C-H bond activation

Carbon-hydrogen bond activation or CH activation may be defined as a reaction that cleaves a carbon-hydrogen bond. Often the term is restricted to reactions involving organometallic complexes and proceeding by coordination of a hydrocarbon to the inner-sphere of metal, either via an intermediate “alkane or arene complex” or as a transition state leading to a M-C intermediate."Organometallic C-H Bond Activation: An Introduction" Alan S. Goldman and Karen I. Goldberg ACS Symposium Series 885, Activation and Functionalization of C-H Bonds, 2004, 1-43] [Arndtsen, B. A.; Bergman, R. G.; Mobley, T. A.; Peterson, T. H. “Selective Intermolecular Carbon-Hydrogen Bond Activation by Synthetic Metal Complexes in Homogeneous Solution.” Accounts of Chemical Research, 1995: 28 (3) 154-162.] [Periana, R. A.; Bhalla, G.; Tenn, W. J., III, Young, K. J. H.; Liu, X. Y.; Mironov, O.; Jones, C.; Ziatdinov, V. R. “Perspectives on some challenges and approaches for developing the next generation of selective, low temperature, oxidation catalysts for alkane hydroxylation based on the CH activation reaction.” , 2004: 220 (1) 7-25. doi|10.1016/j.molcata.2004.05.036] Important to this definition is the requirement that during the CH cleavage event the hydrocarbyl species remains associated in the inner-sphere and under the influence of “M”.

Theoretical studies as well as experimental investigations indicate that CH bonds, which are traditionally considered unreactive, can be cleaved by coordination. Much research effort has been devoted to the design and synthesis of new reagents and catalysts that can effect CH activation. A significant driver for this type of research is the prospect that C-H activation could enable the conversion of cheap and abundant alkanes into valuable functionalized organic compounds.

Historic overview

The first CH activation reaction is often attributed to Otto Dimroth who in 1902 reported that benzene with mercury(II) acetate (See: organomercury), but some scholars do not view this reaction as being truly CH activation. As observed Goldman & Goldberg CH activation resembles aspects of HH activation: both can be achieved by electrophilic or oxidative activation.

The first true CH activation reaction was reported by Joseph Chatt in 1965 ["The tautomerism of arene and ditertiary phosphine complexes of ruthenium(0), and the preparation of new types of hydrido-complexes of ruthenium(II)" J. Chatt and J. M. Davidson, J. Chem. Soc. 1965, 843 DOI|10.1039/JR9650000843] with insertion of a ruthenium atom ligated to dmpe in the C-H bond of naphthalene. In 1966 A.E. Shilov reported that potassium tetrachloroplatinate induced isotope scrambling between methane and heavy water. The pathway was proposed to involve binding of methane to Pt(II). In 1972 the Shilov group was able to produce methanol and methyl chloride in a similar reaction of stoichiometric potassium tetrachloroplatinate, catalytic potassium hexachloroplatinate, methane and water. As Shilov worked and published in Cold War Soviet Union his work was largely ignored by Western scientists. This so-called Shilov system is today one of the few true catalytic systems for mild alkane functionalizations.

On the other side of the spectrum, oxidative addition, M. L. H. Green in 1970 reported on the photochemical insertion of tungsten (as a Cp₂WH₂ complex) in a benzene C-H bond ["Formation of a tangsten phenyl hydride derivatives from benzene " M. L. Green, P. J. Knowles, J. Chem. Soc. D, 1970, (24),1677-1677 DOI|10.1039/C29700001677 ] and George M. Whitesides in 1979 was the first to carry out an intramolecular aliphatic C-H activation ["Thermal generation of bis(triethylphosphine)-3,3-dimethylplatinacyclobutane from dineopentylbis(triethylphosphine)platinum(II)" Paul Foley, George M. Whitesides J. Am. Chem. Soc. 1979; 101(10); 2732-2733. DOI|10.1021/ja00504a041]

The next breakthrough was reported independently by two research groups 1982, by R. G. Bergman with the first photochemical CH activation of completely saturated hydrocarbons cyclohexane and neopentane forming the hydridoalkylmetal complex Cp*Ir(PMe₃)H(C₆H₅) where Cp* is a pentamethylcyclopentadienyl ligand. ["Carbon-hydrogen activation in completely saturated hydrocarbons: direct observation of M + R-H -> M(R)(H) " Andrew H. Janowicz, Robert G. Bergman J. Am. Chem. Soc.; 1982; 104(1); 352-354.DOI|10.1021/ja00365a091]

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W.A.G. Graham found that the same hydrocarbons react with Cp*Ir(CO)₂ to afford iridium hydrido complexes. ["Oxidative addition of the carbon-hydrogen bonds of neopentane and cyclohexane to a photochemically generated iridium(I) complex" James K. Hoyano, William A. G. Graham J. Am. Chem. Soc. 1982; 104(13); 3723-3725. DOI|10.1021/ja00377a032]

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In one study ["Selective Activation and Functionalization of Linear Alkanes Initiated under Ambient Conditions by a Tungsten Allyl Nitrosyl Complex" Jenkins Y. K. Tsang, Miriam S. A. Buschhaus, and Peter Legzdins J. Am. Chem. Soc.; 2007; 129(17) pp 5372 - 5373; (Communication) DOI|10.1021/ja0713633] the alkane pentane is selectively converted to the halocarbon "1-iodopentane" with the aid of a tungsten complex.

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The tungsten complex is fitted with a pentamethylcyclopentadienyl, a nitrosyl, a ³η 1-butene and a neopentanyl CH₂C(CH₃)₃ ligand. It is thermally unstable and when dissolved in pentane at room temperature it loses neopentane (gains a proton) and coordinates with a pentane ligand (loses a proton). This proton exchange proceeds via a 16 electron intermediate with a butadiene ligand after beta elimination. In a separate step iodine is added at -60°C and 1-iodopentane is released.

Arene C-H bonds can also be activated by metal complexes despite being fairly unreactive. One manifestation is found in the Murai olefin coupling. In one reaction a ruthenium complex reacts with N,N-dimethylbenzylamine in a cyclometalation also involving CH activation ["Formation of a Ruthenium–Arene Complex, Cyclometallation with a Substituted Benzylamine, and Insertion of an Alkyne" Chetcuti, Michael J.; Ritleng, Vincent. J. Chem. Educ. 2007, 84, 1014. [http://jchemed.chem.wisc.edu/Journal/Issues/2007/Jun/abs1014.html Abstract] ] :

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An alkene C-H bond activation with a rhodium catalyst is demonstrated in the synthesis of this strained bicyclic enamine ["The Stereoselective Formation of Bicyclic Enamines with Bridgehead Unsaturation via Tandem C-H Bond Activation/Alkenylation/ Electrocyclization" Sirilata Yotphan, Robert G. Bergman, and Jonathan A. Ellman J. AM. CHEM. SOC. 2008, 130, 2452-2453 DOI|10.1021/ja710981b] :

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References