A modular, air-stable nickel precatalyst

Article abstract of DOI:10.1021/acs.orglett.5b00766

The synthesis and catalytic activity of [(TMEDA)Ni(o-tolyl)Cl], an air-stable, crystalline solid, is described. This complex is an effective precatalyst in a variety of nickel-catalyzed transformations. The lability of TMEDA allows a wide variety of ligands to be used, including mono- and bidentate phosphines, diimines, and N-heterocyclic carbenes. Preliminary mechanistic studies are also reported, which suggest that [(TMEDA)Ni(o-tolyl)Cl] can activate by either a Ni-B or Ni-Ni transmetalation event, depending on the reaction conditions.

Full text of DOI:10.1021/acs.orglett.5b00766

Letter
pubs.acs.org/OrgLett
A Modular, Air-Stable Nickel Precatalyst
Jason D. Shields, Erin E. Gray, and Abigail G. Doyle*
Department of Chemistry, Princeton University, Princeton, New Jersey 08544, United States
S
* Supporting Information
ABSTRACT: The synthesis and catalytic activity of [(TMEDA)Ni(o-
tolyl)Cl], an air-stable, crystalline solid, is described. This complex is an
effective precatalyst in a variety of nickel-catalyzed transformations. The
lability of TMEDA allows a wide variety of ligands to be used, including
mono- and bidentate phosphines, diimines, and N-heterocyclic
carbenes. Preliminary mechanistic studies are also reported, which
suggest that [(TMEDA)Ni(o-tolyl)Cl] can activate by either a Ni−B or
Ni−Ni transmetalation event, depending on the reaction conditions.
relatively inexpensive, but modularity is a problem since
he past two decades have witnessed rapid growth in the area
Tof homogeneous nickel catalysis owing to the base metal’s polynuclear complexes can be formed upon ligation, leading to
inactive species.4,5 Furthermore, reducing conditions are often
low cost and unique properties compared to its precious metal
sibling, palladium.1 This transition metal is not only three orders of
required in order to activate the NiX2 precatalyst, limiting the
scope of possible transformations.6,7 Yang, Hartwig, Jamison,
Buchwald, and Percec have recently developed air-stable
precatalysts that are all highly active for specific reactions.8−12
Crucially, however, they are all bound to phosphine ligands,
meaning that their generality is inherently limited to reactions in
which that exact ligand is competent.13 The same limitation
applies to NiL2X2 complexes like Ni(PCy3)2Cl2, which have been
used in Suzuki reactions.14
We aimed to design an air-stable Ni(II) precatalyst with high
modularity and generality. We speculated that the use of weakly
binding amine ligands in place of phosphine ligands would
permit facile ligand exchange, allowing a much wider scope of
σ-donating ligands to bind to the nickel center. Based on the
precedent for using N,N,N′,N′-tetramethylethylenediamine
(TMEDA) as a dummy ligand in the inorganic synthesis of
both diamine and phosphine-ligated nickel and palladium
complexes, we selected this ligand for the preparation of a
modular precatalyst.15 Although [(TMEDA)Ni(Ph)Cl] is
reported to be thermally unstable and air sensitive,16 Shaw and
Yamamoto have shown that use of an o-tolyl or other hindered
aryl substituent on Ni(II)(aryl)Cl complexes bearing phosphine
or bpy ligands confers air stability by shielding nickel from
associative substitution.17,18 On this basis, we hypothesized that
[(TMEDA)Ni(o-tolyl)Cl] (1) would serve as an air-stable and
modular Ni precatalyst.
magnitude less expensive than palladium on a mole-for-mole basis,2
but nickel is also more electropositive and smaller than palladium,
enabling more facile oxidative addition and access to more diverse
oxidation states. Nevertheless, palladium still overwhelmingly
dominates the landscape of group 10 metal catalysis.3 A major
cause of this disparity is the diversity, accessibility, and robustness
of Pd(0) precursors as compared to Ni(0) catalysts. The most
common Ni(0) source for catalysis is Ni(cod)2, which is expensive
and must be stored and used under rigorously air-free conditions.
These limitations hinder both large-scale applications of nickel
catalysis and small-scale reaction discovery efforts. To circumvent
these problems, air-stable, well-defined Ni(II) precatalysts have
been developed, ranging in complexity from NiX2 salts to carefully
designed organometallic complexes. Despite these advances,
Ni(cod)2 remains the most general nickel precatalyst.
