A broadly applicable strategy for entry into homogeneous nickel(0) catalysts from air-stable nickel(II) complexes

Article abstract of DOI:10.1021/om500156q

A series of air-stable nickel complexes of the form L₂Ni(aryl) X (L = monodentate phosphine, X = Cl, Br) and LNi(aryl)X (L = bis-phosphine) have been synthesized and are presented as a library of precatalysts suitable for a wide variety of nickel-catalyzed transformations. These complexes are easily synthesized from low-cost NiCl₂·6H₂O or NiBr ₂·3H₂O and the desired ligand followed by addition of 1 equiv of Grignard reagent. A selection of these complexes were characterized by single-crystal X-ray diffraction, and an analysis of their structural features is provided. A case study of their use as precatalysts for the nickel-catalyzed carbonyl-ene reaction is presented, showing superior reactivity in comparison to reactions using Ni(cod)₂. Furthermore, as the precatalysts are all stable to air, no glovebox or inert-atmosphere techniques are required to make use of these complexes for nickel-catalyzed reactions.

Full text of DOI:10.1021/om500156q

Article
pubs.acs.org/Organometallics
A Broadly Applicable Strategy for Entry into Homogeneous Nickel(0)
Catalysts from Air-Stable Nickel(II) Complexes
Eric A. Standley, Stacey J. Smith,† Peter Muller, and Timothy F. Jamison*
̈
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
S
* Supporting Information
ABSTRACT: A series of air-stable nickel complexes of the
form L2Ni(aryl) X (L = monodentate phosphine, X = Cl, Br)
and LNi(aryl)X (L = bis-phosphine) have been synthesized
and are presented as a library of precatalysts suitable for a wide
variety of nickel-catalyzed transformations. These complexes
are easily synthesized from low-cost NiCl2·6H2O or NiBr2·
3H2O and the desired ligand followed by addition of 1 equiv of
Grignard reagent. A selection of these complexes were
characterized by single-crystal X-ray diffraction, and an analysis
of their structural features is provided. A case study of their use
as precatalysts for the nickel-catalyzed carbonyl-ene reaction is presented, showing superior reactivity in comparison to reactions
using Ni(cod)2. Furthermore, as the precatalysts are all stable to air, no glovebox or inert-atmosphere techniques are required to
make use of these complexes for nickel-catalyzed reactions.
the fact that a high catalyst loading of nickel is often required
(5−20 mol %), there is little economic incentive to use nickel
in place of precious metals such as palladium unless cheaper
sources of nickel can be used. Regardless of cost and ease of use
issues, however, any comparison between nickel and precious
metals (particularly palladium) should recognize that nickel has
demonstrated valuable and unique reactivity and behavior,
which enables an entirely different set of chemical trans-
formations.1
The use of precatalysts in transition-metal catalysis is not a
new idea: indeed, Pd(OAc)2 has been in use as a precursor to
Pd(0) species for close to 50 years,3 though the concept of the
single-component, discrete precatalyst is a somewhat newer
development.4 Several groups (Nolan,5 Buchwald,6 Organ,7 and
others) have greatly advanced the ubiquity of precatalysts in
organic synthesis, with much of the effort focused on palladium
catalysts for cross couplings, amination, and related trans-
formations.8 Likewise, though by far less established than those
for palladium-catalyzed reactions, single-component nickel
precatalysts are not new, with the most frequently employed
being complexes such as (PPh3)2NiCl2.9 Though air stable,
these precatalysts are usually limited to activation by
nucleophilic organometallic reagents, and as such, they must
often be preactivated by addition of an exogenous reductant.10
Such a strategy has been shown to be effective in many
instances but is neither an ideal nor a universal solution.
Complexes such as trans-(PPh3)2Ni(1-naphthyl)Cl have
been known to be air-stable since 1960, when they were first
reported by Chatt and Shaw,11 but these complexes were not
INTRODUCTION
■
Homogeneous nickel catalysis has continued to develop in
recent years as a powerful set of tools for the construction of a
wide variety of carbon−carbon and carbon−heteroatom
bonds.1 Nickel, a base metal, is a low-cost, versatile, and
attractive metal for use in catalytic transformations. Arguably
the greatest barrier to the wider adoption of homogeneous
nickel catalysis for synthesis, however, is the difficulty and cost
of synthesizing and handling nickel(0) sources and the
phosphines often used in conjunction with such complexes. It
is for this reason we aim to further develop nickel(II)-based
precatalysts, as this would greatly increase the accessibility of
homogeneous nickel catalysis in both academic as well as
industrial settings.
Ideally, these precatalysts would (1) be indefinitely air stable,
(2) have a low molecular weight, (3) be highly active, (4) be
simple to synthesize from low-cost materials, (5) be readily
activated under a variety of conditions without producing
interfering byproducts of activation, and (6) be applicable to
virtually any nickel-catalyzed transformation. Precatalysts
possessing many or all of these qualities would greatly add to
the value of new as well as previously established nickel-
catalyzed transformations.
