Indium(III) Isopropoxide as a Hydrogen Transfer Catalyst for Conversion of Benzylic Alcohols into Aldehydes or Ketones via Oppenauer Oxidation

Article abstract of DOI:10.1055/s-0035-1562542

Indium(III) isopropoxide [In(Oi-Pr)₃] was applicable as an Oppenauer oxidation catalyst, and the conversion of primary or secondary alcohols into the corresponding aldehydes or ketones was promoted at room temperature using pivalaldehyde as an oxidant.

Full text of DOI:10.1055/s-0035-1562542

SYNTHESIS
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
© Georg Thieme Verlag Stuttgart · New York
2016, 48, A–F
paper
A
Y. Ogiwara et al.
Paper
Synthesis
Indium(III) Isopropoxide as a Hydrogen Transfer Catalyst for
Conversion of Benzylic Alcohols into Aldehydes or Ketones via
Oppenauer Oxidation
Yohei Ogiwara
Yuji Ono
H
O
O
H
H
O
O
In(OiPr)3 (cat.)
H
H
+
+
H
tBu
tBu
Norio Sakai*
H
Ar
Ar
CHCl3, r.t.
21 examples
9–93% yield
H
Department of Pure and Applied Chemistry, Faculty of Science
and Technology, Tokyo University of Science (RIKADAI), Noda,
Chiba 278-8510, Japan
RO OR
In
RO
O
OR
O
RO
O
OR
sakachem@rs.noda.tus.ac.jp
In
In
O
O
O
via
tBu
Ar
H
tBu
Ar
tBu
Ar
H
H
H
H
H
H
H
H
Received: 28.06.2016
Accepted after revision: 22.07.2016
Published online: 01.09.2016
vealed a new direction for indium complexes in MPV-type
hydride transfer processes, and also suggested their poten-
tial for use in Oppenauer oxidation reactions. Very recently,
our research group developed an indium(III) bromide pro-
moted oxidative coupling of terminal alkynes with alde-
hydes leading to alkynyl ketones (Scheme 1).6 In this reac-
tion, the indium-mediated Oppenauer-type hydride trans-
fer was considered a key oxidation step.7 These results
encouraged us to attempt the use of indium(III) compounds
as catalysts for a simple Oppenauer oxidation of alcohols.
We describe herein, indium(III) isopropoxide as a new
Oppenauer oxidation catalyst, and how an oxidation series
of primary and secondary alcohols effectively proceeded at
room temperature, giving aldehydes and ketones.
DOI: 10.1055/s-0035-1562542; Art ID: ss-2016-f0462-op
Abstract Indium(III) isopropoxide [In(Oi-Pr)3] was applicable as an
Oppenauer oxidation catalyst, and the conversion of primary or second-
ary alcohols into the corresponding aldehydes or ketones was promoted
at room temperature using pivalaldehyde as an oxidant.
Key words indium catalyst, Oppenauer oxidation, primary alcohol,
secondary alcohol, aldehyde, ketone, room temperature
Oppenauer oxidation is a powerful method for the
preparation of ketones or aldehydes from the correspond-
ing secondary or primary alcohols. Because it can be per-
formed under milder reaction conditions than other oxida-
tion strategies, Oppenauer oxidations generally achieve a
highly selective transformation of alcohols into carbonyl
compounds bearing various functional groups.1 Although a
number of main-group- and transition-metal-based
Oppenauer-type oxidations have been reported, the oxida-
tion of primary alcohols to aldehydes remains a challenging
transformation, because of either undesired side-reactions
due to high reactivity of the oxidation product, aldehydes,
as found in the Tishchenko reaction and aldol condensation,
or a reverse Meerwein–Ponndorf–Verley (MPV) reduc-
tion.2,3 In terms of substrate generality and catalytic effi-
ciency for this transformation, the search for undiscovered
metal catalysts that could be potentially applicable to
Oppenauer oxidation is imperative.
O
InBr3 (1.5 equiv)
Et3N (1.5 equiv)
O
+
Ph
Ph
Et2O, 40 °C
H
Ph
Ph
H
3 equiv
O
O
InBr2
H
O
InBr2
H
Ph
Ph
Ph
Oppenauer
oxidation
Ph
Ph
Scheme 1 Our previous result: indium-promoted oxidative coupling of
terminal alkynes with aldehydes via Oppenauer oxidation
Initially, a catalyst screening for the Oppenauer oxida-
tion of 4-methylbenzyl alcohol (1) was conducted (Table 1,
entries 1–7). When the reaction of 1 with 20 mol% of InCl3
using t-BuCHO as a hydrogen acceptor was performed in
0.33 M of dichloromethane at room temperature for three
hours, the expected Oppenauer reaction was not observed
by GC analysis (Table 1, entry 1). Also, no Oppenauer prod-
uct was obtained using other indium(III) salts such as InBr3,
InI3, In(OTf)3, In(OAc)3, and In(OH)3 (entries 2–6). The use of
In(Oi-Pr)3 as a catalyst, however, improved the results dras-
In 2012, Lee and co-workers reported a pioneering ex-
ample of an In(Oi-Pr)3-catalyzed MPV reduction of alde-
hydes leading to primary alcohols, which was the reverse of
Oppenauer oxidation.4 Kirillov and Carpentier et al. also
discovered that a similar reduction of ligands is promoted
with an indium complex, an indium imino-phenolate into
an indium amido-phenolate, by i-PrOH.5 Their studies re-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–F

