Palladium-Catalyzed γ,γ′-Diarylation of Free Alkenyl Amines

Article abstract of DOI:10.1021/jacs.1c04261

The direct difunctionalization of alkenes is an effective way to construct multiple C-C bonds in one-pot using a single functional group. The regioselective dicarbofunctionalization of alkenes is therefore an important area of research to rapidly obtain complex organic molecules. Herein, we report a palladium-catalyzed γ,γ′-diarylation of free alkenyl amines through interrupted chain walking for the synthesis of Z-selective alkenyl amines. Notably, while 1,3-dicarbofunctionalization of allyl groups is well precedented, the present disclosure allows 1,3-dicarbofunctionalization of highly substituted allylamines to give highly Z-selective trisubsubstituted olefin products. This cascade reaction operates via an unprotected amine-directed Mizoroki-Heck (MH) pathway featuring a β-hydride elimination to selectively chain walk to furnish a new terminal olefin which then generates the cis-selective alkenyl amines around the sterically crowded allyl moiety. This operationally simple protocol is applicable to a variety of cyclic, branched, and linear secondary and tertiary alkenylamines, and has a broad substrate scope with regard to the arene coupling partner as well. Mechanistic studies have been performed to help elucidate the mechanism, including the presence of a likely unproductive side C-H activation pathway.

Full text of DOI:10.1021/jacs.1c04261

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Palladium-Catalyzed γ,γ′-Diarylation of Free Alkenyl Amines
Vinod G. Landge, Aaron J. Grant, Yu Fu, Allison M. Rabon, John L. Payton, and Michael C. Young*
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ABSTRACT: The direct difunctionalization of alkenes is an effective
way to construct multiple C−C bonds in one-pot using a single
functional group. The regioselective dicarbofunctionalization of alkenes
is therefore an important area of research to rapidly obtain complex
organic molecules. Herein, we report a palladium-catalyzed γ,γ′-
diarylation of free alkenyl amines through interrupted chain walking
for the synthesis of Z-selective alkenyl amines. Notably, while 1,3-
dicarbofunctionalization of allyl groups is well precedented, the present
disclosure allows 1,3-dicarbofunctionalization of highly substituted
allylamines to give highly Z-selective trisubsubstituted olefin products.
This cascade reaction operates via an unprotected amine-directed
Mizoroki−Heck (MH) pathway featuring a β-hydride elimination to
selectively chain walk to furnish a new terminal olefin which then
generates the cis-selective alkenyl amines around the sterically crowded allyl moiety. This operationally simple protocol is applicable
to a variety of cyclic, branched, and linear secondary and tertiary alkenylamines, and has a broad substrate scope with regard to the
arene coupling partner as well. Mechanistic studies have been performed to help elucidate the mechanism, including the presence of
a likely unproductive side C−H activation pathway.
Scheme 1. Directed Mizoroki-Heck Reactions on Allylic
Substrates
INTRODUCTION
■
Alkenes are important feedstocks in synthetic chemistry due to
their versatility; they are inherently nucleophilic but can easily
be made electrophilic by the addition of certain functional
groups or catalysts.1−3 Alkenes can also serve as activating
groups for adjacent C−H bonds, allowing even greater
synthetic utility.4−7 One of the biggest challenges for alkene
functionalization is to achieve regioselectivity.8−12 While this is
easily overcome for terminal olefins13−16 and cyclization
reactions,17,18 internal alkenes often undergo poor regiochemi-
cally selective reactions without the aid of activating functional
groups. This has spawned a significant research enterprise
exploring how to achieve regioselective transformations in
electronically unbiased alkenes.19−23 For transition metal-
catalyzed reactions, one of the most effective strategies has
been the use of directing groups (DGs). A directing group can
be thought of as an auxiliary ligand on the substrate that
coordinates to the metal, thereby driving the regioselectivity
through the formation of the most accessible cyclometalated
intermediate. Because many metal−alkyl species can undergo
β-hydride elimination and reinsertion, so-called chain walking
