β-Hydride Elimination and C-H Activation by an Iridium Acetate Complex, Catalyzed by Lewis Acids. Alkane Dehydrogenation Cocatalyzed by Lewis Acids and [2,6-Bis(4,4-dimethyloxazolinyl)-3,5-dimethylphenyl]iridium

Article abstract of DOI:10.1021/jacs.6b12995

NaBAr^F₄ (sodium tetrakis[(3,5-trifluoromethyl)phenyl]borate) was found to catalyze reactions of (Phebox)Ir^III(acetate) (Phebox = 2,6-bis(4,4-dimethyloxazolinyl)-3,5-dimethylphenyl) complexes, including (i) β-H elimination of (Phebox)Ir(OAc)(n-alkyl) to give (Phebox)Ir(OAc)(H) and the microscopic reverse, alkene insertion into the Ir-H bond of (Phebox)Ir(OAc)(H), and (ii) hydrogenolysis of the Ir-alkyl bond of (Phebox)Ir(OAc)(n-alkyl) and the microscopic reverse, C-H activation by (Phebox)Ir(OAc)(H), as indicated by H/D exchange experiments. For example, β-H elimination of (Phebox)Ir(OAc)(n-octyl) (2-Oc) proceeded on a time scale of minutes at -15 °C in the presence of (0.4 mM) NaBAr^F₄ as compared with a very slow reaction at 125 °C in the absence of NaBAr^F₄. In addition to NaBAr^F₄, other Lewis acids are also effective. Density functional theory calculations capture the effect of the Na⁺ cation and indicate that it operates primarily by promoting κ²-κ¹ dechelation of the acetate anion, which opens the coordination site needed to allow the observed reaction to proceed. In accord with the effect on these individual stoichiometric reactions, NaBAr^F₄ was also found to cocatalyze, with (Phebox)Ir(OAc)(H), the acceptorless dehydrogenation of n-dodecane.

Full text of DOI:10.1021/jacs.6b12995

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Article
#-Hydride Elimination and C-H Activation by an Iridium
Acetate Complex, Catalyzed by Lewis Acids. Alkane
Dehydrogenation Co-Catalyzed by Lewis Acids and (Phebox)Ir
Yang Gao, Changjian Guan, Meng Zhou, Akshai Kumar, Thomas J Emge, Ashley
M. Wright, Karen I. Goldberg, Karsten Krogh-Jespersen, and Alan S. Goldman
J. Am. Chem. Soc., Just Accepted Manuscript • Publication Date (Web): 18 Apr 2017
Downloaded from http://pubs.acs.org on April 18, 2017
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β-Hydride Elimination and C-H Activation by an Iridium Acetate
Complex, Catalyzed by Lewis Acids. Alkane Dehydrogenation
Co-Catalyzed by Lewis Acids and (Phebox)Ir
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Yang Gao,† Changjian Guan,† Meng Zhou,†, ‡ Akshai Kumar,†, § Thomas J. Emge,†
Ashley M. Wright,∥ Karen I. Goldberg,∥ Karsten KroghꢀJespersen† and Alan S. Goldman*,†
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†Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey,
New Brunswick, New Jersey 08903, United States
‡Department of Natural Sciences, Lawrence Technological University, Southfield, Michigan 48075,
United States
§Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati ꢀ 781039, Assam,
India
∥Department of Chemistry, University of Washington, Box 351700, Seattle, Washington
98195ꢀ1700, United States
Eꢀmail: alan.goldman@rutgers.edu
ABSTRACT: NaBArF (sodium tetrakis[(3,5ꢀtrifluoromethyl)phenyl]borate) was found to catalyze
4
reactions of (Phebox)Ir(III) acetate complexes including (i) βꢀH elimination of (Phebox)Ir(OAc)(nꢀ
alkyl) to give (Phebox)Ir(OAc)(H), and the microscopic reverse, alkene insertion into the IrꢀH bond
of (Phebox)Ir(OAc)(H), and (ii) hydrogenolysis of the Irꢀalkyl bond of (Phebox)Ir(OAc)(nꢀalkyl) and
the microscopic reverse, CꢀH activation by (Phebox)Ir(OAc)(H) as indicated by H/D exchange
experiments. For example, βꢀH elimination of (Phebox)Ir(OAc)(nꢀoctyl) (2-Oc) proceeded on the
timescale of minutes at ꢀ15 °C in the presence of (0.4 mM) NaBArF as compared with a very slow
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reaction at 125 °C in the absence of NaBArF . In addition to NaBArF , other Lewis acids are also
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effective. DFT calculations capture the effect of the Na+ cation and indicate that it operates
primarily by promoting κ2ꢀκ1 dechelation of acetate anion which opens the coordination site needed
to allow the observed reaction to proceed. In accord with the effect on these individual
stoichiometric reactions, NaBArF4 was also found to coꢀcatalyze, with (Phebox)Ir(OAc)(H), the
acceptorless dehydrogenation of nꢀdodecane.
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INTRODUCTION
The selective catalytic dehydrogenation of alkanes and alkyl groups has great potential with
respect to the synthesis of fuels and both commodity and fine chemicals. Transitionꢀmetalꢀbased
catalysts have shown considerable promise in this context, affording high turnover numbers and
the very desirable selectivity for dehydrogenation of the terminal position. To date such catalysts
have generally involved electronꢀrich highly unsaturated (14ꢀelectron) metal centers in low
oxidation states.1ꢀ3
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In 2012, Nishiyama reported that (Phebox)Ir(OAc)2(OH2) (1; Phebox = 2,6ꢀ bis(4,4ꢀ
dimethyloxazolinyl)ꢀ3,5ꢀdimethylphenyl) activates the terminal CꢀH bond of nꢀoctane to form
(Phebox)Ir(OAc)(nꢀoctyl) (2-Oc) at 160 °C in the presence of potassium carbonate.4 The Goldberg
lab reported that if 1 is heated in nꢀoctane to 200 °C (without added base), (Phebox)Ir(OAc)(H) (2-
H) and free octenes are obtained (eq 1). This reaction, shown in eq 1, is the stoichiometric
(heterolytic) dehydrogenation of nꢀoctane by an IrꢀOAc unit.5 The higher temperature of 200 °C,
relative to the CꢀH activation at 160°C, was apparently necessary to induce βꢀH elimination of 2-
Oc.
O
O
N
N
200 °C
72 h
OAc
O
H
+ nꢀoctane
+ octenes
+ HOAc
Ir OH2
OAc
N
Ir
O
ꢀ H2O
N
O
O
1
2-H
(1)
Notably, the reaction shown in eq 1 was not inhibited by the presence of N2 or water,5 in
contrast with the wellꢀknown catalytic dehydrogenation of nꢀalkanes by R4PCP (R4PCP = 2,6ꢀ
(R2PCH2)2C6H3)) pincerꢀiridium complexes1,2 (the rate of eq 1 was even slightly promoted by the
presence of water). Nishiyama proposed that alkane activation by 1 proceeded via a concerted
metallationꢀdeprotonation (CMD) mechanism;4,6ꢀ10 this proposal was later supported by DFT
calculations by Cundari and coꢀworkers.11 We considered that the difference between the alkane
reactions of (R4PCP)Ir and (Phebox)Ir, with respect to inhibition by N2 or water, might be explained
in terms of the intermediacy of Ir(I) intermediates in the case of (R4PCP)Ir and the lack thereof in
the case of (Phebox)Ir.
Subsequently, the Goldberg lab reported that 2-H reacts with O2 in the presence of acetic acid
to regenerate 1.12 In combination with eq 1 this reaction would constitute a catalytic cycle for the
dehydrogenation of nꢀoctane using O2 as a hydrogen acceptor, as illustrated in Scheme 1. On a
practical level this represents a very attractive alternative to the use of olefinic hydrogen acceptors
commonly employed with pincer Ir catalysts. Fundamentally, it further underscores a contrast with
(R4PCP)Ir catalysts which are highly sensitive to oxygen;13 more generally, it highlights the potential
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advantages of catalytic cycles for Irꢀcatalyzed dehydrogenation that do not proceed via lowꢀ
oxidationꢀstate (Ir(I)) species.
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Scheme 1. Hypothetical Cycle for Dehydrogenation of n-Octane by O2, Catalyzed by
(Phebox)Ir(acetate) Complexes, Based on Individually Observed Stoichiometric Reactions
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N
OAc
Ir OH2
OAc
H2O
n-octane
160 °C
(slow)
N
1/2 O2
O
O
O
O
N
O
N
O
Ir
O
Ir
O
CH2(CH2)6CH3
H
N
N
+ HOAc
+ H2O
O
+ HOAc + H2O
200 °C (slow)
β-H elimination
1-octene
Unfortunately, although the reaction of 2-H with O2 proceeded cleanly at room temperature, at
the high temperature (200 °C) required for the reaction shown in eq 1 (which comprises two of the
steps of the catalytic cycle shown in Scheme 1), decomposition occurred in the presence of O2.
Thus it was not possible to achieve the catalytic oxidation of alkanes to alkenes by O2 as indicated
in Scheme 1.
A catalytic cycle for alkane dehydrogenation based on only highꢀoxidation state species offers
several tantalizing possibilities.14 The use of O2 as acceptor, and the tolerance for N2, H2O and
other possible impurities is indicated above; this proposal is supported by reports by Roddick of
pincerꢀligated Ruꢀ and Osꢀbased alkane dehydrogenation catalysts that are much less sensitive to
N2, H2O, and even O2 than (PCP)Ir catalysts.15 In addition, such catalysts might circumvent other
issues that plague cycles based on low oxidation state species (including but not limited to Ir(I)),
such as catalyst inhibition by the olefin product. Many potential tandem systems can be envisioned
that are based on dehydrogenation and a secondary olefin functionalization, but the corresponding
reagents (or coꢀcatalysts) would likely not be tolerated by (PCP)Ir or other low oxidation state
intermediates. Highꢀoxidationꢀstate catalysts might also be less susceptible to inhibition by
functional groups,16ꢀ19 allowing dehydrogenation of potential substrates more complex than
alkanes.
