Pd-Catalysed carbonylative Suzuki-Miyaura cross-couplings using Fe(CO)5under mild conditions: generation of a highly active, recyclable and scalable ‘Pd-Fe’ nanocatalyst

Article abstract of DOI:10.1039/d0gc03036h

The dual function and role of iron(0) pentacarbonyl [Fe(CO)₅] has been identified in gaseous CO-free carbonylative Suzuki-Miyaura cross-couplings, in which Fe(CO)₅supplied COin situ, leading to the propagation of catalytically active Pd-Fe nanoparticles. Compared with typical carbonylative reaction conditions, CO gas (at high pressures), specialised exogenous ligands and inert reaction conditions were avoided. Our developed reaction conditions are mild, do not require specialised CO high pressure equipment, and exhibit wide functional group tolerance, giving a library of biaryl ketones in good yields.

Full text of DOI:10.1039/d0gc03036h

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Pd-Catalysed carbonylative Suzuki–Miyaura cross-
couplings using Fe(CO)5 under mild conditions:
generation of a highly active, recyclable and
scalable ‘Pd–Fe’ nanocatalyst†
Cite this: Green Chem., 2021, 23,
920
Zhuangli Zhu,a,b Zhenhua Wang,a Yajun Jian, a Huaming Sun,a Guofang Zhang,a
Jason M. Lynam, c C. Robert McElroy, c Thomas J. Burden,c Rebecca L. Inight,c
a
Ian J. S. Fairlamb, *c Weiqiang Zhang *a and Ziwei Gao
*
The dual function and role of iron(0) pentacarbonyl [Fe(CO)5] has been identified in gaseous CO-free car-
bonylative Suzuki–Miyaura cross-couplings, in which Fe(CO)5 supplied CO in situ, leading to the propa-
gation of catalytically active Pd–Fe nanoparticles. Compared with typical carbonylative reaction con-
ditions, CO gas (at high pressures), specialised exogenous ligands and inert reaction conditions were
avoided. Our developed reaction conditions are mild, do not require specialised CO high pressure equip-
ment, and exhibit wide functional group tolerance, giving a library of biaryl ketones in good yields.
Received 7th September 2020,
Accepted 23rd November 2020
DOI: 10.1039/d0gc03036h
rsc.li/greenchem
in academic laboratories, for which expertise and specialised
equipment might be limited, with health and safety concerns
Introduction
Pd-Catalysed three-component coupling reactions of aryl being at the forefront of any decision-making process. It is
boronic acids, carbon monoxide (CO) and aryl halides/pseudo- also known that the CO-insertion efficiency is reduced when
halides, generally known as carbonylative Suzuki–Miyaura employing electron-deficient aryl halides,6 which can typically
cross-coupling (C-SMCC) reactions,1 display numerous syn- be overcome by the adoption of an expensive exogenous ligand
thetic advantages, particularly the ready availability of com- or high pressure in CO (Fig. 1a).7
mercially available starting materials, which are typically ther-
Moving the field forward, the development of a carbonyla-
mally-, air- and water-stable. The C-SMCC reactions exhibit tion procedure employing the in situ generation of CO, as a
wide functional group compatibility, accompanied by broad substitute for gaseous CO, is appealing and arguably necessary
substrate scope.2 Typically, the reaction represents a straight-
forward and convenient process allowing access to a myriad of
symmetrical and unsymmetrical biaryl ketones,3 which are
omnipresent in natural products and other synthetic target
compounds, with some exhibiting favourable bioactivity and
material properties.4
Over the last few decades we have seen practical advances
in C-SMCCs, especially enabled through the design of new Pd
(pre)catalysts.5 However, the toxic and flammable CO gas
potentially hinders wider adoption of C-SMCCs, especially so
aKey Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education,
School of Chemistry & Chemical Engineering, Shaanxi Normal University,
199 South Chang’an Road, Xi’an, China. E-mail: zwq@snnu.edu.cn,
zwgao@snnu.edu.cn
bTianjin Normal University, 393 West Binshui Road, Tianjin, China
cDepartment of Chemistry, University of York, Heslington, York, North Yorkshire,
YO10 5DD, UK. E-mail: ian.fairlamb@york.ac.uk
Fig. 1 Pd-Catalysed carbonylative-Suzuki–Miyaura cross-couplings
(C-SMCC)@ (a) historical and industrially relevant carbonylative high
pressure system; (b) two-chamber, with independent generation of CO;
and (c) in situ generation of CO from a metal-based CO–RM, the metal
fragment capable of modifying catalytic efficacy.