Although nickel metal itself is extremely low in cost (∼15
USD/kg at commodity prices), the cost of nickel(0) sources
such as Ni(cod)2 (cod = 1,5-cyclooctadiene) easily exceeds
20000 USD/kg, which often weakens the economic argument
for using nickel in catalytic transformations. Indeed, Ni(cod)2 is
only marginally less expensive than comparable palladium(0)
sources such as Pd2(dba)3 (dba = dibenzylideneacetone) on a
mole-for-mole basis, despite the fact that palladium metal is far
more expensive than nickel metal.2 Taken in conjunction with
Received: February 12, 2014
Published: April 16, 2014
© 2014 American Chemical Society
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Article
utilized in catalytic transformations until many years later.
Relatively few phosphine ligands have been used to prepare
such complexes for use in catalysis,12−14 although several new
types of nickel precatalysts with varying degrees of air stability
have also been developed in the past few years.15
reactions with air ranging from vigorous to violent, yet the
precatalysts derived from each of these ligands are completely
stable to oxygen in the solid phase and can be stored in air
indefinitely.
In some instances, the complexes containing the o-tolyl
moiety were not adequately stable to allow isolation in good
yield and/or did not form air-stable complexes. For example,
trans-(PEt3)2Ni(o-tolyl)Cl can be isolated in good yield
(>90%); however, upon standing in air for several days, it
begins to show clear signs of decomposition. A solution to this
problem was found by increasing the steric bulk of the aryl
group on nickel, which is hypothesized to further shield nickel
from associative substitution.
To synthesize these complexes with more substituted aryl
groups, the phosphine was condensed with NiBr2·3H2O to
yield the corresponding L2NiBr2 complex, which was then
treated with commercially available 2-mesitylmagnesium bro-
mide.18 In this way, several complexes which had proven elusive
could be synthesized to form stable precatalysts. In the case of
tri-n-butylphosphine, trans-(Pn-Bu3)2Ni(o-tolyl)Cl was found
to be a liquid at room temperature that could not be stored for
more than a few days, whereas trans-(Pn-Bu3)2Ni(2-mesityl)Br
(11) is an indefinitely stable solid.
Additionally, [dppp]Ni(o-tolyl)Cl and [dppb]Ni(o-tolyl)Cl
are difficult to synthesize in good yield and purity using this
method. In both instances, the addition of another 1 equiv of o-
tolylmagnesium chloride takes place very readily (which lowers
the yield and purity of the isolated product) and neither
complex is very stable to methanol, leading to a loss of yield
during workup and purification. In both instances, however,
changing the aryl group to a mesityl group solved this problem,
allowing isolation of cis-[dppp]Ni(2-mesityl)Br (13) and trans-
[dppb]Ni(2-mesityl)Br (14). It should be noted, however, that
the complexes containing the o-tolyl ligand can be synthesized
by metathesis starting from trans-(PPh3)2Ni(o-tolyl)Cl (1),
indicating they are indeed stable complexes.13b
During the development of trans-(PCy2Ph)2Ni(o-tolyl)Cl for
use in the coupling reaction of benzyl chlorides with alkenes,16
it became apparent that such complexes could be used for
numerous nickel-catalyzed transformations, since these pre-
catalysts can be activated by nucleophilic reagents (RMgX,
RZnX, R3B, R3SiHby a transmetalation/reductive elimina-
tion sequence) as well as electrophilic reagents (R3SiOTfby a
Lewis acid induced Ni to Ni transmetalation followed by
reductive elimination of a biaryl). Members of this class have
been shown to possess significantly enhanced catalytic activity
in comparison to the combination of Ni(cod)2 and the
corresponding phosphine ligand due to the absence of cod,
which is known to hinder catalysis in some instances.17
RESULTS AND DISCUSSION
Synthesis of the precatalyst complexes is straightforward (see
Scheme 1): NiCl2·6H2O and the desired mono- or bidentate
■
a
Scheme 1. Synthesis of Precatalysts
a
X = Cl, Br. R = alkyl, aryl.
Unfortunately, the switch from o-tolyl to 2-mesityl did not
enable isolation of a stable complex in one instance: PMe2Ph.
Neither the o-tolyl nor the 2-mesityl complexes were stable
under ambient conditions or in the presence of alcohols.
Because PMe2Ph represents the least sterically demanding
phosphine used in this study, it is perhaps unsurprising that its
complex is in turn the most sensitive to nucleophilic attack by
water or alcohols, since nickel is less shielded. As before,
increasing the steric hindrance around nickel provided the
solution. Reaction of trans-(PMe2Ph)2NiBr2 with 2,4,6-
triisopropylphenylmagnesium bromide19 gave trans-
(PMe2Ph)2Ni(2,4,6-triisopropylphenyl)Br (8) in 83% yield.
This complex, in stark contrast to the corresponding o-tolyl and
2-mesityl complexes, demonstrates absolutely no air or water
sensitivity.
However, due to the concern that activation of this
precatalyst may be slow because of the extreme hindrance
provided by the isopropyl groups at the 2- and 6-positions of
the aryl ring, a precatalyst incorporating a 2,6-dimethoxyphenyl
substituent (9) was also prepared and found to be air stable.
As the numerous entries in Table 1 demonstrate, complexes
of this type can be made from a wide range of phosphines,
including electron-rich and electron-poor as well as sterically
demanding and undemanding phosphines. However, a number
of phosphines were not able to be successfully incorporated
into these types of complexes. Those ligands fall into two
categories: electron-poor and sterically hindered (P(4-F-
phosphine are combined in ethanol and briefly refluxed, after
which the L2NiCl2 complex is isolated by a simple vacuum
filtration on a sintered-glass frit. After it is dried under vacuum
to remove residual solvent, the complex is redissolved in THF
or CH2Cl2 and 1 equiv of Grignard reagent (o-tolylmagnesium
chloride, 2-mesitylmagnesium bromide, or similar) is added.
