Carbon–hydrogen bond activation
Carbon–hydrogen bond activation or C–H activation is 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. Important to this definition is the requirement that during the C–H 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 C–H 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 affect 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 and the efficient structural editing of already complex molecules.
The first C–H activation reaction is often attributed to Otto Dimroth who in 1902 reported that benzene reacted with mercury(II) acetate (See: organomercury), but some scholars do not view this reaction as being truly C–H activation. As observed Goldman & Goldberg C–H activation resembles aspects of H−H activation: both can be achieved by electrophilic or oxidative addition.
The first true C–H activation reaction was reported by Joseph Chatt in 1965 with insertion of a ruthenium atom ligated to dmpe in the C–H bond of naphthalene. In 1969 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 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 and George M. Whitesides in 1979 was the first to carry out an intramolecular aliphatic C–H activation
The next breakthrough was reported independently by two research groups 1982, by R. G. Bergman with the first photochemical C–H activation of completely saturated hydrocarbons cyclohexane and neopentane forming the hydridoalkylmetal complex Cp*Ir(PMe3)H(C6H5) where Cp* is a pentamethylcyclopentadienyl ligand.
W.A.G. Graham found that the same hydrocarbons react with Cp*Ir(CO)2 to afford iridium hydrido complexes. The first part of the reaction; the iridium complex reacting with the cycloalkane is an example of oxidative addition where the hydrogen is removed from the alkane and oxidatively added to the metal.
J.F. Hartwig reported a highly regioselective arene and alkane borylation catalyzed by a rhodium complex in 1999 and 2000. In the case of alkanes, exclusive terminal functionalization was observed.
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 C–H activation:
It has also been found by Prof. Roy A. Periana that reactions of late transition metal salts and complexes such of Pt, Pd, Au, and Hg react with methane (CH4), the major component of natural gas, in H2SO4 to yield methyl bisulfate in very low to high yields at very high selectivity.
Most C≠H bond activations proceed under rather harsh reaction conditions (high T, strongly acidic or basic conditions, strong oxidant), significantly lowering their attractiveness. However, more and more quite mild reactions have been developed, significantly expanding the scope of these exciting transformations. Organocatalysis has recently been used as an important approach which has the advantage of being metal-free and cost-effective.
Recently, Hashiguchi et al. discovered that M-hydroxides and aquo complexes can be utilized to carry out CH activation on water soluble arenes in strongly basic conditions. Specifically, they demonstrated a Ru precatalyst with an NNN-pincer ligand, 2,6-diimidizoylpyridine, (IPI), when dissolved in aqueous base generated the associated mixed hydroxide aquo complex, Ru(IPI(OH)n(H2O)m. This complex was then shown to catalyze H/D exchange between the arenes and aqueous base with increasing [KOH] upon initial reduction of Ru(III) to the Ru(II) complex. This was the first demonstrated report of base accelerated CH activation.
Metal centres that contain a large number of electrons and are stable at high oxidation states, such as later transition metals, promote oxidative addition and are therefore ideal candidates to act as catalysts for C–H activation. Furthermore d8 metals that can undergo a square planar arrangement, are potential candidates catalysts as they have two vacant coordination sites and thus steric hindrance is limited.
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