Revisiting Claims of the Iron-, Cobalt-, Nickel-, and Copper-Catalyzed Suzuki Biaryl Cross-Coupling of Aryl Halides with Aryl Boronic Acids

Article abstract of DOI:10.1021/acs.organomet.9b00083

Intrigued by recent reports on the surprisingly excellent activity of a range of cobalt-, iron-, copper-, and nickel-based catalysts in the Suzuki biaryl cross-coupling of simple aryl boronic acids with aryl halides, we undertook a reexamination of the syntheses of representative examples of the reported precatalysts and their application to the catalytic reaction. A reported PNP-Fe pincer complex proved to be a mixture of starting materials; a mono-Schiff base cobalt complex in fact the bis-ligated adduct and a monomeric copper(II) PNP-pincer complex a di- or oligomeric copper(I) species. In our hands, neither these complexes nor any other of the selected precatalysts investigated showed any activity in a Suzuki cross-coupling reaction of an electronically activated aryl bromide with phenyl boronic acid. Meanwhile, switching the nucleophile to the BuLi-activated phenyl boronic pinacol ester gave some promising activity with cobalt precatalysts.

Full text of DOI:10.1021/acs.organomet.9b00083

Article
pubs.acs.org/Organometallics
Cite This: Organometallics XXXX, XXX, XXX−XXX
Revisiting Claims of the Iron‑, Cobalt‑, Nickel‑, and Copper-
Catalyzed Suzuki Biaryl Cross-Coupling of Aryl Halides with Aryl
Boronic Acids
Sanita B. Tailor,† Mattia Manzotti,† Soneela Asghar,†,‡ Benjamin J. S. Rowsell,†
Stephen L. J. Luckham,† Hazel A. Sparkes,† and Robin B. Bedford*,†
†School of Chemistry, University of Bristol, Cantock’s Close, Bristol BS8 1TS, U.K.
‡Department of Chemistry and Chemical Engineering, SBA School of Science & Engineering, Lahore University of Management
Sciences, Lahore 54792, Pakistan
S
* Supporting Information
ABSTRACT: Intrigued by recent reports on the surprisingly
excellent activity of a range of cobalt-, iron-, copper-, and
nickel-based catalysts in the Suzuki biaryl cross-coupling of
simple aryl boronic acids with aryl halides, we undertook a
reexamination of the syntheses of representative examples of
the reported precatalysts and their application to the catalytic
reaction. A reported PNP−Fe pincer complex proved to be a
mixture of starting materials; a mono-Schiff base cobalt
complex in fact the bis-ligated adduct and a monomeric
copper(II) PNP−pincer complex a di- or oligomeric copper-
(I) species. In our hands, neither these complexes nor any
other of the selected precatalysts investigated showed any
activity in a Suzuki cross-coupling reaction of an electronically activated aryl bromide with phenyl boronic acid. Meanwhile,
switching the nucleophile to the BuLi-activated phenyl boronic pinacol ester gave some promising activity with cobalt
precatalysts.
metal, combined with the need to remove it to the low ppm
level from active pharmaceutical intermediates,3 has inspired
the hunt for more sustainable catalysts for Suzuki cross-
coupling based on cheap, readily available first-row transition
metals. Of these, nickel-4−6 and copper-catalyzed7,8 Suzuki
cross-coupling reactions are arguably the most well developed.
Of particular note is the coupling of aryl halides with aryl
boronic acids, as this represents the simplest, yet perhaps most
synthetically valuable, variant of the cross-coupling reactio-
n.4,5,6a,7
INTRODUCTION
■
The Suzuki biaryl cross-coupling reaction1 (Scheme 1) is a
robust and widely used method for the formation of aryl−aryl
Scheme 1. Suzuki Biaryl Cross-Coupling and Selected
Commercial Applications
Cobalt-catalyzed Suzuki biaryl cross-coupling is rapidly
developing9 but is currently largely limited to the coupling of
aryl boronic esters, activated with either an organolithium
reagent or an alkoxide base, rather than free aryl boronic acids.
