Selective Dehydrogenative Mono- or Diborylation of Styrenes by Supported Copper Catalysts

Article abstract of DOI:10.1021/acscatal.9b00761

The selective dehydrogenative borylation of alkenes is an attractive method for synthesizing useful borylalkenes. However, very few catalytic systems have been reported that fulfill this objective. All the reported examples are homogeneous catalysts with

Full text of DOI:10.1021/acscatal.9b00761

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Letter
Selective Dehydrogenative Mono- or Diborylation
of Styrenes by Supported Copper Catalysts
Daichi Yoshii, Xiongjie Jin, Noritaka Mizuno, and Kazuya Yamaguchi
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.9b00761 • Publication Date (Web): 06 Mar 2019
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Selective Dehydrogenative Mono- or Diborylation of Styrenes by
Supported Copper Catalysts
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Daichi Yoshii,† Xiongjie Jin,*,‡ Noritaka Mizuno,† and Kazuya Yamaguchi*,†
†Department of Applied Chemistry, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-
8656, Japan
‡Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku,
Tokyo 113-8656, Japan
ABSTRACT: The selective dehydrogenative borylation of alkenes is an attractive method for synthesizing useful borylalkenes.
However, very few catalytic systems have been reported far that fulfill this objective. All the reported examples are homogeneous
catalysts with special ligands requiring the usage of bases. This study describes the heterogeneously catalyzed dehydrogenative
borylation by supported copper hydroxide catalysts (Cu(OH)x/support). In the presence of Cu(OH)x/support and suitable ketones,
the dehydrogenative borylation of styrenes with bis(pinacolato)diboron efficiently proceeded to selectively afford the corresponding
β-monoboryl- or β,β-diborylstyrenes. The observed catalysis was truly heterogeneous, and the catalysts could be reused several
times though their catalytic performance gradually declined.
KEYWORDS: Copper • Dehydrogenative borylation • Heterogeneous catalysis • Selectivity control • Styrenes
The development of heterogeneous catalysts for liquid-
phase organic functional group transformations, which are
used in the production of fine chemicals and pharmaceuticals,
is becoming increasingly important because of the easy
recovery/reuse of catalysts and minimization of metal
contamination in the synthesized products.1 Moreover, there
has been an upsurge in the need to develop heterogeneous
catalysts for use in continuous flow systems for the on-
demand synthesis of valuable chemicals.2 However, highly
regio- and stereoselective reactions have traditionally been
accomplished using homogeneous catalysts with well-
designed ligands. Recent advances in homogeneous copper-
catalyzed C–B bond formation reactions using N-heterocyclic
carbenes or phosphines as the ligands have allowed to
synthesize a range of valuable organoboron compounds.3,4
However, heterogeneously copper-catalyzed borylation
reactions are very rare.5 Due to the importance of the use of
organoboron compounds as key building blocks in several
organic synthesis reactions, the development of new efficient
heterogeneous copper-based catalysts for selective borylation
reactions is highly desirable from economic and
environmental viewpoints.
dehydrogenative borylation of alkenes.11 Dehydrogenative
borylation can be used to directly convert readily available
alkenes into the corresponding vinyl boronic esters, providing
simple access to a wide range of compounds, including β,β-
disubstituted vinyl boronic esters, which cannot be synthesized
via the hydroboration of alkynes. Recently, rhodium-,12 iron-,13
and copper-based14 homogeneous catalysts are reported to be
effective in the dehydrogenative borylation of alkenes to
monoborylalkenes using alkenes or ketones as the sacrificial
oxidants. Furthermore, the homogeneous palladium-15 and
cobalt-catalyzed16 dehydrogenative diborylation of terminal
alkenes has been recently reported.
