Formation of a C-C double bond from two aliphatic carbons. Multiple C-H activations in an iridium pincer complex

Article abstract of DOI:10.1039/c4sc03839h

The search for novel, atom-economic methods for the formation of C-C bonds is of crucial importance in synthetic chemistry. Especially attractive are reactions where C-C bonds are formed through C-H activation, but the coupling of unactivated, alkane-type C_sp³-H bonds remains an unsolved challenge. Here, we report iridium-mediated intramolecular coupling reactions involving up to four unactivated C_sp³-H bonds to give carbon-carbon double bonds under the extrusion of dihydrogen. The reaction described herein is completely reversible and the direction can be controlled by altering the reaction conditions. With a hydrogen acceptor present a C-C double bond is formed, while reacting under dihydrogen pressure leads to the reverse process, with some of the steps representing net C_sp³-C_sp³ bond cleavage. Mechanistic investigations revealed a conceptually-novel overall reactivity pattern where insertion or deinsertion of an Ir carbene moiety, formed via double C-H activation, into an Ir-C bond is responsible for the key C-C bond formation and cleavage steps.

Full text of DOI:10.1039/c4sc03839h

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RSCPublishing
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DOI: 10.1039/C4SC03839H
ARTICLEꢀ
Formation of a C–C double bond from two aliphatic
carbons. Multiple C–H activations in an iridium
pincer complex
Cite this: DOI: 10.1039/x0xx00000x
a
b
b
a
Alexey V. Polukeev, Rocío Marcos, Mårten S. G. Ahlquist and Ola F. Wendt*
Received 00th January 2012,
Accepted 00th January 2012
The search for novel, atom-economic ways for the formation of C–C bonds is of crucial
importance in synthetic chemistry. Especially attractive are reactions where C–C bonds are
formed through C–H activation, but the coupling of unactivated, alkane type Csp3–H bonds
remains an unsolved challenge. Here, we report iridium mediated intramolecular coupling
reactions involving up to four unactivated Csp3–H bonds to give carbon-carbon double bonds
under the extrusion of dihydrogen. The reaction described herein is completely reversible and
the direction can be controlled by altering the reaction conditions. With a hydrogen acceptor
present a C–C double bond forms while reacting under dihydrogen pressure leads to the
reverse process, with some of the steps representing net Csp3–Csp3 bond cleavage. Mechanistic
investigations revealed conceptually novel overall reactivity pattern where insertion or
deinsertion of an Ir carbene moiety, formed via double C–H activation, into an Ir–C bond is
responsible for the key C–C bond formation and cleavage steps.
DOI: 10.1039/x0xx00000x
www.rsc.org/
Introduction
Previously, we reported on the synthesis of complex trans-
(
PCyP)IrHCl (PCyP = {cis-1,3-bis-[(di-tertbutylphosphino)-
The selective activation of C–H bonds by transition-metal methyl]cyclo-hexyl}) (1) and the attempted synthesis of
complexes is one of the main goals of organometallic (POCyOP)IrHCl (POCyOP
{cis-1,3-bis-[(di-tertbutyl-
=
chemistry, as it may allow for efficient, low-waste methods for phosphinoxy]cyclohexyl}), which resulted in complete
the functionalization of various organic molecules, not the least dehydrogenation and aromatization of the ligand and formation
1
6
of cheap, but relatively inert alkanes. In particular, cross- of the known benzene-based (POCOP)IrHCl complex. We
coupling reactions where a C–C bond is formed via activation have also explored the potential of these aliphatic pincer
2
2d,3
7
of C–H bonds of one or both coupling partners have been complexes as dehydrogenation catalysts.
intensively studied in recent years as a potential alternative to
The introduction of a cyclohexane moiety instead of a
the traditional palladium-catalyzed couplings, where pre- benzene ring in the pincer complex affects its thermal stability.
4
functionalization of both substrates is required. Numerous This thermal instability is most likely related to the behavior of
methods have been developed for the connection of Csp–H, the ligand, and given the aliphatic nature of all the ligand C–H
2
d,3
Csp2–H and Csp3–H bonds with each other,
with coupling of bonds, we reasoned that coordinatively unsaturated species
3d
two Csp3–H bonds being the most challenging. However, in could give rise to interesting reactivity. One way to probe this
the latter case protocols are rather substrate-specific and the was to investigate the ligand transformations using the iridium
scope is limited to substrates with activated Csp3–H bonds; hydrido-phenyl complex, which closely resembles the elusive
3d
strong oxidants like peroxides are used to drive the reaction.
hydrido-alkyl intermediates involved in dehydrogenation
Typically, one coupling partner bears a heteroatom adjacent to reactions. Here we report on C–H activation reactions with the
the Csp3–H bond, which facilitates oxidation and stabilizes the aliphatic ligand involving both the ligand backbone and the
resulting electrophilic species, while the other partner with an tert-butyl groups on the phosphine. This two-site activation is
acidic C–H bond is responsible for generating the nucleofile. In shown to lead to the first example of an intramolecular ring-
this respect, the coupling of unactivated Csp3–H bonds may closing reaction where two carbon atoms with non-activated,
provide a more universal procedure with a high potential in all alkane-like Csp3–H bonds are joined to form a carbon-carbon
branches of synthetic chemistry.
double bond under extrusion of dihydrogen. The reaction is
Benzene-based iridium pincer complexes have been shown mediated by a pincer carbene complex and thus proceeds via
to be effective catalysts for various dehydrogenation reactions, quadruple C–H activations at a single metal center.
including those which involve non-activated Csp3-H bonds.
