Authors: Norelyza Hussein
Source: International Journal of Chemical and Biological Sciences (article, 2025-07-01)
Field: Chemistry — Organic Chemistry

Advances in organocatalytic asymmetric synthesis: Mechanistic insights, applications, and sustainable perspectives Organocatalysis has developed into a theoretical interest into a revolutionary component of asymmetric synthesis today, providing a metal-free, operationally straightforward and environmentally innocent model of assembling chiral molecules. Within the last ten years, extraordinary progress has relegated the boundaries, effectiveness, and relevance of organocatalytic methods taking the lead of sustainable chemical innovation. It is a qualitative review article that consolidates and critically interprets major advances in enantioselective organocatalysis published in 2018-2025 with a stronger emphasis on both mechanistic complexity and practical feasibility. By relying on over 120 peer-reviewed studies, we critically examine the structural and electronic properties of major families of organocatalysts, such as proline derivatives, chiral (thio) ureas, squaramides, N-heterocyclic carbenes (NHCs) and BINOL-based phosphoric acids, and relate them to stereoselectivity results, substrate generality, and functional group tolerance. In addition to catalytic performance, the principles of green chemistry are incorporated in the present review by measuring such metrics as enantiomeric excess (ee), turnover number (TON), E-factor, process mass intensity (PMI), and solvent sustainability. The issues of scalability, catalyst recyclability, and the ability to work with other reaction media (e.g., water, bio-based solvents, solvent-free conditions) are given special consideration. Detailed cross-study evaluations of reaction conditions, yields, stereoselectivity, and environmental footprints are given in the five comparative tables, and catalytic cycles, transition-state models, and overall trends in research are shown in five schematic figures. Significantly, we also put these scientific innovations in the context of larger socioeconomic and policy frameworks - in essence, how they can be incorporated in resource-starved areas where cost, safety and infrastructure constraints require low impact synthetics. The review also ends by outlining remaining knowledge gaps (including the lack of life-cycle evaluations and industrial case studies) and suggests ways of action that can be implemented to align organocatalytic research to the United Nations Sustainable Development Goals (notably SDG 3: Good Health and Well-being, SDG 9: Industry, Innovation and Infrastructure, and SDG 12: Responsible Consumption and Production). It is hoped that this work will encourage a deeper refinement of methodology and a more socially-conscious approach to innovation going forward by balancing the pillars and disciplines of fundamental organic chemistry with the sustainability requirements of the future. Organocatalysis ; Enantioselective synthesis ; Context (archaeology) ; Obsolescence ; Process (computing) ; Sustainable development ; Schematic N-Heterocyclic Carbenes in Organic and Inorganic Chemistry ; Cyclopropane Reaction Mechanisms ; Asymmetric Synthesis and Catalysis