Ni: Vs. Pd in Suzuki-Miyaura sp2-sp2 cross-coupling: A head-to-head study in a comparable precatalyst/ligand system

Article abstract of DOI:10.1039/c9ob00561g

The Suzuki-Miyaura reaction is a cornerstone method for sp²-sp² cross-coupling in industry. There has been a concerted effort to enable the use of Ni catalysis as an alternative to Pd in order to mitigate cost and improve sustainability. Despite significant advances, ligand development for Ni-catalyzed Suzuki-Miyaura cross-coupling remains underdeveloped when compared to Pd and, as a consequence, ligands for Ni-catalyzed processes are typically taken from the Pd arena. In this study we evaluate the effect of using a similar Ni and Pd precatalyst based on a common bidentate ligand (dppf) in a head-to-head format for the most common type of biaryl couplings, establishing the practical implications of direct replacement of Pd with Ni, and identifying the potential origins of these observations in a mechanistic context.

Full text of DOI:10.1039/c9ob00561g

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Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
benzene
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Ni vs. Pd in Suzuki-Miyaura sp2-sp2 Cross-Coupling: A Head-to-
Head Study in a Comparable Precatalyst/Ligand System
Matthew J. West and Allan J. B. Watson*
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
The Suzuki-Miyaura reaction is a cornerstone method for sp2-sp2 for Pd catalysis is extensive to the extent that selection of a
cross-coupling in industry. There has been a concerted effort to ligand to improve a particular cross-coupling has become
enable the use of Ni catalysis as an alternative to Pd in order to intuitive. However, such an understanding has yet to be realized
mitigate cost and improve sustainability. Despite significant for Ni. It is widely recognized that the different properties of Ni
advances, ligand development for Ni-catalyzed Suzuki-Miyaura vs. Pd require unique ligand systems; rational ligand design
cross-coupling remains underdeveloped when compared to Pd and, based on stereoelectronic considerations is at the forefront of
as a consequence, ligands for Ni-catalyzed processes are typically Ni catalysis.18 In addition, several examples have shown that
taken from the Pd arena. In this study we evaluate the effect of ligand systems for Pd can be ineffective for Ni in C–X specific
using a similar Ni and Pd precatalyst based on a common bidentate bond formations.18
ligand (dppf) in a head-to-head format for the most common type The development of bespoke ligands to improve the utility of Ni
of biaryl couplings, establishing the practical implications of direct precatalysts has additional practical considerations: these
replacement of Pd with Ni, and identifying the potential origins of ligands may not be commercially available and the use of
these observations in a mechanistic context.
proprietary ligands can obviate any economic saving afforded
by the change in metal.19 This is especially pertinent on larger
scale where a less effective ligand with lower overall economic
cost by virtue of reduced IP barrier may be preferable to a more
effective ligand.19
The Suzuki-Miyaura (SM) reaction is the primary method for Pd-
catalyzed sp2-sp2 cross-coupling, estimated to account for the
majority of C-C bond constructions in the pharmaceutical
industry (Scheme 1a).1,2 Indeed, the prevalence of the biaryl
unit in marketed drugs has been attributed to the success and
widespread utility of this reaction.3 While Pd remains the
catalyst of choice for the SM reaction, the potential to replace
The use of ligands shown to be effective for Pd-catalyzed SM is
therefore a common, and very practical stopgap approach. The
question remains what limitations this transfer of theoretically
non-ideal ligands imparts and the practical issues this may or
may not cause.
Pd for less expensive transition metals has become
a
Here we detail a head-to-head study of Pd vs. Ni in sp2-sp2
particularly active field of enquiry. In particular, Ni catalysis has
been identified as the main alternative to Pd.4-6 This is based on
a number of attractive attributes including, chiefly, the
significantly lower cost of Ni metal vs. Pd metal (Ni is ca. 1000-
fold less expensive than Pd)4,7 and the increased nucleophilicity
of Ni(0) vs. Pd(0) permitting a more facile oxidative addition and
therefore a wider range of electrophile.4-6
Suzuki-Miyaura cross-coupling using
a comparable and
inexpensive dppf precatalyst system,20 documenting the main
considerations/differences in reaction set up, substrate
compatibility, and observations relating to protodeboronation
of sensitive organoborons.