5
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Results and discussion
At room temperature, three broadened signals from the phenyl
group are observed for 3-syn; they do not VidewemArtoicnlesOtrnalintee
DOI: 10.1039/C4SC03839H
broadening seems to be a result of rest rotation. Interestingly,
Dynamic oxidative addition of benzene in a phenyl-hydride
exchange with deuterobenzene up to 80 ºC and therefore
complex
t
In the presence of BuONa complex (PCyP)IrHCl (1) reacts while for the major isomer (syn/anti ratio = 10:1) the ortho
with benzene under formation of extremely labile phenyl- protons appear as a very broad signal almost at the coalescence
‡
hydride 2 (Scheme 1). At room temperature, complex 2 point (ΔG = 14.0 kcal/mol at 25 ºC), for the minor isomer two
demonstrates dynamic behavior and its NMR signals are broad. doublets are observed, as expected for slow limit of rotation of
Thus, a solution of 2 in methylcyclohexane-d14 reveals a phenyl group. As far as the rate of rotation reflects the degree of
31
1
broadened singlet at 63.1 ppm in the P{ H} NMR spectrum crowding around the metal, it seems reasonable that the
1
and a very broad signal at -47.8 ppm in the H NMR spectrum. preference for the syn isomer is a result of mainly steric factors.
-
At temperatures below ca. -10 ºC, the P–H coupling with the In the IR spectrum, two intense bands are observed at 1951 cm
3
1
1
high-field hydride resonance appears in the P{ H} NMR
1
-1
(3-syn) and 1966 cm (3-anti), corresponding to C-O
spectrum, while in the H NMR spectrum the hydride is stretching vibrations, as well as two more broad, low-intense
observed as a triplet at -48.22 ppm (-40 ºC, JPH = 12.3 Hz), bands at 2124 cm (3-syn) and 2199 cm (3-anti), from Ir-H.
shifted somewhat upfield at lower temperature. The slightly The latter bands moved to lower frequencies (but could not be
distorted shapes of the hydride and phosphorus resonances unambigously assigned) when deuterated benzene was used to
indicate the presence of a small amount of another compound prepare complex 3, while νCOs moved to 1970 and 1983 cm ,
with very close values of its chemical shifts, most likely an correspondingly.
isomer of 2 (in mesitylene-d12, the separation between the
1
2
-1
-1
-1
signals is better, and therefore two distinct hydride resonances
are observed at -40 ºC, and the amount of the isomer is bigger).
It should be noted that the hydride signal remains significantly
1
31
broadened (Δν1/2 = 16 Hz in the H{ P} spectrum at -40 ºC)
down to - 90 ºC, which may indicate the existence of additional
t
dynamic process (likely, a rotation of Bu's). Also, two doublets
and three triplets each integrating as 1H are observed in the
1
aromatic region at low temperatures, consistent with η -
coordination of phenyl group. Complex 2 readily reacts with
nitrogen (even with traces in low-quality argon) to give
6
PCyP)IrN2 and is sensitive to moisture. Hence, it can be
(
considered as a source of a 14e (PCyP)Ir species. In this regard,
2
resembles
the
benzene-based
complex
[2,6-
Bu2PCH2)2C6H3]Ir(H)Ph, which was found to undergo fast
t
(
dissociative arene exchange at room temperature, with the rate
8
being independent of concentration of free benzene. Treating
the coalescence of the two branches of the hydride-coupled
31
1
doublet in the P{ H} NMR spectrum as a result of a simple
exchange between two states of equal population, the barrier for
reductive elimination of benzene from 2 can be estimated as
Schemeꢀ1ꢀReactionsꢀofꢀcomplexꢀ1ꢀwithꢀbenzeneꢀ
‡
ΔG = 14.0 kcal/mol at -3 ºC which is very close to the value
t
for the complex [2,6-( Bu2PCH2)2C6H3]Ir(H)Ph (13.9 kcal/mol
8
at -4 ºC) . The activation energy barrier of the reductive
13
To confirm the arrangement of ligands around Ir, a CO-
1
labelled sample of 3 was prepared. In the H NMR spectrum of
the latter, the hydride resonances appear as doublets of triplets
of doublets; the same multiplicity is observed for the CO
elimination of benzene from 2 was calculated by DFT,
‡
confirming the experimental data (ΔG = 16.0 kcal/mol at -3
13
signals in the non-decoupled C NMR spectrum. Large two-
ºC).
