π-complexation in nickel-catalyzed cross-coupling reactions

Article abstract of DOI:10.1021/jo402259z

The kinetic isotope effect (KIE) is used to experimentally elucidate the first irreversible step in oxidative addition reactions of a zerovalent nickel catalyst to a set of haloarene substrates. Halogenated o-methylbenzene, dimethoxybenzene, and thiophene derivatives undergo intramolecular oxidative addition through irreversible π-complexation. Density functional theory computations at the B3LYP-D3/TZ2P-LANL2TZ(f)-LANL08d level predict η²-bound π-complexes are generally stable relative to a solvated catalyst plus free substrate and that ring-walking of the Ni(0) catalyst and intramolecular oxidative addition are facile in these intermediates.

Full text of DOI:10.1021/jo402259z

Note
pubs.acs.org/joc
π‑Complexation in Nickel-Catalyzed Cross-Coupling Reactions
S. Kyle Sontag,†,∥ Jenna A. Bilbrey,†,‡,∥ N. Eric Huddleston,† Gareth R. Sheppard,† Wesley D. Allen,*,†,‡
and Jason Locklin*,†,§
‡
§
†Department of Chemistry, Center for Computational Chemistry, and College of Engineering, University of Georgia, Athens,
Georgia 30602, United States
S
* Supporting Information
ABSTRACT: The kinetic isotope effect (KIE) is used to
experimentally elucidate the first irreversible step in oxidative
addition reactions of a zerovalent nickel catalyst to a set of
haloarene substrates. Halogenated o-methylbenzene, dimethoxy-
benzene, and thiophene derivatives undergo intramolecular
oxidative addition through irreversible π-complexation. Density
functional theory computations at the B3LYP-D3/TZ2P-
LANL2TZ(f)-LANL08d level predict η2-bound π-complexes
are generally stable relative to a solvated catalyst plus free
substrate and that ring-walking of the Ni(0) catalyst and
intramolecular oxidative addition are facile in these intermedi-
ates.
he Kumada−Tamao−Corriu (KTC) reaction is com-
monly used for carbon−carbon cross-coupling in small
catalyst “chain-walks” along the aromatic polymer backbone,
and the nature of the aromatic system can alter this chain-
walking phenomenon. A recent review by the McNeil group
discusses our limited knowledge of the binding and whether the
substrate is in η2-, η4-, or η6-coordination with Ni(0).9 An
experimental and theoretical understanding of the interaction of
Ni(0) catalysts with aromatic substrates promises to provide
more efficient, selective catalysts for polymerization.
Though the formation of π-complexes plays an important
role in many cross-coupling reactions, isolation or direct
observation is often not possible due to the short lifetimes of
these metastable species.10 However, the kinetic isotope effect
(KIE) can provide information on the atoms involved in the
first irreversible step (FIS) when a catalyst is involved.2c,3a,11 In
reactions such as OA involving bond rearrangements,
substitution of heavier isotopes tends to enhance activation
barriers and reduce reaction rates.12 When probing carbon
isotope effects, substrates containing the lighter 12C atom will
preferentially react, leaving 13C enrichment at the active site in
recovered starting material. An increased KIE (>1.000 relative
to an internal standard) at an atomic position indicates
involvement of this site in the FIS. Carbon-specific KIEs can be
quantified by 13C NMR through comparison of 13C ratios in the
substrate before and after reaction.13 In this case, deliberate
isotopic labeling is unnecessary because the natural abundance
of 13C is sufficient for high-field NMR methods.
