Oxygen transfer from sulfoxides: Selective oxidation of alcohols catalyzed by polyoxomolybdates

Article abstract of DOI:10.1021/jo0255577

Benzylic, allylic, and aliphatic alcohols are oxidized to aldehydes and ketones in a reaction catalyzed by Keggin-type polyoxomolybdates, PV_xMo_(12-x)O₄₀^-(3+x) (x = 0, 2), with DMSO as a solvent. The oxidation of benzylic alcohols is quantitative within hours and selective, whereas that of allylic alcohols is less selective. Oxidation of aliphatic alcohols is slower but selective. Further mechanistic studies revealed that, for H₃PMo₁₂O₄₀ as a catalyst and benzylic alcohols as substrates, the sulfoxide is in fact an oxygen donor in the reaction. Postulated reaction steps as determined from isotopelabeling experiments, kinetic isotope effects, and Hammett plots include (a) sulfoxide activation by complexation to the polyoxometalate and (b) oxygen transfer from the activated sulfoxide and elimination of water from the alcohol. The mechanism is supported by the reaction kinetics.

Full text of DOI:10.1021/jo0255577

Oxygen Tr a n sfer fr om Su lfoxid es: Selective Oxid a tion of Alcoh ols
Ca ta lyzed by P olyoxom olybd a tes
Alexander M. Khenkin and Ronny Neumann*
Department of Organic Chemistry, Weizmann Institute of Science, Rehovot, Israel, 76100
ronny.neumann@weizmann.ac.il
Received J anuary 28, 2002
Benzylic, allylic, and aliphatic alcohols are oxidized to aldehydes and ketones in a reaction catalyzed
-
(3+x)
by Keggin-type polyoxomolybdates, PV
x
Mo(12-x)
O
40
(x ) 0, 2), with DMSO as a solvent. The
oxidation of benzylic alcohols is quantitative within hours and selective, whereas that of allylic
alcohols is less selective. Oxidation of aliphatic alcohols is slower but selective. Further mechanistic
3
studies revealed that, for H PMo12O40 as a catalyst and benzylic alcohols as substrates, the sulfoxide
is in fact an oxygen donor in the reaction. Postulated reaction steps as determined from isotope-
labeling experiments, kinetic isotope effects, and Hammett plots include (a) sulfoxide activation
by complexation to the polyoxometalate and (b) oxygen transfer from the activated sulfoxide and
elimination of water from the alcohol. The mechanism is supported by the reaction kinetics.
In tr od u ction
schemes. First, via a free radical-type autoxidation
notably using Co(III) in combination with N-hydroxy-
phthalimide, but also with soluble chromium species.
Second, using stable nitroxyl radicals as catalyst precur-
sors allows reactions to be carried out using a variety of
cocatalysts.9
The selective oxidation of alcohol substrates to alde-
hydes and ketones is an important goal in the develop-
ment of modern and environmentally friendly methods
for chemical synthesis.1 In this context, the use of
oxidants such as molecular oxygen from air and hydrogen
peroxide, which are intrinsically non-waste-producing, is
of special importance. Homogeneous aerobic oxidations
usually proceed by a â-hydride elimination process of an
alkoxy-metal intermediate or by a so-called oxometal
pathway. The former pathway is often observed in
reactions catalyzed by late transition metal compounds
7
8
We have had an ongoing interest in the catalytic
1
0
activity of polyoxometalates in oxidation reactions, with
oxygen donors such as molecular oxygen, hydrogen
peroxide, ozone, nitrous oxide, iodosobenzene, periodate,
and others. In this context, it has also been found that
polyoxometalates, most advantageously the phospho-
5
-
2
vanadomolybdate, PV Mo10O40 , Figure 1, effectively
2
3
4
and complexes based on Ru(II), Pd(II), and Cu(I/II),
whereas the latter mechanism is more typical of high-
catalyze the oxidative dehydrogenation of alcohols, es-
pecially benzylic alcohols, using either active carbon
supports or quinones as cocatalysts.11
We have now undertaken a reinvestigation of our
earlier research in this area in an effort to expand the
-
5
valent RuO
4
4
and OsO . Recently, alcohol oxidation in
aqueous media was shown to be possible using a water
6
soluble palladium(II) bathophenanthroline catalyst. Aero-
bic alcohol oxidation is also possible by other mechanistic
(
5) Marko, I. E.; Giles, P. R.; Tsukazaki, M.; Chell e´ -Regnaut, I.;
(
1) Sheldon, R. A.; Arends, I. W. C. E.; Dijksman, A. Catal. Today
000, 57, 157-166.