Meanwhile, despite growing success in iron-catalyzed Suzuki
couplings,10 simple biaryl cross-coupling under mild con-
ditions11 remains limited to either highly activated 2-pyridyl or
2-pyrimidyl halide substrates,10a or aryl halide substrates that
can engender directed aryl halide activation.12 Again, in all of
these cases, the free boronic acid cannot be exploited, rather a
tetraorganoborate or an activated aryl boronic ester is required.
bonds. Commercial applications that have exploited Suzuki
biaryl bond formation include the synthesis of 2-cyano-4′-
methyl biphenyl, an intermediate in the production of a range
of the sartan class of drugs for the treatment of hypertension,
and boscalid, a broad-spectrum fungicide used in crop
protection.2
A vast majority of Suzuki biaryl cross-coupling reactions rely
on palladium-based catalysts. However, the high cost of this
Received: February 8, 2019
© XXXX American Chemical Society
A
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A series of apparent exceptions to the failure to exploit
simple aryl boronic acids using Fe and Co (as well as Cu and
Ni) precatalysts have recently been published across five
papers by Bhat and co-workers.13 The authors reported that
attractively simple precatalysts based on the easily produced
ligands 1−3 and closely related ligands all show good to
excellent activity in the highly desirable Suzuki coupling of aryl
halides with aryl boronic acids. Intrigued as to why these
classes of ligands should confer such exceptional activity in a
profoundly important, yet previously elusive, process, we
undertook a reexamination of the authors’ reported syntheses
of representative examples of precatalysts based on these
ligands, as well as structurally well-defined or previously
reported analogues, and their application in Fe-, Co-, Ni- and
Cu-catalyzed Suzuki biaryl cross-coupling, and the results from
this study are summarized below.14
consistent with [MH]+, the complete absence of any isotopic
pattern is highly surprising, if not incredible, not least due to
the large contribution to the pattern expected for the 37Cl
isotope, which is entirely absent.19 It is also worth noting that
while the peak in the mass spectrum is labeled as appearing at
m/z = 568.10, the x-axis on the spectrum would seem to put
the peak nearer to m/z = 584, clearly inconsistent with the
formulation.13c The nanospray-MS spectrum we recorded for
the purple compound does not show this unusual peak but
instead, among others, significant peaks at m/z = 506.5,
1012.0, and 1518.5. The observed masses and isotope patterns
are consistent with either the iron-containing species, being a
monomer, dimer, and trimer of an as yet undetermined
composition, or fragmentation of the trimeric species.
Taken together, the data are inconsistent with the
formulation of 6a. Structurally characterized examples of bis-
Schiff base Fe(III) chloride complexes of the general type 6 are
surprisingly rare with, to the best of our knowledge, only two
reported in the literature,20 while the products of reactions of
FeCl3 with Schiff base ligands are highly dependent on the
presence or absence of water (note here water is used as a
cosolvent in ethanol at reflux temperature) and the presence or
absence of base.18 Nevertheless, the purple solid “6a*” was
used, as is, in subsequent Suzuki cross-coupling reactions (vide
infra). Meanwhile, we prepared the previously reported, closely
related complex 6b20b and used the same synthetic approach to
prepare what we believe is a genuine sample of 6a. The HR-
electrospray ionisation-mass spectrometry (HR-ESI-MS) of 6a
prepared this way showed a peak at m/z = 568.0820
corresponding to [MH]+ (calculated m/z = 568.0847), with
the expected isotope distribution pattern (see Figure S4,
Supporting Information). Both of the complexes 6a and 6b
were investigated in the Suzuki reaction (vide infra).
RESULTS AND DISCUSSION
■
Attempted Syntheses of the Precatalysts. The Co and
Ni complexes of ligand 2 (salophen), complexes 4 and 5,
respectively, have been reported many times; indeed, they are
commercially available and were readily prepared by Bhat’s
procedures.13d The IR data we obtained for the complexes
were in agreement with the data reported in the literature,15
while the NMR spectroscopic data of the diamagnetic Ni(II)
complex 5 were in accord with literature values.15b Bhat
reported a value of 1.23 μB for the solid-state magnetic
moment of complex 4,13d which we note is far too low for a
pure sample; low-spin square-planar cobalt(II) complexes
typically show “normal” room-temperature magnetic moments
in the range 2.1−2.9 μB,16 while the room-temperature
magnetic moment of closely related cobalt(II) salen has
variously been reported in the range 2.2−2.7 μB.17 We
obtained a room-temperature magnetic moment for 4 of
3.02 μB, essentially identical to a previously reported value.15d
The synthesis of the bis-Schiff base iron complex 6a was
attempted according to Bhat’s method from hydrated iron(III)
chloride and ligand 3a in aqueous ethanol at reflux temper-
ature.13c As reported by Bhat, we obtained a purple solid and
the IR and UV spectroscopic data (see the Supporting
Information) were in broad agreement with the reported
data. Bhat reported a magnetic moment of 1.8 μB for complex
6a,13c which is a little surprising given that iron(III) chloride
bis-Schiff base adducts are reported to be high-spin (S = 5/
2).18 Indeed, a density functional theory (DFT) computational
analysis of the ground-state structure of 6a (B3LYP-D3BJ/cc-
pVTZ//cc-pVDZ) showed the S = 5/2 configuration to be
preferred over the S = 1/2 configuration by around 23 kcal/
mol.