Removal of the solvent by rotary evaporation and addition of
methanol precipitates the complex and dissolves the
magnesium chloride or bromide; isolation by vacuum filtration
on a glass frit followed by washing with the appropriate solvent
yields the complex. No further purification of the powder
obtained this way is necessary, though recrystallization can be
carried out if desired.
At present, we have prepared more than 20 such complexes,
with the most significant examples shown in Table 1. The
selection of ligands is intended to encompass a variety of mono-
and bidentate phosphines commonly used in organic synthesis,
as well as a number of less frequently employed ligands. Many
of the ligands in the latter category, particularly the low-
molecular-weight, liquid phosphines, find less frequent use in
organic synthesis at least in part because they are difficult to
synthesize and handle safely and because they are expensive to
purchase due to the high cost of shipping pyrophoric and/or
highly flammable goods. Triethylphosphine (10), dimethylphe-
nylphosphine (8, 9), tricyclopentylphosphine (5), tri-n-
butylphosphine (11), and tribenzylphosphine (6) all undergo
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a
Table 1. Nickel Phosphine Complexes Synthesized
isolated yield (%)
LnNi(R)X
compd
ligand
geometry
R
X
LnNiX2
overall
Monodentate Ligands
1
PPh3
trans
trans
trans
trans
trans
trans
trans
trans
trans
trans
trans
o-tolyl
o-tolyl
o-tolyl
o-tolyl
o-tolyl
o-tolyl
o-tolyl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Br
Br
Br
91
92
95
97
99
96
99
95
95
95
89
89
81
88
87
90
90
81
83
87
88
90
81
75
84
84
89
86
80
79
83
84
80
2
PCyPh2
PCy2Ph
PCy3
3
4
5
PCyp3
6
PBn3
7
PPh2Me
PMe2Ph
PMe2Ph
PEt3
8
2,4,6-triisopropylphenyl
2,6-dimethoxyphenyl
2-mesityl
9
10
11
P(n-Bu)3
2-mesityl
Bidentate Ligands
12
13
14
15
16
17
18
19
dppe
cis
o-tolyl
Cl
Br
Br
Cl
Cl
Cl
Cl
Cl
98
89
96
94
97
98
86
90
84
85
86
97
95
83
92
82
82
76
83
91
92
81
79
74
dppp
cis
2-mesityl
2-mesityl
o-tolyl
dppb
trans
cis
(S)-BINAP
dppf
cis
o-tolyl
dcpf
trans
trans
cis
o-tolyl
Xantphos
pyphos
o-tolyl
o-tolyl
a
Abbreviations: dppe, 1,2-bis(diphenylphosphino)ethane; dppp, 1,3-bis(diphenylphosphino)propane; dppb, 1,4-bis(diphenylphosphino)butane;
BINAP, 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl; dppf, 1,1′-bis(diphenylphosphino)ferrocene; dcpf, 1,1′-bis(dicyclohexylphosphino)ferrocene;
Xantphos, 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene; pyphos, 2-[2-(diphenylphosphino)ethyl]pyridine.
Figure 1. Complexes analyzed by single-crystal X-ray diffraction. Thermal ellipsoids are drawn at the 50% probability level, and hydrogen atoms are
not included. Disorder of the o-tolyl ligand (6, 15, 18, 19) and solvent molecules of crystallization (6, 15, 17, 18) are not shown.
C6H4)3, P(o-tol)3, and P(o-anis)3) and extremely sterically
hindered phosphines, regardless of their electronic nature (P(t-
Bu)3,20 (9,9-dimethyl-9H-xanthene-4,5-diylbis(di-tert-butyl-
phosphine)), and 1,2-bis((di-tert-butylphosphino)methyl)-
benzene). In all instances the L2NiX2 or LNiX2 complexes
did not form, precluding attempts to synthesize the
corresponding arylnickel complexes by this synthetic route.
Although our principal interest in these complexes is their
catalytic activity, it is also important to understand their
structural features, geometry, and bonding, as this may afford
deeper insight that would enable further development of new
complexes, types of precatalysts, or alternative modes of
activation.
The complexes strongly favor a square-planar arrangement,
and whether the two phosphorus atoms are in a cis or trans
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a
Table 2. Screening of the Ni-Catalyzed Carbonyl-Ene Reaction
b
yield (%)
entry
ligand
Ni source
20
21
combined
20:21
1
2
3
4
5
6
PPh3
Ni(cod)2
6
7
78
81
21
20
56
2
84
88
73
74
73
20
7:93
PPh3
1
8:92
PCy2Ph
PCy2Ph
PCyPh2
PCy3
Ni(cod)2
52
54
17
18
71:29
73:27
23:77
90:10
3
2
4
a
See the Supporting Information for complete data for all complexes. Reactions were carried out on a 0.50 mmol scale with 20 mol % of catalyst and
b
run for 48 h. Yields determined by gas chromatography calibrated against an internal standard of n-dodecane.
arrangement at nickel is readily discerned from inspection of
each complex’s 31P NMR spectrum. Complexes derived from
monodentate phosphines were universally found to adopt a
trans geometry, as indicated by the presence of only one singlet
in the 31P NMR spectrum. This arrangement presumably
results from the minimization of steric interaction between the
ligands on nickel, and the magnitude of the steric repulsion is
evidently large enough to overwhelm any thermodynamic trans
effects that might favor a cis arrangement.21
angles are 91.264(13) and 91.642(13)°, very close to the ideal
90° for a square plane. Because of this, it is appropriate to
describe the two phosphorus atoms as trans to one another.
