Cp* iridium precatalysts for selective C-h oxidation with sodium periodate as the terminal oxidant

Article abstract of DOI:10.1021/om301252w

Sodium periodate (NaIO₄) is shown to be a milder and more efficient terminal oxidant for C-H oxidation with CpIr (Cp* = C ₅Me₅) precatalysts than ceric(IV) ammonium nitrate. Synthetically useful yields, regioselectivities, and functional group tolerance were found for methylene oxidation of substrates bearing a phenyl, ketone, ester, or sulfonate group. Oxidation of the natural products (-)-ambroxide and sclareolide proceeded selectively, and retention of configuration was seen in cis-decalin hydroxylation. At 60 C, even primary C-H bonds can be activated: whereas methane was overoxidized to CO₂ in 39% yield without giving partially oxidized products, ethane was transformed into acetic acid in 25% yield based on total NaIO₄. ¹⁸O labeling was demonstrated in cis-decalin hydroxylation with ¹⁸OH₂ and NaIO ₄. A kinetic isotope effect of 3.0 ± 0.1 was found in cyclohexane oxidation at 23 C, suggesting C-H bond cleavage as the rate-limiting step. Competition experiments between C-H and water oxidation show that C-H oxidation of sodium 4-ethylbenzene sulfonate is favored by 4 orders of magnitude. In operando time-resolved dynamic light scattering and kinetic analysis exclude the involvement of metal oxide nanoparticles and support our previously suggested homogeneous pathway.

Full text of DOI:10.1021/om301252w

Article
pubs.acs.org/Organometallics
Cp* Iridium Precatalysts for Selective C−H Oxidation with Sodium
Periodate As the Terminal Oxidant
†
,⊥
†
‡
†
§
Meng Zhou, Ulrich Hintermair, Brian G. Hashiguchi, Alexander R. Parent, Sara M. Hashmi,
,§
,‡
,†
,†
Menachem Elimelech,* Roy A. Periana,* Gary W. Brudvig,* and Robert H. Crabtree*
†Department of Chemistry and Energy Sciences Institute, Yale University, P.O. Box 208107, New Haven, Connecticut 06520, United
States
‡
The Scripps Energy & Materials Center, Department of Chemistry, The Scripps Research Institute, Jupiter, Florida 33458, United
States
§
Department of Chemical and Environmental Engineering, Yale University, P.O. Box 208286, New Haven, Connecticut 06520,
United States
*
S Supporting Information
ABSTRACT: Sodium periodate (NaIO ) is shown to be a
4
milder and more efficient terminal oxidant for C−H oxidation
with Cp*Ir (Cp* = C Me ) precatalysts than ceric(IV)
5
5
ammonium nitrate. Synthetically useful yields, regioselectivities,
and functional group tolerance were found for methylene
oxidation of substrates bearing a phenyl, ketone, ester, or
sulfonate group. Oxidation of the natural products (−)-ambroxide and sclareolide proceeded selectively, and retention of
configuration was seen in cis-decalin hydroxylation. At 60 °C, even primary C−H bonds can be activated: whereas methane was
overoxidized to CO in 39% yield without giving partially oxidized products, ethane was transformed into acetic acid in 25% yield
2
1
8
18
based on total NaIO . O labeling was demonstrated in cis-decalin hydroxylation with OH and NaIO . A kinetic isotope effect
4
2
4
of 3.0 ± 0.1 was found in cyclohexane oxidation at 23 °C, suggesting C−H bond cleavage as the rate-limiting step. Competition
experiments between C−H and water oxidation show that C−H oxidation of sodium 4-ethylbenzene sulfonate is favored by 4
orders of magnitude. In operando time-resolved dynamic light scattering and kinetic analysis exclude the involvement of metal
oxide nanoparticles and support our previously suggested homogeneous pathway.
INTRODUCTION
oxidized in this way, but examples of selective methylene and
■
21,24
methine oxidation are rare.
Useful regioselectivity via C−H
Two types of selective metal-catalyzed oxidation of strong,
unactivated C−H bonds have been reported. One involves the
formation of a hydridometal-carbyl or a metal-carbyl inter-
mediate by a metal-centered C−H activation pathway
pathway 1 in Figure 1), while the other proceeds through a
activation without a directing group has been realized for the
2
21
oxidation of sp C−H bonds, but not for aliphatic substrates.
1
−11
Conversely, C−H oxidation involving oxidant activation has
13,14,25−31
proven effective for various aliphatic C−H bonds.
In
(
12
alkane oxidation, selectivity is typically set by the C−H bond
strength, where reactivity increases as methyl ≪ methylene <
methine. However, this trend can be overcome through a
molecular recognition unit that orients the substrate to steer
high-valent metal oxo species via an oxidant activation
pathway (pathway 2 in Figure 1).
13−20
The majority of C−H oxy-functionalization reactions via C−
H activation in the literature utilize a directing group to achieve
32−37
21−23
2
oxidation selectivity in a biomimetic approach.
Selective
useful regioselectivity.
Methyl and sp C−H groups can be
methylene over methine oxidation may also be achieved via
3
8,39
catalyst design.
Aliphatic C−H oxidation in the presence of
a functional group can be applied in organic synthesis, but it is
not yet well-developed.
Selective methane oxidation
40−42
43−47
by metal oxo species is rare.
It is expected that the reaction, if occurring at all, would yield
highly oxidized products such as CO due to preferential
2
oxidation of the initial products (i.e., methanol, formaldehyde,
and formic acid), all having weaker C−H bonds than
48
methane. However, total oxidation of methane to CO ,
2
Received: December 24, 2012
Published: February 6, 2013
Figure 1. Two types of mechanisms for selective C−H oxidation.
©
2013 American Chemical Society
957
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Article
a
when driven electrochemically, is a key process in methane fuel
cells.
Table 1. Oxidation of THF with NaIO4
4
9,50
b
b
c
d
yield (γ-butyrolactone) yield (succinic acid) RSM
mass balance
81%
BACKGROUND
We recently reported that Cp*Ir complexes (Cp* = C Me )
catalyze cis-decalin hydroxylation with retention of config-
uration at the methine carbon. H O served as source of oxygen
and ceric(IV) ammonium nitrate ([NH ] [Ce (NO ) ],
CAN) as a one-electron oxidant. The near-complete
stereoretention with cis-decalin ruled out a free radical
mechanism because the fast isomerization of cis-9-decalyl
41% 33% 7%
■
a
Conditions: Precatalyst 1 (0.006 mmol, 1% catalyst loading), THF
0.6 mmol, 1 equiv, limiting reagent), 4 equiv of NaIO (2.4 mmol) in
5
5
(
1
4
0 mL of D O under N at 23 °C for 1 h. Product analysis was carried
2 2
1
b
2
IV
out by H NMR spectroscopy using an internal standard. Yield =
4
2
3 6
c
mole of product/mol of total starting material. RSM = recovered
5
1
d
unreacted starting material. Mass balance = (mole of total products +
mole of recovered unreacted starting material)/mol of total starting
material.