can even lead to significant changes in regioselectivity but still
under the control of the DG (Scheme 1a).24−28 Several
different DGs have been applied to alkene functionaliza-
tion,29−32 1,2-difunctionalization,33−37 and 1,3-difunctionaliza-
tion (by taking advantage of chain walking).38
Received: April 23, 2021
Published: June 23, 2021
Notably, unprotected alkenylamines have not traditionally
been targets for alkene functionalization or difunctionalization
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a
reactions (although tertiary or N/O-substituted alkenylamines
are commonly prepared via hydroamination).39−41 This is due
to primary or secondary alkenylamines being prone to
oxidation,42 allylic deamination,43 and intramolecular cycliza-
tion of the alkene,44−46 issues which are not as significant when
the alkene is part of an aromatic ring.47 Protected alkenyl-
amines have therefore been the preferred entry point for these
reactions, serving as substrates for regioselective Mizoroki-
Heck (Scheme 1b),48−51 1,1-difunctionalization,52 1,2-difunc-
tionalization,53 and even 1,3-difunctionalization reactions.38
Specifically, the protecting group is generally regarded as also
providing a directing effect in these reactions. However, as with
all DG-mediated reactions, the need for installation and
subsequent removal of the DG significantly increases the
process mass intensity and step economy of these trans-
formations, decreasing their industrial relevance.54
While transient DGs have been explored that obviate some
of these concerns for transition metal-catalyzed organometallic
derivatization of amines via C−H activation,55−59 the instances
of transient DGs for alkene functionalization are still relatively
limited and not generally applied to amines. On the basis of
our interest in amine functionalization,60,61 we recently
reported a CO2-mediated regioselective Mizoroki-Heck
reaction of unprotected allylamines (Scheme 1c).62 The
method provided rapid access to 3,3-difunctionalized allyl-
amines and worked with terminal allyl, cinnamyl, and even
aliphatic alkenylamines. Notably, no chain walking was
observed, owing to the directing effect of the amine group.
Considering the ability of Pd-insertion intermediates to chain
walk, we wondered if the high γ-selectivity for these allylamine
substrates could be diverted toward selective 1,3-difunctional-
ization upon the addition of a β-alkyl substituent. Many
difunctionalization reactions proceed in a 1,2-fashion where
the metalated intermediate intercepts an additional nucleophile
or electrophile, followed by a second cross-coupling.63−65 One
of the challenges to overcome in this area is actually
competitive β-hydride elimination,66,67 which when overcome
can enable 1,1-68,69 or 1,3-70 difunctionalization. However, we
hypothesized that in our case, the amine could facilitate direct
arylation at the γ-position, followed by chain walking via
regioselective β-hydride elimination, which would then
facilitate a second arylation at γ′ to furnish the γ,γ′-diarylated
products (Scheme 1d).
Table 1. Optimization of Reaction Conditions
a
entry
reaction conditions
Standard conditions
yield (%)
1
73
43
68
71
<4
55
43
64
67
<4
<4
48
46
<4
<4
40
68
39
2
3
4
5
Pd(acac)2 instead of Pd(OAc)2
Pd(dba)2 instead of Pd(OAc)2
PdCl2(PPh3)2 instead of Pd(OAc)2
Pd(OAc)2 omitted
6
7
8
9
10
11
12
13
14
15
16
17
18
AgOAc instead of AgTFA
Ag2CO3 instead of AgTFA
AgO instead of AgTFA
Ag2SO4 instead of AgTFA
AgNO3 instead of AgTFA
AgTFA omitted
Toluene instead of THF
DCE instead of THF
MeCN instead of THF
TFA omitted
Reaction Performed at 50 °C
Reaction Performed at 90 °C
Reaction time was 5 h
a
Reaction conditions: 1a (0.15 mmol), 2a (0.6 mmol), Pd(OAc)2 (10
mol %), AgTFA (0.45 mmol), and mixture of THF:TFA (8:2) 1 mL,
heated at 70 °C for 14 h.
The amine is actually the superior functional group for this
transformation, as several protected amines either decomposed
or gave mixtures of products (see SI for details), although
picolinamides have previously been used for 1,3-diarylation of
methacryl groups.73 Among a variety of different palladium
precatalysts, Pd(OAc)2 proved to give the best results (Entries
1−4). Other transition metal catalysts were unsuccessful for
this transformation (see SI for details). Furthermore, in the
absence of Pd, no product was observed (Entry 5).