Complex 18 (derived from Xantphos) adopts a distorted-
square-pyramidal geometry in the solid state. The oxygen atom
of the ligand occupies the apical position and the two
phosphorus atoms are in equatorial positions trans to each
1
other. In solution, two isomers are observed by H and 31P
NMR, the second perhaps being the true square-planar isomer,
Conversely, complexes derived from bidentate phosphines
were more often observed to adopt a cis arrangement, but
several counterexamples were also seen. The preferred
arrangement appears to depend on the bite angle of the ligand,
its rigidity, and the identity of the substituents on phosphorus.
For example, the complex derived from dppf (16) exists only
as the cis, square planar isomer in solution, whereas the closely
related dcpf (17) adopts a distorted trans, square planar
geometry, as illustrated in its single-crystal X-ray structure and
in its 31P NMR spectrum. In this instance, the change from
phenyl groups to cyclohexyl groups on phosphorus is enough
to alter the preferred geometry, despite the fact that both
complexes are built on the same ferrocene scaffold.
A selection of these precatalysts have been characterized by
single-crystal X-ray diffraction (Figure 1). Crystal structures
were determined following established procedures,22 and
complete details are given in the Supporting Information.
Complexes derived from PBn3 and PMe2Ph both adopt nearly
ideal trans, square planar structures and are, for the most part,
structurally unremarkable. Complex 15 (derived from (S)-
BINAP) adopts a nearly ideal square planar structure with a cis
arrangement, yielding a dihedral angle of 73.24(3)° between
the two naphthalene rings of BINAP. The most interesting
feature of this complex, though, is the fact that it forms
diastereomers due to the two possible arrangements of the o-
tolyl group. These diasteromers are both crystallographically
and spectroscopically (1H and 31P NMR) observable,
suggesting that interconversion is either slow or does not
take place at any appreciable rate near room temperature.
The complex derived from dcpf (17) is another interesting
case: its 31P NMR spectrum exhibits one singlet, despite the
fact that it is a bidentate phosphine. XRD analysis showed a
geometry at nickel that is best described as square planar, but
with significant distortion toward tetrahedral.23 For example,
the P(1)−Ni−P(2) bond angle is ca. 145°, well shy of the ideal
180°. However, the P(1)−Ni−Cl and P(2)−Ni−Cl bond
without oxygen coordinated at nickel.
Pyphos (19), being an unsymmetrical, bidentate ligand, can
form at least two structural isomerschloride could be trans to
either phosphorus or to nitrogen. The 31P NMR spectrum
shows only one, sharp singlet, which suggests that one isomer is
dominant in solution. Single-crystal X-ray diffraction analysis
showed 19 to adopt a square-planar structure with chlorine
trans to phosphorus. This geometrical arrangement presumably
indicates that the thermodynamic trans effect dominates the
ground-state conformation, rather than any potential steric
interaction between the diphenylphosphino moiety and the o-
tolyl ligand.
To demonstrate the utility and advantages these precatalysts
present over other means of entry into nickel(0), we have used
the nickel-catalyzed carbonyl-ene reaction, which couples a
terminal alkene (or ethylene), an aldehyde, and a silyl triflate to
form allylic or homoallyic silyl ethers (Table 2).24 Preliminary
experiments demonstrated that catalysts 3 and 1 were indeed
catalytically competent and provided the desired allylic (20)
and homoallylic (21) products, respectively. In both instances,
the selectivity and yields were observed to be comparable to
those of reactions using Ni(cod)2. However, the rate was
observed to be higher than when cod is presentfollowing
studies demonstrated that the reaction reaches completion in
ca. 18 h, rather than the 36−48 h required when using Ni(cod)2
as the nickel source.
A comprehensive screen of precatalysts 1−19 was carried out
to demonstrate the ease with which screening of ligands can be
accomplished (abbreviated results are shown in Table 2; see the
Supporting Information for complete data). The use of these
single-component, air-stable precatalysts reduces the effort
involved to an exercise which can be carried out on the
benchtop with no exclusion of air during setup of the reactions.
This approach, while convenient, may however not be
applicable in all instances, as it is necessary to have already
synthesized the desired precatalysts. For researchers frequently
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LnNi(aryl)X. LnNiX2 was placed in an oven-dried round-bottom flask
containing a magnetic stir bar. Solvent (THF or CH2Cl2) was added,
the solution was cooled to 0 °C with an ice bath, and Grignard reagent
was added dropwise with vigorous stirring. The solution was stirred for
15 min at 0 °C, after which the stir bar was removed and the solution
was evaporated to dryness under reduced pressure. MeOH was added,
and the mixture was sonicated until a uniform suspension was
obtained (approximately 5 min). After the suspension was cooled to 0
°C, the precipitate was collected by vacuum filtration, washed with two
portions of cold MeOH, and dried under high vacuum to yield the
complex.