Scheme 1. The dehydrogenative monoborylation and di-
borylation of styrenes using Cu(OH)x/support
Here, we report that the copper hydroxide species on
suitable metal oxide supports (Cu(OH)x/support) can act as an
efficient heterogeneous catalyst for the dehydrogenative
borylation of styrene and its derivatives with
bis(pinacolato)diboron (B2pin2) to selectively produce β-
monoboryl- or β,β-diborylstyrenes (Scheme 1). Both
monoboryl- and diborylalkenes are useful compounds for
serving as building blocks to selectively synthesize a range of
multisubstituted alkenes via C–C and C–heteroatom bond-
forming reactions.6 Monoborylalkenes have been prepared via
the hydroboration of alkynes,7 the borylation of alkenyl
halides,8 alkene cross-metathesis,9 the boryl–Heck reaction
using electrophilic boron reagents,10 or via the
In this work, Cu(OH)x/CeO2 was found to efficiently
promote the dehydrogenative borylation of styrene and its
derivatives using benzophenone as the HBpin acceptor, to
selectively afford β-monoborylstyrenes in moderate to high
yields with high regioselectivities (Scheme 1). Furthermore,
dehydrogenative diborylation was used to produce β,β-
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diborylstyrenes through a simple modifcation of the reaction
Table 1. Optimization of the reaction conditions of the
dehydrogenative borylation of styrene (1a) to β-
monoborylstyrene (2a) and β,β-diborylstyrene (3a)
conditions, e.g., increasing the amounts of B2pin2, the HBpin
acceptor 2-adamantanone, and the Cu(OH)x/Al2O3 catalyst
(Scheme 1). In the proposed Cu(OH)x/support-catalyzed
dehydrogenative borylation reaction, additives, such as special
ligands and bases, which were found to be necessary in the
previously reported homogeneously catalyzed systems,12‒16
were not required. To the best of our knowledge, the present
work is the first report on dehydrogenative borylation using
heterogeneous catalysts.
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Yield (%)
Entry
Catalyst
Acceptor
With reference to the previously reported homogeneous
2a
31
<1
<1
<1
4
3a 3a'
copper-catalyzed
C‒B
bond
formation
reactions,14
1a,b
2a,c
3a
4a
5a
6a
7a
8a
9a
10a
11a,d
12a,e
13a,e
14a,e
15f
16f
17f
18f
Cu(OH)x/CeO2
Cu(OH)x/CeO2
CuCl2/CeO2
Cu(OAc)2/CeO2
Cu(OH)2
—
5
2
heterogeneous copper-based catalysts were initially examined
for the borylation of styrene (1a) with B2pin2 on the assumption
of the mechanism shown in Scheme 2a. Surprisingly, out of all
of the catalysts examined for the borylation of 1a under the
conditions described in Table 1 (entries 1–11, without HBpin
acceptors), significant amounts of 2a were only afforded in the
—
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
8
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
2
—
—
—
CuO
—
<1
<1
4
presence
of
supported
copper-hydroxide
catalysts
(Cu(OH)x/support,17,18 Figure S1), and it was observed that the
use of Cu(OH)x/CeO2 gave 2a in 31% yield (Table 1, entry 1).
No reactions were observed to proceed in air, even in the
presence of Cu(OH)x/CeO2 (Table 1, entry 2). The borylation
reaction did not proceed in the presence of CuCl2 or Cu(OAc)2
(OAc = acetate) supported on CeO2 (Table 1, entries 3 and 4), or
in the absence of catalysts or the presence of a CeO2 support
alone (Table 1, entry 11). Other simple CuI and CuII salts, such
as CuCl, CuCl2, and Cu(OAc)2, were not effective in the
catalysis of the borylation reaction (Table 1, entries 8–10). The
borylation reaction barely proceeded in the presence of bulk
copper hydroxide Cu(OH)2 or copper oxides (Table 1, entries 5–
7). Therefore, it was concluded that the use of a highly dispersed
copper hydroxide species is crucial for the borylation reaction to
proceed.
Cu2O
—
CuCl2
—
CuCl
—
<1
2
Cu(OAc)2
CeO2
—
—
<1
87
Cu(OH)x/CeO2
benzophenone
Cu(OH)x/CeO2 2-adamantanone 75
7
3
Cu(OH)x/Al2O3
Cu(OH)x/CeO2
benzophenone
benzophenone
64
14
10
58
59
31
84
1
15
5
Cu(OH)x/CeO2 2-adamantanone <1
Cu(OH)x/Al2O3
benzophenone
55
5
4
Cu(OH)x/Al2O3 2-adamantanone
<1
aReaction conditions: 1a (0.5 mmol), B2pin2 (1.25 mmol), catalyst (Cu:
4 mol%), acceptor (0.75 mmol), mesitylene (2 mL), 120 °C, Ar (1 atm),
20 h. Yields were determined by GC analysis using n-hexadecane as an
internal standard. bThe hydroborated products and ethylbenzene were also
significantly produced in 29% (α/β = 2.6:1) and 26% yields, respectively.