With the above points in mind we have begun to explore routes to promoting the kinetics of
dehydrogenation (e.g. eq 1) by (Phebox)Ir species. Here we report that Lewis acids are found to
increase by orders of magnitude the rate of the step shown in Scheme 1 with the highest barrier, βꢀ
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H elimination by 2-alkyl. In addition, CꢀH activation by 2-H is promoted by Lewis acids. We report
that 2-H catalyzes acceptorless dehydrogenation and that the rate of this reaction is substantially
increased by the presence of Na+.
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RESULTS AND DISCUSSION
In view of the success of (R4PCP)Ir complexes in CꢀH activation and alkane
dehydrogenation,1,2,20 the starting point of our study was an effort to address the possibility that
(Phebox)Ir complexes might undergo reactions with alkanes via the 14ꢀelectron (Phebox)Ir(I) unit
itself, in analogy with the isoelectronic (R4PCP)Ir unit. To this end we attempted to generate a
(Phebox)Ir(I) precursor, (Phebox)Ir(C2H4), in analogy with several examples of (R4PCP)Ir(C2H4) as a
catalyst precursor.20,21 A solution (10 mM) of 2-H in benzeneꢀd6 under 1 atm of ethylene showed no
reaction after 24 h at room temperature (r.t.) or 80 °C, while 5% 2-Et and 4% 2-Ph were formed
after 25 h at 90 °C (corresponding to ꢀG‡ = ca. 32 kcal/mol for ethylene insertion). Upon addition of
2.5 equiv NaOtBu, after 24 h at r.t., one major product was obtained which was determined by NMR
spectroscopy and Xꢀray crystallography to be (Phebox)Ir(η2ꢀC2H4)2 (3)22 (eq 2, Figure 1).23
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O
O
N
N
O
H
+ NaOAc
+ HOtBu
benzeneꢀd6
25 °C, 24 h
NaOtBu
25 mM
+
Ir
O
Ir
+
(1 atm)
N
N
O
O
2-H
3
10 mM
(2)
Figure 1. Crystal structure of complex 3, ORTEP diagram shown at 50% probability level.
Hydrogen atoms omitted for clarity. Selected bond lengths (Å) and angles (deg): Ir(1)−C(1),
1.995(9); Ir(1)ꢀN(2), 2.074(8); Ir(1)ꢀN(1), 2.096(8); Ir(1)ꢀC(19), 2.129(9); Ir(1)ꢀC(21), 2.136(10);
Ir(1)ꢀC(22), 2.161(10); Ir(1)C(20), 2.165(10); C(19)ꢀC(20), 1.425(15); C(21)ꢀC(22), 1.444(14); C(1)ꢀ
Ir(1)ꢀN(2), 77.9(3); C(1)ꢀIr(1)ꢀN(1), 77.7(3); C(1)ꢀIr(1)ꢀC(19), 90.4(4); C(1)ꢀIr(1)ꢀC(21), 94.7(4)
Complex 3 showed some activity as a catalyst for alkane transfer dehydrogenation, but less
than that of (R4PCP)Ir complexes. For example, an nꢀoctane solution of 3 (2 mM) and the hydrogen
acceptor tertꢀbutylethylene (TBE, 0.4 M), at 170 °C, gave 24 mM and 57 mM octenes (and equal
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amounts of 2,2ꢀdimethylbutane) after 1 h and 24 h, respectively. (R4PCP)Ir catalysts have been
reported to give much faster rates at lower temperatures; for example, using (iPr4PCP)IrH4 (1 mM)
as catalyst precursor, 106 mM and 265 mM octenes are obtained at 150 °C after 15 min and 60
min, respectively under otherwise similar conditions.24 Likewise, a refluxing (216 °C) nꢀdodecane
solution of 3 (2 mM), under conditions typically used to effect acceptorless dehydrogenation,25
gave dodecene in concentrations of 11 mM and 26 mM, after 1 h and 24 h respectively, which is
significantly less than that obtained with (R4PCP)Ir complexes.25
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Lewis-acid-catalyzed Ir-H addition to olefins. Quite surprisingly, the addition of only 0.22
equiv NaOtBu (instead of 2.5 equiv) to a solution of 2-H otherwise identical to that described
above, under ethylene (1 atm), led to the complete disappearance of 2-H after 1 h at 25 °C, and
the formation of a new complex (Phebox)Ir(OAc)(CH2CH3) (2-Et) as the main product (eq 3).
Complex 3 was also formed, but only in 14% yield.
O
O
O
N
N
N
O
O
H
benzeneꢀd6
25 °C, 24 h
+
NaOtBu
+
+
Ir
O
Ir
O
Ir
(1 atm)
2.2 mM
N
N
N
O
O
O
2-H
3
2-Et
(no reaction in the absence of
NaOtBu, 24 h, 25 °C or 80 °C)
10 mM
1.4 mM
8.5 mM
(3)
Subsequent addition of acetic acid (10 mM) to the solution resulted in the complete conversion
of 3 to 2-Et. The 1H NMR spectrum (benzeneꢀd6) of 2-Et revealed a triplet (3H, 0.97 ppm, JHꢀH
=
7.5 Hz) and a quartet (2H, 0.64 ppm, JHꢀH = 7.4 Hz) attributable to the ethyl group. The 13C NMR
spectrum showed a signal at δ ꢀ11.4 ppm, assigned to the Irꢀbound methylene group. These
parameters are similar to those of 2-Oc as reported by Nishiyama.4 The molecular structure of 2-Et
was confirmed by Xꢀray diffraction.23
The formation of 3 (1.4 mM) in reaction 3 is easily attributed to the elimination of acetic acid
promoted by the strong base NaOtBu (2.2 mM added). Complex 2-Et (8.5 mM) by contrast, is not
an acidꢀbase reaction product; 2-Et is the net product of ethylene insertion into the IrꢀH bond of
2-H. The role of NaOtBu in the formation of 2-Et is thus apparently catalytic, but the mechanism of
the catalysis, a priori, was not obvious. Considering the possibility that the Na+ cation (rather than
the tꢀBuOꢀ anion) may play the key role, we exposed a benzeneꢀd6 solution of 2-H (10 mM) and
NaBArF (0.2 mM; BArF = tetrakis[(3,5ꢀtrifluoromethyl)phenyl]borate) to 1 atm ethylene. Within 5
4
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min, 2-H had undergone conversion to 2-Et as the only product in 99% yield (eq 4).
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O
O
3
4
5
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8
NaBArF
(0.2 mM)
N
N
O
H
O
+
Ir
O
Ir
O
benzeneꢀd6
25 °C
(1 atm)
N
N
5 min
O
O
2-H
2-Et
9
10 mM
99% yield
(4)
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Notably, NaBArF is apparently not soluble enough in pure benzeneꢀd6 to afford an observable
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1H NMR spectrum.26 In the presence of 2-H, however, the BArF ꢀ protons are easily observed (as
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singlets at δ 8.4 (8H) and δ 7.7 ppm (4H)), indicating an interaction between NaBArF and 2-H that
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is sufficiently favorable to solubilize the NaBArF4. Accordingly, the 1H NMR spectrum of 2-H
changed slightly upon addition of NaBArF ; all signals in the 2-H 1H NMR spectrum were
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broadened and the hydride signal shifted slightly, from δ ꢀ33.8 ppm to ꢀ34.0 ppm. Confirming the
role of the sodium cation in the catalysis of eq 4, when the Na+ꢀcoordinating crown ether27 15ꢀ
crownꢀ5 (1,4,7,10,13ꢀpentaoxacyclopentadecane, 12 mM) was added to an identical solution prior
to addition of ethylene, the rate of ethylene insertion was negligible; less than 3% conversion was
observed after 2 days at room temperature.
NaBArF4 was also found to catalyze insertion of other nꢀalkenes into the IrꢀH bond of 2-H
(Scheme 2). When 1 atm propene was added to a solution of 2-H (10 mM) and NaBArF (0.2 mM),
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complete conversion to (Phebox)Ir(OAc)(nꢀpropyl) (2-Pr) occurred. In the 1H NMR spectrum, two
multiplets (2H, 1.82ꢀ1.54 ppm; 2H, 0.68ꢀ0.44 ppm) and one triplet (3H, 1.04 ppm, JH—H = 7.3 Hz)
were observed, attributable to the n-propyl group. Reactions of 1ꢀpentene (50 mM) or 1ꢀoctene
(100 mM) proceeded similarly, both reaching completion within 1 h with the formation of
(Phebox)Ir(OAc)(CH2(CH2)nCH3) (n = 3, 6). Excess nꢀalkene was converted to predominantly
internal olefins during the course of this reaction (note that no isomerization was observed in a
control experiment with 1ꢀpentene, under the same conditions but without added Na+). Conversely,
within 1 h the reaction of transꢀ2ꢀpentene with 2-H gave the nꢀpentyl complex 2-Pe, i.e. the same
nꢀalkyl complex as was obtained from the reaction with 1ꢀpentene.
Scheme 2. Reaction of 2-H with n-Alkenes
O
O
R
N
N
(R = Me, nꢀPr, nꢀhexyl)
1-alkenes
NaBArF
O
H
O
+
Ir
O
Ir
O
benzeneꢀd6
25 °C
or
nꢀalkyl
N
N
15ꢀ60 min
O
O
2-H
trans-2-pentene
10 mM
93 ꢀ 98% yield
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The catalytic activity of NaBArF , its greater activity relative to that of NaOtBu, and the inhibition
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of catalysis by added crown ether, all indicate that the Na+ cation is acting as a Lewis acid.
