Palladium(II)-catalyzed oxidation of alcohols to aldehydes and ketones by molecular oxygen

Article abstract of DOI:10.1021/jo9906734

A novel combination of Pd(OAc)₂/pyridine/MS3A catalyzes the aerobic oxidation in toluene of a variety of primary and secondary alcohols into the corresponding aldehydes and ketones in high yields. Various substituents and protecting groups are compatible with this oxidation. The ca. 2:3 ratio of O₂ uptake to product yield is observed, whereas in the absence of MS3A, the ratio is ca. 1:1, suggesting the in situ formation of H₂O₂ and its decomposition by MS3A into water and oxygen. A catalytic cycle including the formation of a Pd(II)-alcoholate followed by β-elimination of a Pd(II)H species and a carbonyl compound and then the formation of a Pd(II)OOH species is proposed.

Full text of DOI:10.1021/jo9906734

6
750
J . Org. Chem. 1999, 64, 6750-6755
P a lla d iu m (II)-Ca ta lyzed Oxid a tion of Alcoh ols to Ald eh yd es a n d
Keton es by Molecu la r Oxygen
Takahiro Nishimura, Tomoaki Onoue, Kouichi Ohe, and Sakae Uemura*
Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University,
Sakyo-ku, Kyoto 606-8501, J apan
Received April 21, 1999
2
A novel combination of Pd(OAc) /pyridine/MS3A catalyzes the aerobic oxidation in toluene of a
variety of primary and secondary alcohols into the corresponding aldehydes and ketones in high
yields. Various substituents and protecting groups are compatible with this oxidation. The ca. 2:3
ratio of O
2
uptake to product yield is observed, whereas in the absence of MS3A, the ratio is ca.
and its decomposition by MS3A into water and oxygen.
1
:1, suggesting the in situ formation of H O
2 2
A catalytic cycle including the formation of a Pd(II)-alcoholate followed by â-elimination of a
Pd(II)H species and a carbonyl compound and then the formation of a Pd(II)OOH species is proposed.
In tr od u ction
The oxidation of alcohols to aldehydes and ketones is
alcohols using molecular oxygen as a sole reoxidant in
977, many efforts have been made to find a synthetically
1
7-10
useful method for Pd-catalyzed oxidation.
For ex-
1
a fundamental reaction in organic synthesis. For envi-
ronmental and economical reasons, metal-catalyzed reac-
tions using molecular oxygen as a reoxidant are particu-
larly attractive. Many procedures using metal catalysts
ample, the effective aerobic oxidation of benzylic and
allylic alcohols was accomplished by using Pd clusters
8
in the presence of molecular oxygen without co-oxidants.
2 2
A Pd(OAc) /DMSO/O catalytic method has also been
2
3
4
5
6
such as Ru, Co, Cu, Pt, and Rh have been reported.
Since the first example of the Pd-catalyzed oxidation of
9
reported. These studies are quite interesting, but these
systems are not applicable to a wide range of alcohols,
especially for the effective transformation of primary and
secondary aliphatic alcohols to aldehydes and ketones.
(
1) For example: (a) Sheldon, R. A.; Kochi, J . K. Metal-Catalyzed
Oxidations of Organic Compounds; Academic Press: New York, 1984.
b) Hudlicky, M. Oxidations in Organic Chemistry; ACS Monograph
Series; American Chemical Society: Washington, DC, 1990.
2) (a) Tang, R.; Diamond, S. E.; Neary, N.; Mares, F. J . Chem. Soc.,
Chem. Commun. 1978, 562. (b) Matsumoto, M; Ito, S. Synth. Commun.
(
Recently, we have reported the palladium-catalyzed
aerobic oxidation of some alcohols to aldehydes and
ketones using a catalytic amount of Pd(OAc) , pyridine,
2
(
and MS3A under oxygen atmosphere.11 The goal for our
investigation is the elaboration of an operationally simple
and environmentally safe method using commercially
available reagents and oxygen as a sole oxidant, which
should have high selectivity, yield and compatibility with
different functional groups. In this paper, we describe the
full scope and some mechanistic aspects of this aerobic
oxidation.
1
4
1
984, 14, 697. (c) Matsumoto, M.; Watanabe, N. J . Org. Chem. 1984,
9, 3435. (d) Bilgrien, C.; Davis, S.; Drago, R. S. J . Am. Chem. Soc.
987, 109, 3786. (e) B a¨ ckvall, J . E.; Chowdhury, R. L.; Karlsson, U. J .