B
Y. Ogiwara et al.
Paper
Synthesis
tically to form the corresponding benzaldehyde 2 in an 82%
GC yield (entry 7). This result revealed that indium(III)
alkoxide functions as an effective catalyst for Oppenauer
oxidation, as well as for MPV reduction.4 Solvents were next
investigated for the reaction. Oxidation in chloroform led to
a slightly increased yield of 2 (entry 8), and the use of other
solvents, such as toluene, Et2O, THF, and MeCN, also result-
ed in moderate to good yields of 2 (entries 9–12). Increasing
the initial concentration of 1 in CHCl3 from 0.33 to 0.5 M,
resulted in an 88% increase in the GC yield of 2 (entry 13).
Other oxidizing agents, such as acetone (3 equiv) in chloro-
form, or chloroform by itself as both an oxidizing agent and
a solvent,8 were not suitable for this In(Oi-Pr)3 catalyst sys-
tem.
10, respectively, in high yields (entries 5–8). Both nitrogen-
and sulfur-containing functional groups were tolerated in
the reaction, and the oxidation products 11 and 12 were
obtained in good yields (entries 9 and 10). However, sub-
strates with electron-deficient aromatic rings, which have
halogen atoms as well as both cyano- and methoxycarbonyl
groups, showed a relatively lower level of reactivity for the
oxidation, giving 13–18 (entries 11–16). The reactions of
benzyl alcohols, composed of a fused aromatic ring, a het-
erocycle, and a vinyl system, also afforded the correspond-
ing aldehydes 19–22, although a further optimization was
necessary to improve the yields (entries 17–20). In contrast,
when the other primary aliphatic alcohols, not benzylic
ones, such as 1-decanol and 2-phenylethanol, were used as
substrates for this procedure, unfortunately the corre-
sponding aldehydes were not obtained and the starting al-
cohols were completely recovered.
Table 1 Optimization for Oppenauer Oxidation of the Primary Alcohol 1a
OH
H
O
InX3 (20 mol%)
tBuCHO (5 equiv)
H
H
r.t., 3 h
Table 2 Scope of the Oppenauer Oxidation of Primary Alcohols Lead-
ing to Aldehydesa
1
2
In(OiPr)3 (20 mol%)
Entry
InX3
Solvent
GC results (%)
OH
H
O
tBuCHO (5 equiv)
H
Conv. of 1
Yield of 2
R
R
H
CHCl3 (0.5 M)
r.t., 3 h
1
2
InCl3
CH2Cl2 (0.33 M)
CH2Cl2 (0.33 M)
CH2Cl2 (0.33 M)
CH2Cl2 (0.33 M)
CH2Cl2 (0.33 M)
CH2Cl2 (0.33 M)
CH2Cl2 (0.33 M)
CHCl3 (0.33 M)
toluene (0.33 M)
Et2O (0.33 M)
30
29
20
2
0
Entry
R
Product
Yield (%)b
InBr3
0
0
3
InI3
1
2
Ph
3
4
93
61
50
35
80
83
71
85
71
80
30
50
9
4
In(OTf)3
0
4-t-BuC6H4
4-PhC6H4
2-MeC6H4
5
In(OAc)3
In(OH)3
1
0
3
5
6
98
85
>99
97
89
94
44
>99
0b
4
6
7
In(Oi-Pr)3
In(Oi-Pr)3
In(Oi-Pr)3
In(Oi-Pr)3
In(Oi-Pr)3
In(Oi-Pr)3
In(Oi-Pr)3
82
83
81
73
77
37
88 (87)c
5
4-MeOC6H4
4-PrOC6H4
3-PhOC6H4
4-HOC6H4
4-Me2NC6H4
4-MeSC6H4
4-FC6H4
7
8
6
8
9
7
9
10
11
12
13
8
10
11
12
13
14
15
16
17
18
19
20
21
22
THF (0.33 M)
9
MeCN (0.33 M)
CHCl3 (0.5 M)
10
11c
12
13c
14
15
16c
17
18
19
20
a Reaction conditions: 1 (0.5 mmol), InX3 (0.1 mmol), t-BuCHO (2.5 mmol),
4-ClC6H4
r.t., 3 h.
b Complex mixture.
c Isolated yield.