2) (a) Matsumoto, M.; Ito, J . J . Chem. Soc., Chem. Commun. 1981,
07. (b) Tang, R.; Diamond, S. E.; Neary, N.; Mares, F. J . Chem. Soc.,
Urch, C. J .; Brown, S, M. J . Am. Chem. Soc. 1997, 119, 12661. (b)
Colemab, K. S.; Lorber, C. Y.; Osborn, J . A. Eur. J . Inorg. Chem. 1998,
1673. (c) Coleman, K. S.; Coppe, M.; Thomas, C.; Osborn, J . A.
Tetrahedron Lett. 1999, 40, 3723. (d) Lenz, R.; Ley, S. V. J . Chem.
Soc., Perkin Trans. 1 1997, 3291.
(6) ten Brink, G.-J .; Arends, I. W. C. E.; Sheldon, R. A. Science 2000,
287, 1636.
2
(
9
Chem. Commun. 1978, 562. (c) Bilgrien, C.; Davis, S.; Drago, R. S. J .
Am. Chem. Soc. 1987, 109, 3786. (d) B a¨ ckvall, J .-E.; Chaudhury, R.
L.; Karlsson, U. J . Chem. Soc., Chem. Commun. 1991, 473. (e) Wang,
G.-Z.; Andreasson, U.; B a¨ ckvall, J .-E. J . Chem. Soc., Chem. Commun.
(7) Iwahama, T.; Sakaguchi, S.; Nishiyama, Y.; Ishii, Y. Tetrahedron
Lett. 1995, 39, 6011.
1
994, 1037. (f) Hanyu, A.; Takezawa, E.; Sakaguchi, S. Ishii, Y.
Tetrahedron Lett. 1998, 5557. (g) Dijksman, A.; Arends, I. W. C. E.;
Sheldon, R. A. Chem. Commun. 1999, 1591.
(8) Chen, J . D.; Lempers, H. E. B.; Sheldon, R. A. J . Chem. Soc.,
Faraday Trans. 1996, 92, 1807.
(
3) (a) Blackburn, T. F.; Schartz, J . J . Chem. Soc., Chem. Commun.
(9) (a) Semmelhack, M. F.; Scmid, C. R.; Cort e´ s, D. A.; Chou, C. S.
J . Am. Chem. Soc. 1984, 106, 3374. (b) Dijksman, A.; Arends, I. W. C.
E.; Sheldon, R. A. Chem. Commun. 1999, 1591. (c) Ben-Daniel, R.;
Alsters, P.; Neumann, R. J . Org. Chem. 2001, 66, 8650. (d) Cecchetto,
A.; Fontana, F.; Minisci, F.; Recupero, F. Tetrahedron Lett. 2001, 42,
6651.
(10) (a) Mizuno, N.; Misono, M. Chem. Rev. 1998, 98, 199. (b) Hill,
C. L.; Prosser-McCartha, C. M. Coord. Chem. Rev. 1995, 143, 407. (c)
Kozhevnikov, I. V. Chem. Rev. 1998, 98, 171. (d) Neumann, R. Prog.
Inorg. Chem. 1998, 47, 317-370.
(11) Neumann, R.; Levin, M. J . Org. Chem. 1991, 56, 5707. (b)
Khenkin, A. M.; Vigdergauz, I.; Neumann, R. Chem. Eur. J . 2000, 6,
875.
1
1
1
977, 157. (b) A ¨ı t-Mohand, S.; H e´ nin, F.; Muzart, J . Tetrahedron Lett.
995, 36, 2473. (c) A ¨ı t-Mohand, S.; Muzart, J . J . Mol. Catal. A 1998,
29, 135. (d) Nishimura, T.; Onoue, T.; Ohe, K.; Uemura, S. Tetra-
hedron Lett. 1998, 39, 6011.