Although silver has several proposed roles in C−H arylation
reactions involving aryl iodides,74−76 in this chemistry we
assumed that it might be required to activate the C−I bond
and to sequester the byproduct iodide as AgI. We observed a
critical role for Ag, as the presence and identity of the silver salt
were important, with AgTFA giving the best yield of 3a
(Entries 6−10). As expected, when Ag was omitted, no
product was observed (Entry 11). Although THF proved to be
the optimal solvent, toluene and DCE both yielded the
product, albeit in lower yields, while acetonitrile was
completely ineffective (Entries 12−14). Despite the effective-
ness of a mixture of THF and TFA in the ratio of 8:2 (1 mL),
other mixtures of these two solvents also yielded the product
(see SI). However, omission of TFA led to no product
formation (Entry 15). In this case, between 50 and 60% of the
starting material could be recovered on different trials,
suggesting a role for TFA beyond just protecting the amine
through protonation.77−79 Lowering the temperature led to
decreased yield, although starting material was also recovered
(Entry 16) suggesting simply poor reaction efficiency at the
lower temperature. The reaction was tolerant of increased
temperatures, and performance of the reaction at 90 °C gave
the γ,γ′-diarylated product in 68% yield (Entry 17). A
METHODOLOGY AND RESULTS
■
We began our study on the γ,γ’-diarylation of β-alkylallyl-
amines using (E)-N-(tert-butyl)-2-methyl-3-phenylprop-2-en-
1-amine (1a) and iodobenzene (2a) as model substrates. In
the presence of Pd(OAc)2 and AgTFA and with the use of a
solvent mixture of THF and TFA, in the ratio of 8:2 at 70 °C
for 14 h, product 3a was obtained in 73% yield (Table 1, Entry
1) (see Support Information for experimental details).
Although the E/Z ratio of the starting material was only 6:1,
the reaction is completely selective for the Z-product. Notably,
while our previous report on the Pd-catalyzed Mizoroki-Heck
reaction of allylamines demonstrated a key role for CO2 as a
protecting group, in the present transformation, CO2 offered
no significant advantage. As the most significant decom-
position products from that study were found to be oxidation
of the allylic C−N bond, we hypothesize that in the present
system, the added group at the β-position slows this
degradation pathway sterically,71,72 thereby obviating the
need for CO2 as a protecting group.
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a
Table 2. Scope of Aryl Iodide for γ,γ′-Diarylation of α-Methyl Cinnamylamines
a
All reactions were performed on 0.15 mmol scale with 4 eq of aryl halide in 1 mL of solvent (8:2 THF:TFA mixture), in at least duplicate, and the
average yield reported.
shortening of the reaction time to 5 h also led to lower product
yield (Entry 18).
reaction conditions (3u and 3v). Having established the
substrate scope for this methodology, we next wanted to
demonstrate that it could be scaled-up effectively. This is
necessary considering the heterogeneity of these reactions due
to the significant amount of precipitate that forms during the
reaction. Using 3d as our target, we increased the reaction
scale from 0.15 to 4.5 mmol or an increase of 30-fold.
Gratifyingly, the product was still obtained in 56% isolated
yield (Scheme 2).
With our optimized reaction conditions in hand, we next
investigated the γ,γ′-diarylation of model substrate (E)-N-(tert-
butyl)-2-methyl-3-phenylprop-2-en-1-amine (1a) with various
iodoarenes. In addition to simple phenyl (Table 2, 3a), we
could readily install mono or disubstituted arenes containing
relatively electronically neutral substituents (3b−3d) in good
yields and also with complete Z-selectivity. While the NMR
data showed reasonably clearly that the two newly installed
arenes were installed at the γ,γ′-positions, X-ray analysis of 3d·
HCl further confirmed the regioselectivity of the products (see
SI). Various conjugated iodoarenes such as biphenyl and
fluorene also worked in the reaction, giving the desired
products in 53% and 61% yields, respectively (3e and 3f).
Sterically accessible meta and para-substituted iodoanisole
proved to be viable coupling partners, as was the more
sterically hindered ortho-iodoanisole (3g−3i).
Scheme 2. Reaction Scale-Up
The present reaction conditions were also compatible for
ethereal CF3 or CHF2 groups as well as halides (3j−3n).
Electron deficient groups such as trifluoromethyls, esters, or
nitro groups were also tolerated (3o−3r). Highly lipophilic
coupling partners, such as a mentholate ester or octylox-
ybenzene, were also suitable substrates (3s and 3t). We were
pleased to find that even steroid esters derived from trans-
androsterone and epiandrosterone also worked well under the
We next studied the scope of secondary amines under the
optimized conditions (Table 3). The reactions upon sterically
hindered amines proceeded smoothly and afforded the γ,γ′-
diarylation amine products (4a−4c) in up to 78% yield.