Representative Syntheses. (PMePh2)2NiCl2. NiCl2·6H2O (17.42
mmol, 4.141 g), EtOH (55 mL), and a magnetic stir bar were placed in
a 100 mL round-bottom flask. The flask was sealed with a rubber
septum, the solution was sparged with nitrogen for 15 min, and then
PPh2Me (38.32 mmol, 7.672 g, 7.13 mL) was added portionwise over
5 min. The flask was equipped with a reflux condenser, and the
mixture was heated to 80 °C for 30 min then cooled to room
temperature. Once cool, the flask was chilled to 0 °C for 10 min, after
which the solid was collected by vacuum filtration and washed twice
with ethanol (5 mL). Drying under vacuum yielded S7 (9.111 g, 99%)
as a deep maroon, crystalline solid.
involved in screening of nickel-catalyzed reactions, however,
such an approach could be valuable.
CONCLUSION
■
In summary, we have synthesized and characterized 19 air-
stable Ni(II) complexes derived from a range of mono- and
bidentate phosphine ligands commonly used in synthesis.
These complexes are accessed from low-cost NiCl2·6H2O
rather than from an expensive and air-sensitive Ni(0) source
such as Ni(cod)2. These complexes can function as precatalysts
for a range of nickel-catalyzed reactions, as they are readily
converted to Ni(0) phosphine complexes by treatment with
reagents such as RMgX, RZnX, R3B, RLi, R3SiH, and R3SiOTf
among others, allowing their convenient use in Ni(0)-catalyzed
reactions. Many of these reactions, which previously employed
Ni(cod)2 as the Ni(0) source and thus required the use of a
glovebox or glovebag, can now be carried out with no exclusion
of air or water during setup, which greatly facilitates the use of
nickel catalysis as a tool for synthesis. These benefits have been
demonstrated in the context of the nickel-catalyzed carbonyl-
ene reaction, where the use of a precatalyst provided a
significant rate enhancement for the target reaction while
maintaining selectivity equivalent to that of reactions catalyzed
by Ni(cod)2.
trans-(PMePh2)2Ni(2-MePh)Cl (7). (PMePh2)2NiCl2 (8.29 mmol,
4.394 g) was placed in an oven-dried, 100 mL round-bottom flask
containing a magnetic stir bar. THF (55 mL) was added, the solution
was cooled to 0 °C with an ice bath, and o-tolylmagnesium chloride
(8.29 mmol, 0.856 M in THF, 9.68 mL) was added dropwise with
vigorous stirring. Near the end of the addition, the solution began to
turn orange. The solution was stirred for 15 min at 0 °C, after which
the stir bar was removed and the solution was evaporated to dryness
under reduced pressure. MeOH (25 mL) was added, and the mixture
was sonicated until a uniform suspension was obtained (approximately
2 min). After the suspension was cooled to 0 °C, the bright yellow
precipitate was collected by vacuum filtration, washed with two
portions of cold MeOH (10 mL), and dried under high vacuum to
yield 7 (3.940 g, 81%)25 as a fine, bright yellow powder. Mp: 139−140
°C dec. Anal. Calcd for C33H33ClNiP2: C, 67.67; H, 5.68. Found: C,
EXPERIMENTAL SECTION
■
General Considerations. Dichloromethane, THF, and acetoni-
trile were degassed by sparging with nitrogen and dried by passage
through a column of activated alumina. Ethanol (200 proof, <0.1%
water) and n-butanol (99.9%) were roughly degassed by sparging with
nitrogen and were not further dried prior to use. Methanol (>99.8%,
<0.1% water) was used as received. Manipulation of all air-sensitive
reagents was carried out in a glovebox filled with dry nitrogen. Bis(1,5-
cyclooctadiene)nickel(0) was purchased from Strem Chemicals
(Newburyport, MA) and stored at −30 °C in a glovebox. All other
chemicals were purchased from Sigma-Aldrich (Milwaukee, WI), Alfa
Aesar (Ward Hill, MA), TCI America (Portland, OR), or Oakwood
Products, Inc. (West Columbia, SC).
1
67.41; H, 5.78. H NMR (500 MHz, C6D6, δ): 7.84 (br s, 4H), 7.62
(br s, 4H), 7.12−6.94 (m, 13H), 6.72−6.64 (m, 1H), 6.64−6.53 (m,
2H), 2.75 (s, 3H), 1.08 (s, 6H). 31P{1H} NMR (121 MHz, C6D6, δ):
8.32. 13C{1H} NMR (126 MHz, C6D6, δ): 153.09 (t, J = 33.7 Hz),
143.27, 136.02 (t, J = 3.8 Hz), 134.99 (t, J = 20.3 Hz), 133.84 (t, J =
5.2 Hz), 133.46 (t, J = 20.8 Hz), 133.26 (t, J = 5.4 Hz), 129.79, 129.56,
124.03, 122.55, 26.56, 12.94 (t, J = 15.7 Hz). IR (ATR, cm−1): 3051
(w), 1570 (w), 1561 (w), 1484 (w), 1434 (m), 1372 (w), 1335 (w),
1309 (w), 1285 (w), 1186 (w), 1160 (w), 1098 (m), 1074 (w), 1027
(w), 1012 (w), 999 (w), 895 (m), 887 (s), 878 (s), 850 (w), 740 (s),
729 s), 692 (s).