1
13
bond H- C couplings of 42.9 Hz and 42.5 Hz for 3-syn and 3-
anti, correspondingly, indicate a mutual trans arrangement of
The existence of two hydride signals for 2 at low
temperatures can be explained by the lack of a horizontal plane
of symmetry and the presence of two isomeric compounds - syn
and anti with respect to the mutual orientation of C(α)–H and
Ir–H. These isomers can be trapped by addition of CO, giving
9
hydride and CO ligands; therefore, the phenyl group occupies
1
13
the position opposite to the pincer ligand. A three-bond H- C
coupling of 3.3 Hz is consistent with anti mutual orientation of
C(α)–H and Ir–CO in 3-syn, and the smaller coupling of 1.1 Hz
implies syn arrangement for 3-anti, according to the well-
known dependence of couplings from the dihedral angle. The
1
and 49.1 in the P{ H} NMR spectra as well as signals at -9.27
8e adducts 3-syn and 3-anti, characterized by signals at 45.1
1
31
3
3
3
(
3
td, JPH = 17.0, JHH = 1.6 Hz,) and -8.76 (td, JPH = 19.0 Hz,
3
same trend is observed for JHH, which is 1.6 Hz for 3-syn (syn
arrangement of C(α)–H and Ir-H) and 2.3 Hz for 3-anti (anti
1
JHH = 2.3 Hz) ppm in the H NMR spectra, correspondingly.
2
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arrangement of C(α)–H and Ir-H). Finally, despite a lower product is the result of a formation of a C–C double bond from
14
content in the mixture, X-ray quality crystals of 3-anti were non-activated Csp3–H bonds.
obtained, and the structure determination verified the A few examples of a somewhat related, stoichiometric,
View Article Online
DOI: 10.1039/C4SC03839H
conclusions based on spectroscopic data (Fig. 1).
dehydrogenative cross-coupling of C–H bonds to give olefin
moieties have been reported in the literature, but they are all
based on significantly more reactive benzylic C–H bonds of
15
substituted arylphosphines.
Fig.ꢀ 1ꢀ Molecularꢀ structureꢀ ofꢀ complexꢀ 3-antiꢀ withꢀ thermalꢀ ellipsoidsꢀ atꢀ 30%ꢀ
probabilityꢀlevel.ꢀHydrogenꢀatoms,ꢀexceptꢀforꢀtheꢀoneꢀatꢀC1,ꢀhaveꢀbeenꢀomittedꢀ
forꢀclarity.ꢀSelectedꢀbondsꢀ(Å)ꢀandꢀanglesꢀ(°):ꢀIr1-C1ꢀ2.193(7),ꢀIr1-C11ꢀ2.155(8),ꢀ
Ir1-C9ꢀ 1.904(7),ꢀ Ir1-P1ꢀ 2.365(2),ꢀ Ir1-P2ꢀ 2.358(2),ꢀ C9-O1ꢀ 1.145(9),ꢀ C1-Ir1-C11ꢀ
Fig.ꢀ 2ꢀ Molecularꢀ structureꢀ ofꢀ complexꢀ 4ꢀ (oneꢀ ofꢀ twoꢀ moleculesꢀ fromꢀ theꢀ
asymmetricꢀ unitꢀ isꢀ shown)ꢀ withꢀ thermalꢀ ellipsoidsꢀ atꢀ 30%ꢀ probabilityꢀ level.ꢀ
Hydrogenꢀatomsꢀhaveꢀbeenꢀomittedꢀforꢀclarity.ꢀSelectedꢀbondsꢀ(Å)ꢀandꢀanglesꢀ(°):ꢀ
Ir2-C41ꢀ 2.200(4),ꢀ Ir2-C62ꢀ 2.156(4),ꢀ Ir2-C51ꢀ 2.092(5),ꢀ Ir2-P3ꢀ 2.291(1),ꢀ Ir2-P4ꢀ
1
76.5(3),ꢀP1-Ir-P2ꢀ158.06(7).ꢀ
2
.290(1),ꢀC41-C62ꢀ1.425(7),ꢀC41-Ir1-C51ꢀ164.0(2),ꢀP1-Ir-P2ꢀ160.05(5).ꢀ
C–C coupling reaction in 2
Upon heating a benzene solution of 2 to 120 °C, the NMR
signals of 2 descend and a new AX system appears in the
Hydrogenation of the olefin complex 4. С–С bond cleavage
31
1
Interestingly, the process is reversible and the C=C bond in 4
can be cleaved under certain conditions. Thus, exposure of a
solution of 4 in C D at room temperature to 1 atm of hydrogen
P{ H} NMR spectrum. Gratifyingly, upon addition of tert-
butylethylene as a hydrogen acceptor, complex 4 is formed in
1
almost quantitative yield. H and, to some extent, C{ H}
13
1
6
6
results in a simultaneous formation of a mixture of complexes 5
and 6 in a ca. 93:7 ratio (Scheme 2). This ratio is temperature
and hydrogen-pressure dependent, with the amount of 6 being
raised under conditions favoring the solubility of H2 in benzene
and the equilibrium is established quite fast. For example,
NMR spectra of compound 4 are very complex due to a number
3
of overlapping signals. Doublets at 1.90 ( JPH = 13.0 Hz) and
3
.91 (d, JPH = 9.7 Hz) ppm from methyls point to the activation
0
of one of the tert-butyl groups. The =CH– proton resonates at
3
.95 ppm (d, JPH = 20.5 Hz). In the C{ H} NMR spectrum
13
1
1
2
2
under 1.5 atm of H , the proportion 5:6 is 74:26 at 4 ºC, 86:14
2
the olefinic signals are observed at 76.6 ( JP2C = 13.1 Hz, JP1C
31
1
at 25 ºC and 98:2 at 80 ºC. The P{ H} NMR spectrum of 5