T
molecule synthesis.1 In such reactions, a zerovalent nickel
catalyst undergoes a fundamental catalytic cycle involving
oxidative addition (OA) to a reactive substrate, transmetalation
with a Grignard reagent, and reductive elimination to form a
carbon−carbon bond. The OA reaction, which initiates the
catalytic cycle by conversion of starting materials to reactive
intermediates, is known to be a two-step process with the
transition metal catalyst first undergoing initial complexation
with the substrate followed by nickel insertion.2 The resulting
intermediate is generally stable and proceeds as the substrate
for transmetalation in organometallic reactions. Some computa-
tional work has examined the role of oxidative addition for
zerovalent group 10 metals in various cross-coupling reactions,
mostly focusing on the nickel insertion step with limited
substrates.3
In the KTC system, a π-complex is formed between the
Ni(0) d-orbitals and the antibonding π-orbitals of the aryl
substrate prior to halogen bond cleavage.4 For an aryl bromide
substrate initial π-complexation drives preferential bond
activation even in the presence of a more reactive aryl iodide
substrate.5 This selectivity suggests that the Ni(0) species does
not dissociate from the π-complex and must move along the
conjugated framework (ring-walk) toward the active carbon−
halogen site. Recently, small molecule competition reactions by
the McNeil group have shown that intramolecular oxidative
addition occurs.6
The nickel-mediated cross-coupling reaction is often used in
the synthesis of near monodisperse, conjugated polymers.7 The
π-complexation of zerovalent nickel with aromatic substrates
plays a critical role in polymerization control, and weak
association leads to uncontrolled polymerization.8 The Ni(0)
In this report, we perform KIE experiments on various
haloarene derivatives to elucidate the OA mechanism. Aryl
halides are coupled with alkyl or aryl magnesium halides using
Received: October 10, 2013
© XXXX American Chemical Society
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Figure 1. Computed reaction profile for intramolecular oxidative addition of Ni(dppp) with o-bromotoluene (solid red) and o-chlorotoluene
(dashed blue). Energies relative to THF-Ni(dppp) + free substrate are listed for each step. Experimental KIEs are given using the shorthand notation
defined in the text with an asterisk denoting the internal standard.
dppp-ligated nickel catalysts. Several thiophene derivatives are
also investigated to understand Ni(0) interactions with
aromatic rings containing a heteroatom. Additionally, reaction
pathways were computed using B3LYP-D3/TZ2P-LANL2TZ-
(f)-LANL08d density functional theory. Initial π-complexation
thermodynamically stabilizes the benzene and thiophene
derivatives by up to 17 and 33 kcal mol−1, respectively, relative
to the solvated catalyst and free substrate, and all cross-
couplings are exothermic with low barriers to OA. Theoretical
KIEs for Ni(0) insertion were calculated using simple transition
state theory12 and found to differ from the observed KIEs,
providing further evidence that the initial step for all studied
substrates is not direct oxidative addition.
Scheme 1. Ring-Walking and Forward Nickel Insertion of
Ni(dppp) with o-Bromotoluene
a
To examine substrate influence on the OA reaction, KIEs
were measured for a set of haloarenes varying in halogen type
(benzene derivatives), added electron-withdrawing groups, and
substituent position (thiophene derivatives). Increased KIEs
only in the immediate vicinity of the halogenated carbon would
indicate that Ni(0) insertion is the first irreversible step and
that π-complexation is reversible. Conversely, increased ratios
distributed over the aryl ring would imply mechanistic
involvement of carbons away from the OA reaction site,
suggesting that π-complexation is the FIS, and once the catalyst
coordinates to the substrate then intramolecular OA occurs
without dissociation of Ni(0). Our measured KIE values are
reported in the figures below in a succinct notation. Differences
are given with respect to the methyl internal standard, set at
1.000, and are reported as multiples of 0.001. For example, a
KIE of +8 corresponds to 1.008 in the standard notation.
The stability of π-complexation varying by halogen type was
first investigated for substituted o-halotoluenes (Figure 1). The
experimental 13C KIE values for the brominated substrate are
(+5, +4, +6, +6, +8, +2), while the corresponding KIEs for the
chlorinated substrate are (+17, +13, +2, +6, +17, +10). The
enlargement in positions away from the site of oxidative
addition indicates that π-complexation is the FIS. Intra-
molecular OA is expected for both species. This matches
literature reports confirming chain-growth character in the
KTC polymerization.14
a
Initial binding can occur at any position (CPx).
THF solvent.15 The THF is replaced by the aryl halide
substrate at the start of the reaction sequence. This process
cannot be described as a single step through a well-defined
transition state on the potential energy surface. While
theoretical investigation of complicated exchange mechanisms
among Ni(0) π-complexes is beyond the scope of this report,
the associated thermodynamic effects are accounted for by
computing relative energies based on the reaction THF-
Ni(dppp) + substrate → substrate-Ni(dppp) + THF.