The ideal precatalyst would satisfy four criteria: (1) low cost,
(2) air stability, (3) modularitycompatibility with any desired
ligand class, and (4) generalityactivity in a wide range of
reactions. Previously reported precatalysts fall short in at least
one of these areas. Ni(cod)2 and methallylnickel chloride dimer
can be used with many different ligands but are expensive and
air sensitive (Figure 1). NiX2 salts and their glyme adducts are
Initially, our synthesis of 1 began from (TMEDA)NiMe2,
originally prepared by Wilke in his seminal studies of
organonickel chemistry.15b We were pleased to find that 1 was
indeed stable to air and ambient temperature. Samples have
been stored for 3 months on the benchtop with no detectable
decomposition. In a second generation synthesis, we used
o-chlorotoluene as the reaction solvent in a one-pot reaction
Received: March 16, 2015
Published: April 17, 2015
Figure 1. Prior art in nickel precatalysts.
© 2015 American Chemical Society
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Heterocyclic coupling partners are tolerated (entries 2, 3, and 5),
as are other polar coordinating groups (entries 1, 6, 7, and 9).
Precatalyst 1 also tolerates a variety of solvents, ranging in polarity
from toluene (entries 4 and 7) to s-butanol (entry 5). In most cases,
the yield was equivalent or superior to the original report.
For entries 3 and 8, it was found that TMEDA poisons the original
catalyst system;27 this is an inherent limitation of precatalyst 1, but
it should be noted that free 1,5-cyclooctadiene can also negatively
affect reactions when Ni(cod)2 is used as a precatalyst.10a,28
Precatalyst 1 works on gram scale (87% yield, entry 1) and with low
catalyst loadings (0.5 mol %, entry 2). Control reactions for each
entry were conducted using NiCl2·glyme as the precatalyst, as this
nickel source is low cost and air stable, and in every example except
entries 1 and 2, the yield with this precatalyst was substantially
lower than with complex 1 after the same reaction time.27
Temperature is the main limitation to the generality of
complex 1. The precatalyst does not activate at room temp-
erature, and the test reactions suggest that 60 °C is the lower
bound of activation. For example, the oxidative coupling
reported by Dong in entry 9 takes place at 30 °C with Ni(cod)2,
but no conversion to product is observed with precatalyst 1 at
this temperature. Attempts to preactivate complex 1 by heating it
in the presence of ligand and various other reaction components
prior to conducting the reaction were unsuccessful. However,
simply running the oxidative coupling at elevated temperature
recovered reactivity (86% yield).
Scheme 1. Synthesis of Nickel Precatalyst 1
from commercially available Ni(acac)2 and Al(OEt)Me2
(Scheme 1). Under these conditions, which have been run on
a gram scale with 88% yield, complex 1 crashes out of the reaction
solution as red crystals, obviating the need for a purification step.
X-ray crystallography of these crystals confirms the structure
of complex 1 (Figure 2).19 The complex is square planar, as
The success of precatalyst 1 in a wide variety of reactions
prompted us to investigate its mechanism of activation. For
entries 1−5, a fairly straightforward mechanism may explain the
generation of the presumed Ni(0) active catalyst. Namely, a
boron-to-nickel transmetalation would produce a nickel biaryl
species and rapidly generate Ni(0) upon reductive elimination
(Scheme 2a). Similarly, coordination of morpholine and
Figure 2. X-ray crystal structure of complex 1. Ellipsoids are set to 30%
probability. Hydrogen atoms on the TMEDA ligand have been removed
for clarity.
Scheme 2. Mechanisms for Precatalyst Activation
expected for tetravalent Ni(II), and the methyl group from the
tolyl substituent projects above the plane of the complex, as
predicted by Shaw.17
In order to probe the generality of this precatalyst, we selected
nine nickel-catalyzed reactions, including Suzuki−Miyaura
(sp2 and sp3 electrophiles), Buchwald−Hartwig, cyclization,
and oxidative coupling reactions (Table 1).9,11,14a,20−25 In each
case, the original precatalyst was replaced with equimolar
quantities of complex 1; the same stoichiometry of ligand was
then used. Empirically, we found that the addition of K3PO4
improved the reaction yields with precatalyst 1, so it was included
in reactions even if the original report did not do so.26 The other
reaction components, solvents, and temperatures were identical
to the original literature reports, with the exception of entry 9,
which was run at 100 °C instead of 30 °C (vide infra).
The results indicate a high degree of modularity. In addition
to monodentate and bidentate phosphines, diimine ligands
(entry 5) and N-heterocyclic carbene (NHC) ligands (entries 8
and 9) can be used. This wide range of ligand classes highlights
the importance of modularity to precatalyst design. For example,
complex 1 would be an effective nickel source for the large
ligand screening efforts that accompany reaction development.