Accordingly, various Lewis acids were screened for catalytic activity for the reaction of 2-H with
ethylene. As indicated in Scheme 3, NaBF4, NaBPh4 and NaOAc were investigated. No ethylene
insertion was observed even after 24 h at r.t. but none of these salts were detected in the reaction
solution by 1H NMR or 19F NMR spectroscopy, indicating that they are insoluble in benzene. The
lithium salt [Li(OEt2)3][B(C6F5)4] , however, catalyzed an immediate insertion at room temperature.
In addition to these simple metal cations, boranes were investigated. BPh3 and B(C6F5)3 were both
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found to greatly promote ethylene insertion, albeit less dramatically than either NaBArF or
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[Li(OEt2)3][B(C6F5)4]. As noted above, in the absence of a Lewis Acid, no insertion was observed
even at 80 °C (even though the equilibrium lies fully to the right, as demonstrated by catalyzing the
reaction with NaBArF at that temperature).
4
Scheme 3. Catalysts Screened for Ethylene Insertion
O
O
N
N
catalyst
O
H
O
+
Ir
O
Ir
O
benzeneꢀd6
(1 atm)
N
N
O
O
2-H
2-Et
10 mM
catalyst
no additive
NaBArF
5% yield (90 °C, 25 h)
99% yield (25 °C, 6 h)
no reaction (25 °C, 24 h)
98% yield (25 °C, 5 min)
99% yield (50 °C, 48 h)
99% yield (25 °C, 6 h)
NaOAc, NaBF4, NaBPh4
[Li(OEt2)3][B(C6F5)4]
BPh3
B(C6F5)3
The kinetics of the NaBArF ꢀcatalyzed insertions of ethylene and propene into the IrꢀH bond of
4
2-H were investigated. Reactions of ethylene (10 °C) and propylene (10 °C and 25 °C) proceeded
with kinetics that were zero order in 2-H (Figure 2). Superficially at least, this is easily attributed to
the catalyst (NaBArF ) being saturated with substrate (2-H); note that 2-H is present in excess.
4
Since the NaBArF is not soluble in pure benzene, but dissolves in the presence of 2-H, it would
4
indeed be expected that all NaBArF in solution is initially bound to 2-H. However, NaBArF also
4
4
binds to the product 2-Et, so we would expect, assuming a fixed amount of NaBArF in solution,
4
that a decreasing fraction of it would be bound to 2-H as the reaction proceeds, and the rate would
decrease accordingly over the course of the reaction. Given the difficulties in quantifying the
amount of NaBArF in solution, however, we chose not to pursue the detailed kinetics of this
4
system further; instead we turned to kinetic investigations with a Lewis acid that is simpler to
characterize in solution, [B(C6F5)3].
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Lewisꢀacid catalyzed reactivity of (Phebox)Ir(III)(OAc)
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(a)
(b)
(c)
Figure 2. Insertion of olefin into the IrꢀH bond of 2-H catalyzed by NaBArF ; plots of [2-H] vs. time.
(a) Ethylene, 1 atm, 10 °C. (b) propene, 1 atm, 10 °C. (c) propene, 1 atm, 25 °C.
4
The initial rate of reaction of 2-H with ethylene, catalyzed by B(C6F5)3 (1 mM), was 0.107(4)
mM/min, independent of [2-H]o for initial concentrations 5 mM, 10 mM and 15 mM (Figure 3). Over
time the reaction rates decreased, with departure from the initial rate being pronounced at ca. 50%
completion. This is consistent with the B(C6F5)3 catalyst binding competitively with the reaction
product, 2-Et, as its concentration accumulates. The initial reaction rate showed a linear
dependence on the concentration of B(C6F5)3 (Figure 4). The initial reaction rate also varied
linearly with ethylene pressure (Figure 5).
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Lewisꢀacid catalyzed reactivity of (Phebox)Ir(III)(OAc)
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Figure 3. Insertion of ethylene (1 atm) into the IrꢀH bond of 2-H catalyzed by B(C6F5)3 (1 mM),
varying [2-H]o; plots of [2-H] vs. time.
(a)
(b)
Figure 4. Insertion of ethylene (1 atm) into the IrꢀH bond of 2-H catalyzed by B(C6F5)3, varying
[B(C6F5)3]. (a) plots of [2-H] vs. time. (b) plot of initial rates vs. [B(C6F5)3].
(a)
(b)
Figure 5. Insertion of ethylene into the IrꢀH bond of 2-H catalyzed by B(C6F5)3 (1 mM); varying
PC2H4. (a) plots of [2-H] vs. time. (b) plot of initial rates vs. [C2H4].
The firstꢀorder dependence of the initial rates on [B(C6F5)3] and on [C2H4], and the zeroꢀorder
dependence on [2-H], as shown in Figures 3ꢀ5, are explained simply in terms of saturation of the
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Lewisꢀacid catalyzed reactivity of (Phebox)Ir(III)(OAc)
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Lewis acid catalyst in substrate 2-H, as indicated in Scheme 4 which is a MichaelisꢀMenten28 type
scheme.
5
6
7
Scheme 4
8
9
k1
2-H + LA
2-H•LA (LA = Lewis acid)
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kꢀ1
k2
2-H•LA + C2H4
2-Et + LA
From the MichaelisꢀMenten equation28 we obtain:
k2[C2H4][LA]o[2-H]
ꢀd[2-H]/dt =
kꢀ1 + k2 [C2H4]
[2-H] +
k1
In the limit k1 [2-H] >> kꢀ1 + k2 [C2H4] :
ꢀd[2-H]/dt = k2 [C2H4][LA]o
Lewis-acid-catalyzed β-hydride elimination. For the dehydrogenation of nꢀoctane by
(Phebox)Ir(OAc)2(H2O) to afford 2-H plus octenes (eq 1), βꢀhydride elimination of the intermediate 2-
Oc was found to be the rateꢀdetermining step,5 only proceeding at a significant rate at ca. 200 °C.
Remarkably, upon addition of NaBArF to a cyclohexaneꢀd12 solution of 2-Oc (10 mM), the βꢀhydride
4
elimination proceeded readily at 55 °C, to give 30% conversion to 2-H after 30 min. After 3 h the
reaction appeared to have reached equilibrium, with 42% conversion. The kinetics are complicated
by an equilibrium between 2-Oc and 2-H plus 1ꢀoctene (eq 5), combined with isomerization of the 1ꢀ
octene to give equilibrium concentrations of cis and trans 2ꢀ, 3ꢀ, and 4ꢀoctene (the internal octenes
were the major species present, as determined by 1H NMR). The data were simulated using the
COPASI program.29 A good fit to a kinetic model was obtained (see discussion in SI and Figure S1)
with values constrained to be consistent with the known thermodynamics30 of 1ꢀoctene and internal
octenes, and an equilibrium constant for eq 5 (for 1ꢀoctene) of 1.2 × 10ꢀ5 M (which was extrapolated
from the concentrations observed after 3 h and the thermodynamic ratio30 of 1ꢀoctene to internal
octenes). The kinetic model implies that a small concentration of 1ꢀoctene (ca. 3.4 × 10ꢀ4 M) is very
rapidly produced by βꢀhydride elimination; this concentration then decreases as the 1ꢀoctene
undergoes isomerization and the ratio of 2-H to 2-Oc increases. However, the combination of
reactions introduces too many degrees of freedom into the fitting process to allow us to determine
any meaningful individual rate constants.
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Lewisꢀacid catalyzed reactivity of (Phebox)Ir(III)(OAc)
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O
O
O
N
N
Ir
O
O
H
NaBArF (0.5 mM)
Ir
O
O
+ octenes
nꢀoctyl
cyclohexaneꢀd12
55 °C
N
N
O
(5)
2-Oc
2-H
10 mM
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In the case of the NaBArF ꢀcatalyzed βꢀhydride elimination of 2-Pe at 70 °C ([2-Pe]o = 8.6 mM)
4
the reaction apparently reached equilibrium ([2-H] = 2.9 mM; 34% conversion) after 40 min, with 2ꢀ
pentenes observed in the 1H NMR spectrum as the major organic products. This data was likewise
fit29 using a kinetic model involving fast βꢀhydride elimination followed by relatively slow
isomerization (Figure S2).
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To directly obtain the rate of βꢀhydride elimination, we conducted the reaction of 2-Oc (10 mM
in nꢀoctane) in the presence of ethylene. Ethylene is expected to undergo insertion into the IrꢀH
bond of 2-H more rapidly, and more exothermically, than 1ꢀoctene at the low concentrations which
would be produced by the βꢀH elimination reaction of 2-Oc (and even more so relative to the
isomerized, internal, octenes). In the absence of NaBArF , under 1 atm C2H4 at 125 °C, only 9%
4
conversion of 2-Oc to 2-Et was observed after 13 h (eq 6). (Interestingly there was also 13%
conversion to 2-vinyl.) This corresponds to a pseudoꢀfirstꢀorder rate constant of ca. 1.9 x 10ꢀ6 sꢀ1 at
this temperature, and ꢀG‡ = 33.9 kcal/mol. In marked contrast, when a solution was prepared with
NaBArF (0.38 mM in tolueneꢀd8), addition of 1 atm C2H4 resulted in quantitative conversion of 2-Oc
4
to 2-Et within 45 minutes at -15 °C (Figure 6).
O
O
O
N
N
O
O
+
Ir
O
Ir
O
+ octenes
nꢀoctyl
N
N
O
(6)
2-Oc
2-Et
10 mM
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Lewisꢀacid catalyzed reactivity of (Phebox)Ir(III)(OAc)
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Figure 6. Plot of [2-Et] vs. time (eq 6). Reaction conditions: [2-Oc]o = 10 mM, 1 atm C2H4, 0.38 mM
NaBArF in tolueneꢀd8, ꢀ15 °C.
