Theoretical Study On The Mechanism Of Intermolecular Asymmetric Aldol Reaction Catalyzed By The Novel Prolinamide Phenol

In this thesis the theoretical research on the mechanism and transition state structures of the prolinamide catalyzed Aldol reaction (Schemel) by using TS theory and enamine mechanism was carried out.The transition structures associated with the C-C bond formation step were studied using HF at 6-31g(d) level and Density Functional Theory method at B3LYP/6-31g level, respectively.1. Theoretical research on model direct Aldol reaction using Hartree-Fock theory and DFT theoryAll calculations were implemented in Gaussian03 suits of program. All reactants, products and TS structures were optimized in HF/6-31G (D ) level using OPT key word for reactant and product, and OPT (TS, CALCFC, NOEIGEN) key word for TS structures. For the stereo-controlling and rate-determining step, four possible reactive channels, named as syn-R, syn-S, anti-R, anti-S, have been analyzed (Figure.1). For each TS structure, the stationary points were characterized by frequency calculation in order to verify that minima and transition structures have zero and one imaginary frequency, respectively. The intrinsic reaction coordinate (IRC) paths were traced in order to check the energy profiles connecting each transition structure to the two associated minima of the proposed mechanism. These frequency calculations and IRC paths were taken to check the structure whether a saddle in potential-energy surfaces (PES). The MP2/6-31G** energies with the final optimized structures at HF/6-31G(d) or B3LYP/6-31G level are in good agreement with experimental results respectively. This work, not only gave the stereoselectivity a well explanation, but also clarified that it is a reasonable right strategy to introduce a rigid conjugated aromatic ring in our catalytic synthesis work.2. Theoretical research on the direct Aldol reaction using Hartree-Fock theory between cyclo-ketone and o-nitrobenzaldehyde.For each TS structure (Figure.2), the stationary points were characterized by frequency calculation in order to verify that minima and transition structures have zero and one imaginary frequency, respectively. The intrinsic reaction coordinate (IRC) paths were traced in order to check the energy profiles connecting each transition structure to the two associated minima of the proposed mechanism. These frequency calculations and IRC paths were taken to check the structure whether a saddle in potential-energy surfaces (PES). 3. Energy calcutions to predict anti/syn and ee valueBecause the good accordance between theoretical research and experimental results, we applied the same research into two chiral pool product Aldol reaction. From the active energies, we found that anti isomer will be excess and ee ration will be better. And the experimental results indeed did so. Comparing all of the channels, the TS energy indicated that RR-1-1,RS-1-1,SR-1-1,SS-1-1 channels are more preferable which is correspongding to the more stable reactant aldehyde.