Notably, we observed regioselective 1,3-diarylation products
only and no γ',γ′-diarylation that might be postulated to arise
through migration of the alkene and subsequent diarylation of
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the reaction conditions (see SI), we found that simply
replacing the silver trifluoroacetate with silver sulfate was
sufficient to allow less sterically hindered substrates to be
diarylated, although the reason for this is currently unclear.
Under the revised conditions, various branched and
carbocyclic secondary amines gave the expected products
(4d−4j) in good yields. Gratifyingly, simple linear alkyl chains
also afforded the desired products in moderate isolated yields
under the Ag2SO4 conditions (4k−4m). Other secondary
amines containing heterocycles such as tetrahydrofuran or
thiophane (4n and 4o) can also be regioselectively arylated
under these conditions. A valine ester-derivatized substrate
could also be used under the revised reaction conditions (4p).
We could even use the reaction to selectively arylate a
leelamine derivative (4q). While carbonyl-based protecting
groups were not viable substrates, a Bn-protected product
could also be prepared (4r).
Table 3. Scope of γ,γ′-Diarylation of α-Methyl
a
Cinnamylamines
We anticipated that chelation control would only allow
chain walking to generate the β,γ′-olefin prior to the second
arylation. As expected, when aliphatic substituents were
present at the γ-position, arylation was still observed
exclusively at the γ,γ′-positions, with no chain walking to
other sites (4s−4u). The diarylation also occurs when other
aryl substituents are present at the γ-position (4v and 4w).
When there is an arene at both the γ and γ′-positions already,
then one arene is added at the γ-position while the double
bond shifts to the β,γ′-position (4x). In the case of a β-alkyl
substituted substrate, where the second arylation was not
expected to occur, the reaction proceeded and still gave
complete Z-selectivity for the formation of the β,γ′-olefin
1
product (4y) as judged by the crude H NMR of the reaction
mixture prior to purification.
Considering the sensitivity of the conditions to the level of
substitution of the secondary amines, at least with regard to
what silver salt was necessary to best promote the diarylation
reaction, we wondered how easily the reaction could be
extended to other more or less bulky amines. We therefore
sought to evaluate the scope of tertiary amines and found that
simple (E)-N,N-diethyl-2-methyl-3-phenylprop-2-en-1-amine
(5a) could be readily diarylated with representative iodoarenes
under the reaction conditions (Table 4; 6a−6d). Cyclic
tertiary amine substrates based on morpholine and piperidine
also gave the desired products using the silver sulfate
conditions (6e and 6f). Despite our efforts, we were unable
to find effective conditions for the diarylation of primary β-
alkyl cinnamylamines due to their apparent decomposition
during the reaction.
We next embarked on studying the mechanism to delineate
a plausible catalytic pathway. In this regard, several control
experiments were performed under the standard conditions
(Scheme 3). Key questions to address included the
determination of whether the cis and trans isomers
interconverted prior to the arylation reactions, whether or
not there is a background C−H activation reaction, and
whether or not the arylation occurs through an inertion or a
reductive elimination pathway. To establish whether or not
isomerization or C−H bond activation occurs on the alkenyl
amine substrates, we carried out the reaction using deuterated
trifluoroacetic acid in the absence of an aryl iodide coupling
partner (Scheme 3a). After performing the reaction, we found
that no alkene isomerization had occurred with the free amine
as a directing group.80 Meanwhile, the trans-starting material
was partially deuterated at the γ-position, while the cis-starting
a
All reactions were performed on a 0.15 mmol scale with 4 eq of aryl
halide in 1 mL of solvent (8:2 THF:TFA mixture) and in triplicate
with the average yield reported. Ag2SO4 (1.5 equiv)
b
the terminal olefin or a competitive C−H activation.
Surprisingly, when we performed the reaction with the less
sterically hindered (E)-N-isopropyl-2-methyl-3-phenylprop-2-
en-1-amine, product 4a was not observed. After rescreening
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Table 4. Scope of Aryl Iodide and Tertiary Amines for γ,γ′-
Scheme 3. Mechanistic Studies
a
Diarylation of α-Methyl Cinnamylamines
a
All reactions were performed on a 0.15 mmol scale with 4 eq of aryl
halide in 1 mL of solvent (8:2 THF:TFA mixture) and in triplicate
with the average yield reported.
material was not. Neither isomer experienced any deuterium
enrichment at the γ′-CH3. These experiments point toward the
reversible C−H activation of the trans but not the cis substrate
and rule out reversible/productive C−H activation at the γ′-
position.