Chem. Soc., Chem. Commun. 1991, 473. (f) Murahashi, S.-I.; Naota,
T.; Hirai, N. J . Org. Chem. 1993, 58, 7318. (g) Ley, S. V.; Norman, J .;
Griffith, W. P.; Marsden, S. P. Synthesis 1994, 639. (h) Wang, G. Z.;
Andreasson, U.; B a¨ ckvall, J . E. J . Chem. Soc., Chem. Commun. 1994,
1
037. (i) Inokuchi, T.; Nakagawa, K.; Torii, S. Tetrahedron Lett. 1995,
6, 3223. (j) Mark o´ , I. E.; Giles, P. R.; Tsukazaki, M.; Chell e´ -Regnaut,
3
I.; Urch, C. J .; Brown, S. M. J . Am. Chem. Soc. 1997, 119, 12661. (k)
Lenz, R.; Ley, S. V. J . Chem. Soc., Perkin Trans. 1 1997, 3291. (l)
Hanyu, A.; Takezawa, E.; Sakaguchi, S.; Ishii, Y. Tetrahedron Lett.
1
9
998, 39, 5557. (m) Hinzen, B.; Lenz, R.; Ley, S. V. Synthesis 1998,
77. (n) Kaneda, K.; Yamashita, T.; Matsushita, T.; Ebitani, K. J . Org.
Resu lts a n d Discu ssion
Chem. 1998, 63, 1750. (o) Matsushita, T.; Ebitani, K.; Kaneda, K.
Chem. Commun. 1999, 265.
On the basis of our previous studies, aerobic oxidation
of alcohols (1.0 mmol) using oxygen as an oxidant was
generally carried out in the presence of Pd(OAc) (0.05
2
mmol), pyridine (0.2 mmol), and MS3A (500 mg) in
toluene (10 mL) under stirring at 80 °C for 2 h (a
standard condition for the oxidation).
(
3) (a) Yamada, T.; Mukaiyama, T. Chem. Lett. 1989, 519. (b)
Iwahama, T.; Sakaguchi, S.; Nishiyama, Y.; Ishii, Y. Tetrahedron Lett.
995, 36, 6923.
4) (a) Munakata, M; Nishibayashi, S; Sakamoto, H J . Chem. Soc.,
1
(
Chem. Commun. 1980, 219. (b) Bhaduri, S.; Sapre, N. Y. J . Chem. Soc.,
Dalton Trans. 1981, 2585. (c) Semmelhack, M. F.; Schmid, C. R.;
Cort e´ s, D. A.; Chou, C. S. J . Am. Chem. Soc. 1984, 106, 3374. (d)
Driscoll, J . J .; Kosman, D. J . J . Am. Chem. Soc. 1987, 109, 1765. (d)
Capdevielle, P.; Sparfel, D.; Baranne-Lafont, J .; Cuong, N. K.; Maumy,
M. J . Chem. Res., Synop. 1993, 10. (e) Liu, X.; Qiu, A.; Sawyer, D. T.
J . Am. Chem. Soc. 1993, 115, 3239. (f) Mark o´ , I. E.; Giles, P. R.;
Tsukazaki, M.; Brown, S. M.; Urch, C. J . Science 1996, 274, 2044. (g)
Mark o´ , I. E.; Tsukazaki, M.; Giles, P. R.; Brown, S. M.; Urch, C. J .
Angew. Chem., Int. Ed. Engl. 1997, 36, 2208. (h) Wang, Y.; DuBois, J .
L.; Hedman, B.; Hodgson, K. O.; Stack, T. D. P. Science 1998, 279,
(7) Blackburn, T. F.; Schwartz, J . J . Chem. Soc., Chem. Commun.
1977, 157.
(8) (a) Kaneda, K.; Fujii, M.; Morioka, K. J . Org. Chem. 1996, 61,
4502. (b) Kaneda, K.; Fujie, Y.; Ebitani, K. Tetrahedron Lett. 1997,
38, 9023.
(9) Peterson, K. P.; Larock, R. C. J . Org. Chem. 1998, 63, 3185.
(10) Other examples of palladium-catalyzed aerobic oxidation, see:
(a) Hronec, M.; Cvengrosov a´ , Z.; Kizlink, J . J . Mol. Catal. 1993, 83,
75. (b) G o´ mez-Bengoa, E.; Noheda, P.; Echavarren, A. M. Tetrahedron
Lett. 1994, 35, 7097. (c) Noronha, G.; Henry, P. M. J . Mol. Catal. A
1997, 120, 75.
5
37. (i) Chaudhuri, P.; Hess, M.; Fl o¨ rke, U.; Wieghardt, K. Angew.
Chem., Int. Ed. 1998, 37, 2217. (j) Mark o´ , I. E.; Gautier, A.; Chell e´ -
Regnaut, I.; Giles, P. R.; Tsukazaki, M.; Urch, C. J .; Brown, S. M. J .
