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FRINATEK-Fri prosj.st. mat.,naturv.,tek

Revealing the Elusive World of Main-Group Organometallic Chemistry: An Adventure with Computational Chemistry

Alternative title: Til oppdagelsen av den unnvikende verden av hovedgruppe organometallisk kjemi: Et eventyr med beregninger

Awarded: NOK 11.8 mill.

The Grignard reaction, discovered in 1900, is used to form carbon-carbon bonds, a crucial step for the synthesis of a large variety of molecules. However, the original process, based on an organic magnesium chloride derivative, needed to be improved and adapted to the modern criteria for synthetic chemistry: reactions using non-toxic species and mild conditions (no extreme temperature or pressure), and having maximal selectivity (minimal amounts of unwanted products). A new generation of reagents based on non-toxic main group elements such as Li, Mg moved significant steps in that direction. However, because of their everchanging structures in solution, little is known about the way these systems operate. This lack of knowledge hampers further necessary optimization of these important reagents. Recently, by adopting a physically appropriate computational representation of both the solute and solvent, we determined the nature of the solvated Grignard reagent and its reactivity. This winning computational strategy will be used in this project to investigate important variants of this compound and, and their reactions. The global goal is to design more efficient reagents at milder experimental conditions, moving in particular from standard polluting organic solvents to greener setup. We will first explore the structure of pure lithium salts in various solvents. We will then study why the addition of LiCl to magnesium reagents boosts significantly their reactions. Additional two-metal synergies (for example, with Zinc), empirically found but not yet understood, will be also explored. An important goal for the project will be to look at newly-found settings where the Grignard reaction works very well in the presence of green solvents. Finally, the project will move some first steps toward the design of sodium-based reagents, the Shangri-la of organometallic chemistry, for its minimal costs and practically no environmental impact.

We will use computational modelling based on ab initio molecular dynamics to acquire for the first time a rational structure-based control on the molecular features and reactivity patterns of alkali and alkaline-earth organometallic reagents. Main group organometallic compounds are complex chemical systems constituting potent, selective, and group-tolerant variants of the 120-year-old Grignard reagent. They are widely used in academic and industrial laboratories for the synthesis of a broad range of compounds. Despite their prominence, their molecular structures in solution and associated reaction mechanisms are little understood because of their dynamic nature. Recently, we presented a thorough computational investigation of the Grignard reaction (Peltzer et al., J. Am. Chem. Soc. 2020, 142, 2984). By using a physically appropriate representation of the dynamic and thermodynamic properties of both the solutes and solvent, we identified all solvated species and determined their associated reaction patterns. Exploiting this winning computational strategy, in this project we will tackle the ambitious task of characterising at the molecular level the structure and reactivity of important variants of the Grignard reagent. Exploiting the acquired insights, we will design new, more efficient reactive compounds and reaction conditions, moving in particular from standard polluting organic solvents to greener setups. Our study will include the synergistic effect of LiCl on the notorious polar organomagnesium Turbo-Grignard and Turbo-Hauser reagents, and on a Mg/Zn hybrid complex. In parallel, we will investigate the enhanced performance of pure Grignard reagents in a non-miscible mixture of organic and green deep eutectic solvents, and how these conditions can be better exploited by self-assembled surfactants. Finally, by studying the solubility of organosodium species in organic solvents, we will move a crucial step toward the use of an even greener, more abundant metal.

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FRINATEK-Fri prosj.st. mat.,naturv.,tek