2-ClC6H4
4-BrC6H4
60
13
40
68
51
21
21
4-NCC6H4
4-MeO2CC6H4
1-naphthyl
2-naphthyl
2-pyridyl
Examination of the Oppenauer oxidation of a variety of
primary alcohols was then conducted under the optimal
conditions (Table 2). The oxidation of a benzyl alcohol af-
forded benzaldehyde (3) in a 93% yield (Table 2, entry 1),
and several benzyl alcohols bearing a carbon substituent at
the aromatic ring, such as 4-t-Bu, 4-Ph, and 2-Me, were also
applicable to the oxidation giving the corresponding prod-
ucts 4–6 in moderate yields (entries 2–4). Substrates with
electron-donating alkoxy, aryloxy, and hydroxy groups at
the 4- or 3-positions were converted into benzaldehydes 7–
(E)-cinnamyl
a Reaction conditions: alcohol (0.5 mmol), In(Oi-Pr)3 (0.1 mmol), t-BuCHO
(2.5 mmol), CHCl3 (1 mL), r.t., 3 h.
b Isolated yields.
c Reaction performed in 1.5 mmol scale.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–F

C
Y. Ogiwara et al.
Paper
Synthesis
1H, 13C{1H} NMR spectra were recorded on a 300 or 500 MHz spec-
trometer. Chemical shifts in the 1H, 13C{1H} NMR spectra were report-
ed in ppm relative to residual solvent peaks such as that of CHCl3 (δ =
7.26 for 1H, and δ = 77.0 for 13C) or of the internal reference TMS (δ =
0.00 for both 1H and 13C). GC analyses were performed using a DB-5
capillary column (30 m × 0.25 mm, film thickness = 0.25 μm). The
substrates of alcohols were prepared via the reduction of the starting
ketone or aldehyde using NaBH4. The commercially available solid
substrate, In(Oi-Pr)3, was purchased from Wako and purified by dry-
ing under reduced pressure vacuum prior to use. Pivalaldehyde was
purchased and purified by vacuum transfer prior to use. CHCl3 was
dried and distilled over P2O5 and stored over molecular sieves. Unless
otherwise noted, all reactions were performed under a N2 atmo-
sphere.
Conversions of secondary alcohols into ketones were
also achieved using the In(Oi-Pr)3/t-BuCHO oxidation sys-
tem (Scheme 2). Acetophenone (23), benzophenone (24),
and the alkynyl ketone 25 were obtained in high yields
from their corresponding secondary alcohols.
In(OiPr)3 (20 mol%)
OH
R2
O
tBuCHO (5 equiv)
CHCl3 (0.5 M), r.t.
H
R1
R1
R2
O
O
O
Ph
Ph
Me
Ph
Ph
Ph
25, 86% (5 h)
23, 96% (3 h)
24, 88% (5 h)
Scheme 2 Oppenauer oxidation of several secondary alcohols leading
to ketones. Reagents and conditions: alcohol (0.5 mmol), In(Oi-Pr)3 (0.1
mmol), t-BuCHO (2.5 mmol), CHCl3 (1 mL), r.t. Isolated yields are
shown.
Oppenauer Oxidation of Alcohols Using In(i-OPr)3; General Proce-
dure
To a screw tube in a glovebox was added In(Oi-Pr)3 (29.2 mg, 0.1
mmol). The tube was then sealed and removed from the glovebox,
and CHCl3 (1 mL), alcohol (0.5 mmol), and pivalaldehyde (280 μL, 2.5
mmol) were added under N2 in this order. After stirring the mixture
at r.t. for 3 h, H2O (1.0 mL) was added to the reaction mixture, which
was then extracted with EtOAc. The organic phase was dried
(Na2SO4), and evaporated under reduced pressure. The crude material
was purified by silica gel column chromatography (Table 2 and
Scheme 2).
The proposed catalytic cycle for the oxidation of prima-
ry alcohols is illustrated in Scheme 3. This was based on the
assumption that the oxidation would proceed through a
typical aluminum-based Oppenauer oxidation: (i) depro-
tonation of a benzyl alcohol by an indium alkoxide, (ii) coor-
dination of the hydrogen acceptor, t-BuCHO, to the indium
center, (iii) hydride transfer from the benzylic carbon to the
aldehyde, and (iv) regeneration of the indium tri(alkoxide)
catalyst with the release of the oxidation product.
4-Methylbenzaldehyde (2)9
General procedure was followed with 4-methylbenzyl alcohol (1)
(61.1 mg, 0.5 mmol). Column chromatography (40:1 hexane/EtOAc)
afforded 2 as a colorless oil (52.9 mg, 87%).
1H NMR (CDCl3, 500.2 MHz): δ = 2.44 (s, 3 H, CH3), 7.33 (d, J = 8.0 Hz, 2
H, ArH), 7.78 (d, J = 8.0 Hz, 2 H, ArH), 9.97 (s, 1 H, CH).
O
OH
OR
In
H
Ar
H
Ar
H
13C NMR (CDCl3, 125.8 MHz): δ = 21.9, 129.7, 129.8, 134.2, 145.5,
RO
OR
192.0.
ROH
LRMS (EI): m/z (%) = 120 (M+, 84), 106 (41), 91 (100), 79 (38), 77 (41),
65 (25).
OR
RO OR
In
In
Benzaldehyde (3)10
O
O
O
OR
General procedure was followed with benzyl alcohol (54.1 mg, 0.5
mmol). Column chromatography (40:1 hexane/EtOAc) afforded 3 as a
colorless oil (49.3 mg, 93%).
