Mechanistic Insights On The Metal-free Lewis Acid-catalyzed Activation And Functionalization Of H-H,C-N And C-H Bonds

Chemical reaction is a process in which a covalent or ionic bond is formed or broken.The inert chemical bonds can be cleaved mediated by a catalyst in many reactions.The activation and functionalization of inert chemical bonds provides a direct way for synthesis of high-value compounds.In the past several decades,metal catalyzed activation of chemical bonds have achieved important progresses.However,these metals are always precious,toxic and difficult to remove from the end products.Many efforts have been made to develop metal-free catalysts that can mimic metallic systems.Improving the catalytic activity of the metal-free catalysts is the focal point in the research field of the metal-free catalyzed reaction.Thus,people need to understand the detailed mechanism of the metal-free catalyzed reaction for optimizing the reaction conditions and designing new metal-free catalyzed reaction.Theoretical chemistry has proven to be an important tool for studying various chemical reactions.Density functional theory is a cost-effective theoretical method for providing reasonably accurate results.So we carried out quantum chemical calculations to investigate various aspects of Lewis acid catalyzed activation reactions of chemical bonds.Our calculation results reported herein provide explanations of selectivity,elucidations of mechanisms,and predictions of reactivity that will continually advance the scientific community in future endeavors,especially in the field of organic chemistry.In chapter 3,we report the reaction mechanism for the full hydrogenation of 2-phenyl-6-methyl-pyridine catalyzed by the Lewis acid C6F5(CH2)2B(C6F5)2.Our calculations show that a plausible reaction pathway of the hydrogenation of pyridine contains five stages:(1)The generation of a new borane C6F5(CH2)2B(C6F5)2 from the hydroboration of the alkene,which forms a frustrated Lewis pair(FLP)with a pyridine;(2)The activation of H2 by FLP to yield an ion pair intermediate;(3)Intramolecular hydride transfer from the boron atom to the pyridinium cation in the ion pair intermediate to produce the 1,4-dihydropyridine;(4)Hydrogenation of the 1,4-dihydropyridine by the FLP to form the 1,4,5,6-tetrahydropyridine;(5)Hydrogenation of the 1,4,5,6-tetrahydropyridine by the FLP to yield the final piperidine.The last two hydrogenation processes follow the similar pathway,which include four steps:(a)Proton transfer from the pyridinium moiety to the substrate;(b)Dissociation of the newly generated pyridine;(c)Hydride migration from the hydridoborate moiety to the protonated substrate to produce the hydrogenated product;(d)Release of the hydrogenated product to regenerate the free borane.The full hydrogenation of pyridine is calculated to be exothermic by 16.9 kcal/mol,relative to the starting reactants.The rate-limiting step is the proton transfer in the second hydrogenation step,with a free energy barrier of 28.2 kcal/mol in gas phase(27.9 kcal/mol in toluene)at room temperature and 1.0 atm.Our results can account for the observed experimental facts.Chapter 4 describes the mechanism of the intramolecular addition of X-CN(X=N,O)bonds to alkenes catalyzed by the Lewis acid B(C6Fs)3.For the intramolecular addition of N-CN bonds to alkenes catalyzed by the Lewis acid B(C6F5)3,our studies suggest that this addition process proceeds in a novel mechanism,in which an asynchronous and concerted transition state is involved.The free energy barrier of this addition process is 29.1 kcal/mol.This Lewis acid promoted intramolecular alkene addition reaction will be effective if the substrate consists of a strong electron-withdrawing group at the nitrogen atom and a strong electron-donating group on the alkene moiety,and a strong Lewis acid is used.For the intramolecular addition of O-CN bonds to alkenes catalyzed by the Lewis acid B(C6Fs)3,our calculations show that the reaction may proceed in two competing pathways.One pathway is concerted and asynchronous,which is similar to that of the intramolecular addition of the N-CN bond to alkene,with a free energy barrier of 23.9 kcal/mol in tetrahydrofuran.The other pathway is a stepwise process involving a seven-membered ring intermediate,with a free energy barrier of 25.1 kcal/mol in tetrahydrofuran.Chapter 5 reports the mechanism of the C-H bond activation and functionalization of toluene mediated by a hypervalent iodine compound.Our calculations suggest that the first step of the C-H bond activation is the substitution of hydroxyl group and tosyloxyl group with TfOH to generate a new hypervalent iodine compound.Then partial transfer of electrons(0.359 e)from the toluene to the hypervalent iodine moiety occurs in the charge-transfer complex,leading to the activation of the C-H bond at the para position of toluene.Subsequently,the C-H bond of toluene is activated by the hypervalent iodine center with the assistance of the triflate anion.The related free energy barrier is only 19.6 kcal/mol,which is consistent with the observed experimental facts.This mechanism can be considered as the concerted iodination/deprotonation(CID)mechanism.Thus the hypervalent iodine compound induced C-H bond activation of arenes occurs via a charge transfer-induced bond activation mechanism.Our calculations demonstrate that the efficacy of the C-H bond of toluene would be optimal if a strong Br(?)nsted acid is used.In addition,we found that the hypervalent bromine compound induced functionalization of arenes proceeds by a single-electron-transfer(SET)mechanism.Based on the studies above,we also designed two functionalization reactions of the C-H bonds,in which the transformation of C-H bonds to C-N and C-C bonds are achieved,with a free energy barrier of 25.1 and 30.1 kcal/mol,respectively.Our calculations provide important theoretical guidance for designing hypervalent iodine regent catalyzed cross-coupling of arenes.