†Electronic supplementary information (ESI) available: Experimental details and
characterization. See DOI: 10.1039/d0gc03036h
920 | Green Chem., 2021, 23, 920–926
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for general synthetic chemistry laboratories. With this point in nanoparticles in situ, which can be further recycled in multiple
mind several research teams have replaced CO gas with safer reaction runs (Fig. 1c).
sources of molecular CO, i.e. in the form of CO-surrogates.8,9
Indeed, leaders in the field are Skrydstrup10 et al., who have
developed Pd-catalysed carbonylation reactions using ex situ
Results and discussion
CO generated from CO-surrogates and a specially designed
two-chamber reactor (Fig. 1b). Several CO surrogates have been
employed, e.g. 9-methyl-9H-fluorene-9-carbonyl chloride
(COgen), silacarboxylic acids (SilaCOgen), alcohols, carbon
The C-SMCC of p-iodo-acetophenone 1a with phenylboronic
acid 2a to give 3a was chosen as the benchmark reaction to
evaluate the viability of Fe(CO)5 as a CO source and Pd catalyst
dioxide, metal carbonyls and formic acid. These CO-surrogates
modifier. A reaction pathway to the non-carbonylative Suzuki–
degrade in a controllable manner, by different mechanisms,
Miyaura cross-coupled product 3a′ is competitive; thus it is
supplying CO gas for Pd-catalysed carbonylation reactions.10,11
With synthetic verstaility in mind, the well-controlled in situ
generation of CO is essential for the development of a safe and
convenient one-pot C-SMCC methodology. Transition metal
carbonyls (TMCs) have been utilised as CO releasing molecules
(CO-RMs) for therapeutic delivery of CO in biological
critical to identify reaction conditions enabling high selectivity
for 3a. The reaction parameters, including (pre)catalysts, sol-
vents and bases, were screened to establish the best system
for the gaseous CO-free C-SMCC methodology (Table 1).
Interestingly, without a phosphine ligand, all Pd precursors,
Pd(OAc)2 {note: Pd3(OAc)6}, Pd2(dba)3 (dba = 1,4-dibenzylidene
systems,12 a field which we have contributed to independently,
acetone), Pd(acac)2 (acac = acetylacetonate) and polymeric
and for which much is now known about CO-release rates in
PdCl2, exhibited high conversion and selectivity (entries 1–5),
different media. Many readily available homoleptic TMCs are
using as little as 0.5 mol% Pd (pre)catalyst loading (entry 2).
attractive CO-RMs, since many carbonyls per CO-RM can in
The presence of phosphine ligands suppressed the carbonyla-
principle be delivered in solution. More importantly, the
tion product 3a yield (entries 6–12). Poor product selectivity
cleavage of the M–CO bond of TMCs can be controlled by the
shows that the phosphine ligands are able to facilitate the oxi-
variation of temperature. Ni(CO)4 has been employed in the
dative addition of 1a to the in situ generated “L–Pd0” species,
aminocarbonylation of vinyl halides13a and carbonylative
but slow down the subsequent CO insertion into the Pd–C
olefination of aryl halides.13b Larhed et al.14 pioneered Pd-
bond. We also recognise that the phosphine ligands could
catalysed carbonylation of O, N nucleophiles using Cr(CO)6
and Mo(CO)6. The solid CO-RMs were activated by microwave
heating, and CO was generated in situ for carbonylation.
