Regioselective Synthesis of Polyfunctional Arenes by a 4-Component Catellani Reaction

Full text of DOI:10.1016/j.chempr.2020.06.021

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Article
Regioselective Synthesis of Polyfunctional
Arenes by a 4-Component Catellani Reaction
Jing Wang, Cheng Qin,
Jean-Philip Lumb, Xinjun Luan
jean-philip.lumb@mcgill.ca (J.-P.L.)
xluan@nwu.edu.cn (X.L.)
HIGHLIGHTS
A 4-component Catellani reaction
affords an efficient synthesis of
substituted arenes
The well-known ortho effect is
used as a constructive element of
reaction design
Predictable chemo- and
regioselectivity result from subtle
substituent effects
Atom and step economic
synthesis of polyfunctional arenes
Polyfunctional arenes are essential chemicals with wide-ranging applications.
Herein, we describe their preparation by a 4-component Catellani reaction.
Multicomponent reactions assemble simple and inexpensive building blocks into
functional molecules of much higher value. To do this effectively, bond formation
between components must be orchestrated with high precision and must
discriminate subtle differences between reactive centers. We accomplish these
tasks by overcoming the long-standing ‘‘ortho effect’’ and show that it can become
a predictable and constructive element of reaction design.
Wang et al., Chem 6, 1–13
August 6, 2020 ª 2020 Elsevier Inc.
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Regioselective Synthesis of Polyfunctional
Arenes by a 4-Component Catellani Reaction
1,4,
Jing Wang,1,3 Cheng Qin,1,3 Jean-Philip Lumb,2, and Xinjun Luan
*
*
SUMMARY
The Bigger Picture
Polyfunctional arenes touch the
lives of nearly every human on
earth. They are integral
Polyfunctional arenes are an important part of the chemical value chain.
To improve the efficiency of their synthesis, we have investigated a
multicomponent approach built upon the Catellani platform. Here,
we describe a 4-component coupling of aryl iodides lacking an ortho
substituent that installs 3 discrete functional groups on the arene in a
single step. The process is regio- and chemoselective and uncovers
remote substituent effects that have a pronounced influence over inter-
mediate Pd-(II) complexes. These intermediates have been a long-
standing focus of the Catellani-reaction development, but persistent
challenges have given rise to the well-known ‘‘ortho effect.’’ We now
show that the ortho effect can be a positive element of reaction design,
and that previously problematic iodides can now be used in
complexity-generating transformations. In expanding the scope of
the Catellani platform, we hope to provide mechanistic considerations
to guide future reaction design, while also improving the environ-
mental footprint of synthesizing polyfunctional arenes.
components of the chemical value
chain with wide-ranging
applications in the pharmaceutical
and agrochemical sectors. In this
work, we describe a new way of
synthesizing polyfunctional
arenes by multicomponent
coupling. Multicomponent
reactions are attractive, because
they assemble simple and
inexpensive building blocks into
functional molecules of much
higher value. If each component
can be varied, the resulting
transformation can rapidly search
chemical space around a given
scaffold at low cost with minimal
waste. To do this effectively, bond
formation between components
must be orchestrated with high
precision and must often
INTRODUCTION
By introducing more than one functional group in a single transformation, multicom-
ponent coupling reactions can provide an efficient synthesis of polyfunctional mol-
ecules.1–4 In the particular case of substituted aromatic rings, Catellani’s conditions,
combining palladium (Pd) and norbornene (NBE) provide a versatile platform for a
number of 3-component coupling reactions (Scheme 1A).5–9 The inclusion of NBE
promotes a characteristic 1,2-transposition (1,2-T) of Pd following oxidative addition
(OA), that allows functionalization of both ortho- and ipso-carbons of the starting
halide (C6 and C1, respectively, see Scheme 1A for numbering).9 High chemo-
and regioselectivity result from the distinct coordination environments of Pd, which
change over the course of the catalytic cycle. The Pd-(II) center at C1 is relatively
electropositive and coordinatively unsaturated, making it well suited for migratory
insertion (MI) or transmetalation (TM), whereas the Pd-(II) center at C6 is relatively
electron rich, making it better suited for OA.10 While the complementarity of these
environments has led to the successful combination of many pairs of coupling part-
ners, a persistent limitation requires an ortho substituent on the starting aromatic
halide to ensure high degrees of selectivity.11–31 In its absence, the Pd-(II) centers
at C1 and C6 behave quite differently, and a number of competitive pathways erode
selectivity in what is commonly referred to as the ortho effect or constraint
(Scheme 1B).32–34 This includes products of over functionalization at both C2 and
C6,10,14–17,21 as well as additional NBE-containing by-products (not shown, see
Maestri et al.,33 Wang et al.,34 and Lei et al.35). A series of elegant studies addressing
aspects of this limitation were recently described by Dong and co-workers, whose
carefully engineered NBE derivatives restore steric effects in classical 3-component
reactions (Scheme 1C).34,36–38 These examples illustrate the influence of remote-
discriminate subtle differences
between reactive centers. Our
work accomplishes this task by
advancing the Catellani platform
to a 4-component coupling that
can provide polyfunctional arene
products containing up to 6
unique substituents in a single
transformation.
