Theoretical Studies Of Several Organocatalytic Asymmetric Reactions And Platinum(Ⅱ)-Catalyzed Cycloaddition Reaction

Asymmetric catalysis has been a new research frontier in the field of current asymmetric synthesis owing to constructing complex molecular scaffold with high efficiency and high selectivity. The past decade has witnessed the extraordinary success of new catalysts and new methodologies. Moreover, many new concepts have been developed.Despite the extraordinary achievements in the experimental side for asymmetric catalysis, our knowledge most of them about the mechanistic details remains as well as the origin of enantioselectivity still remains elusive. The theoretical studies can provide useful information on the mechanism and the transition state of asymmetric catalysis and rationalize the experimental observations. We studied a series of H-bond induced asymmetric catalystic reactions. In addition, the cycloaddition catalyzed by transition metal has become a powerful tool for construction of cyclic compounds in asymmetric or ganocatalysis. Hence, we studied a cycloaddition with a generation of platinum-containing carbonyl ylides with electron-rich alkenes have been explored. It is expected to provide a close collaboration between experiment and theory and hence bring new insight into other similar reactions, as well as further promote the development on the catalytic asymmetric formation of a carbon-carbon bond and H-bond induced asymmetric catalystic reaction.The hydrogen-bonding interaction is weak molecular interaction, which has important impact on natures of substances. It is also of importance in chemistry, biology and materials science and now more attention is paid to the experimental and theoretical investigations. In the past few years, the utilization of hydrogen bonding as an activation force has become a powerful tool in asymmetric or ganocatalysis. Significant advances have been made in this emerging field. However, our knowledge most of them about the mechanistic details remains a puzzle, as well as the corresponding concept system has not yet formed, which hinder the development and wide application of hydrogen induced asymmetric catalysis.In this dissertation, we studied four asymmetric catalystic reactions based on hydrogen induction catalyzed by amine catalysis with density functional theory (DFT) calculations. Our purposes are to illuminate the mechanistic details of the amine catalyzed asymmetric reactions and hence obtain a better interplay between theory and experiment. In addition, the cycloaddition with a generation of platinum-containing carbonyl ylides with electron-rich alkenes have been explored. By further detailed mechanistic investigation elucidate the origin of the regio-and stereoselectivities of the reactions. Our results provided a close collaboration between experiment and theory and hence bring new insight into other similar reactions, as well as further promote the development on asymmetric catalystic reaction.The important and valuable results in this dissertation can be summarized as follows:1. Our calculations provide the theoretical detailed information on the mechanism of asymmetric epoxidation of2-cyclohexen-1-one with aqueous H2O2as oxidant, chiral diamine as catalyst, and TFA as co-catalyst. Four possible pathways associated with different conformations of ketiminium, which proceed via sequential nucleophilic addition and ring-closure processes, have been explored in detail. The calculated results indicate that without the assistance of TFA anion and H2O the catalytic epoxidation presents very high barriers and a narrow energy gap between two favorable R-and S-pathways, which can not correlate well with the experimentally observed rate and enantioselectivity. We have analyzed the effects of TFA anion and H2O on the catalytic epoxidation, and found that TFA anion acts as a counterion to stabilize all the transition states of the catalytic epoxidation by hydrogen-bond acceptance, resulting in decreases in the barriers of the nucleophilic addition and ring-closure processes especially the ring-closure step of the Z-R-pathway. It is also found that water cooperates with TFA anion to increase the reaction rate significantly, and the differential stabilization of the TS structures imparted through H-bond interactions dictates the observed enantioselectivity. Our calculated results rationalize the roles of TFA anion and H2O in the catalyzed reaction and explain the experimental findings well.2. DFT calculations were employed to elucidate the origin of enantioselectivity and the role of Br(?)nsted acid in the primary amine-catalyzed epoxidation of cyclic enones. The roles of covalent and non-covalent interactions on the low-lying transition states have been discussed. It was found that a Csp2H…O interaction between the benzene ring of the catalyst and the bridging water is primarily responsible for the observed chiral discrimination. The Br(?)nsted acid counterion does not play a direct role in control of enantioselectivity. However, it is still essential for achieving high reactivity and enantioselectivity, because it increases the rigidity of the TSs structures and allows efficient formation of the Csp2H…O H-bond.3. Computational studies to elucidate the origin of enantioselectivity in the (1R,2R)-1,2-diphenylethane-1,2-diamine (DEPN)-Br(?)nsted acid (TFA and TRIP) catalyzed epoxidation of2-cyclohexen-l-one have been performed using density functional theory. Transition states for conjugate addition and ring closure steps of the epoxidations catalyzed by three different catalyst systems were characterized. Our calculations show that Csp2H…O H-bond interaction between the benzene ring of the catalyst and H2O is mainly responsible for the chiral discrimination observed. Moreover, we explain why two catalysts with different absolute configurations at their chiral centers [(1R,2R)-DPEN and (1S,2S)-DACH] combining with achiral TFA and chiral (R)-,(S)-TRIP, respectivily, display similar enantioselectivities.4. We provide the theoretical detailed information on the asymmetric direct aldol reactions of2-cyclohexen-l-one with4-nitrobenzaldehyde catalyzed by a chiral primary-tertiary diamine catalyst by performing density functional theory calculations. Focused on the crucial C-C bond-forming steps, we located several low-lying transition states and predicted their relative stabilities. Eight possible pathways associated with four different conformations of enamine intermediates have been explored in detail. The asymmetric aldol reaction under solvent-free condition leads to main anti-product. While when the reaction catalyzed by a chiral primary-tertiary diamine combined with succinic acid under solvent-free condition give main syn-product. The theoretical results are accord with the experimentally observed stereoselectivities and provide a reasonable explanation for the stereo outcome of aldolization under very mild condition. The results are helpful for the designing the new efficient catalyst and choosing suitable co-catalyst.5. Platinum(Ⅱ)-catalyzed reaction of acyclic γ,δ-ynones with alkenes has been investigated using DFT by analyzing the generation of platinum-containing carbonyl ylides and the cycloaddition reaction of these ylides with electron-rich alkenes. Our calculation confirms that the platinum-containing carbonyl ylides are formed by attack of the carbonyl oxygen of γ,δ-ynones on the alkyne in a6-endo manner. Three pathways for the reaction of ylides with methyl vinyl ether have been investigated, which include [3+2] cycloaddition/1,2-hydrogen shift,[3+2] cycloaddition/two sequential1,2-alkyl migrations/1,2-hydrogen shift, and [4+2] cycloaddition/1,2-alkyl migration/1,2-hydrogen shift. Our calculation indicates that the substrate substitution pattern dictates the reaction mechanism. Regarding the exo/endo selectivity, computational results show the steric hindrance between the substitutions of vinyl ether and the chlorine atom of the catalyst contributes substantially to the observed exo/endo selectivity. In addition, distortion-interaction analyses are carried out and unveil that the enantioselectivity originates from the energetic difference in distortion energies of the key transition states in the chiral PtCl2(bisphosphine)-catalyzed asymmetric reaction.