Organo Sulfonic Peracids. 4.1 the Reaction of Arenesulfonylimidazoles with H2O2 in the Presence of Ketones. A New Entry to Dioxiranes

Article abstract of DOI:10.1021/jo9610164

The reaction of ketones (acetone, 1,1,1-trifluoropropan-2-one) with the oxidation system (arene-sulfonyl)imidazole (2)/H₂O₂/NaOH permits the in situ generation of the corresponding dimethyl-and methyl(trifluoromethyl)dioxirane in various solvents. This has been established by the chemoselective oxidation of azomethines 6, the diastereoselective oxidation of cholesterol (12), and ¹⁸O-labeling experiments. Because only 5 equiv of ketone are used, the dioxirane oxidation pathway appears to be virtually exclusive one in this system. One example for the nonaqueous in situ generation of dimethyldioxirane (1a) is given.

Full text of DOI:10.1021/jo9610164

188
J . Org. Chem. 1997, 62, 188-193
Or ga n o Su lfon ic P er a cid s. 4.1 Th e Rea ction of
Ar en esu lfon ylim id a zoles w ith H2O2 in th e P r esen ce of Keton es.
A New En tr y to Dioxir a n es
Manfred Schulz,* Stephan Liebsch,2 and Ralph Kluge
Institute for Organic Chemistry, Martin Luther University Halle-Wittenberg, Geusaer Str.,
D-06217 Merseburg, Germany
Waldemar Adam
Institute for Organic Chemistry, University of Wu¨rzburg, Am Hubland, D-97074 Wu¨rzburg, Germany
Received May 31, 1996X
The reaction of ketones (acetone, 1,1,1-trifluoropropan-2-one) with the oxidation system (arene-
sulfonyl)imidazole (2)/H2O2/NaOH permits the in situ generation of the corresponding dimethyl-
and methyl(trifluoromethyl)dioxirane in various solvents. This has been established by the
chemoselective oxidation of azomethines 6, the diastereoselective oxidation of cholesterol (12), and
18O-labeling experiments. Because only 5 equiv of ketone are used, the dioxirane oxidation pathway
appears to be virtually exclusive one in this system. One example for the nonaqueous in situ
generation of dimethyldioxirane (1a ) is given.
Sch em e 1
During the last two decades a new class of electrophilic
oxidants, the dioxiranes, has been developed and brought
to extended synthetic use in modern oxidation chemistry.
The application of especially the well-known and power-
ful dimethyldioxirane (DMD) (1a ) and the even stronger
methyl(trifluoromethyl)dioxirane (MTFD) (1b) for the
oxidation of different types of organic compounds, i.e.
olefins, sulfides, amines, and saturated hydrocarbons has
been extensively reviewed.3
The most convenient method for both the in situ
generation and the formation with isolation (as a solution
in the parent ketone) of the dioxiranes is the reaction of
potassium peroxomonosulfate (caroate) with an excess of
the corresponding ketone under strictly controlled pH
conditions. By this procedure it is possible to obtain ∼0.1
M solutions of 1a in acetone and 0.8-1.0 M solutions of
1b in trifluoroacetone (1,1,1-trifluoropropan-2-one, TFP)4
(Scheme 1). Another method, the photochemical conver-
sion of carbonyl oxides into dioxiranes, has been applied
succesfully for the preparation of the first stable and
crystalline dioxirane, dimesityldioxirane (1c),5 but this
approach is not suitable for common substrate oxidation
at present.
Over time the application of the standard generation
method by using caroate has led to a few problems, whose
overcoming is of great interest: e.g. (i) the preparative
use of bulky substituted water insoluble ketones which
may be advantageous for diastereoselective oxidations
and (ii) the use of expensive optical active ketones as
precursors of optical active dioxiranes. In these cases the
standard caroate procedure is ineffective. To overcome
these problems, attempts were made to carry out this
reaction in a two phase system under PTC conditions
(phase-transfer catalyst n-Bu4N+HSO4-).6-8 However,
especially in the case of nonfluorinated ketones long
reaction times were necessary to obtain satisfactory
conversions and yields.7 Besides this, the efficiency of
dioxirane production in a two-phase system is influenced
by the structure and the water solubility of the ketone
precursor. Very recently, a new approach to this problem
has been introduced involving the incorporation of the
phase-transfer capability and the carbonyl functionality
into one molecule.8 In this publication the first example
of an actual catalytic generation of a dioxirane from 1-n-
dodecyl-1-methyl-4-oxopiperidinium triflate in a two-
phase system was described. Nevertheless, (iii) the
catalytic use of ketones for the generation of dioxiranes,
which is of special interest for the application of optical
active dioxiranes in enantioselective oxidations, remains
a general problem in dioxirane chemistry.
X Abstract published in Advance ACS Abstracts, December 1, 1996.
(1) Part III: Kluge, R.; Schulz, M.; Liebsch, S. Tetrahedron 1996,
52, 5773.
(2) Liebsch, S. Dissertation in progress, Martin Luther University,
Halle-Wittenberg.
