Theoretical study of reaction mechanism and solvent effect in the reaction between TMSCH2Li and N-benzoylpyrrolidine ​

Organolithium reagents are compounds that find application in a wide area of organic chemistry. Their importance stems from the polarity of the carbon-lithium bond, which confers strong nucleophilicity and the ability to react with almost all electrophiles. These reagents tend to form aggregates, the size of which depends on the structure of the carbanion, the polarity of the solvent, and the presence of ligands. Lithium typically coordinates four ligands, which can be carbanions and other basic groups such as the solvent, chelating groups, and secondary interactions with organic fragments. The reaction between N-benzoylpyrrolidine and trimethylsilyl methyl lithium leads to the conversion of amides into α,β-unsaturated ketones. The use of two different solvents, in this case, THF and CPME, results in the formation of two different products. The purpose of this study is to clarify the mechanisms that lead to these two different outcomes, using density functional theory (DFT) with the meta-hybrid functional M062X. Subsequently, the energy is refined through single-point calculations using the Def2-TZVP basis set. A preliminary part of the research focused on identifying an appropriate calculation method as DFT calculations suggest the need to explicitly consider the solvent and any aggregate forms to properly model the system. ​ Abstract della tesi in inglese