Selenium-Catalyzed Baeyer-Villiger Reactions
J . Org. Chem., Vol. 66, No. 7, 2001 2431
Ta ble 2. Solven t Effect on th e Oxid a tion of
Cyclop en ta n on ea
the solution had virtually no effect on the activity or
selectivity of 1.26 The absence of this base effect also
indicates that for the oxidation of cyclopentanone cata-
lyzed by 1, the formation of side products is not predomi-
nantly caused by (unselective) acid-catalyzed Baeyer-
Villiger reaction or acid-catalyzed hydrolysis of the
lactone. It is more likely that this is caused by a
competing pathway21 catalyzed by 1, as discussed above.
Su bstr a te Scop e. With an optimized system in hand
we tested a range of ketones and aldehydes (Table 3).
Overall, the carbonyl compounds are converted faster
and with higher selectivities than with most existing
catalyst systems. The cycloalkanones give the corre-
sponding lactones in good selectivities and show little
tendency to give ring contraction to cycloalkanecarboxylic
acids. The observed relative reactivities are in accordance
with values from literature, where increased ring strain
and electron density give higher reaction rates. Due to
these effects, linear ketones react more slowly to their
corresponding esters, and reaction times up to 24 h are
required to obtain appreciable conversions. When prod-
ucts are formed that are sensitive toward hydrolysis, such
as linear esters or strained lactones, the use of dichlo-
romethane as a solvent is recommended instead of the
very polar 2,2,2-trifluoroethanol. In dichloromethane this
hydrolysis process is slower, partly due to decreased
polarity and partly due to the biphasic nature of water-
CH2Cl2 mixtures. Nevertheless, after longer reaction
times the difference may become negligible. It should be
noted that conversions may be significantly lower in
CH2Cl2 compared with CF3CH2OH.
The highly electron-rich 3,4,5-trimethoxybenzaldehyde
gives a fast migration of the phenyl ring to yield the ester
of formic acid and free 3,4,5-trimethoxyphenol. With the
less electron-rich p-tolualdehyde there is a competing
phenyl and hydrogen migration leading to the formation
of a mixture of almost equal amounts of p-cresol (∼55%)
and p-toluic acid (∼45%). With the electron-poor p-
nitrobenzaldehyde it is the hydrogen atom which exclu-
sively migrates to yield p-nitrobenzoic acid. Similarly,
octanal and 3-phenylpropionaldehyde are selectively
oxidized to octanoic acid and 3-phenylpropionic acid,
respectively. Last, a 1,2-dione such as phenanthrene-
quinone can be oxidized to form an anhydride which
hydrolyzes under the reaction conditions to a dicarboxylic
acid.
solvent
conversion (%)b
selectivity (%)b,c
CF3CHOHCF3
CF3CH2OH
CH2Cl2
ClCH2CH2Cl
C6H5Cl
100
62
53
49
26
18
46
42
92
95
93
95
86
75
82
72
C6H5CF3
CH3NO2
C4H8SO2
d
a
Conditions: 1 mol % 1, 2 mmol cyclopentanone, 4 mmol 60%
H2O2, 0.4 mmol Bu2O as internal standard, 2 mL of solvent, 20
b
°C, 4 h. Determined by GC. c Selectivity to δ-valerolactone,
byproducts are a.o. cyclobutanecarboxylic acid, 5-hydroxypentanoic
d
acid. Sulfolane at 30 °C (mp ) 27 °C).
This would involve addition of some selenium species to
the double bond of the enol-tautomer. This reaction is
indeed favored by more electron-rich seleninic acids.19,21,22
Steric hindrance would probably also have a larger
deleterious effect on a Wagner-Meerwein type reaction
than on a Baeyer-Villiger type reaction. This might
explain why the selectivity for lactones is higher with
ortho-substituted diaryl diselenides. Increasing the elec-
tron-poor nature of the catalyst by having two trifluo-
romethyl groups at the meta positions leads to increased
selectivity in combination with high reactivity. All tested
diselenides are far superior in terms of activity and
selectivity to selenium dioxide, which is used frequently
in both lab-scale22 and bulk-scale23 reactions.