cUnder an air atmosphere. dCeO2 (80 mg). ep-Xylene was used as a solvent
instead of mesitylene. fReaction conditions: 1a (0.2 mmol), B2pin2
(1.0 mmol), catalyst (Cu: 8 mol%), acceptor (0.6 mmol), p-xylene (2 mL),
120 °C, Ar (1 atm), 20 h. See also Tables S1 and S2.
Scheme 2. The assumed mechanism of the copper-catalyzed
dehydrogenative borylation of styrenes
The Cu K-edge x-ray absorption near edge structure
(XANES) spectrum and its first-derivative spectrum of freshly
prepared Cu(OH)x/CeO2 were recorded to be quite similar to
those of Cu(OH)2 (Figure S2), indicating that Cu(OH)x/CeO2
possesses CuII hydroxide species dispersed on CeO2 support.
After the catalyst was used in the reaction of 1a or treated with
B2pin2 under an Ar atmosphere, the CuII species in
Cu(OH)x/CeO2 was reduced to CuI and Cu0 species
(Figure S2). In a separate experiment, we prepared Cu0/CeO2
by the treatment of Cu(OH)x/CeO2 with H2 (1 atm) at 200 °C
for 1 h,19 and the borylation of 1a was performed with the
catalyst; however, no reaction proceeded. Thus, the in situ
formed CuI species is likely the true active species in the
borylation reaction. We treated Cu(OH)x/CeO2 (100 mg) with
B2pin2 (30 mg) in benzene-d6 at 120 °C for 10 min, and the
catalyst was removed by the filtration. 11B NMR (Figure S3)
and GC-MS analyses of the filtrate revealed that HOBpin was
produced during the pre-catalyst reduction step. It is possibly
that B2pin2 and surface hydroxy species and/or trace amounts
of water contained in the catalyst (and/or solvent) act as
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reductants to form the reduced copper species according to the
or was a result of the presence of leached Cu species in the
solution, the catalyst was removed by hot filtration (at 55%
yield of 2a) under the conditions described in Figure S6, and
the reaction was restarted with the filtrate under the same
conditions. The production of 2a immediately ceased upon the
removal of the catalyst (Figure S6). Additionally, after the
reaction, the filtrate was analyzed using inductively coupled
plasma-atomic emission spectroscopy (ICP-AES), and it was
observed that the Cu species was barely detectable (Cu:
<0.01%). Thus, the observed catalysis for the present
dehydrogenative borylation was determined to be truly
heterogeneous.25 Furthermore, Cu(OH)x/CeO2 was retrieved
from the reaction mixture by simple filtration under an Ar
atmosphere, and repeated reuse experiments were carried out
using the retrieved Cu(OH)x/CeO2. Although the catalsyt could
be reused several times, its catalytic performance gradually
declined during the repeated reuse experiments.26
first step in Scheme 2a, although the detailed reduction
mechanism remains unclear.20 Further, we have reported that
Cu(OH)2 can be easily reduced than other CuII species, such as
CuCl2·2H2O and Cu(OAc)2·H2O.19 Therefore, Cu(OH)x/CeO2
can be used to easily generate the active reduced copper
species and thus exhibit high catalytic activity in the
borylation reaction.
