From the onset, we found that the trifluorinated ketoester was a convenient spectroscopic handle on benchtop 19 F nuclear magnetic resonance (NMR) spectroscopy for real time, quantitative analysis of the rates of formation and absolute concentrations of reaction intermediates and product formation as a function of time. Since these instruments do not require deuterated solvents with proton lock capabilities, crude reaction mixtures or reaction aliquots could be directly analyzed in the instrument without further processing, and on analytical scale, reactions could themselves be performed in standard 5 mm NMR tubes for rapid, high throughput reaction condition screening and optimization (Figure ), and indeed we previously reported the use of 19 F NMR spectroscopy for reaction condition optimization for a scalable synthesis of other fluorinated small molecules . To make this workflow quantitative, reaction mixtures were spiked with an internal standard, and for the purposes of this study, α,α,α-trifluorotoluene was selected over hexafluorobenzene as an internal standard. An initial screen of a variety of Lewis acid catalysts revealed that 8 mol % ytterbium (III) triflate in acetonitrile most efficiently catalyzed the Biginelli condensation between ethyl 4,4,4,-trifluoroacetoacetate, thiourea, and 3hydroxybenzaldehyde to the corresponding tetrahydropyrimidinone (Table ) .