This project aims at studying the mechanism of the Hock rearrangement, an oxidative cleavage of allylic or benzylic hydroperoxides into carbonyl compounds, and at expending its application scope in organic synthesis thanks to a combination of experimental and theoretical studies. This acid-catalyzed rearrangement indeed produces a reactive oxocarbonium intermediate that could be exploited in numerous tandem synthetic methods involving reactions with various nucleophiles, thus interrupting the classical Hock mechanism. RHOCKI will thus target three objectives: 1. Demonstration of the mechanism of this reaction and determination of key parameters; 2. Design of new reactions based on interrupted Hock processes, as supported by computation; 3. Applications of Hock and interrupted Hock reactions in synthesis of valuable compounds. By revisiting the Hock rearrangement, RHOCKI thus proposes an ambitious and eco-compatible strategy for the development of new reactions.

“Nickelate” project intends to explore the full potential of novel Nickel derived ate-complexes in the field of modern catalysis. The design of these catalysts and the optimization of their abilities in diastereo- and enantioselective transformations are envisioned through various C-H functionalization and addition reactions. Thereby, a convenient in situ formation of the active species, as versatile ion pairs, is proposed from readily available metal and organic entities. A cooperative action mode of the ion-pairing species is envisaged as well as a dual-metal catalysis strategy to expand the scope of these methodological developments. A marked endeavor is proposed to shed light on the nature of the catalytic intermediates thanks to outstanding mass spectrometry technics. Finally, the reaction mechanisms will be tackled based on DFT molecular modelling approaches. In case of success, the “Nickelate” project would overcome methodology limitations that currently hampers the synthesis of complex chiral molecular targets.

The necessity to access chiral molecules by targeting a given enantiomer is of utmost importance. As a result, transition metal catalysis with complexes bearing chiral ligands has become the best ally of synthetic chemists. This ligand-based approach often relies on the use of highly bulky ligands to trigger steric repulsions influencing transition state geometry during a given enantiodetermining step. The alternative Asymmetric Couteranion-Directed Catalysis approach features both steric effects and non-covalent interactions. However, 15 years later, the field did not bloom as much as expected. This probably results from poorly defined and flexible special arrangements of the chiral phosphate-cation pairs. In this context, we established that tethering the chiral anion to the metal center would afford geometrical constraints and molecular organization to the intermediates involved in catalytic processes to generate high enantioselectivities. The TCDCat project intends to develop and establish the Tethered Counterion-Directed Strategy as an unavoidable strategy in enantioselective transition metal catalysis. In this purpose, the project will tackle the synthesis of novel bifunctional complexes of various transition metal and the application of these complexes as chiral catalysts in enantioselective reactions involving remote-to-metal cationic intermediates.

The TC4SC project aims at developing new theoretical tools that can be applied to describe strongly correlated molecular systems. The strongly correlated systems are implied in many important physico-chemical applications (for instance, transition metals ions are implied in catalisys or biological processes) and remain one of the major challenges of theoretical chemistry. The latter has been considerably developed in last decades, especially thanks to the DFT-based approaches. Unfortunately, current DFT approaches are unable to describe the strongly correlated systems. To overpass these limitations, the mathematical framework for describing the strongly correlated systems has naturally become the wave function theory (WFT), which nevertheless has stronger computational scaling. As a consequence, the reduction of the computational cost of WFT thanks to controled approximations has become a very intense field of research. The TC4SC project proposes a new approach to overcome the present bottlenecks of WFT : using the flexibility of the so-called "transcorrelated" WFT approaches. These approaches allow, via an original mathematical framework, to considerably reduce the length of the WFT approaches using a so-called correlation factor. The TC4SC relies on two main axis : 1) adapt the state-of-the-art WFT approaches to the transcorrelated formalism, 2) develop new accurate correlation factors in order to considerably compact the wave function. This project relies on the expertise of Emmanuel Giner in terms of method development in WFT and transcorrelated approaches. The final objective of the TC4SC project is to obtain controled approximations having maoderated computational cost in order to be applicable to realistic strongly correlated systems.

The goal of the project is to describe at the atomic level how chemical reactivity is modified by vibrational strong coupling in microfluidic devices. At this end, we will develop a molecular simulation approach based on system-cavity quantum modeling. Microfluidic experiments will be performed to better decipher the role of different parameters in modifying chemical reactivity. Remarkable new experiments have shown that ground state chemistry can be altered by strong coupling of molecular vibrations with the quantum electromagnetic field of a microfluidic cavity (a Fabry-Perot cavity), a situation denoted vibrational strong (or ultra-strong) coupling (VSC). In particular, rate constants can be modified by this coupling as well as reaction selectivity. First applications were in the field of organic chemistry but VSC has now been demonstrated also on enzymatic reaction. The present project aims at understanding the influence of these hybrid light-matter states on chemical reactions through a joint theoretical and experimental effort. We plan to develop an extension of the Path-Integral approach to include the coupling of molecular vibrations with a resonant cavity mode for an ensemble of molecules coupled by the cavity electro-magnetic field. These simulations will be first tested on model systems and then applied to realistic ones. In parallel, microfluidic experiments with specific easy-to-use design will be performed. Simulations will focus in particular on two aspects which can modify the reaction kinetics (and selectivity): the energy-transfer, or vibrational energy dissipation, and the free energy barrier. For the energy transfer, simulations will allow to identify how the vibrational strong coupling change the molecular dynamics and vibrational energy flow. The impact of the strong coupling on the reaction free energy threshold will be also obtained from simulations. Combining the two aspects, with the help of appropriate kinetic theories (like Kramers or Grote-Hynes) it will be possible to obtain and interpret the global effect of VSC on the reactivity. Experiments will be done to assist simulations in defining the pertinent physical-chemical parameters which can impact the effect of vibrational strong coupling. The microfluidic set-up will also be optimized to provide a simple tool to generalize the use of this approach as catalytic device. In this context, the theoretical development will provide a toolbox to investigate each new reactions. One important outcome, in fact, will be the distribution of a software which may be used to perform atomistic simulations under vibrational strong coupling. This toolbox will be designed as portable software which can be interfaced to established codes able to perform quantum chemistry and molecular dynamics simulations. Overall the project aims at expanding the chemist toolbox to manipulate chemical reactions in a non-invasive approach and without the need for an external energy source.