[dppe]NiCl2. NiCl2·6H2O (9.6 mmol, 2.282 g), EtOH (30 mL), and
a magnetic stir bar were placed in a 50 mL round-bottom flask. The
flask was sealed with a rubber septum, the solution was sparged with
nitrogen for 15 min, the septum was removed, and then dppe (9.66
mmol, 3.849 g) was added in one portion. The flask was fitted with a
reflux condenser, and the mixture was heated to 80 °C for 30 min and
then cooled to room temperature. Once cool, the flask was chilled to 0
°C for 10 min, after which the solid was collected by vacuum filtration
and washed twice with ethanol (5 mL). Drying under vacuum yielded
S12 (4.956 g, 98%) as a fine, orange powder.
cis-[dppe]Ni(2-MePh)Cl (12). [dppe]NiCl2 (3.92 mmol, 2.07 g) was
placed in an oven-dried, 250 mL round-bottom flask containing a
magnetic stir bar. THF (200 mL) was added, the mixture was cooled
to 0 °C with an ice bath, and o-tolylmagnesium chloride (3.92 mmol,
0.986 M in THF, 3.98 mL) was added dropwise with vigorous stirring.
Partway through the addition, the solution became completely
homogeneous and began to turn yellow. After complete addition of
the Grignard reagent, the solution was stirred for 15 min at 0 °C, after
which the stir bar was removed and the solution was evaporated to
dryness under reduced pressure. MeOH (20 mL) was added, and the
mixture was sonicated until a uniform suspension was obtained
(approximately 5 min). After the suspension was cooled to 0 °C, the
Melting points were determined on an electrothermal apparatus
using glass capillaries open to air except where specified. The material
used for the determinations was not recrystallized but was ground to a
fine powder using a metal spatula before analysis.
NMR spectra were obtained in CDCl3 (99.8% atom D), C6D6
(99.5% atom D), or CD2Cl2 (99.9% atom D) purchased from
1
Cambridge Isotope Laboratories (Andover, MA). H NMR spectra
were obtained at either 300 or 500 MHz, 13C spectra were recorded at
126 MHz with 1H decoupling, and 31P spectra were recorded at 121 or
202 MHz with 1H decoupling. Chemical shifts (1H and 13C) are
reported in parts per million relative to TMS (δ = 0.00 ppm) and were
referenced to the residual solvent peak (1H, CDCl3 7.26 ppm, C6D6
7.16 ppm, CD2Cl2 5.32 ppm; 13C, CDCl3 77.16 ppm, C6D6 128.06
ppm, CD2Cl2 53.84 ppm); 31P NMR spectra are reported in parts per
million relative to an external standard of 85% phosphoric acid (δ 0.00
ppm). The following designations are used to describe multiplicities: s
(singlet), d (doublet), t (triplet), q (quartet), br (broad), app
(apparent).
General Procedure. LnNiX2. NiCl2·6H2O or NiBr2·3H2O, EtOH,
and a magnetic stir bar were placed in a round-bottom flask. The flask
was sealed with a rubber septum, the solution was sparged with
nitrogen for 15 min, the septum was removed, and then the phosphine
was added in one portion. The flask was fitted with a reflux condenser,
and the mixture was heated to 80 °C for 30 min and then cooled to
room temperature. Once cool, the flask was chilled to 0 °C for 10 min,
after which the solid was collected by vacuum filtration and washed
twice with ethanol (and twice with ether in some instances). Drying
under vacuum yielded the product.
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dx.doi.org/10.1021/om500156q | Organometallics 2014, 33, 2012−2018

Organometallics
Article
yellow precipitate was collected by vacuum filtration, washed with two
portions of cold MeOH (5 mL), and dried under high vacuum to yield
12 (1.92 g, 84%) as a fine, bright yellow powder. Mp: 190−192 °C
dec. Anal. Calcd for C33H31ClNiP2: C, 67.90; H, 5.35. Found: C,
Pd2(dba)3 as a result of the reagents required for their synthesis, yield
of the reaction, and cost of purification.
(3) Stephenson, T. A.; Morehouse, S. M.; Powell, A. R.; Heffer, J. P.;
Wilkinson, G. J. Chem. Soc. 1965, 3632−3640.
