Iridium-catalyzed oxidative dimerization of primary alcohols to esters using 2-butanone as an oxidant

Article abstract of DOI:10.1055/s-2005-868492

Oxidative dimerization of primary alcohols with 2-butanone in the presence of an amino alcohol-based Ir bifunctional catalyst was accomplished for the first time. The reaction proceeds with 1-2 mol% of the catalyst and 0.3 mol equivalents of K₂CO₃ in 2-butanone at room temperature to give the corresponding dimeric esters in 30-93% yield. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-868492

LETTER
1453
Iridium-Catalyzed Oxidative Dimerization of Primary Alcohols to Esters
Using 2-Butanone as an Oxidant
I
T
ridium-Catalyz
a
ed
O
xidati
k
ve
D
imerizat
e
ion of Prim
y
aryAlcohols
ut oEsters ki Suzuki,* Tomohito Matsuo, Kazuhiro Watanabe, Tadashi Katoh*
Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-Ku, Sendai, Miyagi 981-8558, Japan
Fax +81(22)2752013; E-mail: suzuki-t@tohoku-pharm.ac.jp; E-mail: katoh@tohoku-pharm.ac.jp
Received 28 February 2005
Recently, we have developed an Ir aminoalkoxide com-
plex, which catalyzes the oxidative lactonization of diols
and Oppenauer oxidation of primary alcohols.1 In this
Abstract: Oxidative dimerization of primary alcohols with 2-bu-
tanone in the presence of an amino alcohol-based Ir bifunctional
catalyst was accomplished for the first time. The reaction proceeds
7,18
with 1–2 mol% of the catalyst and 0.3 mol equivalents of K CO in paper, we present the Ir complex-catalyzed oxidative
2
3
2
-butanone at room temperature to give the corresponding dimeric dimerization of various primary alcohols at room temper-
esters in 30–93% yield.
ature. This reaction is also the first example for the use of
Key words: alcohols, esters, hydrogen transfer, iridium catalyst, ketone as a cooxidant.19
oxidative dimerization
When a mixture of 3-phenylpropanol (1a) in 2-butanone
2.7 equiv) containing the Ir complex 31 and K CO (2-
7a
(
2 3
butanone:1a:3:K CO = 270:100:2:30) was stirred at
2
3
For the synthesis of dimeric esters, oxidative
room temperature for 20 hours, 3-phenyl-1-propyl 3-phe-
nylpropanoate (2a) was obtained in 89% yield (Table 1,
entry 4). The reaction proceeded similarly in acetone, 3-
pentanone (entries 5, 6). To obtain the dimeric ester in
high yield, the uses of K CO and high-concentration con-
1
dimerization of primary alcohols is an important method
2
as well as the Tishchenko reaction of aldehydes
(
Scheme 1).
2
3
oxidative dimerization
ditions are crucial. Without the base, the reaction in 2-bu-
tanone proceeded in only 30% yield after 20 hours (entry
1). However, the yield increased to 76% in the presence of
oxidant
2
RCH2OH
RCO2CH2R
1
2
20
Tishchenko reaction
just 5 mol% of K CO (entry 2). The reaction using 0.3
2 3
2
RCHO
RCO CH R
M 2-butanone solution (37 equiv) was slower and gave
only 9% yield (entry 3).
2
2
4
2
Scheme 1
Table 1 Oxidative Dimerization of 1aa
To date, various reaction systems have been developed,
3
which include stoichiometric oxidation using Na Cr O ,
2
2
7
Ir
4
5
5
6
HN
O
Br –HMPT, Ca(OCl) , NaOCl, NaBrO , NaBrO –
NaHSO , PCC–Al O , and so on. Recently, Bobbitt et
al. reported oxidative dimerization of polyfunctional
primary alcohols using oxoammonium salts. Kita et al.
2
2
8
2
3
O
7
3
2
3
Ph Ph
OH
3
O
9
ketone,
K2CO3
r.t., 20 h
1a
2a
have developed an oxidative methyl esterification of
primary alcohols using a hypervalent iodine reagent.10
Several catalytic methods have been developed using, for Entry
Ketone
K
CO
Conversion Yield of 2a
2
3
1
1
12
(equiv)
None
0.05
0.3
(%)
33
78
81
92
86
87
(%)
30
76
9
example,
Pd(OAc) –CCl ,
Ru (CO) –tolane,
2
1
4
3 12
3
14
RuH (PPh ) (180 °C), Pd(OAc) –PhBr, BTMA–Mo
2
3 4
2
1
2-Butanone
2-Butanone
2-Butanone
2-Butanone
Acetone
(
benzyltrimethylammonium tetrabromooxomolybdate)–
1
5
16
2
t-BuOOH, MoO –Sb O (300 °C, dehydrogenation).
3
2
4
However, these catalytic reactions require heating. More-
3b
1
2
13
over, except for the Shvo and Murahashi methods,
benzyl alcohols are usually difficult substrates for oxida-
tive dimerization by catalytic or stoichiometric methods,
and the major products are not the dimeric esters, but ben-
4
5
0.3
89
82
85
0.3
4
,5,7,8,11,14
zaldehydes.
Thus, an efficient oxidative dimer-
6
3-Pentanone
0.3
ization with broad generality has not yet been developed.
a
Unless otherwise stated, the reaction was carried out using 1a
(
1.0 mmol), ketone (2.7 mmol), 3 (0.02 mmol, 2 mol%), and K CO
2
3
(
0–0.3 mmol) at r.t. for 20 h.
SYNLETT 2005, No. 9, pp 1453–1455
Advanced online publication: 25.04.2005
0
1.
0
6.
2
0
0
5
b
3
7 Equiv of 2-butanone were used.
DOI: 10.1055/s-2005-868492; Art ID: U05305ST
©
Georg Thieme Verlag Stuttgart · New York