Modeling the full OA reaction of Ni(dppp) with o-
bromotoluene reveals that Ni(0) favorably complexes in an
η2 fashion with neighboring sp2 carbons followed by ring-
walking and nickel insertion, as shown in Scheme 1. In the KIE
experiments, a free Ni(0) would initially be complexed to the
Figure 1 displays the computed reaction profile for
intramolecular OA of Ni(dppp) with the brominated (solid
red trace) and chlorinated (dashed blue trace) derivatives.
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Initial π-complexation with the substrate provides 14−17 kcal
mol−1 of thermodynamic stabilization depending on the
binding position. All ring-walking steps have low energetic
barriers of 3−7 kcal mol−1. Ni(dppp) can migrate around the
ring to the active site in either a forward direction away from
the methyl substituent or in a reverse direction passing over the
methyl moiety. OA occurs via a three-coordinate transition
state (TSOA) involving either C1−C6 or C1−C2 for forward
and reverse ring-walking, respectively.
halotoluene derivatives, the unsubstituted site C4 is favored by
6.2 kcal mol−1. While the barriers to ring-walking out of the
deepest CP4 and CP1 minima are 7−12 kcal mol−1, the others
are only 2−5 kcal mol−1. The barrier nickel insertion from the
unhindered side is only slightly higher barrier to nickel
insertion at 6.8 kcal mol−1. No transition state was located
for nickel insertion from the hindered side.
The experimental KIEs (+7, +10, +14, +10, +0, +6) for 1-
bromo-2,5-dimethoxybenzene are elevated around the ring. In
contrast, the theoretical KIEs for nickel insertion (+3, +2, +1,
−1, +0, +0) exhibit noticeably increased values only at the two
carbons involved in the three-coordinate OA transition state
(C1 and C2). The theoretical KIEs for nickel insertion do not
reflect trends in the experimental KIEs, implying π-complex-
ation is the apparent FIS.
Thiophene compounds were investigated to study heter-
oatom effects on the OA mechanism, which are of relevance in
small molecule cross-couplings and conjugated polymers.7b,18 A
key difference between the toluene and thiophene derivatives is
the mode of ring-walking. Nickel can complex with toluene
derivatives at any adjacent pair of aryl carbons, but thiophene π-
complexation only occurs at the C2−C3 and C4−C5 positions,
as outlined in Scheme 2. No stationary points were found on
the potential energy surface for Ni(dppp) complexed with the
sulfur atom of thiophene.
The main difference between the bromo- and chlorotoluene
substrates is the nickel insertion barrier, which is somewhat
higher for the chloro derivative. The insertion barriers in the
forward direction are 4.6 and 9.0 kcal mol−1 for the bromo and
chloro derivatives, while those in the reverse direction are 8.0
and 11.2 kcal mol−1. In the forward ring-walking reaction with
the brominated substrate, the barrier for insertion is lower in
energy than that of ring-walking, which suggests extremely
facile intramolecular oxidative addition. The reaction profiles of
Figure 1, especially in the o-chlorotoluene case, suggest fast pre-
equilibrium between the intermediates, allowing application of
the Curtin−Hammett principle16 or the energetic span
model.17 In particular, the apparent activation energy for nickel
insertion in the reverse direction is predicted to be 12.5 kcal
mol−1, the difference between the energy of TSOAr and the
lowest-energy intermediate CP6. The thermodynamic driving
force for OA after π-complexation exceeds 45 kcal mol−1.
The experimental KIEs for the brominated derivative
exhibited sizable enlargement on every aryl carbon, making π-
complexation the apparent FIS. In contrast, for the nickel
insertion step, our theoretical KIEs for C1 through C6 are (+4,
+5, +2, +0, +0, +2) and (+5, +2, +0, +1, +3, +5) for the forward
and reverse directions, respectively. The clear disparity between
these theoretical values and the observed KIEs supports the
conclusion that nickel insertion is not the FIS. For the
chlorinated substrate, our theoretical KIEs for nickel insertion
in the forward and reverse direction are (+6, +5, +1, −1, +0,
+2) and (+8, +1, −1, −1, +2, +4). Again, substantial
enlargement is only present on the active carbon and its
neighbors, which does not match experiment, indicating nickel
insertion is not the FIS.