(4) For reviews of palladacycles in synthesis from 2001 and earlier,
1
68.28; H, 5.66. H NMR (500 MHz, CD2Cl2, δ): 8.16 (dd, J = 10.9,
7.3 Hz, 4H), 7.77 (ddd, J = 9.2, 7.1, 1.8 Hz, 2H), 7.62−7.41 (m, 9H),
7.31 (t, J = 7.1 Hz, 1H), 7.20 (dt, J = 8.4, 4.7 Hz, 1H), 7.07 (td, J = 7.7,
2.6 Hz, 2H), 6.71 (dd, J = 10.8, 7.6 Hz, 2H), 6.59 (dd, J = 6.0, 2.9 Hz,
2H), 6.45−6.39 (m, 1H), 2.58−2.34 (m, 2H), 2.34−2.09 (m, 4H),
1.60 (tdd, J = 14.4, 11.7, 6.7 Hz, 1H). 31P{1H} NMR (121 MHz,
CD2Cl2, δ): 53.09 (d, J = 17.9 Hz), 35.78 (d, J = 17.8 Hz). 13C{1H}
NMR (126 MHz, CD2Cl2, δ): 158.03 (dd, J = 86.1, 38.5 Hz), 143.71
(t, J = 2.0 Hz), 136.17 (dd, J = 3.1, 1.7 Hz), 134.97 (d, J = 11.2 Hz),
134.08 (d, J = 11.2 Hz), 133.14 (d, J = 10.3 Hz), 132.20 (d, J = 8.4
Hz), 131.92 (d, J = 2.6 Hz), 131.66 (d, J = 1.5 Hz), 131.28 (d, J = 2.1
Hz), 130.87 (dd, J = 47.8, 0.6 Hz), 130.73 (d, J = 2.3 Hz), 130.39 (dd,
J = 31.9, 0.8 Hz), 130.35 (d, J = 2.7 Hz), 129.72 (dd, J = 56.0, 5.0 Hz),
129.38 (d, J = 9.2 Hz), 129.28 (d, J = 10.5 Hz), 129.02 (dd, J = 6.3, 2.4
Hz), 128.94 (d, J = 9.4 Hz), 127.94 (d, J = 10.1 Hz), 123.49 (dd, J =
6.3, 1.7 Hz), 122.71 (t, J = 1.2 Hz), 29.34 (dd, J = 27.7, 21.7 Hz),
25.50 (q, J = 1.7 Hz), 22.22 (dd, J = 26.0, 11.4 Hz). IR (ATR, cm−1):
3051 (w), 1561 (w), 1434 (m), 1421 (w), 1098 (m), 1026 (m), 1012
(w), 999 (w), 873 (w), 817 (m), 749 m), 742 (s), 708 (m), 692 (s),
679 (m), 652 (m).
see: (a) Herrmann, W. A.; Bohm, V. P. W.; Reisinger, C.-P. J.
Organomet. Chem. 1999, 576, 23−41. (b) Dupont, J.; Pfeffer, M.;
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̈
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916−920 and references therein.
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(b) O’Brien, C. J.; Kantchev, E. A. B.; Hadei, N.; Valente, C.; Chass, G.
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Chem., Int. Ed. 2012, 51, 3314−3332.
ASSOCIATED CONTENT
* Supporting Information
(8) An excellent overview of these precatalysts is provided in:
(a) 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. J. Org. Chem. 2010, 75, 6477−6488. (b) Johansson
Seechurn, C. C. C.; Parisel, S. L.; Colacot, T. J. J. Org. Chem. 2011, 76,
7918−7932.
■
S
Text, figures, tables, and CIF files giving experimental
procedures and spectral data for complexes 1−19, X-ray
crystallographic data for complexes 6, 9, 15, 17, 18, 19, a
description of single-crystal X-ray diffraction experiments, and
full reaction screening information and procedures. This
material is available free of charge via the Internet at http://
pubs.acs.org.
(9) (a) For the first instance of zinc reduction of (PPh3)2NiCl2 to
access Ni(0), see: Kende, A. S.; Liebeskind, L. S.; Braitsch, D. M.
Tetrahedron Lett. 1975, 39, 3375−3378. (b) For an overview of the
development of nickel precatalysts, see: Rosen, B. M.; Quasdorf, K.
W.; Wilson, D. A.; Zhang, N.; Resmerita, A.-M.; Garg, N. K.; Percec,
V. Chem. Rev. 2011, 111, 1346−1416.
(10) For an example of the use of a Grignard reagent to preactivate a
Ni(II) catalyst, see: Wolfe, J. P.; Buchwald, S. L. J. Am. Chem. Soc.
1997, 119, 6054−6058.
(11) (a) Chatt, J.; Shaw, B. L. J. Chem. Soc. 1960, 1718−1729.
(b) Cross, R. J.; Wardle, R. J. Chem. Soc. A 1970, 840−845.
(12) For a selection of some recent examples, see: (a) Chen, C.;
Yang, L.-M. Tetrahedron Lett. 2007, 48, 2427−2430. (b) Gao, C.-Y.;
Yang, L.-M. J. Org. Chem. 2008, 73, 1624−1627. (c) Zhou, L.; Feng,
X.; He, R.; Bao, M. J. Coord. Chem. 2009, 62, 2824−2831. (d) Fan, X.-
H.; Yang, L.-M. Eur. J. Org. Chem. 2010, 2457−2460. (e) Fan, X.-H.;
Yang, L.-M. Eur. J. Org. Chem. 2011, 1467−1471. (f) Zhang, N.;
Hoffman, D. J.; Gutsche, N.; Gupta, J.; Percec, V. J. Org. Chem. 2012,
77, 5956−5964. (g) Leowanawat, P.; Zhang, N.; Safi, M.; Hoffman, D.
J.; Fryberger, M. C.; George, A.; Percec, V. J. Org. Chem. 2012, 77,
2885−2892. (h) Park, N. H.; Teverovskiy, G.; Buchwald, S. L. Org.
Lett. 2014, 16, 220−223.
AUTHOR INFORMATION
Corresponding Author
*E-mail for T.F.J.: tfj@mit.edu.
