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

  • Caihua ZhouEmail author
  • Tao Yang
  • Guang Fan
Regular Article


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.


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



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).


  1. 1.
    Raub S, Jansen G (2001) A quantitative measure of bond polarity from the electron localization function and the theory of atoms in molecules. Theor Chem Acc 106:223–232CrossRefGoogle Scholar
  2. 2.
    Berski S, Durlak P (2016) The mechanism of Claisen rearrangement of allyl phenyl ether from the perspective of topological analysis of the ELF. New J Chem 40:8717–8726CrossRefGoogle Scholar
  3. 3.
    Pérez P, Domingo LR (2015) A DFT study of inter- and intramolecular Aryne Ene reactions. Eur J Org Chem 2015:2826–2834CrossRefGoogle Scholar
  4. 4.
    Domingo LR, Ríos-Gutiérrez M, Chamorro E, Pérez P (2016) Aromaticity in pericyclic transition state structures a critical rationalization based on the topological analysis of electron density. Chem Sel 1(18):6026–6039Google Scholar
  5. 5.
    Arroniz C, Denis JG, Ironmonger A, Rassias G, Larrosa I (2014) An organic cation as a silver(I) analogue for the arylation of sp 2 and sp 3 C–H bonds with iodoarenes. Chem Sci 5:3509–3514CrossRefGoogle Scholar
  6. 6.
    Weibel JM, Blanc A, Pale P (2008) Ag-mediated reactions: coupling and heterocyclization reactions. Chem Rev 108:3149–3173CrossRefGoogle Scholar
  7. 7.
    Xu Y, Young MC, Wang C-P, Magness DM, Dong GB (2016) Catalytic C(sp 3)–H arylation of free primary amines with an exo directing group generated in situ. Angew Chem Int Ed Engl 55:9084–9087CrossRefGoogle Scholar
  8. 8.
    Dydio P, Reek JNH (2014) Supramolecular control of selectivity in transition metal catalysis through substrate preorganization. Chem Sci 5:2135–2145CrossRefGoogle Scholar
  9. 9.
    Mo F, Dong G (2014) Regioselective ketone α-alkylation with simple olefins via dual activation. Science 345:68–72CrossRefGoogle Scholar
  10. 10.
    Li S, Chen G, Feng CG, Gong W, Yu JQ (2014) Ligand-enabled γ-C–H olefination and carbonylation: construction of β-quaternary carbon centers. J Am Chem Soc 136:5267–5270CrossRefGoogle Scholar
  11. 11.
    Zhang FL, Hong K, Li TJ, Park H, Yu JQ (2016) Functionalization of C(sp 3)–H bonds using a transient directing group. Science 351:252–256CrossRefGoogle Scholar
  12. 12.
    Xiao KJ, Lin DW, Miura M et al (2014) Palladium (II)-catalyzed enantioselective C(sp 3)–H activation using a chiral hydroxamic acid ligand. J Am Chem Soc 136:8138–8142CrossRefGoogle Scholar
  13. 13.
    Li S-H, Zhu R-Y, Xiao K-J, Yu J-Q (2016) Ligand-enabled arylation of γ-C–H bonds. Angew Chem Int Ed 55:4317–4321CrossRefGoogle Scholar
  14. 14.
    Chan KS, Wasa M, Chu L, Laforteza BN, Miura M, Yu J-Q (2014) Ligand-enabled cross-coupling of C(sp 3)–H bonds with arylboron reagents via Pd(II)/Pd(0) catalysis. Nat Chem 6:146–150CrossRefGoogle Scholar
  15. 15.
    Chan KS, Fu HY, Yu J-Q (2015) Palladium(II)-catalyzed highly enantioselective C–H arylation of cyclo-propylmethylamines. J Am Chem Soc 137:2042–2046CrossRefGoogle Scholar
  16. 16.
    Wu YW, Chen YQ, Liu T, Eastgate MD, Yu J-Q (2016) Pd-catalyzed γ-C(sp 3)–H arylation of free amines using a transient directing group. J Am Chem Soc 138:14554–14557CrossRefGoogle Scholar
  17. 17.
    Chu L, Xiao K-J, Yu J-Q (2014) Room-tempeature enantioselective C–H iodination via kinetic resolution. Science 346:451–455CrossRefGoogle Scholar
  18. 18.
    Dang YF, Qu SL, Tao Y, Deng X, Wang ZX (2015) Mechanistic insight into ketone α-alkylation with unactivated Olefins via C–H activation promoted by metal–organic cooperative catalysis (MOCC): enriching the MOCC chemistry. J Am Chem Soc 137:6279–6291CrossRefGoogle Scholar
  19. 19.
    Yang K, Li Q, Liu YB, Li GG, Ge HB (2016) Catalytic C–H arylation of aliphatic aldehydes enabled by a transient ligand. J Am Chem Soc 138:12775–12778CrossRefGoogle Scholar
  20. 20.
    Liu Y-B, Ge H-B (2017) Site-selective C–H arylation of primary aliphatic amines enabled by a catalytic transient directing group. Nat Chem 9:26–32CrossRefGoogle Scholar
  21. 21.
    Frisch MJ et al (2009) Gaussian 09, Revision E.01. Gaussian Inc., WallingfordGoogle Scholar
  22. 22.
    Becke AD (1993) Density-functional thermochemistry. III. The role of exact exchange. J Chem Phys 98:5648–5652CrossRefGoogle Scholar
  23. 23.
    Martin F, Zipse H (2005) Charge distribution in the water molecule—a comparison of methods. J Comput Chem 26:97–105CrossRefGoogle Scholar
  24. 24.
    Zhao Y, Truhlar DG (2008) The M06 suite of density functionals for main group thermochemistry, thermochemical kinetics, noncovalent interactions, excited states, and transition elements: two new functionals and systematic testing of four M06-class functionals and 12 other functionals. Theor Chem Acc 120:215–241CrossRefGoogle Scholar
  25. 25.
    Marenich AV, Cramer CJ, Truhlar DG (2009) Universal solvation model based on solute electron density and on a continuum model of the solvent defined by the bulk dielectric constant and atomic surface tensions. J Phys Chem B 113:6378–6396CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Chemistry and Chemical EngineeringXianyang Normal UniversityXianyangChina
  2. 2.Materials of Physics, School of ScienceXi’an Jiaotong UniversityXi’anChina

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