Mechanistic Investigation On Transition Metal Mediated C-S/C-C Bond Activation And Transformation

Transition metal mediated C-S/C-C bond activation and transformation have received increasing attention in the past century,and show great utility in organic synthesis,pharmaceutical chemistry and bio-chemistry.In this area,despite of the encouraging experimental success,many mechanistic details,especially the structure and physico-chemical property/reactivity relationship,the detailed energy/electron transformation and the origin of the selectivity,are still obscure.The recent development of quantum chemistry calculation sheds light on this problem.Motivated by the aforementioned mechanistic ambiguity,we carried out systematic study with the aid of density functional theory(DFT)calculations.The key research contents are as follows:Chapter 1 gives the brief introduction,and Chapter 2 mainly reviews the widely used theoretical methods,the basic concept of quantum chemistry and the photocatalysis mechanism.Chapters 3 to 7 describe the research topics accomplished in my PhD studies:In Chapters 3 and 4,given that the lack of experimental data of the physico-chemical property of organosulfur compounds,efforts were first put in the examination of different DFT methods and basis sets.On this basis,the prediction of the pKa values of 290 thiols and the bond dissociation energy(BDE)of 54 disulfides were conducted with the recommended method.Furthermore,the structure-reactivity relationship of these sulfur-involved compounds were also analyzed.In Chapter 5,we mainly focused on firstly presented Pd-catalyzed C-S/C-H coupling of azoles with aryl thioethers,the most feasible catalytic cycle was proposed with the aid of B3LYP method.The coupling consists of aromatic C-S bond activation,NaO'Bu mediated C-H palladation,and reductive elimination.Analyzing the origin of chemoselectivity,we found that the easiness of Pd catalyzed C-S activation is independent of the C-S bond strengths in the thioether substrates.By contrast,the d-?*back-donation in CAr-Pd-S intermediates is the main driving force for the favorable CAr-S activation(over the Calkyi-S activation).Inspired by rapid development of environment-friendly photocatalysis,we selected the outstanding researches on C-C bond activation(especially the photocycloaddition)as our target reaction.In Chapter 6,we mainly focused on the recent dioxygen-mediated,Cr complex catalyzed photoredox Diels-Alder reaction between two electron-rich substrates,which represents the first example of first-row transition metal photocatalysis.Systematic density functional theory(DFT)calculations were performed.The calculation results show that O2 shuttles an electron via the inner-sphere mechanism(in the form of[Cr-O2]complexes)during the photoredox catalytic cycle.Meanwhile,the overall transformations involve the excitation&quench of Cr complex,single electron oxidation,asynchronous cycloaddition,and single electron reduction(instead of superoxide proposed by experimental research).On this basis,the origin of the chemo-,regio-and stereo-selectivity have been identified.Moreover,the low energy barrier of the[2+2]dimerization of the dienophiles indicates the plausibility of such transformations.In Chapter 7,we mainly focused on the recent thioxanthone sensitizer catalyzed intermolecular[2+2]cycloaddition induced by visible light irradiation.The catalytic mode of photosensitizer(energy transfer,bi-electron exchange and hydrogen transfer are all possible mechanisms)was analyzed with the aid of DFT methods.The results indicate that the energy transfer pathway is more favorable than the bi-electron exchange and the hydrogen transfer pathways.Meanwhile,the overall transformations involve the complexation&excitation of photosensitizer,the first C-C bond formation,the dissociation of the sensitizer,triplet to singlet electronic state crossing and the second C-C bond formation.Herein,synergistic energy&electron transfer from photosensitizer to substrate moieties takes place along the first C-C bond formation process.On this basis,the effect of olefin substrates on the stereoselectivity was finally analyzed.The aforementioned researches were conducted with DFT calculations based on the previous experimental study.The calculation results show good correlations with the experimental observations.These research works not only supplement the lack of experimental data,but also illustrate inherent rutines behind the experimental observations(such as the optimized structure parameters and energetics of intemediates and transition states,and the origin of high reactivity and selectivity).We hope the provided insights could benefit the deep understanding of transiton metal catalysed C-S and C-C bond activation/transformation and the development of new catalyst and synthetic strategies.