1
454
T. Suzuki et al.
LETTER
Table 2 Oxidative Dimerization of Primary Alcohols Catalyzed by
an Ir Catalyst 3
Having succeeded in optimizing the reaction conditions,
we next investigated the catalytic oxidative dimerization
of other substrates. As shown in Table 2,2 both aliphat-
ic and benzylic alcohols could be converted to the corre-
sponding dimeric esters in high yields. The esters 2c,d,
which are used as perfume materials (apple flavor), were
obtained in 83% and 72% yields, respectively. The reac-
tion of alcohol containing a b-oxygen proceeded in 73%
yield. Benzyl alcohol afforded benzyl benzoate in 93%
yield (entry 6). A gram-scale reaction can be performed in
the presence of even 1 mol% catalyst (entry 7). The reac-
tion proceeds smoothly even in the case of benzyl alco-
hols with an electron-donating group (entries 8–10). To
our knowledge, this represents the first successful oxida-
tive dimerization of benzylic alcohols with an electron-
donating group. Moreover, the oxidation of benzyl alco-
hol with a substituent such as sulfide, which is susceptible
to oxidation, proceeded without any difficulty (entry 9).
Benzyl alcohols with an electron-withdrawing group were
also good substrates (entries 11–13). The reaction of the
unsaturated alcohol 1m gave 2m in 67% yield, albeit with
a longer reaction time. However, the reaction of cinnamyl
alcohol 1n gave 2n in only 30% yield, along with a mix-
ture of partially or fully saturated products.23
a
1,22
Entry Alcohol
1
Time Conversion Yield
b
(
h)
(%)
(%)
20
92
89 (97)
OH
1
1
1
a
b
c
2
3
4
40
48
48
93
87
76
86 (92)
83 (95)c
72 (95)c
OH
OH
OH
O
1
1
d
e
5
48
81
73 (90)d
OH
6
7
25
45
95
86
93 (98)
81 (94)e
OH
1f
8
9
1
1
1
1
26
26
25
25
24
48
92
93
93
97
95
84
89 (97)
87 (94)
86 (92)
91 (94)
91 (96)
80 (95)
OH
MeO
1g
A probable mechanism for the Ir-catalyzed oxidative
dimerization is shown in Scheme 2. At first, the Ir com-
plex 3 oxidizes primary alcohol 1 to give the correspond-
ing aldehyde 5, which reacts with another alcohol 1 to
give hemiacetal 6. Then, the second oxidation of the
hemiacetal 6 affords the dimeric esters 2. The role of 2-
butanone as a co-oxidant is confirmed by the observation
OH
MeS
1h
0
1
2
3
OH
Me
1i
1
of 2-butanol in H NMR after the reaction.
OH
OH
In conclusion, we have developed a highly efficient cata-
lytic oxidative dimerization of various primary alcohols
with high yield. This simple and economical process
should be useful for contemporary organic synthesis. Fur-
ther details and an extension of this work will be reported
in due course.
Cl
1j
Br
1k
OH
Acknowledgment
O2N
1
1
1
l
This work was financially supported by a Grant-in-Aid for
Encouragement of Young Scientists (B) from JSPS. We also thank
Professor Yoshio Okawa of Tohoku Pharmaceutical University for
the use of the GC.
1
4
5
96
17
76
98
67 (88)d
30 (31)
OH
m
n
1
OH
References
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a
Unless otherwise stated, the reaction was carried out using 1 (1.0
mmol), 2-butanone (2.7 mmol), 3 (0.02 mmol, 2 mol%), and K CO
0.3 mmol) at r.t.
Yield in parentheses are based on the consumed alcohols.
Yields of esters and recovered alcohol were determined by GC.
Yields of recovered alcohol were determined by GC.
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2
3
(
b
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Synlett 2005, No. 9, 1453–1455 © Thieme Stuttgart · New York

LETTER
Iridium-Catalyzed Oxidative Dimerization of Primary Alcohols to Esters
1455
O
OH
O
R
OH
1
R
OH
R
H
R
O
R
R
O
R
1
5
6
2
Ir
Ir
Ir
Ir
H
H
N
O
H
H
O
N
O
H
H
O
N
N
Ph
Ph
Ph
Ph
Ph
Ph
H
4
H
4
Ph
Ph
3
3
OH
O
OH
O
Scheme 2
(
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(
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(
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(
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to remove the catalyst. The yields for the products of 2c and
2d were determined by gas chromatography using authentic
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1
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(
22) Although TONs were not optimized at the moment, they
were roughly calculated to be in range between 17 and 23 for
most substrates [with single entry as high as 40 (entry 7)].
23) The mechanism of saturation is not clear at present. Partially
saturated products were observed even without K CO under
(
2
3
a high-concentration condition (4.2 M). However, such
saturated products were not observed with K CO under a
2
3
diluted condition (0.08 M). See also ref. 17c.
Synlett 2005, No. 9, 1453–1455 © Thieme Stuttgart · New York