Mechanism analysis of transient ligand-induced β-C–H arylation of α-methyl pentanone

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Based on a comprehensive DFT mechanism study, the reaction characteristics of β-C–H arylation of α-methyl pentanone with iodobenzene are revealed. In this reaction, glycine plays an important role as organic transient ligand, which can directly activate β-C–H of α-methyl pentanone together with metal Pd(II). And in the whole reaction, the formation of N=C bond during the condensation of pentanone and glycine and the breaking of N=C bond are two rate-determining steps. The energy barrier of TS4 and TS23 is 57.5 kcal/mol and 41.9 kcal/mol, respectively, which is higher than other transition states. Correspondingly, metal Pd(II) still is a wonderful catalyst in this reaction, which can flexibly coordinate with nonmetal atom (N, O, C) and form different inorganic metal intermediates. And these inorganic metal intermediates have significant function in further decreasing reaction energy barrier and inducing the formation of β-C–H arylation.

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This project was supported by the Science Foundation of Shaan’xi Province (No. 2018JM2033), Shaan’xi Provincial Education Department Project (No. 18JK0836), Undergraduate Training Programs for Innovation (No. 201828004) and the Teaching Reform Project (No. 2017Y007).

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Correspondence to Caihua Zhou.

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Zhou, C., Yang, T. & Fan, G. Mechanism analysis of transient ligand-induced β-C–H arylation of α-methyl pentanone. Theor Chem Acc 139, 10 (2020).

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  • Transient ligand
  • Density functional theory
  • Reaction mechanism
  • β-C–H arylation