Mechanism of Amine-Catalyzed Intermolecular Aldol Reactions

1 Mechanism of Amine-Catalyzed Intermolecular Aldol Reactions 

We begin by examining the computational results for the intermolecular amine-catalyzed aldol reaction. The most likely mechanisms posit an enamine intermediate that then attacks an aldehyde to produce the aldol product. Boyd and coworkers ° examined this entire reaction pathway for the reaction of acetone and 

Dual proline-catalyzsd TS Carboxylic-acid-catalyzed TS 

For the gas-phase reaction, surprisingly, the step where the new C-C is formed is not rate limiting. The barrier for this step (49 50) is 13.7kcalmol (It should 

There are two important conclusions to be carried forward first, that solvation is likely to be of critical importance and should be included in the computations, and second, that focusing on the C-C forming step is appropriate. This C-C forming step is critical in accounting for the stereochemical outcome of the aldol reaction. 

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