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A
B
C
D
E
Scheme 1. Pd/NBE Catalysis
steric effects in selective aromatic C–H functionalization, which continue to motivate
new designs for catalysis.39–41
Our own interest in remote substituent effects surfaced recently, while attempting to
design a 4-component Catellani reaction (Scheme 1E). We were interested in func-
tionalizing two aromatic C–H bonds in a single transformation with distinct coupling
partners, recognizing its potential value for the synthesis of 1, 2, 3-tri-substituted
arenes. We were also interested in a more fundamental question of chemoselectivity
and whether the ortho effect could be leveraged in order to differentiate the 2 and 6
positions of an ortho-unsubstituted aromatic iodide. The only examples where
distinct groups have been introduced to the ortho positions of an iodide come
from Lautens, who used a tethered electrophile at the meta position of the iodide
(Scheme 1D).42–46 To our knowledge, the introduction of distinct substituents on
simple, ortho-unsubstituted iodides has not been previously reported, so far pre-
venting a 4-component coupling, as we describe here (Scheme 1E).
1Key Laboratory of Synthetic and Natural
Functional Molecule of the Ministry of Education,
College of Chemistry & Materials Science,
Northwest University, Xi’an 710127, China
2Department of Chemistry, McGill University,
Montreal, QB H3A 0B8, Canada
3These authors contributed equally
4Lead Contact
*Correspondence:
jean-philip.lumb@mcgill.ca (J.-P.L.),
xluan@nwu.edu.cn (X.L.)
At the center of this challenge are the subtle differences between the Pd-(II) complexes
that would occupy C2 and C6 over the evolution of a 4-component coupling (Scheme
2A). The Pd-(II) complex at C2 [C2-Pd-(A)] lacks a substituent at C6, whereas the
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A
B
Scheme 2. Mechanistic Framework for Reaction Design
downstream complex at C6 [C6-Pd-(C)] possesses the substituent previously introduced
at C2. Since C2 and C6 are not in direct electronic communication, we speculated that
the principal difference between these complexes would derive from a remote-steric
interaction between the C2 substituent and the hydrogen atom on the NBE bridge.
We questioned whether this remote-steric effect could be used constructively in order
to functionalize C2-Pd-(A) and C6-Pd-(C) with distinct coupling partners (Scheme 2B).
We reasoned that complex A would not be constrained by steric effects and might,
therefore, favor the coupling partner that could best coordinate to the Pd-(II) center.
By contrast, complex C would have a substituent at C2 and would, therefore, progress
to Pd-(IV) intermediate C6-Pd-(D) by the least sterically demanding pathway possible.33
RESULTS AND DISCUSSION
As a point of departure, we considered the 4-component coupling between iodoben-
t
zene (1a), benzoic anhydride (2a), benzyl bromide (3a), and Bu-acrylate (4a), with the
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Table 1. Optimization of the Reaction Conditions
Entry
Catalyst
Ligand
Solvent
Yield(%)a
6a
5a
15
11
<5
31
26
44
12
62
56
53
37
26
7a
0
8a
<5
7
1
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(TFA)2
PdCl2
PPh3
THF
10
20
<5
11
13
9
2
P(o-tol)3
THF
0
3
P(p-OMeC6H4)3
P(p-FC6H4)3
P(p-ClC6H4)3
P(2-furyl)3
P(2-furyl)3
P(2-furyl)3
P(2-furyl)3
P(2-furyl)3
P(2-furyl)3
P(2-furyl)3
THF
0
0
4
THF
0
9
5
THF
0
11
7
6
THF
<5
0
7
THF
61
10
5
0
8
THF
5
16
19
25
7
9
[Pd(allyl)Cl]2
Pd(CH3CN)2Cl2
PdCl2
THF
13
7
10
11
12
THF
5
DME
1,4-dioxane
13
<5
0
PdCl2
19
32
Reaction conditions: 1a (0.3 mmol), 2a (0.45 mmol), 3a (0.45 mmol), 4a (0.36 mmol), Pd (10 mol%), ligand
(20 mol%), NBE (0.6 mmol), and base (1.2 mmol) in the indicated solvent (3 mL) at 90 ꢀC for 12 h under a
nitrogen atmosphere.
