Heterogeneously Ni-Pd nanoparticle-catalyzed base-free formal C-S bond metathesis of thiols

Article abstract of DOI:10.1039/d1cc00995h

This study rationally designed a heterogeneously catalyzed system (i.e., using Ni-Pd alloy nanoparticles supported on hydroxyapatite (Ni-Pd/HAP) under an H₂atmosphere) achieving an efficient base-free formal C-S bond metathesis of various thiolsviasuppression of the Ni catalysis deactivation.

Full text of DOI:10.1039/d1cc00995h

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21 April 2021
Pages 3727–3826
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Chemical Communications
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COMMUNICATION
Takafumi Yatabe, Kazuya Yamaguchi et al.
Heterogeneously Ni–Pd nanoparticle-catalyzed base-free
formal C–S bond metathesis of thiols

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Heterogeneously Ni–Pd nanoparticle-catalyzed
base-free formal C–S bond metathesis of thiols†
Cite this: Chem. Commun., 2021,
57, 3749
Kanju Mitamura, Takafumi Yatabe, * Kidai Yamamoto, Tomohiro Yabe,
Received 22nd February 2021,
Accepted 22nd March 2021
Kosuke Suzuki
and Kazuya Yamaguchi
*
DOI: 10.1039/d1cc00995h
rsc.li/chemcomm
This study rationally designed a heterogeneously catalyzed system or lithium thiolate, which did not affect the Pd catalysis unlike H2S
(i.e., using Ni–Pd alloy nanoparticles supported on hydroxyapatite or thiols. In addition, the byproducts were formed as precipitates to
(Ni–Pd/HAP) under an H2 atmosphere) achieving an efficient base- promote the desired thioether production based on the equili-
free formal C–S bond metathesis of various thiols via suppression of brium constraint of the metathesis reaction system. Thus, an excess
the Ni catalysis deactivation.
amount of LiHMDS effectively played multiple roles. In other
words, even the formal s-bond metathesis of C–S bonds cannot
Metathesis is typically a bond exchange reaction that involves be realized without any strong bases. The same formal s-bond
[2+2]-cycloaddition to form a four-membered ring metallacycle metathesis of C–S bonds catalyzed by homogeneous Ni complexes
transition state.1 The metathesis between various bonds,
including s-bonds, has recently emerged as a new synthetic
tool,2 although the scope of catalytic s-bond metathesis is still
limited.3 The C–S bonds of thiols are attractive targets for the
s-bond metathesis to synthesize thioethers, which are widely
found in polymers and pharmaceuticals.4 However, to the best
of our knowledge, the thioether synthesis by the catalytic C–S
bond metathesis of thiols via the [2s+2s] transition state has
not yet been reported. Two difficulties are encountered with the
s-bond metathesis of thiols: (i) poisoning of metal catalysis due
to thiols/thiolates and/or H2S coordinating strongly toward
metal catalysts;5 and (ii) disulfide formation via easy thiol
oxidation.6
While no catalytic C–S bond metathesis occurs via the [2s + 2s]
transition state, a formal s-bond metathesis comprising three steps
(i.e., oxidative addition, ligand exchange, and reductive elimination)
can realize difficult bond exchange reactions, including C–S bonds.
Morandi et al. recently reported the first pioneering formal s-bond
metathesis between thiols and thiols/thioethers to synthesize
thioethers by a homogeneous Pd catalyst in the presence of a
strong base of lithium bis(trimethylsilyl)amide (LiHMDS) (Fig. 1a).7
An excess amount of LiHMDS was essential in suppressing the
thiol-derived catalyst poisoning, thanks to the lithium thiolate
intermediate formation. Consequently, the byproducts were Li2S
Department of Applied Chemistry, School of Engineering, The University of Tokyo,
7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan. E-mail: kyama@appchem.t.u-
tokyo.ac.jp, yatabe@appchem.t.u-tokyo.ac.jp; Fax: +81-3-5841-7220
† Electronic supplementary information (ESI) available: Experimental details,
additional experimental results, characterization data, and spectral data of
compounds (PDF). See DOI: 10.1039/d1cc00995h
Fig. 1 Formal C–S bond metathesis of thiols and overview of this work.
Chem. Commun., 2021, 57, 3749–3752 | 3749
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were also reported, although an excess amount of LiHMDS was still
indispensable.8 Therefore, the catalytic C–S bond metathesis of
thiols without any strong bases is challenging, and a novel catalyst
design should be developed to achieve the base-free formal
metathesis of thiols.
Focusing on the rational design of heterogeneous catalysts
for new organic molecular transformations,9 we achieved
herein the formal C–S bond metathesis of thiols to thioethers
and H2S without any strong bases using hydroxyapatite-
supported Ni–Pd alloy nanoparticle catalysts (Ni–Pd/HAP)
under an H2 atmosphere (Fig. 1b). To our knowledge, this is
