Theoretical Studies On The Mechanisms Of C-N/C Formation And Cleavage Promoted By Transition Metal Complexes

Nitrogen is a key atom in nature, found in several well known natural product families such as amino acids, alkaloids, porphyrins and penicillins. Moreover, nitrogen is ubiquitous in biology, with synthetic drugs generally containing more nitrogen than natural products. Its ability to act as a hydrogen bond donor and/or acceptor strongly influences the interaction between the medicinal agent and its target. In addition, the pKas of amines are often in the range of physiological pH, a physical property essential for improving the bioavailability of drugs. Nitrogen is also important in material sciences, where its presence in the structures of polymers can have a profound effect on their physical, electronic or surface properties.Therefore, there has been much effort which aims at the development of the methodology for formation of C-N/C and cleavage of C-N bond. Now the reaction mechanisms are widely applied in the field of the preparation of new substances, materials and drugs. In this paper, based on the molecular orbital theory and the transition state theory, the involving systems have been investigated using Density Functional Theory (DFT), the polarized continuum model (PCM) and the natural bond orbital (NBO). The structures of the species (including the transition states) along the reaction paths have been optimized. The calculations provided the reaction profiles, the thermodynamic datum as well as the information of orbitals, which can be used to analyze the corresponding reaction mechanism and supply the theoretical reference for relative experimental research.The whole paper consists of six chapters.Chapter 1 mainly reviews the aziridination and the insertion of C-H bond catalysed by transition metal complexes (formation of C-N bond), cleavage of C-N bond, the mechanism of the insertion of C-H bond and cyclopropanation promoted by monocarben and biscarbene. Besides, the main works in this paper are introduced.The second chapter summarizes the theory of quantum chemistry and calculation methods of this paper. It offers useful and reliable theoretical basis for the paper.In chapter 3, the mechanisms on dirhodium-catalyzed intramolecular amination and aziridination have been investigated using density functional theory calculations done at the BPW91 level of theory. Our calculations suggest: (1) The metal-nitrene is the active center of transitive nitrogen atom. (2) When the substate is alkene with double bond (C=C next to C of amination), metal-nitrene triplets are the dominant reactive states in both amination and aziridination. (3) Compared to Rh2(OAc)4, the catalyst Rh2(S-nap)4 would greatly enhance the ratio of amination, which is in agreement with the experimental results. Because electronegative nitrogen in triplet metal-nitrenes would attack electropositve H in amination and it's the nucleophilic reaction. Nitrogen in the metal-nitrene from Rh2(S-nap)4 is more electronegative and hydrogen attacked is more electropositive. Therefore it can be predicted that enlarging the electronegativity difference of coordination atoms on catalyst-Rh2II,II would enhance the ratio of amination product.In chapter 4, the mechanisms of intramolecular and intermolecular amination have been investigated using density functional theory calculations done at the BPW91 level of theory. Our calculations suggest: (1) that singlet metal-nitrene is the dominant states for 3°H and 2°H of intramolecular amination. The product ratio of 3°H is highest. (2) As for intermolecular amination, singlet metal-nitrene is the dominant state for 3°H while triplet for 2°H. The product ratio of 2°H is highest. These results are consistent with the experimental results.In chapter 5, density functional theory (DFT) calculations at the B3LYP level of theory were performed to elucidate the reaction mechanism for the reduction of amides to aldehydes using Cp2Zr(H)Cl as a reducer. The first step of the reaction is the insertion of the C=O moiety into Zr-H through an"inside"mode of action that leads to the formation of a Zr-O intermediate that has been observed in previously reported experiments. Under anhydrous conditions, the cleavage of the O-C bond of the Zr-O intermediate results in the formation of an iminium cation, but this process is both kinetically and thermodynamically unfavorable. Nevertheless, under hydrous conditions, the cleavage of the O-C bond of the Zr-O intermediate leads to the formation of a highly active iminium cation intermediate, and this process occurs with the assistance of water hydrogen bonding. This step is also the rate-determining step, and the activation energy was determined to be 19.8 kcal/mol. Subsequently a water molecule attacks the iminium cation to produce an amine intermediate. Finally, the water-catalyzed elimination reaction including the cleavage of C-N bonding occurs to yield the aldehyde product. Water hydrogen bonding plays an important role in assisting the cleavage of the O-C and the C-N bonds during the reaction. The above reaction mechanism indicates that the sources of the aldehyde-group oxygen and the hydrogen in the aldehyde product are H2O and Cp2Zr(H)Cl, respectively, which is consistent with the experimental observations of Georg and co-workers.In chapter 6, we have studied the mechanism of the C-H insertion and cyclopropanation promoted by monocarbene [Os(F20-TPP)(CPh2)CO] and biscarbene [Os(F20-TPP)(CPh2)2] in detail using density functional theory calculations done at the B3LYP level of theory. This chapter mainly refers to the active comparision of the C-H insertion and cyclopropanation between monocarbene and biscarbene, the substituent effects and electronic effects of biscarbene. The conclusions are as follows: (1) biscarbene is more active than monocarbene for C-H insertion and cyclopropanation. (2) The activity only changes slightly when the H on the para-position of biscarbene-C is replaced by CH3 or Cl. (3) When biscarbene reacts with HSi(CH3)3 and HN(CH3)2, respectively, the activation energy of the reaction between bicarbene and HSi(CH3)3 is 2.9 kcal/mol lower than that of HN(CH3)2. It's because the N atom is more electronegative than Si.