A discrete, air, protic, and thermally stable (NNC)Ir(III) pincer complex was synthesized that catalytically activates the CH bond of methane in trifluoroacetic acid; functionalization using NaIO_4 and KIO_3 gives the oxy-ester

Ess, Daniel H.

Goddard, William A., III

Meier, Steven K.

Oxgaard, Jonas

Periana, Roy A.

Stewart, Timothy

Young, Kenneth J. H.

English

Caltech Authors - Main

Experimental realization of catalytic CH_4 hydroxylation predicted for an iridium NNC pincer complex, demonstrating thermal, protic, and oxidant stability

Experimental realization of catalytic CH4 hydroxylation predicted
for an iridium NNC pincer complex, demonstrating thermal, protic,
and oxidant stabilityw
Kenneth J. H. Young,a Jonas Oxgaard,ab Daniel H. Ess,bc Steven K. Meier,a
Timothy Stewart,a William A. Goddard, III*b and Roy A. Periana*c
Received (in Cambridge, UK) 5th January 2009, Accepted 12th March 2009
First published as an Advance Article on the web 23rd April 2009
DOI: 10.1039/b823303a
A discrete, air, protic, and thermally stable (NNC)Ir(III) pincer
complex was synthesized that catalytically activates the CH
bond of methane in triﬂuoroacetic acid; functionalization using
NaIO4 and KIO3 gives the oxy-ester.
The most eﬃcient methane hydroxylation catalysts utilize
PdII, PtII, HgII, or AuI/III cations that operate by a sequence
of electrophilic CH bond activation (CHA)1 followed by
reductive oxy-functionalization (ROF).2 Because of their
electrophilic character, these catalysts are highly susceptible
to poisoning by water or methanol, requiring strong acid
solvents to minimize this inhibition. To minimize this inhibition
we are modifying the highly eﬀective Pt(bipyrimidine)Cl2
motif1b,3 to reduce its electrophilicity by increasing the
electron density at the metal center.
In 2003 Goddard and co-workers4a used the mechanism
that they had established4b for the (bpym)PtCl2 system to set
up a quantum mechanical rapid prototyping (QMRP) strategy
enabling 1000s of ligand–metal oxidation state and solvent
conditions to be sampled rapidly. This study showed that IrIII
complexed to an NNC ligand motif (a simpliﬁed version of
1-TFA) should react with methane by CHA with an activation
barriero30 kcal mol1, should not be poisoned by H2O, and
could undergo reductive functionalization through an IrV
intermediate to generate a functionalized product.
We report here the experimental realization of this predicted
system. This study provides a lesson in using QM theory to
examine a large number of systems to quickly narrow the
candidates down to a select few, and shows the experimental
processes required to develop a stable functional catalyst.
The ﬁrst step was to extend the functional groups in the
simpliﬁed NNC ligand to form a stable framework using
donating C-ligands.3d However, the key challenges are
ensuring catalyst stability, maintaining eﬃcient CHA,5-7 and
developing compatible oxy-functionalization reactions.3a,8,9
Because Ir(I) to Ir(III) conversion is likely with electron-
donating ligands under protic and oxidizing conditions
(e.g. Scheme 1A),8 we focused our eﬀorts on catalytic systems
based on CHA with Ir(III) followed by either direct O-atom
insertion10 from YO and then hydrolysis (Scheme 1B) or
oxidation by YO to an IrV–CH3 species, followed by
ROF (Scheme 1C).9 We observed that treatment of
(NN)(NC)Ir(III)(Me)OTf (NN = k2-4,40-di-tert-butyl-2,20-
bipyridine, NC = Z2-(N,C-3)-6-phenyl-2,20-bipyridine) with
