Microballs Containing Ni(0)Pd(0) Nanoparticles for Highly Selective Micellar Catalysis in Water

Article abstract of DOI:10.1021/acscatal.9b02316

Both Ni(0) complexes and nanoparticles (NPs) are unstable in water, which poses a significant hindrance to their application in aqueous synthetic catalysis. To overcome these barriers, ligated Ni(0) nanoparticles (diameter <1 nm) containing a minimum amount of Pd(0) in the microballs formed of amphiphile PS-750-M are developed and applied in the highly selective carbamate cleavage. Selectivity and functional group tolerance are thoroughly investigated. Control experiments revealed the importance of an individual component of the nanocatalyst. Use of our proline-based amphiphile PS-750-M is critical for achieving microball architecture, the stability of nanoparticles, and desired catalytic activity. Once formed, microballs can be isolated and stored at ambient temperature. Catalyst is thoroughly characterized by X-ray photoelectron spectroscopy, scanning electron microscopy, high-resolution transmission electron microscopy, thermogravimetric analysis, infrared, and cyclic voltammetry. For selective catalysis, zero oxidation state of both Ni and Pd is crucial. On the basis of catalyst characterization and control experiments, the plausible reaction mechanism is proposed.

Full text of DOI:10.1021/acscatal.9b02316

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Article
Microballs Containing Ni(0)Pd(0) Nanoparticles
for Highly Selective Micellar Catalysis in Water
Manisha Bihani, Pranjal P Bora, Maarten Nachtegaal, Jacek
B. Jasinski, Scott Plummer, Fabrice Gallou, and Sachin Handa
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.9b02316 • Publication Date (Web): 10 Jul 2019
Downloaded from pubs.acs.org on July 13, 2019
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ACS Catalysis
Microballs Containing Ni(0)Pd(0) Nanoparticles for Highly Selective
Micellar Catalysis in Water
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Manisha Bihani,† Pranjal P. Bora,† Maarten Nachtegaal,‡ Jacek B. Jasinski,§ Scott Plummer,ǁ Fabrice
Gallou,# Sachin Handa*†
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†Department of Chemistry, University of Louisville, Louisville, Kentucky 40292, United States
‡Paul Scherrer Institute, Forschungsstrasse 111, 5232 Villigen, Switzerland
§Materials Characterization, Conn Center for Renewable Energy Research, University of Louisville, Louisville, KY 40292,
USA
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ǁNovartis Institutes for Biomedical Research, 250 Massachusetts Ave, Cambridge, MA 02139, United States
#Novartis Pharma AG, Basel, 4056, Switzerland
Supporting Information Placeholder
microballs formed with the aid of a proline-based amphiphile PS-
750-M and a minimal amount of Pd in water. The high solubility of
gases in the lipophilic cores of micelles22,23 and association of
nanocatalysts with the PEGylated amphiphile24,25 can also be
leveraged to conduct catalysis at ambient hydrogen pressure
(Figure 1). To our delight, these aqueous nanoparticles catalyze
highly selective carbamate cleavage in the presence of other
sensitive functional groups, a reaction heavily used in the organic
synthesis, especially in the pharmaceutical industry.26,27 Notably,
Pd catalysts cleave carbamates non-selectively.26
ABSTRACT: Both Ni(0) complexes and nanoparticles (NPs) are
unstable in water, which poses a significant hindrance to their
application in aqueous synthetic catalysis. To overcome these
barriers, ligated Ni(0) nanoparticles (diameter < 1 nm) containing
a minimum amount of Pd(0) in the microballs formed of
amphiphile PS-750-M, are developed and applied in the highly
selective carbamate cleavage. Selectivity and functional group
tolerance are thoroughly investigated. Control experiments
revealed the importance of an individual component of the
nanocatalyst. Use of our proline-based amphiphile PS-750-M is
critical to achieve the microball architecture, the stability of
nanoparticles, and desired catalytic activity. Once formed,
microballs can be isolated and stored at ambient temperature.
