The CBS-QB3 method was used to calculate the gas-phase free energy difference between 20 phenols and their respective anions, and the CPCM continuum solvation method was applied to calculate the free energy differences of solvation for the phenols and their anions. The CPCM solvation calculations were performed on both gas-phase and solvent-phase optimized structures. Absolute pK(a) calculations with solvated phase optimized structures for the CPCM calculations yielded standard deviations and root-mean-square errors of less than 0.4 pK(a) unit. This study is the most accurate absolute determination of the pK(a) values of phenols, and is among the most accurate of any such calculations for any group of compounds. The ability to make accurate predictions of pK(a) values using a coherent, well-defined approach, without external approximations or fitting to experimental data, is of general importance to the chemical community. The solvated phase optimized structures of the anions are absolutely critical to obtain this level of accuracy, and yield a more realistic charge separation between the negatively charged oxygen and the ring system of the phenoxide anions.

The potential energy profile of Rh(I)-catalyzed hydrogenation of enamides has been studied for the simple model system [Rh(PH 3 ) 2 (R-acetamidoacrylonitrile)] + using a nonlocal density functional method (B3LYP). Intermediates and transition states along four isomeric pathways for dihydrogen activation have been located, and pathways for interconversion between isomeric reaction pathways have been explored. The general sequence of the catalytic cycle involves coordination of H 2 to [Rh(PH 3 ) 2 (R-acetamidoacrylonitrile)] + to form a five-coordinate molecular H 2 complex, followed by oxidative addition of the coordinated molecular hydrogen to form a dihydride complex, [RhH 2 (PH 3 ) 2 (R-acetamidoacrylonitrile)] + . This dihydride is converted into an alkyl hydride by a migratory insertion reaction. Reductive elimination of the hydrogenated acetamidoacrylonitrile completes the catalytic cycle. No computational support for alternate H 2 activation pathways, such as direct conversion of H 2 and [Rh(PH 3 ) 2 (R-acetamidoacrylonitrile)] + to an alkyl hydride, was found. Four isomeric pathways for hydrogenation are followed, corresponding to the four distinct dihydride isomers resulting from cis addition of H 2 to [Rh(PH 3 ) 2 (R-acetamidoacrylonitrile)] + . Two of these pathways are excluded from further consideration by virtue of their surprisingly high activation barriers for formation of molecular H 2 complexes. Of the two pathways with low barriers to formation of dihydride complexes, only one has a sufficiently low barrier for migratory insertion to contribute significantly to catalytic product formation. Overall, we find that formation of a dihydride is endergonic, rapid, and reversible. Migratory insertion to form an alkyl hydride constitutes the turnover-limiting step in the catalytic cycle. This conclusion is supported by comparison of computed and experimental isotope effects in catalytic enamide hydrogenation.

The G3, CBS-QB3, and CBS-APNO methods have been used to calculate ∆H and ∆G values for deprotonation of seventeen gas-phase reactions where the experimental values are reported to be accurate within one kcal/ mol. For these reactions, the mean absolute deviation of these three methods from experiment is 0.84 to 1.26 kcal/mol, and the root-mean-square deviation for ∆G and ∆H is 1.43 and 1.49 kcal/mol for the CBS-QB3 method, 1.06 and 1.14 kcal/mol for the CBS-APNO method, and 1.16 and 1.28 for the G3 method. The high accuracy of these methods makes them reliable for calculating gas-phase deprotonation reactions, and allows them to serve as a valuable check on the accuracy of experimental data reported in the National Institutes of Standards and Technology database.

Hybrid molecular orbital/molecular mechanics calculations are used to determine the origin of the “anti‐lock‐and‐key” behavior in asymmetric catalytic hydrogenation. The computations provide a simple model to explain this behavior (see scheme), and agree with all relevant empirical data.