Síntesis asimétrica organocatalítica de derivados de ciclohexano

Abstract

The development of organic synthesis methodologies that favor the formation of asymmetric products represent a great advantage in the pharmaceutical market, this type of strategies are facilitated by the organocatalisis that is developed with the use of organic molecules of low molecular weight and easy accessibility . The polysubstituted cyclohexanes are widely used nowadays as active principles of anti-influenza drugs such as oseltamivir or as precursors of the spirocycles that present anticancer effect, according to this the development in effective methodologies for the formation of cyclohexanes represents a great importance for the pharmaceutical industry. This work evaluated the reactivity tendency between a series of aliphatic enalts (2-butenal, 2-pentenal, 2-hexenal, 2-heptenal, 2- octenal) and the α-nitro ketones specifically the benzoylnitromethane in the presence of two different catalysts: proline and Jorgensen's catalyst (10% molar relative to benzoylnitromethane) in order to evaluate the effect of these in the reactions for the formation of polysubstituted cyclohexanes after the Michael reaction and the intramolecular aldolic reaction. In general, the reactions were carried out with dichloromethane as solvent, at room temperature, visible light, with a duration of hours under constant agitation. The reactions were followed by thin layer chromatography; the products were separated and purified by column chromatography and taken to proton nuclear magnetic resonance analysis for elucidation. The reactions showed a tendency to form the expected polysubstituted cyclohexane product, hemiacetals and polysubstituted cyclobutanes, and a smaller amount of byproducts was also observed in the reactions where the jorgensen catalyst was used due to the steric hindrance presented by the latter when activating via ion. iminio due to the tendency to form polysubstituted cyclobutanes in the reactions where the 2- entenal and 2-hexenal were involved, the effect of the ultraviolet light was evaluated maintaining the other conditions, in this way an increase in stereoselectivity was shown by this type of cycles. In accordance with the above, the michael-aldol type reaction was characterized between benzoylnitromethane and enals of different carbon chains of radicals between 1 and 4 carbons (2-butenal to 2-octenal), said reaction showed the formation of new C-C bonds, which are of great interest above all for the generation of stereogénicos centers that represent biological importance that can be used for pharmacological purposes.