Enantioselective Eliminative and Carbonylative Heck Reactions Using In Situ Generated Arenediazonium Salts. New Developments in Tandem Strategies and Synthetic Applications

• Grant number: 25/08477-8
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2025
• End date: October 31, 2028
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Carlos Roque Duarte Correia
• Grantee: Carlos Roque Duarte Correia
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• City of the host institution: Campinas

Abstract

The proposal aims to use palladium-catalyzed Heck reactions by diazonium salts generated in situ through the tandem/domino/cascade or "one-pot" reaction strategy. Intermolecular and intramolecular reactions will be investigated, seeking to expand the relevance and applicability of the catalytic process aiming at synthetic applications with the application of sustainability concepts (greater operational safety involving compounds with higher energy content, fewer synthesis steps, greater operational simplicity, fewer unit operations, easily accessible reagents, increased overall synthetic efficiency). Thus, the proposal goals is to synthesize complex structures from anilines and nitroarenes containing donor, withdrawing and electronically neutral groups in the aromatic ring, evaluate the reaction scope of the eliminative version (inter and intramolecular) of the Heck-Matsuda domino reaction, perform the scope of the carbonylative version in the intramolecular version, using various nucleophiles for the capture of the acyl-palladium intermediate, as well as cross-couplings with boronic acids and other organometallic reagents (stannanes, for example).The project will produce several complex organic compounds, in particular benzofurans, benzoxacins and spiro compounds, all of them with potential as bioactive compounds. The pharmacological activity of these compounds and synthetic intermediates will also be evaluated. The determination of the relative and absolute stereochemistry of the products will be determined by X-ray diffraction and/or Vibrational Circular Dichroism (VCD), a spectroscopic technique that, associated with computational calculations, has been extremely valuable in determining absolute stereochemistry of organic compounds. The technique does not require the use of crystals, nor does it require a high enantiomeric ratio for the determination of the absolute stereochemistry of optically active substances. The reaction mechanisms, as well as the subtleties of these catalytic processes, will also be the subject of evaluation/research. In these aspects, we will have the collaboration of experienced researchers in the area of Medicinal Chemistry and Computational Chemistry with whom the research group has been collaborating for some time. (AU)