Ar
H
tBu
H
Ar
H
H
H
1H NMR (CDCl3, 500.2 MHz): δ = 7.54 (t, J = 8.0 Hz, 2 H, ArH), 7.62–
7.65 (m, 1 H, ArH), 7.89 (d, J = 8.0 Hz, 2 H, ArH), 10.03 (s, 1 H, CHO).
13C NMR (CDCl3, 125.8 MHz): δ = 129.0, 129.7, 134.4, 136.4, 192.4.
LRMS (EI): m/z (%) = 106 (M+, 100), 77 (97), 64 (19).
RO
OR
O
In
O
O
H
tBu
Ar
H
tBu
H
H
Scheme 3 Proposed catalytic cycle
4-tert-Butylbenzaldehyde (4)10
General procedure was followed with 4-tert-butylbenzyl alcohol
(82.1 mg, 0.5 mmol). Column chromatography (40:1 hexane/EtOAc)
afforded 4 as a colorless oil (49.5 mg, 61%).
1H NMR (CDCl3, 500.2 MHz): δ = 1.36 (s, 9 H, CH3), 7.56 (d, J = 8.0 Hz, 2
H, ArH), 7.82 (d, J = 8.0 Hz, 2 H, ArH), 9.98 (s, 1 H, CHO).
13C NMR (CDCl3, 125.8 MHz): δ = 31.1, 35.3, 126.0, 129.7, 134.1, 158.4,
192.1.
In summary, an indium-catalyzed Oppenauer oxidation
of primary and secondary alcohols was achieved. A combi-
nation of indium(III) isopropoxide as a catalyst and pivalal-
dehyde as a hydrogen acceptor was found to be an effective
oxidation tool for alcohols. Also, the oxidizing system pro-
duced not only a variety of benzaldehyde derivatives but
also aromatic ketones at room temperature. Further im-
provements of the Oppenauer oxidation for aliphatic alco-
hols by In(Oi-Pr)3/t-BuCHO are now in progress.
LRMS (EI): m/z (%) = 162 (M+, 100), 147 (100), 119 (63), 103 (11), 91
(94), 77 (24).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–F

D
Y. Ogiwara et al.
Paper
Synthesis
4-Phenylbenzaldehyde (5)9
LRMS (EI): m/z (%) = 198 (M+, 100), 181 (19), 169 (43), 141 (34), 114
(14), 77 (28).
General procedure was followed with 4-phenylbenzyl alcohol (92.1
mg, 0.5 mmol). Column chromatography (40:1 hexane/EtOAc) afford-
ed 5 as a colorless solid (45.6 mg, 50%); mp 59–60 °C.
4-Hydroxybenzaldehyde (10)13
1H NMR (CDCl3, 500.2 MHz): δ = 7.42 (t, J = 7.5 Hz, 1 H, ArH), 7.48 (t,
J = 7.5 Hz, 2 H, ArH), 7.64 (d, J = 7.5 Hz, 2 H, ArH), 7.76 (d, J = 7.5 Hz, 2
H, ArH), 7.96 (d, J = 7.5 Hz, 2 H, ArH), 10.06 (s, 1 H, CHO).
General procedure was followed with 4-hydroxybenzyl alcohol (62.1
mg, 0.5 mmol). Column chromatography (20:1 hexane/EtOAc) afford-
ed 10 as a colorless solid (51.9 mg, 85%); mp 110–111 °C.
1H NMR (CDCl3, 500.2 MHz): δ = 6.37 (s, 1 H, OH), 6.99 (d, J = 8.5 Hz, 2
H, ArH), 7.83 (d, J = 8.5 Hz, 2 H, ArH), 9.87 (s, 1 H, CHO).
13C NMR (CDCl3, 125.8 MHz): δ = 127.4, 127.7, 128.5, 129.0, 130.3,
135.2 139.7, 147.2, 191.9.
13C NMR (CDCl3, 125.8 MHz): δ = 116.0, 129.8, 132.6, 161.6, 191.3.
LRMS (EI): m/z (%) = 122 (M+, 93), 121 (100), 93 (39), 66 (30).
LRMS (EI): m/z (%) = 182 (M+, 100), 151 (17), 126 (7), 90 (3), 75 (14),
64 (4).
2-Methylbenzaldehyde (6)10
4-(Dimethylamino)benzaldehyde (11)14
General procedure was followed with 2-methylbenzyl alcohol (61.1
mg, 0.5 mmol). Column chromatography (40:1 hexane/EtOAc) afford-
ed 6 as a colorless oil (21.0 mg, 35%).
General procedure was followed with 4-(dimethylamino)benzyl alco-
hol (75.6 mg, 0.5 mmol). Column chromatography (40:1 hexane/EtOAc)
afforded 11 as a colorless solid (52.9 mg, 71%); mp 71–73 °C.
1H NMR (CDCl3, 500.2 MHz): δ = 2.68 (s, 3 H, CH3), 7.26 (d, J = 7.5 Hz, 1
H, ArH), 7.36 (t, J = 7.5 Hz, 1 H, ArH), 7.48 (t, J = 7.5 Hz, 1 H, ArH), 7.80
(d, J = 7.5 Hz, 1 H, ArH), 10.27 (s, 1 H, CHO).