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Under the proposed Cu(OH)x/support-catalyzed system, the
CuI‒Bpin species is likely to form readily. The CuI–Bpin
species is involved in an insertion reaction with 1a, followed by
β-hydride elimination to produce β-monoborylstyrene (2a) and a
CuI–H species (Scheme 2a). To complete the catalytic cycle, an
appropriate HBpin acceptor is required to regenerate the CuI–
Bpin from CuI–H (Scheme 2a). Although Cu(OH)x/CeO2 is an
excellent catalyst for the borylation of 1a, the yield of 2a was
only 31%, even in the quantitative conversion of 1a without the
use of a HBpin acceptor (Table 1, entry 1). The reason the yield
of 2a cannot theoretically exceed 50% is that in the absence of a
HBpin acceptor, 1a itself acts as the HBpin (or hydride)
acceptor. As can be seen in Table 1, entry 1, the hydroboration
products and ethylbenzene were also produced in 29% and 26%
yields, respectively. Therefore, the search began for an optimal
HBpin acceptor for use in the Cu(OH)x/CeO2-catalyzed
borylation of 1a (Table S1, entries 1–5). Fortunately, several
ketones, such as benzophenone and 2-adamantanone, were
found to be effective (Table 1, entries 12 and 13), and
benzophenone was found to give the best result, with the desired
compound 2a being obtained in 87% yield (Table 1, entry 12).
Among various supprorted copper-hydroxide catalysts
examined, such as Cu(OH)x/CeO2, Cu(OH)x/Al2O3,21
Cu(OH)x/TiO2, and Cu(OH)x/ZrO2, Cu(OH)x/CeO2 showed the
best catalyitic performance (Table 1, entries 12 and 14, see
also Table S1). In the presence of benzophenone, the
hydroboration and hydrogenation of styrene barely proceeded.
1H NMR analysis was used to confirm that the hydroboration
product of benzophenone was also produced during the
reaction. Furthermore, when using β,β-dideuteriostyrene (1a-
D2) as the substrate, the deuterium content at the α-position of
the hydroborated benzophenone was 64%.22 Thus, the
hydrogen at the β-position of styrene is mostly transferred to
benzophenone through a β-elimination process (Scheme 2a)
and hydride addition sequence (Scheme 2b).
Under the conditions described in Table 1, entry 12, the
main product was the monoborylated compound 2a alongside
a small amount of the diborylated compounds 3a and 3a'.
Next, the reaction was attempted using an increased amount of
B2pin2 (five equivalents with respect to 1a) to selectively
obtain the β,β-diborylated product 3a. Although the reaction
using Cu(OH)x/CeO2 and benzophenone preferentially resulted
in the formation of the β,β-diborylated compound 3a in 58%
yield, the α,β-diborylated product 3a' was also concomitantly
produced in 15% yield (Table 1, entry 15). After the various
reaction-condition optimization experiments, the target
product 3a could be selectively obtained in 84% yield using
Cu(OH)x/Al2O3 as the catalyst and 2-adamantanone as the
HBpin acceptor (Table 1, entries 15–18, Figure S4).23 Several
control experiments were conducted using 2a as the starting
material and revealed that 2-adamantanone was more able to
promote the second dehydrogenative borylation than
benzophenone (Figure S5).24
With the optimized reaction conditions, the substrate scope
for the proposed Cu(OH)x/CeO2-catalyzed dehydrogenative
monoborylation reaction was investigated in the presence of
benzophenone as the HBpin acceptor (Figure S7). As shown in
the left of Table 2, various styrene derivatives could be
converted into the corresponding β-monoborylstyrenes in an
E-selective fashion. When styrenes substituted with a methyl
group at the ortho-, meta-, or para-position (1b, 1c, and 1d)
were used as the substrates, the borylation reaction proceeded
efficiently to give the corresponding β-monoborylstyrenes in
moderate to high yields, indicating that the influence of the
steric hindrance of the benzene-ring substituents is not
considered significant. Styrenes with a range of electronically
diverse substituents at the para-position, including methyl
(1b), tert-butyl (1e), methoxy (1f), dimethylamino (1g), fluoro
(1h), phenyl (1i), trifluoromethyl (1j), and acetal (1k) groups,
were applicable to this proposed system. In addition, the
reaction of vinylfuran (1l) afforded the corresponding
borylated product, but vinylpyridine did not undergo this
transformation. Unfortunately, the reaction of styrenes with
chloro, nitro, cyano, phosphine, and hydroxyl group at para-
position generated unidentified byproducts, and the
corresponding β-monoborylstyrenes were hardly obtained. The
Cu(OH)x/CeO2-catalyzed monoborylation of α-substituted
styrenes (1m, 1n, and 1o) was also explored to produce α-
substituted β-monoborylstyrene, which cannot be synthesized
via the hydroboration of alkynes. However, the desired
monoborylation products were obtained in low yields (<40%)
under the standard reaction conditions using benzophenone.
