Copper(I)- and Mesoionic-Hydroxyamide-Catalyzed Chemoselective Aerobic Oxidation of Primary Benzylic Alcohols

Article abstract of DOI:10.1055/s-0037-1611698

A new aerobic oxidation system consisting of Cu(I)I, 2,2'-bipyridine, N -methyl imidazole, and a mesoionic hydroxyamide was developed, with which selective oxidation of a broad range of benzylic alcohols was achieved.

Full text of DOI:10.1055/s-0037-1611698

SYNLETT
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
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©
Georg Thieme Verlag Stuttgart · New York
2019, 30, 315–318
letter
315
en
Synlett
Y. Matsukawa, T. Hirashita
Letter
Copper(I)- and Mesoionic-Hydroxyamide-Catalyzed Chemo-
selective Aerobic Oxidation of Primary Benzylic Alcohols
Yuta Matsukawa
Mesoionic nitroxy catalyst
Base metal system
Ph
Tsunehisa Hirashita*
0
0
0
0-0
0
0
1-
7
1
9
6-3
3
3
9
N
N
N
Compatible with electron-
deficient substrates
Selective for
benzylic alcohols
N
Life Science and Applied Chemistry, Graduate School of
Engineering, Nagoya Institute of Technology, Gokiso-cho,
Showa-ku, Nagoya, Aichi, 466-8555, Japan
hirasita@nitech.ac.jp
N
OH
Ph
OH
R
5
mol%
O
R
CuI (5 mol%), bpy (5 mol%),
NMI (10 mol%), MeCN, air, r.t.
X
Y
X
Y
53–99%
X = Cl, NO2, OMe, CO2Me Y = CH, N
No over-oxidation
Received: 19.10.2018
Accepted after revision: 06.11.2018
Published online: 04.01.2019
– e, – H+
– e
N
N
O
N
O
DOI: 10.1055/s-0037-1611698; Art ID: st-2018-u0682-l
OH
TEMPOH
TEMPO
TEMPO+
Abstract A new aerobic oxidation system consisting of Cu(I)I, 2,2'-bi-
pyridine, N-methyl imidazole, and a mesoionic hydroxyamide was de-
veloped, with which selective oxidation of a broad range of benzylic al-
cohols was achieved.
Equation 1
We have recently focused on mesoionic 1,3-diphenyl-
tetrazolium-5-hydroxyamide 1, and have developed an ef-
Key words mesoionic compounds, aerobic oxidation, copper, benzylic
alcohols, aldehydes
9
ficient and chemoselective aerobic oxidation method using
10a
5
-nitroso-1,3-diphenyltetrazolium tetrafluoroborate
in-
The aerobic oxidation of alcohols has recently attracted
attention and has been widely explored because it is a high-
ly environment-friendly approach, with water as the only
volving a reversible redox couple with 1 as a catalyst similar
to TEMPO (Equation 2).1
0b
1
Ph
Ph
Ph
stoichiometric by-product. Copper is an easily available
N
– e, – H+
N
N
N
N
N
N
– e
N
N
base metal and its salts are relatively inexpensive and of
low toxicity, which makes it beneficial for use as a catalyst
for practical synthetic applications instead of precious met-
als. Homogenous Cu-catalyzed reactions thus continue to
be one of the pivotal processes in synthetic chemistry, such
as Cu-TEMPO-mediated aerobic oxidation of alcohols [TEMPO
N
N
N
N
1
OH
N
O
N
O
Ph
Ph
Ph
Equation 2
+
The redox potential of 1 is 0.10 V vs. Ag/Ag in acetoni-
trile,10a which is lower than that of TEMPO. This electro-
chemical property of 1 prompted us to apply it in a (bpy)Cu
system instead of nitroxyl catalysts, with the expectation
that the reoxidation of the catalyst would proceed more
easily. In our previous study on the aerobic oxidation of al-
cohols in the presence of nitric acid, the catalytic cycle op-
erates between 1 and its nitroso form through a two-elec-
tron-transfer process. The Cu–TEMPO redox reaction is,
however, considered to function as a one-electron process
between TEMPO and TEMPOH. Provided the mesoionic hy-
droxyamide 1 behaves like TEMPO in the oxidation of alco-
hols in the presence of a copper salt, a unique mesoionic
radical would be expected to participate in the redox cycle.
