Uma abordagem organocatalítica para a vaulfenilação de olefinas

Abstract

The Sulfa-Michael addition consists of a sulfur nucleophile addition to an activated multiple bond by an electron withdrawing group, leading to the formation of the C-S bond. Several catalytic approaches have been developed using thiols as nucleophiles. Specifically, in the case of methylsulphenylation, methanethiol or its sodium salt would be the most appropriate nucleophiles for this reaction. Alternatively, hydrogen sulfide may be used followed by methylation in the presence of a base. Although well established, these reagents are expensive, difficult to handle, and exhibit high toxicity and low boiling point. Several papers in the literature point out the utility of Dimethyl sulfoxide (DMSO) as a promising methylsulphenylation reagent because it is a commercially available, easy to handle and significantly cheaper than other sulfur-based reagents. However, there are no reports of its application to sulfa-Michael reactions. In this work, three new methylsulphenylation methodologies using α,β-conjugated systems and saturated carbon, DMSO as the source of sulfur are presented. The first methodology was developed during trichloromethylation attempts of dibenzylidene acetones (DBA's). By analysis of NMR spectrum, high-resolution mass spectrometry (HRMS) and control experiments, it was found that the product formed was methylsulfenylated derivative. In order to investigate the scope of this reaction, substrates such as different types of chalcones, DBA's, MBH adduct derivatives were employed in the presence of the salt of trichloroacetate (KTCA salt), camphorsulfonic acid (CSA) as organocatalyst, acetic acid at 100 °C and DMSO as solvent and methylsulphenylation reagent, under microwave irradiation. In an attempt to elucidate the mechanism, experimental studies and theoretical calculations using the DFT method were performed. Through these results it was possible to propose a mechanism that passes for a deoxygenation of DMSO and formation of the sulfonium ion, key species in this work. This ion was intercepted when the acetic acid was replaced by a fatty acid which led to the formation of the MTM ester. The second methylsulphenylation methodology consists of a reaction employing chalcones, MTM ester, ACS, sodium acetate, acetic acid at 100 °C and DMSO. The MTM ester is necessary, but its role is not well understood. The third methodology is simpler and involves derivatives of MBH adducts. In this reaction only acetic acid, sodium acetate and DMSO are required. All methodologies are original, efficient and lead to the formation of sulfenylated products in moderate to high yields.