From the outset, the reported formulation of the cobalt
complex 713e appeared extremely unlikely to us, first, because
the proposed κ3-N,O,O-chelation appeared impossibly strained,
as is clearly apparent from the distorted tetrahedral and square-
planar geometries obtained from DFT calculations (B3LYP-
D3BJ/cc-pVDZ) of both the high- and low-spin ground-state
configurations, respectively (Figure 1). Second, while many
Figure 1. DFT (B3LYP-D3BJ/cc-pVDZ)-calculated high-spin (left)
and low-spin ground-state geometries for the putative complex 7.
Single point energy calculations at the B3LYP-D3BJ/cc-pVTZ//cc-
pVDZ level of theory indicate that the high-spin structure is preferred
by around 12.2 kcal/mol.
structurally characterized cobalt bis-Schiff base complexes are
known, monoadducts of simple aryl Schiff bases are rare.21
Furthermore, Bhat reported that complex 7 has a low-spin (S =
1/2) ground-state electronic configuration,13e based on a
(presumably ambient temperature) solid-state magnetic mo-
ment measurement of 1.26 μB,13e a value far too low for a
typical Co(II) low-spin complex. In addition, the low-spin
assignment is perhaps unexpected for a five-coordinate Co(II)
with only a single Schiff base ligand and moderate to weak-field
Perhaps, the most important data in support of the proposed
formulation is the ESI mass spectrum of 6a presented by
Bhat,13c which shows a single mass peak at m/z = 568.10, as
well as single mass peaks consistent with the loss of chloride
and the appearance of free Schiff base ligand. While this mass is
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coligands. Indeed, DFT calculations (B3LYP-D3BJ/cc-
pVTZ//cc-pVDZ) of the putative complex 7 revealed a
significant preference for a high-spin ground-state config-
uration at room temperature of around 12.2 kcal/mol,
suggesting that the reported low-spin configuration for this
mononuclear complex is unlikely, at least at room temper-
ature.22
Following the synthetic procedure reported by Bhat for
complex 7,13e namely, heating 1 equivalent of ligand 3a with
hydrated cobalt(II) chloride in ethanol gave a red-brown solid,
the same solid was produced on reaction of cobalt chloride
with 2 equivalents of 3a (see Figure S10, Supporting
Information for UV−vis spectroscopic data). The IR
spectroscopic data for the sample produced from a 2:1 ratio
of 3a/CoCl2·6H2O matched the data reported by Bhat.13e
Taken together, the data do not support the reported
formulation of 7 but indicate that the reaction instead yields
a bis-Schiff base adduct, 8a, irrespective of the ratio of ligand to
metal used. The high-resolution spectrum supported the
formulation of 8a, with a peak at m/z = 596.1338
corresponding to the [MH]+ ion (calculated m/z =
596.1358), with the anticipated isotope distribution pattern
(Figure S11, Supporting Information).23 The room-temper-
ature magnetic moment recorded of 4.02 μB is consistent with
a tetrahedral S = 3/2 Co(II) complex. Finally, it should be
noted that Bhat reported separately that, in sharp contrast, the
equivalent reaction with the analogous Schiff base derived from
salicylaldehyde gives the bis-Schiff base complex 8b,13c
finding with which we concur.