Org. Chem. 1998, 63, 7576.
(5) (a) Heyns, K.; Blazejewicz, L. Tetrahedron 1960, 9, 67. (b) J ia,
C.-G.; J ing, F.-Y.; Hu, W.-D.; Huang, M.-Y.; J iang, Y.-Y. J . Mol. Catal.
(11) (a) Nishimura, T.; Onoue, T.; Ohe, K.; Uemura, S. Tetrahedron
Lett. 1998, 39, 6011. (b) Application of a similar catalytic system for
the reaction of tert-cyclobutanols: Nishimura, T.; Ohe, K.; Uemura,
S. J . Am. Chem. Soc. 1999, 121, 2645.
1
1
994, 91, 139.
6) Martin, J .; Martin, C.; Faraj, M.; Br e´ geault, J .-M. Nouv. J . Chim.
984, 8, 141.
(
1
0.1021/jo9906734 CCC: $18.00 © 1999 American Chemical Society
Published on Web 08/06/1999

Palladium(II)-Catalyzed Oxidation of Alcohols by Molecular Oxygen
J . Org. Chem., Vol. 64, No. 18, 1999 6751
Ta ble 1. P d (II)-Ca ta lyzed Oxid a tion of Ben zyl Alcoh ol
by Molecu la r Oxygen in th e P r esen ce of Va r iou s
a
P yr id in e Der iva tives
F igu r e 1. Time profile of the oxidation of p-chlorobenzyl
alcohol: effect of the amount of pyridine to product yield.
lower temperatures the rate of oxidation was slower. On
the other hand, in refluxing toluene, the color of the
reaction mixture immediately turned from yellow to black
and the catalyst became deactivated. In solvents such as
CH Cl , THF, Et O, and 1,4-dioxane the product yield
2 2 2
greatly diminished.
Further results obtained with a wide variety of alcohols
together with mechanistic considerations are described
below.
Oxid a tion of Ben zylic Alcoh ols. The scope of this
optimized procedure for the oxidation of various benzylic
alcohols is indicated by the results listed in Table 2.
Primary benzylic alcohols were converted to the corre-
sponding aldehydes in 92-96% yields within 2 h (Table
a
Reaction conditions: Pd(OAc)2 (0.05 mmol), benzyl alcohol (1.0
mmol), base (0.2 mmol), toluene (10 mL), MS3A (500 mg), O2, 80
°
b
C, 2 h. Bibenzyl was used as an internal standard.
2
, entries 1-8). It is noteworthy that this catalytic system
shows the tolerance of a variety of substituents on
aromatic nuclei. The amount of Pd(OAc) could be
The rate of oxidation largely depends on the organic
bases employed. Although a previous study indicated that
pyridine assured the best yields of carbonyl compounds,
different pyridine derivatives were examined in the
oxidation of benzyl alcohol (eq 1, Table 1). 2-Substituted
pyridines did not show significant differences from
pyridine, but pyridines with bulky substituents at the
2
reduced to 1 mol %, but a longer reaction time was
required for quantitative conversion (12 h, Table 2, entry
5
). For practical purposes, a slightly large-scale oxidation
of p-methoxybenzyl alcohol (1.38 g, 10.0 mmol) was
carried out to give p-methoxybenzaldehyde (1.29 g, 9.50
mmol, Table 2, entry 6). In the oxidation of 3-phenoxy-
benzyl alcohol (Table 2, entry 8), the Pd metal precipi-
tated under the standard conditions, but the reaction
again proceeded smoothly without precipitation of Pd
metal when excess pyridine (1 mmol) was employed.
Secondary benzylic alcohols were also easily oxidized to
the corresponding ketones in high yields (Table 2, entries
2
,6-position were found to be less effective (Table 1,
entries 2-5). Interestingly, when 2,2′-bipyridine was
used, Pd was produced and the reaction did not proceed
catalytically (Table 1, entry 6). Next, the effect of the
amount of pyridine on the oxidation of p-chlorobenzyl
alcohol was investigated (Figure 1). In the absence of
pyridine, oxidation was slow. To achieve efficient catalytic
9
-11). However, the oxidation of benzoin was relatively
oxidation, at least 4 molar equiv of pyridine to Pd(OAc)
is needed.
2
slow, and the corresponding diketone was obtained in
only 63% isolated yield even after 19 h (Table 2, entry
The concentration of substrates is also crucial for the
successful oxidation of alcohols. When the reaction was
carried out with 0.2 M of benzyl alcohol under the above-
described conditions, the reaction mixture turned black
and Pd was produced, resulting in slow reaction. Even
in this case, the addition of excess pyridine improved the
product yield and reaction rate.