4) (a) Skibida, I. P.; Sakharov, A. M. Catal. Today 1996, 27, 187.
b) Sakharov, A. M.; Skibida, I. P. J . Mol. Catal. 1988, 48, 157. (c)
(
(
Marko, I. E.; Giles, P. R.; Tsukazaki, M.; Brown, S. M.; Urch, C. J .
Science 1996, 274, 2044. (d) Marko, I. E.; Giles, P. R.; Tsukazaki, M.;
Chell e´ -Regnaut, I. Gautier, A.; Brown, S. M.; Urch, C. J . J . Org. Chem.
1
999, 64, 2433. (e) Marko, I. E.; Gautier, A.; Chell e´ -Regnaut, I.; Giles,
P. R.; Tsukazaki, M.; Urch, C. J .; Brown, S. M. J . Org. Chem. 1998,
6
3, 7576.
1
0.1021/jo0255577 CCC: $22.00 © 2002 American Chemical Society
Published on Web 09/05/2002
J . Org. Chem. 2002, 67, 7075-7079
7075

Khenkin and Neumann
TABLE 1. Aer obic Oxid a tion of Ben zylic Alcoh ols
Ca ta lyzed by H5P V2Mo12O40 in DMSOa
conversion,
mol %
substrate
benzyl alcohol
product
benzaldehyde
c
∼100 (85)
4
4
4
4
2
-methylbenzyl alcohol 4-methylbenzaldehyde
-methoxybenzyl alcohol 4-methoxybenzaldehyde
-bromobenzyl alcohol
-nitrobenzyl alcohol
-phenylethanol
∼100
c
∼100 (84)
4-bromobenzaldehyde
4-nitrobenzaldehyde
acetophenone
∼100
c
∼100 (86)
98
benzhydrol
4
benzophenone
4-pyridinecarboxaldehyde
100
100 (81)
-pyridinemethanolb
c
a
Reaction conditions: 1 M benzylic alcohol, 1 mM H5PV2Mo10O40
b
in 1 mL DMSO under 1 atm of O2 at 135 °C for 4 h. Reaction
time ) 10 h. c Isolated yields.
x
F IGURE 1. H(3+x)PV Mo(12-x)O40 polyoxometalate. Black ball
)
Mo, V; white ball ) O; P in center (not visible).
scope of the alcohol oxidative dehydrogenation and to
better understand the mechanism of such polyoxometa-
late-catalyzed reactions. During our search for a suitable
solvent for such a mechanistic investigation, we discov-
ered that dimethyl sulfoxide (DMSO) was by far a
superior solvent for polyoxomolybdate-catalyzed oxida-
tion of alcohols. Such success with DMSO has been
reported in the past for Pd(OAc)
2
-catalyzed reactions,12
and it has just recently been shown that in that case the
solvent acts as a ligand to prevent Pd(0) aggregation.13
Since DMSO activated by a variety of electrophilic
reagents is a well-known stoichiometric oxidant of sig-
nificant synthetic importance,14 it becomes clear that the
present mechanistic investigation must also consider the
possibility that the sulfoxide is a catalytically activated
oxygen donor in such systems.15
F IGURE 2. Rate of oxidation of benzyl alcohol catalyzed by
various polyoxometalates. Reaction conditions: 1 mmol of
benzyl alcohol, 1 µM polyoxometalate in 1 mL of DMSO at 135
2
°C under 1 atm of O .
but anaerobic conditions stopped within 2.5 h of reaction
at ∼40% conversion (400 turnovers) with formation of a
dark blue reduced form of the polyoxometalate; (d)
dimethyl sulfide was formed in the reaction, on average
Resu lts a n d Discu ssion
The initial oxidation reaction that was surveyed was
the aerobic oxidation of benzylic alcohols catalyzed by the
H PV Mo10O40 polyoxometalate in DMSO as a solvent,
5 2
∼
0.6 mol of dimethyl sulfide per mol of benzylic aldehyde.
In Figure 2 the initial rate of oxidation of benzyl alcohol
catalyzed by various polyoxometalates is presented.
