Theoretical studies on a number of novel C–B and C–C bond formation reactions are reported in this thesis.

Part I: Reactions of the lithium boryl, LiB(R'NCH=CHNR') (R' = 2,6-ⁱPr₂C₆H₃), with organohalides (RX) giving RB(R'NCH=CHNR') and/or XB(R'NCH=CHNR') were studied computationally using DFT calculations at the B3LYP level. Our calculations indicate that the boryl anion in the lithium boryl can undergo nucleophilic attack at an organohalide on the halide-bonded carbon atom and/or the halogen atom to form RB(MeNCH=CHNMe) (an expected S_N2 substitution product) and/or XB(MeNCH=CHNMe) (a halogen-abstraction product), respectively. Our calculation results show that an organohalide having a halogen with lower electronegativity and higher ability to engage in hypervalent bonding prom...[ Read more ]

Theoretical studies on a number of novel C–B and C–C bond formation reactions are reported in this thesis.

Part I: Reactions of the lithium boryl, LiB(R'NCH=CHNR') (R' = 2,6-ⁱPr₂C₆H₃), with organohalides (RX) giving RB(R'NCH=CHNR') and/or XB(R'NCH=CHNR') were studied computationally using DFT calculations at the B3LYP level. Our calculations indicate that the boryl anion in the lithium boryl can undergo nucleophilic attack at an organohalide on the halide-bonded carbon atom and/or the halogen atom to form RB(MeNCH=CHNMe) (an expected S_N2 substitution product) and/or XB(MeNCH=CHNMe) (a halogen-abstraction product), respectively. Our calculation results show that an organohalide having a halogen with lower electronegativity and higher ability to engage in hypervalent bonding promotes the halogen abstraction pathway. Benzyl halides were also found to promote the halogen abstraction pathway due to conjugation effects which stabilize a benzyl anion in the transition state during the halogen abstraction process.

Part II: Iridium-catalyzed C–H borylation is an attractive method for functionalization of arenes and heteroarenes. While steric effects are clearly dominant, regioselectivity arising from electronic effects cannot be ignored. DFT calculations of the pK_a values for various C–H bonds show a good correlation of the pK_a values with the observed regioselectivity in the C–H borylation reactions of a number of substituted quinolines and unsymmetrical 1,2-disubstituted benzenes. The correlation suggests that the iridium-catalyzed C–H borylation reactions proceeded through an σ-bond metathesis mechanism in which the boryl ligands in Ir–boryl intermediates deprotonate the substrates.

Part III: The reaction mechanism for the borylation of unactivated alkyl halides catalyzed by nickel complexes, in which the reaction rates of different alkyl bromides follow the order of tertiary > secondary > primary, has been studied using DFT calculations at the B3LYP level. The results of our DFT calculations support a Ni(I)/Ni(III) catalytic cycle which involves four fundamental steps, namely transmetallation, atom transfer, radical attack and reductive elimination. The atom transfer and radical attack steps together can be viewed as the oxidative addition process. The results indicate that the oxidative addition process is rate-determining. The order of relative reaction rates (tertiary > secondary > primary) involved in the borylation reactions is related to the relative stability of the alkyl radicals generated in the atom transfer.

Part IV: Using DFT calculations at the B3LYP level, we calculated the Ni(I)/Ni(III) catalytic cycle for the nickel-catalyzed alkyl–alkyl cross-couplings of unactivated alkyl halides, in which the experimentally observed reaction rates of different alkyl bromides follow the order of primary > secondary >> tertiary. The calculation results indicate that the reductive elimination process is rate-determining. It was found that the inaccessibility of the alkyl–alkyl cross-coupling reactions for unactivated tertiary alkyl halides is due to the extremely high reductive elimination barrier. We proposed on the basis of our calculations that the high reductive elimination barrier can be lowered by employing “push-pull” bidentate ligands and electron-withdrawing olefin additives.

Part V: The reaction mechanism for the palladium-catalyzed competitive cross-coupling reaction of benzyl versus phenyl bromide with a vinylstannane reagent, resulting in the selective coupling of benzyl bromide, was studied using DFT calculations at the B3LYP level. The calculations indicate that a Pd(II)/Pd(IV) catalytic cycle is involved in the selective coupling of benzyl bromide. The Pd(II)/Pd(IV) cycle for the reaction consists of three fundamental steps, namely transmetallation, oxidative addition and reductive elimination. The oxidative addition is the rate-determining step. The selectivity of benzyl bromide over phenyl bromide involved in the cross-coupling reaction is related to that a benzyl ligand has stronger electron-releasing ability than a phenyl ligand, which stabilizes the Pd(IV) intermediate formed after oxidative addition more significantly.

The successful application of modern computational techniques to understand chemistry has been demonstrated. Through the theoretical studies, the reaction mechanisms of a number of C–B and C–C bond formation reactions are understood. Furthermore, studies of reaction mechanisms are important in designing better and effective catalysts, and selecting appropriate substrates.