Synthesis, structural characterization, and coordination chemistry of (Trineopentylphosphine)palladium(aryl)bromide dimer complexes ([(Np3P)Pd(Ar)Br]2)

Article abstract of DOI:10.1021/acs.inorgchem.9b02164

A series of [(PNp₃)Pd(Ar)Br]₂ complexes (PNp₃ = trineopentylphosphine, Ar = 4-tolyl, 4-tert-butylphenyl, 2-tolyl, 4-methoxy-2-methylphenyl, 2-isopropylphenyl, and 2,6-dimethylphenyl) were synthesized and structurally characterized by X-ray crystallography and density functional theory optimized structures. The trineopentylphosphine ligand is able to accommodate coordination of other sterically demanding ligands through changes in its conformation. These conformational changes can be seen in changes in percent buried volume of the PNp₃ ligand. The binding equilibria of the [(PNp₃)Pd(Ar)Br]₂ complexes with pyridine derivatives were determined experimentally and analyzed computationally. The binding equilibria are sensitive to the steric demand of the pyridine ligand and less sensitive to the steric demand of the aryl ligand on palladium. In contrast to previous studies, the binding equilibria do not correlate with pyridine basicity. The binding equilibria results are relevant to fundamental ligand coordination steps in cross-coupling reactions, such as Buchwald-Hartwig aminations.

Full text of DOI:10.1021/acs.inorgchem.9b02164

Article
pubs.acs.org/IC
Cite This: Inorg. Chem. XXXX, XXX, XXX−XXX
Synthesis, Structural Characterization, and Coordination Chemistry
of (Trineopentylphosphine)palladium(aryl)bromide Dimer
Complexes ([(Np3P)Pd(Ar)Br]2)
Huaiyuan Hu, Monica Vasiliu, Trent H. Stein, Fengrui Qu, Deidra L. Gerlach, David A. Dixon,*
and Kevin H. Shaughnessy*
Department of Chemistry and Biochemistry, The University of Alabama, Box 870336, Tuscaloosa, Alabama 35487-0336, United
States
S
* Supporting Information
ABSTRACT: A series of [(PNp3)Pd(Ar)Br]2 complexes (PNp3
=
trineopentylphosphine, Ar = 4-tolyl, 4-tert-butylphenyl, 2-tolyl, 4-methoxy-2-
methylphenyl, 2-isopropylphenyl, and 2,6-dimethylphenyl) were synthesized
and structurally characterized by X-ray crystallography and density functional
theory optimized structures. The trineopentylphosphine ligand is able to
accommodate coordination of other sterically demanding ligands through
changes in its conformation. These conformational changes can be seen in
changes in percent buried volume of the PNp3 ligand. The binding equilibria
of the [(PNp3)Pd(Ar)Br]2 complexes with pyridine derivatives were
determined experimentally and analyzed computationally. The binding
equilibria are sensitive to the steric demand of the pyridine ligand and less
sensitive to the steric demand of the aryl ligand on palladium. In contrast to
previous studies, the binding equilibria do not correlate with pyridine basicity.
The binding equilibria results are relevant to fundamental ligand coordination steps in cross-coupling reactions, such as
Buchwald−Hartwig aminations.
disubstituted aryl bromides.5 Whereas simple palladium/
INTRODUCTION
■
phosphine precatalysts are often ineffective for coupling of
hindered aryl halides and amines, NHC-palladium precata-
lysts,6 phosphatrane/palladium complexes,7 and diketiminate
complexes8 are effective for sterically demanding substrates.
Our group has explored neopentylphosphines in palladium-
catalyzed cross-coupling reactions. Catalysts derived from
di(tert-butyl)neopentylphosphines ((t-Bu)2PNp) are effective
for cross-coupling of aryl bromides and chlorides with a variety
of nucleophilic coupling partners.9 The (t-Bu)2PNp ligand has
limited flexibility, and catalysts derived from it generally give
low conversion with sterically demanding substrates. In
contrast, trineopentylphosphine (PNp3) is able to tolerate
sterically demanding substrates to afford high yields in
couplings with amines, arylboronic acids, and ketones.9d,10
We have hypothesized that the conformational flexibility of
PNp3 shown in solid state structures allows it to accommodate
sterically demanding substrates. A kinetic study of the oxidative
addition of aryl bromides to Pd(PNp3)2 showed that the
reaction rate is unaffected by the steric effects of the aryl
bromide.11
Oxidative addition of aryl halides to palladium(0) to afford
LnPd(Ar)X complexes is a fundamental step in all palladium-
catalyzed cross-coupling reactions. With less reactive sub-
strates, such as aryl chlorides and sulfonates, this step is often
rate limiting. Significant effort has been devoted to the
development of ligands affording highly active catalysts capable
of promoting cross-coupling of challenging substrates. Steri-
cally demanding, electron-rich ligands, such as dialkylbiar-
ylphosphines,1 trialkylphosphines,2 bis(dialkylphosphine) li-
gands,3 and N-heterocyclic carbenes,4 are particularly useful in
promoting these reactions. The strong electron-donating
ability of these ligands promotes the oxidative addition step.
Sterically demanding ligands promote transient low-coordinate
LPd(0) species that are highly reactive toward oxidative
addition. In addition, sterically demanding ligands can promote
reductive elimination in cases where that is the rate limiting
step.
Commonly used sterically demanding, electron-rich ligands,
such as P(t-Bu)3, Buchwald-type ligands (S-Phos, RuPhos, X-
Phos), and NHCs (IPr, IMes), have relatively rigid structures
with fixed steric demand. Sterically demanding ligands can
limit the ability of complexes to couple sterically demanding
substrates. For example, commonly used catalyst systems based
on tri-tert-butylphosphine (P(t-Bu)3) or S-phos give low yields
in the coupling of 2,6-disubstituted anilines and 2,6-
To gain a better understanding of the ability of PNp3 to
facilitate coupling of sterically demanding substrates, we sought
Received: July 19, 2019
© XXXX American Chemical Society
A
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to prepare and characterize a series of [(PNp3)Pd(Ar)Br]2
complexes where the aryl group would have zero, one, or two
ortho substituents. Examples of isolated and structurally
characterized palladium complexes with 2,6-disubstituted aryl
substituents are rare in the literature.12 Successful isolation of
products of oxidative addition of 2,6-disubstituted aryl halides
to triphenylphosphine13 and tri(ortho-tolyl)phosphine14 palla-
dium complexes have been reported, but no examples had
been structurally characterized prior to our work in this area.
We have previously reported the synthesis of 2-tolyl and 2,6-
dimethylphenyl palladium complexes with PNp3 as the
supporting ligand.10,11 Herein, we report additional examples
of [(Np3P)Pd(Ar)Br]2 complexes and provide a more detailed
structural and computational analysis of these complexes. We
also report an experimental and computational study of the
dimer cleavage reaction of [(PNp3)Pd(Ar)Br]2 with pyridine
derivatives having varied steric demand to afford (PNp3)Pd-
(Ar)(pyridine)Br complexes as well as synthesis of (PNp3)-
Pd(Ar)amine complexes relevant to Buchwald−Hartwig
amination reactions.
Figure 1. Thermal ellipsoid plot (50% probability) of the planar
molecular structure of 3a. Hydrogen atoms and disorder are omitted
for clarity.
RESULTS AND DISCUSSION
bridged dimer structure with inversion symmetry relating the
two (PNp3)Pd(4-C6H4Me)Br units similar to that seen in
complexes 3b−3f. The other molecule (Figure S20, Support-
ing Information) in the asymmetric unit has a butterfly
geometry in which the angle between the two palladium square
planes is 148.1°. Palladium dimer 3e crystallized as a
symmetric planar halide-bridged dimer with similar structural
features to the previously reported 3b, 3c, and 3f (Figure 2).
■
Synthesis of Aryl Palladium Dimers and Solid State
Geometry. Halide bridged aryl palladium complexes of the
formula [(PNp3)Pd(Ar)Br]2 (Ar = 4-tolyl (3a), 4-tert-
butylphenyl (3b), 2-tolyl (3c), 4-methoxy-2-methylphenyl
(3d), and 2-isopropylphenyl (3e)) were synthesized from the
oxidative addition of the corresponding aryl bromide (2a−2e)
to Pd(PNp3)2 (1) in toluene at 70 °C (eq 1). Complex 3f
cannot be prepared by oxidative addition to 1 and was
prepared by the reaction of (COD)Pd(CH2TMS)2 with 2f and
PNp3.11 The syntheses of 3b,10 3c,10 and 3f11 have been
previously reported by us. Newly reported complexes 3a, 3d,
and 3e were obtained in 65−80% isolated yield as air-stable
solids. In solution, the complexes exist as equilibrium mixtures
of stereoisomers. For example, complex 3a gives two
resonances in the 31P NMR spectrum in a 7.7:1 ratio in
C6D6 due to trans and cis dimeric structures. Complexes 3d
and 3e give four resonances due to trans and cis dimeric
structures and anti and syn relationships between the ortho
substituents.10 Crystal structures of complexes 3b (Supporting
Figure 2. Thermal ellipsoid plot (50% probability) of the molecular
structure of 3e. Hydrogen atoms are omitted for clarity.
Structural Comparison of Solid State Structures of
[(PNp3)Pd(Ar)Br]2. Comparison of the palladium−ligand
bond lengths shows how increasing steric demand of the aryl
ligand affects bonding to the palladium center (Table 1). The
Pd−C bond lengths for structures 3a−3f show no statistically
significant difference as ortho substituents are added. The
increased steric demand of the aryl ligand does have a small
but statistically significant effect on the Pd−P bond distance,
however. The Pd−P bond distances are 2.248(1) and 2.245(1)
Å for 3a and 3b, respectively, whereas the ortho-substituted
compounds (3c, 3e, and 3f) have longer Pd−P bond lengths
Information, Figure S24),10 3c (Figure S25),10 and 3f (Figure
S26)11 have been previously reported by us. X-ray quality
crystals of 3a and 3e were grown by slow evaporation in a
mixture of methylene chloride and heptane at 22 °C. Complex
3a (Figure 1) crystallized with two molecules in the
asymmetric unit. One molecule (Figure 1) has a planar halide
B
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(2.266(3)−2.282(2) Å). The Pd−Br bonds were similar for all
of the complexes. The Pd−Br1 bond is longer than Pd−Br2 for
each of the complexes due to the stronger trans effect of the
aryl substituent compared to the phosphine. Comparison of
the PNp3 complexes with [(Et3P)Pd(4-tolyl)Cl]2 (4) shows a
similar trend. The Pd−C bond for 4 is the same as those seen
with complexes 3a−3f. The smaller PEt3 ligand has a shorter
Pd−P bond length (2.219 Å) compared to 3a (2.248 Å),
indicating the increased steric effect of the neopentyl
substituents compared to ethyl.
The bond angles around the palladium center show more
variation as a result of an increased steric demand due to the
aryl ligand (Table 1). For complexes 3a and 3b with para-
substituted aryl ligands, the angles around palladium are all
close to 90° as expected in a square planar geometry. The
values for 3b are similar to that of the PEt3 complex (4). For
the complexes with ortho-substituted aryl ligands, the square
planar geometry is distorted to accommodate the bulky PNp3
and aryl ligands. In each case (3c, 3e, 3f), the Br1−Pd−P angle
is significantly increased (97.5−98.5°). In complexes 3c and
3e, the CAr−Pd−P angle decreases by approximately 2° as does
the Br2−Pd−CAr angle. The 2,6-dimethylphenyl complex (3f)
has a larger CAr−Pd−P angle than 3c or 3e due to increased
steric repulsion, which results in smaller Br2−Pd−CAr and
Br1−Pd−Br2 angles (85.52, 86.68°). The overall effect is that
ortho substituents cause the PNp3 and aryl ligands to move
away from Br1 and toward Br2 in the square plane.
