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). Many electrophilic metal centers undergo this Friedel-Crafts-like reaction.
Joseph Chatt observed the addition of C-H bonds of
naphthalene by Ru(0) complexes. Chelation-assisted C-H activations are prevalent. Shunsuke Murahashi reported a
cobalt-catalyzed
chelation-assisted C-H functionalization of 2-phenylisoindolin-1-one from (
E)-N,1-diphenylmethanimine. 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 involving a
stoichiometric amount of
potassium tetrachloroplatinate, catalytic
potassium hexachloroplatinate, methane and water. Due to the fact that Shilov worked and published in the Soviet Union during the
Cold War era, 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. In some cases, discoveries in C-H activation were being made in conjunction with those of
cross coupling. In 1969, Yuzo Fujiwara reported the synthesis of (
E)-1,2-diphenylethene from
benzene and
styrene with Pd(OAc)2 and Cu(OAc)2, a procedure very similar to that of cross coupling. On the category of 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 In 1977, Deno
et al summarized the state of the art as: "oxidizing agents [that] have the singular character of attacking alkanes far faster than functional groups...are
R2NHCl+ with light or FeII, amine oxides and dialkylhydroxylamines with FeII the [peroxytrifluoroacetic acid] hydroxylations described herein, and a multitude of microbiological hydroxylations." The next breakthrough was reported independently by two research groups in 1982.
R. G. Bergman reported the first transition metal-mediated intermolecular C–H activation of unactivated and completely saturated hydrocarbons by oxidative addition. Using a
photochemical approach, photolysis of Cp*Ir(PMe3)H2, where Cp* is a
pentamethylcyclopentadienyl ligand, led to the coordinatively unsaturated species Cp*Ir(PMe3) which reacted via oxidative addition with
cyclohexane and
neopentane to form the corresponding complexes, Cp*Ir(PMe3)HR, where R = cyclohexyl and neopentyl, respectively. W.A.G. Graham found that the same hydrocarbons react with Cp*Ir(CO)2 upon irradiation to afford the related complexes Cp*Ir(CO)HR, where R = cyclohexyl and neopentyl, respectively. In the latter example, the reaction is presumed to proceed via the oxidative addition of alkane to a 16-electron iridium(I) intermediate, Cp*Ir(CO), formed by irradiation of Cp*Ir(CO)2. : The selective activation and functionalization of alkane C–H bonds was reported using a
tungsten complex outfitted with
pentamethylcyclopentadienyl,
nitrosyl,
allyl and neopentyl ligands, Cp*W(NO)(η3-allyl)(CH2CMe3). : In one example involving this system, the alkane
pentane is selectively converted to the
halocarbon 1-iodopentane. This transformation was achieved via the
thermolysis of Cp*W(NO)(η3-allyl)(CH2CMe3) in pentane at
room temperature, resulting in elimination of
neopentane by a pseudo-first-order process, generating an undetectable electronically and sterically unsaturated
16-electron intermediate that is coordinated by an
η2-
butadiene ligand. Subsequent intermolecular activation of a pentane solvent molecule then yields an
18-electron complex possessing an
n-pentyl ligand. In a separate step, reaction with
iodine at −60 °C liberates 1-iodopentane from the complex. == Mechanistic understanding ==