(3) (a) Curci, R.; Dinoi, A.; Rubino, M. F. Pure Appl. Chem. 1995,
67, 811. (b) Adam, W.; Hadjiarapoglou, L. P.; Curci, R; Mello, R. In
Organic Peroxides; Ando, W., Ed.; Wiley New York, 1992; Chapter 4,
pp 195-219. (c) Murray, R. W. Chem. Rev. 1989, 89, 1187. (d) Adam,
W.; Curci, R.; Edwards, J . O. Acc. Chem. Res. 1989, 22, 205.
(4) Adam, W.; Bialas, J .; Hadjiarapoglou, L. P. Chem. Ber. 1991,
124, 2377.
Until now the formation of dioxiranes has been con-
sidered only in terms of the function of the ketone and
(6) Curci, R.; Fiorentino, M.; Serio, M. R. J . Chem. Soc., Chem.
Commun. 1984, 155.
(7) Curci, R.; D’Accoli, L.; Fiorentino, M.; Rosa, A. Tetrahedron Lett.
1995, 36, 5831.
(5) Kirschfeld, A.; Muthusamy, S.; Sander, W. Angew. Chem., Int.
Ed. Engl. 1994, 33, 2212.
(8) Denmark, S. E.; Forbes, D. C.; Hays, D. S.; DePue, J . S.; Wilde,
R. G. J . Org. Chem. 1995, 60, 1391.
S0022-3263(96)01016-X CCC: $14.00 © 1997 American Chemical Society

Organo Sulfonic Peracids
Sch em e 2
J . Org. Chem., Vol. 62, No. 1, 1997 189
Ta ble 1. Oxid a tion of Azom eth in es 6c,d w ith 2a ,b/H2O2/
Na OH in th e P r esen ce of Keton esa
yield (%)c
azo-
2
ketone R conv
(%)c
entry methine (equiv)b (equiv)b
9
8c
1
2
3
4
5
6
7
8
9
6c
6c
6c
6c
6c
6c
6c
6c
6d
6d
6c
6c
2a (1.5)
95 9c, 61d
87 9c, 45
100 9c, 43
80 9c, 19
88 9c, 26
96 9c, 18
90 9c, 54
100 9c, 42
2a (1.5) CH3 (3)
2a (1.5) CH3 (10)
2a (1.5) CH3 (50)
2a (1.5) CF3 (3)
2a (1.5) CF3 (10)
2b (1.5) CH3 (3)
2b (1.5) CF3 (3)
2a (1.3) CH3 (2.6)
2a (1.3) CF3 (2.6)
f(1.5) CH3 (3)
30
43
57
62
72
18
42
80 9d , 23d 17 (19e)
80 9d , 27d 32 (26e)
100 9c, 56d
10
11
12
f(1.5) CF3 (3)
100 9c, 74
7
a
All reactions were carried out in MeOH at 5 °C, reaction time
max. 3 h. With respect to 6 introduced. c Determined by 1H NMR
b
d
analysis, experimental error ( 3%. Yield of chromatographically
pure isolated material. e Yield of isolated 11. f Oxidation with
caroate/NaHCO3.
Sch em e 3
the phase-transfer catalyst, respectively. To the best of
our knowledge no investigations to substitute caroate
have been carried out. Therefore new alternative routes
to dioxiranes are of interest. Arenesulfonic peracids 5,
which can be regarded as organic derivatives of caroate,
are supposed to act in a caroate-like manner. Recently
we reported the in situ generation of 59 from the corre-
sponding azole derivatives 2-4 (Scheme 2) in a variety
of solvents. Consequently, the advantage of the peracids
5 could be their solubility in organic solvents (CH3CN,
Sch em e 4
t
DMF, THF, MeOH, BuOH), providing a possibility to
generate dioxiranes in a homogeneous medium.
We present in this paper our experimental results
dealing with the proof of the in situ formation of diox-
iranes using the system 2/H2O2/NaOH in the presence
of ketones. As it was previously shown, the arenesulfonic
peracids 5 formed under analogous conditions in the
absence of ketones are strong oxidants themselves and
have been used for the diastereoselective epoxidation of
olefins and oxidation of compounds containing nitrogen
and/or sulfur functionalities. For this reason the oxida-
tion of suitable substrates showing significant differences
in the chemoselective or diastereoselective course of the
oxidation was thought to be a promising approach to
distinguish between the dioxirane oxidation and the
peracid oxidation in the system 2/H2O2/NaOH/ketone.
Additionally, 18O-labeling experiments with [18O]acetone
should provide unambiguous evidence for the in situ
generation of 1a by the generation of 5 in the presence
of acetone. All reactions were carried out under standard
conditions,1,9 shown to give high yields of the oxidants 5,
and were not optimized to date with respect to the
generation of dioxiranes (for a detailed investigation
concerning the optimized generation of dioxiranes with
caroate, see ref 8).
low yields (12-23%) along with the aldehydes 8a -c as
major products (31-53%), presumably as a result of an
oxidative cleavage of the CdN bond10 (Scheme 3). By
contrast, the oxidation of 6a -d with peroxy acids,11
caroate,12 or sulfonic peracids1 results in the exclusive
formation of oxaziridines 9a -d .