aAll yields were determined by 1H-NMR using dibromomethane as the internal standard.
goal of preparing 1, 2, 3-tri-substituted benzene (5a) (Table 1). While in principle, there
could be two complementary pathways to achieve selective product formation (see
Scheme S1 for a complete comparison), our initial design was to functionalize C2 by acyl-
ation before benzylation at C6, following the mechanistic rationale presented in Scheme
2B.17,19,47–52 Among the many competitive pathways that could erode selectivity for 5a,
di-benzylation to provide 6a and di-acylation to provide 7a or 8a were anticipated, and
would reflect poor selectivity in either of the two OA steps (See Table 1). These pathways
have been observed in previous Catellani reactions when using ortho-unsubstituted ar-
omatic iodides,17,52,53 and indeed, exposure of our coupling partners to standard Cat-
ellani conditions consisting of Pd(OAc)2 (10 mol %), PPh3 (20 mol %) and NBE (2 equiv) in
THF at 90ꢀC led to the formation of 5a and 6a in 15% and 10% yields, respectively (Table
1, entry 1). We also observed appreciable quantities of benzyl benzoate (9) from a
competitive background reaction between the carbonate base, the anhydride, and
the bromide (See Table S1). While selectivity for the desired pathway could be improved
to some extent by using a less electron-donating phosphine ligand (Table 1, compare
entries 1–3 with 4–5), it was not until we evaluated tris-2-furyl-phosphine that we
observed a significant improvement for the formation of 5a (Table 1, entry 6). Initially,
we attributed this effect to the decreased steric demands of P(2-furyl)3 relative to
PPh3, as well as its reduced donating ability to Pd, and thought that it would create a
more electropositive and less sterically encumbered Pd-(II) center (C2-Pd-(A) in Scheme
3B). In turn, we thought that this would favor coupling with the more Lewis basic and
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sterically demanding anhydride partner. In addition to this ligand effect, we also
observed a noticeable counterion effect and obtained our highest yield of 62% for 5a
by using PdCl2 as the pre-catalyst (Table 1, entry 8). The beneficial effects of PdCl2 in
previous Cattelani reactions have been noted, but the reasons behind the effect remain
unclear.18,19,21 Results with additional pre-catalysts, including the allyl-Cl Pd-(II) dimer
(Table 1, entry 9) and the bis-acetonitrile PdCl2 complex (Table 1, entry 10), were also
superior to most other Pd-pre-catalysts, but did not offer an improvement to the results
obtained with PdCl2. Therefore, we selected the conditions of entry 9 for additional
development. Before advancing, we note an important solvent effect, as selectivity
decreased dramatically for 5a when we used solvents other than THF, including DME
or 1,4-dioxane (Table 1, entries 11 and 12). We will return to this solvent effect below.
Finally, we wish to mention that additional NBE derivatives did not improve upon the re-
sults of entry 8. Therefore, we did not pursue this line of reaction optimization, and
instead, focused on the use of NBE itself and the scope of the reaction.