1
2).
Oxid a tion of P r im a r y Alcoh ols. Next, we investi-
gated the oxidation of the saturated primary alcohols
Table 3). Aliphatic primary alcohols were smoothly
(
oxidized to the corresponding aldehydes selectively in
high yields without any formation of carboxylic acids or
their esters. The oxidation of 1-octadecanol afforded
Other palladium reagents, i.e., PdCl
Pd(OCOCF , Pd(dba) , and Pd(PPh
2
, PdCl
proved ineffective.
2
, but continuous bubbling
2 3 2
(CH CN) ,
1
-octadecanal in 95% isolated yield within 2 h (Table 3,
3
)
2
2
3 4
)
entry 1). It should be noted that this catalyst system
showed the compatibility with various hydroxyl protect-
ing groups such as tetrahydropyranyl ether (THPO, Table
Air could be used instead of O
was required over long reaction times.12 The conversion
of benzyl alcohol was complete at 80 °C for 2 h, but at
3
3
, entry 4), tert-butyldimethylsilyl ether (TBSO, Table
, entries 5 and 6) and benzyl ether (BnO, Table 3, entry
(
12) The oxidation of benzyl alcohol with air gave benzaldehyde in
7
4% yield after 2 h.
7). When the oxidation by the present procedure was

6
752 J . Org. Chem., Vol. 64, No. 18, 1999
Nishimura et al.
Ta ble 2. P d (II)-Ca ta lyzed Oxid a tion of Ben zylic
Alcoh ols by Molecu la r Oxygen a
Ta ble 3. P d (II)-Ca ta lyzed Oxid a tion of P r im a r y Alcoh ols
by Molecu la r Oxygen a
a
Reaction conditions: see footnote a of Table 2. b The value in
c
parentheses is the conversion of the alcohol (%). In the absence
of MS3A. d Pyridine (1 mmol), for 4 h.
Ta ble 4. P d (II)-Ca ta lyzed Oxid a tion of Diols by
Molecu la r Oxygen a
a
Reaction conditions: Pd(OAc)2 (0.05 mmol), alcohol (1.0 mmol),
pyridine (0.2 mmol), MS3A (500 mg), toluene (10 mL), O2, 80 °C,
b
2
(
h. The value in parentheses is the conversion of the alcohol
c
d
e
%). GLC yield. 1 mol % Pd(OAc)2, for 12 h. 10-Fold scale
reaction using 1 mol % Pd(OAc)2 and 1.00 g of MS3A for 12 h.
f
g
Pyridine (1 mmol), for 5 h. For 19 h.
a
b
Reaction conditions: see footnote a of Table 2. Substrates
applied to R,ω-primary diols (Table 4), the corresponding
were completely consumed. c GLC yield. d Determined by H NMR.
1
lactones were obtained in good yields as expected (entries
1
-3).13 A selective oxidative lactonization of unsym-
hols were also readily oxidized using the same catalytic
system as summarized in Table 5. Acetate group was not
affected during the reaction (Table 5, entry 4). Further-
more, even in the reaction of sterically hindered second-
ary alcohols such as borneol (Table 5, entry 5) and
menthol (Table 5, entry 6), the corresponding ketones
were obtained in high yields.
Oxid a tion of Alk en ic Alcoh ols. The oxidation of
alkenic alcohols including allylic ones was carried out
under the same condition. The oxidation of cinnamyl
alcohol was sluggish and Pd metal precipitated, resulting
in a formation of only 65% of cinnamaldehyde even by
prolonging the reaction time to 12 h under the identical
condition (Table 6, entries 1 and 2). However, the
production of Pd metal could be avoided using a quite
excess of pyridine (25 times as much compared with that
of the standard condition) and cinnamaldehyde was
obtained in 91% isolated yield after 4 h (Table 6, entry
metrical diol such as shown in entry 4 of Table 4 has
been accomplished by using ruthenium and rhodium
1
4
15
catalysts in the presence of a hydrogen acceptor, and in
these cases the lactone 2 was obtained selectively;
namely, a sterically less hindered hydroxyl group can be
oxidized first, followed by the formation of lactol and then
the oxidation to lactone. A similar type oxidation cata-
lyzed by palladium using bromobenzene as cooxidant was
also reported, but the selectivity was low (1/2 ) 62/38).16
Unfortunately, the oxidative lactonization of unsym-
metrical diol in our system did not show any chemo-
selectivity (Table 4, entry 4).
Oxid a tion of Secon d a r y Alcoh ols. Secondary alco-
(
13) Procter, G. In Comprehensive Organic Synthesis; Ley, S. V., Ed.;
Pergamon: Oxford, U.K., 1991; Vol. 7, pp 312-318.