Later, other solid TMCs were evaluated as CO-RMs for tran-
Table 1 Optimization and effects of the reaction parametersa
sition metal-catalysed organic transformations.10 In all
cases, the metal is thought to be a waste element within the
reaction. Indeed, a limitation identified was that the low
valence transition metal residue could poison the active Pd
catalyst species, with reactions being sluggish, leading to
poor yields of the carbonylative products,15a a potential issue
for more challenging substrates.15b,c Maes et al. have devel-
oped methodologies employing isocyanides as CO-surrogates
in Pd-catalysed cross-couplings, offering an alternative
approach.16
In light of highly effective and catalytically competent
Pd/Fe nanoparticles being discovered for C–C cross-coupling
reactions,17 we recognised that iron carbonyls could poten-
tially play the role of CO–RMs, while modifying the pro-
perties and catalytic activity of the Pd catalyst through ben-
eficial interactions with Fe, i.e. where the CO ligands are
utilised for the carbonylation process and the waste Fe
(oxidised) creating a more efficient Pd–Fe catalytic system
in situ. Due to the low-price and earth abundance of iron,
we envisaged that an economical, safer and environmentally
friendly Pd-catalysed C-SMCC methodology using Fe(CO)5
could be developed.
Ligand
3a
3a’
b
Entry
Catalyst
Solvent/base
%
Effect of catalyst and ligand (1 : 1)
1
2
3
4
5
6
7
8
Pd(OAc)2c
Pd(OAc)2
Pd2(dba)3
Pd(acac)2
PdCl2
PdCl2(PPh3)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
90
86
80
89
80
5
64
31
71
70
40
48
7
8
7
7
18
94
31
22
21
25
12
14
PPh3
CyJohnPhos
PCy3
Dppf
Xphos
9
10
11
12
Xantphos
Effect of solvent (3 mL) and base (2 eq.)
13
14
15
16
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Toluene/K2CO3
Dioxane/K2CO3
Anisole/K3PO4
Anisole/DIPEA
87
60
83
51
11
7
10
1
a Reaction conditions: 1a (0.434 mmol), 2a (1.75 eq.), Fe(CO)5
(0.15 mmol), and [Pd] (1 mol%, unless otherwise stated), 80 °C, 12 h.
Entries 1–12: anisole and K2CO3 were used. b Detected by 1H NMR and
confirmed by purification by silica gel chromatography. c Pd3(OAc)6,
referred to as Pd(OAc)2, (0.5 mol% in Pd).
Herein, we report a benign C-SMCC reaction methodology,
which does not require the use of CO gas or exogenous special-
ised ligands, where Fe(CO)5 provides CO for the reaction, gen-
erating well-defined, stable and catalytically competent Fe/Pd
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Table 3 Synthesis of biaryl ketones via different arylboronic acids
influence Pd catalyst speciation, negatively in terms of the
carbonylation selectivity in this system.
The effects of the solvent and base were further examined. It
was found that the C-SMCC reaction proceeded well in relatively
less polar solvents, such as anisole and toluene. The inorganic
bases, K2CO3 and K3PO4, exhibited high substrate conversion
and superior selectivity when compared against the organic
base, DIPEA (entries 13–16). Other TMCs were also assessed as
CORMs. Indeed, the ferrous-system performed considerably
better than Mo(CO)6 and Cr(CO)6 (Table S2, see the ESI†). It is
of particular note that using gaseous CO (balloon pressure) in
place of Fe(CO)5 failed to effect a successful C-SMCC reaction,
with only the SMCC biaryl product 3a′ being formed. The
outcome demonstrates that Fe(CO)5 not only acts as a CO
source, but also functions positively vide infra to enhance this
specific Pd-catalysed C-SMCC reaction in some way.