Catalyst is thoroughly characterized by XPS, SEM, HRTEM, TGA,
IR, and cyclic voltammetry. For selective catalysis, oxidation zero
states of both Ni and Pd is crucial. Based on catalyst
characterization and control experiments, the plausible reaction
mechanism is proposed.
For amines, benzyl carbamate (Cbz) is an extremely valuable
protecting group that survives in many harsh conditions. The
protecting group strategy using Cbz is commonly used in synthesis
of pharmaceuticals, proteins, materials, and other building blocks.
However, when nitrile, benzyl ether, benzyl amines, halide, and
olefin functional groups are present in the compound, the use of
Cbz group is avoided due to possible complications related to its
selective cleavage. Either tert-butyloxycarbonyl (Boc) or
fluorenylmethyloxycarbonyl (Fmoc) protecting groups are
typically used in such circumstances;28,29 however, these groups are
highly sensitive to acidic and basic conditions, respectively. These
complications lead to chemistry that is tedious and overly
specialized. Herein, we report a Ni-based nanotechnology that is
very simple to use, sustainable, affordable, reproducible at variable
scales, and extremely selective for clean Cbz group deprotection.
KEYWORDS: micellar catalysis, organometallic catalyst, green
chemistry, sustainability, chemistry in water
Introduction. Water is a cheap, clean, and environmentally benign
solvent for conducting sustainable organic synthesis.1-3 Its usage as
a gross reaction medium in Ni catalysis under ambient conditions
is mostly prohibited due to the instability of Ni in the zero-
oxidation state.4-8 However, due to its earth-abundant status and
better activity, it is preferred over other precious metals.9-14 Despite
this preference, control on the rate and selectivity in reaction
pathways is always considered as a crucial parameter while
implementing any Ni- or Pd(0)-mediated technologies from the
discovery to the process stage.15-17 One way to further enhance the
rate and selectivity in the catalytic pathways mediated by Ni(0) is
to control the catalyst structure and oxidation state of Ni at the
nanoscale.18,19 For example, the catalytic activity of a nanoparticle
(diameter < 1 nm) will differ from larger nanoparticles and may be
selective due to a change in surface free energy.20 Although
catalytic activity is enhanced with the decrease in nanoparticle size,
the standard potential shifts toward the negative.21 This shift is
mostly inversely proportional to the radius of the nanoparticle,
which means oxidation of smaller nanoparticles is much fast. This
faster oxidation deactivates the catalyst and shut down catalysis.
Although the stability of Pd(0) nanoparticles in water is well
documented, Ni(0) nanoparticles are highly-unstable. Stability of
Ni(0) can be potentially enhanced by doping its nanoparticles with
Pd. Our efforts to solve these issues led to the development of
nanoparticles (particle size < 1 nm) of Ni(0) located in porous
Figure 1. Ni(0)Pd(0) nanoparticles in porous balls for selective
reaction pathway in water.
Results and Discussion. The hypothesis behind the development
of this nanotechnology is: (i) the minimal amount of Pd in an
inexpensive Ni salt could lead to the formation of highly active and
selective nanoparticle catalyst that remains stable in the porous
microballs suspended in water, which are in-situ formed with the
aid of our proline-based amphiphile; (ii) high solubility of
hydrogen gas in the micellar interior provides sufficient spillover
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hydrogen30 for Cbz cleavage; (iii) control on the oxidation state of
trifluoromethyls, and amides (Table 2, 2-32). Many representative
cases afford good-to-excellent isolated yields as illustrated in Table
2, 3. A broad range of aromatic and heteroaromatic arrays,
containing both the electron-rich as well as electron-deficient O-
benzyl groups are well tolerated. Notably, benzyl group with
variable electronic and steric residues on the same nitrogen where
Cbz group is bound, did not interfere with the selectivity and
catalytic activity (26-32), which is uncommon in any reported
method and commercially available catalysts.26,28
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both Ni and Pd could lead to reaction selectivity. We disclose such
a discovery: a technique that takes a readily available Ni salt and
minimal Pd, and processes it, in a single step, into highly active
nanoparticle catalyst containing Ni(0), capable of highly-selective
Cbz deprotection in water.