2
2
=
doublets of doublets. An estimation (hampered due to overlap)
4.8 Hz) and 49.5 ( JP2C = 12.3 Hz, JP1C = 1.3 Hz,) ppm as
2
consists of an AX system (75.7, 7.2 ppm, JP1P2 = 344.0 Hz),
1
while in the H NMR spectrum three separate hydride signals
1
of JCH which is around 156 Hz, is consistent with the expected
2
sp hybridization of the olefinic carbons. The structure of
appear as rather complex multiplets due to couplings with two
non-equivalent phosphorus nuclei, two hydrides and the olefin
2
moiety. From those, a JHH = 10.7 Hz should be mentioned as a
complex 4 was confirmed using X-ray crystallography (Fig. 2).
This unambiguously shows that the α-carbon and one of the
methyl groups of the t-butyl have been coupled to form a new
olefin functionality that the iridium(I) coordinates. The iridium
atom has a distorted square-planar arrangement; average (from
two molecules in the asymmetric unit) Ir–C bonds lengths of
rare example of a coupling between two mutually trans non-
16
equivalent hydride ligands. The hydrides in complex 5 do not
exchange positions up to 80 ºC. In accordance with the
increased oxidation state of the Ir atom, the NMR signals of the
olefin moiety in 5 are shifted downfield compared 4; for
2
fall in the range observed for electron-rich Ir olefin
.16 and 2.20 Å as well as a C=C bond bond length of 1.42 Å
3
example -CH= proton resonates at 2.51 ppm (dd, JP2H = 21.7
3
Hz, J = 3.3 Hz and the quaternary carbon signal is observed
10
P1H
complexes . During the formation of 4 from 1, three Csp3–H
bonds are activated intramoleculary in addition to one external
at 81.3 ppm (m).
11
Csp2–H bond. A cyclometallation of tert-butyls or other
groups
12,13
bound to phosphorus is not unprecedented in the
chemistry of iridium pincer complexes, but in the case of 4 it
results in the formation of a new C–C double bond. To the best
of our knowledge, this is the first example where the main
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reverse direction when H2 pressure is applied. Remarkably, the
transformation from 5 to 7 corresponds to a net ruVpietuwrAertioclfe OanClin–e
C double bond, while the transformation from 6 to 7 is a net
DOI: 10.1039/C4SC03839H
cleavage of a nearly unstrained, unactivated Csp3–Csp3 bond,
17
with few precedents previously reported. Together with the
18
tandem catalytic systems for alkane metathesis, this process is
a rare example of an organometallic compound capable of a net
cleavage of unactivated Csp3–Csp3 bonds.
Computational studies
To understand each step of the whole transformation we
performed DFT calculations on the key reactions for forming
and breaking C–C bonds, based on the experimentally observed
species. Several mechanistic scenarios were considered for the
formation of complex 7, where the one with the lowest barrier
and which is fully consistent with the experimental conditions
is depicted on Fig. 3. First, from complex 5, a double bond
insertion into the Ir–H bond leads to intermediate 8, which can
be transformed to the experimentally observed Ir(V) complex 6
via an oxidative addition of dihydrogen. The calculated barrier
of ca. 20 kcal/mol is in qualitative agreement with the rate of
establishment of the equilibrium (few minutes) at ambient
temperature. Intermediate 8 undergoes an α-alkyl elimination
and carbene 9 is formed. The activation barrier is calculated at
Schemeꢀ2ꢀReactionsꢀofꢀcomplexꢀ4ꢀwithꢀhydrogen.ꢀ
Complex 6 is characterized by an AB-system (69.8, 63.3 ppm,
2
31
JP1P2 = 312.9 Hz) in the P{ H} NMR spectrum as well as a
1
2
1
triplet resonance at -10.07 ppm ( JPH(avg) = 9.5 Hz) in the H
NMR, integrating as 4H. 2D NMR spectra strongly argue that 6
is a product of insertion of the olefin moiety into one of the Ir–
H bonds, which added one molecule of hydrogen. For instance,
in contrast to 5, no -CH- type carbons reveal a cross-peak with
1
13
the hydride resonance in H- C HMBC, while three
correlations with -CH2- type carbons are observed, with two of
them belonging to -CH2P- groups and one to the former -CH=
group.