For these α-substituted styrenes, the yields of the target
products could be enhanced using 2-adamantanone as the
HBpin acceptor and by increasing the reaction temperature
from 120 °C to 130 °C. The reaction of 1m or 1n gave the
corresponding α-substituted β-monoborylstyrene in a high
yield with an E-selective fashion. For the reaction of 1o, a
mixture of E- and Z-isomers was obtained, with the
preferential formation of the E-isomer (E/Z = 3.7:1). In addi-
tion, the reaction of trans-β-methylstyrene (1p) gave the cor-
responding β-monoborylated product (2p) in 73% isolated
yield with high Z-selectivity (E/Z = 1:19) (Scheme 3a). In
contrast, when cis-β-methylstyrene (1p') was subjected to the
same conditions, the yield was relatively low (48%), and the
E-isomer was mainly obtained (E/Z = 2:1) (Scheme 3b). These
results are consistent with the assumed reaction mechanism
shown in Scheme 2 including sequential migratory insertion
and β-hydride elimination (Scheme 3c). When alkyl alkenes,
To establish whether the observed catalysis for the
borylation of 1a occurred heterogeneously on Cu(OH)x/CeO2
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Table 2. Substrate scope of the dehydrogenative monoborylation and diborylation reactionsa
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aSet of reaction conditions A (monoborylation): 1 (0.5 mmol), B2pin2 (1.25 mmol), Cu(OH)x/CeO2, (Cu: 4 mol%), benzophenone (0.75 mmol), p-xylene (2
mL), 120 °C, Ar (1 atm), 20 h. Set of reaction conditions B (diborylation): 1 (0.2 mmol), B2pin2 (1.0 mmol), Cu(OH)x/Al2O3, (Cu: 8 mol%), 2-
1
adamantanone (0.6 mmol), p-xylene (2 mL), 120 °C, Ar (1 atm), 20 h. Yields were determined by H NMR and the values in parentheses are the isolated
yields. b2-Adamantanone was added instead of benzophenone and the reaction was carried out at 130 °C. c2d was also obtained in 38% yield.
dCu(OH)x/CeO2 was used instead of Cu(OH)x/Al2O3. e2i was also obtained in 49% yield. f2j was also obtained in 41% yield. g2k was obtained 70% yield. h2l
was obtained 30 % yield. i2-Adamantanone (0.8 mmol) was added and the reaction was carried out at 130 °C for 64 h.
such as 4-phenyl-1-butene, were examined, multiple indistin-
guishable mixtures of monoborylated products were unfortu-
nately obtained.
Scheme 3. Dehydrogenative monoborylation of (a) trans-β-
methylstyrene and (b) cis-β-methylstyrene, and (c) the as-
sumed reaction mechanism
Next, we attempted to synthesize β,β-diborylstyrenes using
the Cu(OH)x/Al2O3-catalyzed dehydrogenative diborylation
reaction. Several styrenes containing a range of electronically
diverse aryl groups were selectively converted into the
corresponding β,β-diborylstyrenes in moderate to high yields
with high regioselectivities (right of Table 2). However, 3d, 3i,
3j, 3k, and 3l were obtained in low yields because a
significant amount of the monoborylated intermediates (2d, 2i,
2j, 2k, and 2l) remained unreacted. Further, the reaction of 1m
gave the diborylated product 3m in only 8% yield, even
though complete conversion of 1m and 2m was achieved. This
is because the double bond isomerization and borylation of 2m
and 3m may occur at the α-methyl substituent. In contrast, the
diborylation products 3n and 3o could be obtained using the
present Cu(OH)x/Al2O3-catalyzed system.
In conclusion, for the first time, a heterogeneous catalytic
system was developed using Cu(OH)x/support for the
dehydrogenative borylation of styrene and its derivatives with
B2pin2 under ligand- and base-free conditions. The desired
reaction was tested using suitable ketones as HBpin acceptors.
Various types of β-monoborylstyrenes were synthesized in
moderate to high yields and high regioselectivities. Moreover,
dehydrogenative diborylation was also realized by simply
modifying the reaction conditions, leading to selective
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Catal. 2016, 6, 7585–7589. (b) Jiang, S.; Quintero-Duque, S.; Roisnel,
T.; Dorcet, V.; Grellier, M.; Sabo-Etienne, S.; Darcel, C.; Sortais, J.-B.