a
1
species of the formulation 11. First, the H NMR spectrum
showed peaks in the standard range for a diamagnetic complex,
whereas, as formulated, the monomeric complex 11 should be
paramagnetic, with S = 1/2. Second, the 31P spectrum showed,
in addition to some free ligand 1, an AB system with broad
doublets observed at δ 24.1 and 20.3 ppm with a mutual
coupling of around 166 Hz and a very broad, featureless peak
centered at around ∼17 ppm. Interestingly, the same AB
pattern was observed when the reaction was repeated with
copper(I) acetate as the precursor, along with other peaks
indicative of di- or polymetallic products. In addition, the ESI-
MS of the product mixture indicated some oxidation of the
ligand 1 to a diphosphine oxide, which in turn coordinated to a
copper center.24 Taken together, the data indicate that if the
mononuclear copper(II) complex 11 is indeed produced at any
stage, it undergoes very facile reduction to copper(I) with
concomitant oxidation of the phosphine residues.25 This is
perhaps not surprising in view of the well-known instability of
Cu(II)−phosphine adducts with respect to facile reduction to
Cu(I), especially in the presence of even trace amounts of
adventitious water,26 such as the water of crystallization in the
copper(II) acetate used in the reported synthesis of 11.13b
Furthermore, reported copper(I) often consists of dimetallic or
higher-order copper clusters rather than monometallic
complexes; indeed, dinuclear Cu(I) complex formation has
been demonstrated previously for ligand 1.27
We next reexamined the reported syntheses of iron, cobalt,
and copper complexes of the PNP−pincer ligand 1. The
synthesis of the iron-containing complex 9 was attempted
following Bhat’s reported procedure,13b which consisted of
heating ligand 1 with [Fe(OH2)6]SO4·H2O in tetrahydrofuran
(THF) at reflux temperature for 4 h. In our hands, this gave a
pale brown precipitate that proved insoluble in THF,
dichloromethane, acetonitrile, and acetone. An IR spectrum
of the precipitate was essentially identical to that of the starting
material, hydrated iron(II) sulfate (see Figure S15), dominated
by a large, broad peak at 1081 cm−1 corresponding to the
sulfate ion. Removal of the solvent from the supernatant from
the synthetic reaction gave a pale brown residue, which proved
1
to be predominantly the free ligand 1, as determined by H
and 31P NMR spectroscopy. In summary, in our hands at least,
no reaction was obtained between ligand 1 and hydrated
ferrous sulfate. The same results were obtained on repeated
attempts.
The reaction of ligand 1 with cobalt(II) acetate, employing
the method of Bhat,13a gave a brown solid whose IR spectrum
(Figure S19) had some similar peaks to those reported for
complex 10, most notably those associated with the acetate
ligands. The ESI-MS spectrum of a methanol solution (Figure
S20) showed, along with higher mass peaks, a peak of m/z =
627.1 consistent with loss of an acetate ligand from 10 and
coordination of a solvent molecule. Attempts to produce
crystals of 10 suitable for X-ray analysis were unsuccessful, and
at this stage, we remain hesitant about the assignment of the
structure.
Our attempts to produce the reported copper complex 11 by
the method described by Bhat from Cu(OAc)2·H2O proved
fruitless.13b The NMR spectroscopic data obtained (see
Figures S21−S24, Supporting Information) for the product
mixture was entirely inconsistent with a monometallic Cu(II)
In view of the facile reduction of the putative intermediate
11 to a mixture of dimeric (or higher nuclearity) Cu(I) species
and in light of the proven catalytic activity of copper(I)
complexes in the Suzuki coupling of aryl iodides with aryl
boronic esters,8f we decided instead to focus our efforts on a
well-defined Cu(I) complex of ligand 1, the previously
reported dimeric copper(I) iodide species, complex 12,
which could be readily prepared and isolated according to a
literature method.27a
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Similarly, our lack of success in preparing complex 9 as
reported, or indeed any tractable material other than starting
materials, led us to investigate another closely related iron-
based analogue containing ligand 1. The best catalytic activity
reported for the material described as complex 9 was obtained
in acetonitrile.13 Therefore, we reasoned that if 9 were indeed
accessible, when dissolved in acetonitrile, as per the reported
catalytic conditions, it would be highly likely to form the
adduct [Fe(1)(NCMe)3]2+, 13, which has previously been
reported and structurally characterized as the tetrafluoroborate,
[13][BF4], by Kirchner and co-workers.28 This complex was
therefore synthesized and examined as a well-defined
precatalyst (vide infra).