(a) The Suzuki-Miyaura reaction
The reactivity of Ni(0) complexes (e.g., Ni(cod)2) is both an
advantage and disadvantage: the enhanced nucleophilicity
comes with the price of reactivity towards O2 and H2O.8
Accordingly, this has led to development of more practicable
Ni(II) precatalysts that significantly simplify reaction set up.5-7,9-
Ni or Pd cat.
• Most used cross-coupling reaction
• Cornerstone reaction in industry
• Ni and Pd catalysis viable
X
B(OR)2
aryl halide
organoboron
C–C bond
(b) Pd vs. Ni in sp2-sp2 Suzuki-Miyaura: a head-to-head study with comparable phosphine precatalyst
17
Comparable air-stable precatalysts
Key questions
The choice of ligand, however, is perhaps the most difficult.
PPh2
PPh2
• Is a direct switch from Pd to Ni possible?
• Substrate compatibility and reaction set up?
• How do the precatalysts compare?
The knowledge base, as well as the range of effective ligands,
o-tol
Cl
Cl
Ni
Pd
Fe
Fe
Cl
PPh2
PPh2
• Can incompatibilities be explained/overcome?
Ni(dppf)(o-tol)Cl
Pd(dppf)Cl2
EaStCHEM, School of Chemistry, University of St Andrews, North Haugh, St Andrews,
Fife, KY16 9ST, UK. Email: aw260@st-andrews.ac.uk
Electronic Supplementary Information (ESI) available: Experimental procedures,
characterisation data, copies of spectra. See DOI: 10.1039/x0xx00000x
Scheme 1. (a) The Suzuki-Miyaura reaction and (b) key questions from
a head-to-head study using precatalysts derived from dppf.
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Benchmark reaction and optimization. Dppf-based precatalysts operated comparably effectively under very similar
View Article Online
DOI: 10.1039/C9OB00561G
precatalysts were selected as Pd(dppf)Cl2 is a highly effective, conditions.
Pd or Ni cat.
inexpensive, and routinely used precatalyst for SM cross-
Ar1
Ar2
1.1 equiv
Ar1
Ar2
X
B(OH)2
base, solvent, T °C
coupling, and dppf has been reported to be effective for specific
1 equiv
3a-ak
Ni-catalyzed SM as well as other coupling processes; Ni(dppf)(o-
Ni: Ni(dppf)(o-tol)Cl (2 mol%), K3PO4 (3 equiv), 1,4-dioxane, 80 °C, 4 h
Pd: Pd(dppf)Cl2 (4 mol%), K3PO4 (3 equiv), H2O (5 equiv) 1,4-dioxane, 80 °C, 4 h
tol)Cl is
a
comparable precatalyst that is air stable.21
(a) Aryl bromide survey (Ar2 = Ph)
Accordingly, this would represent a head-to-head study using
precatalyst systems that are routinely used, available, and
relatively well understood. The benchmark reaction with main
observations (deviations from optimized conditions) is shown in
Table 1.
Me
F
N
N
N
N
BnN
N
N
Br
Br
Br
Br
Br
1d
1e
1a
1b
1c
Ni: 0%
Pd: 0%
Ni: 98%
Pd: 98%
Ni: 86%
Pd: 85%
Ni: 9%
Pd: 57%
Ni: 96%
Pd: 93%
Table 1. Main observations in a benchmark reaction.
O
CHO
CHO
Br
B(OH)2
Pd or Ni cat.
conditions
Me
O
CN
OMe
F
Br
1g
Ni: 100%
Pd: 96%
Br
1a
(1 equiv)
2a
(1.1 equiv)
F
3a
Br
1j
Ni: 92%
Pd: 69%
Br
Br
1f
1h
Ni: 95%
Pd:94%
1i
Ni: Ni(dppf)(o-tol)Cl (1 mol%), K3PO4 (3 equiv), 1,4-dioxane, 80 °C, 4 h
Pd: Pd(dppf)Cl2 (4 mol%), K3PO4 (3 equiv), H2O (5 equiv) 1,4-dioxane, 80 °C, 4 h
Ni; 91%
Pd: 99%
Ni: 83%
Pd: 89%
CN
O
O
Entry
Deviation from ‘standard’ conditions
Ni method: No change
Yield (%)a
CHO
Me
N
Me
OMe
1
2
3
4
5
6
>99
>99
>99
68
S
Ni method: 4 mol% catalyst
Ni method: 2 mol% catalyst
Ni method: 5 equiv H2O
Ni method: 50 °C
Br
Br
1l
Br
Br
Br
1k
Ni: 100%
Pd: 98%
1m
Ni: 96%a
Pd: 70%a
1n
Ni: 92%
Pd: 96%
1o
Ni: 86%
Pd: 91%
Ni:100%
Pd: 74%
93
NO2
HN
N
N
O
SO2Me
Pd method: No change
>99
Me
Me
a Determined by 19F NMR analysis using an internal standard.
