Periodic Reporting for period 4 - DoReMI (Dominating redox mechanisms in iron-mediated C-C bond formations: reactivity, new paradigms and applications)
Période du rapport: 2025-01-01 au 2025-06-30
In this project, we aim at developing new and efficient methods for promoting the formation of C-C bonds starting from hydrocarbons as starting material, associated with iron-based catalysts. Since iron is a cheap, abundant and non-toxic metal, such a transformation represents a particularly appealing synthetic way in terms of green chemistry.
However, this strategy faces important challenges, such as the understanding of the reactivity of iron catalysts, especially of compounds displaying a carbon-iron bond, which are commonly met as reactive intermediates in catalytic cycles. The C-Fe bond is particularly elusive, highly reactive, and the corresponding intermediates are usually air- and moisture-sensitive. Moreover, they are often paramagnetic, precluding their characterization and monitoring by classic techniques.
The first goal of this project is thus to unveil the main mechanistic parameters governing the reactivity of such compounds (WP1). In a second time, elementary steps for the activation of inert hydrocarbons by tailor-made iron catalysts is optimized (WP2), and catalytic applications for the C-C bond formations are then envisioned (WP3).
Overall, this project will afford new and sustainable C-C bond formations processes with a low energetic footprint, relying on the use of green and eco-friendly iron-based catalysts.
At the end of this project, we have been able to elucidate some of the underlying mechanisms of iron low-valent chemistry that have remained elusive for decades (WP1). Moreover, on the basis of those mechanistic studies, new C-H or E-H activation paths and catalytic applications have been discovered (WP2-3). We were also able to develop new families of highly reactive iron catalysts from the redox-active area, and demonstrated their high reactivity in numerous transformations, either implemented in the starting project (reductive cross-coupling, electron transfer processes), or which have been established by serendipitous findings (cycloadditions). This projects also unveiled unprecedented bimetallic synergies between the on-purpose designed iron catalysts and main-group cations brought by reducing additives. This synergy has been explored in the two last years of the project and enabled to meet some milestones in reductive coupling chemistry.
However, this strategy faces important challenges, such as the understanding of the reactivity of iron catalysts, especially of compounds displaying a carbon-iron bond, which are commonly met as reactive intermediates in catalytic cycles. The C-Fe bond is particularly elusive, highly reactive, and the corresponding intermediates are usually air- and moisture-sensitive. Moreover, they are often paramagnetic, precluding their characterization and monitoring by classic techniques.
The first goal of this project is thus to unveil the main mechanistic parameters governing the reactivity of such compounds (WP1). In a second time, elementary steps for the activation of inert hydrocarbons by tailor-made iron catalysts is optimized (WP2), and catalytic applications for the C-C bond formations are then envisioned (WP3).
Overall, this project will afford new and sustainable C-C bond formations processes with a low energetic footprint, relying on the use of green and eco-friendly iron-based catalysts.
At the end of this project, we have been able to elucidate some of the underlying mechanisms of iron low-valent chemistry that have remained elusive for decades (WP1). Moreover, on the basis of those mechanistic studies, new C-H or E-H activation paths and catalytic applications have been discovered (WP2-3). We were also able to develop new families of highly reactive iron catalysts from the redox-active area, and demonstrated their high reactivity in numerous transformations, either implemented in the starting project (reductive cross-coupling, electron transfer processes), or which have been established by serendipitous findings (cycloadditions). This projects also unveiled unprecedented bimetallic synergies between the on-purpose designed iron catalysts and main-group cations brought by reducing additives. This synergy has been explored in the two last years of the project and enabled to meet some milestones in reductive coupling chemistry.
The success of WP1 has been acknowledged by publication of an unprecedented coupling mechanism mediated by iron catalysts, as we were able to demonstrate that genuine two-electron processes were at play in Kumada-type cross-couplings (Organometallics 2021, 40, 19, 3253-3266, ACS Organic and Inorganic Au 2022, 2, 4, 359-369).
On the basis of mechanistic studies unveiled in WP1, new tailor-made redox-active platforms were synthesized and characterized by multiple spectroscopic methods, and their ligand dynamics subjected to in-depth investigations (ACS Catal. 2023, 13, 4882–4893, J. Organomet. Chem. 2023, 999, 4122796). Their serendipitous high reactivity in cycloaddition systems has also been unveiled and discussed in those references.