Scheme 2. Intramolecular Oxidative Addition of Ni(dppp)
with 2-Bromo-3-methylthiophene
The addition of methoxy substituents alters the relative
energies of the various π-complexes (Figure 2). Instead of all
binding positions being of comparable energy, as for the
Figure 3 shows the computed reaction profiles and
experimental KIEs for bromothiophene derivatives. The
substrate 2-bromo-3-methylthiophene has increased KIEs at
C4 and C5 of +22 and +12. The lack of an increased KIE at C3
and the much smaller increase at C2 indicate that nickel
insertion is not the FIS. When the methyl substituent is in the
5-position, experimental KIEs are spread throughout the ring at
(+17, +4, +6, +16). The theoretical KIEs for nickel insertion
are (+4, +5, +3, +0) for 2-bromo-3-methylthiophene and (+3,
+6, +4, +1) for 2-bromo-5-methylthiophene. This disparity
suggests π-complexation is the FIS.
In the 3-methyl and 5-methyl thiophene derivatives, the
barriers to forward ring-walking are 14.5 and 13.5 kcal mol−1,
respectively, much larger than found in the halogenated toluene
derivatives. The corresponding barriers to nickel insertion in
Figure 2. Computed reaction profile for intramolecular oxidative
addition of Ni(dppp) with 1-bromo-2,5-dimethoxybenzene. The
energies listed for each step are relative to THF-Ni(dppp) + free
substrate. Experimental KIEs are inset.
C
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calculated through the standard 13C formula (see Supporting
Information for more details).13
1-Bromo-2-methylbenzene. 1-Bromohexane (96 mmol, 15.83 g)
was added dropwise to refluxing magnesium metal (96.8 mmol, 2.35
g) in 80 mL of diethyl ether, stirred for 1 h, and then added dropwise
to a mixture of o-bromotoluene (80 mmol, 13.68 g) and 2 mol %
Ni(dppp)Cl2 (1.6 mmol) at 0 °C. The reaction was stirred for 24 h at
room temperature, then quenched with 1 M HCl, washed with water
(3×) and brine (3×), and dried over MgSO4. Distillation yielded 3.39
g (83% conversion) of starting material, 0.90 g of toluene, and 7.25 g
1
of the coupled product. (Af,Pf) = (3.39 g, 83%); H (CDCl3, 300
MHz) δ (ppm): 7.43−7.49 (m, 1H), 7.14−7.16 (m, 1H), 7.08−7.12
(m, 1H), 6.92−6.95 (m, 1H), 2.38 (s, 3H); 13C{1H} (CDCl3, 600
MHz) δ (ppm): 23.1, 125.2, 127.5, 127.6, 131.0, 132.5, 137.9.
1-Chloro-2-methylbenzene. 1-Bromohexane (144 mmol, 23.75
g) was added dropwise to refluxing magnesium metal (145 mmol, 3.53
g) in 100 mL of diethyl ether, stirred for 1 h, then added dropwise to a
mixture of o-chlorotoluene (120 mmol, 15.19 g) and 2 mol %
Ni(dppp)Cl2 (2.4 mmol) at 0 °C, and stirred for 24 h at room
temperature. The reaction was quenched with 1 M HCl, washed with
water (3×) and brine (3×), and dried over MgSO4. Distillation yielded
1.52 g (90% conversion) of starting material and 16.40 g of coupled
Figure 3. Computed reaction profiles and experimental KIEs for 2-
bromo-3-methylthiophene (solid blue trace) and 2-bromo-5-methyl-
thiophene (dashed red trace). Energies are listed for each step relative
to THF−Ni(dppp) + free substrate.
the forward direction are 9.8 and 8.0 kcal mol−1, comparable to
the bromotoluene values.
1
product. (Af,Pf) = (1.52 g, 90%); H NMR (CDCl3, 300 MHz) δ
(ppm): 7.24−7.27 (m, 1H), 7.11−7.14 (m, 1H), 7.05−7.08 (m, 1H),
7.00−7.04 (m, 1H), 2.36 (s, 3H); 13C{1H} (CDCl3, 500 MHz) δ
(ppm): 20.4, 127.0, 127.6, 129.5, 131.4, 134.8, 136.4.
In summary, Kumada coupling reactions were carried out
here on a collection of halogenated arene derivatives.
