Visible-Light Radical–Radical Coupling vs. Radical Addition: Disentangling a Mechanistic Knot

• Published in: Catalysts 2021-08, Vol.11 (8), p.922
• Main Authors: Aguilar-Galindo, Fernando, Rodríguez, Ricardo I., Mollari, Leonardo, Alemán, José, Díaz-Tendero, Sergio
• Format: Article
• Language: English
• Subjects: asymmetric synthesis; Catalysts; Chemical reactions; Coupling; density functional theory; Enantiomers; Energy; Hydrogen; Imines; Investigations; Knots; photocatalysis; pyrroline derivative; Quantum chemistry; radical addition; radical–radical coupling; Reduction
• ISSN: 2073-4344; 2073-4344
• DOI: 10.3390/catal11080922

A highly enantioselective protocol has been recently described as allowing the synthesis of five-membered cyclic imines harnessing the selective generation of a β-Csp3-centered radical of acyl heterocyclic derivatives and its subsequent interaction with diverse NH-ketimines. The overall transformation represents a novel cascade process strategy crafted by individual well-known steps; however, the construction of the new C-C bond highlights a crucial knot from a mechanistically perspective. We believe that the full understanding of this enigmatic step may enrich the current literature and expand latent future ideas. Therefore, a detailed mechanistic study of the protocol has been conducted. Here, we provide theoretical insight into the mechanism using quantum chemistry calculations. Two possible pathways have been investigated: (a) imine reduction followed by radical–radical coupling and (b) radical addition followed by product reduction. In addition, investigations to unveil the origin behind the enantioselectivity of the 1-pyrroline derivatives have been conducted as well.