Estudos da viabilidade catalítica de amino compostos, derivados de Laminoácidos e do D-manitol, em reações de adição do tipo Michael, em reações de adição aldólica e em reações do tipo Mannich

Abstract

The synthesis of stereoisomerically enriched compounds is highly important for a diversity of fields, especially for medicinal chemistry. Organocatalysis stands out as one of the most important tools to access asymmetric derivatives, especially when using amino compounds derived from amino acids as catalysts. Among the different transformations for the synthesis of these derivatives, the Michael-type, the aldol addition and Mannich-type reactions can be highlighted. This thesis describes the preparation of four diastereoisomerically pure amino compounds, derived from Lamino acids and D-mannitol, and its potential application as catalysts in organic reactions. The catalytic activity of these four derivatives was evaluated in Michaeltype reactions between chalcones and thiophenol or aniline. All amino catalysts afforded thiol-Michael products in yields ranging from 43-93%; on the other hand, only two amino compounds led to the formation of aza-Michael products, in 14 and 16% yield. For both transformations, all products were obtained as racemates. The use of amino compounds was also studied for the aldol addition reaction between different cyclohexanones and aldehydes. The four catalysts mediated solvent-free diastereo and enantioselective aldol reaction, tolerating the use of sterically bulky aldehydes and substituted cyclohexanones. The best results were obtained for the amino catalyst derived from L-proline, providing the desired adducts in up to 95% yield, with a diastereoisomeric ratio of up to 19.0:1.0 (anti/sin) and an enantiomeric excess of up to 98%. DFT calculations and control experiments were performed aiming a better comprehension of the asymmetric induction process and indicated that various hydrogen bond interactions between the aldehyde and the enamine intermediate are responsible for the chiral induction, and that the trifluoroacetate counteranion is crucial for the attainment of higher stereoselectivities. The amino compound derived from L-proline was also evaluated as a catalyst in Mannich-type reactions between cyclohexanone and different aldehydes and anilines. In all reaction conditions, the product was obtained in good conversions and low disteroisomeric ratios, with the best result found out when using toluene as solvent, in which the product was prepared in 99% conversion and with a diastereoisomeric ratio of 5.6:1.0 (anti/sin). On the other hand, the products were accessed in the form of racemates.