Experimental and computational methods were combined to
elucidate the reactions of zerovalent nickel with aromatic
substrates. Kinetic isotope effects (KIEs) were obtained from
13C NMR integrations of starting material before and after
cross-coupling. Inverse-gated decoupling allowed for accurate
peak integration, and the relaxation agent Cr(acac)3 signifi-
cantly decreased the NMR acquisition time. Our joint
experimental and theoretical analysis indicates that the first
irreversible step (FIS) in the oxidative addition of Ni(0) with
haloarenes is π-complexation, followed by intramolecular nickel
insertion. The observed characteristics of π-complexation are of
mechanistic importance in the Kumada catalyst-transfer
polymerization of these substrates, as dissociation of the
Ni(0) catalyst between the reductive elimination and
subsequent oxidative addition step results in a loss of chain-
growth behavior. Initial π-complexation is a contributing factor
to obtaining a chain-growth polymerization with low dispersity
and controlled end groups.
1-Bromo-2,5-dimethoxybenzene. 1-Bromohexane (120 mmol,
19.80 g) was added dropwise to refluxing magnesium metal (121
mmol, 2.94 g) in 100 mL of diethyl ether, stirred for 1 h, then added
dropwise to a mixture of 2-bromo-1,4-dimethoxybenzene (100 mol,
21.705 g) and 2 mol % Ni(dppp)Cl2 (2 mmol) at 0 °C, and stirred for
24 h at room temperature. The reaction was quenched with 1 M HCl,
washed with water (3×) and brine (3×), and dried over MgSO4.
Distillation yielded 1.70 g (92% conversion) of starting material, 1.05 g
of dimethoxybenzene, and 13.85 g of coupled product. (Af,Pf) = (1.70
g, 92%); 1H NMR (CDCl3, 400 MHz) δ (ppm): 7.10 (s, 1H), 6.79 (s,
2H), 3.80 (s, 3H) 3.72 (s, 3H); 13C{1H} (CDCl3, 600 MHz) δ (ppm):
55.8, 56.8, 111.8, 112.8, 113.4, 119.0, 150.1, 153.9.
2-Bromo-3-methylthiophene. NBS (17.798 g, 100 mmol) was
added to 3-methylthiophene (9.818g, 100 mmol) in 100 mL of THF
at 0 °C and stirred overnight. The product was purified through an
alumina plug with hexanes to yield 13.2 g of 2-bromo-3-methylthio-
phene (75%). Isopropylmagnesium chloride (92.8 mmol, 46.4 mL)
was added dropwise to a solution of 2-bromothiophene (92.8 mmol,
15.12 g) in 100 mL of THF at 0 °C. After complete conversion, the 2-
thienylmagnesium chloride was added dropwise to a solution of 2-
bromo-3-methylthiophene (92.8 mmol, 16.44 g) and 3 mol %
Ni(dppp)Cl2 (2.8 mmol) in 100 mL of THF at 0 °C and stirred
overnight. The reaction was quenched with 1 M HCl, and the solvent
was removed. The crude mixture was dissolved in hexanes, washed
with water (3×), and dried over MgSO4. Distillation yielded 125 mg
(98% conversion) of starting material and 12.93 g of coupled product
EXPERIMENTAL SECTION
■
Experimental Methods. ortho-Toluene substrates were used in
order to aid in cross-coupling reactions.19 The exchange reagent
(RMgCl) for each reaction was selected to allow facile separation of
starting material from products and minimize magnesium halogen
exchange. The use of n-hexyl magnesium chloride as the Grignard
reagent ensured the coupled product acquired a significantly higher
boiling point than the starting material, allowing ease of separation via
distillation. Furthermore, it is well documented that thienyl halides
participate in magnesium halogen exchange processes,20 which give
rise to a number of different products and influences KIE values. To
minimize this complication, thienyl halide substrates were reacted with
thiophen-2-yl magnesium chloride instead of n-hexyl magnesium
chloride.
1
(55 °C, 200 mtorr). (Af,Pf) = (125 mg, 98%); H NMR (CDCl3, 300
MHz) δ (ppm): 7.28−7.32 (dd, 1H), 7.13−7.16 (m, 2H), 7.05−7.09
(t, 1H), 6.86−6.92 (d, 1H), 2.40 (s, 3H); 13C{1H}(CDCl3, 500 MHz)
δ (ppm): 15.6, 109.8, 125.6, 129.7, 137.4.
