Autosustenable enantioselective Heck-Matsuda reactions via in situ generated aryldiazonium salts directly from anilines or nitroaryl derivatives in a one-pot strategy.

Abstract

This research project aims to develop new sequential enantioselective Heck arylation reactions of non-activated olefins, with the in situ generation of arenediazonium salts directly from substituted anilines and/or nitrobenzenes. The reactions will be carried out in cascade, without isolating the products generated during a tandem process. Starting from the reduction of substituted nitrobenzenes, the anilines generated in the medium will undergo a diazotization reaction, producing the respective diazonium salts, which in the presence of olefins will undergo enantioselective Heck-Matsuda reactions promoted by the participation of chiral N,N-ligands present in the reaction medium. Sequential reactions will be carried out intermolecularly and intramolecularly, extending the challenge to the synthesis of complex compounds with potential application in the construction of bioactive compounds.Aiming at greater practicality and more informative results on the arylations, the sequential reactions will involve processes of desymmetrization of non-activated olefins, having initially as substrates olefins previously investigated by the research group.The intramolecular version will also involve eliminative and carbonylative Heck arylation reactions, with the expectation of building benzoxacinic and spiro systems, including quaternary centers. Variations both in the aromatic ring and in the olefinic part should provide an expressive number of highly complex products in an enantioselective way.Among the many benefits expected from this new process, there are: (i) Formation of high value-added diastereo- and enantioenriched building blocks whose skeleton can be found in several natural products with biological activity, (ii) Development of practical, sequential methods , effective and self-sustaining that demonstrate the generality and robustness of the tandem enantioselective Heck Matsuda reactions, (iii) The study of the interactions between the substrates generated in cascade, the palladium catalyst, the chiral ligand and the reaction medium during the process involving two or three distinct reactions will bring important contributions not only to the research group but also to the field of organometallic chemistry and catalysis as a whole.An important objective, even if apparently secondary to the proposal, is to test these new organic compounds for their pharmacological potential, since this PD project is linked to the Center for Research, Innovation and Dissemination (CEPID/CIBFar), Center for Innovation in Biodiversity and Drugs (Fapesp 2013/07600-3), coordinated by Prof. Glaucius Oliva, valid until 06/30/2024, which has as one of its objectives to explore bioactive compounds against diseases such as malaria, cancer, Chagas disease and the discovery of new compounds with antibacterial activity.