| The organic transition metal complexes have attracted considerable attention due to their specific catalytic properties including high selectivity and high reactivity. Particularly, owing to the unique electron configuration of gold, homogeneous gold catalyst is a powerful π-acid catalyst for the selective activation of multiple bonds, such as alkene and alkyne, towards a variety of nucleophilic addition, thus promoting the chemical reaction under milder conditions. In recent years, the field of already rich homogeneous gold chemistry is substantially broaden by the introduction of Selectfluor-mediated transition-metal-catalyzed coupling reactions, which is a powerful strategy for the constructing of carbon-heteroatoms bond and synthesis of various organic compounds. Homogeneous organic gold catalysts have attracted much more attention due to their wide applications in organic synthesis, nanoscience, green chemistry, bioscience and pharmaceuticals. However, despite the rapid development of transition element chemistry, the correlative theoretical study is relatively behindhand. The mechanism involved in these reactions, especially the lately developed coupling reactions, is not clear yet, and the theory system for homogeneous gold catalysis has not been set up. This, to a certain extent, limited the improvement of the existing catalytic system and the design of new fashioned organic synthetic reaction, even then the application and development of homogeneous gold catalysis. Therefore, theoretical studies should prove invaluable in understanding the nature of the catalytic species and paving the way for the rational design of improved catalytic systems.In this dissertation, we present density functional theory (DFT) investigations of several representative organic reactions by quantum chemical tools. The results of our computational calculation show that the gold-catalyzed coupling reactions always proceed via an Au(Ⅰ)/Au(Ⅲ) redox cycle. In the redox cycle, the oxidation of Au(Ⅰ) species is companied by a formation of F-Au bond, and then the Au(Ⅲ) species undergoes reductive elimination to afford the the final coupling product. Furthermore, Selectfluor plays two primary roles in homogenous gold-catalyzed reactions, they are electrophilic fluorinating reagent and external oxidant. And the accurate function of Selectfluor in reaction is influenced by many factors, such as substrate and reaction condition. The computational results provide key insights into the role of Selectfluor in homogeneous gold-catalyzed reactions, as well as the role of water in improving the cross-coupling reaction. In addition, a systematic theoretical investigation was performed to understand the fluorination process of aromatic compounds with Selectfluor and get a deep insight into the character of Selectfluor. Together, the detailed mechanism was illuminated at the atomic level and the experimental findings was rationalized. Our aim is to afford a mechanistic guide to inspire future discovery of new homogeneous catalysts reactions.The important and valuable innovations in this dissertation can be listed as follows:1. The mechanism of the Selectfluor-mediated Au-catalyzed homogeneous oxidative C-O bond-forming reaction has been investigated in details by means of DFT calculation methods. We first investigated the three cycles mentioned in the literature with methyl propargylic benzoate as model substrate. The first cycle was proposed by Zhang, which involve oxidation of a Au(Ⅰ) π-allene complex by Selectfluor(Cycle Ⅰ). The other two cycles favored in the literature (Cycles Ⅰ and Ⅱ) involve oxidation of Au(Ⅰ) phosphine catalyst and Au(Ⅰ) π-alkyne by Selectfluor, respectively. Cycles Ⅰ, Ⅱ, and Ⅲ involve Au(Ⅰ)/Au(Ⅲ) redox mechanisms, in which Selectfluor serves as an external oxidant. Our calculations indicate that all the oxidation processes from Au(Ⅰ) to Au(Ⅲ) need to overcome high energy barriers. Furthermore, we also considered a novel mechanism involving an electrophilic fluorination/defluorination cycle rather than an Au(Ⅰ)/Au(Ⅲ) redox cycle, where the Selectfluor functions as an electrophilic fluorinating reagent (Cycle Ⅳ). This process does not involve Au(Ⅰ)/Au(Ⅲ) chemistry. Surprisingly, it was found that Cycle Ⅳ exhibits the lowest activation barriers. In other words, in contrast to prevailing views in the literature, Selectfluor acts as an electrophilic fluorinating reagent, not an external oxidant, in Au-catalyzed homogeneous oxidative C-O bond-forming reactions.2. We explored the reaction mechanism for Selectfluor-mediated gold-catalyzed homocoupling reaction. Our data show that in the case of cyclopropyl propargylic benzoates, the reaction proceed along the electrophilic fluorination/defluorination and homocoupling pathways need the energy of 22.7 and 24.2kcal/mol, respectively. Such a small difference between these two catalytic cycles indicates that the homocoupling reaction is thermodynamically accessible, and the reaction should give a mixture of the 1-benzoxyvinyl ketone and the enone dimer byproduct (56:28). It is necessary to point out that the mixture is observed experimentally. This can be rationalized by the conjugation interaction of the bent bonds of the cyclopropyl with the neighboring carbonyl C=O bond. For cyclohexyl propargylic benzoates, the predicted difference in free energy barriers between these pathways is 4.2 kcal/mol, supporting the exclusive formation of 1-benzoxyvinyl ketone. Again, this is consistent with experimental data. Together, these results explain the experimental observations well and provide key insights into the mechanism of gold-catalyzed homocoupling reactions.3. The mechanism of Selectfluor-mediated Au-catalyzed intramolecular [3+2] annulation involving direct aryl Csp2-H functionalization has been investigated theoretically. Four pathways involving Au(Ⅰ)/Au(Ⅲ) redox cycles are considered, where either the alkylgold(Ⅰ) (Cycle Ⅰ), phosphine Au(Ⅰ) precatalyst (Cycle Ⅱ), gold(Ⅰ) π-alkene complex (Cycle Ⅲ) and arylgold(I) (Cycle Ⅳ) were oxidized by Selectfluor. We also consider two pathways that don’t involve