Furthermore, the diversity in ligands allows an expansive scope
of reactions that can conceivably be run with precatalyst 1. This
feature distinguishes 1 from the air-stable Ni(II) precatalysts
recently reported in the literature, which all require ligation of a
phosphine in a previous synthetic step.
subsequent reductive elimination could furnish Ni(0) in the
Buchwald−Hartwig reaction (entry 6). The [4 + 2], the
[2 + 2 + 2], and the dehydrogenative coupling reactions
shown in entries 7−9, however, do not have an obvious
transmetalating agent or amide ion. Instead, we speculated that
a nickel−nickel transmetalation event was taking place, leading
to an inactive nickel dihalide and an active nickel biaryl species
(Scheme 2b).10a Indeed, our observation of 2,2′-dimethylbi-
phenyl in the [4 + 2] reaction (entry 7) indicates a nickel−nickel
transmetalation pathway is operative. However, the Suzuki−
Miyaura cross-coupling reaction with aryltosylates (entry 1)
yielded 2-methylbiphenyl rather than 2,2′-dimethylbiphenyl,
suggesting boron-to-nickel transmetalation is preferred in the
presence of boronic acid. These observations demonstrate that,
depending on the reaction conditions, either nickel−boron or
nickel−nickel transmetalation are possible mechanisms for
precatalyst activation.
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Table 1. Activity of Precatalyst 1 in Reactions Selected from the Literature
a
b
The scale and concentrations were identical to the original report. See the Supporting Information for full details. This reaction was also run on
c
4 mmol (∼1 g) scale. Entry 6 was run without K3PO4 as this was empirically found to result in higher yield.
Nickel catalysis has a rich history in spite of the air
sensitivity of Ni(0). Numerous cross-coupling, cyclization,
and redox reactions have been developed despite the lack
of a low-cost, air-stable, modular, and general precatalyst.
With the introduction of complex 1, which satisfies all of
these criteria, we anticipate that nickel catalysis will become
even more practical and widespread. The modularity of
complex 1 renders it ideal for reaction development, and its
low cost and stability may make it applicable on large scale.
Future work will focus on expanding the temperature range
for activation, thus increasing the generality of precatalyst 1
still further.
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(15) (a) Byers, P. K.; Canty, A. J.; Jin, H.; Kruis, D.; Markies, B. A.;
Boersma, J.; van Koten, G.; Hill, G. S.; Irwin, M. J.; Rendina, L. M.;
Puddephatt, R. J. Inorg. Synth. 1998, 32, 162. (b) Kaschube, W.;
ASSOCIATED CONTENT
* Supporting Information
Experimental procedures, spectroscopic data, and X-ray
crystallographic data. This material is available free of charge
via the Internet at http://pubs.acs.org.
■
S
Porschke, K. R.; Wilke, G. J. Organomet. Chem. 1988, 355, 525.
̈
(16) Marshall, W. J.; Grushin, V. V. Can. J. Chem. 2005, 83, 640.
(17) Moss, J. R.; Shaw, B. L. J. Chem. Soc. A 1966, 1793.
(18) Uchino, M.; Asagi, K.; Yamamoto, A.; Ikeda, S. J. Organomet.
Chem. 1975, 84, 93.
AUTHOR INFORMATION
Corresponding Author
■
(19) The structure shown represents the majority conformation
(∼80%). See SI for a whole molecule disorder model.
(20) Graham, T. J. A.; Doyle, A. G. Org. Lett. 2012, 14, 1616.
(21) Tobisu, M.; Shimasaki, T.; Chatani, N. Angew. Chem., Int. Ed.
2008, 47, 4866.
(22) Zhou, J.; Fu, G. C. J. Am. Chem. Soc. 2004, 126, 1340.
(23) Ohashi, M.; Takeda, I.; Ikawa, M.; Ogoshi, S. J. Am. Chem. Soc.
2014, 133, 18018.
*E-mail: agdoyle@princeton.edu.
Notes
The authors declare no competing financial interests.
ACKNOWLEDGMENTS
■
(24) Kumar, P.; Thakur, A.; Hong, X.; Houk, K. N.; Louie, J. J. Am.
Chem. Soc. 2014, 136, 17844.
(25) Whitaker, A. M.; Dong, V. M. Angew. Chem., Int. Ed. 2015, 54,
Financial support from NIGMS (R01 GM100985-02) and
Princeton University is acknowledged. This material is based
upon work supported by the National Science Foundation
Graduate Research Fellowship under Grant No. DGE-1148900
(to E.E.G.). We thank Phil Jeffrey of Princeton University for
X-ray crystallographic structure determination and Grant
Margulieux of Princeton University for helpful discussions.
Precatalyst 1 will be commercially available from Sigma-Aldrich.
1312.
(26) The positive effect of K3PO4 additive in most of the test reactions
suggests the possible intermediacy of a Ni-hydroxo complex as described
by Monfette and coworkers at Pfizer: Christian, A. H.; Muller, P.;
Monfette, S. Organometallics 2014, 33, 2134. We have been unable to
isolate any such intermediates, though work in this area is ongoing.
(27) See the Supporting Information for details.
(28) Shields, J. D.; Ahneman, D. T.; Graham, T. J. A.; Doyle, A. G. Org.
Lett. 2014, 16, 142.
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