13C NMR (CDCl3, 125.8 MHz): δ = 19.5, 126.3, 131.7, 132.0, 133.6,
134.1, 140.6, 192.8.
1H NMR (CDCl3, 500.2 MHz): δ = 3.09 (s, 6 H, NCH3), 6.71 (d, J = 7.5 Hz,
2 H, ArH), 7.74 (d, J = 7.5 Hz, 2 H, ArH), 9.75 (s, 1 H, CHO).
13C NMR (CDCl3, 125.8 MHz): δ = 40.1, 110.9, 125.1, 132.0, 154.3,
190.3.
LRMS (EI): m/z (%) = 149 (M+, 100), 132 (78), 120 (57), 105 (67), 91
(51), 77 (83), 64 (45).
LRMS (EI): m/z (%) = 120 (M+, 98), 108 (21), 91 (100), 77 (6), 66 (25).
4-Methoxybenzaldehyde (7)10
4-(Methylthio)benzaldehyde (12)3a
General procedure was followed with 4-methoxybenzyl alcohol (69.1
mg, 0.5 mmol). Column chromatography (40:1 hexane/EtOAc) afford-
ed 7 as a colorless oil (54.5 mg, 80%).
General procedure was followed with 4-(methylthio)benzyl alcohol
(77.1 mg, 0.5 mmol). Column chromatography (40:1 hexane/EtOAc)
afforded 12 as a colorless oil (60.8 mg, 80%).
1H NMR (CDCl3, 500.2 MHz): δ = 3.89 (s, 3 H, OCH3), 7.00 (d, J = 8.5 Hz,
2 H, ArH), 7.84 (d, J = 8.5 Hz, 2 H, ArH), 9.88 (s, 1 H, CHO).
13C NMR (CDCl3, 125.8 MHz): δ = 55.5, 114.2, 129.9, 131.9, 164.5,
1H NMR (CDCl3, 500.2 MHz): δ = 2.54 (s, 3 H, SCH3), 7.33 (d, J = 8.5 Hz,
2 H, ArH), 7.78 (d, J = 8.5 Hz, 2 H, ArH), 9.92 (s, 1 H, CHO).
13C NMR (CDCl3, 125.8 MHz): δ = 14.7, 125.2, 130.0, 132.9, 147.9,
190.7.
191.2.
LRMS (EI): m/z (%) = 136 (M+, 100), 107 (33), 92 (36), 77 (66), 66 (19).
LRMS (EI): m/z (%) = 152 (M+, 100), 123 (48), 108 (26), 79 (29), 77
(22), 69 (21), 66 (16).
4-Propoxybenzaldehyde (8)11
General procedure was followed with 4-propoxybenzyl alcohol (83.1
mg, 0.5 mmol). Column chromatography (40:1 hexane/EtOAc) afford-
ed 8 as a colorless oil (68.1 mg, 83%).
1H NMR (CDCl3, 500.2 MHz): δ = 1.53 (t, J = 7.5 Hz, 3 H, CH3), 1.81–
1.88 (m, 2 H, CH2), 4.00 (t, J = 7.0 Hz, 2 H, CH2), 6.99 (d, J = 8.0 Hz, 2 H,
ArH), 7.82 (d, J = 8.0 Hz, 2 H, ArH), 9.87 (s, 1 H, CHO).
13C NMR (CDCl3, 125.8 MHz): δ = 10.4, 22.3, 69.7, 114.7, 129.6, 131.9,
164.2, 190.8.
LRMS (EI): m/z (%) = 164 (M+, 58), 121 (100), 109 (41), 92 (13), 77 (9),
65 (17).
4-Fluorobenzaldehyde (13)15
General procedure was followed with 4-fluorobenzyl alcohol (189.1
mg, 1.5 mmol). Column chromatography (40:1 hexane/EtOAc) afford-
ed 13 as a colorless oil (55.8 mg, 30%).
1H NMR (CDCl3, 500.2 MHz): δ = 7.21–7.24 (m, 2 H, ArH), 7.91–7.93
(m, 2 H, ArH), 9.98 (s, 1 H, CHO).
13C NMR (CDCl3, 125.8 MHz): δ = 116.2 (d, J = 22.0 Hz), 132.1 (d, J = 9.9
Hz), 132.9 (d, J = 2.8 Hz), 166.4 (d, J = 255.1 Hz), 190.4.
LRMS (EI): m/z (%) = 124 (M+, 97), 123 (100), 95 (86), 75 (25).
4-Chlorobenzaldehyde (14)15
3-Phenoxybenzaldehyde (9)12
General procedure was followed with 4-chlorobenzyl alcohol (71.3
mg, 0.5 mmol). Column chromatography (40:1 hexane/EtOAc) afford-
ed 14 as a yellow solid (35.2 mg, 50%); mp 47–49 °C.
1H NMR (CDCl3, 500.2 MHz): δ = 7.52 (d, J = 8.5 Hz, 2 H, ArH), 7.82–
7.84 (m, 2 H, ArH), 9.99 (s, 1 H, CHO).
13C NMR (CDCl3, 125.8 MHz): δ = 129.5, 130.9, 134.7, 140.9, 190.9.