Table 1. Ligand optimization for Ni(0)Pd(0) nanoparticle-mediated
selective Cbz cleavagea
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Table 2. Selective Cbz cleavage in the presence of N-and O-benzyl
groupsa
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The success of this technology depends upon the confluence of
several reaction variables: the source of Ni salt, how Ni is
converted to nanoparticles located inside the porous microballs,
and the use of aqueous proline-based surfactant PS-750-M. Hence,
using inexpensive Ni(OAc)2 (>99% purity, 10 mol %) containing
minimal Pd (ca. 1 mol %) admixed with a ligand and dissolved
specifically in THF, treatment with two equivalents of a MeMgBr
at room temperature followed by a quick addition of proline-based
amphiphile PS-750-M immediately affords porous microballs
containing Ni(0)Pd(0) nanoparticles. The resulting microballs
containing small nanoparticles, either directly or after solvent
removal in vacuo, can be used for selective Cbz deprotection in
water using hydrogen gas at ambient pressure. In the model
reaction of 1, a substrate is introduced into the aqueous solution of
PS-750-M containing Ni(0) nanocatalyst, leading to free aryl amine
2 while benzyl ether is unaffected (Table 1). Use of amphiphile and
Pd dopant is essential. Ligand choice is crucial, with 3,4,7,8-
tetramethyl-1,10-phenanthroline (15) and 4,7,-diphenyl-1,10-
phenanthroline (17) affording the best results. Further substrate
screening revealed 15 provides the most robust catalytic activity.
Vigorous stirring and ambient hydrogen pressure at temperatures
between rt and 45 °C, depending upon the extent of crystallinity of
the substrate, is sufficient for clean and selective transformation.
Alternatively, NaBH4 could also be used in place of hydrogen gas
without affecting the overall reaction yield. However, due to
generation of more waste by use of NaBH4, it was not preferred in
our study.
aConditions: substrate (0.5 mmol), Ni(OAc)2 (10 mol %), 15 (10 mol %),
Pd(OAc)2 (1.0 mol %), MeMgBr (20 mol %), 3 wt % PS-750-M in H2O (1
mL), H2, 45 oC. Reported yields are isolated yields.
Table 3. General Cbz cleavagea
The scope of this nanotechnology has been thoroughly examined
to see whether it is generally applicable for Cbz cleavage on a
variety of substrates with O-benzyl, N-benzyl, or other sensitive
functionalities
such
as
olefins,
nitriles,
fluoroaryls,
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aConditions: substrate (0.5 mmol), Ni(OAc)2 (10 mol %), 15 (10 mol %),
Pd(OAc)2 (1.0 mol %), MeMgBr (20 mol %), 3 wt % PS-750-M in H2O (1
mL), H2, 45 oC. Reported yields are isolated yields.
Pyrazole and triazole residues could potentially bind with the
nanocatalyst and alter the activity and selectivity, but both these
functional groups did not interfere in the catalysis (23, 24, 31-32).
Some benzyl residues may act as transient ligands on the
nanoparticle surface and facilitate the catalysis,31 to broadly rule
out this possibility, catalytic activity and selectivity have also been
tested on a broad range of substrates lacking the benzyl group
(Table 3). Notably, a steric hindrance on the nitrogen that already
possesses the Cbz group did not affect the catalytic outcome in this
Scheme 1. Further applications of nanotechnology. a) Catalytic use
of microballs in highly challenging examples; b) catalytic activity
of fresh and aged microballs in one-pot reactions; c) direct
comparison with the state-of-the art catalyst.