In the two last years of the project, a strong bimetallic synergy between iron catalysts treated in reducing media and main-group cations used as additives has also been unveiled, and the key role of this synergy illustrated in C-H / B-H activations (JACS Au 2024, 4, 2, 512-524, Adv. Synth. Cat. 2024, 8, 1782-1787) as well as in E-H bond addition on alkynes (E = Si, Ge; ACS Catal. 2024, 14, 12163-12172). Those references are particularly relevant of WP2-3. In-depth mechanistic studies of this bimetallic synergy along with catalytic applications of redox-active complexes in reductive coupling have also been achieved and reported in 2025 in the frame of WP1-3 (JACS Au 2025, 5, 5, 2135–2147). It is of note that this article features the first example of iron-mediated bisaryl linkage formation in a reductive coupling approach, making it a milestone in the field.
On the basis of mechanistic studies unveiled in WP1, new tailor-made redox-active platforms were synthesized and characterized by multiple spectroscopic methods, and their ligand dynamics subjected to in-depth investigations (ACS Catal. 2023, 13, 4882–4893, J. Organomet. Chem. 2023, 999, 4122796). Their serendipitous high reactivity in cycloaddition systems has also been unveiled and discussed in those references.
In the two last years of the project, a strong bimetallic synergy between iron catalysts treated in reducing media and main-group cations used as additives has also been unveiled, and the key role of this synergy illustrated in C-H / B-H activations (JACS Au 2024, 4, 2, 512-524, Adv. Synth. Cat. 2024, 8, 1782-1787) as well as in E-H bond addition on alkynes (E = Si, Ge; ACS Catal. 2024, 14, 12163-12172). Those references are particularly relevant of WP2-3. In-depth mechanistic studies of this bimetallic synergy along with catalytic applications of redox-active complexes in reductive coupling have also been achieved and reported in 2025 in the frame of WP1-3 (JACS Au 2025, 5, 5, 2135–2147). It is of note that this article features the first example of iron-mediated bisaryl linkage formation in a reductive coupling approach, making it a milestone in the field.
The DoReMI project allowed us to go beyond the state of the art of iron catalysis field from two standpoints.
First, mechanistic studies led to the rationalization of transformations which had been known in literature for several decades but whose mechanism remained obscure. We unveiled unprecedented redox events, such as the 2-electron iron-mediated coupling process that we evidenced experimentally for the first time.
The fine control of iron coordination sphere in tailor-made redox-active scaffolds also gave us the opportunity to develop highly efficient catalysts for cycloaddition reactions, as well as for reductive cross-couplings. For example, we reported the first solely-based iron system enabling the construction of bisaryl linkages using a reductive coupling strategy.
Next, the discovery, in the course of the project, of a two-metal synergy between iron catalysts and main-group cations paved the way to synthetic strategies enabling the generation of highly reactive unsaturated iron catalysts, that we applied to numerous key transformations of organometallic catalysis (cycloadditions, hydroelementations with Si, Ge partners, reductive couplings, ...). This synergy proved to considerably enhance the kinetics of those transformations, and led to new guidelines in terms of Earth-abundant catalyst design.
First, mechanistic studies led to the rationalization of transformations which had been known in literature for several decades but whose mechanism remained obscure. We unveiled unprecedented redox events, such as the 2-electron iron-mediated coupling process that we evidenced experimentally for the first time.
The fine control of iron coordination sphere in tailor-made redox-active scaffolds also gave us the opportunity to develop highly efficient catalysts for cycloaddition reactions, as well as for reductive cross-couplings. For example, we reported the first solely-based iron system enabling the construction of bisaryl linkages using a reductive coupling strategy.
Next, the discovery, in the course of the project, of a two-metal synergy between iron catalysts and main-group cations paved the way to synthetic strategies enabling the generation of highly reactive unsaturated iron catalysts, that we applied to numerous key transformations of organometallic catalysis (cycloadditions, hydroelementations with Si, Ge partners, reductive couplings, ...). This synergy proved to considerably enhance the kinetics of those transformations, and led to new guidelines in terms of Earth-abundant catalyst design.