Domino and Cascade Reactions in Sustainable Synthesis: Activation Modes, Assessment Boundaries, and the Molecular-Process Discrepancy
Year: 2026
Type: preprint
Abstract: Domino and cascade reactions construct molecular complexity through sequential transformations and can reduce intermediate isolation. Their contribution to sustainable synthesis depends on whether these advantages persist when precursor preparation, catalyst production, reaction operation, and product recovery are included. This targeted narrative review examines thirteen mechanistic examples across seven activation or propagation modes and develops the molecular-process discrepancy (MPD) as a framework for testing that translation. MPD connects a specific reaction-level claim to the additional material and energy requirements introduced by expanding the assessment boundary. It complements atom economy, process mass intensity, E-factor, life-cycle assessment, and process benchmarks without replacing their measurements. Four case studies distinguish the roles of feedstock and product recovery in Ambrox synthesis, oxidant substitution in coumestan formation, advanced-substrate preparation in lasalocid A biosynthesis, and operational consolidation in oseltamivir synthesis. Together, they show why atom conservation, selective ring construction, and fewer isolations provide different forms of efficiency that must be evaluated separately. The analysis identifies precursor access, dilution, separation, catalyst lifetime, and heat, light, or oxygen delivery as specific targets for process improvement. MPD provides a procedure for determining whether a proposed cascade advantage is retained, attenuated, reversed, or unresolved across explicit assessment boundaries.
Source: ChemRxiv
Author: Khang T. Hoa
Institution: Can Tho University
Language: English
Subfield: Environmental Chemistry
Field: Environmental Science
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7213444237