While the data we obtained for complex 10 were not entirely
inconsistent with those reported by Bhat,13a in the absence of
definitive structural characterization, we were keen to also
target a well-defined cobalt precatalyst. During catalysis, it is
highly likely that bromide ligands from the aryl bromide
substrates will coordinate to the metal center, suggesting that
the bromide-containing adducts of the PNP-Co motif should
be catalytically competent. Indeed, Bhat proposed that the
acetate ligands in 10 are lost during precatalyst activation to be
replaced by a halide on oxidative addition.13a Accordingly, we
synthesized the cobalt dibromide adduct of ligand 1, complex
14. The single-crystal X-ray structure of 14 is shown in Figure
2a, and the structure is broadly similar to that for the
previously reported chloride analogue.29 Recrystallization of 14
from acetonitrile/acetone gave the cationic complex 15, the
crystal structure of which is shown in Figure 2b, supporting the
assertion made above that acetonitrile is likely to replace halide
ligands during catalysis. In both cases, the distorted square-
based pyramidal structures obtained are consistent with low-
spin (S = 1/2) five-coordinate Co(II) complexes. This ground
state is further supported by a value of 2.22 μB for the effective
magnetic moment of 14 recorded in solution (Evans’ method)
at room temperature, a value which is in line with the data
published for a range of Co(II)−PNP complexes, including the
dichloride analogue of 14.29
Figure 2. Single-crystal X-ray structures of (a) complex 14 and (b)
complex 15. Hydrogen atoms (except for H-bond in 15) and solvent
molecules are omitted for clarity, with thermal ellipsoids set at 50%
probability.
note is the fact that the MS data presented by Bhat are
remarkably devoid of any isotope patterns and the [MH]+ peak
appears to be in the wrong place in the spectrum shown in
their supplementary material. The complex 6a could, however,
be isolated by an alternative synthetic procedure. Similarly,
ligand 3a does not, in our hands, give a monoligated Co(II)
complex 7 but rather the bis-ligated adduct 8a, the structural
analogue of 8b, a complex also reported by Bhat, irrespective of
the ligand-to-metal ratio used in the synthesis. Furthermore,
the magnetic data for “7” presented by Bhat and co-workers
does not support their formulation, and the proposed chelating
tridentate nature of the Schiff base ligand is highly improbable;
indeed, a search of the CCDC database revealed no such motif
in any crystallographically characterized complex.30 Turning to
the PNP ligand 1, this may possibly give the cobalt(II) acetate
adduct 10 as reported (we believe, there is insufficient data
across Bhat’s and our work to state this definitively), but no
reaction was obtained between 1 and ferric sulfate, while the
reaction with copper(II) acetate led to the formation of di- or
oligomeric copper(I) species, rather than the monomeric
copper(II) adduct claimed. Accordingly, we also synthesized
well-defined Co(II), Fe(II), and Cu(I) adducts of the ligand 1
for the catalytic testing described in the following section.
Suzuki Biaryl Cross-Coupling Reactions. Across the
papers reported by Bhat and co-workers,13 particularly good
results were claimed in the coupling of the electronically
activated aryl bromide substrate, 4-bromocyanobenzene, 16,
with phenyl boronic acid, 17, to give 4-cyanobiphenyl 18,
using a variety of bases and solvents (Scheme 2a). Indeed,
replotting the catalytic data obtained by Bhat in this reaction,
Summarizing our synthetic efforts, we were able to
reproduce Bhat’s syntheses of the previously very well known
Co- and Ni-salophen complexes 4 and 5, although we note that
Bhat’s reported value for the magnetic susceptibility of 4 is far
too low for a pure sample, but were unable to conclusively
reproduce most of the otherwise previously unreported claims.