the Au(Ⅰ)/Au(Ⅲ) catalysis, in which the Selectfluor serves as a reactive source of an electrophilic [F+] species. Our computational results show that Cycles Ⅰ and Ⅱ have lower barriers than Cycles Ⅲ-Ⅵ (26.4 kcal/mol for both Cycles Ⅰ and Ⅱ,37.4 kcal/mol for Cycle Ⅲ,51.0 kcal/mol for Cycle Ⅳ, and 120 kcal/mol for both Cycles Ⅴ and Ⅵ), indicating that the Cycles Ⅰ and Ⅱ are preferred over Cycles Ⅲ-Ⅵ, and the reaction would undergo the energy favored pathways (Cycles Ⅰ and Ⅱ).In addition, the steps in Cycles Ⅰ and Ⅱ are equivalent to a multistep and [3+2] annulation between the aniline moiety and the C=C double bond and afford the cis-product, while the steps in Cycles Ⅰ and Ⅱ are equivalent to a multistep syn [3+2] annulation and deliver the trans-product. It was reported that a cis-product was formed highly selectively when a deuterium-labeled trans-R1 was used. According to the calculational data, it is obvious that the formation of the cis-product is much favored with respect to the trans-product, which is in agreement with the diastereoselectivity observed experimentally. Additionally, regioselectivity in this reaction is suggested to be controlled by the [3+2] annulation addition manner(anti or syn).4. The addition of H2O was reported to play an important role in improvement of the reaction yield, and H2O is believed to enhance the solubility of Selectfluor. We attempt to establish whether H2O is involved in the reaction processes by adding a H2O molecule in the the structures of reductive elimination step, which is calculated to be the determining step. To our delight, there is an strong H-bond interaction formed between H2O and the fluorine atom bonded to Au(Ⅲ). As a result, the energy demand for water-mediated reductive elimination is calculated to be significantly lower than the corresponding process without water, suggesting that water participates in the reductive elimination and reduces the activation barrier of the reductive elimination. With these results in hand, we conclude that, H2O not only helps in the enhancement of the solubility of Selectfluor but also improves the catalytic reaction by facilitating reductive elimination, which may provide a more accurate explanation for the experimental data. And we hope these insights serve as a mechanistic guide to inspire future discovery of new water-accelerated transition state-catalyzed reactions.5. To get informations regarding the number of metal centers involved in redox transformations and address the role of metal centers in the redox steps, we present a detailed theoretical study of Selectfluor-mediated digold-catalyzed intramolecular C-C cross-coupling reaction. Firstly, the pathways favored in literature are investigated. On the basis of calculation results, it can be seen that although the bimetallic oxidation (Path Ⅰ) is preferred over monometallic oxidation(Path II), but the calculated energy barrier of bimetallic reduction is higher than monometallic reduction. That is to say, there would be a cross point of the free energy profiles for Paths Ⅰ and Ⅱ.We would like to propose another mechanism bassed on the computational energy data, namely Path Ⅲ. At the entrance of the reaction, oxidation addition of dppm(AuBr)2 by Selectfluor takes place via an bimetallic (2-electron 2-center) manner affording an AuaⅡ-AubⅡ complex, which then undergoes disproportionation to afford the AuaⅢ-AubⅠ complex, followed by monometallic reduction from AuaⅢ-AubⅠ complex leading to the final product. Obviously, Path III involving bimetallic oxidation, disproportionation and monometallic reduction is the most preferred mechanism, and the Selectfluor-mediated dppm(AuBr)2-catalyzed intramolecular C-C cross-coupling reaction would undergo the energy favored Path III.6. The selective fluorination of aromatic compounds with Selectfluor has been studied theoretically. The molecular ESP iso-surface of Selectfluor has been extracted. We focus on the N1-F region of Selectfluor, where the electrostatic potentials around F are all positive with a slightly more positive cap (a-hole) which is narrowly confined on the elongation of the N1-F covalent bond axis, indicating that the covalent fluorine atom of Selectfluor has the possibility to form fluorine bonding. The structural and energetic features of π complexes of substituted benzenes with Selectfluor are investigated, and the fluorine bond (F/π) has been found to make an important contribution to the stabilization of the π complexes. NBO calculation for these π complexes formed by Selectfluor and substituted benzene suggests that the main contribution to the stabilization is the orbital interactions between the π-electron donor orbital σ(π) of the benzene ring and the N1-F acceptor orbital σ* (N1-F). Electronic density analysis by the AIM method confirm that the fluorine bonds here belong to weak interactions, and have the similar order of magnitude with hydrogen bonds.The selective fluorination of aromatic compounds with Selectfluor proceed through two transition state structures for a-complex formation and proton abstraction, and the formation of the a-complexes is rate-determining. Our calculations indicate that the SET mechanism, which involves one electron transfer from the aromatic substrate (D) to Selectfluor (A), is preferred over the SN2 mechanism. And the energy barrier of the fluorination reaction reduces as the electron donating ability of the substituents increases. A two-state model analysis, as well as the characteristics of avoiding crossing between the DA and D+A- states of benzene/Selectfluor are addressed to obtain deep insight into the features of the SET mechanism. And the potential energy curves of the charge localized diabatic states along the fluorine transfer process suggests that the electron transfer and the fluorine transfer occur successively rather than simultaneously. In addition, the analysis of the minimum energy path (MEP) suggests that the DABCO moiety of Selectfluor seems to take an active role in the fluorination of aromatic compounds with Selectfluor. |
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