Compared to commonly used sterically demanding
trialkylphosphines, such as tri-(tert-butyl)phosphine, trineo-
pentylphosphine has a higher degree of conformational
flexibility. This flexibility can be seen in the conformation
changes of the PNp3 coordinated to metal centers with
different coordination numbers. In the two-coordinate Pd-
(PNp3)2 complex, the neopentyl groups adopts a C3
symmetrical conformation in which the substituents are
oriented toward the metal center with small Pd−P−C−C
dihedral angles (34°).10 In contrast, when PNp3 is coordinated
to four-coordinate metal centers, as in the case of complexes
3a−3f, the neopentyl groups adopt a conformation in which
one neopentyl group is approximately anti to the Pd−P bond.
The other two neopentyl substituents adopt pseudogauche
conformations relative to the Pd−P bond and are positioned
above and below the Pd2Br2 plane. The trineopentylphosphine
conformation is similar to that seen in [(Et3P)Pd(4-tolyl)Cl]2
(4).15
The conformation of the PNp3 ligand in the [(PNp3)-
PdArBr]2 complexes is affected by the presence of ortho-
substituents on the aryl ligand (Figure 3). When the aryl group
has no ortho substituents (3a and 3b), the PNp3 ligand adopts
a conformation with pseudomirror plane symmetry in which
one neopentyl substituent (C1) is nearly eclipsed with the Pd−
CAr bond (C1−P−Pd−CAr = 4.93 (3a), 6.94 (3b); Table 1)
and has an anti relationship to the Pd−P bond (Pd−P−C1−C
177−180°). The other two neopentyl groups are oriented
above and below the palladium square plane with roughly
gauche relationships to the Pd−P bond (Pd−P−C−C = 50−
56°). The anti-neopentyl substituent (C1) repels the other two
neopentyl substituents, resulting in large C1−P−C2 and C1−
P−C3 angles (107.9−108.8°). As a result, the C2−P−C3 angle
is much smaller (99.2° (3a), 100.6° (3b)). In contrast, the C−
P−C angles of the PEt3 ligand in 4 are all similar (104−105°).
The P−C−C bond angle for all three neopentyl groups are
significantly expanded (122−127°) with the anti-neopentyl
Figure 3. Trineopentyl conformations observed for 3a−3f.
Pseudomirror plane (3a, 3b) and pseudo-C3 (propeller type, 3c, 3e,
and 3f).
group having the largest P−C−C bond angle. These values are
considerable larger than the P−C−C angles for the ethyl
substituents in 4 (112−116°).
When ortho substituents are present on the aryl ligand, the
PNp3 ligand adopts a pseudo-C3 propeller-type geometry
(Figure 3). In the case of 3c with a 2-tolyl ligand, the
phosphine rotates to move the C1 neopentyl substituent
toward the methyl substituent on the 2-tolyl ligand (C1−P−
Pd−CAr = 30.2°). The Pd−P−C1−C dihedral angle decreases
to 152.48°, consistent with the neopentyl group rotating away
from the ortho methyl and toward the face of the arene. The
C2 neopentyl has a larger Pd−P−C2−C dihedral angle (72°)
to accommodate the C1 neopentyl group. The dihedral angle
for the C3 neopentyl group is similar to that in 3a and 3b. The
C1−P−C2 angle (108.4°) for 3c is still larger than the C2−P−
C3 (104.4°) and C3−P−C1 (104.8°) angles, but the
difference is smaller than for 3a and 3b. The P−C1−C angle
is again the largest (129°) in 3c, but the P−C3−C angle is also
expanded (124°) in response to the strain on this substituent.
Complex 3e gives similar structural parameters.
The PNp3 ligand in the 2,6-dimethylphenyl complex (3f)
adopts a similar pseudo-C3 conformation to that seen in the
complexes with mono-ortho-substituted aryl ligands (3c and
3e). The dihedral angle between the aryl ligand and the C1
neopentyl group (14.86°) is smaller than in 3c but larger than
3a or 3b. Like 3c, the C1 neopentyl group in 3f is not
completely anti (Pd−P−C1−C = 163.9°) to the Pd−P bond.
The dihedral angle for the C2 neopentyl substituent (60.9°) is
larger than for the C3 neopentyl group, although not as large as
observed for 3c or 3e. To accommodate the larger aryl ligand,
the P−C1−C3 and P−C2−C3 angles are smaller (101.6°) in
3f than in 3c (104°). As a result, the PNp3 ligand is more
pyramidalized than in the other complexes (ΣC−P−C: 3a =
315.9°, 3b = 317.7°, 3c = 317.6°, 3e, 316.9°, 3f = 311.84°).
The two neopentyl substituents projected toward the
palladium center have larger P−C2−C and P−C3−C angles
than in 3a−3e to accommodate the additional strain.
The most notable evidence of the steric strain experienced
by the PNp3 ligand is the expanded P−C−C bond angles in
the neopentyl substituents, particularly the anti-oriented
neopentyl (P−C1−C). Complex 3f has the largest P−C1−C
value of 128.7°. The bond angles at the neopentyl methylene
carbons are among the largest reported in the literature for a
tetravalent carbon. Examples of molecules with comparable
bond angles at a methylene carbon include di(tert-butyl)-
methane (121−128°)17 and CH2(SF5)2 (126°).18
These conformational changes have a noticeable effect on
the steric demand of the PNp3 ligand as measured by the
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Figure 4. Steric contour maps obtained from the SambVca 2.0 Web Application.16 The metal is at the center of a sphere with a radius of 3.5 Å.
Positive values (yellow-red) reflect substituents projecting into the lower hemisphere past the metal. (a) 3a, (b) 3c, (c) 3f.
percent buried volume (%Vb). The %Vb parameter calculated
using the SambVca 2.0 Web Application16 was determined
from the solid state structures of 3a, 3b, 3c, 3e, and 3f, as well
as previously reported complex 4 (Table 1). In Pd-
(PNp3)2Pd,10 in which the neopentyl substituents all point
toward the metal center, the %Vb is 42.3%. This value
decreases in complexes 3a (36.3%) and 3b (37.4%) as the
PNp3 conformation changes. The addition of ortho-methyl
substituents in 3c (34.7%), 3e (34.3%), and 3f (32.3%) results
in a further decrease in the buried volume as the ligand is
repelled away from the aryl ligands.
reaction and the effect of the steric demand of the aryl ligand
on ligand binding.
Complexes 3a, 3c, 3d, and 3f were reacted with pyridine
(5a), 2-picoline (6b), and 2,6-lutidine (5c) in CD2Cl2 (eq 3).
The decrease in buried volume for the ligands appears to
result from a combination of structural changes. As ortho
substituents are added to the aryl ligand, the sum of the P−
C2−C and P−C3−C angles increases (3a, 245.5°; 3c, 246.5°;
3f, 252.1°). In the case of 3f, there is also a significant increase
in the pyramidalization at phosphorus, although 3c and 3e
have similar ΣC−P−C angles to 3a and 3b. These structural
changes have the effect of moving the −C(CH3)3 group away
from the metal center, particularly for 3f. Steric contour maps
for complexes 3a, 3c, and 3f show that the neopentyl methyl
groups closest to the metal center, for example, C2 and C56 in
3a, move away from the metal center and have a decreased
steric impact as the steric demand of the aryl ligand increases
(Figure 4).
Bromide Bridge Cleavage by Pyridines. Cleavage of the
halide-bridged palladium aryl complexes by nucleophilic
ligands is anticipated to be a key step in cross-coupling
reactions with sterically demanding monodentate ligands. For
example, in the Buchwald−Hartwig amination, the amine
nucleophile cleaves the dimer to give an amine adduct that is
deprotonated, leading to the coupled product.14 The
mechanism of the cleavage of square planar, halide bridged
palladium and platinum complexes with amine19 and alkene20
ligands has been studied. Kinetic studies are consistent with an
associative mechanism with a competitive solvent-mediated
pathway. As expected for an associative process, steric demand
of the incoming ligand decreases the rate of the dimer cleavage
reaction.19c In contrast, binding equilibria are more dependent
on the basicity of the incoming ligand. In the cleavage of
[(Pr3P)PdI2]2 with pyridine derivatives, 2,6-lutidine gave a
higher equilibrium constant (2670) than pyridine (596)
presumably due to the high basicity of lutidine.19b In studying
the mechanism of the Pd/PNp3-catalyzed amination reaction,
we found that aniline gave no observable reaction with
palladium dimers 3b and 3c.11 We therefore sought to use
more strongly coordinating nitrogen ligands to analyze this
Upon the addition of the pyridine derivative, a new peak was
observed by 31P NMR spectroscopy located upfield of the
halide-bridged dimer corresponding to the pyridine adduct
(6). In the majority of cases, incomplete conversion to the
pyridine adduct was observed. For each combination, the
reactions reached equilibrium by the time the samples could be
analyzed (<5 min) and the relative concentrations of 3, 5, and
6 did not change over time. In most cases, a single pyridine
adduct was observed by 31P NMR spectroscopy. When
complex 3a was reacted with 2-picoline, two new resonances
were observed by 31P NMR spectroscopy in a 4:1 ratio. Both
peaks were in the region where the other pyridine adducts
were observed. We hypothesize that these peaks may indicate
the presence of two stereoisomers of 6ab in solution. For
combinations with larger equilibrium constants, it was possible
to crystallize the adducts. X-ray quality crystals of 6aa, 6ca,
6da, and 6db were grown by slow evaporation of methylene
chloride solutions containing excess pyridine (Figure 5 and
S27−S29). In each case, the pyridine adduct is a monopalla-
dium complex with the pyridine ring coordinated cis to the aryl
group and trans to the phosphine. This geometry places the
weakest trans-effect ligand (Br) trans to the strongest (aryl).
This stereochemistry suggests a potential isomerization during
the cleavage reaction. In the dimer, the Br trans to the aryl
ligand has a longer Pd−Br bond and would be expected to be
more easily cleaved. The resulting product with pyridine trans
to the aryl ligand would not be expected to be thermodynami-
cally preferred, however. The observation of two 31P NMR
resonances for 6ab suggests that both stereoisomers may exist
in equilibrium in solution.
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(pyridine)2Pd(2,6-Me2C6H3)Br (7) was isolated instead of
complex 6fa. A similar product is formed when ((t-Bu)3P)Pd-
(2-tol)Br is reacted with pyridine.21 X-ray quality crystals of 7
were obtained, which allowed the structure to be confirmed as
the trans-dipyridine complex (Figure S31). Observation of the
reaction of complexes 3a, 3c, and 3d with excess pyridine by
31P NMR spectroscopy showed no evidence of displacement of
PNp3 by a second equivalent of pyridine. The decreased steric
demand of PNp3 compared to P(t-Bu)3 likely results in a
tighter coordination to palladium, preventing displacement by
pyridine. The sterically demanding 2,6-dimethylphenyl ligand
increases the lability of PNp3, however, resulting in slow
displacement of the phosphine in this case.
