanalytical techniques with statistical modeling to interrogate reaction mechanisms. Our results uncovered how Co(I) complexes add into a carbon–bromine bond through a specific oxidative addition mechanism. In an extension to that study, we have investigated how Co(I) complexes with different ligand scaffolds can change the mechanism of activation of the substrate to alternative processes, including the transfer of an electron into the carbon–bromine bond (concerted dissociative electron transfer). Additionally, we expand our studies beyond the confines of Co(I) complexes to include other transition metals. In doing so, we have formulated a platform to globally understand and predict reactivity between metals and organic molecules that can be used to design new reactions for pharmaceutical and agrochemical synthesis.
With knowledge of how these reactions occur mechanistically, we have sought to develop new carbon–carbon and carbon–heteroatom bond forming reactions using the combination of electrochemistry and nickel catalysis. The ElectroNick project has realized early studies indicating that the functionalization of simple carbon–hydrogen bonds can be achieved by these techniques, and work to expand these principles to transformative new reactions remains ongoing within the research groups.

Altogther, ElectroNick has thus far afforded four open access publications in scientific journals, was presented at two interantional conferences and eight invited seminars, and been disseminated to the wider public through social media, video clips and outreach activities.
ElectroNick is offering a new platform for designing reactivity by combining electroanalytical techniques and statistical modeling to build a thorough understanding of the intricate effects which affect reaction mechanisms. Work in this vein continues to build a global model to comprehend how electrocatalysts interact with organic substrates, facilitating future rational deisgn by the synthetic community. Additionally, ElectroNick has used statisical modeling tools to interrogate new synthetic transformations which combine electrocatalysis and nickel cross-coupling, with possible applications in both pharmaceutical and agrochemical synthesis. The researcher has developed key skills, both scientific/technical (electroanalysis, statistical modeling, organometallic synthesis) and transferable (dissemination, mentorship, outreach), which was integral to developing the researcher into a world-leader in these areas and will be transformative in his future academic career as a PI. Finally, the work conducted throughout ElectroNick has focused on designing new sustainable chemical transformations; this goal of societal sustainability will be the legacy our generation leaves to benefit those of the future.
ElectroNick Results