class of compounds (42-44). Functionalities including
t
trifluoromethyl (21), dioxanes (22), sulfonamides (25, 37), Boc
(31, 44), silyl ethers (33), phosphonates (34), nitriles (35),
sulfonates (35, 36), amides (38), ketones (39), and hydroxyls (46),
can all be found among these examples. No hydrodefluorination
(39) and nitrile reduction (35) is observed in any case, although Ni
and Pd-based catalysts are known for these events.32 Several types
of heteroaromatic arrays are also amenable (23-25, 30-32, 45; also
see Scheme 1) including nitrogen-containing moieties which may
deteriorate the architecture of porous microballs.
Cbz group cleavage in compounds containing nucleoside and
heterocycles with many nitrogen atoms is always troublesome,33
and sometimes, cleavage does not occur with commercial or
existing catalysts. With the present nanocatalyst, however, highly
challenging substrates such as nucleoside-like compounds bearing
benzyl (49) and silyl ether (48) undergo clean Cbz cleavage in good
yield as illustrated in Scheme 1a. A substrate containing free NH-
group (50) was also well tolerated. Furthermore, substrates
containing sitagliptin (51) and cholesterol (52) are amenable to
smooth transformation with high selectivity. Side reactions are not
observed in these examples (51-53), which is especially a
noteworthy given the propensity of nickel to promote olefin
reduction and hydrodefluorination.32 Notably, the one-month aged
catalyst was equally effective as a fresh catalyst as described in the
Scheme 1b. Cbz cleavage in a ligand-like substrate containing a
binaphthyl core, triazoles, and alkyl amines would be problematic
with traditional techniques since the resulting product could
strongly chelate with a catalyst and deactivate it; however, our
nanocatalyst caused clean Cbz cleavage to the diamine, which,
upon mono-protection with Boc in the same pot, afforded the
monoamine (Scheme 1b).
The nature of the nickel source plays a crucial role in the activity
of the resulting nanocatalyst, as does the manner in which porous
balls are formed. Attempts to use Ni(NO3)2 and NiO (see
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Supporting information, Table S3) led to the almost inactive
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catalyst. Analysis of a commercially available source of Ni(OAc)2
by atomic absorption-ICP led to the finding that ca. 130 ppm Pd
were inherently available, and nanoparticles formed from this
source were catalytically active. Adding 1.0 mol % Pd into pure
Ni(OAc)2 (99.99%) and then converting them into the microballs
containing desired nanoparticles resulted in a highly potent,
reproducible, and selective catalyst. Attempts to use Pd in the
absence of pre-formed nanocatalyst led to virtually no reaction,
suggesting that the release of palladium into the aqueous medium
is not responsible for the catalysis observed (See SI). Nanocatalyst
was also compared with the state-of-the-art Pd/C catalyst, and no
selectivity was observed when Pd/C was used as a catalyst (Scheme
1c)
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The catalytic activity requires the presence of both Ni(0) and Pd(0)
within the nanoparticle, as determined by several control reactions
(Scheme 2, also see Tables S4-S8 in section 3 of SI). Reactions
attempted using just Pd(OAc)2 with 15 as a ligand in various ratios
led to no product formation. Likewise, use of 10 mol % pure
Ni(OAc)2 together with Pd(OAc)2 and 15, without prior treatment
with Grignard reagent and PS-750-M, afforded none of the desired
product. However, upon reduction of 10 mol % pure Ni(OAc)2 with
20 mol % MeMgBr in the presence of Pd(OAc)2 and 15 followed
by treatment of the resulting mixture with aqueous PS-750-M, a
highly active nanocatalyst is generated that mediated the desired
selective Cbz cleavage in 85% isolated yield. Notably, doping the
pure Ni with other metals salts, such as CuI, Cu(OAc)2, TiO2,
CoCl3 led to the formation of inactive catalyst (see SI, Table S4).
aFor details, see pages S19-S24 (sections 4, 5) in Supporting Information.
