Strongly Polarized Carbon: Taming Fundamental Intermediates and Their Applications

Project Information

CC-CHARGED

Grant agreement ID: 101077332

DOI

10.3030/101077332

EC signature date 21 December 2022

Start date 1 April 2023

End date 31 March 2028

Funded under

• European Research Council (ERC)

Total cost

€ 1 499 960,00

EU contribution

€ 1 499 960,00

Coordinated by

TECHNISCHE UNIVERSITAT DORTMUND
Germany

Periodic Reporting for period 1 - CC-CHARGED (Strongly Polarized Carbon: Taming Fundamental Intermediates and Their Applications)

Reporting period: 2023-04-01 to 2025-09-30

Summary of the context and overall objectives of the project

CC-CHARGED is a fundamental project at the interface of organic chemistry and main-group chemistry aimed at generating new compounds and organic reagents with unusual electronic structures based on the central element of organic chemistry, carbon. While most classes of compounds in organic synthesis have been studied for decades, few remain virtually unexplored, only suggested as reactive intermediates. CC-CHARGED aims to tame elusive and reactive intermediates into hitherto unknown classes of room temperature stable compounds. A central motif for achieving stability is predicted to be based on the polarization of the C—C bond, which can lead to either zwitterions (charged +/-) or diradicals. Highly polarized systems are currently little investigated. Strong nucleophiles have applications in several areas of chemistry, such as transition metal, main group, organic synthesis or polymer chemistry. In addition, this fundamental research project aims to develop new reagents for organic synthesis. Based on novel unsaturated diazo compounds, the aim is to introduce CN2 fragments and C-atoms into organic molecules. There is a lack of synthetic reagents and methods to transfer such moieties with high yields and selectivities. New reagents that allow the introduction of single C-atoms are highly sought after and represent a new and more efficient way to assemble complex molecules. In particular, the combination of such reagents in post-functionalisation chemistry allows synthesis shortcuts and contributes to cleaner and more sustainable synthetic processes that could in the long run be implemented in industrial processes, for example for the production of pharmaceuticals.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

To date, we have successfully synthesized a number of highly polarized compounds, including mesoionic pyridine-based olefins and N-heterocyclic olefins based on imidazopyridines. The nucleophilicities of these new classes of compounds have been quantified and their reactivity has been investigated. Mesoionic pyridine-derived olefins can react as 1,3-dipoles, while alkynyl-substituted imidazopyridines undergo cyclization reactions to give novel π-delocalized heterocycles. We have also quantified the nucleophilicities of mesoionic 1,2,3-triazole-derived olefins and used them as polymerization initiators or in main group chemistry for P4 activation. Further applications of such systems are in progress.

Importantly, we have developed new routes to unsaturated diazo compounds using azides or nitrous oxide as diazo transfer reagents. We have shown that the products (diazoalkenes) undergo exchange reactions in which dinitrogen can be exchanged with CO, isocyanides or carbenes.

Two milestones of the ERC project were the synthesis of reagents allowing C(sp2) atom transfer (Ph3PCN2; Science 2024, 385, 305) and C(sp3) atom transfer (Ph2SCN2; Science 2025, 387, 885). A short synthetic route using N2O as the diazo transfer reagent was developed and the electronic structure and reactivity of the reagents were analyzed in detail. These reagents allow new disconnections in organic synthesis (carbonyl to alkynes or 1,3-butatrienes) and allow the creation of 3D structures containing spiropentane fragments including rigid tricyclic cores. The generalization of the fragment transfer concept (C atom or CN2) is part of the ongoing work in the group.

Furthermore, the new diazo compounds provided direct access to novel paramagnetic compounds that could be characterized by EPR and ENDOR spectroscopy at low temperatures. We were able to show that monosubstituted carbon diradicals such as Ph3P→C represent a unique class of compounds that can be considered as an adduct of carbon in its electronic ground state (3P) and a neutral ligand (PPh3). Current work is aimed at increasing the stability and investigating applications of such fundamental compounds in organic synthesis.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

To date, we have established several classes of new highly polarized olefins that represent a fundamental contribution to organic synthesis. Some of the compounds are among the most nucleophilic carbon-based donors described to date. These should be of interest for further applications in organic synthesis, but also for ligand design in main-group or transition metal chemistry. The application of such systems in organocatalysis may also be successful and may attract interest for commercialization.

CC-CHARGED has pioneered C-atom transfer reagents. The reagents developed to introduce C-atoms appear highly attractive for a broad organic market, while the products of 3D carbon atom transfer, tricyclic rigid compounds, appear highly interesting as novel bioisosters in areas related to medical research. We have filed a patent application on the work described in Science 2025, 387, 885 with a perspective to developing commercial solutions. Further research in this area is needed to investigate the stability, scope and scalability of the reagents, paving the way for a rich chemistry of tricyclic molecules including applications in drug design.