Contra-Thermodynamic Chain-Walking Isomerization: A Sustainable Tool for Selective Molecular Editing in Green Chemistry.

Contra-thermodynamic chain-walking isomerization has emerged as a powerful strategy in green chemistry for the selective transformation of alkenes and functionalized hydrocarbons under relatively mild (typically below 100°C) conditions. Unlike conventional thermodynamically driven isomerizations that favor the most stable olefin products, contra-thermodynamic processes enable the migration of double bonds toward less stable, yet more synthetically valuable positions. This directional control allows access to otherwise difficult-to-obtain isomers without the need for pre-functionalized substrates or multistep synthesis. By employing tailored, selective transition-metal catalysts, light-driven systems, or redox-mediated pathways, contra-thermodynamic chain-walking can proceed with high atom economy and minimal waste generation. Moreover, this methodology enables even the late-stage functionalization and valorization of biomass-derived feedstocks. Continued development of more efficient and recyclable catalytic systems is expected to further expand the environmental and industrial relevance of contra-thermodynamic chain-walking isomerization.