Steric Effects on the Cleavage Equilibrium. The effect
of both the steric demand of the incoming pyridine ligand and
the aryl ligand on the equilibrium constant could be evaluated
independently in this study. For each of the dimer complexes
(3), increasing steric hindrance of the pyridine resulted in a
significant decrease in the binding equilibrium constant (Table
2). For example, complex 3a with a sterically undemanding 4-
tolyl aryl group reacted stoichiometrically with pyridine at all
Pd/pyridine ratios. When complex 3a was reacted with 2-
picoline, the equilibrium constant was 3.8 × 102, which
corresponds to at least a 2 orders of magnitude decrease in K.
The equilibrium constant for 2,6-lutidine (5.8, 6ac) was
approximately 2 orders of magnitude less than for 2-picoline
(6ab). Complexes 3c, 3d, and 3f showed similar trends. The
2,6-lutidine complex could not be observed for these
complexes even at high lutidine/Pd ratios. Whereas our results
show that the steric demand of the pyridine derivative has a
significant effect on the binding equilibria, prior studies with
[(Pr3P)PdI2]2 showed that the increased basicity of 2,6-
lutidine compared to pyridine resulted in a larger equilibrium
constant.19b Presumably, steric effects dominate in complexes
3a−3f with the more sterically hindered PNp3 and aryl ligands.
The steric demand of the aryl ligand also affects the
equilibrium constant, although generally to a smaller extent.
For all three pyridine derivatives, complex 3a had a larger
equilibrium constant than the complexes with ortho-substitu-
ents. With pyridine, the number or size of the ortho-substituent
did not significantly impact the equilibrium constant, with 3c,
3d, and 3f all giving similar values. With the more hindered 2-
picoline, the number of ortho substituents did have a larger
effect. The equilibrium constant for 3a was 1 order of
magnitude higher than that of the mono ortho-substituted
complexes (3c and 3d). The di-ortho-substituted complex 3f
had an equilibrium constant that was 3 orders of magnitude
lower than that of 3c or 3d. In the case of 2,6-lutidine, only the
unhindered complex 3a was able to form an observable
amount of adduct.
Figure 5. Thermal ellipsoid plot (50% probability) of the molecular
structure of 6db. Hydrogen atoms and disorder are omitted for clarity.
Both the aryl and pyridine ligand are approximately
perpendicular to the palladium square plane. The structures
of the pyridine complexes are similar to the corresponding
halide-bridged dimer (Table S10). In complexes 3 and 6, the
P−Pd−Br angle is the largest angle between the cis ligands and
becomes larger when the aryl ligand has an ortho substituent.
The bond angles for the neopentyl ligands in 3a (Ar = 4-tolyl)
and 6aa (Ar = 4-tolyl, L = pyridine) or in 3c (Ar = 2-tolyl) and
6ca (Ar = 2-tolyl, L = 2-picoline) are very similar to each other.
This result suggests that the aryl substituent cis to PNp3 plays
the largest role in determining the conformation of the
phosphine, whereas the trans ligand does not have a significant
effect on the PNp3 conformation. A comparison of 6da and
6db where the aryl group (2-isopropylphenyl) is the same but
the trans pyridine group is different (6da = pyridine, 6db = 2-
picoline) again shows qualitatively similar structures. The main
difference is that the CAr−Pd−P−C1 dihedral angle for 6da
(17.0°) is significantly smaller than for 6db (34.12°). The
additional rotation of the PNp3 ligand in 6db is likely due to
repulsion between the ortho-methyl group on 2-picoline and
the C2 neopentyl group of the phosphine. The limited effect of
the pyridine ligands on the PNp3 ligand can also be seen in the
%Vb values. The values for the pyridine adducts (6) are nearly
identical to those for the halide dimers (3). For example, 4-
tolyl complex 3a and its pyridine adduct (6aa) have the same
%Vb value of 36.3%. Notably, the identity of the ortho
substituent on the aryl ligand (methyl vs isopropyl) does not
affect the buried volume (6ca (33.9%) vs 6da (33.9%)).
Changing the pyridine ligand from pyridine to 2-picoline in
6da (33.9%) and 6db (34.4%) also has little effect on the
buried volume.
As noted above, complex 3f is converted to a bis(pyridine)
complex upon exposure to excess pyridine over an extended
period. To ensure that this process did not affect the
equilibrium values measured for 3f, the rate of this process
In an attempt to isolate complex 6fa by crystallization from a
solution of methylene chloride and excess pyridine,
a
Table 2. Equilibrium Constants (K) for the Reaction of 3 with Pyridine Derivatives to Afford 6
5
3a
3c
3d
3f
b
pyridine
2-picoline
2,6-lutidine
>1 × 104(6aa)
1.9 0.5 × 102 (6ca)
15 5 (6cb)
4.6 2.4 × 102 (6da)
13 0.6 (6db)
1.2 0.3 × 102 (6fa)
8.6 3 × 10−2 (6fb)
3.8 0.2 × 102(6ab)
5.8 0.8 (6ac)
c
c
c
<1 × 10−3(6cc)
<1 × 10−3(6dc)
<1 × 10−3(6 fc)
a
b
c
K = [6]2/([3][5]2) 100% conversion to pyridine adduct was observed at all pyridine concentrations. No lutidine adduct was observed.
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was followed by 31P NMR spectroscopy. Complex 3f (3.5
mM) was treated with pyridine (35 mM) in CH2Cl2 at room
temperature. Immediately after the addition of pyridine,
analysis by 31P NMR spectroscopy showed that 3f was
completely consumed and the only resonance observed was
that of (PNp3)Pd(2,6-Me2C6H3)(pyridine)Br (6fa, Scheme 1).
Scheme 1. Reaction of 3f with Pyridine to Give 7
Figure 6. Thermal ellipsoid plot (50% probability) of the molecular
structure of 9c. Hydrogen atoms and disorder are omitted for clarity.
Selected bond lengths (Å) and angles (deg): Pd1−N1, 2.1512(13);
Pd1−Br1, 2.5322(2); Pd1−C16, 2.0147(16); Pd1−P1, 2.2818(4);
N1−Pd1−Br1, 85.17(4); P1−Pd1−Br1, 94.220(12); N1−Pd1−P1,
173.00(4); C16−Pd1−Br1, 173.21(5); C16−Pd1−P1, 90.46(4);
C16−Pd1−N1, 90.78(6).
No free PNp3 was observed, which indicates that no
conversion to complex 7 had occurred in this time. After 14
h at room temperature, 16% of 6fa was converted to
bis(pyridine) complex 7 (Figure S58, Supporting Informa-
tion). Heating the reaction to 60 °C for an additional 200 min
resulted in 70% conversion of 6fa to 7. The rate of conversion
of 6fa to 7 is too slow at room temperature to affect the
analysis of the equilibrium ratios in this study. Significantly, no
free PNp3 was observed in any of the equilibrium studies.
Coordination of Amines to Complex 3f. The reaction of
the most sterically demanding palladium aryl dimer (3f) with
amine substrates used in Buchwald−Hartwig reactions was
next explored. We previously reported that bromide-bridged
dimers related to 3a−3f do not form a stable adduct with
aniline, although they effectively catalyzed the arylation of
aniline.11 As expected, the reaction of dimer 3f with an excess
of aniline gave no evidence of formation of an aniline complex
(9a) based on the 31P NMR spectrum of the reaction mixture.
Reaction of 3f with the more basic amines, such as isobutyl
amine (8b) or morpholine (8c) provides stable amine
complexes (9b−9c, eq 4). Complex 9c afforded X-ray quality
dimethylphenyl substituent with the chloride, the palladium
center is less sterically hindered and more electron-deficient.
The more accessible and electron-deficient palladium center
binds more readily to aniline than 3f. Complex 11 gave X-ray
quality crystals that allowed the structure to be determined
(Figure S33). The solid state structure is a distorted square
plane with a trans arrangement of the phosphine and amine
ligands. As in 9b, aniline coordinates as a neutral ligand.
Computational Results. Optimized geometries and vibra-
tional frequencies for complexes 3 and 6 were calculated at the
density functional theory22 level with the B3LYP23 exchange-
correlation functional. The calculations used the DZVP224
basis set for the first and second row atoms (H, C, N, P), the
DZVP24 basis set for Br, and the pseudopotential (PP) based
aug-cc-pVDZ-PP correlation-consistent basis set25 for Pd. As
shown in Tables 1 (3a−3f) and S10 (6aa−6db), the calculated
structural parameters are in good agreement with experimental
results. The Pd−Br, Pd−P, and Pd−N dative bonds are
predicted to be 0.05 to 0.10 Å too long (on the order of up to
4%). This is typical of what is found in comparing the
geometries of molecules with dative bonds to transition metal
atoms using gradient corrected functionals with DFT. The
calculated Pd−C covalent bond distances are in much better
agreement with experimental results. The calculated and
experimental bond angles are in agreement within a few
degrees. The percent buried volumes obtained from DFT-
optimized gas phase structures were consistently smaller (1.6−
3°) than those obtained from solid-state structures but
followed the same trends as those obtained from solid-state
structures. The underestimation of the buried volume is likely
due in part to the overestimation of the Pd−P bond length,
which would decrease the steric interaction in the metal
coordination sphere.
crystals that allowed confirmation of the structure as an adduct
in which the morpholine coordinates as a neutral ligand
(Figure 6). The amine coordinates cis to the aryl substituent as
seen with the pyridine complexes.
Reaction of aniline with [Pd(TNpP)Cl2]2 (10)9g cleanly
affords aniline complex 11 (eq 5). By replacing the 2,6-
The calculated energetics using five different DFT func-
tionals in both the gas phase and in solution for the dimer−
monomer equilibrium (eq 6) reaction for different substituted
aromatics are reported in Tables 3 and S29. The B3LYP results
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computationally using the B3LYP, M06, and ωB96xD
functionals (eq 7, Tables 4 and S30). All three functionals
Table 3. Calculated Solution Phase (CH2Cl2) Bromine-
Bridge Dissociation Reaction Free Energies for eq 6 at 298
K (kcal/mol)
B3LYP-
Ar
C6H5 (3g)
4-MeC6H4 (3a)
4-t-BuC6H4 (3b)
2-MeC6H4 (3c)
2-i-PrC6H4 (3g)
B3LYP M06 ωB97xD
D3BJ
B97D3BJ
Table 4. Calculated trans−cis Free Energy Differences (eq
7) at 298 K in CH2Cl2 Solution (kcal/mol)
−15.7
−10.8
−12.4
−14.0
−1.7
0.9
7.8
6.9
2.7
19.0
0.3
1.9
8.7
8.0
4.4
17.0
1.7
8.1
14.4
14.0
10.4
23.1
7.7
2.5
8.4
8.1
4.7
17.9
2.3
3
5
6
B3LYP M06 ωB97xD
C6H5 (3g)
pyridine (5a)
2-picoline (5b)
2,6-lutidine (5c) 6gc
pyridine (5a)
2-picoline (5b)
2,6-lutidine (5c) 6ac
pyridine (5a)
2-picoline (5b)
2,6-lutidine (5c) 6cc
pyridine (5a)
2-picoline (5b)
2,6-lutidine (5c) 6dc
6ga
6gb
2.5
4.4
6.5
1.4
5.5
9.3
0.8
2.2
4.9
3.9
7.3
8.3
3.1
3.7
2.4
2.0
4.1
5.9
−0.3
4.7
7.5
−0.1
0.8
4.7
2.4
6.8
1.9
4.0
6.7
0.2
5.3
9.4
0.5
1.3
5.9
3.8
7.8
9.6
3.1
2.9
2.6
2-Me-4-OMeC6H3
(3e)
−16.4
4-MeC6H4 (3a)
2-MeC6H4 (3c)
2-i-PrC6H4 (3d)
6aa
6ab
2,6-Me2C6H3(3f)
−15.3
1.3
2.9
9.1
3.2
6ca
6cb
predict that formation of the monomer (12) is always highly
favored in dichloromethane solution, except for 3d, where
monomer formation is weakly favored. In contrast, dimer
formation is always favored in the gas phase with the B3LYP
functional (Table S29). The other four functionals, which are
expected to handle the nonbonded van der Waals interactions
in these sterically bulky systems in a more even manner,
predict that dimer 3 is heavily preferred in the gas phase. The
dimer is favored in solution, as well, for all four functionals, but
with smaller energy differences. On the basis of the
calculations, complexes 3g, 3c, 3e, and 3f may be in
equilibrium with small concentrations of their corresponding
monomer complexes in solution. Stable three-coordinate
palladium aryl complexes have been characterized, but the
known examples require highly sterically demanding ligands,
such as tri-tert-butylphosphine or triadamantylphosphine.26 On
the basis of the observation of four stereoisomers for
complexes 3c and 3d in solution,10 complexes 3a−3f are
expected to exist primarily as halide-bridged dimers in solution.