With the optimised reaction conditions in hand
{0.15 mmol Fe(CO)5, 1 mol% Pd(OAc)2, anisole and K2CO3},
various functional biaryl ketones were synthesized using the
new C-SMCC reaction differentiated by changes in aryl substi- sessing methoxy groups at para-, meta- and ortho-positions
tuents, either electron-donating or electron-withdrawing, of were isolated in good yields, with 74% for 3e, 53% for 3i and
aryl iodides (Table 2) and those of phenylboronic acids 78% for 3m, respectively. Meanwhile, as the length of the alkyl
(Table 3), to evaluate the scope and limitations of the new chain was increased to ethyl a 66% yield of 3d was recorded.
C-SMCC methodology.
As for electron-withdrawing substituents, similar trends were
Table 2 shows the effects of substituents in the reactions of noted. For example, the weakly electron-withdrawing ester
aryl iodides. Under the best identified reaction conditions, the group, p-CO2Me, gave a good yield of 80% (3q), with the
para-halogenated (Cl, Br, and F) aryl iodides gave diaryl p-CO2Et group giving a 73% yield of 3u. In addition, the stron-
ketones in good yields (p-F, 3b, 79%, p-Cl, 3f, 73%, and p-Br, ger electron-withdrawing substituents only lower the yields mar-
3n, 74%). However, ortho-Cl and Br substituents led to only ginally (p-CF3, 3h, 57%, p-NO2, 3p, 68%, and m-NO2, 3t, 65%).
modest yields of cross-coupled products with 50% (3j) and We further succeeded in synthesizing the biaryl ketones con-
30% (3o) biaryl ketone products being generated respectively. taining naphthalene (3r, 55%) and thiophene (3s, 54%), which
We tentatively attribute the lowering of the yield to steric are key intermediates to interesting luminescent materials.19
effects, which retard the oxidation addition step.18 The pres-
As shown in Table 3, different organoboronic acids were uti-
ence of a methyl group at para-, meta- and ortho-positions led lised in our new C-SMCC methodology. Most of the organo-
to good product yields (p-Me, 3c, 84%, m-Me, 3g, 74%, and boronic acids underwent carbonylative coupling with good
o-Me, 3k, 72%). The corresponding biaryl ketone products pos- yields. The halogenated aryl iodides were converted into diaryl
ketones in very good yields (e.g. p-F, 3b, 84%, p-Cl, 3f, 89%,
and p-Br, 3n, 74%). Both electron-donating (p-Me, 3c, 88%
and p-OMe, 3e, 80%) and electron-withdrawing substituents
(p-CO2Me, 3q, 84%) also gave good yields. The 9-fluorenyl aryl-
Table 2 Pd catalyzed carbonylative Suzuki coupling reaction
boronic acid (4d, 74%) was pleasingly formed with a good
yield. Notably, thio-moieties were well tolerated. Thus, the biar-
ylketone products bearing p-MeS and 2-thiophene were both
isolated in 65% yield (4a and 3s). A sterically encumbered sub-
stituent, o-iPr, gave rise to a 73% yield of 4b, whilst the organo-
boronic acids bearing several fluorine atoms or a p-SO2Me
group gave lower yields of 23% (4c) and 37% (4e), respectively.
Encouraged by the results presented above, we sub-
sequently carried out a C-SMCC reaction on a gram scale to
demonstrate its practical utility. With 5 mmol of 1a, product
3a was formed in 86% yield under our optimised conditions
(Scheme 1). Furthermore, the phenylenebis–phenylmetha-
nones were synthesized via the C-SMCC reactions of various
diiodobenzenes with phenylboronic acid, in up to 86% yield
(Scheme 1, 5a–c). The results highlight the significant poten-
tial of this C-SMCC for practical applications.
