Electrophilic activation of hydrogen peroxide: Selective oxidation reactions in perfluorinated alcohol solvents

Article abstract of DOI:10.1021/ol006287m

The catalytic electrophilic activation of hydrogen peroxide with transition metal compounds toward reaction with nucleophiles is a matter of very significant research and practical interest. We have now found that use of perfluorinated alcoholic solvents such as 1,1,1,3,3,3-hexafluoro-2-propanol in the absence of catalysts allowed electrophilic activation of hydrogen peroxide toward epoxidation of alkenes and the Baeyer-Villiger oxidation of ketones.

Full text of DOI:10.1021/ol006287m

ORGANIC
LETTERS
2
000
Vol. 2, No. 18
861-2863
Electrophilic Activation of Hydrogen
Peroxide: Selective Oxidation Reactions
in Perfluorinated Alcohol Solvents
2
Karine Neimann and Ronny Neumann*
Department of Organic Chemistry, Weizmann Institute of Science,
RehoVot 76100, Israel
ronny.neumann@weizmann.ac.il
Received July 2, 2000
ABSTRACT
The catalytic electrophilic activation of hydrogen peroxide with transition metal compounds toward reaction with nucleophiles is a matter of
very significant research and practical interest. We have now found that use of perfluorinated alcoholic solvents such as 1,1,1,3,3,3-hexafluoro-
2-propanol in the absence of catalysts allowed electrophilic activation of hydrogen peroxide toward epoxidation of alkenes and the Baeyer−
Villiger oxidation of ketones.
The activation of aqueous hydrogen peroxide has captivated
researchers interested in the use of this high oxygen content,
relatively inexpensive, and environmentally friendly oxidant
for oxidation transformations in synthetic chemistry. Mecha-
nistically, hydrogen peroxide may be basically activated in
three ways. First, hydroxy and hydroperoxy radicals may
be formed by a Haber-Weiss mechanistic scheme in the
presence of many metal compounds. These radicals usually
lead to nonselective transformations of organic substrates.
o
(d ), mostly on Ti, V, Mo, W, and Re, metal complexes.
2
Some very notable effective catalysts are titanium silicates,
3
4
peroxophosphotungstates, manganese triazocyclononane,
5
and methylrhenium trioxide. From a mechanistic point of
view, both the carboxy group in the peracid and the high
valent metal centers in the transition metal compounds lead
to the formation of electrophilic oxygen atom. It is believed
by many that subsequent oxygen transfer to a nuclephile such
as an alkene takes place via a butterfly type transition state.6
More succinctly it seems clear that any compound that
will reduce the electron density at the oxygen atom of
-
Second, under basic conditions, the strong HOO nucleophile
is formed which is active for epoxidation of electrophilic
alkenes such as â-unsaturated ketones or carboxylic acid
derivatives. The third and probably most important synthetic
application of hydrogen peroxide has been in the area of
heterolytic oxidation as in the epoxidation of alkenes. Very
often, hydrogen peroxide was and is still used for the separate
and in situ formation of percarboxylic acids, which are active
for example in epoxidation, oxidation of sulfides, and the
Baeyer-Villiger oxidation of ketones to esters. Mostly,
environmental and safety concerns associated with the use
(2) Clerici, M. G.; Bellussi, G.; Romano, U. J. Catal. 1991, 129, 159.
(
(
3) Venturello, C.; Alneri, E.; Ricci, M. J. Org. Chem. 1983, 48, 3831.
4) De Vos, D. E.; Sels, B. F.; Reynaers, M.; Rao, Y. V. S.; Jacobs, P.
A. Tetrahedron Lett. 1998, 39, 3221.
5) Herrmann, W. A.; Fischer, R. W.; Rauch, M. U.; Scherer, W. J. Mol.
Catal. 1994, 86, 243.
6) (a) Bartlett, P. D.; Leffler, J. E. J. Am. Chem. Soc. 1950, 72, 3030.
(b) Chong, A. O.; Sharpless, K. B. J. Org. Chem. 1977, 42, 1587.
7) There are recent reports of trifluoroethanol as a “magic” solvent for
(
(
(
catalytic epoxidation reactions. (a) van Viliet, M. C. A.; Arends, I. W. C.
E.; Sheldon, R. A. Chem. Commun. 1999, 821. (b) van Viliet, M. C. A.;
Arends, I. W. C. E.; Sheldon, R. A. Chem. Commun. 1999, 263. (c) Shryne,
T. M.; Kim, L. US Patent 4024165, 1977.
1
of peracids has led over the past generation to the research
into catalytic alternatives based on the use of high valent
(8) Reactions were carried out in 5 mL vials by mixing the organic
substrate, hydrogen peroxide, and solvent in the quantities given in the tables.
The vials were magnetically stirred at ambient temperature, ∼22 °C, or in
a thermostated bath at 60 °C. The mixtures were analyzed by GC (HP 5890)
and GC-MS (HP 5973) using a 30 m 5% phenyl methyl silicone column
(ID 0.32 mm, coating 0.25 µm).
(
1) Recently, peroxomonocarbonate has been suggested as an environ-
mentally attractive anionic peracid. (a) Yao, H.; Richardson, D. E. J. Am.
Chem. Soc. 2000, 122, 3220. (b) Richardson, D. E.; Yao, H.; Frank, K. M.;
Bennett, D. A. J. Am. Chem. Soc. 2000, 122, 1729.
1
0.1021/ol006287m CCC: $19.00 © 2000 American Chemical Society
Published on Web 08/10/2000