■
Present Address
†Department of Chemistry and Biochemistry, Brigham Young
University, Provo, UT 84602.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Dr. Georgiy Teverovskiy and Prof. Stephen Buchwald are
acknowledged for insightful discussion and advice. Financial
support has been provided by the NIGMS (GM63755) and by
an NSF Graduate Research Fellowship (E.A.S.). X-ray
crystallography was carried out on instrumentation purchased
with the help of NSF grant CHE-0946721. NMR spectroscopy
was carried out on instruments purchased in part with funds
provided by the NSF (CHE-9808061 and CHE-8915028).
(13) For the use of these precatalysts for cross-coupling polymer-
ization, see: (a) Miyakoshi, R.; Yokoyama, A.; Yokozawa, T. J. Am.
Chem. Soc. 2005, 127, 17542−17547. (b) Bronstein, H. A.; Luscombe,
C. K. J. Am. Chem. Soc. 2009, 131, 12894−12895.
REFERENCES
(14) McNeil and co-workers have carried out detailed studies into
use of this type of precatalyst for the synthesis of poly(thiophene) and
related polymers: (a) Lanni, E. L.; McNeil, A. J. J. Am. Chem. Soc.
2009, 131, 16573−16579. (b) Lanni, E. L.; McNeil, A. J. Macro-
molecules 2010, 43, 8039−8044. (c) Lanni, E. L.; Locke, J. R.; Gleave,
C. M.; McNeil, A. J. Macromolecules 2011, 44, 5136−5145. (d) Lee, S.
R.; Bryan, Z. J.; Wagner, A. M.; McNeil, A. J. Chem. Sci. 2012, 3,
1562−1566. (e) Lee, S. R.; Bloom, J. W. G.; Wheeler, S. E.; McNeil, A.
J. Dalton Trans. 2013, 42, 4218−4222. (f) Bryan, Z. J.; McNeil, A. J.
Chem. Sci. 2013, 4, 1620−1624. (g) Bryan, Z. J.; McNeil, A. J.
Macromolecules 2013, 46, 8395−8405.
■
(1) (a) Wilke, G. Angew. Chem., Int. Ed. 1988, 27, 185−206. (b)
Modern Organonickel Chemistry; Tamaru, Y., Ed.; Wiley-VCH:
Weinheim, Germany, 2005. (c) Hu, X. Chem. Sci. 2011, 2, 1867−
1886. (d) Rosen, B. M.; Quasdorf, K. W.; Wilson, D. A.; Zhang, N.;
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1416. (e) Mesganaw, T.; Garg, N. K. Org. Process Res. Dev. 2013, 17,
29−39. (f) Yamaguchi, J.; Muto, K.; Itami, K. Eur. J. Org. Chem. 2013,
19−30.
(2) Palladium metal is more than 1500 times more expensive than
nickel metal, yet the cost of Ni(cod)2 is only ca. 50% less than
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(15) (a) Ge, S.; Hartwig, J. F. Angew. Chem., Int. Ed. 2012, 51, 1−6.
(b) Ge, S.; Hartwig, J. F. J. Am. Chem. Soc. 2014, 136, 1617−1627. See
also ref 17a.
(16) Standley, E. A.; Jamison, T. F. J. Am. Chem. Soc. 2013, 135,
1585−1592.
(17) (a) Ge, S.; Hartwig, J. F. J. Am. Chem. Soc. 2011, 133, 16330−
16333. (b) For a detailed report examining the role of dba in
zerovalent palladium catalysis, see: Amatore, C.; Jutand, A.; Khalil, F.;
M’Barki, M. A.; Mottier, L. Organometallics 1993, 12, 3168−3178.
(18) The change from chloride to bromide is merely for convenience,
since 2-mesitylmagnesium bromide is commercially available, while the
chloride is not. The identity of the halogen does not appear to alter the
behavior of the complexes as precatalysts.
(19) This particular Grignard reagent was selected for the isopropyl
groups at the 2- and 6-positions, with the isopropyl group in the 4-
position not expected to play a role in the complex’s stability. This
reagent is commercially available as a 0.5 M solution in THF.
(20) It is known, for example, that P(t-Bu)3 reacts with NiBr2 in
ethanol to form [P(t-Bu)3NiBr3]−[HP(t-Bu)3]+. See: Alyea, E. C.;
Costin, A.; Ferguson, G.; Fey, G. T.; Goel, R. G.; Restivo, R. J. J. Chem.
Soc., Dalton Trans. 1975, 1294−1298.
(21) Quagliano, J. V.; Schubert, L. Chem. Rev. 1952, 50, 201−260.
(22) Muller, P. Crystallogr. Rev. 2009, 15, 57−83.
̈
(23) This deviation in geometry is also likely to be the reason this
complex is red, as opposed to the normal bright yellow.
(24) (a) Ng, S.-S.; Jamison, T. F. J. Am. Chem. Soc. 2005, 127,
14194−14195. (b) Ho, C.-Y.; Ng, S.-S.; Jamison, T. F. J. Am. Chem.
Soc. 2006, 128, 5362−5363. (c) Ng, S.-S.; Ho, C.-Y.; Jamison, T. F. J.
Am. Chem. Soc. 2006, 128, 11513−11528.
(25) Complex 7 is somewhat soluble in methanol, causing the lower
yield in comparison to other complexes. The yield can be further
raised by collecting a second crop of solid from the filtrate.
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