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Table 4 Quantitative and qualitative metrics for the synthesis of 3a
(note: a ‘Fe(CO)2’ fragment is qualitatively a side product from the
overall transformation)
Finally, we have tested the C-SMCC methodology using
4-bromo-anisole and 4-bromo-6-methyl-2-pyrone as exemplar
brominated substrates (employing standard conditions as
described in Table 2, in the presence and absence of activating
DPPF and Xantphos ligands which we hypothesised might
assist with C–Br bond activation and CO-migratory insertion
steps). However, in the case of 4-bromo-anisole it was left
unreacted. For 4-bromo-6-methyl-2-pyrone, a small amount of
4-phenyl-6-methyl-2-pyrone was formed (7%) when the exogen-
ous Xantphos ligand was added (by traditional SMCC reaction).
Green metrics using the CHEM21 toolkit
Metric
Method A
Flag Method B
Flag
Clark et al. developed a unified metrics toolkit to evaluate the
global sustainability of chemical reactions. It was a successful
toolkit developed by the CHEM21 consortium consisting of
academic and industrial members.20a The toolkit is built upon
a comprehensive and holistic range of criteria enabling the
measurement of how green a reaction is. The toolkit has been
applied in the assessment of the synthesis of multicomponent
products,20b opioid scaffolds,20c dialkyl chloramines,20d ionic
liquids,20e solvents,20f peptides20g and tryptophan C–H bond
functionalization chemistry.20i,h We recognized that the toolkit
would be useful for initial appraisal of the newly developed
C-SMCC methodology described above. The synthesis of 3a
from 4-iodoacetophenone 1a and phenylboronic acid 2a
(Scheme 1) was compared with a relevant synthesis involving
Yield
86%
99.0%
100%
99%
Conversion
Selectivity
94.3%
91.2%
Reaction mass efficiency (RME) 23.2%
Atom economy (AE)
Solvents
16.7%
42.0%
Toluene
39.2%
Anisole
Health and safety
H300, H330
H360, H372
Process mass intensity (PMI)
PMI (reaction chemicals)
PMI (reaction solvents)
Catalyst
40.0
4.3
35.7
Yes
25.5
6.0
19.5
Yes
Reactor
Elements
Energy
Batch
B, Pd, I
80 °C
Batch
B, Pd, I
120 °C
an activated Pd precatalyst possessing
a
bis-chelating
N-heterocyclic carbene ligand.21 The literature procedure
employed 13.8 bar (200 psi) of CO and 0.01 mol% of Pd pre-
catalyst. The methodology from the Chem21 Metrics Toolkit at
the first path (key reaction) level was adopted to compare the
results, which are collated in Table 4, including the reagent
and product stoichiometries.
the final product (note: the final destination for Fe is in the
form of Fe2O3 vide infra which is required for Pd catalyst
enhancement). However, the AE is dominated by the iodine
and boronic acid leaving groups, a necessary and mandatory
requirement for the arylation process. More significant
however is the Reaction Mass Efficiency (RME) being signifi-
cantly better for our work. This is because the CO–RM, Fe
(CO)5, is an efficient and mild CO source, while the reported
reaction conditions employ a 23 molar excess under significant
pressure. The same effect can be seen in the Process Mass
Intensity (PMI) reaction chemicals. These results are likely
more significant, as 3× refills and purges of CO are necessary
for the reported21 pressurised reaction vessel. The inclusion of
this practical and necessary requirement gives an RME of 6.7%
and a PMI of 14.9. Neither reaction scores well on health and
safety, due to the need for liberation of CO (which is formally a
necessary requirement for a carbonylation reaction). Lastly, the
lower temperature and absence of the need to pressurize give
an improved energy demand for our C-SMCC methodology.
The data in Table 4 show that the green metrics for the two
synthetic methodologies are broadly similar. Surprisingly, this
includes atom economy (AE), with our work only being slightly
poorer due to one fragment of “Fe(CO)2” not making it into
Mechanistic studies
To assess further the properties of the metal species formed in
the catalytic C-SMCC reactions, a series of control experiments
were conducted (Scheme 2). Initially, addition of Hg (known to
generally suppress surface catalysis) diminished the catalytic
activity of the Pd–Fe catalytic system, with neither the carbony-
Scheme 1 Examples and gram-scale reaction in practical applications.