8
−1
radical to trans-9-decalyl radical (>10 s ) would have resulted
in loss of stereochemistry if a free radical intermediate was
background reaction was observed with NaIO in the absence
of a precatalyst even with the most activated substrate, THF.
4
V
formed by hydrogen atom abstraction. A high-valent Ir oxo
III
intermediate, formed by successive oxidation of an Ir aqua
We therefore focused on NaIO as the most promising
4
52−56
complex, was proposed as the active oxidant.
Further
oxidant. Accordingly, NaIO was next tested in cis-decalin
4
experimental and DFT computational studies supported the
hydroxylation catalyzed by 1. With 1 in 4:1 acetone/H O
2
V
idea that a high-valent Ir oxo complex can give cis-decalin
(Scheme 2 and entry 1 of Table 2), cis-decalin hydroxylation
hydroxylation in the singlet state via a stereoretentive direct
57
oxene insertion rather than an oxyl radical rebound pathway.
Scheme 2. cis-Decalin Hydroxylation with Complex 1 or 2
Using the strongly oxidizing and highly acidic CAN reagent,
the reaction suffered from low yields and limited substrate
scope due to background oxidation by CAN, which can
57
unselectively oxidize both substrate and product. The varying
degree of unselective overoxidation complicated kinetic
analyses, and co-precipitation of ceria prohibited methods for
testing catalyst homogeneity by dynamic light scattering (DLS).
We thus looked for an alternative oxidant in order to increase
the synthetic efficiency of the catalytic system and make it more
amenable to mechanistic studies.
a
Table 2. cis-Decalin Hydroxylation with Complex 1 or 2
RESULTS AND DISCUSSION
Oxidant Screening. Water-soluble oxidants KBrO3,
■
5
8
t
NaClO(aq), NaIO , NaIO , oxone, BuOOH(aq), H O , and
3
4
2
2
IV
mCPBA, as well as heterogeneous Pb O , were tested in the
2
oxidation of tetrahydrofuran (THF) in D O with water-soluble
2
precatalyst 1 (Scheme 1 and Supporting Information). The
Scheme 1. Evaluation of Oxidants with Complex 1
a
Conditions: cis-Decalin (0.3 mmol, limiting reagent), NaIO4 (3
mmol, 10 equiv), at 23 °C under N with 1 or 2 (0.015 mmol, 5%
2
b
catalyst loading), in 4:1 acetone/H O (10 mL). Yield = mole of cis-
2
c
decalol/mol of total starting material. Ratio obtained from calibrated
GC-FID analysis.
gave cis-decalol in 62% yield and a 22:1 cis/trans ratio after 24 h
at 23 °C, showing that NaIO is able to drive the oxidation of
4
an unactivated C−H bond. Similar to previous results with
CAN, the reaction proceeds with retention of configuration at
51
the methine carbon. The reaction mixture remained near-
neutral (pH 6 by pH paper) through to completion, showing
that the current system is much less acidic than in the case of
CAN, where the solution pH is typically below 2. Again, no
background reaction was observed for cis-decalin hydroxylation
1
product identity was determined and yield measured by H
NMR spectroscopy without workup (Table 1). We chose THF
oxidation as the benchmark reaction for screening oxidants
because it dissolves in D O and is very reactive toward C−H
oxidation, as reported in our previous work with Cp*Ir and
with NaIO in the absence of 1, and the starting decalin was
2
4
recovered quantitatively. Cp*Ir(o-phenylpyridine)Cl (2), like 1,
catalyzed cis-decalin hydroxylation with retention of config-
uration, giving cis-decalol in 64% yield and a 36:1 cis/trans ratio
(Scheme 2 and entry 2 of Table 2).
CAN, allowing relatively rapid screening.
59−61
NaIO , recently found by Parent et al.
to be effective for
4
driving water oxidation with Cp*Ir precatalysts, is effective as a
terminal oxidant for C−H oxidation of THF catalyzed by 1.
The reaction gives γ-butyrolactone in 41% yield and succinic
acid in 33% yield. All other oxidants failed to drive the desired
chemistry, giving <1% yield of products. Importantly, no
18
O labeling experiments could not determine whether H O
2
or NaIO serves as a source of oxygen because of the rapid
4
oxygen exchange between periodate and H O in aqueous
2
62
solution. This exchange means that the reaction could be
9
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Organometallics
Article
useful for pharmaceuticals in bringing about 18O labeling of
RuO is the active species formed in situ. We do not yet know
63
4
5
1,63
organic molecules.
Indeed, cis-decalin hydroxylation using
what species is involved in this case, but further work is
currently being carried out on this system.
1
and 16O-NaIO in OH gives 95% O-labeled cis-decalol
18
18
4
2
(
Supporting Information).
Cyclooctane Oxidation. Oxidation of the methylene
The progress of the reaction of cyclooctane to give
cyclooctanone with the most effective precatalysts 1 and 2
was monitored over time (Figure 2 and Supporting
64
groups in cyclooctane (C−H bond strength: 95.7 kcal/mol )
was carried out with NaIO and Ir precatalysts 1 to 7 (Scheme
4
3
and Table 3). Shorter reaction times (5 h) were used than for
Scheme 3. Precatalyst Screening in Cyclooctane Oxidation
Figure 2. Monitoring cyclooctane oxidation over time (lines are drawn
to guide the eye). Conditions: cyclooctane (0.372 mmol, limiting
reagent), 1 or 2 (0.022 mmol, 6% catalyst loading), NaIO (3.72
4
mmol, 10 equiv), in 4:1 acetone/H O (10 mL), at 23 °C under N .
2
2
Information). Higher concentrations of precatalyst and reagents
were used than those in precatalyst screening (Table 3) so that
the yields in the initial stage of the reaction are higher and can
be more accurately measured and compared. With 1, the
reaction started off quickly, giving 19% yield of product in 30
min. After 6 h the reaction had essentially stopped at
cyclooctanone yields of 50%. With 2, the reaction started off
slowly, giving only 3% yield after 30 min, but progressively
caught up with the case of 1. After 3 h, 29% cyclooctanone was
produced, and after 15 h a maximum yield of 52% was
obtained. Overall, the two precatalysts gave very similar yields
after 15 h, but the initial rate for 1 clearly exceeded that for 2.