The reaction of ligand 3c under the conditions described yields
a purple complex with the same IR and UV−vis spectroscopic
data as that reported by Bhat, but in toto the data obtained by
Bhat and us do not support the formulation of 6a. Of particular
D
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Iron−salen-type complexes have been successfully exploited
in both the coupling of secondary alkyl Grignard reagents with
activated aryl chlorides33 and the coupling of aryl Grignard
reagents with primary and secondary alkyl halides,34 while the
latter reactions can also be catalyzed by an iron Schiff base
complex;35,36 however, it appears that here the use of phenyl
boronic acid and an aryl bromide as substrates is beyond the
scope of these catalyst types. The lack of activity with the
cobalt and nickel complexes 4, 5, and 8a is in accord with the
previous observation that salen complexes of Co(II) and
Ni(II), in contrast with the Fe(III) analogue, give only traces
of cross-coupled product in the coupling of alkyl halides with
aryl Grignards.34
Scheme 2. (a) Unsuccessful and (b) Successful Suzuki Biaryl
Cross-Coupling Reactions
a b c d e f g h i
, , , , , , , ,
Similarly, no cross-coupled product 18 was obtained using
the cobalt PNP−pincer complex tentatively ascribed as 10, nor
with the structurally authenticated analogue, complex 14.
Neither was any catalytic activity observed with the preformed
iron complex of ligand 1, complex 13, nor with the intractable
residue “9*” obtained under Bhat’s synthetic conditions (most
likely the starting material, [Fe(OH2)6]SO4, vide supra).
Likewise, neither the ill-defined solid “11*”, obtained under
Bhat’s conditions, nor the well-defined copper(I) adduct of 1,
complex 12, showed any activity. Instead, in all cases, we
observed peaks in the GC-MS corresponding with unreacted
16 and the trimeric cyclic ester of phenyl boronic acid,
(PhBO)3 (see Figure S33, Supporting Information for a
representative example).
a
Full conditions for the reactions are given in the Supporting
Information. All attempted couplings of 16 with 17 were repeated
independently by (at least) two separate authors. 1,4-Dioxane,
K2CO3, 110 °C. MeCN, NEt3, 80 °C. 6a*, 9*, and 11* refer to the
solids obtained according to Bhat’s synthetic procedures, incorrectly
b
c
d
e
formulated by Bhat as 6a, 9, and 11, respectively. Toluene, K2CO3,
f
g
h
110 °C. MeCN, CS2CO3, 80 °C. MeCN, K2CO3, 80 °C. Lack of
conversion to product demonstrated by GC-MS (see Figure S33).
i
1
Spectroscopic yield, determined by H NMR spectroscopy (1,3,5-
(MeO)3C6H3, internal standard).
Following our complete failure to reproduce any of the
catalysis reported by Bhat using a simple aryl boronic acid
substrate with an electronically activated aryl bromide, we
decided to briefly investigate the application of selected cobalt
precatalysts in the coupling of the electronically deactivated
aryl bromide 19 with the activated nucleophilic substrate, 20,
under conditions that we have previously reported (Scheme
2b).9b While the salophen complex 4 and the PNP−pincer
complex 14 gave only low spectroscopic yields of the desired
cross-coupled product 21, a modest spectroscopic yield (47%)
was obtained when the bis-Schiff base complex 8a was
employed as a precatalyst.
using acetonitrile as the solvent at 80 °C and a selection of
precatalyst types13a−c (Figure 3), shows a remarkable
CONCLUSIONS
■
In conclusion, while we were able to substantiate some of
Bhat’s simpler synthetic claims, notably of complexes that have
previously been reported multiple times, the majority of the
complexes reported for the first time by Bhat proved to be
either starting materials or to have structures very different
from those claimed. An examination of some of the reported
mass spectra pivotal to Bhat’s reported formulations raise
intriguing questions regarding lack of observable isotope
patterns and positions of peaks. Contrary to Bhat’s findings,
none of the Fe, Co, Cu, or Ni complexes, nor structurally
closely related examples, proved, in our hands at least, to be
viable catalysts in the Suzuki biaryl cross-coupling of a simple
aryl boronic acid with an electronically activated aryl bromide.
While we did not screen all of the reported complexes, we
believe that the examples chosen reflect the wider set of
catalysts reported and we are confident that the selected
examples represent a fair cross section. Interestingly, while we
observed no reaction with phenyl boronic acid, some activity
was observed with cobalt catalysts when a BuLi-activated aryl
pinacol boronic ester was employed under our previously
reported conditions;9b we are currently examining this
Figure 3. Replotting of Bhat’s reported data13a−c for the claimed
coupling of 16 with 17 in acetonitrile at 80 °C, catalyzed by the
PNP−Fe, −Co, and −Cu complexes (9−11) and the Fe(II) and
Co(II) bis-Schiff base complexes 6a and 8b.
