Extending the Scope of the Rule “Exchange in a Group of Three (EIGT)” beyond Fischer Projection: A Unified Method for <i>R</i> / <i>S</i> -Assignment

The correct assignment of absolute configuration to chiral molecules is fundamental for a comprehensive understanding of their three-dimensional structures. The descriptors used for distinguishing between a pair of enantiomers are R (Rectus) and S (Sinister) based upon the Cahn–Ingold–Prelog (CIP) system. The CIP system necessitates the determination of ligand priorities attached to an sp3-stereocenter in chiral molecules, guided by an established set of rules. However, students often struggle with the practical application of these methods, especially when the lowest priority group does not point away from the observer, thus complicating the assignment of R/S descriptors. This paper introduces a student-friendly unified approach utilizing the well-known “Exchange in a Group of Three (EIGT) rule”, traditionally applied to Fischer projections, to facilitate the assignment of absolute configurations across various representations, including wedge-dash, Fischer, Newman, Sawhorse, and chair conformations (for cyclohexane derivatives). The method aims to simplify the process for introductory stereochemistry students, enabling them to confidently determine CIP-based absolute configurations even when the least priority group is not optimally positioned. A student-based evaluation validated the utility of the proposed method. However, like most mnemonic-based approaches, the EIGT method may not be equally effective in all stereochemical contexts; for instance, certain complex three-dimensional arrangements (e.g., specific Newman projections) may still require additional visualization aids or supplementary instructional tools.