In summary, en route to preparation of a novel trifluorinated analog of monastrol, an antiproliferative dihydropyrimidinone small molecule, we determined that the Biginelli multicomponent reaction proceeds through an enamine mechanism preferentially over the imine mechanism when a 4,4,4-trifluoro-β-ketoester is used in lieu of conventional, non-fluorinated β-ketoesters. The mechanistic investigation of this reaction was enabled by benchtop 19 F NMR spectroscopy, with which the rates of formation and reaction of fluorinated intermediates and products could be quantified.