14) (a) Ishii, Y.; Osakada, K.; Ikariya, T.; Saburi, M.; Yoshikawa,
(
S. J . Org. Chem. 1986, 51, 2034. (b) Murahashi, S.-I.; Naota, T.; Ito,
K.; Maeda, Y.; Taki, H. J . Org. Chem. 1987, 52, 4319.
(
15) Ishii, Y.; Suzuki, K.; Ikariya, T.; Saburi, M.; Yoshikawa, S. J .
Org. Chem. 1986, 51, 2822.
16) Tamaru, Y.; Yamada, Y.; Inoue, K.; Yamamoto, Y.; Yoshida, Z.
J . Org. Chem. 1983, 48, 1286.
3
). This effect suggests that the strong complexation of
palladium by the alkene, which might accelerate the
reduction of Pd(II), could be inhibited by the coordination
7
(

Palladium(II)-Catalyzed Oxidation of Alcohols by Molecular Oxygen
J . Org. Chem., Vol. 64, No. 18, 1999 6753
Ta ble 5. P d (II)-Ca ta lyzed Oxid a tion of Secon d a r y
a
Alcoh ols by Molecu la r Oxygen
F igu r e 2.
Sch em e 1. P la u sible Rea ction P a th w a y
a
b
Reaction conditions: see footnote a of Table 2. The value in
c
parenthesis is the conversion of the alcohol (%). In the absence
of MS3A.
Ta ble 6. P d (II)-Ca ta lyzed Oxid a tion of Alk en ic Alcoh ols
a
by Molecu la r Oxygen
some sterically hindered pyridine derivative such as 2,6-
lutidine, but a significant difference in selectivity was not
observed.
Rea ction P a th w a y. We suppose that the divalent
palladium complex works as an active species throughout
the reaction (Scheme 1). The reaction proceeds via the
1
7
formation of a Pd(II)-alcoholate from an alcohol and a
Pd(II)-pyridine complex18 followed by â-elimination of a
Pd(II)-hydride species from the alcoholate. The Pd(II)-
hydride species can react with molecular oxygen to give
a Pd(II)-hydroperoxide species, and this reactive species
subsequently undergoes ligand exchange with alcohol to
a
Reaction conditions: see footnote a of Table 2. b The value in
c
parentheses is the conversion of the alcohol (%). For 12 h.
d
Pyridine (5 mmol), for 4 h. GLC yield. f For 15 h. Pyridine (5
e
g
19
mmol), for 6 h.
of excess pyridine. Some allylic alcohols could be oxidized
to the corresponding aldehydes and ketones in good yields
using an excess of pyridine (Table 6, entries 4 and 5). In
the oxidation of citronerol, the effect of the use of excess
pyridine was small (Table 6, entries 6 and 7).
Lim itation s. Although it was revealed that the present
catalytic system was effective for the oxidation of a wide
variety of alcohols, there were some limitations for
substrates to be oxidized (Figure 2). The compounds 1
and 2, which were not oxidized with other reagents such
as tetrapropylammonium perruthenate (TPAP),2g also
failed to undergo the oxidation. The oxidation of the
alcohols 3-5 was relatively slow, and many unidentified
products were obtained in every case even using an
excess of pyridine. The compounds 6 and 7 failed to be
oxidized. The chemoselective oxidation between primary
and secondary hydroxyl groups was attempted using
reproduce the Pd(II)-alcoholate and H . To detect H
2
O
2
2 2
O
produced, the qualitative test for H O with KI containing
2
2
starch was carried out for an aqueous layer extracted
from the reaction mixture (Scheme 2). The rapid change
of the color from light yellow to dark blue was observed
in the layer obtained from the reaction without MS3A
(Scheme 2, entry 2). On the other hand, the same test
was negative for that obtained from the reaction with
MS3A (Scheme 2, entry 3). These results suggest that
2 2
H O is produced during the reaction and absorbed and/
(
17) Tsuji, J . In Palladium Reagents and Catalysis; J ohn Wiley; New
York, 1995; p 105.
18) Kravtsova, S. V.; Romm, I. P.; Stash, A. I.; Belsky, V. K. Acta
Crystallogr. 1996, C52, 2201.
19) For the formation of a PdOOH species from a palladium species
(
(
and an oxygen, see, for example: (a) Hosokawa, T.; Murahashi, S.-I.
Acc. Chem. Res. 1990, 23, 49. (b) Takehira, K; Hayakawa, T.; Orita,
H. Chem. Lett. 1985, 1835 and references therein.

6
754 J . Org. Chem., Vol. 64, No. 18, 1999
Nishimura et al.
