Density functional theory（DFT） method was used to explore the origin of the regioselectivity of Cocatalyzed hydroacylation of 1,3-dienes.The reaction of 2-methyl-1,3-butadiene and benzaldehyde with1,3-bis（diphenylphosphino）propane ligand was chosen as the model reaction.The energies of the intermediates and transition states in the stages of oxidative cyclization,β-H elimination and C-H reductive elimination were investigated.Computational results show that β-H elimination is the ratedetermining step for the whole catalytic cycle.C1-Selective oxidative cyclization is favored over C4-selective oxidative cyclization.Besides.C4-selective oxidative cyclization is kinetically disfavored than all the steps in C1-hydroacylation mechanisms,consistent with the experimentally obtained C1-selective hydroacylation products.Analyzing the reason for such observation,we suggest that both electronic and steric effects contribute to the C1-selectivity.On the electronic aspect,C1 is more electron rich than C4 due to the methyl group on C2,which makes the electrophilic attack of aldehyde carbon on C1 more favorable.On the steric aspect,the methyl group locates farther from the ligands in the transition state of C1-selective oxidative cyclization than in that of C4-selective oxidative cyclization.
As the rate-determining step in native chemical ligation reactions, the thiol–thioester exchange step is important in determining the efficiency of the ligations of peptides. In the present study, systematic theoretical calculations were carried out on the relationships between the structure of different thioesters and the free energy barriers of the thiol–thioester exchange step. According to the calculation results, the thiol–thioester exchange step is disfavored by the steric hindrance around the carbonyl center, while the electronic effect（i.e. conjugation and hyper-conjugation effects） becomes important when the steric hindrance is insignificant.
Trifluoromethylation reactions are important transformations in the research and development of drugs, agrochemicals and functional materials. An oxidation/reduction process of trifluoromethyl-containing compounds is thought to be involved in many recently tested catalytic trifluoromethylation reactions. To provide helpful physical chemical data for mechanistic studies on trifluoromethylation reactions, the redox potentials of a variety of trifluoromethyl-containing compounds and trifluoro- methylated radicals were studied by quantum-chemical methods. First, eoB97X-D was found to be a reliable method in predicting the ionization potentials, electron affinities, bond dissociation enthalpies and redox potentials of trifluoromethylcontaining compounds. One-electron absolute redox potentials of 79 trifluoromethyl substrates and 107 trifluoromethylated radicals in acetonitrile were then calculated with this method. The theoretical results were found to be helpful for interpreting experimental observations such as the relative reaction efficiency of different trifluoromethylation reagents. Finally, the bond dissociation free energies （BDFE） of various compounds were found to have a good linear relationship with the related bond dissociation enthalpies （BDE）. Based on this observation, a convenient method was proposed to predict one-electron redox potentials of neutral molecules.
A theoretical study is carried out on Gaunt＇s palladium-catalyzed selective C（sp3）-H activation of unprotected aliphatic amines. In this reaction, the methyl group is proposed to be activated through a four-membered cyclometallation pathway even though an ethyl group is present in the substrate. Our calculation shows that the methyl and ethyl activation processes proceed in nitrogen-atom-directed pathway rather than carbonyl-directed one. More important, methyl activation is more favorable than ethyl activation with nitrogen atom as the directing group. Further studies on the structural parameters show that the lactone structure in cyclic substrate is the origin of the selective methyl activation. When the lactone moiety is changed to ketone, ether or alkyl, the selectivity could be reversed so that the ethyl activation becomes more favorable. This result validates the pro- oosal that lactone structure is key to selective methyl activation.