PhI(TFA)2 (PITFA)
8c leads to eﬃcient ROF to generate
methyl oxy-esters, presumably via an IrV–CH3 intermediate,
we designed a catalyst that would activate the methane CH
bond with an Ir(III) motif and then utilize a similar ROF route.
We report an (NNC)IrIII pincer complex (NNC = Z3-6-
phenyl-2,20-bipyridine) that catalytically activates and func-
tionalizes methane. Scheme 2 shows the synthetic route to the
trans(Et,TFA)-(NNCtBu)Ir(TFA)(C2H4)Et, 1-TFA (TFA =
triﬂuoroacetate). Treatment of 6-phenyl-4,40-di-tert-butyl-
2,20-bipyridine (NNCtBu) with [Ir(C2H4)2Cl]2 led to the corres-
ponding tridentate trans(Cl,Et)-(NNCtBu)IrCl(C2H4)Et complex
(1-Cl) inB66% yield as an air-stable solid. 1-Cl has been fully
characterized. Treatment of 1-Cl with AgTFA in CH2Cl2
replaces the Cl with the less coordinating triﬂuoroacetate,
CF3CO2
, group to generate (NNCtBu)Ir(Et)(TFA)(C2H4),
1-TFA, which has been fully characterized. Fig. 1 shows the
X-ray crystal structure. Formation of 1-TFA is also supported
by appearance of a new resonance at 78.99 ppm in the
19F spectra.
Dissolution of 1-TFA in triﬂuoroacetic acid (HTFA)
releases ethane with formation of (NNCtBu)Ir(TFA)2(C2H4)
(1-TFA2), which has been fully characterized.
11 Heating
1-TFA2 in HTFA solvent leads to loss of ethylene with
formation of a solution of the solvent complex,
Scheme 1 Alternative catalytic schemes for hydrocarbon hydroxylation.
Y is an O carrier.
aUniversity of Southern California, Los Angeles, CA, 90089, USA
bMaterials and Process Simulation Center, California Institute of
Technology, Pasadena, CA, 91125, USA.
E-mail: wag@wag.caltech.edu
c The Scripps Research Institute, Scripps Florida, Jupiter, FL, 33458,
USA. E-mail: rperiana@scripps.edu; Fax: +1 561-228-3064;
Tel: +1 561-228-2457
w Electronic supplementary information (ESI) available: Experimental
details and DFT xyz coordinates. CCDC 697907–697909. For ESI and
crystallographic data in CIF or other electronic format see DOI:
10.1039/b823303a
3270 | Chem. Commun., 2009, 3270–3272 This journal is c The Royal Society of Chemistry 2009
COMMUNICATION www.rsc.org/chemcomm | ChemComm
(NNCtBu)Ir(TFA)2(HTFA), 1A, and the k
2-acetate complex,
1B, (from NMR). These complexes could not be isolated.
However, consistent with the formation of these complexes,
trapping with pyridine leads to quantitative formation of the
expected pyridine complex, (NNCtBu)Ir(TFA)2(Py), see ESIw.
In situ NMR analysis (see ESIw) indicates 1-TFA2 is thermally
stable in HTFA after heating at 180 1C for 1 h.
Heating a stirred solution of DTFA–CH4 with 1-TFA
(0.3 mol%) for 2 h at 180 1C leads to rapid and extensive
methane H/D exchange. Analysis of the reaction gas phase by
GC-MS indicated that B30% of the CH4 was converted to
21.2% CH3D, 6.6%, CH2D2, 1.3% CHD3, 0.6% CD4, TON
E 153, TOF E 2.12  102 s1. Note that under identical
conditions, related complexes such as (NN)(NC)Ir(III),
(NNC)Pt(II), and Pt(bpym)Cl2 show no H/D exchange.
1b,3d,8c
The rate of methane CH activation is comparable to the
Pt(bpym)Cl2–H2SO4 system, the most eﬃcient CH activation
system that catalyzes methane hydroxylation.
Kinetic analysis shows that the rate of formation of the
various isotopologs is consistent with a Schultz–Flory type of
reaction sequence for a reaction mechanism where each
encounter methane molecule with the catalyst leads to a single
H/D exchange. This contrasts with our results on (bpym)PtCl2
where each encounter can lead to more than one exchange and