Direct synthesis of dicarbonyl PCP-iron hydride complexes and
catalytic dehydrogenative borylation of styrene. Dalton Trans. 2016,
45, 11101–11108.
(14) Mazzacano, T. J.; Mankad, N. P. Dehydrogenative Borylation
and Silylation of Styrenes Catalyzed by Copper-Carbenes. ACS Catal.
2017, 7, 146–149.
(15) (a) Takaya, J.; Kirai, N.; Iwasawa, N. Efficient Synthesis of
Diborylalkenes from Alkenes and Diboron by a New PSiP-Pincer
Palladium-Catalyzed Dehydrogenative Borylation. J. Am. Chem. Soc.
2011, 133, 12980–12983. (b) Kirai, N.; Iguchi, S.; Ito, T.; Takaya, J.;
Iwasawa, N. PSiP-Pincer Type Palladium-Catalyzed Dehydrogenative
Borylation of Alkenes and 1,3-Dienes. Bull. Chem. Soc. Jpn. 2013, 86,
784–799.
ASSOCIATED CONTENT
Supporting Information
The supporting information is available free of charge on the ACS
Publication website: experimental details, additional experimental
results, characterization data, and NMR spectra (PDF).
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AUTHOR INFORMATION
Corresponding Author
*E-mail: kyama@appchem.t.u-tokyo.ac.jp, t-jin@mail.ecc.u-
tokyo.ac.jp
Notes
The authors declare no competing financial interests.
ACKNOWLEDGMENT
This work was financially supported by JSPS KAKENHI Grant
No. 15H05797 in Precisely Designed Catalysts with Customized
Scaffolding. D. Y. was supported by the JSPS through the
Research Fellowship for Young Scientists (Grant No. 18J21337).
REFERENCES
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(4) Recently, dehydrogenative borylation of alkynes using first row
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Sortais, J.-B.; Darcel, C. Iron-Catalyzed Dehydrogenative Borylation
of Terminal Alkynes. Adv. Synth. Catal. 2018, 360, 3649–3654. (b)
Romero, E.-A.; Jazzar, R.; Bertrand, G. (CAAC)CuX-catalyzed hy-
droboration of terminal alkynes with pinacolborane directed by the X-
ligand. J. Organomet. Chem. 2017, 829, 11–13. (c) Romero, E.-A.;
Jazzar, R.; Bertrand, G. Copper-catalyzed dehydrogenative borylation
of terminal alkynes with pinacolborane. Chem. Sci. 2017, 8, 165–168.
(5) (a) Grirrane, A.; Corma, A.; Garcia, H. Stereoselective Single
(Copper) or Double (Platinum) Boronation of Alkynes Catalyzed by
Magnesia-Supported Copper Oxide or Platinum Nanoparticles. Chem.
Eur. J. 2011, 17, 2467–2478. (b) Zhou, X.-F.; Wu, Y.-D.; Dai, J.-J.;
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alkyl bromides catalyzed by Cu2O nanoparticles. RSC Adv. 2015, 5,
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(17) Supported copper hydroxide catalysts were prepared according to
our previous reports: (a) Oishi, T.; Katayama, T.; Yamaguchi, K.;
Mizuno, N.; Heterogeneously Catalyzed Efficient Alkyne–Alkyne
Homocoupling by Supported Copper Hydroxide on Titanium Oxide.
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Katayama, T.; Mizuno, N. A Supported Copper Hydroxide on
Titanium Oxide as an Efficient Reusable Heterogeneous Catalyst for
1,3-Dipolar Cycloaddition of Organic Azides to Terminal Alkynes.
Chem. Eur. J. 2009, 15, 10464–10472. (c) Oishi, T.; Yamaguchi, K.;
Mizuno, N. Conceptual Design of Heterogeneous Oxidation Catalyst:
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(18) The XRD patterns of freshly prepared Cu(OH)x/CeO2 and
Cu(OH)x/Al2O3 were the same as those of the parent CeO2 and Al2O3
support, respectively; no signals due to copper metal (clusters) and
copper oxides were observed (Figure S1).