Scheme 3. Role of PS-750-M in the catalytic activity.a
Solid microballs containing nanoparticle catalyst were isolated and
analyzed by SEM, TEM, and XPS (Figures 2 A–D). As illustrated
in Figures 2 A and B, SEM analysis revealed the porous ball-like
morphology. Careful examination shows that most of the Ni is
embedded in these microballs. To confirm this, microballs broken
with a sharp nanoneedle were subjected to HRTEM analysis, which
confirmed the existence of Ni-Pd nanoparticles with average size
ca. 1 nm in the interior (Figures 2C–D, see SI Table S13). XPS
analysis revealed that the material is composed of significant
amounts of carbon (64.3%), oxygen (19.7%), magnesium (1.8%),
bromine (8.4%), nitrogen (2.5%), nickel (2.8%), and palladium
(0.3%) (see SI, Table S14). The high levels of carbon and oxygen
are associated with residual THF and amphiphile integrated within
these clusters; the C-O appears as a shoulder in the C1s spectrum
(284.5 eV; see Figure S8). Remarkably, only 2.8% nickel (Ni
2p3/2, 853.2 eV; see SI Figure S6) and 0.3% Pd (Pd 3d5/2, 3d3/2,
335.2 and 340.6 eV; see SI Figure S7) are found in the microball
composite being used as a catalyst, which was obtained from a
reduction of 10 mol % Ni(OAc)2 and ca. 1 mol % Pd(OAc)2 with
MeMgBr; this translates into only 711 ppm Ni present based on
total weight. The oxidation state of Ni in the microballs is zero
while some Ni(II) is also detected due to air exposure of the finally
grounded analyte (Figure 2E). In contrast, palladium remained
stable zero-oxidation state even after air-exposure (Figure 2F).
aFor details, see pages S12-S22 in SI.
Scheme 2. Control experiments revealing the importance of
both Ni and Pd in nanodot formation.a
A series of experiments were performed to confirm the role of
amphiphile PS-750-M in the catalytic activity, thermal stability of
active nanocatalyst, and catalyst reactivation. (Scheme 3, also see
SI, sections 4, 5). Nanocatalyst was thermally stable. Catalytic
selectivity was retained even after heating the catalyst at 80 oC for
12 h. Selectivity was also retained after thoroughly washing the
nanoparticles with degassed water under argon atmosphere.
However, when nanoparticles washed with water were exposed to
oxygen environment, catalyst selectivity was completely lost, and
both Cbz and benzyl groups were cleaved to afford 2a. Unwashed
nanocatalyst retained the activity and selectivity after exposing to
air. This indicates that excess PS-750-M is required to retain the
catalyst selectivity. Notably, catalytic activity was regained after
treating washed and air-exposed nanoparticles (NP1) with
MeMgBr and PS-750-M. Nanomicelles of PS-750-M were also
crucial for the selectivity as reactions in neat water and ethanol as
solvent provided a mixture of 2 and 2a (also see SI, section 5).
To complement these studies and control experiments described in
Scheme 2, which indicated that Pd might be bound to nickel, cyclic
voltammetry (CV) was used to confirm whether traces of Pd in
nanocatalyst are separate entity or a part of Ni-based nanoparticles.
Distinct single-electron (SE) reductions of Ni2+ at –1.18 and –1.52
V in the active catalyst (Figure 2E, in blue) compared to the
material without Pd (SE reductions of Ni at –1.02 and –1.38 V),
and material without Ni (reduction of Pd at –1.49 V) also revealed
that Pd is integrated into the Ni nanoparticle. Binding of ligand 15
with the Ni was also confirmed by IR spectroscopy (see SI, Figure
S11). After exposing the desired nanocatalyst to selective Cbz
deprotection, the recycled catalyst was collected, washed with
degassed water, and analyzed by CV to assess the surface status.
No significant changes in the CV and the retention of catalytic
activity was observed (see SI, Figure S10).