2-Bromo-5-methylthiophene. Thiophene (200 mmol) and 200
mL of THF were cooled to −78 °C followed by dropwise addition of
n-BuLi (200 mmol, 125 mL). MeI (240 mmol, 34.05 g) was added
dropwise and stirred overnight. The crude material was flashed
through an alumina plug with hexanes to yield 9.76 g of 2-
methylthiophene (51%). The product (183.1 mmol, 17.98 g) was
dissolved in 200 mL of DMF with NBS (183.1 mmol, 32.58 g) and
stirred for 24 h. The crude product was distilled to yield 31 g of 2-
bromo-5-methylthiophene (97%). Isopropylmagnesium chloride (175
mmol, 87.93 mL) was added dropwise to 2-bromothiophene (175
mmol, 28.53 g) in 100 mL of THF at 0 °C and stirred for 2 h. This
solution was added dropwise to 2-bromo-5-methylthiophene (175
mmol, 30.98 g) and 3 mol % Ni(dppp)Cl2 (5.25 mmol) in 140 mL of
THF at 0 °C and stirred for 48 h. The reaction was quenched with
The determination of KIEs by NMR requires integration of the 13C
spectra for the substrate before reaction and for recovered starting
material after reaction. Cr(acac)3 was used as a relaxation agent to
lower the half-life (T1) of nuclear relaxation, which significantly
decreased the time necessary to acquire spectra with a signal-to-noise
of 1000:1.21 The pulse width was set to 90°, followed by a relaxation
delay of at least five T1. Nuclear Overhauser effects were suppressed
using the inverse gated decoupling technique. The integral values of
the peaks before and after reaction were compared, and the KIEs were
D
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dilute HCl, and the solvent was removed. The crude mixture was
dissolved in hexane, washed with water (3×) and brine (3×), and
dried over MgSO4. Distillation yielded 6.4 g (80% conversion) of
coupled product along with 2,2′-dimethyl-2,2′-bithiophene, bithio-
phene, and starting material. (Af,Pf) = (6.40 g, 80%); 1H NMR
(CDCl3, 300 MHz) δ (ppm): 7.06−7.10 (dd, 1H), 6.88−6.91 (t, 1H),
6.74−6.78 (dd, 1H), 2.51 (s, 3H). 13C{1H} (CDCl3, 500 MHz) δ
(ppm): 15.9, 109.1, 126.1, 130.1, 141.7.
S.; Lindhardt, A. T.; Norrby, P.-O.; Skrydstrup, T. J. Am. Chem. Soc.
2011, 134, 443. (d) McMullin, C. L.; Jover, J.; Harvey, J. N.; Fey, N.
Dalton Trans. 2010, 39, 10833.
(4) Massera, C.; Frenking, G. Organometallics 2003, 22, 2758.
(5) Zenkina, O. V.; Karton, A.; Freeman, D.; Shimon, L. J. W.;
Martin, J. M. L.; van der Boom, M. E. Inorg. Chem. 2008, 47, 5114.
(6) Bryan, Z. J.; McNeil, A. J. Chem. Sci. 2013, 4, 1620.
(7) (a) Sheina, E. E.; Liu, J.; Iovu, M. C.; Laird, D. W.; McCullough,
R. D. Macromolecules 2004, 37, 3526. (b) Miyakoshi, R.; Yokoyama,
A.; Yokozawa, T. J. Am. Chem. Soc. 2005, 127, 17542.
(8) Bridges, C. R.; McCormick, T. M.; Gibson, G. L.; Hollinger, J.;
Seferos, D. S. J. Am. Chem. Soc. 2013, 135, 13212.
(9) Bryan, Z. J.; McNeil, A. J. Macromolecules 2013, 46, 8395.
(10) (a) Zenkina, O. V.; Karton, A.; Freeman, D.; Shimon, L. J. W.;
Martin, J. M. L.; van der Boom, M. E. Inorg. Chem. 2008, 47, 5114.
(b) Lanni, E. L.; Locke, J. R.; Gleave, C. M.; McNeil, A. J.
Macromolecules 2011, 44, 5136.
