| Theoretical studies of Cu(I and II)-catalyzed synthesis of cyclic alkenyl ethers from O-alkynylbenzaldehydes, CuBr-catalyzed synthesis of highly substituted furans from2-(1-alkynyl)-2-alken-l-ones and CuBr-catalyzed synthesis of ring-fused indoles from N-(o-alkynylphenyl)imines were investigated using density functional theory done at the BhandHLYP level. The important factors affectting the reaction mechanisms were explored in detail, including the functions of transition metal Cu catalyst, the roles of solvent DMF and the effect of metallic valence of copper on the selectivity and yield of reaction. All the conclusions we have obtained can afford a better idea for the design of more effective catalyst in transition metal catalyst system.1. DFT study on the mechanisms of Cu(â… and â…¡)-catalyzed cyclization of O-alkynylbenzaldehydes:the crucial factors to affect the reaction mechanismThe mechanisms of Cu(â… and â…¡)-catalyzed synthesis of cyclic alkenyl ethers from O-alkynylbenzaldehydes with nucleophile (MeOH) were investigated using density functional theory computations done at the BhandHLYP/6-31G*(LANL2DZ for Cu) level. The theoretical study reveals that the two main processes, cycloaddition and hydrogen-transfer, are included in all possible reaction pathways. Our calculation results suggested that a) CuCl serves as a metal catalyst to lower significantly the free energy barrier and promote the intramolecular cycloaddition reaction, b) The solvent DMF is critical in a stepwise proton-transport process involved in the intermolecular nucleophilic addition reaction because it acts as a proton shuttle to lower the activation free energy barrier of the hydrogen-transfer process. In addition, we found that the substrate MeOH also plays the similar role in the proton-transport catalysis strategy. c) Cyclic alkenyl ethers is synthesized selectively in catalytic system consisting of CuCl and DMF, whereas the combination of CuCl1and DMF loses the selectivity for the synthesis of cyclic alkenyl ethers P1and gives the products P1and P2in1:1ratio. Our theoretical calculations reproduce the experimental results very well. The theoretical discovery of the role of DMF and MeOH in the hydrogen shift process suggests that a transition metal-catalyzed reaction involving a similar hydrogen shift step can be accelerated when solvent with the nature of Lewis base is used. The present study is expected to help ones understand other Cu(I and II)-catalyzed reactions involving Lewis base solvents and to give guidance for future design of new catalysts and new reactions.2. Study on the mechanisms of CuBr-catalyzed synthesis of highly substituted furans from2-(1-alkynyl)-2-aIken-l-onesA computational study with the BhandHLYP density functional was carried out to elucidate the mechanisms of the CuBr-catalyzed synthesis of highly substituted furans from2-(1-alkynyl)-2-alken-l-ones with nucleophile MeOH in DMF medium. Our calculations confirmed that the combination between metal catalyst CuBr and solvent DMF can give a good result for the synthesis of highly substituted furans. Calculations reveal the following two issues:a) In intramolecular cycloaddition, the metal catalyst CuBr plays an extremely important role, which can greatly reduce the energy barrier of the reaction and promote the reaction to proceed. b) In the stepwise hydrogen-transfer process, solvent DMF acts as a proton shuttle to significantly lower the activation energy barrier of this reaction. Therefore, it is critical in this proton-transport process. In addition, our theoretical study predicts that the activation energy of the rate-determining step is reduced by7.4kJ/mol when the high metal valence CuBr2is used. This suggests that the high metal valence Cu in catalyst has a stronger catalytic activity than its low metal valence in DMF medium, In short, theoretical discovery of the role of the metal catalyst CuBr and DMF in the synthesis of highly substituted furans suggests that the metal catalyst CuBr (and CuBr2) and DMF can be combined into a new catalytic system to accelerate the reaction. This means that other metal catalyst and solvent with the nature of Lewis base can also be combined to drive the reaction involving a similar hydrogen shift step. The present study will also be helpful in understanding other Cu-catalyzed reaction and to give suggestion for future design of new catalysts or catalytic systems and new reactions.3. Theoretical study on the mechanisms of CuBr-catalyzed synthesis of ring-fused indoles from N-(0-alkynylphenyl)imines: the roles of transition metallic catalyst CuBr and solvent DMFTheoretical study on the mechanisms of CuBr-catalyzed synthesis of ring-fused indoles from N-(o-alkynylphenyl)imines was investigated using density functional theory computations done at the BhandHLYP level. The theoretical study reveals that the two main processes, cycloaddition of the C2and N1atoms and two-step hydrogen-transfer assisted by DMF, are included in the optimal reaction pathway. CuBr plays an important role in the cycloaddition. The reaction can be carried out smoothly because of its present. In addition, our calculations showed that solvent DMF molecules are critical in the two-step proton-transport process involved in the cycloaddition of the01and C4. They can serve as proton shuttle to assist hydrogen-transfer from01to C1. This means that in catalytic reactions, solvents with the nature of lewis base and transition metallic catalysts can be combined into a new catalytic system to effectively promote reaction. |