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Ni(0)Pd(0) nanoparticles located in the nanoballs formed of Mg,
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Br, THF, and PS-750-M. The oxidized Ni species possibly not
ligate the Pd(0) or interaction between the Ni(II) and Pd(0) no more
exists, and Pd and Ni are two separate nanoparticles, resulting in
complete loss of selectivity.
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aConditions: 1 mL 3 wt.% PS-750-M in H2O, 45 oC.
Scheme 4. Plausible explanation of selectivity based on
oxidation state of Nia
ICP-MS analysis was performed for Ni and Pd content within
products formed via this technology (see SI, section 12). Less
residual metal contents, i.e., both Ni and Pd <1-2 ppm, in the highly
chelating products 51 and 52, is indicative of the strength of this
nanotechnology.
The nanotechnology was also applicable on a gram-scale reaction
(see SI, page S41), which verifies the reproducibility at a large
scale. This technology can be potentially applied to many other
useful transformations by controlling the size, oxidation state, and
nature of dopant metal, and such reports will be documented from
our labs in due course.
Figure 2. Catalyst characterization. (A, B) SEM analysis; (C,
D) HRTEM analysis; (E, F) XPS analysis; (G) Cyclic
voltammetry experiments of active catalyst, 15-Ni(0), and 15-
Pd(0); (H) TGA analysis of active catalyst.
Conclusions. In concluding remarks, amphiphile PS-750-M is a
key to synthesize highly-selective nanocatalyst. The oxidation
states of both Pd and Ni are critical to achieving the desired
selectivity. Resulting nanocatalyst is highly selective, broadly
practical, applicable on gram-scale, and does not affect highly-
sensitive functional groups such as nitrile, carbonyl, olefin, benzyl,
etc. Most importantly, the reaction medium is water, and therefore,
conditions are non-pyrophoric, and potentially widely acceptable
to the pharmaceutical industry.
TGA analysis of the nanocatalyst revealed about a 10% total drop
in weight between 80-280 °C, corresponding to the loss of THF
bound to microballs (Figure 2H). Up to 450 °C, weight loss
occurred due to loss of amphiphile hydrocarbons. Material heated
beyond 380 °C was found to be very stable up to 600 °C. Notably,
when the catalyst was pre-heated at 80 °C for 12 h (see SI, section
4.1e), no loss of catalytic selectivity was observed, indicating
enough thermal stability of nanomaterial for use in organic
chemistry.
ASSOCIATED CONTENT
Supporting Information
The oxidation state of Ni is crucial for reaction selectivity. To gain
insights about the oxidation state-dependent selectivity of
nanocatalyst and the plausible mechanism, nanoparticles were
exposed to oxygen atmosphere for ca. 48 h. XPS analysis of
resulting nanomaterial revealed the complete oxidation of Ni and
partial oxidation of Pd (see SI, Figures S7-S8). Upon catalysis with
the resulting nanomaterial, complete loss of selectivity was
observed and both the benzyl and Cbz groups easily cleaved, albeit,
at a relatively faster rate, i.e., 6 h (Scheme 4). As an explanation to
the plausible mechanism, desired nanoparticle catalyst contains
ligated Ni(0) species, which potentially ligate the Pd(0) to form
The Supporting Information is available free of charge on the ACS
Publications website.
Detailed reaction optimization, general catalytic procedure,
characterization of nanomaterial, analytical data and NMRs of
compounds.
AUTHOR INFORMATION
Corresponding Author
*sachin.handa@louisville.edu
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Notes
The authors declare no competing financial interests.
ACKNOWLEDGMENT
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Financial support provided by the University of Louisville,
Kentucky Science and Engineering Foundation as per grant
agreement #KSEF-148-502-17-396 with the Kentucky Science and
Technology Corporation, ORAU, and Novartis Pharmaceuticals is
warmly acknowledged.
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Identity of many such compounds will be disclosed in future since
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