4
Olefin Insertion/β-Hydride Elimination: DFT Calculations. Since 2-H is an 18e complex, it
may be expected that opening a coordination site would be required to allow the insertion of
ethylene into the IrꢀH bond. With that in mind, we considered that the catalytic effect of Lewis acids
on the insertion/βꢀH elimination reaction might be attributable to dechelation of an acetate ligand
via coordination at oxygen. To investigate this possibility, a series of electronic structure (DFT)
calculations were carried out on the full Pheboxꢀiridium systems using the M06ꢀL functional31 the
SDD effective core potential on Ir,32 and valence basis sets of tripleꢀzeta plus polarization quality
(see Supporting Information for full computational details).32ꢀ36
Coordination of ethylene to 2-H gives complex 2-H-C2H4 (Figure 7a) which bears a dechelated
(κ1) acetate ligand. The reaction is calculated to be endergonic by 17.5 kcal/mol. In the TS for
subsequent insertion of the ethylene ligand into the IrꢀH bond (TS-2-H/Et) the acetate ligand
remains coordinated in a κ1 fashion; both 2-H-C2H4 and transition state TS-2-H/Et have unbound
acetate O atoms 3.46 Å from Ir (Figure 7a). The calculations predict that the free energy of TS-2-
H/Et is only 21.0 kcal/mol (at 25 °C; Figure 7a), well below the value of ca. 32 kcal/mol indicated
by experiment at 90 °C (see above); even after adjustment of the calculated free energies to 90 °C
the predicted barrier is only 23.8 kcal/mol.37,38
Coordination of an ethylene molecule to 2-H trans to the Phebox coordinating carbon (along
with dechelation of the acetate ligand) is computed to be endergonic by 12.2 kcal/mol (15.3
kcal/mol at 90 °C). We were unable to locate a proper TS (a stationary point on the potential
energy surface with just one negative eigenvalue of the force constant matrix) for ethylene
insertion into the IrꢀH bond for this intermediate. This insertion would be expected to lead towards
a very highꢀenergy configuration with the ethyl group (a strongꢀtransꢀinfluence group) positioned
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Lewisꢀacid catalyzed reactivity of (Phebox)Ir(III)(OAc)
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trans to the Phebox coordinating carbon, and a κ1ꢀacetate (a weakꢀtransꢀinfluence group) trans to
a vacant coordination site. Thus, while we cannot locate such a TS, we would expect it to be much
higher in energy than TS-2-H/Et.39,40
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TS-2-H/Et
2-H-C2H4
(dIrꢀO = 3.46)
O
(dIrꢀO = 3.46)
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O
2-Et
1.23
1.29
1.23
1.30
O
1.27
O
2.19
1.69
1.27
O
+
1.27
2.31
[Ir]
2.13
H
1.68
O
2.31
2.09
[Ir]
1.67
TS?
[Ir]
H
O
1.27
2.07
Irꢀcentroid
= 2.00
1.445
2.30
H2C
O
CH3
[Ir]
2.30
21.0
(23.8)
17.5
(20.4)
1.58
-12.8
(ꢀ10.5)
?
H
0.0
2-H
1.23
1.29
O (d
IrꢀO = 3.37)
O
2.24
Irꢀcentroid
2.18
[Ir] = (Phebox)Ir
[Ir]
1.59
H
12.2
(15.3)
(a)
TS-2-H/Et•Na+
(dIrꢀO = 3.46)
2-H•Na+
2-H-C2H4-Na+
Na+2.16O1.29
Na+
O
1.25
(dIrꢀO = 3.49)
1.25
2.09
(dIrꢀO = 3.49)
2-Et•Na+
2.29
Na+ O 1.25
1.27
1.24 O
O
2.29
2.09
1.27
[Ir]
2.12
Na+
2.10
O
1.28
2.16
1.28
2.19
1.57
O
Na+
O
1.69
O
1.26
0.0
+
H
[Ir]
2
.
H
1.75
2.42
2.14
2.15
1
8
[Ir]1.71H
1.67
H
O
2.09
[Ir]
Irꢀcentroid
= 2.01
[Ir]
2.30
Irꢀcentroid
= 2.02
1.434
2.07
1.25
H2C
13.1
CH3
O
6.4
10.7
1.29
2.28
-12.5
2.36O
[Ir]
2.18
Na+
1.59
H
2.54
1.6
(b)
Figure 7. Free energies (kcal/mol) calculated at 25 °C and 90 °C (in parentheses), and selected
bond lengths (Å) of intermediates and transition state for ethylene insertion into the IrꢀH bond of 2-
H. (a) Unassisted by Lewis acid. (b) Promoted by Na+.
The low energy barrier calculated for TS-2-H/Et may suggest that coordination of ethylene to
the 18e κ2ꢀacetate complex 2-H, rather than ethylene insertion, is the rate determining step for the
overall reaction. Indeed, when an ethylene molecule approaches 2-H from an orientation cis to the
coordinating Phebox coordinating carbon, the potential energy of the combined system increases
dramatically, and we were unable to locate a TS for ethylene coordination. Viewing this process in
reverse, i.e. considering the removal of ethylene from 2-H-C2H4, is illustrative. At the minimum
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conformation for 2-H-C2H4, the distances from the Ir atom to the ethylene carbons are nearly
identical at R(IrꢀC1) = 2.123 Å and R(IrꢀC2) = 2.133 Å, respectively, with ꢀG = 17.5 kcal/mol
relative to free 2-H and ethylene (Figure 7a). Using RIrꢀC=C = R(IrꢀC1) = R(IrꢀC2) as a symmetrical
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“reaction coordinate” in a relaxed scan of the potential energy surface, we obtain approximate free
energies ꢀG = 18, 22, 31, 38 and 43 kcal/mol at RIrꢀC=C = 2.1, 2.3, 2.5, 2.7, and 2.9 Å,
respectively. Only at RIrꢀC=C values of ca. 4.0 ꢀ 4.5 Å does the acetate coordination at Ir change
from κ1 to κ2; the potential (and free) energies of the system then decrease in a discontinuous
manner and begin to approach the energies of the free products (2-H and ethylene). The ground
state electronic configuration of the κ1ꢀacetate complex 2-H-C2H4 does not correlate smoothly with
the ground states of κ2ꢀacetate complex 2-H and free ethylene, thus creating a substantial barrier
for ethylene addition(removal) to(from) 2-H. Unfortunately, the TS (and hence barrier magnitude)
for this step cannot be obtained within a single determinant framework such as DFT.
Regardless of whether the rateꢀdetermining step for the overall reaction is coordination of
ethylene or the insertion of coordinated ethylene, the DFT calculations (as well as intuition)
strongly suggest that the acetate ligand in the corresponding TS would be coordinated in a κ1
fashion, and moreover, this would allow it to bind more strongly to Na+ than would κ2ꢀacetate.
Accordingly, the Na+ꢀbound TS for ethylene insertion TS-2-H/Et•Na+ (Figure 7b) has a free energy
only 13.1 kcal/mol above the Na+ꢀbound κ2ꢀacetate complex, 2-H•Na+, plus ethylene. This is 7.9
kcal/mol less than the difference between TS-2-H/Et and 2-H plus ethylene (in the absence of
Na+), which would correspond to an increase in rate of a factor of ca. 105 relative to the
uncatalyzed reaction if this step were rateꢀdetermining. The calculated energy of Na+ binding to the
ethylene adduct intermediate 2-H-C2H4 is even greater, apparently due to an additional interaction
between the Na+ cation and the hydride ligand (Figure 7b). The free energy of 2-H-C2H4•Na+ is
only 6.4 kcal/mol above that of 2-H•Na+, as compared with 17.5 kcal/mol for the corresponding
species without Na+. If this energy difference (11.1 kcal/mol) were similar in the respective TS’s for
coordination of ethylene to form these adducts, the expected rate increase due to Na+ binding
would be a factor of ca. 108.
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The IrꢀO distances (2.19 Å and 3.47 Å) and the geometry of the IrꢀHꢀethene unit in
TS-2-H/Et•Na+ are essentially the same as in the Na+ꢀfree TS-2-H/Et; thus the difference in the
energies of these TSs, relative to 2-H•Na+ and 2-H respectively, appears to be chiefly due to the
favorable energetics of Na+ binding to the nonꢀcoordinated acetate O atom. In accord with this
proposal, the Na+ cation in the TS is tightly coordinated to the nonꢀIrꢀbound O atom, with dNaꢀO
=
2.085 Å (cf. 2.18 Å for the NaꢀO bond lengths in gasꢀphase κ2ꢀCH3CO2Na41). These results
indicate that the origin of the catalytic effect of the Na+ ion is straightforward, specifically, binding
to the acetate terminal oxygen and thereby favoring the κ1 configuration that is required by the
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insertion (or βꢀH elimination) transition state.42 It seems plausible, however, that an additional
interaction of Na+ with the hydride ligand, as seen in 2-H-C2H4•Na+, could also play a role in the
rate determining TS, particularly if the rate determining step is coordination of ethylene.
C-H Addition or Elimination Promoted by Lewis Acids. The ability of a Lewis acid to open a
coordination site in 2-H or 2-R to promote olefin insertion or βꢀH elimination, respectively, raised the
question as to whether Lewis acids could catalyze other reactions that might require a vacant
coordination site. CꢀH bond activation was of particular interest in the context of this class of
complexes and this work. To explore this possibility we initially studied the (energetically downhill)
microscopic reverse, a CꢀH bond elimination, specifically the hydrogenolysis of an IrꢀC bond (eq 7).
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2-R + H2
2-H + RꢀH
(7)
In accord with the above hypothesis, the rate of reaction between 2-alkyl and H2 was
substantially increased by the presence of NaBArF . In the absence of NaBArF , 2-Et did not react
4
4
to any significant extent under an atmosphere of H2 at room temperature. At 50 °C, hydrogenolysis
to afford 2-H and ethane occurred, but in only 3% yield after 24 h. In contrast, in the presence of
NaBArF (1.2 mM), the reaction proceeded at 25 °C to give 75% yield of 2-H, and ethane as
4
revealed by a characteristic signal at δ 0.80 ppm in the 1H NMR spectrum. No ethylene was
observed in solution.
