Lowest-energy transition states, enamine

For the Michael addition between 3-pentanone and nitrostyrene a report by Patil and Sunoj points out a key limitation of the standard enamine derived transition state model when a polar protic reaction medium is employed (Scheme 17.10) [42]. The unassisted transition state inclusive of continuum solvent effects failed to predict the correct stereochemical outcome of the reaction as compared to the experimental observations. The predicted lowest energy transition state has been identified as leading to an incorrect configuration of the newly formed chiral centers as well as the wrong diastereomer. Further refinements to the transition state models were carried out with inclusion of explicit solvent molecules in view of the fact that the reaction being modeled has been conducted in methanol as the solvent. After examining several microsolvated transition states with varying... 

IG and added in the free energy of solvation in DMSO computed with PCM at HF/6-31-l-G(d,p). The lowest energy TS is for the carboxyhc-acid-catalyzed enamine route (Scheme 6.8 D). This barrier is 10.7 kcal mol smaller than that for the barrier without proline acting as a catalyst. The transition state for the enaminium-catalyzed route (Scheme 6.8 B) is 29.0 kcal mol higher than the TS for Scheme 6.8 D. All attempts to locate a TS for the nucleophilic substitution route (Scheme 6.8 A) failed. However, the carbinolamine intermediate that proceeds the TS on path A lies 12.7 kcal mol above the TS for Scheme 6.8... 

The important aspect of their study relates to the stereochemical mode of addition in the most preferred transition state in (a) and (b). In model-(a). Re-face addition of enamine carboxylic acid on the Re-face of the aldehyde is the lowest energy addition leading to an enantiomeric excess of about 99% in favor of (2S,3S) stereoisomer and anti-diastereomer as the major product In model-(b), on the other hand, anti-face addition involving the Si-Re mode respectively between enamine carboxylate and aldehyde is of the lowest energy. This approach predicts... 

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