α-Sulfenilação de Azalactonas: uma investigação teórica do mecanismo via organocatálise enantiosseletiva

Abstract

Currently, computational chemistry has become a valuable ally of synthetic chemists, since it supports the theoretical foundations that facilitate the development of enantioselective organocatalytic protocols. In this context, azalactones stand out, which are versatile heterocycles in stereoselective synthesis, and sulfur-containing compounds, which due to their chemical and structural characteristics have also been explored in the synthesis of biologically functional molecules. This work presents a proposed mechanism for the reaction of α-sulphenylation of azalactone catalyzed by squaramid derived from cinchona alkaloid, which was thoroughly investigated by Density Functional Theory (DFT) calculations. The results indicated that the reaction occur in two stages, it starts with the deprotonation of the α carbon of the azalactone by the catalyst generating an ionic intermediate (azalactone enolate and ammonium salt of the catalyst) which was identified as the limiting step for the formation of the product main. And, in the second step, it proceeds with the formation of the chiral center containing carbon linked to sulfur. For this one, three proposals were investigated that carefully contemplate the different types of interaction between azalactone, sulfur reagent and catalyst, determinant for enantioselectivity. It was possible to exclude enol from azalactone as a key intermediate and point out Münchnone-type activation as the most plausible path associated with secondary hydrogen bonding interactions between the catalyst and sulphenylation reagent, indispensable for the asymmetric induction process