Cross β-arylmethylation of alcohols catalysed by recyclable Ti-Pd alloys not requiring pre-activation

Article abstract of DOI:10.1039/d1cc01388b

Ti-Pd alloy catalysts were developed for the cross β-arylmethylation between arylmethylalcohols and different primary alcohols via a hydrogen autotransfer mechanism. The alloy catalysts could be reused multiple times without the need for pre-activation. Analysis of the reaction solution by inductively coupled plasma atomic absorption spectroscopy indicated that only a minimal amount of Ti and no Pd was leached from the catalyst.

Full text of DOI:10.1039/d1cc01388b

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Cross b-arylmethylation of alcohols catalysed
by recyclable Ti–Pd alloys not requiring
Cite this: DOI: 10.1039/d1cc01388b
pre-activation†
Received 15th March 2021,
Accepted 20th April 2021
Masayoshi Utsunomiya,a Ryota Kondo,a Toshinori Oshima,a Masatoshi Safumi,a
b
a
Takeyuki Suzuki
and Yasushi Obora
*
DOI: 10.1039/d1cc01388b
rsc.li/chemcomm
Ti–Pd alloy catalysts were developed for the cross b-arylmethylation catalytically active layer.6 We have previously reported that such
between arylmethylalcohols and different primary alcohols via a alloys exhibit high catalytic activity during Suzuki–Miyaura
hydrogen autotransfer mechanism. The alloy catalysts could be cross coupling, Mizoroki–Heck cross coupling and the alkyla-
reused multiple times without the need for pre-activation. Analysis tion of amines.7 These materials can also be recycled following
of the reaction solution by inductively coupled plasma atomic absorp- either Suzuki–Miyaura cross coupling or amine alkylation. We
tion spectroscopy indicated that only a minimal amount of Ti and no have also examined the use of Ti–Pd alloys to catalyse cross
Pd was leached from the catalyst.
b-alkylation reactions between primary alcohols via a hydrogen
autotransfer mechanism. This methodology is a well-known
Heterogeneous catalysts have applications in various industrial green reaction that forms C–C bonds with a high degree of
processes and can provide environmental and economic atom economy.8 However, although there have been many
benefits.1 In particular, supported heterogeneous catalysts are reports of cross coupling reactions between alcohols,9 cross
beneficial in organic reactions because they are readily recovered b-branched alkylation of primary alcohols have received mini-
and reused.2 These materials are typically composed of active mal attention. Ramon and colleagues reported cross alkylation
´
metal species fixed on metal oxides, carbon or polymers. However, between primary alcohols using recyclable catalysts made of
pre-activation based on exposure to a flow of hydrogen is often magnetite impregnated with iridium nanoparticles, but this
required to reduce metals on the catalyst surface,3 and the system was prone to leaching of the iridium nanoparticles.10
product is often contaminated as a result of the leaching of Other groups have demonstrated dehydrogenative cross coupling
metals into the reaction solution.4
between aryl ethanol derivatives and benzylic alcohols using
Our work has focused on the study of Ti–Pd alloys as bulk ruthenium and iron complexes as catalysts, respectively.11 Even
metal catalysts. Ti-based alloys are already widely used because so, the separation and recycling of the catalysts remain a sig-
they are highly durable, corrosion-resistant and biocompatible nificant problem in these homogeneous systems. On this basis,
as a consequence of the formation of a stable surface oxide we report the use of a Ti–Pd alloy as catalyst for cross
film.5 Among these materials, Ti–Pd alloys have attracted b-arylmethylation reactions between primary alcohols.
attention as hydrogen storage materials.6 Furthermore, zero
The reaction of 2-phenyl ethanol (1a) with benzyl alcohol
valence Pd has been found on the surfaces of Ti oxide films by (2a) was selected as a model (Table 1). This reaction employing
X-ray photoelectron spectroscopy (XPS), suggesting that these a TiPd alloy containing 1.0 mol% Pd (Ti–1.0Pd) as the catalyst
alloys could function as catalysts for organic reactions, with and Cs2CO3 as the base with toluene as the solvent produced
the zero valence state of Pd initiating the catalytic cycle. In the the desired product (3a) in 76% yield after 48 h at 135 1C (bath
Ti–Pd alloy, zero-valent Pd layer existed on the surface of Ti temperature) in a pressure tube under air (entry 1). The use of
oxide and the outermost Pd(0) layer are exposed as an KOH as a strong base instead of Cs2CO3 also gave the desired
product but in a more moderate yield (entry 2), whereas tBuOK
a Department of Chemistry and Materials Engineering, Faculty of Chemistry,
Materials and Bioengineering, Kansai University, Suita, Osaka 564-8680, Japan.