The stability of dimer complexes 3a−3g compared to the
three-coordinate monomers 12a−12g roughly follows the
steric demand of the ligands, although there are exceptions to
this trend. As expected, the endothermicity of dimer cleavage
decreases going from 4-substituted (3a, 3b) to 2-substituted
(3c) to 2,6-disubstituted (3f) as the steric demand of the aryl
ligand increases. Replacing the 2-methyl substituent in 3c with
isopropyl (3d) results in a significantly higher endothermicity,
which is not expected based on steric effects. If an electron
donating methoxy group is substituted at the 4- position in 3c
to form 3e, the endothermicity is the smallest. This could
reflect an increased trans effect from the more electron-rich
aryl ring. Phenyl-substituted 3g has a nearly identical value to
3e and a much lower endothermicity than 3a or 3b, however.
The tendency of the dimer to cleave appears to depend on
several factors than cannot be clearly assigned to steric and/or
electronic effects.
6da
6db
8.0
2.1
2.0
0.7
2,6-Me2C6H3 (3f) pyridine (5a)
2-picoline (5b)
6fa
6fb
2,6-lutidine (5c) 6 fc
gave similar predicted trends for the relative stabilities of the
two isomers. In the gas phase, the 6-cis isomer is predicted to
be strongly favored for all complexes (Table S30). This trend is
expected based on the preference for the strong trans-effect
aryl ligand to be trans to the weak trans-effect bromide ligand.
The trans isomer would also lead to increased steric strain
between the PNp3, aryl, and pyridine ligands. In solution, the
6-cis isomer is predicted to be favored in nearly all cases, but by
a smaller amount than in the gas phase. For complexes with
zero or one ortho substituent (6ax, 6cx, and 6dx), the energy
difference between the cis and trans isomers increases with
increasing size of the pyridine ligand. For example, the cis and
trans isomers of the 4-tolylpyridine complex (6aa) are
calculated to be nearly thermoneutral in solution. In the case
of the 2-picoline complex (6ab), the cis isomer is predicted to
be approximately 5 kcal/mol more stable than the trans isomer
in solution. The increased preference for the cis isomer is
presumably due to the increased steric strain between 2-
picoline and PNp3 ligands in the 6-trans isomer. The 2,6-
dimethylphenyl complexes (6fx) are predicted to have a small
decrease in energy differences between 6-cis and 6-trans
isomers as the steric demand of the pyridine increases. This
change in behavior likely reflects increased steric strain
between the 2,6-dimethylphenyl and pyridine ligands that
destabilize the 6-cis isomer relative to the 6-trans isomer.
The energetics for the equilibrium reaction of various
pyridines with the three-coordinate monomer complex 12 (eq
8, Tables 5 and S31) and dimeric complex 3 (eq 9, Tables 6
and S32) were predicted using different DFT functionals in
both the gas phase and CH2Cl2 solution. When attempts were
made computationally to add pyridines to dimeric complex 3,
the pyridine ligand did not bind during the optimization. Thus,
the reactions of dimers 3a−3g with pyridines are predicted to
The solid-state structures of the pyridine complexes have a
cis relationship between the pyridine and aryl ligand in each
case. In solution, a single isomer was observed by 31P NMR in
all cases, except 6ab, where two complexes were observed. We
hypothesized that these may correspond to cis and trans
isomers of 6ab. The relative energies of the 6-cis and 6-trans
isomers of the (Np3P)Pd(pyr)(Ar)Br complexes were analyzed
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Experimentally, the binding order is pyridine > 2-picoline >
2,6-lutidine for all complexes tested. For the reactions of 3a,
3c, and 3d, excluding B3LYP, the order of reactivity is
predicted to be 2-picoline > pyridine > 2,6-lutidine. B3LYP, on
the other hand, predicts the correct order of reactivity, even
though the actual reaction free energies are predicted to be too
positive. For 3f, all of the methods predict the correct reactivity
order. The order of the gas phase basicity is pyridine < 2-
picoline < 2,6-lutidine from experimental results, and the
calculations match this order (Table S37). Thus, there is a
balance between the basicity and the steric interactions
governing the experimental ordering. B3LYP accounts for the
least amount of steric interaction so its energetics are
dominated by the basicity. However, the inability to account
for the steric interactions leads to B3LYP’s inability to predict
the amount of binding resulting in free energies that are too
positive. The other methods are able to predict the size of the
steric interactions better than they do predict about the correct
free energies but get some overbinding in terms of the steric
interactions. Thus, the basicity plays too important a role in
the calculated values.
The first step in the formation of dipyridine complex 7
(Scheme 1) is the cleavage of dimer 3f and addition of 2 equiv
of pyridine to give two 6fa (eq 10). This reaction is predicted
to be slightly too exothermic by −0.1 to −6.7 kcal/mol with all
of the functionals (Table 6). The calculated geometry
parameters for 7 are shown in Table S35, where they are
compared to the experimental values. The calculated geometry
parameters are in good agreement with experimental results
with bond distances within better than 0.04 Å. The energetics
for the second step (eq 11 and Tables 7 and S36) are
exothermic by ca. −10 kcal/mol at the B3LYP level. This is
due to the fact that there are fewer steric interactions in 7 than
in 6fa and B3LYP does not incorporate the nonbonded
interactions of the PNp3 group properly. The M06 functional
predicts the reaction to be slightly endothermic consistent with
the observation that 7 is formed. Whether eq 10 is exothermic
or endothermic in solution is within the accuracy of the
method. At the ωB97xD level, the reaction is predicted to be
endothermic by ∼5 kcal/mol so that the nonbonded
interactions are being too heavily weighted with this functional.
This is consistent with the results in Table 6. Equation 11 is
be dissociative processes. In contrast, previously studied
systems are proposed to undergo dimer cleavage through an
associative mechanism.19,20 These systems used less-hindered
complexes, such as [Pd2X6]2− and [(n-alkyl3P)PdX2]2. The
increased steric demand of complex 3 appears to prevent an
associative mechanism.
For the reaction of pyridine with a 3-coordinate monop-
alladium complex (12, eq 8), four of the functionals predict the
reactions to be exothermic in the gas phase and in solution
except for the formation of 6fc from 2,6-lutidine and 12f. In
contrast, the B3LYP functional predicts that pyridine
coordination would be endothermic in all cases in solution.
Complexes 3a−3g exist as halide bridged dimers in solution
as shown above. Thus, the critical thermodynamics are the
ones shown in Table 6 (eq 9), which can be derived by adding
the dissociation values in Table 3 (eq 6) to twice the
corresponding values in Table 5 (eq 8) as two pyridines will
react with the two monomers that are formed. The ωB97xD
functional tends to predict reaction energies that are too
negative as compared to experimental results, but qualitative
agreement with experimental results is found for most of the
reaction energies in solution. The M06, B97D3BJ, and B3LYP-
D3BJ functionals generally predict reaction free energies that
are too positive as compared to experimental results, and again,
qualitative agreement with experimental results is found for
most of the reactions. The B3LYP energies are all much less
negative than experimental results, and in general, all of the
predicted reaction energies are positive. Thus, the experimental
free energies are bracketed by the ωB97xD functional and by
the M06, B97D3BJ, and B3LYP-D3BJ functionals.
Table 5. Calculated Solution (CH2Cl2) Reaction Free Energies at 298 K (kcal/mol) for the Reactions of Pyridines 5a−5c with
(PNp3)PdArBr (12a−12g; eq 7)
12
5
6
B3LYP
M06
ωB97xD
B3LYP-D3BJ
B97D3BJ
C6H5 (12g)
pyridine (5a)
6ga
6gb
6gc
6aa
6ab
6ac
6ca
6cb
6cc
6da
6db
6dc
6fa
6.8
8.4
11.3
6.1
6.6
10.9
7.9
9.7
14.8
0.6
2.6
9.7
−1.6
−3.0
−2.9
−3.1
−5.4
−4.0
−0.7
−1.7
0.1
−8.7
−10.4
−6.0
−1.2
0.4
−4.2
−5.5
−6.1
−5.8
−8.2
−7.4
−3.8
−4.7
−3.4
−10.6
−11.9
−8.1
−4.8
−3.6
2.3
−4.7
−5.9
−6.5
−6.5
−9.0
−7.8
−4.1
−5.0
−3.5
−10.9
−12.2
−8.2
−5.2
−4.2
1.5
−1.5
−2.9
−3.4
−2.9
−5.7
−4.4
−0.9
−1.9
−0.4
−7.8
−9.2
−5.3
−1.6
−0.7
4.7
2-picoline (5b)
2,6-lutidine (5c)
pyridine (5a)
2-picoline (5b)
2,6-lutidine (5c)
pyridine (5a)
2-picoline (5b)
2,6-lutidine (5c)
pyridine (5a)
2-picoline (5b)
2,6-lutidine (5c)
pyridine (5a)
4-MeC6H4 (12a)
2-MeC6H4 (12c)
2-i-PrC6H4 (12d)
2,6-Me2C6H3 (12f)
6.9
10.7
19.7
2-picoline (5b)
2,6-lutidine (5c)
6fb
6 fc
6.1
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Table 6. Calculated and Experimental Solution (CH2Cl2) Reaction Free Energies at 298 K (kcal/mol) for the Reactions of
Pyridines 5a−c with [(PNp3)PdArBr]2 (3a−g) (eq 8)
a
3
5
6
B3LYP
M06
ωB97xD
B3LYP-D3BJ
B97D3BJ
exptl
C6H5 (3g)
pyridine (5a)
6ga
6gb
6gc
6aa
6ab
6ac
6ca
6cb
6cc
6da
6db
6dc
6fa
−2.1
1.0
6.9
1.4
2.5
10.9
1.9
5.5
15.6
−0.5
3.6
17.7
−1.5
6.1
−2.2
−5.2
−4.9
1.7
−3.0
−0.1
1.2
−0.7
2.9
1.7
−6.6
−9.1
−10.3
−2.9
−7.8
−6.0
−3.3
−5.0
−2.4
−4.2
−6.9
0.8
−1.4
−3.8
−5.0
1.5
−3.6
−1.1
2.2
0.4
3.5
1.3
−1.3
6.6
−0.5
−3.3
−4.4
2.6
−2.9
−0.3
2.9
0.9
3.9
2.3
−0.5
7.4
2-picoline (5b)
2,6-lutidine (5c)
pyridine (5a)
2-picoline (5b)
2,6-lutidine (5c)
pyridine (5a)
2-picoline (5b)
2,6-lutidine (5c)
pyridine (5a)
2-picoline (5b)
2,6-lutidine (5c)
pyridine (5a)
4-MeC6H4 (3a)
2-MeC6H4 (3c)
2-i-PrC6H4 (3d)
2,6-Me2C6H3 (3f)
< −5.5
−4.9 0.1
−1.0 0.1
−3.1 0.2
−1.6 0.3
>4.1
−3.6 0.4
−1.5 0.1
>4.1
−1.8
7.1
−1.1
2.1
−6.7
−4.3
7.4
−1.2
0.8
12.1
−0.1
1.7
12.6
−2.8 0.2
1.5 0.2
>4.1
2-picoline (5b)
2,6-lutidine (5c)
6fb
6 fc
24.1
13.6
a
Calculated using equilibrium constants (K) reported in Table 3.