The absence of an induction period seen with 1 could perhaps
cis-decalin hydroxylation (24 h), because it allowed more rapid
assessment of precatalyst activity at an early stage of the
reaction, where overoxidation (see below) has less effect on the
yields. Oxidation-resistant solvents were required for this work.
Satisfactory mixtures for cyclooctane oxidation were 4:1
t
acetone/H O, 4:1 MeCN/H O, and 4:1 BuOH/H O.
2
2
2
Complex 1 gave 31% yield of cyclooctanone with 10 equiv of
NaIO (Table 3); fewer equivalents of oxidant gave lower
4
yields. Side product analysis after 24 h, where cyclooctanone
was produced in 54% yield, showed traces of two regioisomeric
overoxidation products, 1,4-cyclooctanedione (4%) and 1,5-
cyclooctanedione (2%) (Supporting Information). Precatalyst 2
was also active, giving 31% yield of cyclooctanone. Precatalyst 3
was less active than 1 or 2, giving 13% yield of cyclooctanone.
Cationic complex 4 was much less active, giving only <3% yield
of cyclooctanone. Cp*Ir complexes 5 and 6 gave poor yields of
cyclooctanone: 3% and 6%, respectively. The lower activity of 5
and 6, both lacking chelate ligands, could result from the faster
oxidative decomposition to give inactive metal oxide nano-
66
be the result of more facile chloride dissociation aided by π
67
donation from the oxygen lone pair adjacent to the metal.
Cyclooctanone Oxidation. Detection of trace levels of
1,4- and 1,5- cyclooctanedione byproducts in the cyclooctane
oxidation with 1 led us to examine the oxidation of
cyclooctanone (Scheme 4). Functional group tolerance is
important for C−H oxidation to be useful in organic
63,68
synthesis.
Initially, cyclooctanone oxidation in 4:1 acetone/H O was
2
65
particles, shown by time-resolved DLS and electrochemical
inefficient (entry 1 in Table 4), giving only 7% yield of 1,4-
cyclooctanedione (8) and 6% of 1,5-cyclooctanedione (9) with
1. Switching to aqueous hexafluoroisopropanol (4:1 HFIP/
66
quartz crystal nanobalance analysis in our related studies.
Surprisingly, the simple complex IrCl ·3H O (7) was also active
3
2
as a precatalyst for cyclooctane oxidation, giving 17% yield of
cyclooctanone. This is reminiscent of C−H oxidation catalyzed
by RuCl ·3H O with NaIO in aqueous-organic solvent, where
H O) as solvent significantly improved the yield to 17% of 8
2
and 19% of 9 (entry 2). No 1,2- or 1,3-regioisomers were
detected. It is unclear why HFIP/H O improves the yield, but
3
2
4
2
a
Table 3. Yield of Cyclooctanone in Cyclooctane Oxidation
Ir complex
1
2
3
4
5
6
7
none
0%
b
yield (cyclooctanone)
31%
31%
13%
<3%
3%
6%
17%
a
Conditions: Precatalyst (0.01 mmol, 5% catalyst loading), cyclooctane (2 mmol, limiting reagent), NaIO (2 mmol, 10 equiv) in 4:1 acetone/H O
4
2
b
1
solvent (10 mL), at 23 °C under N for 5 h. Yield = mole of cyclooctanone/mol of total starting material, measured by H NMR spectroscopy with
2
an internal standard.
9
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Article
Scheme 4. Cyclooctanone Oxidation
with CAN gave an unselective reaction without significant
dione formation.
57
Methylene Oxidation. In view of our good yields in
cyclooctane and cyclooctanone oxidation, we applied the
optimized system (1 or 2 and NaIO in 4:1 HFIP/H O or
4
2
neat D O) to other substrates (Table 5). Due to the different
2
C−H bond strength in the substrates tested, the reaction
conditions varied. Reactive substrates such as n-butanol and
sodium 4-ethylbenzene sulfonate (EBS) were oxidized under
milder conditions than substrates containing stronger C−H
bonds, such as methane, ethane, and 2-heptanone. Water-
insoluble complex 2 gave higher yields (for example, entry 6 vs
a
Table 4. Cyclooctanone Oxidation
b
b
d
entry precatalyst time (h) yield
8
yield
9
RSM mass balance
c
1
2
3
4
5
1
1
2
2
6
15
14
15
15
14
7%
17%
20%
27%
2%
6%
19%
20%
28%
1%
65%
37%
25%
11%
76%
78%
73%
65%
66%
79%
e
7
in Table 5) than 1, but water-soluble complex 1 had to be
used for reactions carried out in neat D O.
e
,
f
2
n-Butanol was oxidized to n-butyric acid in 94% yield in D O
2
(
entry 1 in Table 5). The chemospecific oxidation of n-butanol
a
Conditions unless noted otherwise: cyclooctanone (0.34 mmol,
limiting reagent), precatalyst (0.017 mmol, 5% catalyst loading),
NaIO (3.4 mmol, 10 equiv), in 4:1 HFIP/H O (10 mL), at 23 °C
under N for ∼15 h. Yield = mole of 8 or 9/mol of total starting
material. Solvent: 4:1 acetone/H O (10 mL). Mass balance = %
yield of 8 and 9 + % RSM. No 1,2- or 1,3-cyclooctanedione was
detected. 2 (10% catalyst loading) was used. No significant increase in
to n-butyric acid showed that the reaction probably did not
proceed via a metal-centered C−H activation pathway well-
4
2
4
b
known for Ir. Instead the result is more consistent with our
2
V
c
d
proposal that an Ir oxo intermediate serves as active oxidant.
2
e
An alcohol oxidation that may possibly proceed via a C−H
activation pathway has been reported with a Pt catalyst, where
oxidation of ethanol gave ethylene glycol as one of the
f
product yield was found by GC-FID after 16 h.
75
products. Water-soluble EBS was selectively and efficiently
oxidized, and a 99% yield of sodium 4-acetylbenzene sulfonate
product was detected with 99% mass balance after only 1 h
HFIP has previously been shown to be an effective solvent in
oxidation and cycloaddition reactions.
The reaction mixture with HFIP has a lower apparent pH of
.5 as a result of the acidic HFIP hydroxyl group (pK = 9.3).
6
9
70
(
entry 2). In control studies, neither light nor air had significant
71
effects on the yield of EBS oxidation (Supporting Information).