(2,2,6,6-tetramethylpiperidin-1-yl)oxyl].2–5 The Cu–TEMPO
11
=
system principally consists of a copper salt, TEMPO, a li-
gand, and a base. Koskinen and co-workers have reported
that use of N-methylimidazole (NMI) as a base in the
(
bpy)CuI–TEMPO system (bpy = 2,2'-bipyridine) promotes
6
the rapid oxidation of alcohols. Recently, Stahl et al. report-
I
I
ed that a (bpy)Cu –TEMPO system consisting of Cu , bpy,
and NMI allows aerobic oxidation to be performed under
milder conditions and with an expanded substrate scope.7
The redox reaction of TEMPO is presented in Equation 1,
and the electrocatalytic activity of TEMPO derivatives is
strongly correlated with their electrochemical potentials.8
©
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Y. Matsukawa, T. Hirashita
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We started by screening a number of copper salts using
benzyl alcohol (2a) as a model substrate under ambient air
conditions, and found Cu(I)I to be suitable for this reaction
Table 2 Comparison of the Yields after 3.0 Hours in the Cu–1 Aerobic
Oxidation Systema
O
CuI (5 mol%), 1 (5 mol%)
(
Table 1, entries 1–8). Among a variety of combinations of
ligands and bases, bpy and NMI provided the best results
entries 8, 11–15). With the optimal combination of salt, li-
gand, and base, MeCN as the solvent gave the best results
entries 8, 16, and 17). The oxidation did not proceed at all
Ph
OH
Ph
H
ligand (5 mol%), base (10 mol%),
3.0 h, MeCN, air, r.t.
2a
3a
(
Entry
Ligand
Base
Yield of 3a [%]b Recovery of 2a [%]b
(
1c
2
bpy
NMI
DBU
NMI
NMI
NMI
NMI
68
33
14
18
78
49
21
52
70
67
16
39
in the absence of 1 (entry 9). The absence of a base led to a
large drop in the yield of benzaldehyde 3a (entry 10).
bpy
3
phen
TMEDA
bpy
Table 1 Optimization of the Cu–1-Catalyzed Aerobic Oxidation of
4
a
Benzyl Alcohol
5d
Ph
6e
bpy
O
N
a
Cu salt (5 mol%), 1 (5 mol%)
N
N
Reaction conditions: 2a (0.40 mmol), CuI (5 mol%), ligand (5 mol%), base
10 mol%), and 1 (5 mol%) in MeCN (4.0 mL) at room temperature.
Determined by GC.
N
(
Ph
OH
Ph
H
ligand (5 mol%), base (10 mol%),
24 h, MeCN, air, r.t.
N
1
OH
b
c
Ph
2a
3a
For a profile at an earlier stage, see Figure S1.
d
e
2
Under O (balloon).
At 40 °C.