pyridine ligand and to a lesser extent the steric demand of the
aryl group on palladium. These results are in contrast to
previous studies with less hindered palladium centers in which
the pyridine basicity was a more important factor in the
binding equilibrium.19b To our knowledge, this is the first
analysis of steric effects of ligand binding in complexes with
sterically demanding ligands relevant to palladium-catalyzed
cross-coupling. Electronic structure calculations suggest that
this ligand substitution process occurs by a dissociative
mechanism, rather than the associative process seen in other
halide dimer cleavage reactions.19,20 This conclusion is based
on the fact that a pyridine adduct of the halide bridged dimers
(3), which would be required in an associative mechanism,
could not be found computationally.
Electronic structure calculations of these systems highlight
that the choice of functional plays a critical role in obtaining
energies that are consistent with experimental results.
Calculations using B3LYP were generally least consistent
with the experiment and the other basis sets used in this study.
The poor performance of B3LYP is thought to be due to its
handling of the extensive van der Waals interactions in these
complexes. None of the functionals were able to accurately
calculate ΔG within 1 kcal/mol for all of the reactions of
pyridine derivatives with the dimer complexes (3), although
the ωB97xD and M06, B97D3BJ, and B3LYP-D3BJ func-
tionals bracketed the experimental values. The agreement of
the computational results with experimental results is
reasonable considering the difficulty in calculating nonbonded
interactions and solvent effects. An error of 1 to 3 kcal/mol in
each component readily accounts for the differences between
the calculated values and experimental results. All of the
functionals except B3LYP overestimated the effect of pyridine
basicity on the binding equilibria relative to the steric effect,
resulting in predictions that 2-picoline would bind more
favorably than pyridine.
Table 7. Calculated Solution (CH2Cl2) Reaction Free
Energies at 298 K (kcal/mol) for eq 10 and eq 11
method
B3LYP
M06
ωB97xD
B3LYP-D3BJ
B97D3BJ
eq 10
eq 11
−1.5
−1.1
−6.7
−0.1
−1.2
−10.4
1.1
4.8
7.2
8.2
even more endothermic with the B3LYP-D3BJ and B97D3BJ
functionals showing that, again, they may be overestimating the
stabilization due to nonbonded interactions.
3f + 2pyr → 26fa
(10)
26fa + 2pyr → 27 + 2PNp3
(11)
CONCLUSIONS
■
Structural analysis of trineopentylphosphine palladium com-
plexes confirms that there is a significant degree of conforma-
tional flexibility in the trineopentylphosphine ligands that
allows accommodation of other sterically demanding ligands in
the coordination environment. There is a dramatic difference
in the conformation of PNp3 coordinated to two-coordinate
palladium (Pd(PNp3)2) and the four-coordinate complexes
discussed here (3 and 6). Within the four-coordinate
complexes, the neopentyl ligands adjust their conformations
to tolerate aryl ligands on palladium. Changes in the torsional
angles of the neopentyl substituents (Pd−P−C-C) and the P−
C−C bond angles are the primary responses to increased steric
demand. In the case of a 2,6-dimethylphenyl substituent, the
phosphine is pyramidalized to move the neopentyl groups
further from the palladium center. These changes in
conformation can be seen through buried volume calculations
that show decreasing %Vb with increasing steric demand of the
aryl ligand on palladium. In contrast to the significant effect of
the cis-aryl ligand on the PNp3 conformation, the ligand trans
to the phosphine has less impact.
EXPERIMENTAL SECTION
■
General Procedure and Materials. PNp3,27 Pd(PNp3)2,10,28
3b,10 3c,10 3f,11 (COD)Pd(CH2TMS)2,29 and 109g were prepared
according to literature procedures. Other reagents were purchased
from commercial suppliers and used as received. Toluene was refluxed
over sodium for an hour and freshly distilled before use. Methylene
The binding equilibria for cleavage of the halide bridged
dimers (3) by pyridine to give pyridine complexes (6) are
dependent primarily on the steric demand of the incoming
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chloride was distilled from CaH2 under nitrogen prior to use.
Reactions were conducted under nitrogen double-manifold inert-
atmosphere techniques, unless noted otherwise.
(PNp3)Pd(morpholine)(2,6-Me2C6H3)Br (9c). 3f (70 mg, 0.065
mmol) was dissolved in methylene chloride (8 mL). Then,
morpholine (13.0 μL, 0.150 mmol) was added into the solution.
After stirring for 1 h, the volatiles were removed under a vacuum to
provide a white solid (78 mg, 96%). Colorless single crystals were
[(PNp3)Pd(4-MeC6H4)Br]2 (3a). Pd(PNp3)2 (97.3 mg, 0.164
mmol) and 4-bromotoluene (96.4 μL, 0.78 mmol) were mixed
together in 10 mL toluene in a two-neck flask under N2. The reaction
mixture was stirred at 70 °C for 14 h. After cooling to RT, all the
volatiles were pumped off, and the remaining solids were washed with
pentane. Then, the collected solids were dissolved in hot toluene
again. The solution was filtered while hot to remove insoluble Pd
black solids. Removal of the solvent under a vacuum afforded a white
solid (73.88 mg, 70%). 1H NMR (500 MHz, C6D6, 283 K): δ 7.64 (d,
J = 5.3 Hz, 4H), 6.93 (d, J = 5.8 Hz, 4H), 1.77 (d, J = 10.7 Hz, 12H),
1.37 (s) 1.27 (brs, 54H). 13C NMR (125 MHz, C6D6, 295 K): δ
148.3, 135.5, 132.2, 108.0, 40.0, 33.5, 32.6, 31.4 (brm), 20.80. 31P
NMR (202.5 MHz, C6D6, 295 K): δ 7.78, 6.14 ppm (1:0.13).
[(PNp3)Pd(2-iPrC6H4)Br]2 (3d). Pd(PNp3)2 (110.2 mg, 0.185
mmol) and 1-bromo-2-isopropylbenzene (142.3 μL, 0.93 mmol) were
mixed together in 10 mL of toluene in a two-neck flask under N2. The
reagent mixture was stirred at 70 °C for 14 h. After cooling to RT, all
the volatiles were pumped off, and the remaining solids were washed
with pentane. Then, the collected solids were dissolved in hot toluene.
The solution was filtered while hot to remove insoluble Pd black
solids. Removal of the solvent under a vacuum afforded a white solid
(80.8 mg, 65%). 1H NMR (500 MHz, C6D6, 283 K): δ 7.74 (m, 2H),
7.10−7.01 (m, 6H), 2.40−1.20 (m, 60H), 0.70 (s, 18H). 13C NMR
(125 MHz, C6D6, 295 K): δ 151.4 (s), 134.3, 134.2 (d, JC−P = 18.7
Hz), 126.4, 126.3 (d, JC−P = 15.0 Hz), 125.4, 124.3, 108.0, 41.6, 37.5,
33.1 (brs), 26.3, 26.2 (d, JC−P = 12.5 Hz), 24.5, 24.4 (d, JC−P = 12.5
Hz). 31P NMR (202.5 MHz, C6D6, 295 K): δ 9.4, 9.2, 8.23, 8.18 ppm.
[(PNp3)Pd(2-Me-4-OMeC6H3)Br]2 (3e). Pd(PNp3)2 (61.6 mg,
0.104 mmol) and 4-bromo-3-methylanisole (88 μL, 0.62 mmol) were
mixed together in 10 mL of toluene in a one-neck flask under N2. The
reagent mixture was stirred at 70 °C for 14 h. After cooling to RT, all
the volatiles were pumped off, and the remaining solids were washed
with pentane. Then, the collected solids were dissolved in hot toluene.
The solution was filtered while hot to remove insoluble Pd black
solids. Removal of the solvent under a vacuum afforded a white solid
(35.8 mg, 64%). 1H NMR (600 MHz, C6D6, 308.5 K): δ 7.54 (d, J =
2.2 Hz, 2H), 6.82 (s, 2H), 6.65 (d, J = 7.0 Hz, 2H), 3.40 (s, 6H), 2.98
(s, 6H), 1.71 (brs, 12H), 1.27 (brs, 54H). 13C NMR (125 MHz,
C6D6, 295 K): δ 157.9, 141.6, 133.9, 116.5, 116.4, 111.0, 54.8, 33.1,
32.5, 27.4, 22.7. 31P NMR (202.5 MHz, C6D6, 295 K): δ 9.3, 9.3, 8.00,
7.95 ppm.
Representative Procedure for Equilibrium Study Experi-
ments of [(PNp3)PdArBr]2 and Pyridine Derivatives. [(PNp3)-
Pd(2-iPrC6H4)Br]2 (3d, 17.6 mg, 1.31 × 10−5 mol) was dissolved in
methylene chloride in a 2.0 mL volumetric flask with the addition of
the standard trimethyl phosphate (8.0 μL, 6.84 × 10−5 mol), which
worked as the stock solution. The stock solution of 3d (500 μL, 6.55
× 10−6 mol) and pyridine (10.6 μL, 1.31 × 10 −5 mol) was transferred
into an NMR tube. The resulting solution was allowed to stand for at
least 5 min and then analyzed by 31P NMR spectroscopy. Equilibrium
constants were calculated according to the integration of 31P signals
(see calculation details in Supporting Information). The pyridine
complexes (6) reverted to equilibrium mixtures of 3x, 5x, and 6xx in
the absence of excess pyridine ligand, so they were only characterized
by 31P NMR. In the case of 6aa, 6ca, 6da, and 6db, X-ray quality
crystals were obtained upon crystallization from solutions containing
excess pyridine or 2-picoline.
(PNp3)Pd((CH3)2CHCH2NH2)(2,6-Me2C6H3)Br (9b). 3f (50 mg,
0.047 mmol) was dissolved in methylene chloride (6 mL). Then,
isobutylamine (10.0 μL, 0.101 mmol) was added into the solution.