Br
Br
Br
Br
Br
The optimal conditions for the simple benchmark coupling of 1a
with 2a delivers the product 3a in quantitative yield (entries 1
(Ni) and 6 (Pd)). The Pd system (entry 6) was based on our
previous work with this and related Pd systems for SM cross-
coupling where these conditions (low [H2O] and elevated
temperature)22-27 promote fast cross-coupling. We attribute
this to promoting formation of Pd(II)(Ar)(OH)27-30 while keeping
the concentration of neutral boronic acid high,27-31 thereby
assisting transmetalation. Translating these conditions to the Ni
precatalyst system was relatively smooth with the main
contrasts as follows: (1) Catalyst loading for Ni could be lowered
significantly as compared to Pd, however, while 1 mol% was
effective for this benchmark reaction, 2 mol% was more
effective upon application to substrates with greater
functionality (vide infra). (2) The Ni system can tolerate
additional H2O but not to the level that Pd can accommodate –
the reaction remained quantitative up to a maximum of 3 equiv,
with efficiency beginning to decline after this (entry 4), likely
due to formation of Ni(II)(OH) dimers as proposed by
Grimaud.32 Under dry conditions (e.g., entry 1) boroxine is
formed from the boronic acid, liberating H2O. Indeed, many Ni-
based systems use the boroxine or boronic esters to allow very
dry reaction set up;4-6 however, this system tolerated the use of
the boronic acid allowing a more practical approach. (3)
Regarding temperature, Ni(dppf)(o-tol)Cl has been reported to
allow room temperature SM of activated aryl chlorides;13
however, in our hands we could not take the temperature
1p
Ni: 96%
Pd: 84%
1q
Ni: 0%
Pd: 96%
1r
1s
Ni: 0%
Pd: 30%
1t
Ni: 57%a
Pd: 100%
Ni: 97%
Pd: 91%
(b) Boronic acid survey (Ar1 = Ph)
SO2Me
NMe2
S
S
NO2
B(OH)2
B(OH)2
B(OH)2
B(OH)2
B(OH)2
2b
Ni: 0%
Pd: 51%
2c
2d
2e
2f
Ni: 36%
Pd: 78%
Ni: 95%
Pd: 97%
Ni: 50%
Pd: 80%
Ni: 56%
Pd: 95%
NH2
OH
Ph
B(OH)2
B(OH)2
B(OH)2
B(OH)2
B(OH)2
2g
Ni: 0%
Pd: 68%
2h
2i
2j
2k
Ni: 79%
Pd: 81%
Ni; 40%
Pd: 67%
Ni: 89%
Pd: 91%
Ni = 72%
Pd = 99%
OMe
SMe
OMe
HN
N
MeO
OMe
B(OH)2
B(OH)2
B(OH)2
B(OH)2
B(OH)2
2l
2m
Ni: 62%
Pd: 90%
2n
2o
2p
Ni = 0%
Pd = 67%
Ni: 9%
Pd: 84%
Ni: 91%
Pd: 93%
Ni: 0%
Pd: 90%
CO2Me
CHO
H
BnN
N
HCl
N
N
Me
B(OH)2
B(OH)2
B(OH)2
B(OH)2
B(OH)2
2q
Ni: 0%
Pd: 0%
2r
2s
2t
2u
Ni: 75%a
Pd: 80%
Ni: 8%
Pd: 51%a
Ni: 90%
Pd: 95%
Ni: 24%
Pd: 91%
below 50 °C (no reaction at room temperature), with 80 °C
being overall more efficient. In brief, however, the similar
Scheme 2. Substrate assessment using optimized conditions for each
a
1
precatalyst. Isolated yields. Determined by H NMR analysis using an
2 | J. Name., 2012, 00, 1-3
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internal
standard.
