Rate Limiting Step Precedes C-C Bond Formation in the Archetypical Proline-Catalyzed Intramolecular Aldol Reaction

The archetypical proline-catalyzed intramolecular aldol reaction, the Hajos-Parrish-Eder-Sauer-Wiechert reaction, has served as a model reaction for the mechanistic study of the ever-growing class of proline-catalyzed conversions. Experimental measurements of the C-13 kinetic isotope effects for this reaction show conclusively that carbon-carbon bond formation is not rate-limiting.