Mechanism of Proline-Catalyzed Intramolecular Aldol Reactions

2 Mechanism of Proline-Catalyzed Intramolecular Aldol Reactions 

The lower barrier through 65a leads to the isomeric product that is found in excess in the experiment, with reasonable agreement with the experimental ee of 42 percent. The two diastereomeric TSs for Reaction 6.25 differ in energy by only 

1 kcal mol k No enantiomeric excess was observed in this experiment.  

Since the pathway involving two proline molecules is inconsistent with new experiments that indicate a reaction that is first order in proline, they did not pursue 

computation indicates that the Hajos-Parrish-Wiechert-Eder-Sauer reaction proceeds by the carboxylic-acid-catalyzed enamine mechanism D, which is consistent with all of the computations for intermolecular proline-catalyzed aldol examples. 

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