Green,
expected/rationalized;
blue, Substituent electronic effects in Ni-catalyzed SM reactions have
View Article Online
DOI: 10.1039/C9OB00561G
unexpected/rationalized; grey, unexpected/not rationalized.
been recently investigated by Grimaud and can exhibit
completely different electronic trends depending on the
Functional group compatibility/comparison. The primary goal
of this study was to determine precatalyst generality under
conditions that are practically accessible and therefore more
likely to be used. Important to this goal was the identification of
functional groups that were problematic for either Ni or Pd.
Accordingly, in a first assessment, a broad range of aryl bromide
and organoboron was assessed (Scheme 2). Aryl bromides were
used exclusively to allow direct comparison of the arene and
avoid potential issues with oxidative addition based on variation
of (pseudo)halide. Similarly, boronic acids were used as the
archetypal organoboron in SM cross-coupling, and this avoids
the preparation of boroxines/esters.
specific conditions, especially relating to the base/H2O
availability, which may explain these observations.32 Despite
this, the extremely low yield for 2s implicates additional
problems with this substrate; this was reinforced by additive
experiments (vide infra). It is important to note that sluggish
transmetalation may affect precatalyst activation, which is
believed to rely upon anion metathesis, transmetalation, and
reductive elimination,13,15 i.e., eqn 1.
Ni(II)(dppf)(o-tol)X
Ni(II)(dppf)(o-tol)(Ar)
®
Ni(II)(dppf)(o-tol)(OH)
Ni(0)(dppf)
®
(1)
®
In terms of the electrophile, these proceeded without major
incident for both Ni and Pd precatalysts, with good synthetic
efficiency typically observed. The benchmark reaction using 1a
operated effectively on 0.25 and 2.5 mmol scale using both Pd
and Ni systems (see Supporting Information). Bromides 1e and
1s were the main exceptions: 1e was entirely unreactive and the
sterically demanding 1s impaired efficiency, especially for Ni.
Two expected observations were made regarding compatibility
of 1c and 1q with the Ni precatalyst. Nicasio reported that Ni(II)
complexes formed from oxidative addition to 2-bromopyridine
(1c) form 6-membered dimer metallocycles that are
catalytically inactive.33 Interestingly, Hazari reports the effective
use of Ni(dppf)(o-tol)Cl for room temperature coupling of o-
chloroquinolines seemingly without this problem.13 Substrate
Lewis basicity also affects the Pd system but to a lower extent.
Nitroarene 1q was unreactive with the Ni system, similar to
previous findings by Percec34 and possibly explained by
formation of (nitroso)Ni(0) complexes, as observed by Kochi.35
While 1q was recovered, we cannot discount the formation of
these complexes based on the low Ni loading. Collectively,
however, the applicability of both Ni and Pd precatalysts was
approximately equal for bromide electrophiles, with the
exceptions noted above.
Nucleophile compatibility was a more extensive issue. Pd
performed effectively, with the exceptions of known challenges
mainly relating to Lewis basic substrates (2l, 2q). The Ni system,
however, was more significantly affected. Transmetalation is
known to be more challenging for Ni than Pd and these
observations may be attributable to this event.34 Nitroarene 2b
experienced the same reactivity issues as the electrophile, 1q.
Several observations were worth noting, however some remain
unsatisfactorily understood. (1) The lower efficiency using
protodeboronation-prone boronic acids37,38 (e.g., 2e, 2f) may
result from competing protodeboronation due to slow
transmetalation in the Ni system (vide infra). (2) Specific ligating
functionalities can impair reactivity either via Lewis basic
heteroatomic sites (2g, 2n) or likely η2 coordination in the case
of 2i,39 again more problematic for Ni vs. Pd. (3) The diminished
reactivity of electron-deficient boronic acids (2c, 2l, 2s, 2u) in
the Ni system may result from the specific reaction conditions
employed that, while effective for the benchmark reaction,
could require tailoring for specific organoboron substrates.