(19) Kim, I.; Itagaki, S.; Jin, X.; Yamaguchi, K.; Mizuno, N.
Heterogeneously catalyzed self-condensation of primary amines to
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secondary amines by supported copper catalysts. Catal. Sci. Technol.
2013, 3, 2397–2403.
(20) Recently, reduction of alkenes, alkynes, and heterocycles using
diboron compounds and water as reducing agents has been reported.
For the examples, see: (a) Cummings, S. P.; Le, T.-N.; Fernandez, G.
E.; Quiambao, L. G. B.; Stokes, J. Tetrahydroxydiboron-Mediated
Palladium-Catalyzed Transfer Hydrogenation and Deuteriation of
Alkenes and Alkynes Using Water as the Stoichiometric H or D Atom
Donor. J. Am. Chem. Soc. 2016, 138, 6107–6110. (b) Xuan, Q.; Song,
Q. Diboron-Assisted Palladium-Catalyzed Transfer Hydrogenation of
N-Heteroaromatics with Water as Hydrogen Donor and Solvent. Org.
Lett. 2016, 18, 4250–4253. (c) Ojha, D. P.; Gadde, K.; Prabhu, K. R.
Generation of Hydrogen from Water: A Pd-Catalyzed Reduction of
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Alkyne Reduction by using Water as the Hydrogen Source. Chem.
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(21) We confirmed by XANES analysis that all CuII species in
Cu(OH)x/Al2O3 were reduced to mainly CuI species after the catalyst
was utilized for the reaction of 1a or treated with B2pin2 (Figure S2).
The reaction profiles revealed that Cu(OH)x/Al2O3 showed the higher
initial rate than Cu(OH)x/CeO2, and Cu(OH)x/Al2O3 gave 2a in 80%
yield after 6 h (Figure S8). However, when prolonging the reaction
time for the Cu(OH)x/Al2O3-catalyzed reaction, the yield of 2a and the
mass balance gradually decreased. In contrast, the yield of 2a
gradually increased and the mass balance was preserved when
prolonging the reaction time for the Cu(OH)x/CeO2-catalyzed reaction.
When 2a was treated with Al2O3 in p-xylene at 120 °C, the mass
balance of 2a significantly decreased (Figure S9). In the case of CeO2,
the mass balance was almost preserved (Figure S9). Therefore,
Cu(OH)x/CeO2 gave the better yield of 2a after 20 h than
Cu(OH)x/Al2O3 in the monoborylation.
(22) After the borylation, the reaction mixture was treated with water,
and benzhydrol (hydrolysis product of the hydroborylated
benzophenone) was isolated by silica gel column chromatography.
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Then, the deuterium content at the α-position was determined by H
NMR analysis (see the Supporting Information).
(23) Several control experiments using 2a as the starting material
revealed that Cu(OH)x/Al2O3 promoted the second step of the
dehydrogenative diborylation (from 2a to 3a) with high β-selectivity.
The difference in the regioselectivity was caused by the choice of
supports, not ketones (Figure S5). We supposed that 3a and 3a’ were
produced by the insertion of 2a into the Cu–B bond followed by the
β-hydride elimination and that the regioselectivity depended on the
electronic state of Cu species and/or the steric hinderance around Cu
species; therefore, the choice of the supports possibly gave a
difference in the regioselectivity.
(24) We speculated that 1a was most easily adsorbed onto the catalyst,
followed in order by benzophenone, 2a, 2-adamantanone; therefore,
we consider that benzophenone decreased the reaction rate of the
borylation of 2a to 3a.
(25) Sheldon, R. A.; Wallau, M.; Arends, I. W. C. E.; Schuchardt, U.
Heterogeneous Catalysts for Liquid-Phase Oxidations:ꢀ Philosophers'
Stones or Trojan Horses? Acc. Chem. Res. 1998, 31, 485–493.
(26) The reaction profiles and the final yields of the repeated reuse
experiments for the Cu(OH)x/CeO2-catalyzed monoborylation of 1a
are summarized in Figure S10. In addition, the details of the reuse
experiments for the Cu(OH)x/Al2O3-catalyzed diborylation of 1a are
also summarized in Figure S11.
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