Therefore the competitive formation of products 8c and
9c in the oxidation of 6c with the oxidants 2/H2O2/NaOH
in the presence of various amounts of ketones was used
as a test for the intermediate formation of 1a and 1b
(Scheme 4 and Table 1).
From the results presented in Table 1 it is evident that
the product ratio 8c:9c depends both on the type and the
amount of ketone introduced. With increasing amount
of ketone, the yield of the cleavage product 8c is also
increased. TFP is shown to be more effective in dioxirane
formation compared to acetone under the same conditions
A. Ch em oselectivity Test. In order to distinguish
between dioxirane oxidation and the oxidation with 5,
azomethines 6 were found to be good model substrates
since it was shown that the oxidation of 6a -c using
“isolated” 1a yields the corresponding nitrones 7a -c in
(10) Boyd, D. R.; Coulter, P. B.; McGuckin’, M. R.; Sharma, N. D.;
J ennings, W. B.; Wilson, V. E. J . Chem. Soc., Perkin Trans. 1 1990,
301 and references cited therein.
(11) Emmons, W. D. Chem. Heterocycl. Compd. 1964, 19, 624.
(12) Crandall, J . K.; Reix,T. J . Org. Chem. 1992, 57, 6759.
(9) Kluge, R; Schulz, M.; Liebsch, S. Tetrahedron 1996, 52, 2957.

190 J . Org. Chem., Vol. 62, No. 1, 1997
Schulz et al.
Ta ble 2. Oxid a tion of Ch olester ol (12) w ith th e System
(Ar en esu lfon yl)a zole (2a ,c,d 3a , or 4d )/H2O2/Na OH in th e
P r esen ce or Absen ce of Aceton ea
(entries 5 and 6) as a result of its more electrophilic
carbonyl group. Moreover the ratio 8c:9c also depends
on whether 2a or 2b is employed. In comparison to the
oxidation system 2a /H2O2/NaOH, the use of 2b/H2O2/
NaOH leads to less dioxirane oxidation products. This
result may be interpreted by the stronger oxidative power
of 5b compared to 5a (see ref 9), resulting in a lower
chemoselectivity.
Under comparable conditions (temperature, solvent,
pH, time), the application of caroate afforded no or
negligible amounts of DMD or MTFD oxidation products
(Table 1, entries 11 and 12). This is in agreement with
observations12 that only 9a -c were formed under condi-
tions typical for the in situ generation of 1a due to either
the slower formation of the ketone-caroate adduct or the
slower reaction of this adduct to the corresponding
dioxirane 1 compared with the peracid-like oxidation of
azomethines by caroate.12
No comments have been made in the literature10 on
the fate of the amine part resulting from the oxidative
cleavage. We have found in the oxidation of 6c with 2a
or 2b/H2O2/NaOH in the presence of acetone or TFP that
by adding a minimal amount of aqueous NaOH to the
reaction mixture, a blue-green color appeared immedi-
ately (λ ) 677 nm, MeOH) characteristical for 2-methyl-
2-nitrosopropane (10).13 Attempts to determine the yield
of 10 failed due to its high volatility.
In order to quantify the N-oxidation product, we
examined 6d under the same conditions (entries 9 and
10) as described for 6c. The cyclohexanone oxime (11)
was isolated as the sole N-oxidation product (yield 22-
26%). The yield of 11 correlates well with the amount
of 8c formed (Table 1, entries 9 and 10). Experiments
in the absence of ketones showed only oxaziridine forma-
tion and no cleavage products. Therefore hydrolysis of
the azomethine, as previously proposed10 in the oxidation
with 1a , cannot play a significant role in the formation
of the cleavage products 8c and 10 or 11.
B. Dia st er eoselect ivit y Test . The epoxidation of
cholesterol (12) and related compounds has been inves-
tigated with different types of oxidants, e.g. peroxy
acids,14 dioxiranes,15 and organo sulfonic peracids.9 Be-
cause of distinct changes in the diastereoselectivity
comparing the epoxidation with arenesulfonic peracids
5 (R-13/â-13 ) 80/20 to 90/10)9 and dioxiranes (R-13/â-
13 ) 50/50 to 40/60),15 respectively, 12 was chosen as a
stereochemical probe in order to gain further evidence
that dioxiranes 1 are formed when the mixture 2/H2O2/
NaOH in the presence of ketones is used (Scheme 5).
