INNOVATIVE STRATEGIES IN ORGANIC SYNTHESIS: DEVELOPMENT OF ECO-FRIENDLY PROTOCOLS FOR CONSTRUCTING COMPLEX MOLECULES VIA C–H ACTIVATION

Abstract

Background: Development of sustainable C–H activation protocols has dramatically remodeled contemporary organic synthesis by offering strategies toward construction of complex molecules in terms of both atom and step economy. Conventional routes for synthesis are typically based on a pre-functionalized substrate, leading to large waste generation and harsh reaction conditions. C–H activation is a direct and atom-economical approach to functionalization of C–H bonds under green chemistry guidelines and enhances synthetic efficiency in general. Aim: The goals of the present research effort were to discover new and sustainable methods to build complex molecular architectures by utilizing C–H activation, with transition-metal catalysis, photo-redox catalysis, and electrochemical solutions serving as platforms to achieve these goals. Method: The optimization of the reaction conditions for different substrates such as arenes, heterocycles and alkanes was part of the investigation procedures. Metalic catalysts including Pd(OAc)₂, Co(OAc)₂, Ni(acac)₂ and visible-light photocatalysts, such as Mes-Acr-Me⁺ and Ru(bpy)₃Cl₂ were used. Moreover, the graphite–Pt couple was employed in electrochemical cells to achieve the oxidative C–H/N–H coupling reactions under mild condition. Green chemistry measures were also measured—atom economy, E-factor, and process mass intensity. Results: Notably, high efficiencies were observed in all systems, with biaryl coupling as high as 92%, photo-redox thiolation 85% and electrochemical indole formation over 79%. Both the electrochemical and the photo-redox methods presented better values of atom efficiency (up to 95%) and low environmental impact, demonstrating their usefulness as green synthetic protocols. Conclusion: This work delivers environmentally benign, scalable and mild C–H activation protocols as part of the wider effort for sustainable molecule construction in organic chemistry. It is anticipated that these methods should find wide applications in pharmaceuticals, materials, and agrochemical synthesis.