Surprisingly, H 40, which was inactive in other
Table 1. From Table 1 one may observe that reactions
with a 0.1 mol % catalyst load are quantitative and highly
selective within 4 h, except for that with 4-pyridinemeth-
anol, which required 10 h, at 135 °C. The following
additional points connected to the results described in
Table 1 are worth noting: (a) even though the medium
is acidic, no byproduct formation of dibenzylic ether was
observed; (b) DMSO was a unique solvent, compared to
other polar and nonpolar solvents such as benzonitrile,
nitroethane, N-methypyrrolidone, sulfolane, nitroben-
zene, and xylene, which yielded significantly lower
conversions and selectivity (mostly formation of diben-
zylic ether); (c) oxidation of benzyl alcohol under identical
3
PMo12O
11
alcohol oxidation systems and other solvents, gave
results that were even slightly superior to those observed
with H
observation that ∼1 mol of dimethyl sulfide per mol of
benzylic aldehyde was formed in catalysis by H
Neutral Q PV 40 (Q ) tetra-n-
butylammonium) was significantly less effective as a
catalyst, while H 40 was ineffective.
It was also possible using H PV 40 or H
5 2
PV Mo10O40. Important here, however, is the
3
40
PMo12O .
5
2 3
Mo10O40 or Q PMo12O
3
PW12O
5
2
Mo10
O
3 40
PMo12O
under aerobic conditions to oxidize aliphatic and allylic
alcohols, Table 2. However, as may be observed, reactivity
in the case of aliphatic alcohols is reduced but selectivity
is retained, whereas for allylic alcohols, reactivity is high
but selectivity is lower.
(
12) (a) Peterson, K. P.; Larock, R. C.; J . Org. Chem. 1998, 63, 3185.
b) van Benthem, R. A. T. M.; Hiemstra, H.; van Leeuwen, P. W. N.
M.; Geus, J . W.; Speckamp, W. N. Angew. Chem., Int. Ed. Engl. 1995,
(
The results mentioned above, that ∼0.6 mol of di-
3
4, 457.
methyl sulfide per mol of benzylic aldehyde was formed
(13) Steinhoff, B. A.; Fix, S. R.; Stahl, S. S. J . Am. Chem. Soc. 2002,
1
24, 766.
(
in aerobic oxidation with H
dimethyl sulfide per mol of benzylic aldehyde was formed
in aerobic oxidation with H 40, indicated that for
40 the sulfoxide was the only oxidant, whereas
PV 40 was used both oxygen and the
5
PV
2
Mo10
O
40 but ∼1 mol of
14) (a) Mancuso, A. J .; Swern, D. Synthesis 1981, 165. (b) Tidwell,
T. T. Org. React. 1990, 39, 297. (c) Tidwell, T. T. Synthesis 1990, 857-
70.
15) (a) Kukushkin, V. Y. Coord. Chem. Rev. 1995, 139, 375. (b)
3
PMo12O
8
(
3
H PMo12O
Arterburn, J . B.; Perry, M. C. Org. Lett. 1999, 1, 769. (c) Coleman, K.
S.; Bedel, L. J . L.; Osborn, J . A. C. R. Acad. Sci. IIc 2000, 3, 765. (d)
Lobler, C. Y.; Pauls, I.; Osborn, J . A. Bull Soc. Chim. Fr. 1996, 133,
when H
5
2
Mo10O
sulfoxide were oxygen donors. Indeed, anaerobic oxida-
7
55.
tion of benzylic alcohols to quantitative yields was
7
076 J . Org. Chem., Vol. 67, No. 20, 2002

Oxygen Transfer from Sulfoxides
TABLE 2. Aer obic Oxid a tion of Alip h a tic a n d Allylic
a
Alcoh ols Ca ta lyzed by H5P V2Mo12O40 in DMSO
time,
h
product
(selectivity, mol %)
conversion,
mol %c
b
substrate
cinnamyl alcohol
0.75 cinnamaldehyde (100) ∼100
(
(
E)-2-hexen-1-ol
Z)-2-hexen-1-ol
2
(E)-2-hexenal (82)
(Z)-2-hexenal (78)
1-octen-3-one (90)
cyclohexen-2-one (52)
carvone (75)
79
2
3
0.5
3
83
1
-octen-3-ol
80 (48)d
82
cyclohexen-2-ol
carveol
96
geraniol
10
citral (43)
61
cyclooctanol
cyclohexanol
24
24
24
cyclooctanone (100)
cyclohexanone (100)
3-octanone
77
30
25
3
-octanol
a
Reaction conditions: 1 M alcohol, 1 mM H5PV2Mo10O40 in 1
b
mL of DMSO under 1 atm of O2 at 135 °C. Mol % of aldehyde
product of all products. Mol % of substrate reacted. d Isolated
yield.