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The chemical state of the Pd–Fe nanoparticle surface was
analysed by XPS (Fig. 3 and ESI S3†). Fig. 3 shows the XPS core
level spectra for Pd 3d and Fe 2p, characterized by spin–orbit
splitting (Pd 3d5/2, 3d3/2 and Fe 2p3/2, 2p1/2 components),
where the peaks at 335.6 and 340.8 eV result from Pd 3d5/2 and
Pd 3d3/2, respectively. The Pd species are characterised as
being in an oxidation state of zero. FeIII was confirmed based
on the peaks at 710.6 and 724.1 eV, corresponding to Fe 2p3/2
and Fe 2p1/2, respectively. The side peaks were attributed to
the oxide; thus Fe exists in the form of Fe2O3. The EDAX
mapping analysis confirmed the composition of the Pd–Fe
nanoparticles deriving from Fe, Pd and O, which is fully con-
sistent with our deduction (ESI S4†). SEM images show the
morphology of the Pd–Fe nanoparticles (Fig. S5, see the ESI†).
Finally, the recyclability of the Pd–Fe nanoparticles was
assessed. The Pd–Fe nanoparticles were first isolated from a
reaction of 1a + 2a → 3a, by filtration, and then sequentially
washed with water and ethyl acetate. The C-SMCC reaction 1a
+ 2a → 3a was then recharged with fresh Fe(CO)5 and the iso-
lated catalyst. At each cycle we found that the isolated catalyst
can be recycled giving 3a, with the yields of 3a going from 90
to 50% over the 4 cycles. The deactivation of the hetero-
geneous Pd–Fe nanocatalyst species can be attributed to an
excess Fe residue being deposited onto the heterometallic
surface, either blocking the catalytically active sites or causing
Scheme 2 Control experiments to probe catalyst behaviour.
lative (3a) nor non-carbonylative cross-coupling products (3a′)
detected (Scheme 2a). The Hg poison test supports a hetero-
geneous/pseudo-heterogeneous Pd-catalysed C-SMCC reaction
using Fe(CO)5.22 We succeeded in separating the catalytic Pd–
Fe nanoparticle material, which also catalysed a subsequent
carbonylative coupling reaction using either additional CORM
or CO gas, proceeding with 67% and 70% yields, respectively.
Surprisingly, the catalytic Pd–Fe nanoparticles produced the
carbonylative product independent of an added CO-source (3a,
in 15% yield), indicating that CO resides within the Pd–Fe par-
ticles, i.e. as a CO-reservoir. FT-IR spectroscopic analysis of the
fresh isolated metal catalyst material revealed three character-
istic CO bands of the particles at 2106, 2029 and 1866 cm−1
(Fig. S6, see ESI†), suggesting that the particle surface consists
of several carbonyl ligands, e.g. η1-Pd-CO and μ2-Fe-CO, which
derive from the transfer process of CO from CO–RM to ketone
products during the Pd-catalysed C-SMCC reaction. It is impor-
tant to note that the C-SMCC reaction does not occur without
added Pd(OAc)2 (Scheme 2b). Starting from Pd(OAc)2, the Pd-
catalysed C-SMCC reaction with CO gas was found to afford
only a 13% yield of biaryl ketone 3a (Scheme 2c), indicating
again that Fe(CO)5 not only acted as a CO–RM, but also
enhanced Pd-catalyst performance.