hydrogen peroxide will lead to a facilitated nucleophilic
attack and heterolytic oxygen transfer. We have now found,
that one can simply carry out oxidation reactions with
hydrogen peroxide in inert and easy to recycle, low boiling
point, perfluorinated alcohols as solvents without the addition
the absolute selectivity to the epoxide product. Other terminal
alkenes such as 1-heptene and 1-decene reacted in a
practically identical manner. As expected the more nucleo-
philic 2-octene was more reactive, and there was no loss of
selectivity. With a yet more nucleophilic and reactive alkene,
2,3-dimethyl-2-butene, reactivity increased significantly;
however, the product epoxide reacted further in acid-
catalyzed type reactions to yield the ring-opened diol and
the rearranged pinocolone (3,3-dimethyl-2-butanone). For
cyclic alkenes, the reactivity was cyclopentene ∼ cyclooctene
> cyclododecene ∼ cyclohexene. Except for cyclohexene
oxide, which proved to be sensitive to further acid-type-
catalyzed reactions, the epoxides were stable under the
reaction conditions. The oxidation of styrene yielded mostly
the carbon-carbon bond cleaved product, benzaldehyde, and
products attributable to acid-catalyzed ring opening of the
epoxide, R-hexafluoropropyloxy-â-hydroxyethylbenzene, and
the rearranged phenylacetaldehyde. Interestingly, meta sub-
stitution with an electron-withdrawing, deactivating nitro
moiety led to selective formation of 3-nitrobenzaldehyde.
Three further observations are worth pointing out. First, the
addition of buffers or basic amines in order to prevent
undesired reactions of acid sensitive compounds led to
deactivation and no reaction. Second, the use of perfluoro-
7
of any metal or nonmetal catalyst. Selective epoxidation of
alkenes and the Baeyer-Villiger oxidation of ketones is
1
17
shown. From the H and O NMR spectra, we deduce that
the strong electron-withdrawing properties of fluorine along
with the hydrogen bonding properties of the O-H hydrogen
atom lead to formation of an electrophilically activated
hydrogen peroxide intermediate, roughly delineated in
Scheme 1. As expected reactivity is increased as a function
Scheme 1
3 3
tert-butyl alcohol, (CF ) COH, as solvent gave virtually the
3 3
of fluorine substitution; CF CHOHCF (1,1,1,3,3,3-hexaflu-
same results in terms of both reactivity and selectivity as
HFIP. Finally, no oxidation products of the perfluorinated
alcohols such as 1,1,1,3,3,3-hexafluoracetone were obtained
under the reaction conditions as measured by GC-MS.9
oroisopropyl alcohol (HFIP) is more active than CF
OH (2,2,2-trifluoroethanol, TFE).
3 2
CH -
First, alkenes were reacted with a slight excess of 30% or
0% H in both TFE and HFIP as solvents. A preliminary
survey of the reactivity of the alkenes is presented in Table
6
2 2
O
The activation of hydrogen peroxide in HFIP was also very
8
1
. Epoxidation of an exemplary difficult to epoxidize
successfully used for the Baeyer-Villiger oxidation of
8
terminal, aliphatic, acyclic alkene, 1-octene, clearly showed
that activity in HFIP was greater than in TFE. Use of non-
fluorine-containing alcohols as solvents such as ethanol and
ketones, Table 2. Thus, cyclic ketones were cleanly con-
verted to lactones in high yield. As is typical for this reaction,
acyclic ketones were much less reactive. Finally, although
2
-propanol showed no activity. Raising the temperature and/
2 2
the oxidation of sulfides to sulfoxides with H O in HFIP
has already been disclosed, it is valuable to state that in
TFE reactions are slower and slightly less selective than those
1
0
or using more concentrated hydrogen peroxide easily in-
creased the conversion. This was possible without comprising
Table 1. Alkene Epoxidation in Perfluorinated Alcoholsa
conversion, mol %, selectivity, mol epoxide/total products
HFIP at 22 °C
TFE at 60 °C
HFIP at 60 °C
substrate
30% H2O2
60% H2O2
30% H2O2
60% H2O2
30% H2O2
60% H2O2
cyclopentene
cyclohexene
cyclooctene
56 (100)
37 (53)c
66 (100)
7 (100)
0
37 (100)
96 (11)d
-
99 (100)
65 (48)e
98 (100)
39 (100)
14 (100)
77 (100)
-
44 (100)
25 (100)
61 (100)
40 (100)
4 (100)
33 (100)
100 (57)f
-
93 (100)
91 (61)g
100 (100)
80 (100)
21 (100)
73 (100)
-
99 (90)f
82 (26)h
99 (100)
85 (100)
30 (100)
74 (100)
-
-
-
-
-
cyclododeceneb
1
2
2
-octene
-octene
,3-diMe-2-butene
59 (100)
97 (100)
-
100l
39k
j
styrene
-nitrostyrene
-
-
-
-
74
13k
3
-
-
a
b
Reaction conditions: 1.2 mmol of substrate, 2 mmol of H2O2, 1 mL of perfluoro alcohol, 20 h. The given mixture of 80:20 cis/trans cyclododecane
c
d
e
gave the same epoxide ratio. 23% 1-(2,2,2-trifluoroethyloxy)-2-hydroxycyclohexane, 24% 1,2-cyclohexanediol. 89% 2,3-dimethyl-2,3-butanediol. 31%
-(2,2,2-trifluoroethyloxy)-2-hydroxycyclohexane, 21% 1,2-cyclohexanediol. 34% 2,3-dimethyl-2,3-butanediol, 9% pinocolone. 39% 1-(1,1,1,3,3,3-
hexafluoroprop-2-yloxy)-2-hydroxycyclohexane. 10% cyclopentanediol. 89% cyclohexanediol. 47% benzaldehyde, 15% phenylacetaldehyde, 32% R-(1,1,1,3,3,3-
hexafluoroprop-2-yloxy)-â-hydroxyethylbenzene, 6% phenol. 100% 3-nitrobenzaldehdye. 53% benzaldehyde, 29% phenylacetaldehyde, 13% R-(1,1,1,3,3,3-
hexafluoroprop-2-yloxy)-â-hydroxyethylbenzene, 9% phenol.
f
g
1
h
i
j
k
l
2862
Org. Lett., Vol. 2, No. 18, 2000