simultaneous generation of all the methane isotopologs.1b,12
Rate data obtained between 105 1C and 135 1C give DHw =
24 3 kcal mol1 for H/D exchange between CH4 and DTFA.
Analysis of the reaction mixture by 1H NMR revealed that
multiple Ir complexes were present but that the NNC-ligand
remained coordinated (at least through an NN binding mode)
to the Ir center. However, extensive deuterium incorporation
into the phenyl ring is observed (see B3LYP calculations).
At temperatures above 150 1C, slow loss of catalytic activity
is observed with 1-TFA and at 180 1C catalysis stops afterB6 h.
1A and 1B are still present in small amounts but the majority
of the solution is composed of two new species. The catalyst is
more stable at lower temperatures and at 105 1C B62 turn-
overs were observed after 45 h without any loss in activity.
H/D exchange does not occur in weaker, more coordinating
acids, such as acetic acid at 180 1C. Consistent with the CHA
reaction proceeding via reversible substrate coordination,
followed by CH cleavage, the addition of DMSO, a strongly
coordinating ligand, leads to complete reaction inhibition.
Further support for a CH activation mechanism is the
observation that methane H/D exchange is also observed in
non-acidic media. Thus, heating a solution of 1-TFA in neat
C6D6 with CH4 (514.7 psi) at 140 1C for 6 h led to methane
H/D exchange (B60 turnovers, 5.3% CH3D, 0.7% CH2D2).
In addition to methane, 1-TFA also catalyzes H/D exchange
with linear and cyclic alkanes such as octane, cyclohexane, and
cyclooctane in triﬂuoroacetic acid. With octane we observed
primarily C-1 and C-2 CHA on the basis of 2H and 13C NMR
analyses.
Having established rapid H/D exchange with 1-TFA, we
examined if added oxidants would facilitate overall catalytic,
selective, oxidation of methane to methyl triﬂuoracetate
(MeTFA). Initial attempts to formMeTFA with the hypervalent
iodine oxidant, PITFA, used with the (NN)(NC)Ir(III)–CH3
system8c were unsuccessful. However, when a solution of
1-TFA in DTFA is heated with methane (514.7 psi) at 180 1C
for 3 h with NaIO4 as the oxidant, MeTFA is produced
(TON = 6.3).z There is a background reaction between
NaIO4 and CH4 in DTFA but the rate of formation
of MeTFA with 1-TFA is faster (see ESIw). Formation of
MeTFA was conﬁrmed by 1H, 13C, and 19F NMR and by
GC-MS and HPLC. When the reaction was carried out
with 100% 13CH4, only
13CH3OC(O)CF3 was observed by
13C NMR and GC-MS. The catalyst activity is o6 h and the
maximum yields of MeTFA based on methane, wereo5%. At
160 1C the reaction is slower, and after 5 h, 2.0 turnovers of
MeTFA were observed with 1-TFA. KIO3, a weaker oxidant,
also generated MeTFA but at lower rates than KIO4. Such
oxidants as nitrous oxide, urea hydrogen peroxide, and
pyridine oxide, did not generate MeTFA. Oxidants such as
Na2S2O8, OsO4, or K2Os(O)2(OH)4 did generate MeTFA, but
with less than 1 turnover.
Several CHA mechanisms were explored using B3LYP
DFT.13 Fig. 2 outlines the three lowest energy reaction
pathways leading to methane C–H bond cleavage by a model
1-TFA complex. We ﬁnd spontaneous loss of ethane and
ethylene from 1-TFA to give an equilibrium between 1A
Scheme 2
Fig. 1 Thermal ellipsoid plot of 1-TFA with 50% probability.
Hydrogens and benzene co-solvent removed for clarity. Selected bond
lengths (A˚): Ir(1)–N(2) 2.019(6), Ir(1)–C(16) 2.078(7), Ir(1)–C(29)
2.081(10) Ir(1)–N(1) 2.166(6), Ir(1)–O(1) 2.210(6). Selected bond
