Elucidating the mechanism of the FeCl₃-Catalyzed quinoline synthesis by A3 multicomponent reaction

Author(s)

Leonarczyk, Ives A. ; Chiavegatti, Attilio ; Pereira, Ariel A. ; Tamega, Giovanna S. ; Tormena, Claudio F. ; Ferreira, Marco A. B.

• Document type: Journal article
• Source: Tetrahedron; v. 150, p. 9-pg., 2023-11-18.

Abstract

Access to the quinoline scaffold through a multicomponent A3 (Aldehyde-Amine-Alkyne) protocol has emerged as a successful synthetic route owing to their experimental simplicity and relevant sustainable potential. Since the original report for A3 synthesis of quinolines based on Cu(I) catalyst, a substantial part of scientific literature has considered propargylamine formation via acetylide metal coupling as the key reaction intermediate for many Lewis acid catalysts, despite the obvious competition with a Povarov-like [4 + 2] cycloaddition mechanism. Considering the positive economic and environmental impacts of using non-precious metal catalysts, and the lack of solid evidence to support the preferential pathway in Fe(III)-catalyzed quinoline synthesis, we employed isotopic labeling and kinetic experiments associated with DFT calculations to support the formal [4 + 2] cycloaddition as the most favorable mechanism in A3-Fe catalyzed MCR protocol under aerobic conditions. (AU)

• FAPESP's process: 20/13563-7 - Prediction and design of catalytic processes using statistical modeling
• Grantee: Attilio Chiavegatti Neto
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 21/12394-0 - Sustainable synthetic methods employing catalysis, benign solvents, safer reagents, and bio-renewable feedstock
• Grantee: Arlene Gonçalves Corrêa
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 21/08132-0 - Ligand parameterization studies aiming to increase the catalytic performance in lignin depolymerization reactions catalyzed by Co(salen) complexes
• Grantee: Ariel de Araújo Pereira
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 22/11314-5 - Data-driven catalyst design: methodological development and mechanistic studies
• Grantee: Marco Antonio Barbosa Ferreira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/10246-0 - Nuclear magnetic resonance spectroscopy: from pulse sequences to structural assignments
• Grantee: Claudio Francisco Tormena
• Support Opportunities: Research Projects - Thematic Grants