Metilsulfenilação de olefinas eletrofílicas

Abstract

Organosulfur compounds are present in all living organisms, being essential to various biochemical systems, where important primary metabolites, such as lipoic acid and coenzymes A and B, exhibits sulfur in their molecular structures. Methylthiolation is an interesting method to access this class of compounds, since molecules containing -SMe groups with biological activity are highly desired. Traditionally, the most used reagent for this type of reaction is methanethiol, which in addition to being flammable has high toxicity and is difficult to handle. In this work, the methylthiolation methodology previously employed by our research group was revisited due to experimental evidence that the DMSO had a contradictory role compared with the initial mechanistic proposal. Thus, a new scope was developed, using sodium acetate and without the addition of methylthiomethyl ester (MTM), with acyl esters and MBH acetates as substrates. The methylthiolated products were accessed with good group tolerance and moderate to excellent yields, confirming the importance to understand the reaction mechanism. The investigation proceeded through several control experiments, as well as by theoretical calculations employing Density Functional Theory (DFT). The results strongly support that a sulfurane and a sulfonium ylide appear as key intermediates and that a Pummerer type rearrangement is also crucial for the formation of the reagent. Furthermore, the methylthiolation mechanism is likely to proceed through the nucleophilic attack of the reagent, followed by an entropically favoured step involving the acetate attack to the positively charged species, then releasing the product. This work was able to elucidate the participation of the MTM ester in the methylthiolation reaction. The reagent, which can be in situ generated or initially added, presents a viable alternative to the use of methanethiol and contributes to the scientific literature involving the formation of the C-S bond.