General procedure was followed with 4-phenoxybenzyl alcohol
(100.1 mg, 0.5 mmol). Column chromatography (40:1 hexane/EtOAc)
afforded 9 as a colorless oil (70.3 mg, 71%).
1H NMR (CDCl3, 500.2 MHz): δ = 7.03 (d, J = 8.0 Hz, 2 H, ArH), 7.16 (t,
J = 8.0 Hz, 1 H, ArH), 7.27 (d, J = 8.0 Hz, 1 H, ArH), 7.36 (t, J = 8.0 Hz, 2
H, ArH), 7.50–7.45 (m, 2 H, ArH), 7.59 (d, J = 8.0 Hz, 1 H, ArH), 9.94 (s,
1 H, CHO).
LRMS (EI): m/z (%) = 140 (M+, 93), 139 (100), 113 (22), 110 (66), 77
(17), 75 (30).
13C NMR (CDCl3, 125.8 MHz): δ = 118.0, 119.4, 124.1, 124.5, 124.6,
130.0, 130.4 138.0, 156.1, 158.3, 191.5.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–F

E
Y. Ogiwara et al.
Paper
Synthesis
2-Chlorobenzaldehyde (15)15
2-Naphthaldehyde (20)10
General procedure was followed with 2-chlorobenzyl alcohol (213.8
mg, 1.5 mmol). Column chromatography (40:1 hexane/EtOAc) afford-
ed 15 as a colorless oil (19.0 mg, 9%).
General procedure was followed with 2-naphthylmethanol (79.1 mg,
0.5 mmol). Column chromatography (40:1 hexane/EtOAc) afforded 20
as a colorless solid (39.8 mg, 51%); mp 60–61 °C.
1H NMR (CDCl3, 500.2 MHz): δ = 7.40 (t, J = 7.5 Hz, 1 H, ArH), 7.46 (d,
J = 7.5 Hz, 1 H, ArH), 7.54 (t, J = 7.5 Hz, 1 H, ArH), 7.93 (d, J = 7.5 Hz, 1
H, ArH), 10.50 (s, 1 H, CHO).
1H NMR (CDCl3, 500.2 MHz): δ = 7.57–7.66 (m, 2 H, ArH), 7.90–8.02
(m, 4 H, ArH), 8.34 (s, 1 H, ArH), 10.16 (s, 1 H, CHO).
13C NMR (CDCl3, 125.8 MHz): δ = 122.7, 127.1, 128.1, 129.08, 129.10,
129.5, 132.6, 134.1, 134.5, 136.4, 192.3.
13C NMR (CDCl3, 125.8 MHz): δ = 127.3, 129.4, 130.6, 132.4, 135.1,
137.9, 189.8.
LRMS (EI): m/z (%) = 156 (M+, 100), 127 (99), 101 (8), 77 (13).
LRMS (EI): m/z (%) = 140 (M+, 99), 139 (100), 128 (18), 111 (53), 77
2-Picolinaldehyde (21)18
(22), 75 (30).
General procedure was followed with 2-pyridylmethanol (54.6 mg,
0.5 mmol). Column chromatography (40:1 hexane/EtOAc) afforded 21
as a yellow oil (11.2 mg, 21%).
1H NMR (CDCl3, 500.2 MHz): δ = 7.53–7.55 (m, 1 H, ArH), 7.88–7.98
(m, 2 H, ArH), 8.79–8.82 (m, 1 H, ArH), 10.09 (s, 1 H, CHO).
13C NMR (CDCl3, 125.8 MHz): δ = 121.6, 127.8, 137.0, 150.2, 152.7,
4-Bromobenzaldehyde (16)15
General procedure was followed with 4-bromobenzyl alcohol (93.5
mg, 0.5 mmol). Column chromatography (40:1 hexane/EtOAc) afford-
ed 16 as a colorless solid (54.9 mg, 60%); mp 56–58 °C.
1H NMR (CDCl3, 500.2 MHz): δ = 7.69 (d, J = 8.0 Hz, 2 H, ArH), 7.76 (d,
J = 8.0 Hz, 2 H, ArH), 9.98 (s, 1 H, CHO).
13C NMR (CDCl3, 125.8 MHz): δ = 129.7, 131.0, 132.4, 135.1, 191.1.
LRMS (EI): m/z (%) = 186 (86), 185 (100), 184 (M+, 87), 183 (99), 77
193.4.
LRMS (EI): m/z (%) = 107 (M+, 56), 79 (100), 55 (17).
Cinnamaldehyde (22)3a
(25), 75 (29).
General procedure was followed with cinnamyl alcohol (67.1 mg, 0.5
mmol). Column chromatography (40:1 hexane/EtOAc) afforded 22 as
a yellow oil (13.9 mg, 21%).
1H NMR (CDCl3, 500.2 MHz): δ = 6.71–6.75 (m, 1 H, CH), 7.43–7.58 (m,
6 H), 9.70 (d, J = 8.5 Hz, 1 H, CHO).
13C NMR (CDCl3, 125.8 MHz): δ = 128.5, 128.6, 129.1, 131.3, 134.0,
152.8, 193.7.