(4) The failure of 2l in the Ni process cannot be easily explained
by formation of metallocycles but seems likely to be related to
catalyst coordination. (5) Finally, the major discrepancy
observed with the cross-coupling of PhB(OH)2 and 5-
bromoindole (1t, Scheme 2a) vs. the analogous coupling of PhBr
with indole-5-boronic acid (2p, Scheme 2b). This simple reversal
in electrophile/nucleophile roles led to complete failure in
catalysis
using
Ni
despite
no
discernible
stereoelectronic/functional group issues. (5) In all cases where
conversion to product was low, the reaction profiles were highly
similar containing only product, unreacted starting materials,
and traces of boronic acid homocoupling. Accordingly, lower
yields appear to stem from lower reactivity rather than side
reactions in most cases (with the exception of boronic acids that
underwent rapid protodeboronation).
Collectively, while synthetically useful yields can be obtained,
the applicability of the Ni precatalyst was comparatively more
problematic than the analogous Pd system and, perhaps more
importantly, the issues cannot always be predicted a priori,
even with relatively simple substrates as used here.
Robustness screen. Additional data on functional group
compatibility was obtained by performing a robustness screen
of the benchmark reaction in the presence of 1 equiv of a
particular additive (Scheme 3).40
As expected, the Pd system was broadly tolerant of the selected
additives, with mostly relatively minor decreases in yield,
except in the case of phenol, where reactivity was impeded, and
thioanisole, where reactivity was completely inhibited. The
impact of certain functional groups on Ni was variable and
occasionally in contrast to the observations made in the
substrate survey. Consistent with the substrate survey, phenol,
thioanisole, and dinitrobenzene all negatively affected the
reaction. Surprising results were observed with DMAP and
benzoic acid, where catalysis was almost completely inhibited.
The addition of indole did not have any impact on the Ni
reaction in this scenario, suggesting the result observed with 1t
and 2p is not based on the indole unit itself but on some
additional interaction between substrate and Ni. Similarly, the
impact of aldehyde functional groups is unclear: aryl aldehydes
were not problematic in the substrate survey when on the aryl
bromide (see 1h, 1l), however, reactivity was significantly
decreased when on the boronic acid (e.g., 2s), and addition of
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octanal impeded this benchmark reaction. Finally, an important Specifically, BPins 5w, 5x, and 5y all displayed noticeably more
View Article Online
DOI: 10.1039/C9OB00561G
observation was the identification of a slight inhibitory impact protodeboronation in the presence of both Ni and Pd than in
of pinacol. While this was not severe and could be mitigated the control reaction. However, this is a preliminary observation
upon extending reaction times, this may have some implications that will need probed more thoroughly.
B(OR)2
Ph
H
Pd or Ni cat.
for the use of BPin substrates in some instances.
Ph Br
R
R
R
conditions
Br
B(OH)2
Pd or Ni cat.
(1 equiv)
B(OH)2: 2c, 2m, 2v-y
BPin: 4c, 4m, 4v-y
(1 equiv)
cross-coupling
3c, 3m, 3v-y
protodeboronation
5c, 5m, 5v-y
conditions
F
1a
(1 equiv)
2a
(1.1 equiv)
F
3
Ni: Ni(dppf)(o-tol)Cl (2 mol%), K3PO4 (3 equiv), 1,4-dioxane, 80 ∞C, 30 min
Pd: Pd(dppf)Cl2 (4 mol%), K3PO4 (3 equiv), H2O (5 equiv) 1,4-dioxane, 80 ∞C, 30 min
Ni: Ni(dppf)(o-tol)Cl (2 mol%), additive (1 equiv), K3PO4 (3 equiv), 1,4-dioxane, 80 °C, 4 h
Pd: Pd(dppf)Cl2 (4 mol%), additive (1 equiv), K3PO4 (3 equiv), H2O (5 equiv) 1,4-dioxane, 80 °C, 4 h
MeO
MeO
B(OR)2
B(OR)2
NMe2
NH2
CN
Me Me
Me
HO
Me
Ph
B(OR)2
no additive
S
MeO2S
N
OMe
2m
4m
OH
N
B(OH)2
BPin
2c
4c
2v
4v
Ni: >99%
Pd:>99%
Ni: >99%
Pd: 73%
Ni: 0%
Pd: >99%
Ni: 70%
Pd: 87%
Ni: >99%
Pd: 90%
Ni: >99%
Pd: 96%
B(OR)2
O
B(OR)2
B(OR)2
F
OH
Me
H
F
Me
6
F
F
N
N
F
O
H
B(OH)2
BPin
2w
4w
2x
4x
2y
4y
Me
Ni: >99%
Pd: 83%
Ni: 93%
Pd: 95%
Ni: 0%
Ni: 73%
Pd: >99%
Ni: 5%
Pd: 59%
Pd: 82%
(a) Product vs. protodeboronation: Boronic acid
O
NO2
SH
100
OH
CHO
90
80
70
60
50
40
30
20
10
0
Me
O2N
MeO
Ni: >99%
Pd: 72%
Ni: >99%
Pd: >99%
Ni: 0%
Pd: 1%
Ni: 0%
Pd: 96%
Ni: 8%
Pd: 98%
3
Scheme 3. Robustness screen on the benchmark reaction under optimized
conditions for each precatalyst. Yields determined by 19F NMR analysis using
an internal standard (see ESI).