F IGURE 4. Rate of reaction as a function of DMSO concen-
tration (inset: the corresponding Lineweaver-Burk plot).
Reaction conditions: 1 mmol of benzylic alcohol, 1 µmol of H -
3
c
PMo12
O
40, 0.1-1.5 mmol of DMSO in 1 mL of nitroethane
under 1 atm of Ar at 135 °C.
F IGURE 3. Reaction profile for oxidation of benzyl alcohol
in DMSO catalyzed by H
mmol of benzylic alcohol, 5 µmol of H
at 135 °C under Ar.
3
PMo12
O
40. Reaction conditions: 1
PMo12 40, 1 mL of DMSO
3
O
F IGURE 5. Hammett plot of the oxidation of benzylic alcohols
in DMSO catalyzed by H PMo O . Reaction conditions: 1
3
12 40
mmol of benzylic alcohol, 5 µmol of H
3
PMo12O40, 1 mL of DMSO
-
1
at 135 °C under Ar. kobs ) 1.92 ( 0.24 min (R ) H); 2.72 (
possible with H
40 in 1 mL of DMSO under 1 atm of Ar at 135
C for 4 h). It was decided to investigate this anaerobic
3
PMo12O40 (1 M benzylic alcohol, 1 mM
-
1
-1
0
.32 min (R ) Me); 6.5 ( 0.42 min (R ) OMe); 3.04 ( 0.32
1
3
H PMo12O
-
-1
-1
min (R ) Br); 4.01 ( 0.38 min (R ) CF
R ) NO ).
3
); 7.3 ( 0.51 min
°
(
2
oxidation of benzylic alcohols with the sulfoxide as an
oxidant more carefully. Under the conditions used, i.e.,
plot) as a function the DMSO concentration. In other
words, the reaction order changes from first order with
respect to DMSO at low concentration to zero order at
higher DMSO concentrations.
The observed or empiric rate equation may be sum-
marized as eq 1.
1
3
mmol of benzylic alcohol, 1 of µmol H PMo12O40 in 1
mL (∼14 mmol) of DMSO under 1 atm of Ar at 135 °C,
the reactions show a linear dependence of conversion as
a function of time, up to a conversion of 75-80% and thus
are concluded to be of an apparent or observed zero order
with respect to the benzylic alcohol, Figure 3. Notably,
at higher conversions, i.e., at benzylic alcohol concentra-
tions < 0.20 M), there is curvature in the plot, indicating
a change in the rate equation at low benzylic alcohol
concentrations.
d[aldehdye]/dt ) -d[alcohol]/dt )
1
1f0
0f1
kobs[POM] [DMSO] [alcohol]
(1)
Generally, reactions were carried out in DMSO as a
solvent. Under such conditions, i.e., excess DMSO, the
reaction kinetics are by definition pseudo zero order with
respect to DMSO. To find the true reaction order in
DMSO, it was necessary to use an alternative solvent
and DMSO as a limiting reagent. Thus, initial rates were
found for reactions carried out in nitroethane (a polar
nonprotic solvent similar to DMSO) at the following
In Figure 5 are presented as a Hammett plot the
results of the kinetics of the benzylic alcohol oxidation
with DMSO. The results indicate two mechanistic re-
gimes, one with a F value of -1.83 for electron-donating
substituents, 4-OCH
another with a F value of 0.65 for electron-withdrawing
substituents, 4-NO , 4-CF , and 4-Br relative to H. Thus,
3 3
and 4-CH relative to H, and
2
3
electron-donating substituents stabilize a positively
charged transition state and electron-withdrawing sub-
stituents stabilize a negatively charged transition state.
