Self-sustaining enantioselective Heck-Matsuda reactions via diazonium salts generated in situ from anilines or nitroarenes in in-tandem or one-pot cascade strategies

Abstract

The research project aims to develop new sequentially enantioselective intermolecular and intramolecular enantioselective Heck arylation reactions of non-activated olefins, with the in-situ generation of arenediazonium salts directly from substituted anilines and/or nitroarenes. The reactions will be carried out in cascade, without isolating the products generated during an in-tandem or "one-pot cascade" process. Starting from the reduction of nitroarenes, the anilines generated in the medium will undergo a diazotization reaction with organic nitrites, producing the respective diazonium salts, which in the presence of olefins will undergo enantioselective Heck-Matsuda reactions promoted by 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, the sequential reactions will involve olefin desymmetrization processes. 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 expected benefits of this project, there are: (i) Formation of diastereo- and enantioenriched building blocks with high added value, whose structures 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 Heck Matsuda's enantioselective cascade reactions, (iii) The study of cascade reactions will bring important contributions not only to the research group but also to the field of organometallic chemistry and catalysis as a whole.The objective is also to test these new organic compounds for their pharmacological potential since this project is associated with the Center for Research, Innovation, and Dissemination (CEPID/CIBFar), Center for Innovation in Biodiversity and Pharmaceuticals (Fapesp 2013/07600-3), coordinated by Prof. Glaucius Oliva, aiming to explore bioactive compounds against diseases such as malaria, cancer, Chagas disease and the discovery of new compounds with antibacterial activity. (AU)