C-H Activation

C-H Activation

Hydrocarbon is an organic compound composed only of two elements, carbon and hydrogen. As an important fuel and chemical raw material, hydrocarbon and its derivatives often play an irreplaceable role in human production and life, and profoundly improve people's lives. C-H activation is an important and hot area that has been developed most rapidly in recent years. Due to its outstanding advantages and great challenges, the direct functional group reaction of the C-H bond is even called the holy grail of the chemical industry. As shown in figure 1, C-H activation is a chemical reaction in which carbon-hydrogen bonds are cleaved and replaced by carbon-X bonds (where X = carbon, oxygen or nitrogen). Catalysts commonly used in the modification process are transition metals such as Pd, Ru and Rh.

Figure 1. C-H bond activation diagram

Catalytic principle

C-H activation can be divided into three broad categories depending on the mechanism:

• Oxidative addition. A carbon-hydrogen bond is inserted at the metal center of the catalyst to cleave the bond and oxidize the metal to produce an intermediate, which is then subjected to reduction elimination to obtain an electrophilic activation of the organometallic reactive intermediate
• S_EAr type reaction. Typically the substrate (electron-rich) undergoes the S_EAr type mechanism.
• σ-bond metathesis. The reaction proceeds through a "four-center" transition state in which the bond is broken and formed in one step. Since carbon bonds with a metal, a hydrogen bond bonds to one of the metals, causing a bond break between the ligand and the metal, thereby achieving breakage of the target hydrocarbon bond.

Applications

• In the field of organic chemistry: Steam reforming is currently used to produce synthesis gas using a large amount of methane, which is a mixture of carbon monoxide and hydrogen. This syngas is then used in a Fischer-Tropsch reaction to synthesize a longer carbon chain product or methanol. Methanol is one of the most important industrial chemical raw materials and has high commercial value. An interesting method of converting these hydrocarbons involves C-H activation. For example, Periana reports complexes containing late transition metals such as Pt, Pd, Au and Hg, and reacts with methane (CH4) to obtain methyl hydrogen sulfate in H₂SO₄.

  Figure 2. The schematic diagram of methane (CH₄) forming methyl hydrogen sulfate in H₂SO₄

• In the field of biochemistry: In academic fields and even industrial production, the development of C-H activation methods has had a major impact on the synthesis of natural products. Our synthetic route to the ideal situation is to minimize the number of synthetic steps and maximize yield.

  Figure 3. The reaction process of indole and enolate formation of hydrazine-carvone intermediate

The products in the above reactions are commonly used scaffolds for a variety of natural products, including hapalindole Q and ambiguine H. The core structure can be formed by C-H activation via a C-C bond. The intrinsic reactivity of indole and enolates leads to the formation of C-C bonds to form indole-carvone intermediates.

Apart from this, the transition metal catalyzed C-H reaction can also be summarized as follows:

Table 1. The reaction types and reaction formulas of C-H Activation

References

1. Crabtree, R. H. (2001). ‘Alkane C-H activation and functionalization with homogeneous transition metal catalysts: a century of progress-a new millennium in prospect’. J. Chem. Soc. Dalton Trans. 17 (17): 2437-2450.
2. Periana,R.A. (1993). ‘A Mercury-Catalyzed,High-Yield System for the Oxidation of Methane to Methanol’. Science. 259 (5093): 340-343.
3. Periana, R. A. (1998). ‘Platinum Catalysts for the High-Yield Oxidation of Methane to a Methanol Derivative’. Science. 280(5363): 560-564.