The Computational Study Of The Roles Of R-H Acidity In Micro-tuning Some Organic Reactions And The Effect Of Ionic Medium On C-H Acidity

The pKa provides a direct measure of the propensity of the R-H bond to donate a proton, which is fundamental for an understanding of many areas of chemistry. In fact, the Bronsted relationship, which has been used not only to predict organic reactivity but also for detecting changes in reaction mechanism and deducing transition state structure, was established on the basis of equilibrium acidity studies. While the Bronsted relationship has been invaluable for diagnosing mechanisms and designing new reactions or catalysts, it is not without limitations, i.e. the Bronsted relationship is unable to provide any information on the relationship between acidity/basicity and enantioselectivity, which is of great value for designing new asymmetric reactions and catalysts. Another example is the observation of anomalous Bronsted value for the reactions between the nitroalkanes and hydroxide, which was later referred to as the nitroalkane anomaly. The limitations of the Bronsted relationship provide a strong impetus for updating the knowledge of the acidity-reactivity-enantioselectivity relationship.Ionic liquids have been widely used as novel solvents for synthesis and catalysis due to their unique solvent properties. Although tremendous progress has been made in this field, there is still only limited information available regarding their intriguing solvent effects. How would important chemical parameter, namely pKa, vary when solvent composition is changed from molecules to ions, remains an unusual challenge for both experimental and computational chemists. To the best of our knowledge, there is no theoretical protocol available for calculating any pKa in ionic liquids up to present. Therefore, it is highly desirable to develop a strategy for ionic medium, especially for reliably predicting pKa constants in ionic liquids, considering that there was basically no acidity measured as absolute value in pure ionic liquids.Triggered by the above-mentioned issues, we systematically investigated micro-tuning organic reactions by R-H acidity and the effect of ionic medium on C-H acidity with quantum chemical calculations in this thesis.(1) Optimizing catalytic activity and enantioselectivity by tuning the O-H acidity of the chiral catalyst through electronic effect was studied computationally. Asymmetric olefin isomerization of β,γ-to α,β-unsaturated butenolides catalyzed by novel cinchona alkaloid derivatives was investigated in-depth using DFT theories. It was found that the tuning of acidity of active site of the catalyst may lead to a mechanism switch. Moreover, the non-covalent interactions in the stereo-controlling transition state structures were identified and their strength was quantitatively estimated. The weak non-conventional C-H…O hydrogen bonding interactions were found to be crucial for inducing the enantioselectivity of the cinchona alkaloid derivatives catalyzed asymmetric olefin isomerization. The enhanced enantioselectivity is originated from a tighten hydrogen binding of substrate with the catalyst, and this causes an enhancement of the stabilizing non-conventional hydrogen interactions in the stereo-controlling transition states.(2) The tuning of the O-H acidity of the chiral catalyst by additives was investigated. The pKa shifts of proline induced by hydrogen-bond donor co-catalysts were computationally evaluated in the gas phase and solution. In addition, it revealed that hydrogen-bond donor co-catalyst interacts with not only proline but also the substrates in the stereo-controlling transition state.(3) The effect of the O-H acidity of achiral catalysts on Bronsted acid catalysis was investigated. The detailed mechanism of N-alkylpyrrole formation from3-pyrroline and2-phenylpropanal catalyzed by a Bronsted acid catalyst was studied theoretically. Two mechanisms proposed earlier for this internal redox process were evaluated and were found not to account perfectly for the transition state and the energetic barrier of its formation. A new mechanism was proposed based on the calculations and previous experimental findings.(4) The unusual inverse order of kinetic and thermodynamic acidities of the nitroalkanes during their reactions with hydroxide ion in water was reinvestigated. The calculations revealed that the hyperconjugation and torsion effects were relevance to the origin of the nitroalkane anomaly.(5) First theoretical protocol for reliably predicting equilibrium acidities in ionic liquid was developed. A SMD implicit-explicit approach was developed that allows prediction of experimental pKa values of various carbon acids in ionic liquid with a mean unsigned error of1.28pKa units, which is comparable in magnitude to those authentic pKa calculations in conventional solvents.