We decided to synthesize the trifluorinated counterparts of monastrol and LaSOM-63 because of the bioorthogonal nature of fluorine and the increased metabolic stability offered by the presence of carbon-fluorine bonds . Of note, while it has been reported that the substitution of a ß-ketoester with a 4,4,4-trifluorinated ketoester can be used to prepare trifluorinated versions of these dihydropyrimidinones and tetrahydropyrimidinones through the Biginelli reaction, the operative mechanism through which the Biginelli proceeds with 4,4,4-trifluoroketoesters has not been investigated. Recent advances in benchtop nuclear magnetic resonance (NMR) spectroscopy have allowed for non-canonical applications of NMR spectroscopy as an analytical tool directly in a synthetic laboratory setting, including real time reaction monitoring. Here, we utilize benchtop 19 F NMR spectroscopy to probe the mechanism of the Biginelli cyclocondensation of trifluorinated ketoesters by tracking the production of various aryl substituted trifluorinated tetrahydropyrimidinones and their reactive intermediates in real time. In this study, a library of various 3-and 4-substituted aromatic aldehydes not only gave access to a diverse library of 6-aryl trifluorinated tetrahydroprymidines, but also provided mechanistic insight into the Biginelli through meta-and para-Hammett linear free energy relationships (LFER) derived from 19 F NMR spectra of crude reaction mixtures . While quantitative measurement of chemical species present in a reaction mixture might be possible with other means, such as high performance liquid chromatography (HPLC), LC-MS, or GC-MS, the quantification of such species by 19 F NMR does not require any reaction workup or further sample processing and can be done within seconds or minutes of set timepoints, in a manner that is not invasive to the reaction mixture and therefore allows for direct measurement of species of interest in an unadulterated setting.