Kinetic isotope effects were measured for the oxidation
conditions: 1 mmol of benzylic alcohol, 1 µmol of H
40, 0.1-1.5 mmol of DMSO in 1 mL of nitroethane
under 1 atm of Ar at 135 °C. As may be observed, Figure
, the reaction is clearly of a Michaelis-Menton type
note the excellent correlation in the Lineweaver-Burk
3
-
PMo12
O
4
(
of XPhCD
2
OH/XPhCH
2
OH (X ) H, 4-OCH
3
, 4-NO
2
)
-
under the following reaction conditions: 0.5 M XPhCD
2
J . Org. Chem, Vol. 67, No. 20, 2002 7077

Khenkin and Neumann
SCHEME 1
OH, 0.5 M XPhCH
2
OH, 3.0 mM H
3
PMo12
O
40 in 1 mL of
From the experimental evidence a possible reaction
pathway for the oxidation may be postulated as follows.
DMSO at 135 °C. Kinetic isotope effects of 2.4-2.6 ( 0.1
were obtained for all three substituents. Additional
isotope-labeling experiments also yielded significant
First, a H
3
PMo12O40-sulfoxide complex is formed that
17
polarizes the S-O bond as evidenced by the O NMR,
1
7
31
insight. First, the O NMR of a solution of 1.4 M DMSO-
although there is no change in the P NMR of H
40 in the presence of DMSO. Additional support
of such a complex was obtained by heating DMSO and
40 in acetonitrile. Despite the fact that each
3
-
1
7
4
O (∼0 ppm, ∼5% enriched) and 2.8 mM Q
3
[PMo12
O
40
]
PMo12O
in nitroethane, heated at 120 °C for 1 h, showed only a
new peak at 182 ppm, indicating a coordination interac-
tion between DMSO and the polyoxomolybdate. This
chemical shift is distinctly different compared to chemical
shifts for bridging and terminal oxygens appearing at
3
H PMo12O
component by itself is soluble in acetonitrile, a precipitate
was formed whose elemental C,H analysis best fits a
complex of the formula (DMSO) H PMo12O40 [exptl (cal-
9 3
1
6
∼
500 and ∼900 ppm, respectively, and rules out oxygen
cd): C 8.78 (8.54); H 2.26 (2.25)]. The Hammett plot
indicates that oxidation of benzylic alcohols by the
DMSO-polyoxomolybdate complex proceeds via different
transition states for electron-donating and electron-
withdrawing substituents. The negative F value for
electron-donating substituents, e.g., methoxy, indicates
a transition with a partial positive charge at the benzylic
carbon, whereas the positive F value for electron-
withdrawing substituents, e.g., nitro, indicates a transi-
tion state with a partial negative charge at the benzylic
carbon. From this we propose, in general terms, oxidation
of benzylic alcohol in two different ways as presented in
Scheme 1.
4
exchange between the sulfoxide and Q
3
[PMo12
O
40]. Sec-
1
8
ond, a reaction between 1 mmol of DMSO- O (85%
enriched), 1 mmol of benzyl alcohol, and 3.3 µmol of
Q PMo12O40 in 1 mL of nitroethane at 135 °C under
3
Ar yielded benzaldehyde with 40% O enrichment.
1
8
17
1
6
Furthermore, a reaction between 1 M benzaldehyde- O
1
8
16
with 1 M H
2
O (95% enrichment) in DMSO- O at 135
°
3 40
C under Ar in the presence or absence of Q PMo12O
yielded after a few minutes benzaldehyde with ∼40% 18O
enrichment, which remained unchanged over time; how-
ever, the DMSO remained unlabeled. Finally, a reaction
using DMSO-d
in 1 mL of DMSO-d
yielded only dimethyl sulfide-d
. The latter is formed in Swern-type reactions, ruling
6
(1 M benzyl alcohol, 1 mM H
under 1 atm of Ar at 135 °C for 4 h)
and no dimethyl sulfide-
3 40
PMo12O
6
For reactions accelerated by electron-donating moi-
eties, the activated oxygen atom of the sulfoxide reacts
by nucleophilic attack at the benzylic carbon leading to
formation of a new carbon-oxygen bond (as indicated by
the isotope-labeling experiments) with the hydroxide
anion as a leaving group. Subsequently, dimethyl sulfide,
a proton, and polyoxometalate are eliminated as shown
with formation of the benzylic aldehyde. For reactions
accelerated by electron-withdrawing moieties, the sig-
6
d
5
out such a mechanism in this case. Furthermore, the use
of diphenylsulfoxide as a solvent is possible in these
reactions; reaction rates are up to 70% faster compared
to DMSO.