angles (1): N(2)–Ir(1)–C(16) 78.8(3), N(2)–Ir(1)–C(27) 161.0(3),
N(2)–Ir(1)–N(1) 76.7(2), C(16)–Ir(1)–N(1) 155.4(3), C(27)–Ir(1)–N(1)
84.3(3)C(29)–Ir(1)–O(1) 170.91(4).
This journal is c The Royal Society of Chemistry 2009 Chem. Commun., 2009, 3270–3272 | 3271
(3.4 kcal mol1) and 1B (0.0 kcal mol1). From 1B, the
k2-bound acetate can rearrange to either of two Z1 conﬁgura-
tions, allowing two diﬀerent methane coordination sites.
Because of the s-electron-donating capacity of the NNC
ligand, breaking the Ir–O bond trans to this ligand, giving
trans-2, is only 3.9 kcal mol1 above 1B, while cis-2 requires
14.9 kcal mol1 to generate the cis open coordination site. The
methane complexes with trans-2 and cis-2 have enthalpies of
4.1 and 6.5 kcal mol1, respectively.
The lowest energy transition states for C–H bond cleavage are
via a six-membered substitution mechanism, cis-TSwith a barrier
of 22.1 kcal mol1 and the trans-TS that is 1.1 kcal mol1 higher
(see ESIw for M06 and M06-2X energies).14
In these six-membered TSs, the CF3CO2
 group assists in
the cleavage of the C–H bond, simultaneously forming Ir–C
and O–H bonds. Intermediate cis-3, generated from cis-TS, is
endothermic by 16.8 kcal mol1 revealing why no Ir–CH3
species was detected.
From cis-2, the TS for methane activation by the cyclo-
metalated phenyl group, OHM-TS (24.1 kcal mol1), is only
2 kcal mol1 higher in energy than cis-TS. This oxidative
hydrogen migration (OHM)15 transition state has a charac-
teristic short Ir–H distance (1.56 A˚) and no intervening iridium
hydride intermediate between cis-2 and cis-4. The intermediate
formed from OHM-TS is cis-4, and is B9 kcal mol1 more
stable than cis-3. Therefore, deuterium incorporation into the
phenyl ring may occur because ofOHM-TS or cis-3 exchanges
of HTFA for DTFA followed by deuterium transfer to the
cyclometalated phenyl group to give deuterated cis-4.
In summary, we have synthesized a discrete, air, protic,
and thermally stable (NNC)Ir(III) pincer motif, 1-TFA, that
catalytically activates the CH bond of methane in triﬂuoro-
acetic acid. Functionalization of 1-TFA using NaIO4 and
KIO3 gives MeTFA.
We thank Chevron Energy Technology Company and
Scripps Florida for ﬁnancial support.
Notes and references
z Representative experimental procedure: a resealable metal reactor
with a glass insert and stir bar was loaded with oxidant NaIO4 (90 mg,
0.4207 mmol), then 10.5 mg of 1-TFA (0.01487 mmol) in 1 mL of
triﬂuoroacetic acid-d1 was added under argon. After ﬂushing with
methane, the reactor was charged with 514.7 psi of methane while
stirring. Control reactions were also prepared under identical condi-
tions only without catalyst. The reactors were heated at 180 1C for 3 h.
The reactors were then opened and 5 mL of acetic acid were then
added. Formation of MeTFA was conﬁrmed by 1H and 13C NMR
analysis, GC-MS, and HPLC, by comparison with an authentic
sample.
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basis set). See Scheme 2 for structure of 1B. Note: IRCs link TSs to
methane coordination structures, not cis-2 and trans-2.
3272 | Chem. Commun., 2009, 3270–3272 This journal is c The Royal Society of Chemistry 2009


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Experimental realization of catalytic CH_4 hydroxylation predicted for an iridium NNC pincer complex, demonstrating thermal, protic, and oxidant stability

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