O
O
O
O
N
N
O
R
O
H
Ir
O
Ir
O
+ H2
(1 atm)
+ RꢀH
benzeneꢀd6
N
N
2-H
R = Et
50 °C, 24 h
NaBArF 25 °C, 24 h
NaBArF 25 °C, 12 h
3% yield
75% yield
75% yield
R = Et
R = Pr
4
4
(8)
Analysis of the NaBArF ꢀcatalyzed reaction of 2-Et or 2-Pr with H2 is complicated by the fact
4
that NaBArF also catalyzes the βꢀH elimination reaction of these species. Since the βꢀH
4
elimination is reversible with the equilibrium lying far to the alkyl side (vide supra) we presumed
that it was not involved in the net hydrogenolysis. Nevertheless we wished to investigate a species
that would preclude this complicating factor in the study of hydrogenolysis (and, in the future,
potentially other reactions as well). Toward this end we synthesized 2-Me, which was
characterized by 13C and 1H NMR spectroscopy and singleꢀcrystal Xꢀray diffractometry. As with 2-
Et and 2-Pr, no reaction of 2-Me with H2 was observed in the absence of NaBArF at 25 °C,
4
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whereas in the presence of NaBArF the complex was converted to 2-H (75% yield) and methane
(δ 0.16 ppm in the 1H NMR spectrum) within 24 h (Figure 8).
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Figure 8. Formation of 2-H in the reaction (eq 7) of 2-Me (10 mM) with H2 (1 atm) in C6D6, at 25
°C, in the absence and in the presence of NaBArF (1.2 mM).
4
Based on microscopic reversibility our results suggest that the reaction of 2-H with alkanes to
give 2-R plus H2 should be catalyzed by Na+ and (perhaps other Lewis acids as well). Since
hydrogenolysis of lateꢀmetal alkyls is generally thermodynamically quite favorable (for the same
reasons and by the same amount that addition of H2 is thermodynamically more favorable than
addition of RꢀH43) we investigated the reverse of hydrogenolysis (eq 8) through H/D exchange
experiments.
nꢀOctaneꢀd18 solutions of 2-H (30 mM) with NaBArF (4.5 mM) and without NaBArF were
4
4
heated to 160 °C. Based on disappearance of the hydride signal in the 1H NMR spectra,
conversion of hydride to deuteride occurred in both cases. However, in the case of the solution
with NaBArF , but not the solution without NaBArF , extensive incorporation of D into the Phebox
4
4
and acetate ligands was also observed, manifest by both integration of the 1H NMR signals and by
isotopic shifts and splitting/broadening of the signals attributable to the oxazole methyl, benzylic,
and acetate protons (Figure 9). Interestingly, of the five positions bearing hydrogen, the only
position where H/D exchange was not observed was the 5ꢀposition (methylene) of the oxazole
rings. This is demonstrated by the fact that the 1H NMR signal of this proton remained unchanged
as a sharp doublet of doublets (the two hydrogens on each ring are chemically inequivalent);
conveniently, this allows the integral of this peak to serve as a calibration standard for integration
of the other ligand proton signals. We presume that the ligand H/D exchange proceeds via H/D
exchange with nꢀoctaneꢀd18 at the hydride position, followed by exchange (probably intermolecular)
with the ligand hydrogens. Thus NaBArF catalyzes H/D exchange of hydride not only with alkane,
4
but at the ligand methyl and aryl positions as well. The more detailed mechanism of these H/D
exchanges will be the subject of future study.
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1
2
3
0% H/D
exchange
12% H/D
exchange
4
5
6
7
8
9
4% H/D
exchange
O
O
N
11% H/D
exchange
N
O
O
160 °C, 24 h
37% H/D
exchange
Ir
O
Ir
O
nꢀC8D18, NaBArF
H
H
26% H/D
10
11
12
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exchange
N
N
O
O
2-H
30 mM
0% H/D
exchange
0% H/D
exchange
0% H/D
exchange
O
N
O
N
0% H/D
exchange
O
O
160 °C, 24 h
0% H/D
exchange
Ir
O
Ir
O
nꢀC8D18
38% H/D
exchange
H
H
N
N
O
O
2-H
30 mM
Figure 9. H/D exchange of 2-H with nꢀoctaneꢀd18 in the presence (4.5 mM) and in the
absence of NaBArF ; percent deuteration at each position of 2-H is indicated in red.
4
Hydrogenolysis and C-H activation: DFT calculations.
Oxidative addition to Cp*Ir(I) fragments44ꢀ46 are the iconic examples of alkane CꢀH bond
activation, first reported by Bergman in 1982. However, reports47 of alkane CꢀH activation by
Cp*Ir(III) complexes followed very soon thereafter. Since then, although Ir(I) has perhaps
maintained its lead status in this area, CꢀH activation by Ir(III) has become increasingly well
established,48,49 including within catalytic cycles for hydrogenation and dehydrogenation.50ꢀ53
DFT calculations suggest that the uncatalyzed hydrogenolysis of 2-Me proceeds via a CMDꢀ
type mechanism. Dechelation of the acetate ligand and addition of H2 trans to the methyl group
gives an intermediate (Phebox)Ir(Me)(κ1ꢀOAc)(H2) (4a) with a fairly low free energy, 10.2 kcal/mol
relative to 2-Me (Figure 10). Transfer of a proton from the coordinated H2 to the acetate ligand
gives the acetic acid complex (Phebox)Ir(Me)[OC(OH)Me](H) (5a-syn), which is also relatively low
in free energy (13.2 kcal/mol); this proton transfer is virtually barrierless (ꢀG‡ = 0.2 kcal/mol in the
reverse, endoergic direction). Rotation around the IrꢀO bond of the acetic acid complex would then
give the rotamer of (Phebox)Ir(Me)[OC(OH)Me](H) (5a-anti), with a free energy of 22.4 kcal/mol.
5a-anti can undergo protonolysis of the Ir–Me group (the reverse of a CMD activation mechanism);
this CMDꢀtype reaction also has a very low barrier (ꢀG‡ = 0.6 kcal/mol). The required rotation
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around the IrꢀO bond to give 5a-anti, however, is sterically very hindered and we are unable to find
an accessible intramolecular pathway for this reaction. Alternatively, the isomerization can be
achieved via loss of acetic acid and then reꢀcoordination to provide the anti orientation. The
coordination of acetic acid could also lead to coordination isomer 5b which can undergo IrꢀMe
protonolysis. Likewise, addition of H2 trans to the Phebox aryl group of 2-Me, to give 4b and then
5c, followed by loss of acetic acid would also give the same intermediate, (Phebox)Ir(Me)(H) (6),
plus free acetic acid. From either intermediate (5a-syn or 5c), however, loss of acetic acid carries
a significant energetic cost; the free energy of 6 plus free acetic acid is calculated as 29.5 kcal/mol.
One might envision more facile pathways for the net rotation reaction, 5a-syn to 5a-anti, e.g.,
intramolecular proton transfer (O2ꢀO1) accompanied by slippage of Ir in the reverse direction, but
as of yet we have been unable to locate such a TS. These results are, at least qualitatively,
consistent with the experimental observation of a slow hydrogenolysis of 2-Me in the absence of
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11
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14
15
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NaBArF , to give a 3% yield in 24 h at 50 °C, which implies a barrier of ꢀG‡ ~ 29 kcal/mol.
4
H
H
O
H
[Ir]
O
O
H
Ir
O
H
[Ir]
HO
O
H2
[Ir]
??
O
4a
O
H
H3C
H3C
O
HOAc Ir-O
rotation/
isomerization
H3C
[Ir]
H3C
13.4
HO
5a-anti
H2 +
H3C 5a-syn
10.2
22.4
23.0
21.7
13.2
2-H
O
[Ir]
H
O
O
O
[Ir]
+ H-CH3
O
O
H3C
ꢀ17.1
H
[Ir]
+ HOAc
(0.0)
2-Me
O
OH
O
O
O
OH
H
[Ir] CH3
4b
H3C
[Ir]
H
[Ir] H2
CH3
[Ir] CH3
H
6
O
[Ir]
H
O
5c
CH3
15.3
H
5b
29.5
H
21.5
10.7
C
16.5
H3
Figure 10. CMDꢀtype pathways for hydrogenolysis of the IrꢀC bond of 2-Me (unassisted by Lewis
acid); calculated free energies (kcal/mol) of intermediates and transition states indicated.
Two alternative pathways for the uncatalyzed hydrogenolysis of 2-Me, which do not involve
CMD, have also been calculated. Each pathway involves initial coordination of H2 to the Ir center,
producing intermediates 4b or 4c respectively, in which CH3 is coordinated trans to the Phebox
aryl and to the acetate group, respectively (Figure 11). 4c is much higher in free energy than
isomers 4a or 4b (32.2 kcal/mol vs. 10.2 kcal/mol and 10.7 kcal/mol, respectively) consistent with a
mutually trans arrangement of the strongꢀtransꢀinfluence aryl and methyl groups. 4c undergoes
oxidative cleavage of the coordinated dihydrogen (Figure 11, top path) with virtually no barrier, to
give an Ir(V) intermediate, 7 (dHH = 1.44 Å) with free energy 31.3 kcal/mol above reactants (the TS
for this reaction is actually lower in free energy than the connected intermediates, although it is a
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maximum (a first order saddle point) on the electronic potential energy surface). One of the hydride
ligands then swings toward the Me group, proceeding through a TS on the potential energy surface
with free energy 31.2 kcal/mol above reactants, essentially equal to the free energy of 7. The TS
for hydrogen migration reveals an increased HꢀH distance, dHH = 1.57 Å, and incipient CꢀH bond
formation as indicated by a decreased CꢀH distance (dCH = 1.88 Å) and the IrꢀMe bond bending
slightly to allow CꢀH bond formation (IrꢀCꢀH angles = 116.9°, 116.2°, 99.2°). As indicated in Figure
11 (upper path), the energy surface is quite flat between the initial dihydrogen adduct 4c and the
CꢀH bond formation TS.