F igu r e 3. Time profile of the oxidation of benzyl alcohol in
the absence of MS3A: the relation of yield and O uptake.
F igu r e 4. Time profile of the oxidation of benzyl alcohol in
the presence of MS3A: the relation of yield and O uptake.
2
2
Sch em e 2. Qu a lita tive An a lysis of Hyd r ogen
P er oxid e
reoxidant. The reaction has been revealed to be compat-
ible with various substituents and protecting groups.
Exp er im en ta l Section
1
H NMR spectra were obtained in CDCl
Si as an internal standard. 13C NMR spectra were
obtained at 67.8 or 100 MHz.
Ma ter ia ls. Pd(OAc) and PdCl
Pure Chemical Ind., Ltd., and used without further purifica-
3
at 270 or 400 MHz
with Me
4
2
2
were purchased from Wako
2
0
21
tion. Pd(OCOCF
and Pd(PPh )
3 4
3
)
2
,
Pd(dba)
2
(dba ) dibenzylideneacetone),
2
2
were synthesized by the literature methods.
Pyridine and other bases were purchased and used without
further purification. Solvents were dried and distilled by
known methods. MS3A was commercially available from
Aldrich Chemical Co., Inc., which was activated by calcination
just before use. All of the alcohols except six described below
were commercially available and purified by normal methods
just before use. Each compound prepared by known method
was purified by column chromatography on silica gel (eluents,
hexane-ethyl acetate).
or decomposed to O
separately confirmed that 30% aqueous H
ately decomposed to generate oxygen in toluene at 80 °C
in the presence of pyridine and MS3A. The step of the
ligand exchange between the Pd(II)-hydroperoxide spe-
cies and alcohol would exist in equilibrium and be
favorable for the Pd(II)-alcoholate under low H con-
centration because of the greater acidity of H O relative
to alcohols. Therefore, the presence of MS3A accelerated
the oxidation by absorbing and/or partly decomposing
2
and H
2
O by MS3A. In fact, we
immedi-
2
O
2
8-(Tetr a h yd r op yr a n -2-yl)oxy-1-octa n ol (Ta ble 3, en tr y
4). The compound was prepared by the protection of one
hydroxyl group of 1,8-octanediol (1 equiv of dihydropyran and
2
3
1
2 2
montmorillonite K10 in CH Cl ): colorless oil; H NMR (400
2
O
2
MHz) δ 1.26-1.90 (m, 19H), 3.38 (dt, J ) 9.3, 6.8 Hz, 1H),
2
2
3
6
)
.47-3.54 (m, 1H), 3.64 (t, J ) 6.8 Hz, 2H), 3.74 (dt, J ) 9.8,
.8 Hz, 1H), 3.87 (ddd, J ) 10.8, 8.4, 3.2 Hz, 1H), 4.57 (dd, J
13
4.4, 2.7 Hz, 1H); C NMR (100 MHz) δ 19.7, 25.5, 25.7, 26.2,
H
2
O
2
to O
2
and water (eqs 2 and 3, Scheme 2). Further-
29.4, 29.4, 29.7, 30.8, 32.8, 62.4, 63.1, 67.7, 98.9.
more, an additional evidence for the proposed mechanism
was obtained from the study of an oxygen uptake in the
oxidation of benzyl alcohol (eq 4). In the oxidation of
benzyl alcohol without MS3A, ca. 1:1 ratio of the oxygen
uptake to benzaldehyde yield was observed (Figure 3),
whereas ca. 2:3 ratio was measured when the reaction
was carried out in the presence of MS3A, showing the in
situ formation of oxygen during the oxidation (Figure 4).
8-ter t-Bu tyld im eth ylsilyloxy-1-octa n ol (Ta ble 3, en tr y
5). The compound was prepared by the protection of one
hydroxyl group of 1,8-octanediol (1 equiv of tert-butylchlo-
2
4
rodimethylsilane and imidazole in dimethylformamide): col-
1
orless oil; H NMR (400 MHz) δ 0.03 (s, 6H), 0.86 (s, 9H), 1.20-
1
.58 (m, 12H), 1.96 (br s, 1H), 3.57 (t, J ) 7.2 Hz, 2H), 3.58 (t,
13
J ) 7.2 Hz, 2H); C NMR (100 MHz) δ -5.3, 18.3, 25.6, 25.9,
9.3, 32.7, 32.8, 62.8, 63.2.