The oxidations of 12 were performed with 2 equiv of
2a , 2c, or 2d in THF with varying amounts of acetone
(from 0 to 50 equiv per mol 2, Table 2). Our results
clearly demonstrate that the diastereoselectivity of the
epoxidation of 12 depends on the amount of acetone
introduced. Applying (toluenesulfonyl)imidazole (2a ) and
(p-nitrobenzenesulfonyl)imidazole (2c), the R/â ratio ap-
proximates to R-13/â-13 ) 41/59 (Table 2, entries 1-9
and 12-15) with increasing amounts of acetone. This
ratio is in excellent agreement with that obtained in the
molar
ratio
acetone/
12
diastereo-
meric
sulfonyl-
azole
con-
version
(%)c,d
yield
(%)c,e
∑ (R/â-13)
ratio
entry
(equiv)b
R-13/â-13c
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16f
17f
18
19
20
21
22
23
24
25
26
2a (2)
2a (2)
2a (2)
2a (2)
2a (2)
2a (2)
2a (2)
2a (2)
2a (2)
3a (2)
3a (2)
2c (2)
2c (2)
2c (2)
2c (2)
2c (2)
2c (2)
2d (2)
2d (2)
2d (2)
4d (2)
4d (2)
h
0
1
4
10
20
40
60
80
100
0
20
0
1
4
20
0
20
0
4
20
0
20
h
i
20
l
82/18
76/24
58/42
50/50
50/50
43/57
44/56
41/59
41/59
83/17
82/18
82/18
75/25
56/44
45/55
80/20
48/52
89/11
76/24
70/30
92/8
43
48
48
36
25
37
20
28
35
100
100
55
65
62
62
53
44
50
43
25
100
100
nd
93
7
85 (76)
77
80 (65)
76
70
87
89
83
89
(93)
(92)
92 (73)
83 (68)
87 (65)
84 (76)
83
88
96 (93)
78 (58)
70
98 (80)g
(96)
91/9
50/50
40/60
45/55
44/56
(90)
(95)
93
(80)
i
k
l
90
a
Reactions carried out at 10 °C in THF (with exception of
entries 10 and 11),9 reaction time ∼3 h. With respect to 12
b
introduced. c Determined by 1H NMR analysis from the crude
product, experimental error ( 3%. With respect to 12. e In
d
parentheses are the yields of isolated diastereomeric mixture of
R-13 and â-13 with respect to conversion. f H2O2 was used as 2 M
solution in Et2O; a 2 M solution of NaOEt in absolute EtOH was
used as the base; byproduct formed 4-NO2-C6H4SO2OEt (3%).
g
h
Pure R-13 recrystallized from acetone. Taken from ref 15a:
oxidation was carried out with in situ generated DMD (excess
caroate and acetone); conversion and experimental details were
i
not given. Taken from ref 15b: oxidation of 3â-acetoxy-5,16-
k
pregnadien-20-one with “isolated” DMD. Oxidation with 1 equiv
l
of caroate/15 equiv of NaHCO3 in MeOH, 48 h. Oxidation with 1
equiv of caroate/15 equiv of NaHCO3 in acetone.
Sch em e 5
oxidation with both isolated 1a and in situ generated 1a
(entries 23 and 24).15 Therefore we deduce that 1a is
formed under the conditions of the system 2/H2O2/NaOH/
acetone and the epoxidation of 12 occurs mainly by the
in situ generated 1a even when only 2 equiv of acetone
were introduced.
(13) Tapuhi, Y.; Grushka, E. In The chemistry of amines, nitroso
and nitro compounds and their derivatives; Patai, S., Ed.; Wiley: New
York, 1982; Chapter 21, p 915.
(14) (a) Mousseron-Canet, M.; Guilleux, J . C. Bull. Soc. Chim. Fr.
1966, 3853. (b) Bingham, K. D.; Blaiklock, T. M.; Coleman, R. C. B.;
Meakins, G. D. J . Chem. Soc. (C) 1970, 2330.
(15) (a) Marples, B. A.; Muxworthy, J . P.; Baggaley, K. H. Tetrahe-
dron Lett. 1991, 32, 533. (b) Bovicelli, P.; Lupattelli, P.; Mincione, E.
J . Org. Chem. 1992, 57, 2182.
Entries 16 and 17 should be noted. In these experi-
ments the oxidation was performed in absolute EtOH by
16
2c and etheral H2O2 with NaOEt in EtOH as base. In

Organo Sulfonic Peracids
J . Org. Chem., Vol. 62, No. 1, 1997 191
Ta ble 3. Ep oxid a tion of (E)-2-Meth ylstyr en e (14) w ith 2c/H2O2/Na OH in th e P r esen ce of [18O]Aceton e
18O contenta
acetone
molar ratios
equiv of
acetoneb
DMD
yield of
15 (%)
entry
14/2c/H2O2/Na18OH
Ac (%)
Bc (%)
15 (%)
oxidationd (%)
conve (%)
1
2
3
4
5
1:1:2:1
1:1:2:1
1:1:2:1
0:1:2:1
1:1:2:1
1
1
10
1
70.5
66.0
66.0
63.5
45.8
44.5
ndf
24.7
21.6
26.4
70
65.5
80
52
43
47
83
88
86
63.3
g
44
82
a
b
Determined by GLC-MS analysis (experimental error ( 0.1%). Relative to 2c. c A: starting material, B: after completion of reaction.
Estimated oxidation by DMD relative to total oxidation, expressed by the ratio: [18O content of 15]/ 0.5 × [18O content of introduced
d
acetone] × 100%. e Determined by 1H NMR and/or GLC-MS analysis. f Not determined because of 10-fold excess acetone introduced.
g
Natural abundance.