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60
Ir(V)
O
CH3
1.104
O
O
O
O
O
O
O
O
O
[Ir]
[Ir] CH3
[Ir] CH3
[Ir] CH3
[Ir] CH3
4c
1
.
1.59
H
1.59
H
H
1.60
1.59
5
1.88
9
H
H
H H
1.03
H
H
H
1.57
0.94
7
1.44
8c
0.9
32.2
31.0
31.3
31.2
O
[Ir]
O
OHM
+ H2
O
H3C
O
O
O
O
1.72
[Ir]
O
O
O
1.71
H
[Ir]
4b
(0.0)
H
H
[Ir]
H
+ HꢀCH3
1.58
[Ir]
CH3
0.83
2-Me
1.44
H
H
H3C
H
H3C
ꢀ17.1
1.137
1.42
8b
2-H
10.7
36.3
32.4
Figure 11. NonꢀCMD (OHM or Ir(V)) pathways for hydrogenolysis of 2-Me (unassisted by Lewis
acid) via H2 adducts 4b or 4c; calculated free energies (kcal/mol) and selected internuclear
distances (Å) indicated.
In the case of the other, closely related, pathway, (Figure 11, lower path), the H2 coordinates
trans to the Phebox aryl group, rather than trans to the acetate ligand, to give the dihydrogen
complex 4b. This pathway then also proceeds through a species that is Ir(V) in character, but it is a
TS, with free energy 36.3 kcal/mol above the reactants. No Ir(V) intermediate was located; thus this
appears to be an example of an oxidative hydrogen migration (OHM) pathway.49
Thus, both of the calculated nonꢀCMD uncatalyzed pathways (Figure 11) appear to have higher
overall barriers (>32 kcal/mol and >36 kcal/mol, respectively) than the CMD pathway of Figure 10
(29.5 kcal/mol), even if the CMD pathway must proceed through loss of acetic acid to achieve the
net rotation around the IrꢀO bond.
We initially considered that a Na+ꢀcatalyzed pathway might proceed analogously to the
uncatalyzed pathway, with Na+ simply favoring the ringꢀopened intermediates and/or TS's; this was
essentially the case for the insertion/βꢀH elimination reactions discussed above. The situation,
however, is apparently not so simple for hydrogenolysis. If we consider the reverse reaction, the
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CMD activation of methane (2-H to 5a-anti or 5b), coordination of Na+ facilitates the dechelation of
acetate, but it strongly lowers the basicity of the unbound O atom. As a result, the proton transfer
from the incoming methane has a TS that is substantially higher in free energy (32.3 kcal/mol
relative to 2-Me plus H2) than the corresponding TS unbound to Na+ (23.0 kcal/mol; Figure 10).
Moreover, the step that was apparently rateꢀlimiting in the uncatalyzed case, namely rotation about
the IrꢀO bond, would still be required subsequent to CMD activation of methane. Thus, rather than
introducing a lower barrier to the CMDꢀtype pathway, coordination of Na+ at the terminal oxygen to
promote dechelation is calculated to leave the highest barrier unchanged, while introducing a new,
even higher, barrier to the overall reaction.
9
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Thus dechelation of the acetate ligand, required for the CMD pathways of Figure 10, is favored
by Na+ coordination but the advantage is more than offset by the resulting decrease in basicity of
the κ1ꢀacetate terminal oxygen. In the (nonꢀCMD) Ir(V) and OHM pathways (Figure 11) however,
no such counteracting effect of Na+ coordination is expected. Coordination of Na+ to an acetate O
atom favors the thermodynamics of dechelation by 5.7 kcal/mol in the case of 4c, and 8.6 kcal/mol
in the case of 4b (Figure 12). Both species then undergo IrꢀMe hydrogenolysis via an oxidative
hydrogen migration pathway (the Na+ꢀcoordinated analogue of the Ir(V) intermediate, 7, in Figure
11 is not a stationary point on the potential energy surface). The calculated barriers are
approximately equal, with the pathway proceeding through 4b calculated to have a slightly lower
overall free energy barrier of 24.5 kcal/mol. This is ca. 8 kcal/mol lower than the overall barrier of
the more favorable of the unassisted nonꢀCMD pathways of Figure 11. It is also more favorable, by
ca. 5 kcal/mol, than the (unassisted) CMDꢀtype pathway (Figure 10), which is calculated to be the
most favorable pathway in the absence of Na+ with a barrier of 29.5 kcal/mol.
The sodium cation presumably facilitates the OHM pathway of Figures 11 and 12 primarily by
favoring the κ1ꢀacetate configuration. In the case of the bottom pathway of Figure 12, however,
(proceeding via 4b•Na+) the Na+ ion appears to play an additional role by interacting with the
incipient hydride of the TS connecting 4b•Na+ with 8b•Na+. In all the κ1ꢀacetate complexes shown
in Figure 2, the Na+ is positioned over the Phebox phenyl ring (Na+ꢀcentroid distances of ca. 2.5 Å
are shown in Figure 12), except for 8b•Na+ and the TS which leads to it. In 8b•Na+ the calculated
NaꢀH (hydride) distance is particularly short at 2.05 Å. Accordingly, an isomer of 8b•Na+ in which
the Na+ cation is located near the Phebox aryl group (Na+ꢀcentroid distance = 2.50 Å) is 5.9
kcal/mol higher in free energy than 8b•Na+. In the case of the TS connecting 4b•Na+ with 8b•Na+
HꢀH bonding is still significant and the H atom does not have full hydride character; nevertheless,
this TS, as shown in Figure 12, is still calculated to be 2.2 kcal/mol lower in free energy than a
conformer of this TS (not shown) in which the Na+ is interacting with the aryl ring (Na+ꢀcentroid
distance = 2.53 Å).
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8
9
10
(Na+ꢀcent
= 2.55)
(Na+ꢀcent
= 2.57)
(Na+ꢀcent
= 2.55)
8c•Na+
Na+
2.10
O
2.21
Na+
2.09
O
Na+
2.09
O
2.12
O
O
O
CH3
2.09
2.20
2.20
[Ir]
1.105
H
[Ir] CH3
[Ir] CH3
1.59
4c•Na+
2.29
2.17
H
O
H
H
H
H
2.28
0.92
O
1.07
2-Me
24.2
(31.0)
ꢀ11.8
(0.9)
2.18
26.5
(32.2)
[Ir]
Na+
Na+
OHM
1.59
O
O
2.17
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2.54
H
+ HꢀCH3
ꢀ17.4
2-H•Na+
[Ir]
2.05
H3C
+ H2
O
O
2.05
2.14
Na+
2.05
Na+
2.10
O
O
2.15
O
2.10
Na+
O
1.75
H
2.23
[Ir]
2.08
H
H
1.75
(0.0)
[Ir]
[Ir]
2.18
H3C
1
H
2.21
(Na+ꢀcent
= 2.53)
0.83
1.29
1.86
H
H
0
8b•Na+
CH3
1.61
H3C
6
.
4b•Na+
1.14
18.4
(32.4)
2.1
24.5
(36.3)
(10.7)
Figure 12. Na+ꢀcatalyzed hydrogenolysis of 2-Me proceeding via H2 adducts 4b•Na+ or 4c•Na+;
free energies (kcal/mol) and selected internuclear distances (Å) of intermediates and transition
states indicated. Energies of analogous species in the unassisted pathway (Figure 11) are shown
(in parentheses) for comparison. "Na+ꢀcent" is the calculated distance between the Na+ cation and
the centroid of the Phebox phenyl ring; this is given for all species for which such an interaction is
calculated (distance < 3.5 Å).
Thus while the sodium ion does not promote the more favorable unassisted pathways (CMD,
Figure 10), it is calculated to lower the barrier to the OHM pathway (Figure 11) to a level below that
of the unassisted CMD pathway. Results of kinetic isotope experiments, in which 2-Me reacted
with either H2 or D2 (eq 8), support the proposal that the Na+ꢀcatalyzed and unassisted reactions
proceed via qualitatively different pathways (or at least different rateꢀdetermining TSs). For the
unassisted reaction, the kinetic isotope effect (KIE) of the hydrogenolysis of eq 8 is found to be
inverse, kH2/kD2 = 0.71 ± 0.14, consistent with a rateꢀdetermining step in which the HꢀH(DꢀD) bond
has been broken and IrꢀH(D) and OꢀH(D) bonds have been formed. The Na+ꢀcatalyzed reaction, by
contrast, reveals a KIE near unity, kH2/kD2 = 1.08 ± 0.21 (error limits at 95% confidence intervals).
The directions of both of these KIEs are consistent with the DFT calculations on the respective
proposed pathways.54
Catalytic alkane dehydrogenation. The sum of the reverse of the hydrogenolysis reaction of
2-alkyl (eq 8), and the βꢀhydride elimination of 2-alkyl, comprises an acceptorless alkane
dehydrogenation system (Scheme 5). Note that both components of this cycle were found to be
catalyzed by NaBArF (the former step much less dramatically than the latter).