While we had initially considered steric effects as the principle determinant of selec-
tivity, our investigation of substituents in the para position of the starting iodide
revealed an unexpected electronic effect that appears to correlate with the substit-
uent’s smeta value. When using THF as solvent, we observed our highest selectivity
for the 4-component coupling when the para substituent was moderately electron
releasing and not inductively withdrawing (Figure 1, entries 1–3). However, as this
substituent became more strongly withdrawing, selectivity changed to favor diben-
zylation (Figure 1, entries 4–7). In the most extreme cases where the para substituent
was either a nitrile or a nitro group (Figure 1, entries 8–9), we only observed small
amounts of acylation, and dibenzylation dominated. If, however, THF was replaced
with 1,4-dioxane, selectivity for the 4-component coupling could be regained. The
effect was most pronounced for moderately withdrawing substituents (Figure 1, en-
tries 13–16), for which the yields of 4-component coupling improved consistently by
ꢁ20%. While the root cause of this solvent effect remains unclear, it appears to have
on overall effect of favoring acylation over benzylation. For relatively electron-rich
iodides (1a–1c), this has a detrimental effect and leads to over acylation and the
increased formation of 6 and 7 (Figure 1, entries 10–12). But for moderately deacti-
vated substrates (1d–1g), this effect is quite positive and improves the yield of the 4-
component coupling to the point of becoming synthetically useful (Figure 1, entries
13–16). We do note that previous mechanistic studies have invoked CsI as a labile
ligand to Pd-(II) in other Catellani reactions47 and speculate that the solvent’s polar-
ity and chelating abilities might affect these interactions.
Equipped with the combination of our optimized conditions in THF and 1,4-dioxane,
we proceeded to explore the reaction’s scope (Figure 2A). In addition to the substit-
uents discussed in Figure 1, our conditions tolerate electron withdrawing aldehyde
(5i), ketone (5j), and ester substituents (5k), as well as a trifluoromethyl ether (5l).
Likewise, a Boc-protected phenol (5m) and a 3ꢀ amide (5n) are similarly tolerated.
Notably, these substrates perform best when 1,4-dioxane is used as the solvent,
consistent with our observations in Figure 1. As the para substituent becomes
increasingly donating, the use of THF is imperative. Under these conditions, a methyl
group (5o), as well as oxygen or nitrogen heteroatoms (5o–5r), could be tolerated.
Certain common functional groups, including phenols or anilines, as well as a
benzylic alcohol, undergo in situ acylation, returning the corresponding products
as their benzoate protected derivatives (5s–5u).
Next, we evaluated the scope of the anhydride, benzyl bromide, and olefin components
(Figures 2B–2D). We selected 4-fluoro-iodo-benzene (1d) as our iodide component, and
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Figure 1. Electronic Effect for the Reaction
aAll yields were determined by 1H-NMR using dibromomethane as the internal standard.bIsolated yields.
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A
B
C
D
Figure 2. Substrate Scope with para-Substituted Aryl Iodides
1 (0.3 mmol), 2 (0.45 mmol), 3 (0.45 mmol), 4 (0.36 mmol), PdCl2 (0.03 mmol), P(2-furyl)3 (0.06 mmol), NBE (0.6 mmol), Cs2CO3 (1.2 mmol) in 1,4-dioxane at
90ꢀC. All yields are isolated yields.
a3s, 3t, and 3u were run with 2.5 equiv of 2a (0.75 mmol) and 5 equiv of Cs2CO3 (1.5 mmol).bDong’s carbonate anhydride was used (Catellani et al.11), and
1o was used instead of 1d.
cMethyl iodide was used instead of benzyl bromide.