Entry Cu salt
Ligand
Base
Yield of Recoveryb
b
3
a [%]
of 2a [%]
1
2
3
4
5
6
7
8
9c
Cu(ClO
CuCl
CuBr
(CuOTf)
4
)
2
∙6H
2
O
bpy
bpy
bpy
bpy
bpy
bpy
bpy
bpy
bpy
bpy
bpy
bpy
bpy
phen
TMEDA
bpy
bpy
NMI
NMI
NMI
NMI
NMI
NMI
NMI
NMI
NMI
4
1
84
87
91
51
41
63
30
6
Having the optimal conditions in hand, we investigated
2
the scope of the alcohols (Scheme 1). Benzylic alcohols
with an electron-withdrawing group such as an ester or
halogen were efficiently oxidized to afford the correspond-
ing aldehydes (3b–e), whereas p-anisalcohol led to a mod-
erate yield (3f). A competitive oxidation between p-nitro-
benzyl and benzyl alcohol showed that oxidation of the for-
mer was strongly favored; p-nitrobenzyl alcohol was
oxidized two times faster than benzyl alcohol. Intriguingly,
p-hydroxy- and p-aminobenzyl alcohols were also oxidized
to the corresponding aldehydes in moderate yields (3g and
2
0
2
∙C
6
H
6
38
47
22
62
94
0
CuBF
CuCl
CuBr
CuI
4 4
∙(MeCN)
CuI
83
42
26
26
68
50
55
81
63
1
0
1
2
3
4
CuI
none
CO
53
72
66
24
32
36
0
3
h), in sharp contrast to the TEMPO–Cu-catalyzed oxida-
1
1
1
1
1
1
CuI
K
2
3
tion, in which such functionalities completely suppress the
conversion. This is presumably due to a strong coordination
CuI
Py
CuI
DBU
NMI
NMI
NMI
NMI
12
to the copper atom. Cinnamyl alcohol was converted into
CuI
cinnamyl aldehyde 3i in a moderate yield. Benzhydrol and
-pyridinemethanol were successfully oxidized to alde-
3
5
CuI
6d
hydes 3j and 3k. In contrast to HNO -catalyzed aerobic oxi-
3
CuI
dation,1 oxidation of aliphatic alcohols occurred with low
0b
1
7e
CuI
20
yields or not at all (3l–n).
a
Reaction conditions: 2a (0.40 mmol), Cu salt (5 mol%), ligand (5 mol%),
base (10 mol%), and 1 (5 mol%) in MeCN unless otherwise noted (4.0 mL) at
room temperature.
Determined by GC.
Without 1.
In THF.
2 2
In CH Cl .
When p-nitrobenzyl alcohol was allowed to react com-
petitively with 1-undecanol, 3c was selectively obtained
and 1-undecanol was completely recovered. Ethyl lactate
(2o) was converted into the corresponding ketone 3o in 31%
yield, while styrene glycol and (2,2-dimethyl-1,3-dioxolan-
b
c
d
e
4-yl)methanol (solketal) were recovered intact. Since a high
The yields of benzaldehyde obtained at an early stage of
the reaction (after 3 h) under a series of conditions showed
the same tendency as that observed above (Table 2, entries
selectivity of benzylic alcohols was revealed in this study, a
preference for primary/secondary alcohols was next exam-
ined by competitive oxidations of benzylic alcohols 2a/1-
phenylethanol (2p) and allylic substrates 2i/2q. In both oxi-
dations, primary 2a and 2i were preferably converted into
the corresponding aldehydes than into secondary alcohols
2p and 2q. The Cu–1 system proved to be capable of oxidiz-
ing 2o as well as 2g and 2h, albeit in modest yield, which
1–4), and the combination of bpy and NMI proved again to
be superior to the others examined. Use of pure oxygen im-
proved the yield (entry 5), whereas heating resulted in a
drop in yield (entry 6).
©
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Y. Matsukawa, T. Hirashita
Letter
OH
R2
1 (5 mol%)
O
observed (Equation 3). This result suggests that radical in-
termediates may not be involved in the Cu–1-catalyzed aer-
obic oxidation, similar to the Cu–TEMPO system.12
R1
R1
R2
CuI (5 mol%), bpy (5 mol%),
NMI (10 mol%), MeCN, air, r.t.
2
3
O
O
O
1
(5 mol%)
2
p
+
O
Ph
OH
Ph
O
H
H
H
CuI (5 mol%), bpy (5 mol%),
NMI (10 mol%), 24 h,
MeCN (4.0 mL), air, r.t.