Sch em e 6
both cases (with or without acetone) the yields and
diastereoselectivities obtained are very close to those
found in the system 2c/aqueous H2O2/aqueous NaOH
(entries 12 and 15). Therefore, we deduce that DMD (1a )
is formed in comparable amounts even under nonaqueous
conditions.
The effects of varying the arene substituents on the
generation of 1a are also shown in Table 2. The applica-
tion of 2c gave nearly the same dependence of the
diastereomeric ratio R-13/â-13 on the acetone concentra-
tion compared to 2a .17 In contrast, when (mesitylene-
sulfonyl)imidazole (2d ) is introduced, only a slight de-
experiments by using doubly labeled caroate (K+ -O-
crease of the R-13/â-13 ratio is observed even when 20
equiv of acetone were used. Therefore, we deduce that
SO218O18OH) and unlabeled ketone or 18O-labeled ketone
and unlabeled caroate have previously been carried out
in the early days of dioxirane chemistry.20
the formation of 1a is less favored under these conditions
(Table 2, entry 20) due to the steric hindrance of the o,o′-
CH3 groups.
In our experiments we employed (E)-2-methylstyrene
(14) as the model substrate and 2c as the representative
precursor for the intermediate arenesulfonic peracids 5
in equimolar amounts, since 2c had been shown to give
the highest conversions in our diastereoselectivity test
(see above). 18O-Labeled acetone (prepared by isotope
exchange of acetone and H218O) was used in varying
amounts from 1 to 10 equiv with respect to 2c and 14.
In order to reduce as far as possible the base-catalyzed
isotope exchange of the [18O]acetone with H2O or HO-
during the reaction, a 2 N solution of NaOH in H218O
was employed.
Other more reactive precursors for 5, namely 1-methyl-
3-(arenesulfonyl)imidazolium tetrafluoroborates (3) or
(arenesulfonyl)-3-nitro-1,2,4-triazoles (4), which have
been found to give similar results in the epoxidation of
12 by the reaction with H2O2/base,9 failed in the in situ
generation of 1a (Table 2, entries 11 and 22). This is
attributed to the strong pH dependence of the formation
of 1a .18 While the generation of 5 starting from 3 and 4
proceeds in a slightly acidic medium (pH ∼ 6), the system
2/H2O2/NaOH maintains the pH at around 7.0-8.5
during the reaction.
Indeed, as shown in Table 3, the epoxide 15 was
partially 18O-labeled (Scheme 6). These results clearly
demonstrate that DMD (1a ) must be involved in the
oxidation of 14 with the system 2c/H2O2/NaOH/acetone
and confirm the 18O-labeling data 20 for the caroate/ketone
system.21 The 18O content found in the epoxide 15 and
in the acetone determined after the reaction corresponded
very well; thus, the amount of oxidation by DMD was
estimated to be ca. 67% in the equimolar experiments
(Table 3, entries 1 and 2). Entry 4 documents that 18O
label loss, which might occur by the decomposition of
DMD similar to the caroate/ketone system,8 does not
apply.22 A control experiment in the absence of acetone
under similar conditions (Table 3, entry 5) indicated the
Experiments with caroate/NaHCO3 instead of 2/H2O2/
NaOH under reaction conditions analogous to entry 5
(Table 2) showed only very little conversion of 12 (7%) to
the diasteromeric epoxides 13 after 48 h (Table 2, entry
25).19
C. 18O-La belin g Exp er im en ts. It was anticipated
that direct proof for the intermediate formation of 1a in
the oxidation reaction with 2c/H2O2/NaOH/acetone de-
scribed above could be obtained by 18O-labeling experi-
ments. If 18O-labeled acetone is involved in the epoxi-
dation of an olefin, then a maximum of 50% of the 18O
label should appear in the epoxide produced. Analogous
(16) CAUTION! Mixtures of more than 30% H2O2 in organic solvents
are potentially detonatable: Swern, D. In Organic Peroxides; Wiley
Interscience: New York, 1970, pp 90-92. The preparation of the
etheral H2O2 solution and the oxidations should be carried out in a
hood behind a safety shield and all protection measures exercised.
(17) The higher conversions achieved with 2c are attributed to the
enhanced reactivity of 5c because of the electron-withdrawing group
(i.e. NO2) and the higher leaving group tendency of the resulting
arenesulfonate.
(20) Edwards, J . O.; Pater, R. H.; Curci, R.; DiFuria, F. Photochem.
Photobiol. 1979, 30, 63.
(21) Very recently (Armstrong, A.; Clarke, P. A.; Wood, A. J . Chem.
Soc., Chem. Commun. 1996, 849), 18O-labeling epoxidation experiments
with the system caroate/[18O]4-tert-butylcyclohexanone under biphasic
conditions have been reported to transfer 16O exclusively, which
indicate that no dioxirane is involved in the oxidation step. This
contrary finding has been rationalized by the authors in terms of other
oxidation mechanisms.