5
Protodeboronation. The majority of Ni-catalyzed SM reactions
use excess of organoboron (typically 2 equiv),4-6 while in the
above analyses we used a very slight excess (1.1 equiv). Based
on the observations of variable efficiency with variation of the
boronic acid, an assessment of the extent of protodeboronation
using sensitive organoborons was conducted using both the
boronic acid and BPin derivatives. Conversion to product and
protodeboronation using Ni and Pd precatalysts under
optimized conditions, as well as background protodeboronation
is provided in Chart 1. The sulfone (2c, 5c) and trimethoxy (2m,
5m) organoborons were included as controls. Thiophene (2v,
5v) and the fluorinated organoborons (2x-y, 5x-y) are all
susceptible to protodeboronation at different rates.35,36 Three
main observations were evident: (1) the majority of
protodeboronation takes place as a competing side reaction, as
evinced by the control (no catalyst) reactions for each
organoboron. The more stable organoborons 2/5c and 2/5m
displayed less protodeboronation, and the extent of
protodeboronation generally corresponded with the stability of
the parent boronic acid. (2) In agreement with this,
protodeboronation could be mitigated by using the BPin, with
the caveat that cross-coupling reactivity was also slightly
diminished, either as a result of slower transmetalation or
hydrolysis to the parent boronic acid and subsequent
transmetalation. The possibility of influence of pinacol on
efficiency cannot be excluded. (3) Lastly, we cannot rule out the
Ni Pd None Ni Pd None Ni Pd None Ni Pd None Ni Pd None Ni Pd None
c
m
v
x
y
w
(b) Product vs. protodeboronation: Bpin
100
90
80
70
60
50
40
30
20
10
0
3
5
Ni Pd None Ni Pd None Ni Pd None Ni Pd None Ni Pd None Ni Pd None
c
m
v
x
y
w
Chart 1. C–C bond formation vs. protodeboronation for Ni and Pd precatalysts
using (a) boronic acids and (b) BPin. Determined by HPLC or NMR analysis
using an internal standard (see ESI).
Conclusions
In summary, the practical viability of direct transfer of
phosphine ligands used for effective Pd-catalyzed sp2-sp2
Suzuki-Miyaura cross-coupling to a comparable Ni system has
been investigated using dppf as in exemplar precatalyst
systems. For electrophiles, this appears to be a relatively
straightforward transfer, with the analogous Ni precatalyst
delivering synthetically useful yields of products. However,
significant issues can manifest with nucleophiles and some of
these could not be predicted a priori. We hope that these
results will support the development of simple and inexpensive
possibility
of
some
on-metal
or
metal-assisted
protodeboronation based on the slight increase in
protodeboronation in certain reactions containing catalyst.
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23 J. W. B. Fyfe, E. Valverde, C. P. Seath, A. R. Kennedy, J. M.
ligands for Ni and promote use of Ni catalysis for routine Suzuki-
Miyaura cross-coupling but also encourage balanced
reasoning for the movement to Ni from Pd, as cost savings,
especially on small scale, are minimal and functional group
compatibility is diminished vs. Pd.
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Acknowledgement
We thank the University of St Andrews for a PhD studentship
(MJW).
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There are no conflicts to declare.
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Organic & Biomolecular Chemistry
Page 6 of 6
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DOI: 10.1039/C9OB00561G
Ni
Pd
Br
● Direct precatalyst head-to-head
● Functional group compatibility
● Protodeboronation comparison
dppf precatalysts
Suzuki-Miyaura
B(OH)2
20 electrophiles
20 nucleophiles
A head-to-head study of comparable pre-catalysts in Suzuki-Miyaura cross-coupling.