3
a
64
Ethylbenzene (benzylic C−H bond strength: 85.4 kcal/mol )
Despite being a secondary alcohol, HFIP is quite oxidation
resistant due to the two polar trifluoromethyl groups adjacent
to the C−H. This was demonstrated in an independent
oxidation in 4:1 acetone/H O gave acetophenone in 49% yield
2
without detectable arene oxidation (entry 3), contrary to the
63
case of RuO4. Aqueous HFIP, a more effective solvent than
aqueous acetone in cyclooctanone oxidation, gave a lower yield
of acetophenone in this case, although carried out under
otherwise similar conditions, possibly due to the further
oxidation of acetophenone.
experiment, where oxidation of aqueous HFIP by 1 and NaIO
4
was studied by 1 F NMR spectroscopy; only 0.2% of the total
HFIP was oxidized to hexafluoroacetone (HFA) under
conditions similar to those for C−H oxidation (Supporting
Information). Methyl(trifluoromethyl)dioxirane, prepared from
methyltrifluoromethylacetone, a compound related to HFA, is a
9
2-Heptanone, bearing relatively unreactive methylene C−H
bonds, nevertheless gave a 44% yield of 2,6-dione and a 18%
yield of 2,5-dione (entry 4) but no other regioisomers. We used
10% catalyst loading in this reaction instead of 5% as in entries
2 and 3. Using 5% catalyst loading in this reaction resulted in
significantly lower product yields (Supporting Information).
The regioselectivity observed here (2.4:1) differs significantly
72
known reagent for stoichiometric alkane oxidation. However,
no cyclohexane oxidation was found for HFA with NaIO in 1:1
HFIP/D O in the absence of 1, excluding the possibility of
HFA being solely involved in alkane oxidation. cis-Decalin
hydroxylation with 1 and NaIO in 4:1 HFIP/H O again
proceeded with retention of configuration, ruling out the
possibility that free radical intermediates could be favored in
this solvent.
Precatalyst 2 also carried out cyclooctanone oxidation
effectively, giving 8 and 9 in similar yields to those with 1
entry 3). Raising the catalyst loading of 2 from 5% to 10%
gave further yield improvements without changing the
4
2
4
2
from that seen in Na
S O
oxidation of the same substrate. The
gave a ratio of 1.15:1 of 2,6- and 2,5-
2
2
8
7
6,77
Na S O oxidation
2 2 8
II
heptanedione products with Fe as an additive and a ratio of
II
1:1.4 without Fe , where the regioselectivity is the opposite of
(
that with 2 and NaIO
radical mechanism was proposed, which should not occur with
our nonradical Cp*Ir/NaIO system, consistent with the
4
. For this reaction an intramolecular free
4
regioselectivity, giving 27% yield in 8 and 28% yield in 9
entry 4). 8, which can be readily separated from 9 by column
(
different product distribution observed. 1,5-Diones are
chromatography, contains a 1,4-dione moiety useful for
asymmetric transannular aldolization. In contrast to our one-
step procedure, this compound (8) was previously prepared
only via a multistep synthesis. No 1,3-cyclooctanedione was
found in the product mixture, although it could have been
common synthetic intermediates that are conventionally
78
made via C−C bond formation strategies instead of direct
C−H oxidation. Methyl hexanoate oxidation gave methyl 5-
oxo-hexanoate and methyl 4-oxo-hexanoate in 61% and 21%
yield, respectively, with quantitative mass balance (entry 5).
The regioselectivity, 2.9:1 in favor of the 5-isomer, is not much
different from the 2.3:1 ratio obtained in a previously described
73
formed and escaped detection via overoxidation. NaIO has
4
been reported to oxidize 1,3-cyclohexanedione to glutaric acid
74
79
and CO as final products. Cp*Ir complex 6, which lacks a
Fe system.
2
chelate ligand, gave a very poor yield of diones (entry 5).
Results from cyclooctanone oxidation show the particular
Oxidation of Light Alkanes. Previous calculations
suggesting that methane oxidation by the intermediate
V
+
advantage of using NaIO as a milder terminal oxidant than
[Cp*Ir (o-phenylpyridine)(O)] should have an accessible
57
4
CAN, because an otherwise identical Cp*Ir-catalyzed oxidation
barrier of 24 kcal/mol prompted us to explore this reaction
9
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Organometallics
Article
a
Table 5. Additional Substrates Tested
a
Conditions unless noted otherwise: substrate (∼0.2 mmol, limiting reagent) in 4:1 HFIP/H O (10 mL), NaIO , at 23 °C under N . NaIO equiv
2
4
2
4
b
c
are relative to the amount of substrate. Mass balance = % total product + % RSM. Yield = mole of product/mol of total starting material.
d
Conditions: 5.5 mM precatalyst, NaIO (limiting reagent, 50 equiv relative to precatalyst), 300 psi gaseous substrate (excess amount), at 60 °C for
4
e
1
5 h unless otherwise stated. Yield is based on total NaIO . 110 psi was used; all other conditions are the same as those shown in footnote d.
4
f
g
h
i
Turnover number (TON) is based on oxidation of first C−H bond. In D O solvent. No other regioisomers were detected. Solvent: 4:1 acetone/
2
H O (10 mL).
2
experimentally. Methane, with a C−H bond strength of 105
3.3 ± 0.1 (with 2), respectively. No background reaction
occurred without added Ir precatalyst for methane and ethane
6
4
kcal/mol, was indeed oxidized with both 1 and 2, but only to
give CO in 25% and 39% yield, respectively, based on NaIO4
oxidation. However, with a precatalyst and NaIO in aqueous
2
4
(
entries 7 and 6). This result follows the usual pattern of
HFIP and in the absence of a substrate, a small amount of
acetic acid was observed (Supporting Information). The acetic
acid is believed to originate from oxidation of the Cp* ligand in
the precatalysts, and this portion of acetic acid formation has
been subtracted in the reported turnover numbers. Propane
electrophilic C−H bond oxidation, where the weaker C−H
bonds of partially oxidized intermediates are preferentially
overoxidized to give the completely oxidized product, CO2.
Although no useful partial oxidization products could be
obtained from methane oxidation with our Cp*Ir/NaIO4
system, this result demonstrates that the precatalysts can
perform such difficult reactions even under relatively mild
conditions.
64
oxidation (secondary C−H bond strength: 98.1 kcal/mol )
gave acetone in 29% yield with 1 (entry 11) and 38% yield with
2 (entry 10), representing 5.3 and 6.6 turnovers, respectively.
64
Cyclohexane (C−H bond strength: 99.5 kcal/mol ) oxidation
is relatively facile with 2, giving 75% yield of cyclohexanone
In contrast, ethane, with a C−H bond strength of 100.5 kcal/
6
4
80,81
mol, was oxidized to acetic acid, a feedstock chemical, in 21%
yield with 1 (entry 9) and 25% yield with 2 (entry 8). These
numbers represent turnover numbers of 2.9 ± 0.1 (with 1) and
(entry 12), a precursor to adipic acid for nylon production.