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therefore, employed 1,4-dioxane as the solvent. By comparison to the pronounced elec-
tronic effects that we had observed on the aryl iodide, substituent effects on these reac-
tion components seems to be attenuated. For the anhydride, this included the more ste-
rically demanding and electron-rich ortho-methoxy benzoate (5v), as well as benzoates
with a Clꢂ or F substituent in the para position (5x and 5y). Substituents other than ben-
zene rings were also tolerated, including 2-napthyl, 2-furan, and 2-thiopene rings (5z–
5ab). Finally, a preliminary step toward the incorporation of esters was investigated using
Dong’s carbonate anhydride, which provided ethyl ester 5ac in an unoptimized but
encouraging yield of 35%.21
The scope of the benzyl bromide revealed a relatively high tolerance for a range of
common functional groups (Figure 2C). These included electron withdrawing sub-
stituents in the para position, such as trifluoromethyl- (5ah), nitro- (5ai), trifluoro-
methyl ether- (5aj), cyano- (5ak), and methanesulfonyl- (5al) groups. Fluorine substi-
tution was also tolerated in both the ortho- (5am) and meta-positions (5ap). Likewise,
halogen substituents, suitable for product diversification, were tolerated in meta-
(5aq) and para-positions (5ae–5ag). An important extension of scope was to methyl
iodide,29 which allows us to incorporate a methyl group at C6 while retaining high
levels of selectivity (5as). Finally, we investigated variations to the acrylate and found
that a range of electron-deficient olefins could be used, including those in conjuga-
tion with an ester, amide, or ketone (5at–5ax), along with an electron-deficient sty-
rene (5ay) or acrylonitrile (5az). A notable extension is to the incorporation of a cyano
group—from Cu–CN. This is a well-known component of the Catellani toolbox that
interfaces nicely with our multicomponent process to rapidly prepare valuable aro-
matic nitriles (5ba and 5bb).15,54,55
Because para-substituted iodides and iodobenzene are symmetrical, the first C–H
insertion is not regiodetermining, and product selectivity is governed at the stage
of OA. If, however, symmetry around the iodide is broken, the first C–H insertion
must become regioselective for C2 in order for the same sequence of acylation fol-
lowed by alkylation to proceed with high positional control (Figure 3). Based upon
literature precedent,31,41,42,44 we anticipated that OA/1,2-T would be selective for
the less sterically encumbered C–H at C2. However, the effects of multiple substit-
uents on the reactivity of C2-Pd-(A) and C6-Pd-(C) were less clear. Therefore, we
were pleased to retain high selectivity across a relatively broad range of these
more challenging substrates. This included simple, meta-substituted iodides (Fig-
ure 3A) that afforded tetra-substituted products with the acyl group at C2, a nitrile
or an olefin at C1, a benzyl or a methyl at C6, and a range of substituents at C5
(11a–11l). Likewise, if the iodide is 4,5-disubstituted (Figure 3B), penta-substituted
arenes are produced with the predicted regioselectivity (11m–11w). The successful
use of 3-iodothiophene in THF to provide 11x also provides a proof of concept for
the application of our strategy on heterocyclic scaffolds. Finally, when the iodide
is tri-substituted (Figure 3C), arenes with up to 6 different substituents can be pre-
pared in a single step, creating a streamlined approach to fully substituted aromatic
rings (11y and 11z). To our knowledge, this is the first multicomponent synthesis of
such highly substituted arenes, which should create interesting opportunities for
future diversification.
Because the 4-component coupling installs functional handles with complementary
reactivity, a range of chemoselective transformations can diversify the polysubsti-
tuted aromatic core (Scheme 3). For example, 5d and 5bb are prepared on gram
scale in isolated yields of 62% and 50%, respectively, and then transformed into a
range of downstream products with different functional properties. This spans the
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A
B
C
Figure 3. Substrate Scope with meta-Substituted Aryl Iodides
9 (0.3 mmol), 2a (0.45 mmol), 3a or MeI (0.45 mmol), 4a or CuCN (0.36 mmol), PdCl2 (0.03 mmol), P(2-furyl)3 (0.06 mmol), NBE (0.6 mmol), Cs2CO3
(1.2 mmol) in 1,4-dioxane at 90ꢀC. All yields are isolated yields.a2.0 equiv 4a was used.bTHF was used instead of dioxane.cMixture of regioisomers: see
Supplemental Information for details.d2.0 equiv 2a and 3a were used.
relatively simple vinyl acid (12) to the increasingly functionalized dihydroisofuran.
(15) The value of incorporating a nitrile at C1 becomes apparent upon chemoselec-
tive hydration or reduction of 5bb, which leads to complementary lactone (18) or iso-
indolinones (19 and 20). Finally, chemoselective oxidation of the benzylic group
affords benzylic bromide (21) and completes a selection of transformations that
selectively manipulates each of the three newly introduced groups.
Conclusion
In this work, we have demonstrated that simple meta- and para-substituted iodides
are effective coupling partners in 4-component Catellani reactions. These
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Scheme 3. Synthetic Utility
Reaction conditions:
(A) 5d (0.3 mmol), TFA (1.8 mmol), in DCM (2.0 mL) at room temperature (RT) for 15 h.
(B) 5d (0.2 mmol), Pd/C (0.4 mmol) in EtOH (2.0 mL) at 80ꢀC for 48 h under 15 atm of hydrogen.
(C) 5d (0.5 mmol), CeCl3$7H2O (0.52 mmol) in MeOH (4.0 mL) at ꢂ20ꢀC for 10 min; then NaBH4 (1.0 mmol) was added, warm to RT for 12 h.