Computational Methods. Modeling the intramolecular OA of a
zerovalent nickel with haloarene substrates was done with density
functional theory (DFT) using the B3LYP functional,22 which yields
accurate molecular geometries for transition-metal complexes.23 All
geometry optimizations and frequency computations used the 6-31G*
basis set for H, C, O, P, and S24,25 and the LANL2DZ basis set and
effective core potential (ECP) for halogens and nickel.26 Final
energetics were computed with the B3LYP-D3 functional, which
appends the Grimme dispersion correction27 to B3LYP, along with a
TZ2P basis set28 contracted as (5s2p/3s2p) for H, (10s6p2d/5s3p2d)
for C and O, and (14s10p2d/7s5p2d) for P and S, as well as the
LANL2TZ(f) basis set and ECP for nickel and the LANL08d basis set
and ECP for halogens.29 This scheme is denoted as B3LYP-D3/TZ2P-
LANL2TZ(f)-LANL08d. Electronic energies were corrected for zero-
point vibrations. All computations employed a radial, angular (75, 302)
grid with the QChem 4.0 package.30 To validate our method, rigorous
coupled-cluster computations were done for the complexation of
Ni(dhpe) + ethene (Table S7). CCSD/TZ2P-LANL2TZ(f) gives a
binding energy of 45.6 kcal mol−1, similar to the 43.4 kcal mol−1 found
by B3LYP-D3/TZ2P-LANL2TZ(f). Transition state theory (TST)
was used to determine theoretical KIEs for nickel insertion.12
Theoretical KIEs were benchmarked against experimental KIEs for
the Diels−Alder reaction of s-trans-isoprene and maleic anhydride.31
(11) Vo, L. K.; Singleton, D. A. Org. Lett. 2004, 6, 2469.
(12) Smith, I. W. M. Kinetics and dynamics of elementary gas reactions;
Butterworth & Co. Publishers Ltd.: Wobrun, MA, 1980.
(13) Singleton, D. A.; Thomas, A. A. J. Am. Chem. Soc. 1995, 117,
9357.
(14) Marshall, N.; Sontag, S. K.; Locklin, J. Macromolecules 2010, 43,
2137.
(15) Helm, L.; Merbach, A. E. Chem. Rev. 2005, 105, 1923.
(16) Seeman, J. I. Chem. Rev. 1983, 83, 83.
(17) Kozuch, S.; Shaik, S. Acc. Chem. Res. 2010, 44, 101.
(18) (a) Vechorkin, O.; Proust, V.; Hu, X. J. Am. Chem. Soc. 2009,
131, 9756. (b) Beryozkina, T.; Senkovskyy, V.; Kaul, E.; Kiriy, A.
Macromolecules 2008, 41, 7817.
(19) (a) Tkachov, R.; Senkovskyy, V.; Komber, H.; Kiriy, A.
Macromolecules 2011, 44, 2006. (b) Doubina, N.; Paniagua, S. A.;
Soldatova, A. V.; Jen, A. K. Y.; Marder, S. R.; Luscombe, C. K.
Macromolecules 2011, 44, 512.
(20) (a) Shi, L.; Chu, Y.; Knochel, P.; Mayr, H. Org. Lett. 2009, 11,
3502. (b) Shi, L.; Chu, Y.; Knochel, P.; Mayr, H. J. Org. Chem. 2009,
74, 2760. (c) Shi, L.; Chu, Y.; Knochel, P.; Mayr, H. Org. Lett. 2012,
14, 2602.
(21) (a) Alger, T. D.; Solum, M.; Grant, D. M.; Silcox, G. D.;
Pugmire, R. J. Anal. Chem. 1981, 53, 2299. (b) Luukko, P.; Alvila, L.;
Holopainen, T.; Rainio, J.; Pakkanen, T. T. J. Appl. Polym. Sci. 1998,
69, 1805.
(22) (a) Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B 1988, 37, 785.
(b) Becke, A. D. J. Chem. Phys. 1993, 98, 5648.
(23) (a) Niu, S.; Hall, M. B. Chem. Rev. 2000, 100, 353. (b) Xu, Z.-F.;
Xie, Y.; Feng, W.-L.; Schaefer, H. F. J. Phys. Chem. A 2003, 107, 2716.
(24) Dill, J. D.; Pople, J. A. J. Chem. Phys. 1975, 62, 2921.
(25) Francl, M. M.; Pietro, W. J.; Hehre, W. J.; Binkley, J. S.; Gordon,
M. S.; DeFrees, D. J.; Pople, J. A. J. Chem. Phys. 1982, 77, 3654.
(26) Hay, P. J.; Wadt, W. R. J. Chem. Phys. 1985, 82, 299.
(27) Grimme, S.; Antony, J.; Ehrlich, S.; Krieg, H. J. Chem. Phys.