a
restructuring of the catalyst surface (Fig. 4A).15,21
Interestingly, in the absence of Fe(CO)5, the isolated Pd–Fe
nanoparticles also independently catalyzed the efficient SMCC
reaction of 1a + 2a → 3a′ (Fig. 4B). A small amount of carbony-
lative product 3a is formed in the first cycle, formed from
residual CO from the Pd–Fe nanoparticle catalyst. Crucially,
To further characterize the catalytically active Pd–Fe par-
ticles, Transmission Electron Microscopy (TEM) measure-
ments were conducted. The experiments showed the presence
of 2 nm sized Pd–Fe nanoparticles over a large area (histogram
inset in Fig. 2a). Lattice fringes were observed in the high-
resolution TEM images (Fig. 2b), showing that the inter-planar
distances approximate to 0.226 nm and 0.198 nm, corres-
ponding to the (200) and (111) planes of the Pd metal. The
assignment was confirmed using Fast Fourier Transform (FFT)
and inverse FFT images (inset in Fig. 2b).
Fig. 3 XPS images of the Pd–Fe catalyst nanoparticle material, with
Fig. 2 (a) HRTEM images of size distribution and (b) lattice fringes.
924 | Green Chem., 2021, 23, 920–926
Fe2O3 and Pd0 prominent species.
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Acknowledgements
This work was supported by the grant from the National
Natural Science Foundation of China (21371112 and
21446014), the 111 Project (B14041), the Fundamental Funds
Research for the Central Universities (No. GK201501005,
GK201503029, and 2016CSY002), the grant from the
Fundamental Doctoral Fund of Ministry of Education of
China (20120202120005), and the Program for Changjiang
Scholars and Innovative Research Team in University
(IRT_14R33). I. J. S. F. is grateful to the Royal Society for
University Research Fellowship (2004-12). We thank Syngenta
and the University of York for the iCASE funding and student-
ship to T. J. B. We also acknowledge the Leverhulme Trust for
funding, enabling us to initiate this research (W. Z., I. J. S. F.,
and J. M. L.).
Fig. 4 Recyclability of the Suzuki–Miyaura carbonylative cross-coup-
ling (cycle A) and feasibility of the Pd–Fe nanoparticle catalyst in the
SMCC reaction of iodobenzene and phenylboronic acid to give benzo-
phenone (cycle B).
Notes and references
the yield of 3a′ was over 80% for the subsequent cycles (2–5).
These results are in accordance with the unique cooperative
activity of a Pd–Fe bimetallic catalytic system reported by
Lipshutz et al. for standard SMCC reactions (Fig. 4B).17
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In conclusion, we have developed a highly efficient synthetic
strategy for accessing biaryl ketones via CO-gas free carbonyla-
tive Suzuki–Miyaura cross-couplings, using anisole as a green
solvent.23 The green credentials of the methodology were com-
pared with those of a recently reported reaction employing a
novel and highly active Pd precatalyst possessing a bis-chelat-
ing carbene ligand. The Fe–Pd nanoparticles generated in situ
from mixing ‘Pd(OAc)2’ and Fe(CO)5 are the key factor in the
high catalytic efficiency observed in our study. The structural
features of the in situ Fe–Pd nanoparticles were evaluated by
TEM, EDAX, XPS, SEM and FT-IR spectroscopy, demonstrating
the narrow size distribution, averaged ∼2 nm, which is the so-
called ‘Goldilocks size’ for effective cross-coupling catalysis
under reducing conditions.24 We believe that the particles
consist primarily of Fe2O3 and the Pd metal, possessing a
relaxed porous surface. Based on the above structural infor-
mation, the efficacy of the C-SMCCs can be reasonably attribu-
ted to the synergistic effect of bimetallic Pd–Fe NPs, demon-
strating the superiority over monometallic catalysis, which
ought to facilitate further applications in catalysis, materials
science, and organic synthesis. Studies directed toward under-
standing metal–metal interactions and cooperativity, particu-
larly in bimetallic NPs,25 and their applications, are currently
underway.
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Conflicts of interest
There are no conflicts to declare.
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926 | Green Chem., 2021, 23, 920–926
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