(D) 14 (0.3mmol), NaH (0.9 mmol) in THF at RT for 12 h.
(E) 5d (0.2 mmol), Pd/C (0.2 mmol) in MeOH (4.0 mL) at 80ꢀC for 48 h under 15 atm of hydrogen.
(F) 5bb (0.2 mmol), Pd/C (0.05 mmol) in MeOH (4.0 mL) at 50ꢀC for 15 h under 10 atm of hydrogen.
(G) 5bb (0.6 mmol), NaBH4 (0.6 mmol) in EtOH (3.0 mL) at 50ꢀC for 1 h, then cooled to 20 ꢀC for 24 h; 2N HCl until weakly acidic reaction, H2O (90.0 mL) at
100ꢀC for 0.5 h.
(H) 5bb (0.6 mmol), KOH (0.02 mmol) in MeCN (6.0 mL) and H2O (0.6 mL) at RT for 3 h.
(I) 19 (0.3 mmol), triethylsilane (3.0 mmol), trifluoroboron etherate (1.0 mmol) in DCM (3.0 mL) at ꢂ15ꢀC for 2 h.
(J) 5bb (0.2 mmol), NaOH (0.2 mmol) in DCM (2.0 mL); then Br2 ( 0.2 mmol) in DCM (3.0 mL) was added, refluxed at 40ꢀC for 6 h.
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conditions provide many opportunities for the efficient and diversifiable synthesis of
aromatic rings with up to 6 distinct substituents. They also set the stage for comple-
mentary diversification reactions, providing an efficient means of diversifying chem-
ical space around a common aromatic core. Historically, simple aromatic iodides
lacking an ortho substituent have been incompatible with standard Catellani proto-
cols, giving rise to the well-known ‘‘ortho effect.’’ By careful analysis of the remote-
steric interactions that give rise to this effect, we have discovered that these sub-
strates are in fact compatible with selective Catellani protocols and that they can
be used in a higher-order, multicomponent coupling with good levels of control.
Over the course of exploring the reaction’s scope, we observed a correlation be-
tween the selectivity in the Pd-(II)/(IV) OA and the nature of a meta-substituent on
the aromatic ring. This correlation serves as a reminder that the aryl iodide is both
a substrate and a ligand in the Catellani process and that its steric and electronic
properties change over the course of the reaction. Given the multitude of effects
that exist for increasingly sophisticated substrates, we see many future opportunities
to investigate and expand the currently accessible substitution patterns. We hope
that the observation of these effects will help others interested in expanding the Cat-
ellani toolbox and also those more generally interested in the remote and often sub-
tle effects that control aromatic C–H functionalization.
EXPERIMENTAL PROCEDURES
Resource Availability
Lead Contact
Further information and requests for resources should be directed to and will be ful-
filled by the lead contact, Xinjun Luan (xluan@nwu.edu.cn).
Materials Availability
All unique reagents generated in this study are available from the lead contact
without restriction.
Data and Code Availability
Crystallographic data have been deposited in the Cambridge Crystallographic Data
Center under accession number CCDC: 1989038, 1989075, 1989077, 1989081,
1989082, 1989090, 1989092, 1989098, 1989103, 1989104, 1989105, 1989106,
1989108, 1989109, 1989110, and 1989112.
SUPPLEMENTAL INFORMATION
Supplemental Information can be found online at https://doi.org/10.1016/j.chempr.
2020.06.021.
ACKNOWLEDGMENTS
We thank the National Natural Science Foundation of China (21925108), the Key Sci-
ence and Technology Innovation Team of Shaanxi (2017KCT-37), and the Key Lab-
oratory Project of Xi’an (201805058ZD9CG42) for financial support. We thank Pro-
fessor Lei Hou for assistance with crystal structure analysis.
AUTHOR CONTRIBUTIONS
J.W. carried out the reaction exploration. J.W. and C.Q. investigated the substrate
scope and application. X.L. and J.L. directed the project and wrote the manuscript
with input from all of the authors.
Chem 6, 1–13, August 6, 2020
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DECLARATION OF INTERESTS
The authors declare no competing interests.
Received: April 13, 2020
Revised: May 22, 2020
Accepted: June 15, 2020
Published: July 10, 2020
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