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Cite this: DOI: 10.1039/x0xx00000x
Received 00th January 2014,
Accepted 00th January 2014
DOI: 10.1039/x0xx00000x
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The quest for C-H activation in transition metal σ-
alkane complexes
A.D. Scotta
The activation of a C-H bond with transition metals has the potential to define the future of
hydrocarbon usage in chemistry. Under ordinary circumstances, the C-H bond is one of the
most notoriously strong and difficult to sever covalent bonds, whether by heterolytic or
homolytic bond fission. However, work pioneered by then released in 1978 by A.E. Shilov†
showcasing his namesake Shilov Process experimented with using a platinum complex catalyst
to achieve activation of an alkane C-H bond at achievable temperatures, paving the way for
potentially viable industrial processes where once there was very little scope for practical
chemistry. This review will cover the ongoing quest for progress in this field.
Introduction
While the challenge of overcoming the inert nature of the C-
H bond seems insurmountable, with a pKa value for the
dissociation of a proton from methane reaching heights of
approximately 483
, it has been successfully achieved by
transition metal catalysis – most notably by platinum species in
the Shilov Process1,2
(Scheme 1).
The ability to sever the C-H bond for later functionalization
is ‘activation’ which has a myriad of potential uses and a strong
influence on both organometallic and organic chemistry.
Evidence of C-H activation in the manner shown in the Shilov
Process was first demonstrated by the deuteration of alkanes
coordinated to these platinum centres, implying that there must
have been a C-H bond breaking event and that such activation,
therefore, was possible. In the past, it was the case that there
was no effective way to overcome the great bond dissociation
energy (BDE) of the C-H bond (for example, in the
petrochemically important methane, this BDE is in the region
of 105kcalmol-1
.)4
With the catalytic pathways investigated by the likes of the
Shilov group1
and Labinger & Bercaw5
, the activation is
achieved under more practical conditions, the potential of
catalytic C-H cleavage began to show. Plentiful petrochemical
alkanes (e.g. methane, hexane) can thusly be functionalised into
other substances (derivatives such as alcohols) without need for
extreme conditions. As we will find as the review progresses,
this can also be a very selective process. This interconverting of
plentiful feedstocks into other less readily available substances
in a commercially viable way can likely be achieved in the near
future as it requires little complex chemistry, is catalytic in
nature and seems to be an efficient process.
One such example of Pt-catalysed functionalization of
methane resulted in a greater than 90% yield of methyl
bisulphate7
as shown in Scheme 2 demonstrating one among
many potential reactions; although certain difficulties with the
lifespan of the catalyst were encountered in this specific case.
As well as the studied potential results of C-H activation,
there are also broadly accepted ideas with regards to the
mechanism(s) by which these reactions proceed, which in turn
give insight into their efficiency and selectivity.
Mechanism of C-H Activation
Association
The first step in activation is the association of the C-H σ-
bond electron density with the metal centre; this is broadly
accepted to be achieved by either an associative or dissociative
pathway2
(or a concerted interchange), dependent on the nature
of the metal catalytic centre, particularly the degree of electron
deficiency at said centre as a result of its oxidation state and the
choice of ligand to surround it.
Scheme 2
Scheme 1

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The bonding electron pair in the C-H bond is drawn to the
metal centre in an agostic interaction (3 centre 2 electron
bonding), which in turn weakens the bond and enables it to be
more easily activated, hence the catalytic action of the metal
centre.
The mechanisms by which the first step proceeds (in which
a linkage is established between the metal centre and the
bonding electron density in the hydrocarbon C-H bond is
formed) are demonstrated in figure 1. An associative pathway
requires a vacant co-ordination site to already be present on the
metal centre, allowing a five-coordinate 18e transition state
(that may or may not be isolable) where the dissociative
pathway generates a vacant co-ordination site through loss of a
ligand to give a three-coordinate 14e transition state before
association of the hydrocarbon fragment. These are two
extremes; an alternative is a concerted process by which the
alkane associates and the ligand leaves simultaneously through
a short-lived five-coordinate transition state; this process is
dubbed ‘interchange’.