2010, 132, 154104.
(28) Gonzales, J. M.; Cox, R. S.; Brown, S. T.; Allen, W. D.; Schaefer,
H. F. J. Phys. Chem. A 2001, 105, 11327.
(29) Roy, L. E.; Hay, P. J.; Martin, R. L. J. Chem. Theory Comput.
2008, 4, 1029.
(30) Shao, Y.; Fusti-Molnar, L.; Jung, Y.; Kussmann, J.; Ochsenfeld,
C.; Brown, S. T.; Gilbert, A. T. B.; Slipchenko, L. V.; Levchenko, S. V.;
O’Neill, D. P.; Distasio, R. A., Jr.; Lochan, R. C.; Wang, T.; Beran, G. J.
O.; Besley, N. A.; Herbert, J. M.; Yeh Lin, C.; Van Voorhis, T.; Hung
Chien, S.; Sodt, A.; Steele, R. P.; Rassolov, V. A.; Maslen, P. E.;
Korambath, P. P.; Adamson, R. D.; Austin, B.; Baker, J.; Byrd, E. F. C.;
Dachsel, H.; Doerksen, R. J.; Dreuw, A.; Dunietz, B. D.; Dutoi, A. D.;
Furlani, T. R.; Gwaltney, S. R.; Heyden, A.; Hirata, S.; Hsu, C.-P.;
Kedziora, G.; Khalliulin, R. Z.; Klunzinger, P.; Lee, A. M.; Lee, M. S.;
Liang, W.; Lotan, I.; Nair, N.; Peters, B.; Proynov, E. I.; Pieniazek, P.
A.; Min Rhee, Y.; Ritchie, J.; Rosta, E.; David Sherrill, C.; Simmonett,
A. C.; Subotnik, J. E.; Lee Woodcock, H., III; Zhang, W.; Bell, A. T.;
Chakraborty, A. K.; Chipman, D. M.; Keil, F. J.; Warshel, A.; Hehre,
ASSOCIATED CONTENT
* Supporting Information
■
S
KIE determination, 13C NMR spectra, benchmark of theoretical
KIE calculations, benchmark of DFT energetics, total electronic
energies, and optimized Cartesian coordinates of all stationary
points. This material is available free of charge via the Internet
at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Authors
*E-mail: wdallen@uga.edu (W.D.A.).
*E-mail: jlocklin@uga.edu (J.L).
■
Author Contributions
∥These authors contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
This work was supported by the National Science Foundation
(CHE 1058631 and DMR 0953112).
■
REFERENCES
■
(1) (a) Tamao, K.; Sumitani, K.; Kumada, M. J. Am. Chem. Soc. 1972,
94, 4374. (b) Jana, R.; Pathak, T. P.; Sigman, M. S. Chem. Rev. 2011,
111, 1417. (c) Corriu, R. J. P.; Masse, J. P. J. Chem. Soc., Chem.
Commun. 1972, 144. (d) Yamamoto, T.; Wakabayashi, S.; Osakada, K.
J. Organomet. Chem. 1992, 428, 223.
(2) (a) Churchill, D. G.; Janak, K. E.; Wittenberg, J. S.; Parkin, G. J.
Am. Chem. Soc. 2003, 125, 1403. (b) Jones, W. D. Acc. Chem. Res.
2002, 36, 140. (c) Gom
111, 4857.
́
ez-Gallego, M.; Sierra, M. A. Chem. Rev. 2011,
(3) (a) Yoshikai, N.; Matsuda, H.; Nakamura, E. J. Am. Chem. Soc.
2008, 130, 15258. (b) Li, Z.; Jiang, Y.-Y.; Fu, Y. Chem.Eur. J. 2012,
18, 4345. (c) Gøgsig, T. M.; Kleimark, J.; Nilsson Lill, S. O.; Korsager,
E
dx.doi.org/10.1021/jo402259z | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
W. J.; Schaefer, H. F., III; Kong, J.; Krylov, A. I.; Gill, P. M. W.; Head-
Gordon, M. Phys. Chem. Chem. Phys. 2006, 8, 3172.
(31) Beno, B. R.; Houk, K. N.; Singleton, D. A. J. Am. Chem. Soc.
1996, 118, 9984.
F
dx.doi.org/10.1021/jo402259z | J. Org. Chem. XXXX, XXX, XXX−XXX