(16) Filowitz, M.; Ho, R. K. C.; Klemperer, W. G.; Shum, W. Inorg.
Chem. 1979, 18, 93.
1
8
4
nificantly higher acidity (many orders of magnitude) of
(17)
3 3
Q [PMo12O40] was used instead of H PMo12O40, despite the
lower rates, because the latter is a hydrate, which would complicate
the interpretation of the results.
(18) Bordwell, F. G. Pure Appl. Chem. 1977, 49, 963.
7
078 J . Org. Chem., Vol. 67, No. 20, 2002

Oxygen Transfer from Sulfoxides
SCHEME 2
Exp er im en ta l Section
Ma ter ia ls a n d Equ ip m en t. Alcohol substrates and DMSO
were all from commercial sources, of the highest purity
available, and used without further purification. H
O was purchased commercially, and H PV
was prepared according to the literature procedure.
40 and Q PV 40 were prepared by adding drop-
wise 5 mmol of the polyoxometalate dissolved in 20 mL water
3
PMo12
40
O ‚
H
2
5
2
Mo12
O
40‚32H
2
O
2
0
3
Q -
PMo12
O
5
2
Mo12O
the benzylic hydrogen leads to a partial negative charge
at the benzylic carbon. We put forth the possibility of
proton abstraction from benzylic alcohol by the DMSO-
+
-
to 20 (30) mmol of n-(C
4 9 4
H ) N Br dissolved in 25 mL of water.
The precipitated product was thoroughly washed with water
1
7
18
and dried under vacuum at 80 °C. O- and O-labeled DMSO
1
7
17
18
18
polyoxometalate complex. The protonated DMSO com-
were prepared using H
using the procedure described in the literature. 4-Methoxy-
benzyl alcohol-R,R-d (97% enrichment) was prepared by
reduction of 4-methoxybenzoic acid with LiAlD in THF.
-Nitrobenzyl alcohol-R,R-d (97% enrichment) was prepared
by reduction of 4-nitrobenzoyl chloride with NaBD according
to the literature method.22 Nitroethane was dried and distilled
2 2
O (10.2% O) and H O (95% O)
2
1
plex19 then may recombine with a carbanionic species
2
leading to formation of the new carbon-oxygen bond. We
believe that this reaction is possible vis- a´ -vis (re)-
protonation because the polyoxomolybdates are powerful
electron acceptors or oxidants leading to formation of an
electrophilic oxygen. As in the previous case, similar
subsequent elimination of a proton, hydroxide, dimethyl
sulfide, and the polyoxometalate leads to formation of the
benzylic aldehyde. In all cases, use of 18O-labeled sulfox-
ide leads to labeled aldehyde; however, the coformation
of water and the fast reaction of the latter with the
4
4
2
4
1
7
over CaH
2
. O NMR was measured at 54.25 MHz on a Bruker
1
7
Avance 400 instrument with H
2
O (2%) as an external
standard. Isotope incorporation into substrates and products
was measured by GC-MS (HP 5973). Reactions were quantified
by GLC (HP 6890) using a 30 m 5% phenylmethyl silicone
capillary column with an ID 0.32 mm and 0.25 µm coating
(
Restek 5MS).
aldehyde leads to 18O to O exchange and a lower
16
18
O
Gen er a l P r oced u r e for Oxid a tion of Alcoh ols. Reac-
content. From the kinetic isotope effect values for deu-
terated benzylic alcohols it is clear that the carbon-
hydrogen bond is being broken in the rate-determining
step in both postulated pathways, although at different
stages of the reaction. Since the DMSO oxygen donor first
tions were carried out in 20 mL glass pressure tubes for aerobic
reactions and in 20 mL Schlenk flasks for reactions under
anaerobic conditions (Ar). Typically, the tubes or flasks were
loaded with the polyoxometalate, sulfoxide, and substrate,
degassed by three successive “freeze-pump-thaw” cycles, and
2
loaded with Ar or O . The solution was brought to the
reacts with the H
3
PMo12
O
40 catalyst to form a H
3
-
appropriate temperature in a thermostated oil bath. After the
reaction was completed and the mixture cooled, GLC and GC-
MS analyses were preformed on aliquots withdrawn directly
from the reaction mixture.