3
1.4 kcal/mol via transition state TS8-9. Complex 9 proceeds
through an α-hydride insertion to form intermediate 10, which
under hydrogen atmosphere conditions undergoes an H2
addition that finally forms the Ir(V) complex 11. The transition
state TS9-10 is calculated at 25.8 kcal/mol on the free energy
surface. This step is followed by C–H reductive elimination by
Ir–Csp3 and Ir–H, which leads to formation of a new Csp3–H
bond in the pincer ligand. The free energy barrier via transition
state TS11-12 is calculated at 11.8 kcal/mol.
When a mixture of 5 and 6 is heated at 140 ºC for 24 h
under an atmosphere of hydrogen, a quantitative conversion to
tetrahydride complex 7 is observed, where the initial structure
of the pincer ligand is recovered. Hence, the observed
formation of a C–C double bond via Csp3–H activation is fully
reversible, and proceeds in the forward direction when a
hydrogen acceptor like tert-butylethylene is used and in the
4
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Fig.ꢀ3.ꢀProfileꢀofꢀtheꢀcalculatedꢀrelativeꢀGꢀ(kcal/mol)ꢀforꢀtheꢀformationꢀofꢀcomplexꢀ7ꢀfromꢀcomplexꢀ5ꢀviaꢀcarbeneꢀcomplexꢀ9.ꢀ
ꢀ
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DOI: 10.1039/C4SC03839H
addition/elimination at the metal have high barriers at least in
part due to repulsion between the bulky alkyl ligands. The
suggested mechanism is supported by the experimental
observation of an α-hydrogen migration to Ir during the
formation of a carbene complex (see below). Also, a number of
1
1
2
3
1 2 3
R migrations from a R M=CR R fragment to M–CR R R are
19
known , with a few precedents reported for vinylidene pincer
20
complexes . It should be noted that for the somewhat related
coupling reaction involving benzylic C–H bonds, a similar
15b,c
reaction sequence was also proposed. . Interestingly, the
previous examples where unactivated Csp3–Csp3 bond were
cleaved proceeded via another mechanism, namely β-carbon
17
elimination . In addition, several examples of 1,2 shifts of
methyl and benzyl groups to give arenium complexes
(
likely proceed through electrophilic attack of R on Cipso are
organometallic analogs of Wheland intermediates), which
+
Fig.ꢀ4.ꢀProfileꢀofꢀtheꢀcalculatedꢀrelativeꢀGꢀ(kcal/mol)ꢀforꢀtheꢀformationꢀofꢀcomplexꢀ
ꢀfromꢀcomplexꢀ5ꢀviaꢀreductiveꢀeliminationꢀfromꢀIr(III)ꢀ(blue)ꢀorꢀIr(V)ꢀ(red).ꢀꢀ
7
21,22
known; these may be followed by subsequent β-elimination.
As mentioned before, the formation of the C–C double bond
is reversible, proceeding in one direction or other depending on
the reaction conditions. In an agreement with the experiment,
under hydrogen atmosphere, formation of complex 7 is favored,
while in the presence of a hydrogen acceptor, such as tert-
butylethylene, the reverse reaction occurs leading to the olefin
complex 5 (Fig. 5). In the reaction with tert-butylethylene, the
overall activation energy barrier corresponds to the C–C bond
Ultimately, the process finishes with an oxidative addition of
one dihydrogen molecule leading to the Ir(V)H4 complex 7. The
overall activation free energy corresponds to the C–C bond
cleavage step (31.4 kcal/mol).
We also considered alternative mechanisms from 8,
involving inter alia C–H reductive elimination to give an
alkane intermediate, which could be followed by Csp3–Csp3
oxidative addition (Fig. 4, red and blue pathways). However,
the activation energies associated with this process were found
formation step (TS9-8) and is calculated at 28.0 kcal/mol.
ꢀ
to
be
prohibitively
high.
C–C
bond
oxidative
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ARTICLEꢀ
Fig.ꢀ5.ꢀProfileꢀofꢀtheꢀcalculatedꢀrelativeꢀGꢀ(kcal/mol)ꢀforꢀtheꢀformationꢀofꢀcomplexꢀ5ꢀwithꢀandꢀwithoutꢀhydrogenꢀacceptor.
high yield and isolate it from other products and so far 16 and
1
Dehydrogenation of the cyclohexyl ring
7 were characterized in situ.
