Estudi computacional de la γ-lactonització esteroselectiva d’enllaços C-H catalitzada per complexes de Mn

Abstract

he oxidation of nonactive C-H bonds for their subsequent functionalization has become

a highly interesting process in the field of chemical synthesis due to its potential to enable

the synthesis of compounds that could not be synthesized by other methods or would

require a long and costly process. Last year, the research groups of Miquel Costas and Josep M. Luis published an article studying the oxidation of primary C-H bonds at the gamma position of carboxylic acids to form γ-lactones in a stereoselective manner controlled by the structural properties of a manganese catalyst. Using this article as a basis, a computational study has been conducted to address several open questions, with the aim of formulating a possible hypothesis to answer them. The first step was to identify the most efficient method for performing computational calculations with the structures described in the article. This was accomplished by comparing various calculation methods with varying capabilities. It was concluded that the best method for performing these calculations is the DFT UB3LYP method with a combination of def2svp and 6-31G basis sets, using the first for the most important atoms due to its higher precision and the other for the remaining ones due to its faster Computation. Subsequently, energy scans were performed on the complexes formed by the binding of each enantiomer of the catalyst to different substrates, while rotating a dihedral angle. Initially, the scans were conducted by freezing most of the atoms of the catalyst, reducing the computational cost. However, this strategy was abandoned due to several issues with the optimizations, and therefore, the scans were ultimately performed with all atoms Unrestricted. Based on the results obtained for different substrates, it was determined that γlactonization only occurs when the lowest energy conformation of the reactive complex has a suitable relative orientation of Mn=O to facilitate the oxidation of the C-H bond. Consequently, for the only substrate for which γ-lactonization is not obtained, in its most stable conformation, the C-H bond to be oxidized is in a not accessible position for the metal-oxo oxidizing unit