(18) The optimum pH range for the caroate-mediated generation of
1a has been established to be 7.5-8.0 (no formation of 1a is observed
below pH 6.5 and above 8.5, see ref 8).
(22) 18O label loss of the acetone by decomposition of 1a in the
system 2/H2O2/NaOH/acetone cannot be completely ruled out, but this
may be compensated by base-catalyzed isotope exchange with Na-
18OH.
(19) For
a comparison concerning the oxidation by dioxiranes
generated from caroate and molar amounts of the ketone, see ref 7
and 8.

192 J . Org. Chem., Vol. 62, No. 1, 1997
Schulz et al.
absence of 18O label in the epoxide 15, which was
obtained in an almost equal yield as in the other
experiments. These results allow us to exclude any 18O
transfer by the system 2c/H2O2/NaOH(in H218O). Since
both the oxidant and the ketone are applied in molar
ratios, the yields of epoxide 15 are moderate to good. This
is rather surprising because the in situ generated sulfonic
peracid 5 is not stable compared to caroate.
In addition to the l8O-labeling experiments, direct
spectroscopic evidence for 1a was achieved by 13C NMR
spectroscopy with simulation of the reaction conditions.
By treating a solution of 1 equiv of each 2a and [2-13C]ac-
etone and 2 equiv of H2O2 in CD3OD with 2 N NaOH, a
signal of the [3-13C]DMD at δ 103.6 was observed in the
13C NMR spectrum a few minutes after the addition of
the 2 N NaOH, which matches well the previously
observed δ 102.3 (measured in acetone).23
mixture over a period of 2-3 h at such a rate that the base
was consumed immediately, and the mixture was only weakly
alkaline (pH 7-8). The end of the reaction was indicated by
the consumption of 2 (TLC) and the increased pH of the
mixture (about 8-9). After complete consumption of 2 the
mixture was extracted with Et2O, and the organic phases were
collected, washed with saturated aqueous NaHCO3, water, and
brine, and dried over MgSO4. After evaporation of the solvent
the crude product was analyzed by 1H NMR spectroscopy. The
product ratio 8:9 was determined by employing the charac-
teristic signals at δ 9.99 (8c) and δ 4.66 (9c) or δ 4.51 (9d ).
Oxid a tion of 6d w ith 2a /H2O2/Na OH/Aceton e. Follow-
ing the above procedure, 3 mmol (0.562 g) 6d was oxidized
with 4 mmol (0.888 g) 2a , 8 mmol H2O2 (33%), and 8 mmol
(0.464 g) acetone. After silica gel chromatography (EtOAc/n-
hexane, 1/2) 140 mg (23%) of 9d , 157 mg of a mixture of 8c
and unchanged 6d (molar ratio 6d /8c ) 1.3/1,1H NMR), and
65 mg (19%) cyclohexanone oxime (11) were obtained. 9d : 1H
NMR (300 MHz, CDCl3) δ [ppm] 7.39-7.33 (m, 5H) 4.51 (s,
1H) 2.04 (m, 1H) 1.90-1.50 (m, 6H) 1.24-1.20 (m, 4H).
Oxid a tion of 6d w ith 2a /H2O2/Na OH/TF P . Again using
this procedure, 3 mmol (0.562 g) 6d , 4 mmol (0.888 g) 2a , 8
mmol H2O2 (33%), and 8 mmol (0.896 g) TFP gave 164 mg
(27%) of 9d , 196 mg of a mixture of 8c, and unchanged 6d
Su m m a r y
Arenesulfonic peracids 5, in situ generated from the
mixture 2/H2O2/NaOH in the presence of ketones, provide
convenient access to the in situ generation of dioxiranes
in homogeneous organic solution. This was proven by
the chemoselective oxidation of azomethines 6, the dia-
stereoselective epoxidation of cholesterol (12), 18O-label-
ing experiments, and direct 13C NMR spectral detection.
Finally, by applying the system 2c/H2O2/NaOEt/acetone
for the oxidation of 12 in absolute EtOH, we confirmed
that 1a was in situ generated, which constitutes the first
example for an in situ oxidation with DMD (1a ) in a
nonaqueous medium. We conclude that arenesulfonic
peracids 5 provide a synthetically useful entry for the in
situ generation of dioxiranes with the potential for
catalytic dioxirane oxidations.
1
(molar ratio 6d /8c ) 1/1.3, H NMR), and 88 mg (26%) of 11.
Gen er a l P r oced u r e for th e Oxid a tion of Ch olester ol
(12). While stirring, 0.2 mmol (0.077 g) 12, 0.4 mmol (arene-
sulfonyl)imidazole 2, 1 mmol H2O2 (70%), and the appropiate
amount of acetone (0.5 to 50 equiv with respect to 2) were
dissolved in 5 mL THF and 0.2 mL of 2 N aqueous NaOH was
added dropwise to the mixture so that the mixture was weakly
alkaline (pH 7-8). After complete consumption of 2 (TLC) the
THF was evaporated in vacuo, water was added, and the
mixture extracted several times with Et2O. The combined
organic phases were washed with saturated aqueous NaHCO3
,
water, and brine, and dried over MgSO4. After evaporation
of the solvent, the crude product was analyzed by 1H NMR
spectroscopy to determine the ratio of diastereomeric epoxides
R-13 and â-13 by integrating of the epoxy-H signals at δ 2.86
(d, J ) 4.4 Hz, R-13) and δ 3.05 (d, J ) 1.7 Hz, â-13).