2
p
3p
38%
Ph
H
61%
Cl
O2N
MeO2C
0.4 mmol
3
a
3b
83%c
(3.0 h)
3c
89%
(3.0 h)
3d
84%
(3.0 h)
Equation 3
b
c
c
9
4% (6%)
24 h)
(
O
O
H
O
O
In summary, mesoionic hydroxyamide 1 and a copper
salt can function as a catalytic system for the aerobic oxida-
H
H
H
tion of benzylic alcohols to the corresponding carbonyl
Ph
MeO
HO
H2N
compounds.1
3–15
In the presence of 1 (5 mol%), CuI (5 mol%),
3
9%
3.0 h)
e
3f
3g
3h
bpy (5 mol%), and NMI (10 mol%), benzyl alcohol and ben-
zylic alcohols bearing electron-withdrawing groups were
oxidized to aldehydes in 83–99% yield, whereas benzylic al-
cohols with amino or oxygenated functionalities, some of
which are incapable of being oxidized by the Cu–TEMPO
catalyst, were transformed into the corresponding alde-
hydes in 30–57% yield. Aliphatic alcohols, in contrast, were
oxidized with low yields or not at all, and thus benzylic al-
cohols can be selectively oxidized in the presence of ali-
phatic alcohols.
c
53% (47%)d
(24 h)
30% (60%)d
(24 h)
d
9
(
57% (43%)
(24 h)
O
H
O
O
Ph
H
Ph
Ph
N
3
i
3j
99%
(3.0 h)
3k
d
c
99%d
(3.0 h)
6
0% (38%)
(
24 h)
O
O
9
O
O
H
8
EtO2C
Supporting Information
3l
3m
3n
0% (98%)
(24 h)
3o
b
4% (86%)b
(24 h)
c
d
Supporting information for this article is available online at
13% (87%)
31% (67%)
(24 h)
(
24 h)
https://doi.org/10.1055/s-0037-1611698.
S
u
p
p
orit
n
g Inform ati
o
n
S
u
p
p
orit
n
g Inform ati
o
n
O
O
O
O
Ph
H
H
References and Notes
H
H
O2N
O2N
9
(
1) Wertz, S.; Studer, A. Green Chem. 2013, 15, 3116.
(2) Brackman, W.; Gaasbeek, C. J.; Smit, P. J. Rec. Trav. Chim. 1966,
5, 437.
3
7%
c
3a
3c
94%d
3l
d
48% (49%)d
d
9
0% (100%)
8
(
3.0 h)
(3.0 h)
(3) Semmelhack, M. F.; Schmid, C. R.; Cortes, D. A.; Chou, C. S. J. Am.
Chem. Soc. 1984, 106, 3374.
(
4) (a) Gamez, P.; Arends, I. W. C. E.; Reedijk, J.; Sheldon, R. A. Chem.
Commun. 2003, 2414. (b) Gamez, P.; Arends, I. W. C. E.; Sheldon,
R. A.; Reedijk, J. Adv. Synth. Catal. 2004, 346, 805.
5) Betzemeier, B.; Cavazzini, M.; Quici, S.; Knochel, P. Tetrahedron
Lett. 2000, 41, 4343.
O
O
O
O
Ph
H
Ph
Ph
H
Ph
(
3a
3p
3i
56% (44%)d
3q
d
36% (47%)d
d
6
5% (8%)
18% (46%)
(
3.0 h)
(3.0 h)
(6) Kumpulainen, E. T. T.; Koskinen, A. M. P. Chem. Eur. J. 2009, 15,
0901.
(7) Hoover, J. M.; Stahl, S. S. J. Am. Chem. Soc. 2011, 133, 16901.
1
Scheme 1 Scope of the Cu–1-catalyzed aerobic oxidation of alcohols.
Reaction conditions: 2 (0.40 mmol), CuI (5 mol%), bpy (5 mol%), NMI
10 mol%), and 1 (5 mol%) in MeCN (4.0 mL) at room temperature. Val-
a
(
8) Hickey, D. P.; Schiedler, D. A.; Matanovic, I.; Doan, V.; Atanassov,
P.; Minteer, S. D.; Sigman, M. S. J. Am. Chem. Soc. 2015, 137,
16179.
(
b
c
ues in parentheses are the recoveries of 2. Determined by GC. Isolat-
ed yield. d Determined by H NMR spectroscopy.
1
(
9) Araki, S.; Yamamoto, K.; Yagi, M.; Inoue, T.; Fukagawa, H.;
Hattori, H.; Yamamura, H.; Kawai, M.; Butsugan, Y. Eur. J. Org.