This ‘σ-alkane’ complex interaction is, in comparison to the
majority of metal-ligand bonds, relatively weak and therefore
contributes a certain thermodynamic instability that must be
overcome. As such, this means that when designing systems
with the mechanism in mind, the reverse process (a reductive
elimination of the hydrocarbon fragment from the metal centre)
is in direct competition. For this reason the choice of ligand
generally leans toward reaction schemes where all other ligands
present in the reaction mixture are weakly coordinating
(including the solvent itself), if the highest levels of reactivity
are to be achieved by the usual associative mechanism.
In order to facilitate an associative mechanism, square
planar complexes are preferred, therefore metal centres that
produce this geometry are required (d8
low-spin Pt(II) being the
classic example). This geometry tends to favour the associative
pathway as there is an accessible A2u orbital – the 18e-
species
generated is exceptionally transient, however, as the reason this
site was vacant in the first place was due to its relatively high
energy (leading to the immediate dissociation of another ligand,
thus preparing the metal centre for the activation step).
For the dissociative pathway (Fig. 1, (b)) to occur
preferentially, the metal centre must be sufficiently electron
rich that the dissociation of the fourth ligand is favoured over
association; neutral complexes with efficient σ-donor ligands
such as aryl groups trans to the departing ligand are a good
example, as the trans-effect (where the donation of the ligand
trans to the leaving ligand ‘pushes’ the other out by electron
repulsion) assists with the dissociation.. Another factor is steric
hindrance – if the bound ligands are obstructive in their size,
associating the hydrocarbon first will be disfavoured.
Activation
Once the σ-alkane complex has been formed, the
association of this σ-electron density in the R-H bond to the
metal centre weakens the bond, preparing it for the activation
processes (Fig. 2). The first mechanism, oxidative addition,
involves the formal cleavage of the R-H bond, associating both
the organic fragment and the hydride to the centre
independently, causing an increase in formal oxidation state
and coordination number. As this involves an increase in
oxidation state, this is more common at centres such as Ir(I) and
Rh(I) whose oxidation state is low and has greater electron
density to ‘spare’ for forming the new metal to ligand bond, as
this stabilises the transition state prior to eliminating the
hydrogen with a departing ligand (‘X’ in Fig. 1, e.g. Cl).
The next mechanism – σ-bond metathesis – is analogous to
oxidative addition but occurs in a concerted process, never
formally increasing the oxidation state of the metal. The σ-
electron density in the R-H and the M-X bonds metathesise to
form the M-R and X-H bonds simultaneously, avoiding formal
oxidation through a formal four-centre four-electron transition
state. This avoidance of formal oxidation allows electron-
deficient metal centres to reach the same products without a
highly unstable increase in co-ordination; particularly useful for
d0
complexes which cannot practically undergo oxidation. It
should be noted that if the ‘X’ group is attached to the metal
centre by a double bond (or greater bond order), a 1,2 addition
can occur by a similar transition state where the co-ordination
number of the metal does not change and an α-hydride transfer
to the ‘X’ group takes place (Fig. 3).
Figure 22
: A summary of C-H activation pathways, with initial binding (1),
oxidative addition (oa), sigma bond metathesis (sbm) and electrophilic
addition (ea).
Figure 12
: A simplified diagram of the initial hydrocarbon association
pathways; the associative pathway (a), dissociative pathway (b) resulting
in further activation (c).

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Electrophilic addition represents the other extreme, where
the hydrocarbon R-H bond is sufficiently weakened by binding
to the metal centre that the acidity of the proton increases to the
point that it can be lost to the solvent or to a suitably basic
group available to bind it, and the oxidation state of the metal
decreases. As such, the electrophilic metal is typically electron
deficient and/or has electron-withdrawing ligands, and the
favourability of the mechanism increases when the LUMO of
the R-H bond is low in energy, facilitating the electrophilic
process. This can result easily with electronegative heteroatoms
nearby drawing away electron density; the most common of
these in organic fragments being carbonyl groups (or multiple
instances of the same) pulls the energy of the LUMO down and
allows it to be more susceptible to attack.