To provide more direct evidence of C−H bond activation,
we subjected 3a to PdCl2 in methanol. From this reaction, we
found that five-membered-ring palladacycle dimer 7 could be
isolated (Scheme 3b); notably, the reaction was less clean
when we performed the reaction with Pd(OAc)2, possibly due
to the formation of a mixture higher order Pd-amine
complexes.81 As expected, treatment of the dimer with PPh3
gave rise to mononuclear palladacycle 8. When 7 was used in
place of Pd(OAc)2 under the standard reaction conditions, the
expected product 5a was observed in 55% yield (Scheme 3c).
Although this does not directly indicate whether the reaction
can be initiated through a C−H activation event, it does show
that formation of the C−H activation intermediate does not
siphon catalyst into a nonproductive reaction pathway. When 7
was combined with silver trifluoroacetate and phenyl iodide
under modified reaction conditions (at 50 °C), only starting
material was recovered.
To further elucidate the potential for intermediate 7 to have
a role in the reaction, we conducted the reaction under
deuterated media (Scheme 3d). Despite the partial enrichment
observed in the absence of the aryl iodide coupling partner, no
deuteration was observed when the reaction was carried out.
This suggests that the first arylation outcompetes the reversible
C−H activation step. We next synthesized the expected
product of the γ-C(sp2)−H activation reaction, 9, and used it
under the standard conditions (Scheme 3e). In this case, no
product was formed, with the starting material being largely
recovered. Since the reaction does not proceed from the
trisubstituted alkene 9, we reasoned that after insertion the β-
hydride elimination occurs exclusively to give the less
substituted olefin 10, which would then participate in the
second arylation reaction. To ensure this was possible, we next
synthesized 10 and submitted it to the standard reaction
conditions (Scheme 3f) and found product 3a in an isolated
yield of 59%.
Conventionally, the more conjugated alkene would be
expected to form, which begged the question of whether the
desired product was formed due to kinetic or thermodynamic
reasons. We reasoned that the sterically encumbered nature of
the system could cause the observed product to be more
thermodynamically favored. For this reason, we turned to DFT
calculations to shed light on the relative stabilities. Notably,
while the unobserved E isomer had the highest energy both in
the gas phase and considering a THF solvation model under all
of the conditions applied (see SI for details), the observed Z-
product was consistently higher energy than the unobserved
conjugated product. On the basis of this, we propose that the
β-hydride elimination occurs selectively, presumably due to a
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kinetic preference, rather than being under thermodynamic
control.
release of the amine. This is proposed to prevent rapid
decomposition of the substrate. Some free amine reduces the
palladium to form palladium nanoparticles, which are
subsequently stabilized by additional amine substrate to form
I.87 While we envision that a Pd0 nanoparticle is formed, PdII
nanoparticles have also been used for Mizoroki-Heck
reactions.88 Free amine can also react with the PdII salt to
give I’, although this is not expected to be a productive
pathway. Conveniently, the insertion pathway is open to both
the cis and trans. The palladium nanoparticles undergo
oxidative addition to aryl iodide, driven by precipitation of
AgI, to form II. Intermediate II undergoes γ-selective
migratory insertion into the olefin to generate III. Although
the formation of a mononuclear four-membered palladacycle is
expected to be less favored than the five-membered pallada-
cycle, the larger nanoparticle obviates this strain by allowing
one Pd to bond with N and a second one to bond with C in
the metallocycle. The insertion is then followed by
regioselective β-hydride elimination to give intermediate IV.
Subsequently, oxidative addition to a second equivalent of aryl
iodide generates V, and the following selective insertion gives
rise to intermediate VI. We propose that the exceptional steric
bulk of the resulting intermediate coupled with the bulky
nanoparticle catalyst drives the final stereoselective β-hydride
elimination, which then furnishes the expected product and
regenerates the active Pd nanoparticle catalyst.
The selective formation of the less stable alkene intermediate
10 and subsequent less stable product 3a could be due to the
size of the catalyst; we had previously demonstrated the
likelihood that Pd nanoparticles (Pd NPs) were formed when
allylamines and Pd were combined in acidic solvents. Notably,
the lack of deuterium incorporation at the γ′-position (Scheme
3a,d) suggested to us that β-hydride elimination might be
irreversible under the reaction conditions, meaning that
elimination from the less substituted site was kinetically
favored after both aryl-insertions. To test if Pd NPs were
formed in the current reaction, the filtered reaction mixtures
were subjected to scanning electron microscopy and dynamic
light scattering, and the formation of particles in the reaction
mixture was clearly observed when Pd is added (see SI for
details). However, this only proved that Pd NPs had formed
and not that they were actually the active catalyst.