After stirring for 1 h, the volatiles were removed under a vacuum to
provide a white solid (52 mg, 92%). 1H NMR (500 MHz, C6D6, 295
K): δ 6. 90 (m, 3H), 2.86 (s, 6H), 2.75 (brs, 2H), 2.27 (s, 4H), 2.23
(br, 1H), 2.03 (brs, 2H), 1.56 (brs, 18H), 1.36 (br, 6H), 0.93 (br,
2H), 0.78 (brs, 9H). 13C NMR (125 MHz, C6D6, 295 K): δ 159.7,
140.2, 126.9, 124.6, 52.1, 43.9, 33.3 (d, JC−P = 35 Hz), 30.2, 27.0,
19.5. 31P{1H} NMR (202.5 MHz, C6D6, 295 K): δ 16.9.
1
formed after slow evaporation of a benzene solution. H NMR (500
MHz, C6D6, 295 K): δ 7.05−6.93 (m, 1H), 6.88 (d, J = 7.2 Hz, 2H),
3.59 (br, 1H), 3.08 (d, J = 12.5 Hz, 2H), 2.83 (s, 6H), 2.73 (m, 6 H),
2.68 (m, 2 H), 2.02 (brs, 2H), 1.54 (s, 18 H), 1.36 (s, 4H), 0.76 (s,
9H). 13C NMR (125 MHz, C6D6, 295 K): δ 160, 140.0, 127.0, 124.6,
67.8, 49.4, 43.9 (d, JC−P= 9.7 Hz), 33.3, 32.8, 26.9. 31P{1H} NMR
(202.5 MHz, C6D6, 295 K): δ 12.0
(PNp3)Pd(C6H7N)Cl2 (11). [(PNp3)PdCl2]2 (100 mg, 0.119
mmol) was dissolved in methylene chloride (8 mL). Then, aniline
(32.3uL, 0.357 mmol) was added into the solution. After stirring for 1
h, the volatiles were removed under a vacuum to provide an orange
solid (116.4 mg, 95%). Orange single crystals were formed after slow
1
evaporation of a benzene solution. H NMR (500 MHz, C6D6, 295
K): δ 7.24 (d, J = 7.8 Hz, 2H), 7.00 (t, J = 7.8 Hz, 2H), 6.85 (t, J = 7.3
Hz, 1H), 3.82 (s, 2H), 2.12 (d, J = 12.8 Hz, 6H), 1.20 (s, 27 H). 13C
NMR (125 MHz, C6D6, 295 K): δ 141.4, 129.1, 124.4, 121.3, 38.6 (d,
J
C−P= 25.2 Hz), 33.2 (d, JC−P = 6.4 Hz), 32.4 (d, JC−P = 4.3 Hz).
31P{1H} NMR (202.5 MHz, C6D6, 295 K): δ 15.5.
X-ray Crystallography. Crystals of appropriate dimension were
mounted on Mitgen cryoloops or a glass filament in a random
orientation. Preliminary examination and data collection for
complexes 3a, 3e, 6aa, 6ab, 6da, 6db, and 7 were performed on a
Bruker Apex2 CCD-based X-ray diffractometer equipped with an
Oxford N-Helix Cryosystem and fine focus Mo-target X-ray tube (λ =
0.71073 Å) operated at 1500 W of power (50 kV, 30 mA). The X-ray
intensities were measured at 223(2) K; the detector was placed at a
distance 6.000 cm from the crystal. The frames were integrated with
the Saint software package30 using a narrow-frame algorithm. Data
were corrected for absorption effects using the multiscan method in
SADABS. The space group was assigned by using XPREP of the
Bruker ShelXTL package,31 solved with ShelXT and refined with
ShelXL 2014/732 and the graphical interface ShelXle.33 All non-
hydrogen atoms were refined anisotropically. H atoms attached to
carbon were positioned geometrically and constrained to ride on their
parent atoms.
Preliminary examination and data collection for complexes 9b and
11 were performed using a Rigaku XtaLAB Synergy R, a DW system,
and a HyPix diffractometer operating at T = 100.00(10) K. Data were
measured using ω scans using Mo Kα radiation. The total number of
runs and images was based on the strategy calculation from the
program CrysAlisPro, and the unit cell was refined using
CrysAlisPro.34 Data reduction, scaling and absorption corrections
were performed using CrysAlisPro. The structure was solved and the
space group determined by the ShelXT35 structure solution program
using intrinsic phasing methods and refined by least-squares using
version 2018/3 of ShelXL36 and graphical interface Olex2.37 All non-
hydrogen atoms were refined anisotropically. H atoms attached to
carbon were positioned geometrically and constrained to ride on their
parent atoms.
The structure of [(PNp3)Pd(4-MeC6H4)Br]2 (3a) was found to
contain multiple two-component disorders. Within the asymmetric
unit, two symmetrically independent molecules were found. In
molecule one (containing a Pd1−Pd2−Br1−Br2 core), “rotation”
two-component disorders were found at both of the two neopentyl
ligands. In molecule two (containing Pd3−Br3A), three sites were
disordered. A two component disorder was found at the 4-tolyl ligand,
within which three pairs of the equivalent atoms of the two moieties
(C45 and C45A; C50 and C50A; C51 and C51A) were constrained
to have identical ADPs (EADP). Disorder was also found at the site of
Br3A and Br3B. The bonds of Pd3−Br3A and Pd3−Br3B were
restrained to have similar distances (SADI). The third disorder in this
molecule was located at the neopentyl ligand. It was modeled as a
“rotation” two-component disorder (C1−C2−C3 vs C1A−C2A−
C3A). Equivalent bonds of the two moieties were restrained to have
similar bond distances (SADI).
K
DOI: 10.1021/acs.inorgchem.9b02164
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Article
The structure of (PNp3)Pd(2-MeC6H3)(Pyr)Br (6ab) was also
found to have a two-component “ring flipping” disorder at the 2-tolyl
ligand. Within these moieties, atoms were subjected to a rigid bond
restraint (RIGU). The two disordered components were restrained to
have similar geometries (SAME command of ShelXL).
The structure of (PNp3)Pd(2-i-PrC6H4)2(2-picoline)Br (6db) was
found to have a two-component “ring flipping” disorder at the 2-
picoline ligand. Within these moieties, atoms were subjected to a rigid
bond restraint (RIGU). Also, as C10 and C10B appeared unstable
when refined anisotropically, they were treated approximately as
isotropic (ISOR).
The structure of (PNp3)Pd(2,6-Me2C6H3)(morpholine)Br (9b)
was found to have a positional disorder on the morpholine ligand at
one of the two molecules in the asymmetric unit. The structure was
successfully modeled by two moieties with an occupancy ratio of
0.6:0.4.
The structure of (PNp3)Pd(aniline)Cl2 (11) was found to have a
rotational disorder on one of the neopentyl ligands. Atoms on the two
moieties were restrained to have similar geometries (SAME).
Computational Methods. The geometries were optimized, and
vibrational frequencies were calculated at the density functional
DFT22 level with the B3LYP23 exchange-correlation functional.
Vibrational frequencies were predicted to ensure that the optimized
structures were minima. The calculations used the DZVP224 basis set
for the first and second row atoms (H, C, N, P), the DZVP24 basis set
for Br, and the pseudopotential (PP)-based aug-cc-pVDZ-PP
correlation-consistent basis set25 for Pd. Single point M0638 and
ωB97xD39 calculations were done at the B3LYP optimized geo-
metries. The gas phase calculations were performed using the
Gaussian 09 program system.40 Calculations in CH2Cl2 solution (ε =
2.02) were performed using a self-consistent reaction field approach41
with the COSMO parameters41,42 using Gaussian 03.43 Additional
single point B3LYP and B97D3 calculations using the D3 version of
Grimme’s dispersion with Becke-Johnson damping44 (will be named
as B3LYP-D3BJ and B97D3BJ)45 were performed using cc-pVDZ for
H;46 aug-cc-pVDZ for C, N,47 and P;48 aug-cc-pVDZ-PP for Br;49 and
cc-pVDZ-PP for Pd as basis sets. The solvation COSMO calculations
were redone using the new basis sets with B3LYP-D3BJ as a
functional. This additional set of calculation was performed using
Gaussian 16.50 The Gibbs free energy in CH2Cl2 solution at 298 K
was calculated from eq 12:
Accession Codes
CCDC 1941334−1941342 contain the supplementary crys-
tallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif, by
emailing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: + 44 1223 336033.
AUTHOR INFORMATION
■
Corresponding Authors
*E-mail: dadixon@ua.edu.
*E-mail: kshaughn@ua.edu.
ORCID
Monica Vasiliu: 0000-0001-7573-4787
Fengrui Qu: 0000-0002-9975-2573
Deidra L. Gerlach: 0000-0002-1246-1192
David A. Dixon: 0000-0002-9492-0056
Kevin H. Shaughnessy: 0000-0002-1375-5563
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Acknowledgment is made to the National Science Foundation
(CHE-1058984) for partial financial support of the exper-
imental work. Structures of 9b and 11 were obtained on an X-
ray diffractometer purchased with support from NSF (CHE
MRI 1828078). Johnson-Matthey is acknowledged for
donation of palladium salts. The computational work was
supported by the Chemical Sciences, Geosciences, and
Biosciences Division, Office of Basic Energy Sciences, U.S.
Department of Energy (DOE) under the Catalysis Center
Program by a subcontract from the Pacific Northwest National
Laboratory (KC0301050-47319). D.A.D. also thanks the
Robert Ramsay Chair Fund of The University of Alabama
for support.
ΔGsol = ΔGgas + ΔGsolv
(12)
REFERENCES
■
(1) Surry, D. S.; Buchwald, S. L. Dialkylbiaryl phosphines in Pd-
catalyzed amination: a user’s guide. Chem. Sci. 2011, 2, 27−50.
(2) Fleckenstein, C. A.; Plenio, H. Sterically demanding
trialkylphosphines for palladium-catalyzed cross coupling reactions-
alternatives to PtBu3. Chem. Soc. Rev. 2010, 39, 694−711.
where ΔGgas is the gas phase free energy at 298 K and ΔGsolv is the
CH2Cl2 solvation free energy at 298 K. The solvation energy is only
the electrostatic term (polarized solute − solvent).
Calculation of %Vb. Percent buried volumes for the complexes
were calculated using the SambVca 2.0 Web Application.16 The metal
was defined as the center of the sphere, and the P of the ligand being
analyzed was used to define the z axis. The following default
parameters were used for all calculations: atomic radii were the bond
radii table scaled by 1.17 in the application, sphere radius = 3.5 Å,
mesh spacing = 0.1 Å, and H atoms were excluded from the
calculations.
(3) (a) Grasa, G. A.; Colacot, T. J. α-Arylation of Ketones using
Highly Active, Air-Stable (DtBPF)PdX2 (X = Cl, Br) Catalysts. Org.
Lett. 2007, 9, 5489−5492. (b) Hartwig, J. F. Evolution of a Fourth
Generation Catalyst for the Amination and Thioetherification of Aryl
Halides. Acc. Chem. Res. 2008, 41, 1534−1544.
(4) (a) Valente, C.; Çalimsiz, S.; Hoi, K. H.; Mallik, D.; Sayah, M.;
Organ, M. G. The Development of Bulky Palladium NHC Complexes
for the Most-Challenging Cross-Coupling Reactions. Angew. Chem.,
Int. Ed. 2012, 51, 3314−3332. (b) Valente, C.; Pompeo, M.; Sayah,
M.; Organ, M. G. Carbon-Heteroatom Coupling Using Pd-PEPPSI
Complexes. Org. Process Res. Dev. 2014, 18, 180−190. (c) Izquierdo,
F.; Manzini, S.; Nolan, S. P. The use of the sterically demanding IPr*
and related ligands in catalysis. Chem. Commun. 2014, 50, 14926−
14937.