Complex 1 is also quite effective for catalyzing cyclohexane
oxidation, giving 67% yield of cyclohexanone in only 1 h
9
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Organometallics
Supporting Information). We thus measured the kinetic
Article
(
4-acetylbenzenesulfonate took place with initial rates as high as
1380 h for 1 (23% conversion after 1 min at 1% catalyst
8
2
−1
isotope effect (KIE) of cyclohexane oxidation with 1 by
separate h -cyclohexane and d -cyclohexane oxidations. A KIE
loading). No phenylethanol intermediate was ever detected,
confirming that alcohol oxidation is much faster than the initial
methylene activation. The mass balance was virtually
quantitative throughout the reaction (Supporting Information).
As observed before, no reaction occurred without Ir precatalyst
(16 h at 23 °C) and no overoxidation products formed even
after prolonged reaction times (24 h).
12
12
of 3.0 ± 0.1 was found at 23 °C. This suggests C−H oxidation
as the rate-limiting step rather than formation of the high-valent
V
Ir oxo intermediate, proposed to be the active oxidant formed
prior to the C−H cleavage.
Natural Product Oxidation. We also looked for possible
selective oxidations of complex natural products (Scheme 5 and
In operando time-resolved DLS during the reaction confirmed
the homogeneity of the system. No scattering intensity above
background was detected over more than 3 h (Figure 3), and
Scheme 5. Natural Product Oxidation
Supporting Information). No reaction occurred with artemisi-
nin, and 89% unreacted starting material was recovered, in
contrast to a previously described Fe system that oxidized the
8
3
C-10 methine. Oxidation of 5-cholestan-3-one was unselec-
tive, unlike the case of methyl(trifluoromethyl)dioxirane, where
72
C-25 methine was selectively hydroxylated. Pregnanedione
oxidation was ineffective, and cuparene oxidation was
unselective. However, (−)-ambroxide oxidation gave sclareolide
in 25% isolated yield with 2, where an activated C−H α to the
oxygen was oxidized. Sclareolide oxidation in turn gave 2-oxo-
sclareolide and 3-oxo-sclareolide in 17% and 5% yield,
respectively, where the unactivated methylene groups were
selectively oxidized in the presence of a lactone and multiple
other C−H bonds.
Figure 3. Scattered light intensity profile of a diffusional reaction
mixture of complex 1 (0.4 mM), sodium 4-ethylbenzene sulfonate (40
mM), and NaIO (400 mM) in H O (5 mL) at 23 °C over time.
4
2
the corresponding autocorrelation functions do not exhibit any
exponential decay that indicates the presence of particles
(resolution limit of 1 nm hydrodynamic diameter) with a
detection limit of 10 ppm. This result rules out both the
formation and potential involvement of metal oxide nano-
particles in the reaction and is a strong indication that
molecular species are performing catalytic C−H oxidation in
this case.
Mechanistic Studies. Whenever organometallic catalysts
are subjected to relatively forcing reaction conditions (e.g.,
irradiation, temperature, pH, or electric or chemical potential),
there is a danger of decomposition of the precursor to a
heterogeneous material. In situ formation of nanoparticles can
be very difficult to detect, and only in the most favorable case
are they a mere deactivation pathway. More often they are
As many Cp*Ir complexes, including 1, are also active
8
4
highly reactive and are the true catalysts at work. We have
precatalysts for water oxidation (WO) with both CAN and
85
52,53
long been interested in this ambiguity and have recently been
NaIO4,
WO is expected to occur as a side reaction during
able to confirm the homogeneity of some of our Cp*Ir
C−H oxidation (CHO) with H O as solvent or cosolvent.
2
66
complexes in water oxidation, both electrode-driven and with
Although relatively good yields can be obtained for the
65
chemical oxidants. Therefore, we set out to test the present
precatalysts under C−H oxidation conditions. We first
attempted to investigate the hydroxylation of cis-decalin,
because the reaction affords important information on the
catalyst through the level of stereoretention in the product.
Unfortunately, the multiphasic reaction conditions obscured in
situ analysis, and the extractive workup procedure resulted in
moderate mass balances, because polar overoxidation products
remained in the aqueous phase and thus escaped detection.
Instead, we decided to take a closer look at the C−H
oxidation of the water-soluble substrate EBS with 1 and NaIO4
oxidation of strong C−H bonds (Table 5) in aqueous systems,
an excess of NaIO is always needed for achieving high product
4
yields, suggesting that WO consumes at least part of the
oxidant. To determine the extent of WO during CHO, we
measured the mole numbers of both WO and CHO products
with EBS and 1 in H O (Scheme 6 and Supporting
2
Information).
After 15 min, sodium 4-acetylbenzenesulfonate and O were
2
1
detected in 0.83 ± 0.06 μmol (by H NMR spectroscopy) and
0.20 ± 0.01 μmol (by Clark-type electrode) amounts,
respectively. Thus, WO indeed occurred during CHO, and at
in neat H O. When the reaction was run at NaIO4
concentrations of 400−500 mM, clean oxidation to sodium
least part of the loss in oxidation efficiency of NaIO with
respect to CHO can be attributed to WO. Considering the
2
4
9
62
dx.doi.org/10.1021/om301252w | Organometallics 2013, 32, 957−965

Organometallics
Article
Scheme 6. C−H Oxidation vs Water Oxidation at 23 °C
relative substrate concentrations, however, we find that CHO is
4
favored over WO by a factor of 1.0 × 10 .
The much faster CHO and good mass balance in this system,
together with confirmed homogeneity, permitted the use of
initial rates of formation of sodium 4-acetylbenzenesulfonate
for kinetic analysis (Supporting Information). Variation of
catalyst loading gave a clear first-order dependence on Ir
concentration over 1 order of magnitude (Figure 4), consistent
Figure 5. Eyring plot of sodium 4-ethylbenzenesulfonate (40 mM)
oxidation with complex 1 (0.2 mM) and NaIO (400 mM) in H O
4
2
(
error bars indicate uncertainty of measurement; line is a linear fit of
2
the 0−23 °C region with R = 0.99).