-t er t -Bu t yld im e t h ylsilyloxy-2-m e t h yl-1-p r op a n ol
Ta ble 3, en t r y 6). The compound was similarly prepared
from 2-methyl-1,3-propanediol (1 equiv of tert-butylchlorodi-
2
3
(
2
4
methylsilane and imidazole in dimethylformamide): colorless
oil; H NMR (400 MHz) δ 0.01 (s, 6H), 0.79 (d, J ) 6.8 Hz,
3
1
H), 0.84 (s, 9H), 1.79-1.92 (m, 1H), 3.09 (br s, 1H), 3.49 (dd,
J ) 9.6, 8.0 Hz, 1H), 3.53-3.54 (m, 2H), 3.64 (dd, J ) 9.6, 4.4
Hz, 1H); 13C NMR (100 MHz) δ -5.7, 13.0, 18.1, 25.7, 37.1,
6
7.6, 68.1.
Although the role of pyridine bases is unknown, we
suppose that pyridines coordinate with Pd(II) to stabilize
the Pd(II)-hydride species preventing reductive elimina-
tion of HX.
(
20) Stephenson, T. A.; Morehouse, S. M.; Powell, A. R.; Heffer, J .
P.; Wilkinson, G. J . Chem. Soc. 1965, 3632.
21) Ukai, T.; Kawazura, H.; Ishii, Y. J . Organomet. Chem. 1974,
65, 253.
(
Con clu sion . A system of simple combination of com-
(
(
(
22) Coulson, D. R. Inorg. Synth. 1972, 13, 121.
23) Hoyer, S.; Laszlo, P.; Orlovic, M.; Polla, E. Synthesis 1979, 618.
24) Corey, E. J .; Venkateswarlu, A. J . Am. Chem. Soc. 1972, 94,
mercially available reagents, Pd(OAc)
has shown a high catalytic activity for aerobic oxidation
of benzylic and aliphatic alcohols using O as a sole
2
/pyridine/MS3A,
2
6190.

Palladium(II)-Catalyzed Oxidation of Alcohols by Molecular Oxygen
J . Org. Chem., Vol. 64, No. 18, 1999 6755
1
3
-Ben zyloxy-2-m eth yl-1-p r op a n ol (Ta ble 3, en tr y 7).
provide a product. Products obtained were determined by H
and 13C NMR and GC/MS. GLC yields were determined using
bibenzyl as an internal standard.
The compound was prepared from 2-methyl-1,3-propanediol
2
5
1
with NaH and benzyl bromide: colorless oil; H NMR (400
MHz) δ 0.87 (d, J ) 7.3 Hz, 3H), 1.97-2.11 (m, 1H), 2.70 (br
s, 1H), 3.42 (dd, J ) 9.1, 7.8 Hz, 1H), 3.51 (dd, J ) 9.1, 7.9 Hz,
8-(Tetr a h yd r op yr a n -2-yl)oxyocta n a l (Ta ble 3, en tr y 4):
1
colorless oil; H NMR (400 MHz) δ 1.10-1.90 (m, 16H), 2.41
1
H), 3.57 (dd, J ) 10.8, 6.3 Hz, 1H), 3.60 (dd, J ) 10.8, 4.9
(td, J ) 7.2, 2.0 Hz, 2H), 3.37 (dt, J ) 9.2, 6.8 Hz, 1H), 3.45-
3.53 (m, 1H), 3.72 (dt, J ) 9.2, 6.8 Hz, 1H), 3.86 (ddd, J )
1
3
Hz, 1H), 4.50 (s, 2H), 7.23-7.36 (m, 5H); C NMR (100 MHz)
δ 13.4, 35.5, 67.7, 73.4, 75.3, 127.6, 127.7, 128.4, 138.0.
10.8, 7.2, 3.6 Hz, 1H), 4.56 (dd, J ) 4.4, 3.0 Hz, 1H), 9.75 (t, J
2
,2-Dim eth yl-1,5-p en ta n ed iol (Ta ble 4, en tr y 4). The
) 2.0 Hz, 1H); 13C NMR (100 MHz) δ 19.7, 22.0, 25.5, 26.0,
compound was prepared by the hydroboration-oxidation of
29.1, 29.2, 29.7, 30.8, 43.9, 62.4, 67.5, 98.9, 202.8.
1
2
0
2
,2-dimethyl-4-pentenal: colorless oil; H NMR (270 MHz) δ
.89 (s, 6H), 1.25-1.35 (m, 2H), 1.48-1.60 (m, 2H), 1.87 (br s,
8
-ter t-Bu tyld im eth ylsiloxyocta n a l (Ta ble 3, en tr y 5):
1
colorless oil; H NMR (400 MHz) δ 0.03 (s, 6H), 0.88 (s, 9H),
1
3
H), 3.33 (s, 2H), 3.64 (t, J ) 6.3 Hz, 2H); C NMR (100 MHz)
1
.24-1.37 (m, 6H), 1.45-1.66 (m, 4H), 2.41 (td, J ) 7.2, 2.0
δ 24.0, 27.0, 34.3, 34.8, 63.6, 71.3.