ASSOCIATED CONTENT
■
S
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.inorg-
chem.9b02164.
(5) (a) Ehrentraut, A.; Zapf, A.; Beller, M. A new improved catalysts
for the palladium catalyzed amination of aryl chlorides. J. Mol. Catal.
A: Chem. 2002, 182−183, 515−523. (b) Rodriguez, S.; Qu, B.;
Haddad, N.; Reeves, D. C.; Tang, W.; Lee, H.; Krishnamurthy, D.;
Senanayake, C. H. Oxaphosphole-Based Monophosphorus Ligands
for Palladium-Catalyzed Amination Reactions. Adv. Synth. Catal.
2011, 353, 533−537.
NMR spectra of isolated complexes, X-ray crystallog-
raphy data, data for pyridine binding experiments,
reaction profile for the addition of pyridine to 3f,
additional reaction energies, proton affinities of the
pyridines, Cartesian coordinates in angstroms for
optimized DFT geometries (PDF)
L
DOI: 10.1021/acs.inorgchem.9b02164
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Article
(6) (a) Organ, M. G.; Abdel-Hadi, M.; Avola, S.; Dubovyk, I.; Hadei,
N.; Kantchev, E. A. B.; O’Brien, C. J.; Sayah, M.; Valente, C. Pd-
catalyzed aryl amination mediated by well defined, N-heterocyclic
carbene (NHC)-Pd precatalysts, PEPPSI. Chem. - Eur. J. 2008, 14,
2443−2452. (b) Tu, T.; Fang, W.; Jiang, J. A highly efficient
precatalyst for amination of aryl chlorides: synthesis, structure and
application of a robust acenaphthoimidazolylidene palladium
complex. Chem. Commun. 2011, 47, 12358−12360. (c) Chartoire,
A.; Frogneux, X.; Boreux, A.; Slawin, A. M. Z.; Nolan, S. P.
[Pd(IPr*)(3-Cl-pyridinyl)Cl2]: A Novel and Efficient PEPPSI
Precatalyst. Organometallics 2012, 31, 6947−6951. (d) Meiries, S.;
Chartoire, A.; Slawin, A. M. Z.; Nolan, S. P. [Pd(IPr*)(acac)Cl]: An
easily synthesized, bulky precatalyst for C-N bond formation.
Organometallics 2012, 31, 3402−3409. (e) Zhu, L.; Ye, Y.-M.; Shao,
L.-X. Well-defined NHC-Pd(II)-Im (NHC = N-heterocyclic carbene;
Im = 1-methylimidazole) complex catalyzed C-N coupling of primary
amines with aryl chlorides. Tetrahedron 2012, 68, 2414−2420.
(f) Bastug, G.; Nolan, S. P. [Pd(IPr*OMe)(cin)Cl] (cin =
Cinnamyl): A Versatile Catalyst for C-N and C-C Bond Formation.
Organometallics 2014, 33, 1253−1258. (g) Lan, X.-B.; Li, Y.; Li, Y.-F.;
Shen, D.-S.; Ke, Z.; Liu, F.-S. Flexible Steric Bulky Bis(Imino)-
acenaphthene (BIAN)-Supported N Heterocyclic Carbene Palladium
Precatalysts: Catalytic Application in Buchwald-Hartwig Amination in
Air. J. Org. Chem. 2017, 82, 2914−2925.
(7) (a) Urgaonkar, S.; Verkade, J. G. Scope and limitations of
Pd2(dba)3/P(i-BuNCH2CH2)3N-catalyzed Buchwald-Hartwig amina-
tion reactions of aryl chlorides. J. Org. Chem. 2004, 69, 9135−9142.
(b) Reddy, C. V.; Kingston, J. V.; Verkade, J. G. (t-Bu)2PN = P(i-
BuNCH2CH2)3N: new efficient ligand for palladium-catalyzed C-N
couplings of aryl and heteroaryl bromides and chlorides and for vinyl
bromides at room temperature. J. Org. Chem. 2008, 73, 3047−3062.
(8) Lee, D.-H.; Taher, A.; Hossain, S.; Jin, M.-J. An efficient and
general method for the Heck and Buchwald-Hartwig coupling
reactions of aryl chlorides. Org. Lett. 2011, 13, 5540−5543.
(9) (a) Hill, L. L.; Moore, L. R.; Huang, R.; Craciun, R.; Vincent, A.
J.; Dixon, D. A.; Chou, J.; Woltermann, C. J.; Shaughnessy, K. H.
Bulky alkylphosphines with neopentyl substituents as ligands in the
amination of aryl bromides and chlorides. J. Org. Chem. 2006, 71,
5117−5125. (b) Hill, L. L.; Smith, J. M.; Brown, W. S.; Moore, L. R.;
Guevera, P.; Pair, E. S.; Porter, J.; Chou, J.; Wolterman, C. J.; Craciun,
R.; Dixon, D. A.; Shaughnessy, K. H. Neopentylphosphines as
effective ligands in palladium-catalyzed cross-couplings of aryl
bromides and chlorides. Tetrahedron 2008, 64, 6920−6934.
(c) Hill, L. L.; Crowell, J. L.; Tutwiler, S. L.; Massie, N. L.; Hines,
C. C.; Griffin, S. T.; Rogers, R. D.; Shaughnessy, K. H.; Grasa, G. A.;
Johansson Seechurn, C. C. C.; Li, H.; Colacot, T. J.; Chou, J.;
Woltermann, C. J. Synthesis and X-Ray Structure Determination of
Highly Active Pd(II), Pd(I) and Pd(0) Complexes of Di-(tert-
butyl)neopentylphosphine (DTBNpP) in the Arylation of Amines
and Ketones. J. Org. Chem. 2010, 75, 6477−6488. (d) Raders, S. M.;
Jones, J. M.; Semmes, J. G.; Kelley, S. P.; Rogers, R. D.; Shaughnessy,
K. H. Di-tert-butylneopentylphosphine (DTBNpP): An Efficient
Ligand in the Palladium-Catalyzed α-Arylation of Ketones. Eur. J.
Org. Chem. 2014, 2014, 7395−7404. (e) Semmes, J. G.; Bevans, S. L.;
Mullins, H. C.; Shaughnessy, K. H. Arylation of diethyl malonate and
ethyl cyanoacetate catalyzed by palladium/di-tert-butylneopentylphos-
phine. Tetrahedron Lett. 2015, 56, 3447−3450. (f) Lauer, M. G.;
Thompson, M. K.; Shaughnessy, K. H. Controlling Olefin Isomer-
ization in the Heck Reaction with Neopentyl Phosphine Ligands. J.
Org. Chem. 2014, 79, 10837−10848. (g) Barnett, K. L.; Howard, J. R.;
Treager, C. J.; Shipley, A. T.; Stullich, R. M.; Qu, F.; Gerlach, D. L.;
Shaughnessy, K. H. Air-Stable [(R3P)PdCl2]2 Complexes of Neo-
pentylphosphines as Cross-Coupling Precatalysts: Catalytic Applica-
tion and Mechanism of Catalyst Activation and Deactivation.
Organometallics 2018, 37, 1410−1424.
Hartwig Amination and Suzuki-Miyaura Reaction. J. Org. Chem. 2013,
78, 4649−4664.
(11) Hu, H.; Qu, F.; Gerlach, D. L.; Shaughnessy, K. H. Mechanistic
Study of the Role of Substrate Steric Effects and Aniline Inhibition on
the Bis(trineopentylphosphine)palladium(0)-Catalyzed Arylation of
Aniline Derivatives. ACS Catal. 2017, 7, 2516−2527.
(12) (a) Calvin, G.; Coates, G. E. Organopalladium compounds. J.
́
Chem. Soc. 1960, 2008−2016. (b) Bartolome, C.; Espinet, P.;
Villafane, F.; Giesa, S.; Martín, A.; Orpen, A. G. (2,4,6-Tris-
(trifluoromethyl)phenyl)palladium(II) Complexes. Organometallics
̃
́
1996, 15, 2019−2028. (c) Bartolome, C.; Espinet, P.; Martín-
Alvarez, J. M.; Villafan
̃
e, F. Monoarylated Fluoromesitylpalladium
Complexes. Eur. J. Inorg. Chem. 2003, 2003, 3127−3138. (d) Jun, H.;
Young, V. G., Jr.; Angelici, R. J. A phosphorus analog (C:P-) of a
bridging cyanide (C:N-) ligand: synthesis and structure of (Cl)-
(PEt3)2Pt(μ-C≡P)Pt(PEt3)2. J. Am. Chem. Soc. 1992, 114, 10064−5.
(13) (a) Wakioka, M.; Nakamura, Y.; Wang, Q.; Ozawa, F. Direct
Arylation of 2-Methylthiophene with Isolated [PdAr(μ-O2CR)-
(PPh3)]n Complexes: Kinetics and Mechanism. Organometallics
2012, 31, 4810−4816. (b) Qian, R.; Liao, Y.-X.; Guo, Y.-L.; Guo,
H. ESI-FTICR-MS Studies on Gas Phase Fragmentation Reactions of
ArPd(PPh3)2I Complexes. J. Am. Soc. Mass Spectrom. 2006, 17, 1582−
1589.
(14) Paul, F.; Patt, J.; Hartwig, J. F. Structural characterization and
simple synthesis of {Pd[P(o-tol)3]2}, dimeric palladium (II)
complexes by oxidative addition of aryl bromides, and corresponding
monometallic amine complexes. Organometallics 1995, 14, 3030−
3039.
(15) Chaudhari, K. R.; Wadawale, A. P.; Jain, V. K. Isolation of
chloro-bridged arylpalladium complexes, [Pd2Ar2(μ-Cl)2(PR3)2], in
palladium catalyzed C-C cross coupling reaction of triarylbismuth
with arylhalides. J. Organomet. Chem. 2012, 698, 15−21.
(16) Falivene, L.; Credendino, R.; Poater, A.; Petta, A.; Serra, L.;
Oliva, R.; Scarano, V.; Cavallo, L. SambVca 2. A Web Tool for
Analyzing Catalytic Pockets with Topographic Steric Maps. Organo-
metallics 2016, 35, 2286−2293.
(17) (a) Bartell, L. S.; Bradford, W. F. Molecular structures of
neopentane and di-tert-butylmethane by vapor-phase electron
diffraction. J. Mol. Struct. 1977, 37, 113−126. (b) Cheng, M.-F.; Li,
W.-K. Structural and Energetics Studies of Tri- and Tetra-tert-
butylmethane. J. Phys. Chem. A 2003, 107, 5492−5498. (c) Liedle, S.;
Oberhammer, H.; Allinger, N. L. The gas-phase structures of some
highly strained compounds: di-t-butylmethane, di-t-butylamine and
di-t-butyl ketone. J. Mol. Struct. 1994, 317, 69−75. (d) Ermer, O.;
̈
Bodecker, C.-D. Structure of di-1-adamantylmethane (DAM) and di-
tert-butylmethane (DTBM). Chem. Ber. 1981, 114, 652−659.
(18) Weiss, I.; Oberhammer, H.; Gard, G. L.; Winter, R.; Seppelt, K.
The molecular structure of bis(pentafluorosulfur)methane (SF5)2CH2
and perfluorovinylsulfur pentafluoride SF5CF = CF2. J. Mol. Struct.
1992, 269, 197−205.