CONCLUSION
Cp*Ir complexes are shown to catalyze the oxidation of strong
C−H bonds with NaIO as a mild and efficient primary oxidant
■
4
with useful selectivity. The KIE of cyclohexane oxidation
suggests the C−H cleavage is rate-determining. In operando
time-resolved dynamic light scattering experiments showed that
no particles larger than 1 nm form during the reaction,
confirming catalyst homogeneity. Competition experiments
revealed that the C−H oxidation of sodium 4-ethylbenzene
sulfonate is faster than water oxidation by 4 orders of
magnitude. Kinetic studies gave a first-order rate dependence
in precatalyst concentration as well as a low activation free
energy of 14.8 kcal/mol in sodium 4-ethylbenzene sulfonate
oxidation. The negative activation entropy of the reaction
together with first-order rate dependence on Ir precatalyst and
substrate H/D kinetic isotope effect suggest association of the
active Ir-oxo species with the C−H bond to be the rate-
determining step. The very challenging catalytic C−H oxidation
transformations reported here are not well-known for Ir
Figure 4. Dependence of initial rates of formation of sodium 4-
acetylbenzenesulfonate from sodium 4-ethylbenzenesulfonate (40
mM) with various amounts of complex 1 and NaIO (400 mM) in
4
H O (5 mL) at 23 °C (error bars indicate uncertainty of
2
measurement; line is a linear fit without intercept).
with our previously suggested mononuclear pathway. CHO
conversions after longer reaction times, however, achieved a
maximum of around 100 TON irrespective of the catalyst
loading.
28
complexes. The direct oxidation of strong C−H bonds in
the presence of a functional group could be applied in organic
synthesis, as an alternative method to C−C bond formation
8
6,87
strategies for the synthesis of oxygenates,
and the light
On varying the temperature of the reaction with 0.5% of
complex 1, we observed a concave profile in the Eyring plot.
Below 23 °C, the initial rate of CHO consistently decreased
with an apparent activation enthalpy of 7 ± 0.6 kcal/mol
alkane oxidation reactions are relevant to the energy research,
where nonpetroleum fossil fuel could be used as a raw material
88−90
for feedstock chemical and fuel productions.
Given the
homogeneity and relatively high activity of the system, ligand
variations and mechanistic studies may yield improved Ir
complexes for C−H oxidation in the future.
(
Figure 5) and activation entropy of −26.5 ± 2.5 cal/mol,
giving an activation free energy of 14.8 ± 0.6 kcal/mol at 295 K.
This low barrier is consistent with the large preference for
CHO over WO seen in this system and might in part be the
result of the moderate C−H bond strength in the EBS
substrate. When the reaction was carried out above 23 °C,
however, the initial rate of CHO did not increase any further
and fewer turnovers were reached at longer reaction times (60
TON at 60 °C vs 100 TON at and below 23 °C after 3 h).
We interpret this behavior as overriding WO activity at
higher temperatures, as vigorous bubble formation was seen in
these experiments immediately on mixing, but alternative
explanations such as periodate or even catalyst decomposition
cannot be ruled out with certainty at this point.
ASSOCIATED CONTENT
Supporting Information
Syntheses of Cp*Ir complexes and procedures for reaction
setup, purification, and analysis. This material is available free of
charge via the Internet at http://pubs.acs.org.
■
*
S
AUTHOR INFORMATION
Corresponding Author
*E-mail: robert.crabtree@yale.edu; gary.brudvig@yale.edu;
rperiana@scripps.edu; menachem.elimelech@yale.edu.
■
9
63
dx.doi.org/10.1021/om301252w | Organometallics 2013, 32, 957−965

Organometallics
Present Address
Department of Chemistry and Chemical Biology, Rutgers
New Brunswick, Busch Campus, 610 Taylor Road, Piscataway,
Article
Fellowship, and U.H. thanks the Alexander von Humboldt
Foundation for a Feodor Lynen Research Fellowship,
supplemented by a grant from the Yale Institute for
Nanoscience and Quantum Engineering. B.G.H. and R.A.P.
acknowledge The Scripps Research Institute for funding. We
thank Seth B. Herzon, Scott J. Miller, and David S. Spiegel (all
Yale University) for helpful discussions, Katalin Barta (Anastas
lab, Yale) for use of the GC-FID, and the Herzon lab for using
the LC-MS.
⊥
New Jersey 08854, United States.
Notes
The authors declare no competing financial interest.
Biographies
REFERENCES
■
(
1) Ess, D. H.; Gunnoe, T. B.; Cundari, T. R.; Goddard, W. A.;
Periana, R. A. Organometallics 2010, 29, 6801.
(2) Oxgaard, J.; Tenn, W. J.; Nielsen, R. J.; Periana, R. A.; Goddard,
W. A. Organometallics 2007, 26, 1565.
(3) Labinger, J. A.; Bercaw, J. E. Nature 2002, 417, 507.
(4) Crabtree, R. H. J. Organomet. Chem. 2004, 689, 4083.
(5) Gaillard, S.; Cazin, C. S. J.; Nolan, S. P. Acc. Chem. Res. 2012, 45,
7
78.
6) Bergman, R. G. Nature 2007, 446, 391.
7) Arndtsen, B. A.; Bergman, R. G.; Mobley, T. A.; Peterson, T. H.
Acc. Chem. Res. 1995, 28, 154.
8) Colby, D. A.; Tsai, A. S.; Bergman, R. G.; Ellman, J. A. Acc. Chem.
Res. 2012, 45, 814.
9) Li, C.-J.; Trost, B. M. Proc. Natl. Acad. Sci. U. S. A. 2008, 105,
3197.
10) Wencel-Delord, J.; Droge, T.; Liu, F.; Glorius, F. Chem. Soc. Rev.
011, 40, 4740.
(
(
(
(
1
(
2
This article is based upon a poster presented by Meng Zhou, Yale
̈
University (pictured at center with Franc o̧ is P. Gabbaı (left) and John
A. Gladysz (right)) and coauthored by David Balcells, Alexander R.
Parent, Ulrich Hintermair, Brian G. Hashiguchi, Nathan D. Schley,
Sara S. Hashmi, James D. Blakemore, Odile Eisenstein, Roy A. Periana,
Gary W. Brudvig, Menachem Elimelech, and Robert H. Crabtree, at
the first Organometallics Symposium at the fall 2012 ACS meeting in
(11) Ye, B.; Cramer, N. Science 2012, 338, 504.
(
(
(
12) Gunay, A.; Theopold, K. H. Chem. Rev. 2010, 110, 1060.
13) Dick, A. R.; Sanford, M. S. Tetrahedron 2006, 62, 2439.
14) Che, C.-M.; Lo, V. K.-Y.; Zhou, C.-Y.; Huang, J.-S. Chem. Soc.
Rev. 2011, 40, 1950.
91
Philadelphia, Pennsylvania.
(
(
(
(
15) Groves, J. T.; McClusky, G. A. J. Am. Chem. Soc. 1976, 98, 859.