insensitivity of catalyst performance to variations in either
the metal (Co, Fe or Cu) or the ligand (PNP−pincer or Schiff
base).31 Unfortunately, under these conditions, we were unable
to produce any of the desired biaryl 18 using the salophen or
Schiff base Co-, Ni-, or Fe-based precatalysts 4, 5, and 6a* (the
purple solid incorrectly formulated as 6a), a genuine sample of
6a prepared by an alternative method, or the closely related
analogue 6b, 8a (the actual formulation for the reported
precatalyst 7), or 8b.32
E
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(4) Han, F.-S. Transition-metal-catalyzed Suzuki−Miyaura cross-
coupling reactions: a remarkable advance from palladium to nickel
catalysts. Chem. Soc. Rev. 2013, 42, 5270−5298.
promising lead further and these results will be published in
due course.
The coupling of simple aryl boronic acids with aryl halides
catalyzed by cobalt or, ideally, iron, remains, in our opinion, a
highly desirable, yet unmet, goal.37
(5) Early examples: (a) Saito, S.; Sakai, M.; Miyaura, N. A synthesis
of biaryls via nickel(0)-catalyzed cross-coupling reaction of chloroar-
enes with phenylboronic acids. Tetrahedron Lett. 1996, 37, 2993−
2996. (b) Saito, S.; Oh-tani, S.; Miyaura, N. Synthesis of Biaryls via a
Nickel(0)-Catalyzed Cross-Coupling Reaction of Chloroarenes with
Arylboronic Acids. J. Org. Chem. 1997, 62, 8024−8030.
ASSOCIATED CONTENT
* Supporting Information
■
S
̈
(6) For selected recent examples, see: (a) Mastalir, M.; Stoger, B.;
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.organo-
met.9b00083.
Pittenauer, E.; Allmaier, G.; Kirchner, K. Air-Stable Triazine-Based
Ni(II) PNP Pincer Complexes As Catalysts for the Suzuki−Miyaura
Cross-Coupling. Org. Lett. 2016, 18, 3186−3189. (b) Zhou, J.;
Berthel, J. H. J.; Kuntze-Fechner, M. W.; Friedrich, A.; Marder, T. B.;
Radius, U. NHC Nickel-Catalyzed Suzuki−Miyaura Cross-Coupling
Reactions of Aryl Boronate Esters with Perfluorobenzenes. J. Org.
Chem. 2016, 81, 5789. (c) Shi, S.; Meng, G.; Szostak, M. Synthesis of
Biaryls through Nickel-Catalyzed Suzuki−Miyaura Coupling of
Amides by Carbon−Nitrogen Bond Cleavage. Angew. Chem., Int.
Ed. 2016, 55, 6959. (d) Malan, F. P.; Singleton, E.; van Rooyen, P. H.;
Landman, M. Facile Suzuki-Miyaura coupling of activated aryl halides
using new CpNiBr(NHC) complexes. J. Organomet. Chem. 2016, 813,
7. (e) Shields, J. D.; Gray, E. E.; Doyle, A. G. A Modular, Air-Stable
Nickel Precatalyst. Org. Lett. 2015, 17, 2166.
xyz coordinate file of the DFT-calculated structures
(XYZ)
Synthesis of complexes and catalytic reactions; spectro-
scopic data including UV−vis absorption spectra, FT-IR
spectra, mass spectra, HRMS, 1H NMR spectra, UV−vis
absorption spectra, 31P NMR spectra, and GC trace of
the organic extracts; reexamination of (lack of) solvent
influence including replotting of Bhat’s claimed catalytic
data; crystallographic data; computational methods; and
DFT calculations (PDF)
(7) Review: Thapa, S.; Shrestha, B.; Gurung, S. K.; Giri, R. Copper-
catalysed cross-coupling: an untapped potential. Org. Biomol. Chem.
2015, 13, 4816−4827.
Accession Codes
CCDC 1885663−1885664 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, or 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.
(8) Selected recent examples: (a) Basnet, P.; Thapa, S.; Dickie, D.
A.; Giri, R. The copper-catalysed Suzuki−Miyaura coupling of
alkylboron reagents: disproportionation of anionic (alkyl)(alkoxy)-
borates to anionic dialkylborates prior to transmetalation. Chem.
Commun. 2016, 52, 11072−11075. (b) Gurung, S. K.; Thapa, S.;
Shrestha, B.; Giri, R. Copper-catalysed cross-couplings of arylboronate
esters with aryl and heteroaryl iodides and bromides. Org. Chem.
