Our interest in trifluorinated hexahydropyrimidines and dihydropyrimidinones was initially motivated out of a desire to prepare trifluorinated analogs of monastrol and other dihydropyrimidinones and tetrahydropyrimidinones (Figure ). Given the modularity of the Biginelli reaction, we employed an ethyl 4,4,4-trifluoroacetoacetate as the origin of the trifluoromethyl group (Figure ). As expected and in concordance with previous literature reports, the Biginelli cyclocondensation involving trifluorinated keto esters failed to undergo final dehydration into the dihydropyrimidinone, instead terminating at the hexahydropyrimidine, and this was ubiquitously observed across a select series of tested Lewis acid catalysts. While the participation of 4,4,4-trifluorinated ketoesters in the Biginelli multicomponent reaction have been previously observed to occur under Bronsted acid catalysts , we report that ytterbium (III) triflate also efficiently catalyzes this reaction.