-Acetoxy-2-p en ta n ol (Ta ble 5, en tr y 4). The compound
was prepared by the protection of a primary hydroxyl group
13
Hz, 2H), 3.58 (t, J ) 7.2 Hz, 2H), 9.75 (t, J ) 2.0 Hz, 1H);
NMR (100 MHz) δ -5.3, 18.4, 22.0, 25.6, 26.0, 29.1, 32.7, 43.9,
3.2, 202.8.
-ter t-Bu tyld im eth ylsiloxy-2-m eth ylp r op a n a l (Ta ble 3,
C
5
6
2
6
of 1,4-pentanediol with acetic anhydride in pyridine: colorless
3
1
oil; H NMR (400 MHz) δ 1.21 (d, J ) 5.9 Hz, 3H), 1.50 (td, J
1
en tr y 6): colorless oil; H NMR (400 MHz) δ 0.05 (s, 6H), 0.88
)
7.8, 5.9 Hz, 2H), 1.62-1.83 (m, 2H), 2.05 (s, 3H), 2.07 (br s,
(
s, 9H), 1.09 (d, J ) 7.3 Hz, 3H), 2.48-2.56 (m, 1H), 3.79 (dd,
1
H), 3.83 (qt, J ) 5.9, 5.9 Hz, 1H), 4.09 (t, J ) 6.6 Hz, 2H);
C NMR (100 MHz) δ 21.0, 23.6, 25.0, 35.5, 64.6, 67.5, 171.3.
J ) 10.2, 6.2 Hz, 1H), 3.87 (dd, J ) 10.2, 5.4 Hz, 1H), 9.74 (d,
1
3
13
J ) 1.6 Hz, 1H); C NMR (100 MHz) δ -5.5, 10.3, 18.2, 25.8,
Gen er a l P r oced u r e for P d (OAc)
of Alcoh ols Usin g Molecu la r Oxygen . A typical experi-
mental procedure is as follows: to a mixture of Pd(OAc) (0.05
mmol) and toluene (6 mL) in a 20 mL two-necked flask were
added pyridine (0.2 or 5 mmol) and MS3A (500 mg). The brown
suspension turned to a yellow-white suspension when pyridine
was added. Oxygen gas was introduced into the flask from an
2
-Ca ta lyzed Oxid a tion
4
8.8, 63.4, 204,7.
3
-Ben zyloxy-2-m eth ylp r op a n a l (Ta ble 3, en tr y 7): col-
2
1
orless oil; H NMR (400 MHz) δ 1.13 (d, J ) 6.8 Hz, 3H), 2.61-
2
6
.71 (m, 1H), 3.64 (dd, J ) 9.5, 5.1 Hz, 1H), 3.68 (dd, J ) 9.5,
.6 Hz, 1H), 4.52 (s, 2H), 7.25-7.37 (m, 5H), 9.72 (d, J ) 1.5
1
3
Hz, 1H); C NMR (100 MHz) δ 10.7, 46.8, 70.1, 73.3, 127.6,
1
27.7, 128.4, 137.9, 203.9.
-Acetoxy-2-p en ta n on e (Ta ble 5, en tr y 4): colorless oil;
H NMR (400 MHz) δ 1.91 (tt, J ) 7.3, 6.4 Hz, 2H), 2.05 (s,
2
O -balloon under atmospheric pressure, and the mixture was
5
heated to 80 °C for ca. 10 min. Then, an alcohol (1 mmol) in
toluene (4 mL) was added using a syringe pump, and the
mixture was stirred for 2 h (or appropriate time) at 80 °C
under oxygen. After the reaction, the mixture was filtered
through a pad of Florisil. Removal of the solvent under the
reduced pressure left an oily residue, which was subjected to
column chromatography (eluents, hexane-diethyl ether) to
1
3
2
2
H), 2.16 (s, 3H), 2.53 (t, J ) 7.3 Hz, 2H), 4.07 (t, J ) 6.4 Hz,
H); 13C NMR (100 MHz) δ 20.9, 22.8, 29.9, 39.9, 63.6, 171.0,
07.6.
Ack n ow led gm en t. T.N. gratefully acknowledges a
Fellowship of the J apan Society for the Promotion of
Science for Young Scientists.
(
25) Fukuzawa, A.; Sato, H.; Masamune, T. Tetrahedron Lett. 1987,
8, 4303.
26) Zhdanov, R. I.; Zhenodarova, S. M. Synthesis 1975, 222.
2
(
J O9906734