11
perfluorinated alcohol solvents. Thus, the shift attributable
1
Table 2. Baeyer-Villigar Oxidations of Ketonesa
to H
9
O
2 2
in the H NMR of 60% H
O
2 2
in solvent varied from
.91 ppm in 2-propanol, 9.18 ppm in TFE, and 8.08 ppm in
HFIP. Similarly, in the O NMR there is a shift for H
from 182.2 ppm in 2-propanol to 177.5 ppm in HFIP. Both
results are interpreted by realizing that according as hypoth-
esized in Scheme 1 the electron-density is reduced on the
oxygen atom upon dissolution in the perfluorinated alcohol.
substrate
conversion, mol %
1
7
O
2 2
cyclopentanone
cyclohexanone
cycloheptanone
cyclooctanone
88b
12
82b
68b
60b
6.5c
2
-octanone
acetophenone
0
1
This leads to an expected upfield shift in both the H and
O NMR. The effect is stronger for HFIP compared to TFE.
a
17
Reaction conditions: 1.2 mmol of substrate, 2 mmol of 60% H2O2, 1
b
c
mL of HFIP, 60 °C, 20 h. Only lactones were obtained. Hexyl acetate
was the only product.
OL006287M
(
10) Ravikumar, K. S.; Begue, J. P.; Bonnet-Delpon, D. Tetrahedron
in HFIP. Typically, reaction selectivity is 100% to sulfoxide
Lett. 1998, 39, 3141. (b) Ravikumar, K. S.; Zhang, Y. M.; Begue, J. P.;
Bonnet-Delpon, D. Eur. J. Org. Chem. 1998, 2937.
(11) H NMR (250 MHz) spectra were carried out on solutions containing
in HFIP and 97 ( 2% in TFE for a wide range of sulfides.
1
17
1
H NMR and natural abundance O NMR were both used
1
7
1
(
2 µL of 60% H2O2, 0.1 mL of solvent in 0.6 mL of CDCl3. O NMR
to investigate the interaction of hydrogen peroxide with the
54.25 MHz) were carried out on solutions of 120 µL of 60% H2O2 in 1
mL of solvent. The spectra were referenced externally to H2O without
locking.
(9) Formation of perfluoroacetone could lead to subsequent formation
of the R-hydroxy hydroperoxides and epoxidation of alkenes. cf. Ganesh-
pure, P. A.; Adam, W. Synthesis 1996, 179.
(12) The 17O shifts assigned to the hydroxyl oxygen are at 40.5 ppm for
2-propanol and at -11.7 ppm for HFIP.
Org. Lett., Vol. 2, No. 18, 2000
2863