E-mail: obora@kansai-u.ac.jp; Fax: +81-6-6339-4026; Tel: +81-6-6368-087
b Comprehensive Analysis Center, The Institute of Scientific and Industrial Research
(ISIR), Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka 567-0057, Japan
† Electronic supplementary information (ESI) available. See DOI: 10.1039/
d1cc01388b
as the base did not produce 3a at all (entry 3) and K2CO3 was
also found to be unsuitable (entry 4). Furthermore, the reaction
did not take place in the absence of a base (entry 5). Other
nonpolar solvents were examined, and solvents have higher
and lower boiling points than toluene such as p-xylene and
hexane, which were found to be compatible with this reaction
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Table 1 Optimisation of the b-alkylation of 2-phenyl ethanol (1a) with
benzyl alcohol (2a) catalysed by Ti–Pd alloysa
Table 2 The scope of alcohols applicable to the b-alkylation reaction as
catalysed by Ti–Pd alloysa
Isolated yields
Convb (%)
Yieldbc (%)
Entry
Base
Solvent
1a
3a
1
2
3
4
5
6
7
8
Cs2CO3
KOH
Toluene
Toluene
Toluene
Toluene
Toluene
p-Xylene
Hexane
1,4-Dioxane
THF
Toluene
Toluene
Toluene
Toluene
Toluene
90
499
97
9
79 [63]d
56
n.d.
2
n.d.
74
77
n.d.
n.d.
33
14
49
tBuOK
K2CO3
None
3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
77
93
3
9
2
10e
11f
12g
13h
14i
45
36
59
76
34
63
15
a
Reaction conditions: 1a (0.5 mmol), 2a (1 mmol), alloy catalyst
(1 mmol) and base (1 mmol) were stirred in solvent (2 mL) at 135 1C
a
The same reaction conditions as for Table 1, entry 1 were used, unless
b
b
c
(bath temperature) for 48 h under air. Yield was determined by GC
otherwise noted. Using a reaction time of 72 h. Using toluene
(1 mL). Using Cs2CO3 (0.5 mmol) at 150 1C.
c
d
based on 1a used (n-tridecane as internal standard). n.d. = not
d
detected by GC. The number in square bracket is the isolated yield.
e
f
g
h
Under Ar. At 120 1C. Using 0.5 mmol Cs2CO3. Using Ti–0.2Pd
i
instead of Ti–1.0Pd. Without an alloy catalyst.
reaction system. Therefore, the reaction of primary alcohols with
arylmethyl alcohols proceeded smoothly and cross b-arylmethylation
products were obtained. However, the use of only aliphatic alcohols
such as n-hexanol and n-octanol was sluggish under these condi-
tions. In addition, competitive reaction of 1a with 4-methoxybenzyl
alcohol/4-(trifluoromethyl)benzyl alcohol gave 3l and 3n in 36% and
37% yield, respectively (eq 1).
We have previously reported that Ti–Pd alloy catalysts can be
reused based on a simple process and so recycling of the
present catalysts was also examined using the same procedure.
Briefly, the alloy catalyst was separated from the reaction
mixture by suction filtration, rinsed with pure water and
methanol (Fig. S1, ESI†), then dried and returned to the
reaction vessel for a subsequent reaction. The results of this
recycling process are summarized in Fig. 1, and demonstrate
that the material retained its catalytic activity over five recycling
trials. The yields were slightly decreased after the fourth and
(entries 6 and 7). However, the reaction did not take place with
polar solvents such as 1,4-dioxane and tetrahydrofuran (THF)
(entries 8 and 9). The reactions under Ar or at 120 1C gave 3a in
low yields (entries 10 and 11). A moderate yield was obtained
when employing sub-stoichiometric amount of Cs2CO3 (entry
12). Ti–0.2Pd, which had a lower Pd content, also showed high
catalytic activity such that 3a was obtained in a good yield (entry
13), whereas a low yield of 3a was observed without Ti–1.0Pd
(entry 14).8c In addition, self-condensation product of 1a was
not observed by GC analysis under these conditions.
The scope of this same b-arylmethylation reaction catalysed
by a Ti–Pd alloy was investigated by assessing the reactivity of a
variety of alcohols (Table 2). The use of 4-methyl, 4-methoxy,
4-chloro aryl ethanol, and 2-(1-naphthyl)ethanol gave the
corresponding desired products 3b–3e. Additionally, 3f, which
included both OMe and Cl groups, was produced in an 84%
yield. A moderate yield of 3g was obtained with g-phenyl
propanol. Aliphatic alcohols bearing alkyl chain were also
investigated, and 1-octanol and 1-hexanol were found to react
with 2a to give the expected products 3h and 3i, respectively, in
t
good yields. Benzyl alcohols substituted with Me, Bu, OMe, Cl
and CF3 groups generated the corresponding products 3j–3n.