Front. 2015, 2, 649−653. (c) Zhang, Z.-Q.; Yang, C.-T.; Liang, L.-J.;
Xiao, B.; Lu, X.; Liu, J.-H.; Sun, Y.-Y.; Marder, T. B.; Fu, Y. Copper-
Catalyzed/Promoted Cross-coupling of gem-Diborylalkanes with
Nonactivated Primary Alkyl Halides: An Alternative Route to
Alkylboronic Esters. Org. Lett. 2014, 16, 6342−6345. (d) Sun, Y.-
Y.; Yi, J.; Lu, X.; Zhang, Z.-Q.; Xiao, B.; Fu, Y. Cu-Catalyzed Suzuki−
Miyaura reactions of primary and secondary benzyl halides with
arylboronates. Chem. Commun. 2014, 50, 11060−11062. (e) Zhou, Y.;
You, W.; Smith, K. B.; Brown, M. K. Copper-Catalyzed Cross-
Coupling of Boronic Esters with Aryl Iodides and Application to the
Carboboration of Alkynes and Allenes. Angew. Chem., Int. Ed. 2014,
53, 3475−3479. (f) Gurung, S. K.; Thapa, S.; Kafle, A.; Dickie, D. A.;
Giri, R. Copper-Catalyzed Suzuki−Miyaura Coupling of Arylboronate
Esters: Transmetalation with (PN)CuF and Identification of
Intermediates. Org. Lett. 2014, 16, 1264−1267.
AUTHOR INFORMATION
Corresponding Author
*E-mail: r.bedford@bristol.ac.uk.
■
ORCID
Mattia Manzotti: 0000-0001-9058-8087
Robin B. Bedford: 0000-0002-8021-8768
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the EPSRC for a studentship (S.B.T.), the provision
of studentships through the EPSRC Centre for Doctoral
Training in Catalysis (M.M. and S.L.J.L.), the Bristol Chemical
Synthesis Centre for Doctoral Training (B.J.S.R.), and the
International Research Support Initiative Program, HEC,
Pakistan, for funding (S.A.).
(9) (a) Neely, J. M.; Bezdek, M. J.; Chirik, P. J. Insight into
Transmetalation Enables Cobalt-Catalyzed Suzuki−Miyaura Cross
Coupling. ACS Cent. Sci. 2016, 2, 935−942. (b) Asghar, S.; Tailor, S.
B.; Elorriaga, D.; Bedford, R. B. Cobalt-Catalyzed Suzuki Biaryl
Coupling of Aryl Halides. Angew. Chem., Int. Ed. 2017, 56, 16367−
16370. (c) Duong, H. A.; Wu, W.; Teo, Y.-Y. Cobalt-Catalyzed Cross-
Coupling Reactions of Arylboronic Esters and Aryl Halides.
Organometallics 2017, 36, 4363−4366.
(10) (a) Bedford, R. B.; Hall, M. A.; Hodges, G. R.; Huwe, M.;
Wilkinson, M. C. Simple mixed Fe−Zn catalysts for the Suzuki
couplings of tetraarylborates with benzyl halides and 2-halopyridines.
Chem. Commun. 2009, 6430−6432. (b) Hatakeyama, T.; Hashimoto,
T.; Kondo, Y.; Fujiwara, Y.; Seike, H.; Takaya, H.; Tamada, Y.; Ono,
T.; Nakamura, M. Iron-Catalyzed Suzuki−Miyaura Coupling of Alkyl
Halides. J. Am. Chem. Soc. 2010, 132, 10674−10676. (c) Hashimoto,
T.; Hatakeyama, T.; Nakamura, M. Stereospecific Cross-Coupling
between Alkenylboronates and Alkyl Halides Catalyzed by Iron−
Bisphosphine Complexes. J. Org. Chem. 2012, 77, 1168−1173.
(d) Hatakeyama, T.; Hashimoto, T.; Kathriarachchi, K. K.; Zenmyo,
T.; Seike, H.; Nakamura, M. Iron-Catalyzed Alkyl−Alkyl Suzuki−
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there is a difference claimed between the performance of the two
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points in each solvent is constant (4.7(1) with 9, 3.89(4) with 11)
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H
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