Visible light driven synthesis of phenanthridin-6(5h)-one derivatives through intramolecular c-h arylation

MICAELA A. CUELLAR; GUILLERMO BRARDA; EVA DANIELA DÍAZ VÁZQUEZ; MICAELA D. HEREDIA; PAULA MARINA UBERMAN; SANDRA E. MARTIN; SILVIA M. BAROLO; MARÍA EUGENIA BUDÉN

Jornada; ACS Summer School on Green Chemistry & Sustainable Energy; 2023

Phenanthridin-6(5H)-ones (1, Figure 1) are core structures found in various natural products and possess pharmacological properties such as antiviral and antifungal activities, among others.1 For example, Oxoassosaine (2, Figure 1) has been reported as an antitumor agent.2These compounds have been extensively studied, and different methods for their synthesis have been reported. Phenanthridinone rings have been successfully synthesized using palladium salts as catalysts, with different ligands and solvents such as DMF at high temperatures.3 Other methodologies for the synthesis of these heterocycles involve intermolecular C-N coupling, employing Cu as a catalyst, air as an oxidant, PPh3 as a ligand, and KOtBu as a base in xylene at 120 ºC.4 Phenanthridinone rings have also been obtained using metal-free methodologies, employing ligands such as vasicine in the presence of KOtBu as a base in sulfolane at 120 °C.5Currently, photocatalyzed reactions have shown to be valuable method for the synthesis of heterocycles and biologically active compounds.6 In 2018, phenanthridinones were successfully synthesized through the intramolecular C-H oxidation of benzamides using Ir[(dCF3ppy)2bpy]PF6 complex as a photocatalyst.7Due to the biological and pharmacological relevance of these nitrogenous heterocycles, the development of new sustainable synthetic methodologies is necessary. In this work, we present a new methodology for the synthesis of phenanthridinones under mild reaction conditions, using less toxic solvents, a metal-free approach, visible light and at room temperature (Eq. 1, Figure 1). The optimal conditions found for this process involve the use of 2-iodophenil-N-methyl amine as precursors, 2 equivalents of KOtBu, DMSO as a solvent, and blue LED (λ=465 nm) at room temperature for 5 hours, achieving a yield of 58%.