4
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Scheme 5. Proposed Catalytic Cycle for Acceptorless Dehydrogenation of n-Alkane
O
N
O
6
7
Ir
O
H
alkene
N
8
9
nꢀalkane
O
O
10
11
12
13
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H2
N
O
Ir
O
nꢀalkyl
N
O
Refluxing a nꢀdodecane (b.p. 216 °C) solution of 2-H (1.0 mM) with a flow of argon above the
condenser25 yields only 3 mM dodecenes after 1 h. By contrast, in the presence of NaBArF , 24
4
mM dodecenes was obtained under the same conditions (Table 1). The reaction rate leveled off
significantly in the run with NaBArF , yielding 47 mM and 78 mM dodecenes after 24 h and 72 h
4
respectively. This is comparable to results obtained with (R4PCP)Ir derivatives, which are the most
effective molecular catalysts for acceptorless dehydrogenation of nꢀalkanes reported to date. For
example, (Ad4PCP)IrH2 (1 mM) yields a total of 71 mM dodecene after 72 h and (iPr4PCP)IrH2 (1
mM) affords 61 mM after 48 h.25 We suspect that the very similar turnover numbers of all these
catalysts at longer reaction times indicates that the rate of olefin formation is not limited primarily
by the activity of the respective catalyst. Rather, as the concentration of olefin increases, the
equilibrium concentration of H2 (ca. 10ꢀ9 M in the presence of 50 mM dodecane30) decreases, and
the rate at which H2 is purged from solution decreases commensurately. In support of this
proposal, the dehydrogenation rate is significantly influenced by the extent to which the
temperature of the oil bath is above the boiling point of the solvent. Thus although the boiling point
of dodecane is 216 °C, the yields of olefin are much greater when the reaction vessel is immersed
in an oil bath at 250 °C than one at 220 °C (Table S2), presumably because refluxing is much
more vigorous at the higher temperature.
Table 1. Acceptorless Dehydrogenation of n-Dodecane by 2a
Dodecenes (mM)
Additive
1 h
3
24 h
46
72 h
78
none
NaBArF4 (0.45 mM)
24
4
47
78
H2O (3.7 M)
48 (27 h)
60
NaBArF4 (0.45 mM) + H2O (1.8 M)
a Conditions: [2-H] = 1.0 mM, 1.5 mL
nꢀdodecane, oil bath temp = 250 °C (nꢀdodecane b.p. = 216 °C).
28
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CONCLUSIONS
Transition metal acetate complexes have received great attention in recent years,55ꢀ58 in part
thanks to the ability to activate CꢀH bonds via a CMD mechanism.7ꢀ10 The present system,
Nishiyama’s Phebox iridium acetate complex, represents an important example of this
phenomenon. Here we report that simple Lewis acids, and particularly Na+, can catalyze two of the
most relevant and fundamental organometallic reactions with this complex: olefin insertion and CꢀH
addition (and their respective microscopic reverse reactions). The results of DFT calculations
indicate that the Lewis acid catalysts primarily operate via coordination to an acetate oxygen atom
which promotes the opening of a vacant coordination site (additional interaction with a hydride or
incipient hydride ligand may in some cases also play a role). For CꢀH addition, the calculations
indicate that acetate dechelation by Na+ promotes a nonꢀCMD, high metalꢀoxidationꢀstate,
pathway. Further investigation is ongoing to determine the scope of the applicability of such Lewis
acids in the context of transition metal acetate chemistry, as well as attempts to apply the
understanding gained in this work toward the development of new, nonꢀacetate, catalysts.
4
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ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website at DOI
xxxx:. Experimental procedures, characterization data, kinetic details, computational data (PDF),
crystallographic data for 2-Me, 2-Et, 3 (CIF)
AUTHOR INFORMATION
Corresponding Authors
*(A.S.G.): Eꢀmail: alan.goldman@rutgers.edu
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS. This work was supported by NSF under the CCI Center for Enabling
New Technologies through Catalysis (CENTC) Phase II Renewal, CHEꢀ1205189.
REFERENCES
(1) Kumar, A.; Goldman, A. S. In Top. Organomet. Chem.; van Koten, G., Gossage, R. A., Eds.; Springer
International Publishing: 2016; Vol. 54, p 307ꢀ334.
(2) Choi, J.; MacArthur, A. H. R.; Brookhart, M.; Goldman, A. S. Chem. Rev. 2011
(3) Dobereiner, G. E.; Crabtree, R. H. Chem. Rev. 2010 110, 681ꢀ703.
(4) Ito, J.ꢀi.; Kaneda, T.; Nishiyama, H. Organometallics 2012 31, 4442ꢀ4449.
, 111, 1761ꢀ1779.
,
,
(5) Allen, K. E.; Heinekey, D. M.; Goldman, A. S.; Goldberg, K. I. Organometallics 2013, 32, 1579ꢀ1582.
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Page 24 of 26
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1
2
(6) Davies, D. L.; Donald, S. M. A.; Macgregor, S. A. J. Am. Chem. Soc. 2005
,
127, 13754ꢀ13755.
3
4
5
6
7
8
9
(7) Gorelsky, S. I.; Lapointe, D.; Fagnou, K. J. Am. Chem. Soc. 2008
(8) Lapointe, D.; Fagnou, K. Chem. Lett. 2010 39, 1118ꢀ1126.
(9) Ackermann, L. Chem. Rev. 2011 111, 1315ꢀ1345.
(10) Gorelsky, S. I. Coord. Chem. Rev. 2013 257, 153ꢀ164.
(11) Pahls, D. R.; Allen, K. E.; Goldberg, K. I.; Cundari, T. R. Organometallics 2014
(12) Allen, K. E.; Heinekey, D. M.; Goldman, A. S.; Goldberg, K. I. Organometallics 2014
(13) Williams, D. B.; Kaminsky, W.; Mayer, J. M.; Goldberg, K. I. Chem. Commun. 2008, 4195ꢀ4197.
(14) Goldberg, K. I.; Goldman, A. S. Acc. Chem. Res. 2017 50, 620ꢀ626.
, 130, 10848ꢀ10849.
,
,
,
,
33, 6413ꢀ6419.
33, 1337ꢀ1340.
,
,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(15) The stability of Roddick's pincerꢀligated Ru and Os alkane dehydrogenation catalysts toward N2, water,
and to some extent even O2 may be attributable to the electronꢀpoor nature of the pincer ligands which
contain perfluoroalkyl groups. It may also be attributable to the oxidation states of the catalytic species,
which are probably no lower than M(II), and which is isoelectronic to the Ir(III) discussed in this work. (a)
Gruver, B. C.; Adams, J. J.; Warner, S. J.; Arulsamy, N.; Roddick, D. M. Organometallics 2011, 30,
5133–5140. (b) Gruver, B. C.; Adams, J. J.; Arulsamy, N.; Roddick, D. M. Organometallics 2013, 32,
6468ꢀ6475.
(16) Owens, C. P.; VarelaꢀAlvarez, A.; Boyarskikh, V.; Musaev, D. G.; Davies, H. M. L.; Blakey, S. B. Chem.
Sci. 2013
(17) Zhou, M.; Hintermair, U.; Hashiguchi, B. G.; Parent, A. R.; Hashmi, S. M.; Elimelech, M.; Periana, R. A.;
Brudvig, G. W.; Crabtree, R. H. Organometallics 2013 32, 957ꢀ965.
(18) Zhou, M.; Johnson, S. I.; Gao, Y.; Emge, T. J.; Nielsen, R. J.; Goddard, W. A.; Goldman, A. S.
Organometallics 2015 34, 2879–2888.
(19) Shin, K.; Park, S.ꢀW.; Chang, S. J. Am. Chem. Soc. 2015
(20) Choi, J.; Goldman, A. S. Top. Organomet. Chem. 2011 34, 139–168.
(21) Kumar, A.; Zhou, T.; Emge, T. J.; Mironov, O.; Saxton, R. J.; KroghꢀJespersen, K.; Goldman, A. S. J.
Am. Chem. Soc. 2015 137, 9894ꢀ9911.
(22) A closely related cationic complex, (pybox)Ir(C2H4)2, has been previously reported: Díez, J.; Gamasa,
, 4, 2590ꢀ2596.
,
,
,
137, 8584ꢀ8592.
,
,
M. P.; Gimeno, J.; Paredes, P. Organometallics 2005, 24, 1799ꢀ1802.
(23) See Supporting Information for details.
(24) Kundu, S.; Choliy, Y.; Zhuo, G.; Ahuja, R.; Emge, T. J.; Warmuth, R.; Brookhart, M.; KroghꢀJespersen,
K.; Goldman, A. S. Organometallics 2009 28, 5432ꢀ5444.
,
(25) Punji, B.; Emge, T. J.; Goldman, A. S. Organometallics 2010, 29, 2702ꢀ2709.
(26) We considered that NaBArF4 was soluble in benzene, even if very slightly, but that due to ionꢀpairing
perhaps the signal was too broad to be observed in the 1H NMR spectrum. We therefore added
NaBArF4 to benzene, filtered, and then added 2-H and then ethylene. No reaction was observed, and
the spectrum of 2-H was no different than in benzene that had not been exposed to NaBArF , indicating
4
that the solubility was much less than even the 0.2 mM that was in solution in the experiment of eq 4.
(27) More, M. B.; Ray, D.; Armentrout, P. B. J. Am. Chem. Soc. 1999, 121, 417ꢀ423.
(28) Berg, J. M.; Tymoczko J. L.; Stryer L. In Biochemistry 5th edition, New York: W H Freeman; 2002.
Available from: https://www.ncbi.nlm.nih.gov/books/NBK21154/
(29) Hoops, S.; Sahle, S.; Gauges, R.; Lee, C.; Pahle, J.; Simus, N.; Singhal, M.; Xu, L.; Mendes, P.;
Kummer, U. Bioinformatics 2006, 22, 3067ꢀ3074.
(30) Afeefy, H. Y.; Liebman, J. F.; Stein, S.E. "Neutral Thermochemical Data" in NIST Chemistry WebBook,
NIST Standard Reference Database Number 69, Eds. P.J. Linstrom and W.G. Mallard, National
Institute of Standards and Technology, Gaithersburg MD, 20899, http://webbook.nist.gov, (retrieved
January 3, 2015)
(31) Zhao, Y.; Truhlar, D. G. J. Chem. Phys. 2006
(32) Andrae, D.; Haeussermann, U.; Dolg, M.; Stoll, H.; Preuss, H. Theor. Chim. Acta 1990
(33) Iron, M. A.; Lucassen, A. C. B.; Cohen, H.; van der Boom, M. E.; Martin, J. M. L. J. Am. Chem. Soc.