Chem. 1998, 121.
are difficult to oxidize with the (bpy)Cu –TEMPO system.7
-Phenylcyclopropylmethanol (2r), a radical clock sub-
strate, was subjected to this aerobic oxidation in order to
gain insight into the mechanism. Although we anticipated
that aliphatic alcohols would be resistant to the oxidation,
as seen in Scheme 1, the corresponding aldehyde 3r was ob-
tained in moderate yield and no ring-opened product was
I
(
10) (a) Matsukawa, Y.; Hirashita, T.; Araki, S. Tetrahedron 2017, 73,
2
6052. (b) Matsukawa, Y.; Hirashita, T.; Araki, S. Eur. J. Org. Chem.
2018, 1359.
(
11) (a) Badalyan, A.; Stahl, S. S. Nature 2016, 535, 406. (b) The redox
+
potential of TEMPO (0.31 V vs. Ag/Ag ) was observed in acetoni-
trile.
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Synlett
Y. Matsukawa, T. Hirashita
Letter
(
12) (a) Hoover, J. M.; Ryland, B. L.; Stahl, S. S. J. Am. Chem. Soc. 2013,
35, 2357. (b) Ryland, B. L.; McCann, S. D.; Brunold, T. C.; Stahl,
ligand (0.02 mmol), base (0.04 mmol), and 1 (0.02 mmol) was
vigorously stirred in MeCN (4.0 mL) at room temperature for 24
h in the presence of PhCN (0.2 mmol) as an internal standard. At
intervals, aliquots were analyzed by GC after being passed
through a SiO column eluted with CH Cl . The yield of benzal-
1
S. S. J. Am. Chem. Soc. 2014, 136, 12166.
(13) Improved Synthetic Procedure for 1,3-Diphenyltetrazolium-
5
-hydroxyamide (1): To a suspension of NH OH•HCl (3.48 g,
2
2
2
2
5
0.0 mmol) in MeCN (200 mL) was added Et N (6.93 mL, 50.0
dehyde 3a (tR = 4.3 min) and the recovery of 2a (tR = 9.4 min)
were calculated on the basis of calibration curves by using
authentic samples.
3
mmol), and the mixture was stirred for 2 h at room tempera-
ture, followed by addition of 5-chloro-1,3-diphenyltetrazolium
tetrafluoroborate (3.44 g, 10.0 mmol). The mixture was stirred
for a further 3 h and then the solvent was evaporated in vacuo.
To the residue was added saturated NaHCO (12.0 g, 143 mmol)
solution. The resulting mixture was extracted with CH Cl and
shaken with 1M HCl (100 mL). The aqueous phase was washed
with CH Cl and basified with saturated NaHCO . The resulting
precipitate was extracted with CH Cl and dried with anhy-
(15) Representative Procedure for the Cu–1-Catalyzed Aerobic
Oxidation of Benzylic Alcohols (Scheme 1, Benzhydrol 2j): A
mixture of benzhydrol 2j (74 mg, 0.40 mmol), CuI (3.7 mg,
0.019 mmol), 2,2'-bipyridine (3.1 mg, 0.020 mmol), N-methyl
imidazole (3.5 mg, 0.043 mmol), and 1 (5.1 mg, 0.020 mmol)
was vigorously stirred in MeCN (4.0 mL) at room temperature
for 3 h. The solvent was evaporated under reduced pressure and
3
2
2
2
2
3
2
2
drous Na SO , and the resulting solution was evaporated in
vacuo to give brown crystals of 1 (1.65 g, 65%).
the residue was passed through a SiO column eluted with
2
4
2
1
CH Cl to give 3j (73 mg, 99%). H NMR (300 MHz, CDCl ): δ 7.49
2
2
3
(
14) General Procedure for the Optimization of the Cu–1-Cata-
lyzed Aerobic Oxidation of Benzyl Alcohol (Table 1): A
mixture of benzyl alcohol 2a (0.4 mmol), Cu salt (0.02 mmol),
(t, J = 7.5 Hz, 4 H), 7.60 (t, J = 7.2 Hz, 2 H), 7.81 (d, J = 6.9 Hz, 4 H).
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2019, 30, 315–318