4-Cyanobenzaldehyde (17)16
General procedure was followed with 4-cyanobenzyl alcohol (66.6
mg, 0.5 mmol). Column chromatography (40:1 hexane/EtOAc) afford-
ed 17 as a colorless solid (8.7 mg, 13%); mp 98–100 °C.
1H NMR (CDCl3, 500.2 MHz): δ = 7.86 (d, J = 8.5 Hz, 2 H, ArH), 8.01 (d,
J = 8.5 Hz, 2 H, ArH), 10.11 (s, 1 H, CHO).
13C NMR (CDCl3, 125.8 MHz): δ = 117.6, 117.7, 129.9, 132.9, 138.7,
190.6.
LRMS (EI): m/z (%) = 132 (M+, 91), 131 (100), 103 (63), 77 (46), 64 (8).
LRMS (EI): m/z (%) = 131 (M+, 93), 130 (100), 102 (82), 76 (51).
Acetophenone (23)18
General procedure was followed with 1-phenylethanol (61.1 mg, 0.5
mmol). Column chromatography (40:1 hexane/EtOAc) afforded 23 as
a colorless oil (57.6 mg, 96%).
1H NMR (CDCl3, 500.2 MHz): δ = 2.60 (s, 3 H, CH3), 7.46 (d, J = 8.5 Hz, 2
H, ArH), 7.56 (m, 1 H, ArH), 7.59 (d, J = 8.5 Hz, 2 H, ArH).
13C NMR (CDCl3, 125.8 MHz): δ = 26.5, 128.2, 128.5, 133.0, 137.0,
198.1.
4-(Methoxycarbonyl)benzaldehyde (18)17
General procedure was followed with 4-(methoxycarbonyl)benzyl al-
cohol (249.3 mg, 1.5 mmol). Column chromatography (40:1 hex-
ane/EtOAc) afforded 18 as a colorless solid (98.4 mg, 40%); mp 61–63 °C.
1H NMR (CDCl3, 500.2 MHz): δ = 3.97 (s, 3 H, CO2CH3), 7.96 (d, J = 8.5
Hz, 2 H, ArH), 8.21 (d, J = 8.5 Hz, 2 H, ArH), 10.11 (s, 1 H, CHO).
13C NMR (CDCl3, 125.8 MHz): δ = 52.6, 129.5, 130.2, 135.1, 139.1,
166.1, 191.6.
LRMS (EI): m/z (%) = 120 (M+, 44), 105 (100), 77 (94).
LRMS (EI): m/z (%) = 164 (M+, 97), 133 (100), 123 (14), 105 (50), 77
(35).
Benzophenone (24)18
General procedure was followed with 1,1-diphenylmethanol (92.1
mg, 0.5 mmol) for 5 h. Column chromatography (40:1 hexane/EtOAc)
afforded 24 as a colorless solid (80.1 mg, 88%); mp 46–49 °C.
1-Naphthaldehyde (19)10
General procedure was followed with 1-naphthylmethanol (79.1 mg,
0.5 mmol). Column chromatography (40:1 hexane/EtOAc) afforded 19
as a colorless oil (53.0 mg, 68%).
1H NMR (CDCl3, 500.2 MHz): δ = 7.56–7.62 (m, 2 H, ArH), 7.68 (t, J =
8.5 Hz, 1 H, ArH), 7.90 (d, J = 8.5 Hz, 1 H, ArH), 7.96 (d, J = 8.5 Hz, 1 H,
ArH), 8.08 (d, J = 8.5 Hz, 1 H, ArH), 9.25 (d, J = 8.5 Hz, 1 H, ArH), 10.38
(s, 1 H, CHO).
1H NMR (CDCl3, 500.2 MHz): δ = 7.49 (t, J = 7.5 Hz, 4 H, ArH), 7.56 (t,
J = 7.5 Hz, 2 H, ArH), 7.81 (d, J = 7.5 Hz, 4 H, ArH).
13C NMR (CDCl3, 125.8 MHz): δ = 129.0, 129.7, 134.4, 136.4, 192.4.
LRMS (EI): m/z (%) = 182 (M+, 94), 104 (100), 77 (94).
1,3-Diphenylprop-2-yn-1-one (25)6
General procedure was followed with 1,3-diphenylprop-2-yn-1-ol
(104.1 mg, 0.5 mmol) for 5 h. Column chromatography (40:1 hex-
ane/EtOAc) afforded 25 as yellow oil (88.6 mg, 86%).
1H NMR (CDCl3, 500.2 MHz): δ = 7.26–7.54 (m, 5 H, ArH), 7.26–7.54
(m, 3 H, ArH), 8.23 (d, J = 7.0 Hz, 2 H, ArH).
13C NMR (CDCl3, 125.8 MHz): δ = 124.8 (2 C), 126.9, 128.4, 129.0,
130.5, 131.3, 133.7, 135.2, 136.6, 193.5.
LRMS (EI): m/z (%) = 156 (M+, 100), 127 (89), 101 (9), 77 (13).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–F

F
Y. Ogiwara et al.
Paper
Synthesis
13C NMR (CDCl3, 125.8 MHz): δ = 86.9, 93.1, 120.1, 128.6, 128.7, 129.6,
130.8, 133.0, 134.1, 136.8, 178.0.
