Generic Enhanced Sub/Supercritical Fluid Chromatography: Blueprint for Highly Productive and Sustainable Separation of Primary Hindered Amines

α,α-Diaryl primary amines are highly important chemical building blocks in agrochemical and pharmaceutical active ingredients. One of the limitations of current chromatographic methodologies for these molecules is the poor greenness factor as a result of high solvent consumption to reach the necessary productivity, as well as the lack of systematic approaches. Herein, we overcome these challenges by introducing a simple and highly efficient enhanced sub/supercritical fluid chromatography (eSFC) approach that enables analysis and purification of over 40 α,α-diaryl primary amine mixtures. This approach translates into several highly desirable features from a simplicity and greenness perspective including (1) improved chromatographic performance and productivity, (2) augmented MS detection that allows for analytical eSFC–MS and preparative MS-directed purifications, and (3) efficient and direct solvent removal. This strategy represents a move toward modernized greener and sustainable separations as demonstrated by a 30-fold improvement of the analytical method greenness score (AMGS) compared to currently available chromatographic approaches.