The Mechanism Investigation Of Fe-catalyzed Cross-coupling Reactions

The application of the transition metal catalysts in the the cross coupling reactions greatly promoted the development of organic synthesis reactions, which can effectively build the C-C, C-X(X=heteroatom) bonds. Now, transition metal catalysts including Pd, Ni, Au, Pt, Rh complexes are used broadly, but they have many disadvantages, such as expensive, difficult to obtain, great damage to the environment and so on. However, iron catalysts have lower price, easy to obtain, environmental friendly and convenient post-processing, so they have paid more attention by synthetic chemists. In recent years, the high efficiency and broad applicability of iron catalysts had gradually proved and recognised. However, the theoretical study of the iron-catalyzed reaction mechanism is few. In this thesis, we selected three cross coupling reactions including the formations of C-C bond and C-N bond. All the intermediates and transition states of the possible reaction paths were optimized completely using Density Functional Theory(DFT) with the B3 LYP hybrid functional following the frequencies analysis. The geometries of some key transition states were comfirmed using the IRC scanning. The mechanism was obtained through analyzing the energy barrier among the different paths. The solvation effect was calculated using the C-PCM polarizable conductor calculation model in this thesis.Main works included:1.The theoretical study of the mechanisms of iron-catalyzed intramolecular C-H bond amination to form C-N bond.The reaction mechanisms of iron(II) bromide catalyzed intramolecular C-H bond amination [1,2]-shift tandem reactions of aryl azides were thoroughly investigated using DFT calculations with B3 LYP method. The tandem reaction is to produce P1 and P2 from R1. Two different mechanisms were studied. One was named as Cycle A which did not pass through the middle product P1, and another was named as Cycle B which passed through the middle product P1. The rate-limiting step forboth mechanisms was the [1,2]-shift process. Our results showed that the mechanism of Cycle B is favored over that of Cycle A, where the energy barrier for the rate-limiting step of the former is 28.7 kcal/mol and that of the latter is 36.6 kcal/mol.The overall catalytic mechanism of the favored Cycle B includes the following basic steps:(I) extrusion of N2 to form iron nitrene;(II) C-H bond amination;(III)formation of the middle product P1;(IV) iminium ion formation;(V) [1,2]-shift process; and(VI) formation of indole P2. Our calculated results also indicated that the transferring preference for the [1,2]-shift component of the tandem reaction is methyl< ethyl.2.The theoretical study of the mechanism of iron-catalyzed biaryl cross-coupling of aryl Grignard reagentsThe reaction mechanisms of the [Fe(Mg Br)2] catalyzed cross-coupling reaction between ortho-chlorostyrene and phenylmagnesium chloride to form biaryl were studied using density functional theory(DFT) calculations. Two mechanisms were investigated. Cycle A included three basic steps:(I) oxidation of [Fe(Mg Br)2] to obtain [Ar-Fe(Mg Br)],(II) addition to yield [Ar-(Phenyl)-Fe(Mg Br)2], and(III)reductive elimination to return to [Fe(Mg Br)2]. Cycle B did not form [Ar-Fe(Mg Br)].In the first step, phenylmagnesium bromide attacks the intermediate of the oxidative addition directly before [Cl-Mg-Br] dissociates to form [Ar-Fe(Mg Br)]. The catalytic Cycle B is favored over the catalytic Cycle A when considering the solvent effect.The rate-limiting step in the whole catalytic cycles for both Cycle A and Cycle B is the reductive elimination of [Ar-(phenyl)-Fe(Mg Br)2] to regenerate the catalyst[Fe(Mg Br)2], where the Gibbs free energy in solvent THF ?Gsol is 82.98 k J?mol-1using the conductor polarized continuum model(CPCM)method.3. The theoretical study of the mechanism of iron-catalyzed direct arylation to form biarylThe reaction mechanisms of the [Fe(OAc)2] catalyzed cross-coupling reaction between iodobenzene and benzene to form biaryl were investigated using density functional theory(DFT) calculations.Three mechanisms were studied. One was theradical mechnism, the second was the single electron transfer mechanism, the third one was oxidation addition. The calculated results showed that the radical mechnism was formed, where the energy barrier for the rate-limiting step was 14.11kcal/mol.