LRMS (EI): m/z (%) = 206 (M+, 83), 178 (100), 129 (98), 105 (20), 89
(15), 77 (36).
rahedron Lett. 2010, 51, 5430. (d) Johnson, T. C.; Clarkson, G. J.;
Wills, M. Organometallics 2011, 30, 1859. (e) Fujita, K.-i.;
Uejima, T.; Yamaguchi, R. Chem. Lett. 2013, 42, 1496. (f) Prakash,
O.; Sharma, K. N.; Joshi, H.; Gupta, P. L.; Singh, A. K. Organome-
tallics 2014, 33, 983.
(4) Lee, J.; Ryu, T.; Park, S.; Lee, P. H. J. Org. Chem. 2012, 77, 4821.
(5) Normand, M.; Kirillov, E.; Roisnel, T.; Carpentier, J.-F. Organo-
metallics 2012, 31, 5511.
Acknowledgment
(6) Ogiwara, Y.; Kubota, M.; Kurogi, K.; Konakahara, T.; Sakai, N.
Chem. Eur. J. 2015, 21, 18598.
This work was supported by JSPS KAKENHI Grant Numbers
JP25410120 and JP16K21400.
(7) (a) Augé, J.; Lubin-Germain, N.; Seghrouchni, L. Tetrahedron
Lett. 2002, 43, 5255. (b) Augé, J.; Lubin-Germain, N.;
Seghrouchni, L. Tetrahedron Lett. 2003, 44, 819.
(8) Jung, H. M.; Choi, J. H.; Lee, S. O.; Kim, Y. H.; Park, J. H.; Park, J.
Organometallics 2002, 21, 5674.
Supporting Information
Supporting information for this article is available online at
(9) Hong, B.-C.; Tseng, H.-C.; Chen, S.-H. Tetrahedron 2007, 63,
2840.
http://dx.doi.org/10.1055/s-0035-1562542.
S
u
p
p
ortioInfgrmoaitn
S
u
p
p
ortiInfogrmoaitn
(10) Lee, K.; Maleczka, R. E. Jr. Org. Lett. 2006, 8, 1887.
(11) Zhu, C.; Yukimura, N.; Yamane, M. Organometallics 2010, 29,
2098.
(12) Inokuchi, T.; Matsumoto, S.; Fukushima, M.; Torii, S. Bull. Chem.
Soc. Jpn. 1991, 64, 796.
References
(1) Selected reviews of Oppenauer oxidation: (a) Graves, C. R.;
Campbell, E. J.; Nguyen, S. T. Tetrahedron: Asymmetry 2005, 16,
3460. (b) Ooi, T.; Miura, T.; Itagaki, Y.; Ichikawa, H.; Maruoka, K.
Synthesis 2002, 279. (c) de Graauw, C. F.; Peters, J. A.; van
Bekkum, H.; Huskens, J. Synthesis 1994, 1007.
(2) (a) Namy, J. L.; Souppe, J.; Collin, J.; Kagan, H. B. J. Org. Chem.
1984, 49, 2045. (b) Ishii, Y.; Nakano, T.; Inada, A.; Kishigami, Y.;
Sakurai, K.; Ogawa, M. J. Org. Chem. 1986, 51, 240. (c) Krohn, K.;
Knauer, B.; Küpke, J.; Seebach, D.; Beck, A. K.; Hayakawa, M. Syn-
thesis 1996, 1341. (d) Ishihara, K.; Kurihara, H.; Yamamoto, H.
J. Org. Chem. 1997, 62, 5664. (e) Ooi, T.; Otsuka, H.; Miura, T.;
Ichikawa, H.; Maruoka, K. Org. Lett. 2002, 4, 2669. (f) Graves, C.
R.; Zeng, B.-S.; Nguyen, S. T. J. Am. Chem. Soc. 2006, 128, 12596.
(3) (a) Suzuki, T.; Morita, K.; Tsuchida, M.; Hiroi, K. J. Org. Chem.
2003, 68, 1601. (b) Gauthier, S.; Scopelliti, R.; Severin, K.
Organometallics 2004, 23, 3769. (c) Moyer, S. A.; Funk, T. W. Tet-
(13) Magano, J.; Chen, M. H.; Clark, J. D.; Nussbaumer, T. J. Org. Chem.
2006, 71, 7103.
(14) Koren-Selfridge, L.; Londino, H. N.; Vellucci, J. K.; Simmons, B. J.;
Casey, C. P.; Clark, T. B. Organometallics 2009, 28, 2085.
(15) Lin, C.-K.; Lu, T.-J. Tetrahedron 2010, 66, 9688.
(16) Kim, B. R.; Lee, H.-G.; Kim, E. J.; Lee, S.-G.; Yoon, Y.-J. J. Org.
Chem. 2010, 75, 484.
(17) Pelletier, G.; Bechara, W. S.; Charette, A. B. J. Am. Chem. Soc.
2010, 132, 12817.
(18) Velusamy, S.; Ahamed, M.; Punniyamurthy, T. Org. Lett. 2004, 6,
4821.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–F