the first report on heterogeneously catalyzed formal C–S bond
metathesis of thiols. The present catalytic system is rationally
designed as follows: (i) Ni species: a catalyst for the formal C–S
bond metathesis of thiols; (ii) Pd species: retainment of active
Ni(0) species with the Ni–Pd alloy; and (iii) H2 atmosphere:
suppression of the poisoning derived from thiols/thiolates and/
or H2S via Pd-promoted reduction of Ni species using H2 as the
reductant (Fig. 1c). This base-free heterogeneously catalyzed
system was applied to thioether synthesis, starting from a wide
range of thiols.
Ni–Pd/HAP was prepared via the simultaneous deposition–
precipitation of Ni and Pd hydroxide species on HAP (Ni/Pd
molar ratio = B1/1), followed by reduction with NaBH4 under
an Ar atmosphere. The Ni K-edge XANES spectrum of Ni–Pd/HAP
was between those of Ni foil and Ni(OH)2 (Fig. 2a); linear
combination fitting revealed that B54% of the Ni species in
Ni–Pd/HAP was present at zero valence (Fig. S1, ESI†).10,11 The
Pd K-edge XANES spectrum was similar to that of the Pd foil,
indicating the Pd valence of zero (Fig. 2b). The HAADF-STEM
image revealed that the metal species were dispersedly sup-
ported on HAP as nanoparticles with an average diameter of
4.9 nm (standard deviation: 1.4 nm) (Fig. 2c and d). STEM-EDS
mapping images showed the presence of both Ni and Pd at the
same nanoparticle site (Fig. 2e–g). The curve fitting analysis of
the Pd K-edge EXAFS spectrum of Ni–Pd/HAP suggested the
presence of the Ni–Pd bond (Fig. S2 and Table S1, ESI†). The
XRD pattern of Ni–Pd/HAP under an Ar atmosphere revealed
that the HAP structure was maintained after supporting the
Ni–Pd nanoparticles, and the peaks derived from Ni or Pd were
hardly detected (Fig. 2h). Based on these results, we speculate
that the Ni–Pd alloy nanoparticles were supported on HAP,
although the other Ni and Pd species were also present on
HAP.12
Fig. 2 Characterization of Ni–Pd/HAP.
The formal C–S bond metathesis of p-toluene thiol (1a) for
the di-p-tolyl sulfide (2a) synthesis was initially examined under Ni species was possibly active for the formal C–S bond metathesis.
an Ar atmosphere, using various supported metal catalysts on The Ni(0) catalyst is more desirable for the inhibition of thiol
HAP (Table 1). Consequently, Ni/HAP showed a relatively high oxidation to disulfides by the Ni(II) species and for the improve-
catalytic activity for the formal C–S bond metathesis, whilst Fe, ment of the oxidative addition activity. Ni(0) species could be
Co, and Pd hardly produced 2a (Table 1, entries 1–4). However, stabilized by alloying with other metals.10 Accordingly, HAP-
a byproduct of di-p-tolyl disulfide (3a) was substantially supported bimetallic catalysts containing Ni were investigated
formed, and Ni/HAP deactivation occurred during the reaction (Table S3, ESI†). As a result, Ni–Pd/HAP showed high catalytic
(Table S2, entry 1, ESI†). The electronic property of Ni/HAP was activity and selectivity for 2a synthesis compared with Ni/HAP
analyzed by XANES, indicating that the Ni(II) species was mainly (Table 1, entry 5). The physical mixture of Ni/HAP and Pd/HAP
supported on HAP (Fig. S3, ESI†).11 The Ni(II) species was showed a lower catalytic activity compared to that of Ni–Pd/HAP
expected to be in situ reduced by 1a to form 3a, and the reduced (Table 1, entry 6), suggesting that the Ni–Pd alloy nanoparticle
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Table 1 Effect of catalysts on the formal C–S bond metathesis of 1a to
synthesize 2aa
Table 2 Substrate scopea
Yield (%)
Entry
Catalyst
2a
3a
1
2
3
4
Fe/HAP
Co/HAP
Pd/HAP
Ni/HAP
Ni–Pd/HAP
Ni/HAP + Pd/HAP
Ni–Pd/HAP
o1
8
3
57
75
62
97
71
35
14
20
4
6
1
5
6
7b
a
Reaction conditions: 1a (0.5 mmol), catalyst (metal: 4 mol% or Ni and
a
b
Reaction conditions: 1 (0.5 mmol), Ni–Pd/HAP (Ni: 4 mol%, Pd: 4 mol%,
100 mg) mesitylene (2 mL), H2 (1 atm), 150 1C, 24 h. Isolated yields are
Pd: 4 mol%) mesitylene (2 mL), Ar (1 atm), 150 1C, 24 h. H2 (1 atm).
Yields were determined by GC using biphenyl as an internal standard.
b
c
shown. Ni–Pd/HAP (200 mg). Triglyme (2 mL) instead of mesitylene,
d
200 1C. GC yields are shown.
formation is important. However, Ni–Pd/HAP deactivation still
occurred to inhibit the production of 2a in the middle of the products were isolated through extraction with aqueous NaOH
reaction (Table S2, entry 2, ESI†). The MS analysis of the evolved and diethyl ether, followed by column chromatography on
gas confirmed that H2S was produced during the reaction using silica gel. When benzenethiols substituted with a methyl group
Ni–Pd/HAP.
at the o-, m-, or p-position were used as the substrates, the
We considered that H2S and/or thiols covering the active Ni reaction efficiently proceeded (2a–2c). The corresponding