Evidence
Much of the initial interest in metal-catalysed C-H
activation, particularly Shilov chemistry, was as a result of
isotope studies; particularly the multiple-deuteration1,14
of
alkanes and arenes (Scheme 3) even at early reaction times,
implying that the bound alkanes did not immediately leave the
coordination sphere of the metal centre16
. In many ways the
evidence for the formation of a σ-alkane or σ-arene complex
has been difficult to attain as the species themselves are
transient under normal conditions; relatively unstable
intermediates that are then fundamental in activation and
functionalisation9
. Much of the supporting evidence was strong
as early as the 1970s1
but direct evidence has surfaced from
crystallographic and spectroscopic techniques beyond educated
conjecture from isotopic and kinetic data.
A study of photochemistry in hexacarbonyl complexes in
1975 experimented with photolysis of said complexes to
generate five-coordinate pentacarbonyls in various solid
matrices including noble gases and, crucially, methane. While
complexes of the sort Cr(CO)5Ar were observed, when in the
presence of methane no such complexes were observed. Perutz
and Turner reported a favoured Cr(CO)5CH4 complex over the
noble gas counterpart10
; these studies were performed at
exceedingly low temperatures (approaching absolute zero) in
order to achieve the lifetimes necessary for analysis by
vibrational spectroscopy.
A later study in 1997 successfully isolated heptane bound in
a σ-alkane complex format by using an iron porphyrin11
, which
they managed to crystallise and characterise by NMR
spectroscopy.
As techniques continued to improve and develop, more
evidence continued to surface. In 2011, a σ-alkane complex of
CpMn(CO)2(R-H) (where the R-H fragment is CH3CH2CH3 or
CH3(CH2)2CH3) was identified by in-situ laser photolysis
(Scheme 4) and subsequent analysis by time-resolved infra-red
spectroscopy and NMR.12
Certain computational experiments
have been conducted using density functional theory (DFT)13
,
and the improved choice of ligand (as with the porphyrin study,
neutral ‘pincer’ ligands to hold complexes in place) has allowed
longer lifetime σ-alkane complexes.
A recent study in 2015 reported the remarkable synthesis of
a rhodium σ-alkane complex that was stable for “months” at
298K9
; synthesised by simple hydrogenation of a single-crystal
sample of a rhodium-norbornadiene complex with chelating
phosphine ligands, which was then crystallised and
characterised by crystallography and multiple types of NMR,
confirming the structure. This study also inferred that the
complex being in the solid state strongly influenced its stability.
With the elucidation of the mechanism complete, we begin
to investigate the more practical challenges with these catalysts
and their use.
σ-Alkane Complex Catalysis
It would now be prudent to show some examples of the
catalysts themselves, and how they satisfy the various criteria
the mechanisms imply as necessary. We will start with the
classic Pt(II) compound used in the 1970s (Fig.4 ).
Shilov’s work used this in conjunction with a Pt(IV) oxidant
(H2PtCl6)1
. In the aqueous medium of the Shilov system, the
oxidant facilitates oxidation of the catalytic species with
molecular oxygen and solvent molecules to give a transient
Pt(IV) species which is then reduced again to liberate the
products (Scheme 5).
Figure 3: An exemplar 1,2 addition across an M=X bond.
Scheme 412
Scheme 3
Scheme 52

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The catalyst performs its function by satisfying the
requirements, firstly, for associative substitution; the R-H
fragment can approach the vacant axial site, coordinate to give
the square pyramidal 5-coordinate 18-electron intermediate.
This is possible due to the d8
Pt centre and its square planar
geometry. Cl is a good ligand for substitution, as suggested in
the explanation of the mechanism. Pt(II) also possesses the
accessible Pt(IV) oxidation state which subsequently allows the
oxidative addition (Fig. 2) pathway, allowing it to function for
C-H activation. This, however, is also in some ways its
downfall; the Pt(II) catalyst was often itself overoxidised, a
process which converted it to the Pt(IV) oxidation state,
rendering it catalytically inert and therefore too wasteful for
any industrial process.
As such, while functional, the Shilov system was better for
the kinetic studies. A superior platinum catalyst was required
for progress toward industrially viable activation processes:
(bypm)PtCl2 (Fig. 5) as used in Scheme 2 (the ‘Periana-
Catalytica’ cycle), is one such possibility.
This possesses many of the same properties but the (bypm)
ligand enabled the catalyst to resist overoxidation in high
temperature sulphuric acid.
