Ir id iu m -Ca ta lyzed Op p en a u er Oxid a tion s
of P r im a r y Alcoh ols Usin g Aceton e or
SCHEME 1. Op p en a u er Oxid a tion of P r im a r y
2
-Bu ta n on e a s Oxid a n t
Takeyuki Suzuki, Kenji Morita, Mika Tsuchida, and
Kunio Hiroi*
Department of Synthetic Organic Chemistry,
Tohoku Pharmaceutical University, 4-4-1 Komatsushima,
Aoba-Ku, Sendai, Miyagi 981-8558, J apan
Received J uly 29, 2002
aldol reaction. On the basis of the present results, we
report herein the first Oppenauer oxidation of primary
alcohols to aldehydes using inexpensive acetone or 2-bu-
tanone as an oxidant (eq 1).
Abstr a ct: The first Oppenauer oxidation of primary alco-
hols with acetone or 2-butanone by an amino alcohol-based
Ir bifunctional catalyst was accomplished. The reaction
proceeds with 1 mol % catalyst in acetone or 2-butanone at
3
0-80 °C to give the corresponding aldehydes in 33-96%
yield.
In 1937 Oppenauer reported that the oxidation of
steroids bearing secondary alcohol functions proceeded
using acetone as an oxidant in the presence of an
1
Al(O-t-Bu)
3
catalyst. The main advantage of this reac-
When a 0.1 M solution of 4-methoxybenzyl alcohol (1b)
in acetone-containing Ir complex 4 (acetone:1b :4 )
13600:100:1) was stirred under Ar at 30 °C for 16 h, we
found that p-anisaldehyde (2b) was obtained in 78% yield
without aldol condensation (Table 1, entry 1). The yield
was improved by raising the temperature (entry 2), and
the best result was obtained by heating the solution in
butanone at 80 °C (entry 3). To obtain the aldehyde in
high yield, the reaction should be performed with a
substrate concentration as low as 0.08 M. The high-
dilution condition has the following two merits: (1)
because the reaction is reversible, use of the excess
oxidant makes the equilibrium shift toward the product
side and (2) the formation of dimeric ester 3, which is a
major side product in the reaction of 1f, is suppressed
tion lies in the high selectivity of various functional
groups, and the method is often used to prepare ke-
tones. However, the oxidation of primary alcohols does
not occur easily for the following reasons (see Scheme
1
): (a) the product aldehyde 2 reacts with acetone to
give an aldol condensation product, (b) water formed
by the aldol condensation deactivates the moisture-
sensitive aluminum alkoxide catalyst, and (c) the product
aldehyde 2 may cause a Tishchenko reaction to give
2
dimeric esters 3.
To date, many attempts for improvements of the
Oppenauer oxidation of primary alcohols using other
3
4
hydrogen acceptors and metal catalyst systems have
been reported, but there has been no report of oxidizing
a primary alcohol to form an aldehyde using inexpensive
acetone or 2-butanone as the oxidant. We have recently
developed an efficient oxidative lactonization of diols
6
under the low-concentration condition (entries 6-8).
Having succeeded in optimizing the reaction condition,
we examined the scope and limitations of the reaction
with substrates. As shown in Table 2, the oxidation of
the benzyl alcohol with an electron-donating substituent
gave the desired aldehyde in high yield (entries 1-3).
Moreover, the oxidation of the substrate 1d with a
substituent such as the sulfide, which is easy to oxidize,
proceeded with no problems (entry 4). The oxidation of
the allyl alcohol 1g afforded the corresponding aldehyde
in good yield. However, the oxidation of the saturated
5
using a novel Ir-ligand bifunctional catalyst, 4. Due to
the neutral character of the catalyst, we hypothesized
that this catalyst system would be effective for the
oxidation of primary alcohols without the accompanying
(
1) Oppenauer, R. V. Recl. Trav. Chim. Pays-Bas 1937, 56, 137-
1
7
44.
(
2) For a review, see: (a) Djerassi, C. Org. React. 1951, VI, 207-
2. (b) de Graauw, C. F.; Peters, J . A.; van Bekkum, H.; Huskens, J .
Synthesis 1994, 1007-1017.
3) Al(O-t-Bu) /benzoquinone: Yamashita, M.; Matsumura, T. J .
Chem. Soc. J pn. 1943, 64, 506-508.
4) (a) (C BOH/t-BuCHO (1-2 mol %, rt): Ishihara, K.; Kuri-
hara, H.; Yamamoto, H. J . Org. Chem. 1997, 62, 5664-5665. (b)
Zr(O-t-Bu) /CCl CHO (20 mol %, 20 °C): Krohn, K.; Knauer, B.;
Kuepke, J .; Seebach, D.; Beck, A. K.; Hayakawa, M. Synthesis 1996,
341-1344. (c) Cp ZrH /benzophenone (2 mol %, 130 °C): Ishii, Y.;
Nakano, T.; Inada, A.; Kishigami, Y.; Sakurai, K.; Ogawa, M. J . Org.
Chem. 1986, 51, 240-242. (d) t-BuSmI /2-furaldehyde (10 mol %, 65
C): Namy, J . L.; Souppe, J .; Collin, J .; Kagan, H. B. J . Org. Chem.
aliphatic alcohol gave octanal in low yield due to the
(
3
lower redox potential of butanone (entry 8).7
(
6 5 2
F )
(6) Although a detailed mechanism has not yet been determined, it
seems possible that the dimeric ester 3 was formed via the correspond-
ing hemiacetal intermediate. The reaction of bromobenzaldehyde (2f)
in the presence of the Ir catalyst 4 (2f:4 ) 100:1 mole ratio) gave a
trace amount of 3f under reflux for 16 h, indicating that the contribu-
tion of the mechanism via the acylhydridometal complex is negligible.
For the mechanism via the acylhydridometal complex, see: Horino,
H.; Ito, T.; Yamamoto, A. Chem. Lett. 1978, 17-20.
4
3
1
2
2
2
°
1
984, 49, 2045-2049.
(
5) Suzuki, T.; Morita, K.; Tsuchida, M.; Hiroi, K. Org. Lett. 2002,
(7) Adkins, H.; Elofson, R. M.; Rossow, A. G.; Robinson, C. C. J . Am.
Chem. Soc. 1949, 71, 3622-3629.
4
, 2361-2363.
1
0.1021/jo0262560 CCC: $25.00 © 2003 American Chemical Society
Published on Web 01/21/2003
J . Org. Chem. 2003, 68, 1601-1602
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