2004 126, 11699ꢀ11710.
(34) Ditchfield, R.; Hehre, W. J.; Pople, J. A. J. Chem. Phys. 1971
(35) Hariharan, P. C.; Pople, J. A. Mol. Phys. 1974 27, 209ꢀ214.
(36) Raghavachari, K.; Binkley, J. S.; Seeger, R.; Pople, J. A. J. Chem. Phys. 1980
, 125, 194101/1ꢀ194101/18.
,
77, 123ꢀ41.
,
,
54, 724ꢀ728.
,
,
72, 650ꢀ654.
(37) It may be noted that the calculated barrier to the actual insertion step, the step subsequent to ethylene
coordination, is only ∆G‡ = 3.5 kcal/mol, thus contributing very little to the overall reaction barrier.
(38) We also investigated the predictions of other functionals, using the same basis set as in the M06ꢀL
calculations described in the text. Briefly, the barrier (∆G‡, kcal/mol) to ethylene insertion calculated by
various popular functionals span an energy range of more than 10 kcal/mol, viz. 21.0 (M06ꢀL); 18.2
(M06); 29.0 (M11ꢀL); 18.8 (M11); 22.7 (PBE); and 29.0 (B3LYP). Inclusion of Grimme’s D3 dispersion
treatment as a singleꢀpoint correction (http://www.thch.uniꢀbonn.de/tc/, accessed September 2016). D3
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scaling parameters not available for the M11ꢀL and M11 functionals) lowers the barriers (kcal/mol)
further to 19.5 (M06ꢀL); 16.1 (M06); 16.5 (PBE); and 21.6 (B3LYP). Thus, DFT calculations generally
favor free energy barrier values significantly lower than the experimental result. Bulk solvation effects
computed via a continuum dielectric model with benzene as the model solvent tend to increase the
computed barrier for ethylene insertion slightly (~1 kcal/mol or less).
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(39) The very large energy difference (>20 kcal/mol) between species 4b and 4c, discussed below in the
context of hydrogenolysis, offers a specific illustration of the large effect of an alkyl ligand coordinated
trans to kappaꢀ1ꢀacetate vs. trans to the Phebox coordinating carbon.
(40) Hasanayn, F.; Achord, P.; Braunstein, P.; Magnier, H. J.; KroghꢀJespersen, K.; Goldman, A. S.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
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42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Organometallics 2012, 31, 4680ꢀ4692.
(41) P.J. Linstrom and W.G. Mallard, Eds., NIST Chemistry WebBook, NIST Standard Reference Database
Number 69, National Institute of Standards and Technology, Gaithersburg MD, 20899,
http://webbook.nist.gov, http://webbook.nist.gov/cgi/cbook.cgi?ID=C127093&Units=SI; (retrieved
November 7, 2016).
(42) We also considered that the Na+ ion might form a complex with a benzene solvent molecule, i.e. the
effective Lewis acid was modeled as a Na+:benzene complex. This does not significantly influence the
reaction energetics, only slightly raising the barrier to ethylene insertion from 13.1 kcal/mol (Figure 7(b))
to 13.8 kcal/mol. Nicholas, J. B.; Hay, B. P.; Dixon, D. A. J. Phys. Chem. A 1999
(43) Labinger, J. A.; Bercaw, J. E. Organometallics 1988 , 926ꢀ8.
(44) Janowicz, A. H.; Bergman, R. G. J. Am. Chem. Soc. 1982
(45) Hoyano, J. K.; Graham, W. A. G. J. Am. Chem. Soc. 1982
, 103, 1394ꢀ1400.
,
7
,
,
104, 352ꢀ354.
104, 3723ꢀ3725.
(46) Arndtsen, B. A.; Bergman, R. G.; Mobley, T. A.; Peterson, T. H. Acc. Chem. Res. 1995
(47) Burger, P.; Bergman, R. G. J. Am. Chem. Soc. 1993 115, 10462ꢀ10463.
(48) For some examples of CꢀH addition to give Ir(V) and closely related reactions see: (a) Klei, S. R.;
Tilley, T. D.; Bergman, R. G. J. Am. Chem. Soc. 2000 122, 1816ꢀ1817. (b) Kawamura, K.; Hartwig, J.
F. J. Am. Chem. Soc. 2001 123, 8422ꢀ8423. (c) KroghꢀJespersen, K.; Czerw, M.; Kanzelberger, M.;
Goldman, A. S. J. Chem. Inf. Comput. Sci. 2001 41, 56ꢀ63.(d) Mohammad, H. A. Y.; Grimm, J. C.;
Eichele, K.; Mack, H.ꢀG.; Speiser, B.; Novak, F.; Quintanilla, M. G.; Kaska, W. C.; Mayer, H. A.
Organometallics 2002 21, 5775ꢀ5784. (e) KroghꢀJespersen, K.; Czerw, M.; Summa, N.; Renkema, K.
B.; Achord, P. D.; Goldman, A. S. J. Am. Chem. Soc. 2002 124, 11404ꢀ11416. (f) Webster, C. E.; Hall,
M. B. Coord. Chem. Rev. 2003 238-239, 315ꢀ331. (g) Brandt, P.; Hedberg, C.; Andersson, P. G.
Chem. - Eur. J. 2003 , 339ꢀ347. (h) Lam, W. H.; Lam, K. C.; Lin, Z.; Shimada, S.; Perutz, R. N.;
Marder, T. B. Dalton Trans. 2004, 1556ꢀ1562. (i) Bernskoetter, W. H.; Lobkovsky, E.; Chirik, P. J.
Organometallics 2005 24, 4367ꢀ4373. (j) Roseblade, S. J.; Pfaltz, A. C. R. Chim. 2007 10, 178ꢀ187.
(k) Hopmann, K. H.; Bayer, A. Organometallics 2011 30, 2483ꢀ2497. (l) Gruber, S.; Pfaltz, A. Angew.
Chem., Intl. Ed. 2014 53, 1896ꢀ1900. (m) Polo, V.; AlꢀSaadi, A. A.; Oro, L. A. Organometallics 2014
33, 5156ꢀ5163. (n) Shin, K.; Park, S.ꢀW.; Chang, S. J. Am. Chem. Soc. 2015 137, 8584ꢀ8592.
(49) (a) Oxgaard, J.; Muller, R. P.; Goddard, W. A.; Periana, R. A. J. Am. Chem. Soc. 2004 126, 352ꢀ363.
(b) Oxgaard, J.; Periana, R. A.; Goddard, W. A., III J. Am. Chem. Soc. 2004 126, 11658ꢀ11665.
(50) (a) Fan, Y.; Cui, X.; Burgess, K.; Hall, M. B. J. Am. Chem. Soc. 2004 126, 16688ꢀ16689. (b) Cui, X.;
Fan, Y.; Hall, M. B.; Burgess, K. Chem.-Eur. J. 2005 11, 6859ꢀ6868.
(51) Cheng, C.; Kim, B. G.; Guironnet, D.; Brookhart, M.; Guan, C.; Wang, D. Y.; KroghꢀJespersen, K.;
Goldman, A. S. J. Am. Chem. Soc. 2014 136, 6672−6683.
, 28, 154ꢀ162.
,
,
,
,
,
,
,
,
9
,
,
,
,
,
,
,
,
,
,
,
(52) Mazuela, J.; Norrby, P.ꢀO.; Andersson, P. G.; Pàmies, O.; Diéguez, M. J. Am. Chem. Soc. 2011, 133,
13634ꢀ13645.
(53) Rimoldi, M.; Fodor, D.; van Bokhoven, J. A.; Mezzetti, A. Chem. Commun. 2013, 49, 11314ꢀ11316.
(54) The factors determining the values of isotope effects for H2 addition to transition metal complexes are
complex, and a full analysis of the predicted isotope effects for these reactions is beyond the scope of
this paper, particularly considering that the calculations do not yield unambiguous predictions for the
rateꢀdetermining transition state within each set of pathways. For inꢀdepth discussion of isotope effects
for H2 addition to transition metal complexes, see: (a) Parkin, G. Acc. Chem. Res. 2009
(a) Janak, K. E.; Parkin, G. J. Am. Chem. Soc. 2003 125, 13219ꢀ13224. (c) AbuꢀHasanayn, F.;
Goldman, A. S.; KroghꢀJespersen, K. J. Phys. Chem. 1993 97, 5890ꢀ5896. (d) AbuꢀHasanayn, F.;
KroghꢀJespersen, K.; Goldman, A. S. J. Am. Chem. Soc. 1993
(55) Daugulis, O.; Do, H.ꢀQ.; Shabashov, D. Acc. Chem. Res. 2009
(56) Cook, A. K.; Sanford, M. S. J. Am. Chem. Soc. 2015
(57) Davies, H. M. L.; Morton, D. J. Org. Chem. 2016 81, 343ꢀ350.
, 42, 315ꢀ325.
,
,
,
,
115, 8019ꢀ8023.
42, 1074ꢀ1086.
,
137, 3109ꢀ3118.
,
(58) He, J.; Wasa, M.; Chan, K. S. L.; Shao, Q.; Yu, J.ꢀQ. Chem. Rev. 2016
.
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Table of Contents Graphic for jaꢀ2016ꢀ12995v
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β-Hydride Elimination and C-H Bond
Activation Catalyzed by Na⁺ cation
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R
CH3CH2R +
H2 +
H2
+
O
O
O
Na+
Na+
CH2CH2R
N
O
N
N
O
O
O
O
Ir
Ir
O
Ir
H
H
N
N
N
O
O
O
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