The exact synthetic processes in which this catalyst was
used will be investigated in the next section, but in summary,
the impracticality arose when the higher oxidation state of the
catalyst itself was the oxidant in the reaction. In this case, the
(bypm)PtCl2 catalyst was stable to oxidation in 101% sulphuric
acid, at 220°C, and gave productive yields of methanol, as
intended; the results of their mechanistic studies revealed that
“contrary to the general teaching that the oxidation of the Pt(II)
to Pt(IV) should be minimised in order to prevent catalyst
deactivation, studiest show that increasing the rate of this over
oxidation of Pt(II) can actually lead to stable systems with a
higher TOF”18
(turnover frequency, denoting catalytic activity
before catalyst exhaustion).
Pt square planar complexes are not the only catalysts
reported to undergo this form of chemistry, however; other
examples include: mercuric triflate (Hg(CF3SO3)2), used to
catalyse the conversion of methane to methyl bisulphate in
100% sulphuric acid19
(another instance of H2SO4 as the
oxidant), Ir/Rh pincer complex catalysts17,20
, a dehydrogenative
Diels-Alder conversion with a Pd(II) bis-sulphoxide-catalyst21
(Scheme 6) and also a biomimetic C-H activation with a cupric
super-oxo complex22
, some of these implying applications
beyond the conversion of petrochemical feedstocks.
In every case, there are certain challenges to overcome (be
they the conditions of the reaction or something problematic
with the reactants themselves) that have thus far prevented the
industrial success of the process.
C-H Activation in Practice
Early studies in C-H activation (as we have seen) focused
on deuteration reactions and some considerable effort was
expended to discover the mechanism and structure of the
intermediate compounds. However, as time moves on, more
and more methods that have promising implications for future
industrial applications, particularly efforts focused on the
conversation of methane to methanol efficiently – a
economically important development that could reduce colossal
energy requirements. Two pertinent but different examples will
be hitherto reported, highlighting the potential for flexibility.
“Periana-Catalytica” System13
The overall equation of the process seems simple (Scheme
7) however there was investigation into myriad possible
pathways through kinetic studies, adding considerable
mechanistic complexity.
The ubiquitously reliable technique of testing the process
with a deuterated solvent (D2SO4 in this case), the study
confirmed exchange of this deuterium with the methane and,
with previous reports on similar systems in mind, stated this to
be a C-H activation reaction.18
The proposed mechanism in fact follows a dissociative
pathway as discussed earlier in the paper (shown in Scheme
8)19
, producing the species that then undergoes oxidation in hot
100% H2SO4 to give methyl bisulphate – a substance that
relatively simply undergoes conversion to methanol.
Figure 4: Potassium tetrachloroplatinate, the key catalyst used in Shilov's
activation studies; figure 5: (bypm)PtCl2; a considerable improvement in
practical C-H activation catalysts
Scheme 621
Scheme 7
Scheme 8

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Diels-Alder Dehydrogenation
The work catalogued by Stang and White21
in their
investigation into the use of sulphonated Pd catalysts in a
traditional organic chemistry reaction shows the applications
beyond the realm of petrochemical conversion; they report a
variety of yields but also some processes where successful
control of stereochemistry has been attained (20:1
diastereomeric ratio23
(d.r. in Scheme 9).
In this reaction, the C-H bonds highlighted in red are the
Pd-activated bonds. The yield of this reaction in particular was
74% with respect to this cycloaddition product, which the paper
cites as likely being the reoxidation (regeneration) of the Pd
catalyst; thus demonstrated is one potential synthetic use for
this variety of chemistry.
Conclusions
As is almost ubiquitous in the abstracts of papers relating to
C-H activation chemistry, it seems certain that there is a
considerable degree of justifiable excitement at the potential of
this chemistry, and has been even since Shilov’s work in the
1960s. The potential to bypass energy-intensive and therefore
economically severe pyrolysis routes – for example in the
conversion of methane to methanol for transport – has far-
reaching implications on the use of petrochemical feedstocks
and the costs involved.
It is safe to say that considerable strides have been made
through the contributions of many groups to discovering the
potential of transition metal catalysed C-H activation; be it in
structure of intermediates, the mechanism of action or the
kinetics of processes. Thorough studies into all of these areas
have brought about considerable revelations even in the most
recent years, to the point that there is likely still much progress
to be made and undoubtedly new and inventive reaction
systems will bring about new mechanistic theories requiring
thorough investigation.