The aromatization process begins with the formation of
For comparison and to gain more insight in the process, we
attempted the thermolysis of the parent, less electron-rich carbene complex 16, which demonstrates a singlet in the
3
1
1
P{ H} NMR spectrum at 66.8 ppm and a remarkable high-
hydrido-chloride complex 1. Heating (PCyP)IrHCl (1) in
toluene at higher temperatures reveals that it undergoes field signal at -4.18 ppm in the H NMR from the β- C–H
aromatization and several intermediates were detected by NMR groups, probably due to the magnetic anisotropy effect of the
1
13
1
spectroscopy during this process (Scheme 3). All steps before C=Ir bond. C{ H} NMR spectrum reveals a resonance at
aromatization are reversible and carrying out the reaction in a 246.9 ppm, corresponding to the α-carbon. This value
23
sealed flask results in the simultaneous presence of compounds dramatically differs from the 66.6 ppm reported by Shaw, who
, 16, 17, 18, 19 in the reaction mixture; to drive the process to proposed a contribution of an ylide-type structure for the
1
completion it is necessary to purge the flask with Ar several related complex 20 (Chart 1) in order to explain the deviation
times or to add a hydrogen acceptor like tert-butylethylene. In a of the observed chemical shift from the expected for carbene
control experiment, a mixture of 1, 16, 17, 18 was indeed complexes around 200 ppm. The ylide character of Shaw's
converted to 1 under a H2 atmosphere at 155 ºC. The ratio of complex entered into several papers and has been the subject of
24
compounds 1, 16, 17, 18, 19 depends on conditions, with the some dicussion. Based on our data, we suggest that there are
percentage of more dehydrogenated products increasing with no reason to invoke an ylide structure for 16, and probably not
increasing temperature. Despite
including solution and solid-state thermolysis of 1 under its concentration was fairly low, and the overall number of
various conditions, we were unable to obtain complex 16 in a signals observed by Shaw was three instead of the five expected
a number of attempts, for 20 either. Complex 20 was characterized in a mixture where
13
C
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from the symmetry of the complex 20. Therefore, given the stability of 18 allows an accumulation (up to 75%) in the
similarity of complexes 20 and 16, it could very well be that the reaction mixture, from which 18 can be isolated by
View Article Online
DOI: 10.1039/C4SC03839H
signal at 66.6 ppm comes from the -CH2- groups adjacent to the chromatography.
carbene moiety since the analogous -CH-groups in complex 16
C–C coupling reaction in complex 1
resonate at 75.0 ppm, while the true low-intense, low-field
signal of the carbene carbon atom of 20 was not observed. In During NMR spectroscopy monitoring of the formation of 18,
2
fact, according to the calculations bonding pattern in complex the appearance of a new AX system (66.3, 23.7 ppm, JP1P2 =
31
1
6 is close to those in Fisher-type carbenes and thus 16 is better 370.0 Hz) was detected in the P{ H} spectrum. The yield of
1
described as an Ir(I) compound (see SI).
the new compound, 21, was low, but we were able to isolate it
by crystallization. The NMR features of 21 are similar to those
of 4, with signals of the olefinic proton and carbons being
significantly high-field shifted, and the X-ray structure of 21
(
Fig. 6) confirms that a similar olefin complex has formed. The
C–C distance (1.441(5) Å) is comparable to that in 4 and the Ir–
C bonds (2.142(4) and 2.112(4) Å) are somewhat shorter. As
shown in Scheme 4, four non-activated Csp3–H bonds are
cleaved during the synthesis of 21 (starting from the ligand
precursor), making this process a rare example of a quadruple
C–H activation at a single metal center. It also shows that the
C–C coupling is a general reaction for this class of compounds.
While for complexes 4 and 21 high ligand binding energy did
not allow to organize a catalytic cycle, we believe that this
reactivity pattern can form a basis for future catalytic cross-
Schemeꢀ3.ꢀAromatizationꢀofꢀtheꢀcyclohexane-basedꢀpincerꢀligand.ꢀ
Formation of complex 16 requires high temperature and at couplings of non-activated Csp3–H and possibly other C–H
these conditions, 16 readily turns into the isomeric compounds bonds under relatively mild conditions. In addition, whereas
1
7, with the equilibrium shifted to the side of the latter one of the reasons for the unreactive nature of Csp3–Csp3 bonds
31
1
complexes. The P{ H} NMR spectrum reveals two isomers of is their low exposure to metal atoms due to the screening by C–
2
1
7 each with an ABX system (67.7, 64.9 ppm, JP1P2 = 336.8 H or other bonds, we here show that at least in some cases such
2
Hz and 66.6, 63.0 ppm, JP1P2 = 335.0 Hz; high-field hydride screening can be used in a beneficial way, during which simple
signals are not decoupled), which indicates the presence of two metallation of one of the C–H bonds leads to a rearrangement
non-equivalent phosphorus nuclei and a lack of the usual where a purely aliphatic fragment is cut into two others.
symmetry of the molecule. The corresponding hydride signals
2
2
are observed at -41.25 (t, JP1H = JP2H = 13.2 Hz) and -44.63 (t,
2
2
JP1H = JP2H = 12.3 Hz) ppm as apparent triplets due to virtually
25
13
1
equal coupling constants with both P atoms. The C{ H}
NMR spectrum confirms the presence of one tetra-substituted
double bond per molecule.
