Strongly Polarized Carbon: Taming Fundamental Intermediates and Their Applications

Informations projet

CC-CHARGED

N° de convention de subvention: 101077332

DOI

10.3030/101077332

Date de signature de la CE 21 Decembre 2022

Date de début 1 Avril 2023

Date de fin 31 Mars 2028

Financé au titre de

• European Research Council (ERC)

Coût total

€ 1 499 960,00

Contribution de l’UE

€ 1 499 960,00

Coordonné par

TECHNISCHE UNIVERSITAT DORTMUND
Germany

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

Période du rapport: 2023-04-01 au 2025-09-30

Résumé du contexte et des objectifs généraux du projet

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.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

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.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

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.