Acta Physico-Chimica Sinica ›› 2019, Vol. 35 ›› Issue (9): 940-953.doi: 10.3866/PKU.WHXB201810052

Special Issue: C–H Activation

• Review • Previous Articles     Next Articles

Theoretical Advances of Transition Metals Mediated C―H Bonds Cleavage

Chunhui SHAN1,*(),Ruopeng BAI2,Yu LAN2,3,*()   

  1. 1 Postdoctoral Station of Biomedical Engineering, Chongqing University, Chongqing 401331, P. R. China
    2 School of Chemistry and Chemical Engineering, and Chongqing Key Laboratory of Theoretical and Computational Chemistry, Chongqing University, Chongqing 401331, P. R. China
    3 College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450001, P. R. China
  • Received:2018-10-23 Accepted:2018-11-21 Published:2018-11-27
  • Contact: Chunhui SHAN,Yu LAN;
  • Supported by:
    The project was supported by the National Natural Science Foundation of China(21822303);The project was supported by the National Natural Science Foundation of China(21772020);Fundamental Research Funds for the Central Universities, China (Chongqing University)(2018CDXZ0002);Fundamental Research Funds for the Central Universities, China (Chongqing University)(2018CDPTCG0001/4);Chongqing Postdoctoral Science Special Foundation, China(XmT2018085)


Transition-metal-catalyzed C―H bond activation, which has been widely applied to construct new covalent bonds, has emerged as one of the most effective strategies in synthetic chemistry due to atom economy and simple procedure. In this review, we have summarized the recent reports on the theoretical mechanistic study of transition-metal-catalyzed C―H bond cleavage. Based on these comprehensive theoretical studies, we have systematically discussed the general modes of C―H bond activation, which involves oxidative addition, base-assisted deprotonation, σ-metathesis, Friedel-Crafts-type electrophilic aromatic substitution, α- or β-hydrogen elimination, and hydrogen atom abstraction. From a mechanistic point of view, C―H bond activation by oxidative addition generally involves a zero-valent transition metal catalyst with strong reducibility, which requires a low activation barrier. The concerted metalation-deprotonation (CMD)-type C―H bond cleavage often occurs via a six-membered cyclic transition state using transition metal carboxylate as the catalyst with a directing group, which is a common mechanism for transition metals with high oxidation states. Base-assisted internal electrophilic substitution (BIES)-type C―H bond activation is commonly performed in the presence of cationic transition metal catalysts, in which electron-rich arenes react preferentially compared to electron-deficient arenes. In some other cases, outer-sphere base-assisted deprotonation can also result in C―H activation, which is dependent on the strength of the base used. The stronger the base used, the lower the energy barrier, and thus, the easier it is to protonate. The σ-metathesis pathway, which could occur via a four-membered cyclic transition state, is often considered an alternative for concerted metalation-deprotonation. If the aromatic hydrocarbon is attacked by electrophiles, the C―H bond can be activated by Friedel-Crafts-type electrophilic aromatic substitution. Elimination of α- or β-hydrogen is also frequently proposed for transition-metal-catalyzed C―H functionalization. Hydrogen atom abstraction could achieve C―H bond activation via a free radical process. Moreover, the C―H bonds of hydrocarbons can be considered weak nucleophiles because the electronegativity of carbon is higher than that of hydrogen, and they could be converted to strong nucleophiles (C―M) in the presence of transition metal catalysts via the different pathways mentioned above. It enables further functionalization with electrophiles or nucleophiles to construct complex molecular skeletons. Summarizing the general modes of C―H bond activation will increase our understanding of the associated chemical mechanism and will pave the way for new synthetic strategies. This review aims to offer theoretical guidance for experimental studies and inspire new reaction design by summarizing the modes of transition-metal-catalyzed C―H bond activation.

Key words: Transition metal, C―H bond cleavage, Theoretical study, Mechanism, Concerted metalation-deprotonation