Schemeꢀ4ꢀQuadrupleꢀC–Hꢀactivationꢀofꢀcyclohexane-basedꢀpincerꢀligand.ꢀ
Chartꢀ1ꢀShawꢀ'sꢀcarbeneꢀcomplexꢀandꢀproposedꢀcontributionꢀofꢀylideꢀstructure.ꢀ
Further dehydrogenation results in the formation of diene
complex 18, which again is characterized by an ABX system in
31
1
2
the P{ H} NMR spectrum (67.7, 60.3 ppm, dd, JP1P2 =
2
34.3), as well as a doublet ( JPH = 8.0 Hz) at 5.61 ppm from
3
the olefinic proton and an apparent triplet at -43.30 ( JP1H =
2
2
JP2H = 12.7 Hz) ppm from the hydride. The =CH- group
13
1
13
31
appears at 117.4 in the C{ H} spectrum and a large C– P
coupling of 44.4 Hz together with 2-D spectra confirms the
position of the double bond near the phosphorus atom. Under
the conditions specified in Scheme 4 the relative kinetic
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and crystallographic data in CIF or other electronic format see
DOI: 10.1039/b000000x/
View Article Online
DOI: 10.1039/C4SC03839H
(a) B. A. Arndtsen, R. G. Bergman, T. A. Mobley and T. H. Peterson,
1
Acc. Chem. Res., 1995, 28, 154; (b) A. E. Shilov and G. B. Shul’pin,
Chem. Rev. 1997, 97, 2879; (c) R. H. Crabtree, J. Chem. Soc., Dalton.
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4
17, 507; (e) R. G. Bergman, Nature, 2007, 446, 391.
2
(a) X. Chen, K. M. Engle, D.-H. Wang and J.-Q. Yu, Angew. Chem. Int.
Ed. 2009, 48, 5094; (b) O. Baudoin, Chem. Soc. Rev., 2011, 40, 4902; (c)
L. Ackermann, Chem. Rev., 2011, 111, 1315; (d) C. Liu, H. Zhang, W.
Shi and A. Lei, Chem. Rev., 2011, 111, 1780; (e) P. B. Arockiam, C.
Bruneau and P. H. Dixneuf, Chem. Rev., 2012, 112, 5879.
3
(a) K. Hirano and M. Miura, Chem. Commun., 2012, 48, 10704; (b) X.
Fig.ꢀ 6ꢀ Molecularꢀ structureꢀ ofꢀ complexꢀ 21ꢀ withꢀ thermalꢀ ellipsoidsꢀ atꢀ 30%ꢀ
probabilityꢀlevel.ꢀHydrogenꢀatomsꢀhaveꢀbeenꢀomittedꢀforꢀclarity.ꢀSelectedꢀbondsꢀ Shang and Z.-Q. Liu, Chem. Soc. Rev., 2013, 42, 3253; (c) S. I.
(
2
1
Å)ꢀ andꢀ anglesꢀ (°):ꢀ Ir1-C1ꢀ 2.142(4),ꢀ Ir1-C22ꢀ 2.112(4),ꢀ Ir1-Cl1ꢀ 2.380(1),ꢀ Ir1-P1ꢀ
.2857(9),ꢀ Ir1-P2ꢀ 2.3153(9),ꢀ C1-C22ꢀ 1.441(5),ꢀ Cl1-Ir1-C1ꢀ 163.4(1),ꢀ P1-Ir-P2ꢀ
60.24(3).ꢀ
Kozhushkov and L. Ackermann, Chem. Sci., 2013, 4, 886; (d) S. A.
Girard, T. Knauber and C.-J. Li, Angew. Chem. Int. Ed., 2014, 53, 74.
4
Metal-Catalyzed Cross-Coupling Reactions, 2nd ed. (Eds.: A. de
Meijere, F. Diederich), Wiley-VCH, Weinheim, 2004.
J. Choi, A. H. R. MacArthur, M. Brookhart and A. S. Goldman, Chem.
Rev., 2011, 111, 1761.
Conclusions
5
In conclusion, we have presented the C–H activation reactivity
of cyclohexane-based iridium pincer complexes. The major
difference between these systems and their arene-based
counterparts is the non-innocent character of the pincer ligand,
where both α- and β-hydrogens can be eliminated. This opened
up for an unprecedented reactivity where non-activated Csp3–H
bonds extrude two molecules of dihydrogen in the formation of
a C–C double bond. This process is reversible and upon
pressurizing with H2 the resulting C–C bond can be
hydrogenated to recover the ligand structure; remarkably, this
happens via a net Csp3–Csp3 bond cleavage. Mechanistic studies
indicate that a key step to open up for such reactivity is the
formation of the carbene complex, which, via migratory
insertion or deinsertion into an Ir–C bond is responsible for C–
C bond formation and cleavage. This knowledge will hopefully
enable a catalytic variety of this transformation allowing the
intermolecular formation of double bonds from the coupling of
two non-activated aliphatic carbons.
