Theoretical Study On The Mechanism Of Palladium,Rhodium And Phosphine Catalyzed Cyclization Reaction

Since the day when quantum chemistry was created,scientists have begun to search about how to explore the nature of chemical reactions through theoretical models and mathematical calculations.During past decades,with the rapid improvement of computer performance and calculation models,the accuracy of computational chemistry has become better and better.Using quantum chemistry methods to explore the mechanism of organic chemical reactions has become one of the most important ways to deeply understand the reaction process and to explain the experimental phenomena.The cyclization reactions are very important in organic chemistry,which is widely used to construct various cyclic compounds.This essay adopts density functional theory(DFT)to conduct detailed theoretical studies on three representative cyclization reactions,which are,palladium-catalyzed carbon-hydrogen bond activation cyclization reaction,phosphine-catalyzed[8+2]ring addition reaction,rhodium-catalyzed enyne amination and cyclization reaction.This thesis is mainly divided into six chapters.The first chapter introduces the background of palladium-catalyzed C-H bond activation cyclization reactions and rhodium/phosphine-catalyzed cycloaddition reactions.The second chapter briefly summarizes the commonly used theoretical models and their development in history.Chapters 3,4,and 5 respectively introduce the theoretical study of palladium-catalyzed carbon-hydrogen bond activation cyclization reaction,phosphine-catalyzed[8+2]cycloaddition reaction,and rhodium-catalyzed enyne amination and cyclization reaction.The sixth chapter is a summary of the research work of the three topics.The following is an overview of the research results of the three topics.1.Theoretical study of palladium-catalyzed C-H bond activation cyclization reactionThe DFT method was used to to conduct a theoretical study on the palladiumcatalyzed aryl C-H bond activation cyclization reaction of α,β-unsaturated ketones.The key steps in the reaction of carbon-hydrogen bond activation and dehydrogenative oxidation were explored in detail.The calculation results of the C-H bond activation process showed that the reaction is initiated by the Heck-type mechanism.In the sixmembered ring palladium species obtained by olefin insertion,the weak coordination of phenolic hydroxyl oxygen with palladium increases the energy barrier of β-H elimination process in the typical Heck reaction.The calculation found that the CMD process is thermodynamically more favorable than the β-H elimination process,which effectively blocking the β-H elimination process.Due to the existence of a palladiumπ coordination bond between the phenyl group of iodobenzene and the palladium,the benzene ring in the substrate cannot rotate freely.The calculation found that the activation energy of this step is 10.3 kcal·mol-1,higher than the activation energy of the CMD process,which means the ligand exchange is thermodynamically unfavorable.Therefore,selectivity of the phenyl ortho C-H bond activation in the experiment is explained.Subsequently,we further explored the process of dehydrogenation.The results showed that the reactant iodobenzene can not only participate in the reaction,but also act as an oxidant,oxidizing Pd(0)to catalytically active Pd(Ⅱ)species.Moreover,the carbonyl oxygen and phenolic hydroxyl oxygen on the substrate can act as direct group and further promote the progress of the reaction.Different from the traditional SaegusaIto oxidation reaction mechanism,the calculation results showed that the reaction has undergone a reduction and elimination process and relies on the assistance of acetic acid.2.Theoretical study of phosphine-catalyzed[8+2]cycloaddition reactionIn order to explore the sequence of the phosphine-catalyzed electrophilic coupling reaction,the DFT method was used to carry out theoretical calculation studies of the[8+2]cycloaddition reaction of heptafulvenes and allenoates catalyzed by trimethylphosphine.There are two possible paths for the reaction,which are initiated by the combination of heptafulvenes and allenoate with phosphine catalyst.The comparism between the calculation results of these two reaction paths showed that due to its strong electrophilicity,the combination between the heptafulvenes and the phosphine catalysts is dynamically and thermodynamically more favorable than allenoates.However,the stable intermediate lead to weak nucleophilicity and difficulty to be attacked by the allenoate substrate.Therefore,heptafulvene reactant should dissociate to release the active phosphine catalyst for nucleophilic attack with allenoate reactant The energy and structure analysis of the different conformations of the key intermediates showed that the interaction of oxygen and phosphorus on the carbonyl group in the intermediates of the favorable path is the key to stabilizing the intermediates.Subsequent Non-covalent interaction(NCI)analysis and Atoms in molecules(AIM)analysis further confirmed the same conclusion.Since the zwitterionic intermediate is obtained during the reaction,the solvent will also also have a certain influence on the reaction.Therefore,the influence of real solvent molecules is simulated by adding methanol molecules around the reaction system.The results showed that methanol solvent can form hydrogen bonds with the oxygen on the barbiturate radical of the substrate,leading to excessive stability,which suppresses the subsequent reactions.When using dicyano substituted methylene cycloheptatriene as a substrate,the obtained intermediate is too stable,so the target product cannot be obtained through the subsequent process.3.Theoretical Study on Rhodium-catalyzed Amination and Cyclization of EnyneThe DFT method was adopted to study the rhodium-catalyzed[3+2]cyclization reaction of secondary amines and arylalkenynes.Calculations have found that although there is a certain steric hindrance between the phosphine ligand in the catalyst and the substrate,the subsequent reaction will be difficult if it dissociates.In addition,we calculated multiple paths to activate the terminal alkyne C-H bonds and found that direct hydrogen transfer is very difficult,and the activation energy is all higher than 50 kcal·mol-1.The hydrogen transfer process assisted by oxygen on the ligand can effectively reduce the activation energy of the reaction.The subsequent hydrogen transfer process of the β-H elimination process of the four-membered ring rhodium species requires the participation of ligands.