5.1 C-H Activation
Activation of C–H bonds in substrates efficiently and selectively is one of the main
challenges in inorganic chemistry [181]. High-valent metal-oxygen species have
been used extensively, following the examples posed by Nature, which often use
first-row transition metals such as iron, copper, or manganese [4–9]; understanding
their reactivity to understand how the transition-metal enzymes function is one of the
goals of biomimetic chemistry. There are two main routes toward this understanding
(spectroscopy and theory), which in recent years have gone more and more in
parallel and are now often used simultaneously within one project [182–184]. However, the characterization of highly reactive complexes remains sometimes preliminary [185, 186] or open for interpretation [26, 187, 188]; experimental evidence for
the existence of (labile) species often comes from isotope labeling, which should/
could lead to shifts in mass spectrometry [185] or Raman spectroscopy [25].
The strength of C–H bonds in substrates [189] determines the potency of different
biomimetic complexes, with strong bonds such as those in methane or benzene as the
more stronger ones (ca. 105–110 kcal mol
À1 ). For these latter bonds, more reactive
complexes are needed; however, at the same time, the more reactive the complex is,
the less likely is that it can be fully characterized by X-ray crystallography or
spectroscopy. Indeed, the first structurally characterized Fe(IV)-oxo complex [190]
is unable to oxidize cyclohexane’s C–H bond (ca. 99 kcal mol
À1 ). Sometimes, the
experimentally observed bond dissociation energies (BDEs) need adapting, as
shown recently by Klein and co-workers [191].
5.1.1 (c)PCET vs. HAT
In the typical oxidation mechanism (see Fig. 7), it is assumed that the electron and
proton move simultaneously (e.g., as a hydrogen in HAT reactions); however, this is
not necessarily always the case and/or not for all spin states. An alternative pathway
could be proton-coupled electron transfer (PCET), which comes in many guises
[192–194], where the proton and electron could be transferred simultaneously or
consecutively and to the same place or to different places. HAT is one example of the
many possibilities, where they are transferred at the same time and to the same place;
concerted PCET is one of the other possibilities, where the transfer is taking place at
the same moment, but to different places; distinguishing between the two options is
not easy and open to interpretation. A major step forward was reported early 2018,
when Klein and Knizia used [195] the intrinsic bond orbital (IBO) [196, 197] view to
investigate two prototypical model systems that cleave C–H bonds. By comparing
the IBOs along the intrinsic reaction coordinate (IRC) profiles, they showed that for
the taurine dioxygenase (TauD-J), an Fe(IV)-oxo active species, a HAT profile was
observed; in the process of cleaving the C–H bond, one electron (here, an α electron)
moves together with the proton and forms a new bond together with a second
electron from the Fe ¼ O moiety (here, a β electron). By plotting the changes in
the IBOs as a function of the reaction coordinate, they were able to show nicely that
210
M. Swart
Activation of C–H bonds in substrates efficiently and selectively is one of the main
challenges in inorganic chemistry [181]. High-valent metal-oxygen species have
been used extensively, following the examples posed by Nature, which often use
first-row transition metals such as iron, copper, or manganese [4–9]; understanding
their reactivity to understand how the transition-metal enzymes function is one of the
goals of biomimetic chemistry. There are two main routes toward this understanding
(spectroscopy and theory), which in recent years have gone more and more in
parallel and are now often used simultaneously within one project [182–184]. However, the characterization of highly reactive complexes remains sometimes preliminary [185, 186] or open for interpretation [26, 187, 188]; experimental evidence for
the existence of (labile) species often comes from isotope labeling, which should/
could lead to shifts in mass spectrometry [185] or Raman spectroscopy [25].
The strength of C–H bonds in substrates [189] determines the potency of different
biomimetic complexes, with strong bonds such as those in methane or benzene as the
more stronger ones (ca. 105–110 kcal mol
À1 ). For these latter bonds, more reactive
complexes are needed; however, at the same time, the more reactive the complex is,
the less likely is that it can be fully characterized by X-ray crystallography or
spectroscopy. Indeed, the first structurally characterized Fe(IV)-oxo complex [190]
is unable to oxidize cyclohexane’s C–H bond (ca. 99 kcal mol
À1 ). Sometimes, the
experimentally observed bond dissociation energies (BDEs) need adapting, as
shown recently by Klein and co-workers [191].
5.1.1 (c)PCET vs. HAT
In the typical oxidation mechanism (see Fig. 7), it is assumed that the electron and
proton move simultaneously (e.g., as a hydrogen in HAT reactions); however, this is
not necessarily always the case and/or not for all spin states. An alternative pathway
could be proton-coupled electron transfer (PCET), which comes in many guises
[192–194], where the proton and electron could be transferred simultaneously or
consecutively and to the same place or to different places. HAT is one example of the
many possibilities, where they are transferred at the same time and to the same place;
concerted PCET is one of the other possibilities, where the transfer is taking place at
the same moment, but to different places; distinguishing between the two options is
not easy and open to interpretation. A major step forward was reported early 2018,
when Klein and Knizia used [195] the intrinsic bond orbital (IBO) [196, 197] view to
investigate two prototypical model systems that cleave C–H bonds. By comparing
the IBOs along the intrinsic reaction coordinate (IRC) profiles, they showed that for
the taurine dioxygenase (TauD-J), an Fe(IV)-oxo active species, a HAT profile was
observed; in the process of cleaving the C–H bond, one electron (here, an α electron)
moves together with the proton and forms a new bond together with a second
electron from the Fe ¼ O moiety (here, a β electron). By plotting the changes in
the IBOs as a function of the reaction coordinate, they were able to show nicely that
210
M. Swart