6
8
7
A. Arunachalampillai, D. Olsson and O. F. Wendt, Dalton Trans., 2009,
626.
A.V. Polukeev, R. Gritcenko, K. J. Jonasson and O. F. Wendt,
Polyhedron, 2014, 84, 63.
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Goldman, J. Am. Chem. Soc., 2000, 122, 11017.
(a) M. Montag, I. Efremenko, R. Cohen, L. J. W. Shimon, G. Leitus, Y.
8
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Diskin-Posner, Y. Ben-David, H. Salem, J. M. L. Martin and D. Milstein,
Chem. Eur. J., 2010, 16, 328; (b) A. V. Polukeev, P. V. Petrovskii, A. S.
Peregudov, M. G. Ezernitskaya and A. A. Koridze, Organometallics,
2
1
013, 32, 1000.
0 (a) A. Friedrich, R. Ghosh, R. Kolb, E. Herdtweck and S. Schneider,
Organometallics, 2009, 28, 708; (b) C. Bianchini, E. Farnetti, M.
Graziani, G. Nardin, A. Vacca, F. Zanobini, J. Am. Chem. Soc., 1990,
1
12, 9190.
1
1 (a) H. A. Y. Mohammad, J. C. Grimm, K. Eichele, H.-G. Mack, B.
Speiser, F. Novak, M. G. Quintanilla, W. C. Kaska and H. A. Mayer,
Organometallics, 2002, 21, 5775. (b) А. V. Polukeev, S. A. Kuklin, P. V.
Petrovskii, F. M. Dolgushin, M. G. Ezernitskaya and A. A. Koridze, Russ.
Chem. Bull., Int. Ed., 2010, 59, 745.
Acknowledgements
Financial support from the Swedish Research Council, the Knut
and Alice Wallenberg Foundation and the Crafoord Foundation
is gratefully acknowledged. Computational resources have been
provided by the National Supercomputer Centre in Linköping ,
Sweden.
1
2 (a) M. Yamashita, Y. Moroe, T. Yano and K. Nozaki, Inorg. Chim.
Acta, 2011, 369, 15; (b) M. A. Esteruelas, M. Olivan and A. Velez, Inorg.
Chem., 2013, 52, 5339.
1
3 For migration of Ir on a benzene ring, assisted by metallation of
2
3 2
chelating -CH -N(CH ) group, see A. A. H. van der Zeijden, G. van
Koten, R. Luijk, R. A. Nordemann and A. L. Spek Organometallics,
1988, 7, 1549.
Notes and references
Centre for Analysis and Synthesis, Department of Chemistry, Lund
a
1
4 It should be noted that formation of olefins from saturated carbons
University, PO Box 124, 22100 Lund, Sweden.
b
Division of Theoretical Chemistry & Biology, School of Biotechnology,
takes place during alkane metathesis, but they are not major products
because of thermodynamical constraints. For details, see ref. 18.
KTH Royal Institute of Technology, Stockholm SE-106 91, Sweden.
1
5 (a) J. Campos, M. F. Espada, J. Lopez-Serrano, E. Carmona, Inorg.
†
Electronic Supplementary Information (ESI) available: Experimental
Chem., 2013, 52, 6694; (b) J. Campos, J. Lopez−Serrano, E. Alvarez and
E. Carmona, J. Am. Chem. Soc., 2012, 134, 7165; (c) W. Baratta, M.
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details, characterization data, cartesian coordinates, additional graphs and
computational details. CCDC 1024127, 1024128 and 1024129. For ESI
6
701; (d) W. Baratta, E. Herdtweck, P. Martinuzzi and P. Rigo,
8
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Organometallics, 2001, 20, 305; (e) M. A. Bennett and P. A. Longstaff, J.
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6 S. Gründemann, H.-H. Limbach, G. Buntkowsky, S. Sabo-Etienne, B.
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1
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0 (a) J. D. Hackenberg, S. Kundu, T. J. Emge, K. Krogh-Jespersen and
(
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1 For a 1,2 shift to an aryl group in Pt pincer complexes, see (a) J.
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1
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2
2 For a 1,2 shift to aryl groups in Rh and Ir pincers complexes, followed
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1
2
5
McDonald, R. Markham, M. C. Norton, B. L. Shaw and B. Weeks, J.
Chem. Soc., Dalton Trans., 1982, 1217.
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4 (a) M. E. van der Boom and D. Milstein, Chem. Rev., 2003, 103, 1759;
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5 Spin simulations suggest that these signals are not virtual triplets,
(
2
2
which one may expect to see in the X part of the ABX system; each of
them can be described as doublet of doublets, which collapsed into a
triplet due to equal coupling constants.
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