Solven t Effect. The choice of solvent is of great
importance in oxidation chemistry. Therefore, 1 was put
to the test in a range of solvents that are polar, aprotic,
noncoordinating, and non-oxidizable (Table 2).
As Table 2 shows, in contrast with epoxidation reac-
tions, the solvent plays a relatively minor role in activity
and selectivity of the catalytic system. We note that
1,1,1,3,3,3-hexafluoro2-propanol is by far the best
solvent,24 but because it is very expensive it is not very
practical to use. More suitable solvents are 2,2,2-trifluo-
roethanol, dichloromethane, and 1,2-dichloroethane, which
differ only slightly in terms of reactivity and selectivity.
When the toxicities of the various solvents are considered,
nitromethane and the halogenated hydrocarbons 1,2-
dichloroethane, chlorobenzene, and R,R,R-trifluorotoluene
would not seem to be the solvent of choice.25 Sulfolane,
on the other hand, is far less toxic, but shows decreased
selectivity. So, recommended solvents for further reac-
tions would be 2,2,2-trifluoroethanol or dichloromethane.
Ba se Effect. Although the Baeyer-Villiger reaction
is acid catalyzed, trace amount of acids in the hydrogen
peroxide have no influence on the reaction, since we
observed no blank reaction in 2,2,2-trifluoroethanol at
room temperature. Addition of sodium acetate to buffer
Con clu sion s
In conclusion, we have shown that Baeyer-Villiger
reactions can be carried out successfully with (aqueous)
hydrogen peroxide as the oxidant at room temperature.
The optimum selenium catalyst for this reaction was
found to be 3,5-bis(trifluoromethyl)benzeneseleninic acid.
This catalyst is easy to prepare and is active and selective
in combination with aqueous hydrogen peroxide. The best
solvents for the Baeyer-Villiger reaction are 1,1,1,3,3,3-
hexafluoro-2-propanol, 2,2,2-trifluoroethanol, and dichlo-
romethane.
(21) Giurg, M.; Mlochowski, J . Synth. Commun. 1999, 29, 2281.
(22) (a) Krief, A.; Hevesi, L. In Organoselenium Chemistry; Springer-
Verlag: Berlin, 1988; vol 1, pp 156-162. (b) Reich, H. J .; Wollowitz,
S.; Trend, J . E.; Chow, F.; Wendelborn, D. F. J . Org. Chem. 1978, 43,
1697.
(23) Higley, D. P. US Patent 4160769, 1977.
Exp er im en ta l Section
(24) Neimann, K.; Neumann, R. Org. Lett. 2000, 2, 2861.
(25) (a) 2,2,2-Trifluoroethanol is a common industrial solvent and
a known metabolite of the inhalation anaesthetics “fluroxene” (2,2,2-
trifluoroethyl vinyl ether) and “halothane” (2-bromo-2-chloro-1,1,1-
trifluoroethane). Selinsky, B. S.; Rusyniak, D. E.; Warsheski, J .;
J oseph, A. P. Biochem. Pharmacol. 1991, 42, 2229. (b) Many chlori-
nated solvents (CH2Cl2, CHCl3, CCl4, ClCH2CH2Cl, CCl3CH3, etc.) are
cancer suspect agents, and their use is an issue of debate. Hileman,
B.; Long, J . R.; Kirschner, E. M. Chem. Eng. News 1994, 72, 12.
Ma ter ia ls. The diselenides 1-5, 8, and 9 were prepared
as outlined in ref 1. Diselenide 7 and SeO2 were purchased
from Acros. Diselenide 6 was prepared via reaction of 1-chloro-
(26) Mares and J acobson observed a beneficial effect from mild bases
in a similar system: Mares, F.; J acobson, S. E. US Patent 4213906,
1978.