5,6-Ep oxych olesta n -3â-ol (13). By starting from 0.2 mmol
(0.077 g) 12, 0.4 mmol (0.101 g) 2c, 1 mmol H2O2 (70%), and
4.0 mmol (0.232 g) acetone, 0.029 g (38%) of recovered 12 and
0.038 g (40%) of 13 were obtained after silica gel chromatog-
raphy (EtOAc/n-hexane, 1/1). The diastereomeric ratio was
found to be R-13/â-13 ) 1:1.23 from 1H NMR measurements
of the crude product.
Oxid a tion of 12 u n d er Non a qu eou s Con d ition s. In a
similar manner to the general procedure 0.1 mmol (0.038 g)
12, 0.2 mmol (0.051 g) 2c, 0.5 mmol H2O2 (2M in Et2O), and
0.118 g (2 mmol) acetone were dissolved in 3 mL of absolute
EtOH and 0.25 mL of a freshly prepared 2 N solution of NaOEt
in EtOH was added successively to the mixture. After the
usual work up, the crude product (39 mg) was analyzed by 1H
NMR spectroscopy which indicated a mixture of 12 and 13
(ratio 12/13 ) 1.48:1). The diastereomeric ratio was found to
be R-13/â-13 ) 1:1.08.
Oxid a tion of 12 w ith 3a /H2O2/K2CO3/P TC/Aceton e. To
a solution of 0.2 mmol (0.077 g) 12, 0.4 mmol (0.123 g) 3a ,
and 4 mmol (0.232 g) acetone in 5 mL of CH3CN/CH2Cl2 (3/1)
at 5 °C were added 0.3 mmol (0.042 g) K2CO3 and 0.02 mmol
(0.007 g) n-Bu4N+ HSO4-, and the mixture was vigorously
stirred. Then 1 mmol H2O2 (70%) was added in portions over
2 h, and the mixture was stirred for further 1 h. The reaction
mixture was concentrated in vacuo, saturated NaHCO3 was
added, and then the mixture was extracted with ether. The
combined ether phases were worked up as described above,
yielding 74 mg (92%) of a mixture of R-13/â-13. The diaster-
eomeric ratio R-13/â-13 ) 4.6:1 was found to be almost
identical with the result obtained in the oxidation without
acetone (R-13/â-13 ) 5.2:1).9
Exp er im en ta l Section
Ma ter ia ls. (Arenesulfonyl)imidazoles 2a ,c,d were prepared
according to the method of Staab.24 Azomethines 6 were
prepared according to the literature.25 (Arenesulfonyl)azoles
2b and 4d , (E)-2-methylstyrene (14), H218O (95% 18O) and
[2-13C]acetone (99%) were commercially available from Aldrich;
TFP and cholesterol (12) were obtained from Fluka. 1-Methyl-
3-[(4-methylphenyl)sulfonyl]imidazolium tetrafluoroborate (3a )
was prepared as described previously.9 Acetone was purified
prior use in the usual way as described for other dioxirane
reactions.3,8 H2O2 was a commercial product and used as 33%
(Merck) or 70% aqueous solution (Peroxid-Chemie GmbH). The
26
etheral solution of H2O2 was prepared by extraction of 70%
aqueous solution of H2O2 with peroxide-free diethyl ether and
drying over MgCO3. This solution may be stored at 4 °C in
the dark for several months without decomposition. The
content of peroxide was determined by iodometric titration
before use. Silica gel was purchased from Mallinckrodt Baker
(silica gel for flash chromatography 40 µm, 60 Å). All solvents
were purified according to standard methods and distilled prior
use.
Gen er a l P r oced u r e for th e Oxid a tion of Azom eth in es
6. The azomethine 6 (1 mmol), 1.5 mmol 2a or 2b, 3 mmol
H2O2 (33%), and the appropriate amount (3-50 mmol) of
acetone or TFP were dissolved in 10 mL of CH3OH at 5 °C,
and 2 N NaOH was added dropwise with stirring to the
(23) (a) Adam, W.; Chan, Y. Y.; Cremer, D.; Scheutzow, D.; Schin-
dler, M. J . Org. Chem. 1987, 52, 2800. (b) Murray, R. W.; J eyaraman,
R.; Pillay, M. K. J . Org. Chem. 1987, 52, 746.
(24) Staab, H. A. Angew. Chem. 1962, 74, 407.
(25) J ennings, W. B.; Wilson, V. E.; Boyd, D. R.; Coulter, P. B. Org.
Magn. Reson. 1983, 21, 279.