species could be desorbed by H2 cleaved on the Pd sites via the thioether was also obtained when dimethyl-substituted benze-
hydrogen spillover.13,14 As we expected, the yield of 2a reached nethiol was used (2d). The relatively low yields of 2c and 2d
up to 97% under an H2 atmosphere in the presence of Ni–Pd/HAP were possibly caused by the steric hindrance of the o-methyl
(Table 1, entry 7). As of 4 h after the reaction started, the 2a groups. Naturally, the formal C–S bond metathesis of benze-
yield under an Ar atmosphere was almost the same as that nethiol without substituents proceeded (2e). Benzenethiols
under an H2 atmosphere (Table S2, entries 2 and 3, ESI†), with methoxy or fluoro groups were effectively converted into
which indicated suppression of the Ni catalysis deactivation the corresponding thioethers in the same manner (2f, 2g). The
using H2 as the reductant. The same tendency was observed proposed system does not require a strong base; hence, it was
using Ni–Ru/HAP under an Ar or H2 atmosphere (Table S2, applicable to the substrates with methyl sulfides or hydroxy
entries 4, 5, 9 and 10, ESI†), which is consistent with the groups that were not applicable in the previously reported
assumption of Ni reduction promotion by the cleavage of H2 system using LiHMDS (2h, 2i).7 A trifluoromethyl-substituted
on precious metals, although the activity of Ni–Ru/HAP was not benzenethiol was also applicable, albeit in a low product yield
comparable to that of Ni–Pd/HAP. Furthermore, even under an (2j). Thiols with naphthyl or pyridyl groups were also applicable
H2 atmosphere, either Ni/HAP or Pd/HAP did not efficiently (2k, 2l). Benzyl thiol gave the corresponding thioethers in a
afford 2a (Table S4, ESI†), revealing that both Ni–Pd alloy and high yield (2m). Furthermore, the system was applicable to an
H2 were necessary for suppressing the deactivation.15
aliphatic thiol (2n). Then, the formal cross-metathesis between
During the reaction under an H2 atmosphere, the catalyst an aromatic thiol and an aliphatic thiol was also investigated,
was removed by hot filtration under an N2 atmosphere and leading to a preferential formation of the corresponding
immediately returned to an H2 atmosphere to continue the unsymmetrical thioether via a formal cross-metathesis conco-
reaction with the filtrate to establish whether the observed mitant with homo-metathesis products (Fig. S5, ESI†).
catalysis for the formal C–S bond metathesis of 1a occurred
Various control experiments were conducted to clarify the
heterogeneously on Ni–Pd/HAP or was a result of the leached reaction mechanism. When 3a was used as a starting material
metal species in the solution. Consequently, the reaction under the optimized conditions, 2a was formed, but the yield
immediately ceased upon the catalyst removal (Fig. S4, ESI†). was significantly lower than that of the reaction from 1a (Fig. 3a
After the reaction, a few Ni and Pd species were detectable in vs. Table 1, entry 7). Moreover, 3a was hardly detected
the solution by ICP-AES (Ni: o0.2% and Pd: o0.1% of Ni and during the reaction from 1a using Ni–Pd/HAP under an H2
Pd used for the reaction, respectively). Thus, the catalysis was atmosphere (Fig. S4, ESI†). Therefore, the reaction pathway via
confirmed to be heterogeneous.16,17
disulfides was revealed not to be the major one. Accordingly,
Under the optimized reaction conditions,18 the formal C–S when 2,6-di-tert-butyl-p-cresol (BHT) was added as a radical
bond metathesis of various thiols (1) proceeded efficiently to scavenger, 2a was obtained in almost the same yield as that in
produce the corresponding thioethers (2) (Table 2). The desired the absence of the radical scavenger (Fig. 3b vs. Table 1, entry 7).
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Notes and references
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elimination to produce the desired thioethers.
This work was financially supported by JSPS KAKENHI Grant
No. 19H02509. A part of this work was conducted at the Advanced
Characterization Nanotechnology Platform of the University of
Tokyo, supported by ‘‘Nanotechnology Platform’’ of the Ministry
of Education, Culture, Sports, Science and Technology (MEXT),
Japan. We thank Mr Hiroyuki Oshikawa (The University of Tokyo)
for his assistance with the HAADF-STEM and EDS analyses. We
also thank Dr Hironori Ofuchi (Japan Synchrotron Radiation
Research Institute, SPring-8) for giving great support for XAFS
measurements in BL14B2 (Proposal No. 2019B1820), Dr Akiko
Nozaki and Dr Tokuhiko Okamoto (Aichi Synchrotron Radiation
Center, AichiSR) for giving many support for XAFS measurements
in BL11S2 (Proposal No. 201905093).
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Conflicts of interest
There are no conflicts to declare.
This journal is © The Royal Society of Chemistry 2021
3752 | Chem. Commun., 2021, 57, 3749–3752