Finally, heteroaromatic alcohols were also successfully
included in this reaction system. The use of 3-pyridine-
methanol furnished the corresponding product 3o in a 61%
isolated yield, while the reaction of 2-furanmethanol with
2a led to the desired product 3p in a 56% yield and
Fig. 1 Recycling of a Ti–Pd alloy catalyst following the b-arylmethylation
2-thiophenemethanol was also found to be applicable to this of an alcohol.
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fifth reuses because the reaction rate was decreased as a result
of base (cesium-containing) adhering to the alloy surface
(for Cs XPS profile, see Fig. S11 in ESI†).
(1)
The surface state of the catalyst before use (sample a) and
after five reactions (sample b) was examined using XPS, and the
resulting Pd 3d5/2 and Pd 3d3/2 spectra are provided in Fig. 2.
The binding energy values determined for Pd in the alloy
(Pd5/2 335.8 and 336.1 eV for sample a and Pd3/2 341.1 and
341.4 eV for sample b) were higher than those for bulk Pd
(Pd 3d5/2 335.1 eV and Pd 3d3/2 340.3 eV). Previous research has
indicated that a positive shift in the Pd(0) binding energy in
Ti–Pd alloys is associated with decreased Fermi levels at Pd
sites that result from the alloying.12 Comparing samples a and
b, it is evident that the peak shift was minimal, confirming that
the Pd valence state remained low even after five uses.
The concentrations of metals leached into the reaction
solution were assessed by inductively coupled plasma atomic
emission spectroscopy (ICP-AES), and the results obtained after
reactions under standard conditions and under Ar are shown in
Tables S1 and S2 (ESI†). Under standard conditions, only a
small amount of Ti was lost to the reaction solution (1.74 ppm,
3.67 Â 10À3%Ti) and the amount of leached Pd was less than
the detection limit of the analytical system (3.05 Â 10À3 ppm).
Following the reaction under Ar, even less Ti was leached
(1.23 Â 10À2 ppm, 2.53 Â 10À5%Ti) and the amount of leached
Pd was again less than the detection limit. The effects of
molecular oxygen with Ti have been researched previously,
although the exact mechanism by which Ti was leached out
of the alloy in the present work is unclear.13 Filter experiment
were also carried out to examine the effect of leached Ti on the
reaction (Fig. 3). The reaction when performed under standard
conditions afforded the desired product 3a in a 41% yield after
24 h and a 76% yield after 48 h. In an additional trial, the
catalyst was removed after 24 h by passing the reaction solution
through a membrane filter, after which additional Cs2CO3
(1.0 mmol) was added and the filtrate was heated and stirred
Fig. 3 Filter experiment of the Ti–Pd alloy catalyst for b-arylmethylation
of alcohols. Yields after 24 h were within the range of 40–41%.
for a further 24 h under the same conditions. A slight increase
in yield caused solely by the effect of the base was observed,
with no acceleration resulting from leached Ti in the reaction
solution. Thus a Ti–Pd catalyst (Pd in this case) efficiently
catalyse the dehydrogenation step (to form aldehyde) in which
step the catalyst plays a major role.
A possible reaction mechanism for this b-alkylation involving
hydrogen autotransfer is presented in Scheme 1. Initially, the
primary alcohols are oxidized to generate the respective alde-
hydes. These aldehydes then undergo cross dehydration conden-
sation promoted by the base to produce an a,b-unsaturated
aldehyde. Finally, the double bond is hydrogenated and the
carbonyl group is reduced to give the desired product.
Experiments with deuterium labelling were also performed
as a means of providing further information concerning the
mechanism (Scheme 2). Initially, possible reaction intermedi-
ates were investigated. In these trials, the a,b-unsaturated
aldehyde product was obtained when using phenylacetalde-
hyde and benzaldehyde instead of 2-phenyl ethanol and benzyl
alcohol, both with and without a catalyst (Scheme 2, entries a
and b). These results indicated that the alloy was not involved
in the dehydration condensation step. The reaction of 2-phenyl
ethanol with benzaldehyde gave the desired product (entry c),
and the a,b-unsaturated aldehyde reacted with benzyl alcohol
to give the same product (entry d).
The relatively low yield of the reaction products appears to
be caused by the decomposition of the unsaturated aldehydes
under heat and base. These findings suggest that both benzyl
alcohol and 2-phenyl ethanol can serve as a hydrogen source in
the reaction. Deuterium labelling experiments were performed
Fig. 2 Pd XPS spectra obtained from a Ti–Pd alloy (a) before use and
(b) after five reactions.
Scheme 1 A plausible reaction mechanism.
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We thank Ms Nao Eguchi of the Comprehensive Analysis
Center, SANKEN (ISIR), Osaka University for ICP-AES analysis.
High resolution mass spectra were performed at Global Facility
Center, Hokkaido University. This work was supported partly by
JSPS KAKENHI Grant Number 19K05573 (YO) and 19K15278
(RK), and ERTDF (2RF-1801) of ERCA (RK).
Conflicts of interest
The authors declare no conflict of interest.
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