Oxid a tion of 12 w ith 4d /H 2O2/Na OH/Aceton e. (Mesi-
tylenesulfonyl)-3-nitro-1,2,4-triazole (4d , 0.4 mmol, 0.118 g),
0.2 mmol (0.077 g) 12, 0.8 mmol H2O2 (70%), and 4 mmol (0.232
g) acetone were dissolved with stirring in 5 mL of anhydrous
THF at -5 to 0 °C, and 0.2 mL of 2 N NaOH were added
(26) Criegee, P. In Houben-Weyl; Mu¨ller, E., Ed; Georg Thieme
Verlag: Stuttgart 1952; Bd. VIII, p 33.

Organo Sulfonic Peracids
J . Org. Chem., Vol. 62, No. 1, 1997 193
dropwise over 30 min to this mixture. After complete con-
sumption of 4d (TLC monitoring) the reaction mixture was
concentrated in vacuo and worked up in the usual way. After
evaporation of the solvent 77 mg (96%) of R-13/â-13 were
isolated. The diastereomeric ratio was determined to R-13/â-
13 ) 10:1 which matches the ratio obtained in the absence of
acetone (R-13/â-13 ) 11:1).9
mL of a 2 N NaOH in H218O [prepared from 17 mg NaOH and
230 mg (207 µL) H218O (95% 18O)]. After complete consumption
of 2c the 18O content of the acetone was determined by GLC/
MS analysis. Water (5 mL) was added, and the mixture was
extracted with Et2O. The ether extracts were washed with
saturated aqueous NaHCO3, water, and brine, and dried with
MgSO4. The 18O content of trans-2-methyl-3-phenyloxirane
(15) was determined by GLC/MS analysis by comparing the
relative mass intensities of the peaks in the mass spectra. 15:
MS EI m/z 134 [M+, 34.81] [18O]15: m/z 136 [M+, 11.46].
Evaporation of the solvent gave 23 mg of a 1.12:1.00 mixture
of unchanged 14 and epoxide 15 whose ratio was determined
Oxid a tion of 12 w ith Ca r oa te/Na HCO3/Aceton e. (a)
Caroate (0.1 mmol, 0.062 g) was dissolved in 1 mL of distilled
water, and the solution was added dropwise to a vigorously
stirred mixture of 0.1 mmol (0.038 g) 12, 1.5 mmol (0.126 g)
NaHCO3, and 2 mmol (0.116 g) acetone in 10 mL of MeOH.
The reaction was terminated after 48 h and worked up as
1
by H NMR spectroscopy from the characteristic signals at δ
1.85 (d, J ) 6.2 Hz, 3H, 14) and δ 1.42 (d, J ) 5.1 Hz, 3H, 15).
1
usual. The crude product was analyzed by H NMR spectros-
copy, indicating the ratios 12/13 ) 13:1 and R-13/â-13 ) 1:1.2.
(b) Cholesterol (12, 0.2 mmol, 0.077 g) was dissolved in 10 mL
of acetone, NaHCO3 (3 mmol, 0.252 g) was added under
stirring, and a solution of 0.2 mmol (0.124 g) caroate in 1 mL
of distilled water was added over 1 h. After further stirring
for 5 h the mixture was worked up in the usual way, yielding
8 mg of 12 recovered and 58 mg (72%) of 13 as diastereomeric
mixture after chromatography (n-hexane/EtOAc 1/1). The
R-13/â-13 ratio in the crude product was 1:1.25 (1H NMR).
Ack n ow led gm en t . Financial support by the
Deutsche Forschungsgemeinschaft-Sonderforschungs-
bereich SFB 347 (University of Wu¨rzburg), Schwer-
punktprogramm: “Sauerstofftransfer/Peroxidchemie”,
and Graduiertenkolleg GRK 134/1-96 (University of
Halle)sis gratefully acknowledged. Furthermore we
thank the Peroxid-Chemie GmbH (Pullach, Germany)
for a gift of potassium peroxomonosulfate (Curox).
[
18O]Aceton e. Acetone (250 mg, 4.3 mmol) and H218O (95%
18O) (250 mg, 12.5 mmol) were transferred into a flask and
stored under argon at room temperature. The isotope ex-
change was monitored by GLC/MS analysis which showed a
content of 70.5% (66.0% and 63.5%, respectively, in the other
experiments) [18O]acetone after approximately two weeks. The
mixtures were used directly for the 18O-labeling experiments.
P r oced u r e for th e 18O-La belin g Exp er im en ts. To a
solution of 0.2 mmol (0.023 g) (E)-2-methylstyrene (14), 0.2
mmol (0.050 g) 2c, 0.5 mmol H2O2 (70%), and 0.2 mmol [18O]-
acetone (0.024 g of the solution described above, 18O content
70.5%) in 2 mL of MeOH were added slowly within 3 h 0.1
Su p p or tin g In for m a tion Ava ila ble: Characteristic data
of the 18O-labeling experiments [GLC retention times of
compounds 14 and 15 ([18O]15); MS data of [18O]acetone, 15,
and [18O]15] in tabulated form (2 pages). This material is
contained in libraries on microfiche, immediately follows this
article in the microfilm version of the journal, and can be
ordered from the ACS; see any current masthead page for
ordering information.
J O9610164