This being said, industrial viability seems achievable within
a relatively short period of time given the progress attained, not
necessarily just in petrochemical plants but in other areas of
synthetic chemistry as well. As work continues to progress, I
have little doubt that this chemistry will continue to attract a
considerable amount of attention due to its potential economic
value to an already enormous industry (and to a lesser extent
for its niche uses in other areas of synthetic chemistry), and
rightly so – we should all look forward to seeing where future
studies in this area lead.
Acknowledgements
My thanks are given to Simon Doherty for reviewing this
article prior to its submission and for his feedback throughout
the process of its production.
Notes and references
a
School of Chemistry, Newcastle University, Newcastle upon Tyne, NE1
7RU, UK.
† While Shilov’s paper was published in 1978, he reports the first
observed C-H bond activation catalysed by metal complexes in 1969. The
first true C-H activation reported was in 1965.6
1. A. E. Shilov, Pure Appl. Chem., 1978, 50, 725
2. M. Lersch, M. Tilset, Chem. Rev., 2005, 105, 2471
3. T.H. Lowry, K.S. Richardson, Mechanism and Theory in Organic
Chemistry, Benjamin-Cummings Publishing Co., New York, 3rd
edition, 1987
4. X. Hu, H. Li, T. Wu, Acc. Chem. Res., 2003, 36, 255-263
5. A. J. Labinger, J. E. Bercaw, Nature, 2002, 417, 507
6. J. Chatt, J. M. Davison, J. Chem. Soc., 1965, 843
7. R. A. Periana, D. J. Taube, S. Gamble, H. Taube, T. Satoh, H. Fujii,
Science, 1998, 280, 560-564
8. J. D. Atwood, Inorganic and Organometallic Reaction Mechanisms,
VCH, New York, 2nd
edition, 1997
9. S. D. Pike, F. M. Chadwick, N. H. Rees, M. P. Scott, A. S. Weller, T.
Krämer, S. A. Macgregor, J. Am. Chem. Soc., 2015, 137, 820-833
10. R. N. Perutz, J. J. Turner, J. Am. Chem. Soc., 1975, 97, 4791-4800
11. D. R. Evans, T. Drovetskaya, R. Bau, C. A. Reed, P. D. W. Boyd, J.
Am. Chem. Soc., 1997, 119, 3633-3634
12. J. A. Calladine, S. B. Duckett, M. W. George, S. L. Matthews, R. N.
Perutz, O. Torres, K. Q. Vuong, J. Am. Chem. Soc. 2011, 133, 2303-
2310
13. M. D. Walter, P. S. White, C. K. Schauer, M. Brookhart, New J.
Chem., 2011, 35, 2884-2893
14. M. A. Long, R. B. Moyes, P. B. Wells, J. L. Garnett, J. Catal., 1978,
52, 206-217
15. M. M. Konnick, S. M. Bischof, M. Yousufuddin, B. G. Hashiguchi,
D. H. Ess, R. A. Periana, J. Am. Chem. Soc., 2014, 136, 10085-10094
16. R. H. Crabtree, J. Chem. Soc., Dalton Trans., 2001, 2437-2450
17. C. M. Jensen, Chem. Commun., 1999, 2443-2449
18. O. A. Mironov, S. M. Bischof, M. M. Konnick, B. G. Hashiguchi, V.
R. Ziatdinov, W. A. Goddard III, Mårten Ahlquist, R. A. Periana, J.
Am. Chem. Soc., 2013, 135, 14644-14658
19. R. A. Periana, D. J. Taube, E. R. Evitt, D. G. Löffler, P. R. Wentrcek,
G. Voss, T. Masuda, Science, 1993, 259, 340-343
20. J. A. Maguire, A. S. Goldman, J. Am. Chem. Soc., 1991, 113, 6706
21. E. M. Stang, M. C. White, J. Am. Chem. Soc., 2011, 133, 14892-
14895
22. R. L. Peterson, R. A. Himes, H. Kotani, T. Suenobu, L. Tian, M. A.
Siegler, E. I. Solomon, S. Fukuzumi, K. D. Karlin, J. Am. Chem.
Soc., 2011, 133, 1702-1705
23. R. E. Gawley, J. Org. Chem., 2006, 71, 2411-2416
Scheme 9