PMo12
O
40-sulfoxide complex, Michaelis-Menton-type
kinetics, Figure 4, are expected and indeed observed for
DMSO. Also, at the beginning of the reaction, the benzylic
alcohol substrate is in large excess with respect to the
Deta iled P r oced u r e for Oxid a tion of Ben zyl Alcoh ol.
Benzyl alcohol (5 mmol, 540 mg) and H
5 µmol, 12.5 mg) were dissolved in 5 mL of DMSO in a 50
mL Buchi glass autoclave. The autoclave was pressurized to
1 atm of O , and the homogeneous mixture was magnetically
5
PV
2
Mo10
O
40‚32H
2
O
3 3 40
initial amount of H PMo12O40 and the H PMo12O -
(
sulfoxide complex. Thus, initially, the reaction is ef-
fectively zero order in benzylic alcohol, Figure 3, but as
the amount of benzylic acid is lowered, the bimolecular
2
stirred at 135 °C for 4 h. After the reaction mixture was cooled
to room temperature, 20 mL of water was added and the
benzaldehyde was extracted with two 5 mL portions of
3
interaction between the H PMo12O40-sulfoxide complex
and the benzylic alcohol is elicited in the rate equation.
The observed reaction kinetics as described in eq 1
support the mechanism.
4
ethylacetate. The organic phase was dried with MgSO , and
the product was purified by column chromatography (silica as
a stationary phase and CHCl3 as an eluent). The yield of
benzaldehyde (>99.5% purity) was 450 mg (85%).
An interesting observation noted above is that with H
PV 40 as a catalyst instead of H 40 under
anaerobic conditions the reaction for benzyl alcohol stops
at ∼40% conversion, whereas for H 40, the reac-
tion is completed. Our explanation for this finding is that
PV 40 can also oxidize alcohols without the direct
involvement of the sulfoxide in the oxidation reaction
5
-
Gen er a l P r oced u r e for Kin etic Exp er im en ts. Reactions
were carried out in 20 mL Schlenk flasks. Typically, the flasks
were loaded with the polyoxometalate, sulfoxide, and sub-
strate, degassed by three successive “freeze-pump-thaw”
cycles, and loaded with Ar. Exact reaction conditions are given
in the figure captions. The solution was brought to the
appropriate temperature in a thermostated oil bath. At the
desired time, 1 µL aliquots were removed for GC analysis.
Conversion was analyzed by evaluation of both disappearance
of the substrate and appearance of the product, which were
found to be in agreement within (2%. Kinetic isotope effects
for the oxidation of the benzylic alcohols were measured by
reacting equimolar mixture of proto- and deutero-alcohols.
Peaks were quantified by comparing the molecular peak
intensities (GC-MS) of the product aldehyde.
2
Mo12
O
3
PMo12O
3
PMo12O
H
5
2
Mo12O
(
∼0.6 mol of dimethysulfide formed per mol of benzyl
alcohol reacted and DMS not oxidized to a significant
amount under reaction conditions), Scheme 2. However,
under anaerobic conditions, this oxidation pathway leads
to a reduced heteropolyblue species that is apparently
catalytically inactive and was not reoxidized directly with
DMSO.
Ack n ow led gm en t. This research was funded by the
Israel Science Foundation and the European Commis-
sion (SUSTOX, G1RD-CT-2000-00347). R.N. is the
Rebecca and Israel Sieff Professor of Organic Chemistry.
Con clu sion
Polyoxomolybdates catalyze the oxidation of primary
and secondary alcohols to aldehydes and ketones, respec-
tively, with sulfoxides as oxygen donors. DMSO is
activated by complexation to the polyoxometalate.
J O0255577
(
(
20) Tsigdinos, G. A.; Hallada, C. J . Inorg. Chem. 1968, 7, 437.
21) Okruszek, A. J . Labelled Compd. Radiopharm. 1983, 20, 741.
(
19) It is conceivable that the proton is delocalized around the
(22) Bonin, A. M.; Glover, S. A.; Hammond, G. P. J . Chem. Soc.,
Perkin Trans. 2 1994, 1173.
polyoxomolybdate.
J . Org. Chem, Vol. 67, No. 20, 2002 7079