(19) (a) Pearson, R. G.; Muir, M. M. Rates of Cleavage of Halogen-
Bridged Complexes of Platinum(II). J. Am. Chem. Soc. 1966, 88,
2163−2166. (b) Cusumano, M.; Giannetto, A.; Ficarra, P.; Ficarra,
R.; Tommasini, S. Metal complexes of benzodiazepines. Part 2. The
reaction of 1,4-benzodiazepines with halide-bridged complexes of
palladium(II) [Pd2X4(PPr3)2] (X - Cl or I). J. Chem. Soc., Dalton
Trans. 1991, 1581−1584. (c) Ryabov, A. D.; Kuz’mina, L.; Polyakov,
V. A.; Kazankov, G. M.; Ryabova, E. S.; Pfeffer, M.; van Eldik, R.
Kinetics and mechanism of halogen-bridge cleavage in dimethylami-
nomethylphenyl-C1,N pallada- and platinacycles by pyridines.
Pressure effects, and crystal structures of the N,N-cis reaction product,
its N,N-trans orthometallated analog and a dimer of similar reactivity.
J. Chem. Soc., Dalton Trans. 1995, 999−1006.
(20) (a) Muir, M. M.; Cancio, E. M. Mechanisms of Reactions of
Binuclear Complexes. I. Cleavage by Olefins of a Halogen-Bridged
Complex of Platinum(II). Inorg. Chim. Acta 1970, 4, 565−567.
(b) Otto, S.; Roodt, A.; Elding, L. I. Bridge-splitting kinetics,
equilibria and structures of trans-biscyclooctene complexes of
platinum(II). Dalton Trans 2003, 2519−2525.
(10) Raders, S. M.; Moore, J. N.; Parks, J. K.; Miller, A. D.; Leißing,
T. M.; Kelley, S. P.; Rogers, R. D.; Shaughnessy, K. H.
Trineopentylphosphine: A Conformationally Flexible Ligand for the
Coupling of Sterically Demanding Substrates in the Buchwald-
M
DOI: 10.1021/acs.inorgchem.9b02164
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Article
(21) Shen, Q.; Shekhar, S.; Stambuli, J. P.; Hartwig, J. F. Highly
reactive, general, and long-lived catalysts for coupling heteroaryl and
aryl chlorides with primary nitrogen nucleophiles. Angew. Chem., Int.
Ed. 2005, 44, 1371−1375.
functionals and systematic testing of four M06-class functionals and
12 other functionals. Theor. Chem. Acc. 2008, 120, 215−241.
(39) Chai, J.-D.; Head-Gordon, M. Long-range corrected hybrid
density functionals with damped atom-atom dispersion corrections.
Phys. Chem. Chem. Phys. 2008, 10, 6615−6620.
(22) Parr, R. G.; Yang, W. Density Functional Theory of Atoms and
Molecules; Springer-Verlag: New York, 1989.
(40) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci,
B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H.
P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.;
Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.;
Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.;
Montgomery, J. A., Jr.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.;
Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Kobayashi,
R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar,
S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, J. M.; Klene, M.; Knox,
J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.;
Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.;
Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.;
Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A.
(23) (a) Becke, A. D. Density functional thermochemistry. III. The
role of exact exchange. J. Chem. Phys. 1993, 98, 5648−5652. (b) Lee,
C.; Yang, W.; Parr, R. G. Development of the Colle-Salvetti
correlation-energy formula into a functional of the electron density.
Phys. Rev. B: Condens. Matter Mater. Phys. 1988, 37, 785−789.
(24) Godbout, N.; Salahub, D. R.; Andzelm, J.; Wimmer, E.
Optimization of Gaussian-type basis sets for local spin density
functional calculations. Part I. Boron through neon, optimization
technique and validation. Can. J. Chem. 1992, 70, 560−571.
(25) (a) Peterson, K. A.; Figgen, D.; Dolg, M.; Stoll, H. Energy-
consistent relativistic pseudopotentials and correlation consistent
basis sets for the 4d elements Y-Pd. J. Chem. Phys. 2007, 126, 124101.
(b) Figgen, D.; Peterson, K. A.; Dolg, M.; Stoll, H. Energy-consistent
pseudopotentials and correlation consistent basis sets for the 5d
elements Hf-Pt. J. Chem. Phys. 2009, 130, 164108.
̈
D.; Farkas, O.; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J.
Gaussian 09, Revision B.1, Gaussian, Inc: Wallingford, CT, 2009.
(41) Tomasi, J.; Mennucci, B.; Cammi, R. Quantum mechanical
continuum solvation models. Chem. Rev. 2005, 105, 2999−3093.
(26) (a) Stambuli, J. P.; Buhl, M.; Hartwig, J. F. Synthesis,
̈
characterization, and reactivity of monomeric arylpalladium halide
complexes with a hindered phosphine as the only dative ligand. J. Am.
Chem. Soc. 2002, 124, 9346−9347. (b) Stambuli, J. P.; Incarvito, C.
(42) Klamt, A.; Schuurmann, G. COSMO: A New Approach to
̈ ̈
Dielectric Screening in Solvents with Explicit Expressions for the
Screening Energy and its Gradient. J. Chem. Soc., Perkin Trans. 2 1993,
2, 799−805.
D.; Buhl, M.; Hartwig, J. F. Synthesis, structure, theoretical studies,
̈
and ligand exchange reactions of monomeric, T-shaped arylpalladium-
(II) halide complexes with an additional, weak agostic interaction. J.
Am. Chem. Soc. 2004, 126, 1184−1194. (c) Chen, L.; Francis, H.;
Carrow, B. P. An “On-Cycle” Precatalyst Enables Room-Temperature
Polyfluoroarylation Using Sensitive Boronic Acids. ACS Catal. 2018,
8, 2989−2994. (d) Chen, L.; Sanchez, D. R.; Zhang, B.; Carrow, B. P.
Cationic” Suzuki-Miyaura Coupling with Acutely Base-Sensitive
Boronic Acids. J. Am. Chem. Soc. 2017, 139, 12418−12421.
(27) King, R. B.; Cloyd, J. C., Jr.; Reimann, R. H. Poly(tertiary
phosphines and arsines). XIII. Some neopentyl poly(tertiary
phosphines). J. Org. Chem. 1976, 41, 972−977.
(43) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
Robb, M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.;
Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.;
Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.;
Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.;
Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao,
O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J.
B.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev,
O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P.
Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.;
Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas,
O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.;
Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.;
Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.;
Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.;
Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen,
W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian 03, Revision
E.01; Gaussian Inc: Wallingford, CT, 2004.
(28) Li, H.; Grasa, G. A.; Colacot, T. J. A Highly Efficient, Practical,
and General Route for the Synthesis of (R3P)2Pd(0): Structural
Evidence on the Reduction Mechanism of Pd(II) to Pd(0). Org. Lett.
2010, 12, 3332−3335.
(29) Pan, Y.; Young, G. B. Syntheses and spectroscopic character-
istics of dialkylpalladium(II) complexes; PdR2(cod) as precursors for
derivatives with N- or P-donor ligands. J. Organomet. Chem. 1999,
577, 257−264.
(44) Grimme, S.; Ehrlich, S.; Goerigk, L. Effect of the Damping
Function in Dispersion Corrected Density Functional Theory. J.
Comput. Chem. 2011, 32, 1456−1465.
(30) Saint Plus, 8.34A; Bruker AXS Inc.: Madison, WI, 2007.
̈
(31) (a) Sheldrick, G. M. SHELXTL, v. 2008; Gottingen University:
̈
Gottingen, Germany, 2008. (b) Sheldrick, G. M. A short history of
(45) Becke, A. D. Density-functional thermochemistry. V. Systematic
optimization of exchange-correlation functionals. J. Chem. Phys. 1997,
107, 8554−8560.
SHELX. Acta Crystallogr., Sect. A: Found. Crystallogr. 2008, A64, 112−
122.
̈
(32) Sheldrick, G. M. SHELXL, 2014/7; Gottingen University:
(46) Dunning, T. H., Jr. Gaussian basis sets for use in correlated
molecular calculations. I. The atoms boron through neon and
hydrogen. J. Chem. Phys. 1989, 90, 1007−1024.
̈
Gottingen, Germany, 2014.
(33) Hubschle, C. B.; Sheldrick, G. M.; Dittrich, B. ShelXle: a Qt
̈
graphical user interface for SHELXL. J. Appl. Crystallogr. 2011, 44,
1281−1284.
(34) CrysAlis Pro Software System, V1.171.40.53; Rigaku Oxford
Diffraction, 2019.
(47) Kendall, R. A.; Dunning, T. H., Jr.; Harrison, R. J. Electron
affinities of the first-row atoms revisited. Systematic basis sets and
wave functions. J. Chem. Phys. 1992, 96, 6796−6806.
(48) Peterson, K. A. Systematically convergent basis sets with
relativistic pseudopotentials. I. Correlation consistent basis sets for the
post-d group 13−15 elements. J. Chem. Phys. 2003, 119, 11099−
11112.
(35) Sheldrick, G. M. SHELXT - Integrated space-group and crystal-
structure determination. Acta Crystallogr., Sect. A: Found. Adv. 2015,
71, 3−8.
(36) Sheldrick, G. M. Crystal structure refinement with ShelXL. Acta
Crystallogr., Sect. C: Struct. Chem. 2015, 71, 3−8.
(37) Dolomanov, O. V.; Bourhis, L. J.; Gildea, R. J.; Howard, J. A.
K.; Puschmann, H. OLEX2: a complete structure solution, refinement
and analysis program. J. Appl. Crystallogr. 2009, 42, 339−341.
(38) Zhao, Y.; Truhlar, D. G. The M06 suite of density functionals
for main group thermochemistry, thermochemical kinetics, non-
covalent interactions, excited states, and transition elements: two new
(49) Peterson, K. A.; Figgen, D.; Goll, E.; Stoll, H.; Dolg, M.
Systematically convergent basis sets with relativistic pseudopotentials.
II. Small-core pseudopotentials and correlation consistent basis sets
for the post-d group 16−18 elements. J. Chem. Phys. 2003, 119,
11113−11123.
(50) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Petersson,
G. A.; Nakatsuji, H.; Li, X.; Caricato, M.; Marenich, A. V.; Bloino, J.;
N
DOI: 10.1021/acs.inorgchem.9b02164
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Article
Janesko, B. G.; Gomperts, R.; Mennucci, B.; Hratchian, H. P.; Ortiz, J.
V.; Izmaylov, A. F.; Sonnenberg, J. L.; Williams-Young, D.; Ding, F.;
Lipparini, F.; Egidi, F.; Goings, J.; Peng, B.; Petrone, A.; Henderson,
T.; Ranasinghe, D.; Zakrzewski, V. G.; Gao, J.; Rega, N.; Zheng, G.;
Liang, W.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.;
Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.;
Throssell, K.; Montgomery, J. A., Jr.; Peralta, J. E.; Ogliaro, F.;
Bearpark, M. J.; Heyd, J. J.; Brothers, E. N.; Kudin, K. N.; Staroverov,
V. N.; Keith, T. A.; Kobayashi, R.; Normand, J.; Raghavachari, K.;
Rendell, A. P.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.;
Millam, J. M.; Klene, M.; Adamo, C.; Cammi, R.; Ochterski, J. W.;
Martin, R. L.; Morokuma, K.; Farkas, O.; Foresman, J. B.; Fox, D. J.
Gaussian 16, revision A.03; Gaussian, Inc: Wllingford, CT, 2016.
O
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