16) Groves, J. T. J. Chem. Educ. 1985, 62, 928.
17) Groves, J. T. J. Inorg. Biochem. 2006, 100, 434.
18) Balcells, D.; Raynaud, C.; Crabtree, R. H.; Eisenstein, O. Inorg.
Meng Zhou, born in Chengdu, China, received his B.S. from Purdue
University and performed his undergraduate thesis work with Mark A.
Lipton on asymmetric catalysis. He further pursued his interest in
catalysis in the lab of Robert H. Crabtree, the corresponding author of
this article, working on C−H oxidation at Yale University, where he
received his Ph.D. In 2012 he joined the lab of Alan S. Goldman as a
postdoctoral associate at Rutgers University. He is interested in
catalysis and seeks an academic career in the future.
Chem. 2008, 47, 10090.
(
(
(
19) Que, L., Jr. Acc. Chem. Res. 2007, 40, 493.
20) Que, L., Jr.; Tolman, W. B. Nature 2008, 455, 333.
21) Neufeldt, S. R.; Sanford, M. S. Acc. Chem. Res. 2012, 45, 936.
(22) Campbell, A. N.; Stahl, S. S. Acc. Chem. Res. 2012, 45, 851.
(23) Giri, R.; Shi, B.-F.; Engle, K. M.; Maugel, N.; Yu, J.-Q. Chem.
Soc. Rev. 2009, 38, 3242.
At Yale since 1977, Bob Crabtree is now Whitehead Professor. He has
been an ACS and RSC organometallic chemistry awardee, Baylor
medallist, Mond lecturer, Kosolapoff awardee, and Stauffer lecturer,
has chaired the ACS Inorganic Division, and is the author of an
organometallics textbook. Early work on catalytic alkane C−H
activation and functionalization was followed by work on H2
complexes, dihydrogen bonding, and catalysis for green and energy
chemistry. He is an ACS Fellow and a Fellow of the American
Academy of Arts & Sciences.
(24) Stowers, K. J.; Kubota, A.; Sanford, M. S. Chem. Sci. 2012, 3,
3
192.
(25) Costas, M. Coord. Chem. Rev. 2011, 255, 2912.
(26) Chan, S. L.-F.; Kan, Y.-H.; Yip, K.-L.; Huang, J.-S.; Che, C.-M.
Coord. Chem. Rev. 2011, 255, 899.
(27) Costas, M.; Chen, K.; Que, L. Coord. Chem. Rev. 2000, 200, 517.
(28) Suzuki, T. Chem. Rev. 2011, 111, 1825.
(29) Newhouse, T.; Baran, P. S. Angew. Chem., Int. Ed. 2011, 50,
3
(
362.
30) Bigi, M. A.; Reed, S. A.; White, M. C. J. Am. Chem. Soc. 2012,
34, 9721.
1
6
ACKNOWLEDGMENTS
■
(31) Vermeulen, N. A.; Chen, M. S.; White, M. C. Tetrahedron 2009,
5, 3078.
This material is based in part upon work supported by the
Center for Catalytic Hydrocarbon Functionalization, an Energy
Frontier Research Center funded by the U.S. Department of
Energy, Office of Science, Office of Basic Energy Sciences,
under Award Number DE-SC0001298 (M.Z., U.H., B.G.H.,
R.A.P., and R.H.C., C−H oxidation) and by the NSF GRFP
and the Division of Chemical Sciences, Geosciences, and
Biosciences, Office of Basic Energy Sciences of the U.S.
Department of Energy (DE-FG02-07ER15909) (A.R.P. and
G.W.B., water oxidation). M.Z. acknowledges the Dox
(32) Fang, Z.; Breslow, R. Org. Lett. 2005, 8, 251.
(33) Das, S.; Incarvito, C. D.; Crabtree, R. H.; Brudvig, G. W. Science
2
(
1
(
4
(
006, 312, 1941.
34) Cook, B. R.; Reinert, T. J.; Suslick, K. S. J. Am. Chem. Soc. 1986,
08, 7281.
35) Breslow, R.; Zhang, X.; Huang, Y. J. Am. Chem. Soc. 1997, 119,
535.
36) Yang, J.; Breslow, R. Angew. Chem., Int. Ed. 2000, 39, 2692.
(37) Ulmann, P. A.; Braunschweig, A. B.; Lee, O.-S.; Wiester, M. J.;
Schatz, G. C.; Mirkin, C. A. Chem. Commun. 2009, 5121.
9
64
dx.doi.org/10.1021/om301252w | Organometallics 2013, 32, 957−965

Organometallics
Article
(
38) Kamata, K.; Yonehara, K.; Nakagawa, Y.; Uehara, K.; Mizuno, N.
Nat. Chem. 2010, 2, 478.
39) He, Y.; Gorden, J. D.; Goldsmith, C. R. Inorg. Chem. 2011, 50,
2651.
40) Ben-Ari, E.; Gandelman, M.; Rozenberg, H.; Shimon, L. J. W.;
Milstein, D. J. Am. Chem. Soc. 2003, 125, 4714.
41) Vetter, A. J.; Rieth, R. D.; Brennessel, W. W.; Jones, W. D. J. Am.
Chem. Soc. 2009, 131, 10742.
(76) Nikishin, G. I.; Troyansky, E. I.; Lazareva, M. I. Tetrahedron Lett.
1984, 25, 4987.
(
1
(
(77) Troyanskii, E. I.; Mizintsev, V. V.; Lazareva, M. I.; Demchuk, D.
V.; Nikishin, G. I. Bull. Acad. Sci. USSR, Div. Chem. 1989, 38, 1879.
(78) Liu, W.-Y.; Xu, Q.-H.; Liang, Y.-M.; Chen, B.-H.; Liu, W.-M.;
Ma, Y.-X. J. Organomet. Chem. 2001, 637−639, 719.
(
(
(
79) Chen, M. S.; White, M. C. Science 2010, 327, 566.
80) Cook, G. K.; Mayer, J. M. J. Am. Chem. Soc. 1994, 116, 1855.
81) Schuchardt, U.; Cardoso, D.; Sercheli, R.; Pereira, R.; da Cruz,
(
(
(
42) Zhou, M.; Crabtree, R. H. Chem. Soc. Rev. 2011, 40, 1875.
43) Muehlhofer, M.; Strassner, T.; Herrmann, W. A. Angew. Chem.,
R. S.; Guerreiro, M. C.; Mandelli, D.; Spinace,
Catal. A: Gen. 2001, 211, 1.
82) Simmons, E. M.; Hartwig, J. F. Angew. Chem., Int. Ed. 2012, 51,
066.