Previous work had demonstrated the formation of catalyti-
cally relevant Pd NPs in a similar mixture of TFA and an
ethereal solvent.82 An indirect test for the role of a NP catalyst
is to perform a mercury drop test.83 In this case, the addition of
mercury prevented any product formation; when mercury was
added midway through the reaction, no further product was
formed. However, since the utility of the mercury drop test for
cyclopalladated complexes has recently been called into
question,84 we also prepared Pd NPs by addition of NaBH4
to an ethanolic solution of Pd(OAc)2 and ran the reaction with
these unstabilized Pd NPs. In this case, the product could still
be found in 57% (Scheme 3g), which we believe provides
further evidence for a Pd NP-catalyzed reaction, although we
cannot rule out the potential for involvement of Ag NPs85 or
mixed Pd/Ag NPs.86
CONCLUSION
■
In summary, we have developed a new γ,γ′-diarylation reaction
of β-alkyl allylamines. The methodology works well for bulky
2° amines and can be extended to less bulky 2° amines and 3°
amines simply by changing the silver salt used in the reaction.
Aside from having broad substrate scope and being reasonably
scalable, our mechanistic experiments provide what we
consider to be a reasonably clear picture of how this 1,3-
difunctionalization reaction occurs. Notably, we have demon-
strated how the unprotected amine gives superior results under
the present conditions when compared with some traditional,
protected amine directing groups.
On the basis of these experiments and previous reports, we
propose the following catalytic cycle (Figure 1): The amine
will be protonated under the acidic conditions, allowing slow
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/jacs.1c04261.
■
sı
Synthesis of amine substrates and iodoarenes, optimiza-
tion and synthesis of γ,γ′-diarylated alkenylamines,
mechanistic experiments, directing group experiments,
1H and 13C spectra of new compounds, X-ray, STEM,
DLS, computational data (PDF)
Accession Codes
CCDC 2075997−2075999 and 2076000−2076002 contain
the supplementary crystallographic 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.
AUTHOR INFORMATION
Corresponding Author
■
Michael C. Young − Department of Chemistry &
Biochemistry, School of Green Chemistry & Engineering, The
Figure 1. Proposed catalytic cycle.
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An Underutilized and Underexplored Catalytic Concept in Olefin
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University of Toledo, Toledo, Ohio 43606, United States of
America; orcid.org/0000-0002-3256-5562;
Email: michael.young8@utoledo.edu
Authors
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Vinod G. Landge − Department of Chemistry & Biochemistry,
School of Green Chemistry & Engineering, The University of
Toledo, Toledo, Ohio 43606, United States of America;
orcid.org/0000-0003-1241-4561
Aaron J. Grant − Department of Chemistry & Biochemistry,
School of Green Chemistry & Engineering, The University of
Toledo, Toledo, Ohio 43606, United States of America
Yu Fu − Department of Chemistry & Biochemistry, School of
Green Chemistry & Engineering, The University of Toledo,
Toledo, Ohio 43606, United States of America
Allison M. Rabon − Department of Chemistry &
Biochemistry, School of Green Chemistry & Engineering, The
University of Toledo, Toledo, Ohio 43606, United States of
America
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Complete contact information is available at:
https://pubs.acs.org/10.1021/jacs.1c04261
Author Contributions
The manuscript was written through contributions of all
authors./All authors have given approval to the final version of
the manuscript.
Funding
This work was supported in part through start-up funds from
The University of Toledo, as well as a generous grant from the
ACS Herman Frasch Foundation (830-HF17). A.J.G. and Y. F.
were supported by funds from the University of Toledo −
Office of Undergraduate Research. J. L. P. wishes to
acknowledge Kenyon College’s Individual Faculty Develop-
ment Account for financial support.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The authors wish to acknowledge Dr. Ian Riddington, Dr.
Kristin Suhr, Ms. Abby Gatmaitan, and Mr. Phuoc Ngo at The
University of Austin’s Mass Spectrometer Facility for collection
of high resolution mass spectrometry data. Dr. Kristin
Kirschbaum is acknowledged for advice with collection of x-
ray diffraction data, and Dr. Jennifer Gadient is acknowledged
for assistance collecting STEM and DLS data. J. L. P wishes to
acknowledge computational resources from the Ohio Super-
computing Center (OSC).
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This paper was published on June 23, 2021. Tables 1 and 2
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