́
E. V.; Pires, E. L. Appl.
Int. Ed. 2002, 41, 1745.
44) Ahrens, S.; Zeller, A.; Taige, M.; Strassner, T. Organometallics
006, 25, 5409.
45) Meyer, D.; Taige, M. A.; Zeller, A.; Hohlfeld, K.; Ahrens, S.;
Strassner, T. Organometallics 2009, 28, 2142.
46) Hashiguchi, B. G.; Bischof, S. M.; Konnick, M. M.; Periana, R. A.
Acc. Chem. Res. 2012, 45, 885.
(
3
(
2
(
(83) Chen, M. S.; White, M. C. Science 2007, 318, 783.
(84) Widegren, J. A.; Finke, R. G. J. Mol. Catal. A: Chem. 2003, 198,
3
17.
(
(85) Crabtree, R. H. Chem. Rev. 2011, 112, 1536.
(
(
86) White, M. C. Science 2012, 335, 807.
87) Fraunhoffer, K. J.; Bachovchin, D. A.; White, M. C. Org. Lett.
(
(
(
(
47) Vedernikov, A. N. Acc. Chem. Res. 2012, 45, 803.
48) Labinger, J. A. J. Mol. Catal. A: Chem. 2004, 220, 27.
49) Park, S.; Vohs, J. M.; Gorte, R. J. Nature 2000, 404, 265.
50) Golisz, S. R.; Gunnoe, T. B.; Goddard, W. A.; Groves, J. T.;
2
005, 7, 223.
88) Haibach, M. C.; Kundu, S.; Brookhart, M.; Goldman, A. S. Acc.
Chem. Res. 2012, 45, 947.
89) Choi, J.; MacArthur, A. H. R.; Brookhart, M.; Goldman, A. S.
Chem. Rev. 2011, 111, 1761.
90) Conley, B. L.; Tenn, W. J.; Young, K. J. H.; Ganesh, S. K.;
(
Periana, R. A. Catal. Lett. 2011, 141, 213.
51) Zhou, M.; Schley, N. D.; Crabtree, R. H. J. Am. Chem. Soc. 2010,
32, 12550.
52) Hull, J. F.; Balcells, D.; Blakemore, J. D.; Incarvito, C. D.;
Eisenstein, O.; Brudvig, G. W.; Crabtree, R. H. J. Am. Chem. Soc. 2009,
31, 8730.
53) Blakemore, J. D.; Schley, N. D.; Balcells, D.; Hull, J. F.; Olack,
(
(
1
(
(
Meier, S. K.; Ziatdinov, V. R.; Mironov, O.; Oxgaard, J.; Gonzales, J.;
Goddard, W. A.; Periana, R. A. J. Mol. Catal. A: Chem. 2006, 251, 8.
1
(
(
91) Gladysz, J. A.; Bochmann, M.; Gabbaı, F. P.; Lichtenberger, D.
̈
L.; Liebeskind, L. S.; Marks, T. J. The Inaugural 2012 Organometallics
G. W.; Incarvito, C. D.; Eisenstein, O.; Brudvig, G. W.; Crabtree, R. H.
J. Am. Chem. Soc. 2010, 132, 16017.
Symposium. Organometallics 2012, 31, 7303−7305.
(
54) Brewster, T. P.; Blakemore, J. D.; Schley, N. D.; Incarvito, C. D.;
Hazari, N.; Brudvig, G. W.; Crabtree, R. H. Organometallics 2011, 30,
65.
55) Graeupner, J.; Brewster, T. P.; Blakemore, J. D.; Schley, N. D.;
9
(
Thomsen, J. M.; Brudvig, G. W.; Hazari, N.; Crabtree, R. H.
Organometallics 2012, 31, 7158.
(
56) Ip, H.-F.; So, Y.-M.; Lee, H. K.; Williams, I. D.; Leung, W.-H.
Eur. J. Inorg. Chem. 2012, 2012, 3289.
57) Zhou, M.; Balcells, D.; Parent, A. R.; Crabtree, R. H.; Eisenstein,
O. ACS Catal. 2011, 2, 208.
(
(
(
58) Connelly, N. G.; Geiger, W. E. Chem. Rev. 1996, 96, 877.
59) Parent, A. R.; Blakemore, J. D.; Brudvig, G. W.; Crabtree, R. H.
Chem. Commun. 2011, 47, 11745.
60) Parent, A. R.; Brewster, T. P.; De Wolf, W.; Crabtree, R. H.;
Brudvig, G. W. Inorg. Chem. 2012, 51, 6147.
61) Parent, A. R.; Crabtree, R. H.; Brudvig, G. W. Chem. Soc. Rev.
013, DOI: 10.1039/C2CS35225G.
(
(
2
(
62) Pecht, I.; Luz, Z. J. Am. Chem. Soc. 1965, 87, 4068.
(
63) McNeill, E.; Du Bois, J. J. Am. Chem. Soc. 2010, 132, 10202.
(
64) In Comprehensive Handbook of Chemical Bond Energies; CRC
Press: Boca Raton, FL, 2007; p 19.
65) Hintermair, U.; Hashmi, S. M.; Elimelech, M.; Crabtree, R. H. J.
Am. Chem. Soc. 2012, 134, 9785.
66) Schley, N. D.; Blakemore, J. D.; Subbaiyan, N. K.; Incarvito, C.
D.; D’Souza, F.; Crabtree, R. H.; Brudvig, G. W. J. Am. Chem. Soc.
011, 133, 10473.
67) Schley, N. D.; Halbert, S.; Raynaud, C.; Eisenstein, O.; Crabtree,
R. H. Inorg. Chem. 2012, 51, 12313.
(
(
2
(
(
(
(
(
(
68) McNeill, E.; Du Bois, J. Chem. Sci. 2012, 3, 1810.
69) Neimann, K.; Neumann, R. Org. Lett. 2000, 2, 2861.
70) Saito, A.; Ono, T.; Hanzawa, Y. J. Org. Chem. 2006, 71, 6437.
71) Begue, J. P.; Bonnet-Delpon, D.; Crousse, B. Synlett 2004, 18.
72) Bovicelli, P.; Lupattelli, P.; Mincione, E.; Prencipe, T.; Curci, R.
J. Org. Chem. 1992, 57, 5052.
(73) Chandler, C. L.; List, B. J. Am. Chem. Soc. 2008, 130, 6737.
(74) Wolfrom, M. L.; Bobbitt, J. M. J. Am. Chem. Soc. 1956, 78, 2489.
(75) Labinger, J. A.; Herring, A. M.; Bercaw, J. E. J. Am. Chem. Soc.
1
990, 112, 5628.
9
65
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