Dramatic Change of Carbonyl Oxide Reactivity by the Potent Electron-Withdrawing Trifluorompthyl Group

Article abstract of DOI:10.1021/jo961728u

α,α,α-Trifluoroacetophenone oxide, generated by ¹O₂ oxidation of Ph(CF₃)CN₂, reacted electrophilically with sulfoxides (ρ = -0.74 vs σ r = 0.95) affording sulfides as the major product. The intermediacy of persulfoxides formed via cyclic peroxidic sulfuranes in the novel deoxygenation was evidenced by an ¹⁸O-tracer study and by the formation of benzaldehyde in the reaction with benzyl phenyl sulfoxide. Olefins were oxidized to epoxides during the photooxidation of Ph(CF₃)CN₂. From the fact that the epoxidation proceeded almost stereospecifically and the substituent effect on styrenes resulted in the negative ρ-value of -1.66 vs σ(r = 0.97), a dioxirane was proposed as the second intermediate which might be formed by the isomerization of carbonyl oxide. Trapping experiments with styrenes and sulfoxides suggested that the cyclization of carbonyl oxide is competitive with the reaction with sulfoxides. In contrast to the known nucleophilic nature of carbonyl oxides, the present oxide is shown to have an electrophilic character, indicating that the reactivity of carbonyl oxides could be controlled by substituants.

Full text of DOI:10.1021/jo961728u

J . Org. Chem. 1997, 62, 2387-2395
2387
Dr a m a tic Ch a n ge of Ca r bon yl Oxid e Rea ctivity by th e P oten t
Electr on -With d r a w in g Tr iflu or om eth yl Gr ou p
Takayuki Nojima, Yukimichi Hirano, Katsuya Ishiguro, and Yasuhiko Sawaki*
Department of Applied Chemistry, Faculty of Engineering, Nagoya University,
Chikusa-ku, Nagoya 464-01, J apan
Received September 10, 1996X
1
R,R,R-Trifluoroacetophenone oxide, generated by O2 oxidation of Ph(CF3)CN2, reacted electrophili-
cally with sulfoxides (F ) -0.74 vs σ; r ) 0.95) affording sulfides as the major product. The
intermediacy of persulfoxides formed via cyclic peroxidic sulfuranes in the novel deoxygenation
was evidenced by an 18O-tracer study and by the formation of benzaldehyde in the reaction with
benzyl phenyl sulfoxide. Olefins were oxidized to epoxides during the photooxidation of Ph(CF3)-
CN2. From the fact that the epoxidation proceeded almost stereospecifically and the substituent
effect on styrenes resulted in the negative F-value of -1.66 vs σ (r ) 0.97), a dioxirane was proposed
as the second intermediate which might be formed by the isomerization of carbonyl oxide. Trapping
experiments with styrenes and sulfoxides suggested that the cyclization of carbonyl oxide is
competitive with the reaction with sulfoxides. In contrast to the known nucleophilic nature of
carbonyl oxides, the present oxide is shown to have an electrophilic character, indicating that the
reactivity of carbonyl oxides could be controlled by substituents.
In tr od u ction
suggested that carbonyl oxides are best described as the
zwitterionic form (2a , 2b).
The structure and chemical properties of 1,3-dipolar
peroxidic species 1 such as ozone (X ) O), nitroso oxides
(X ) R-N), and carbonyl oxides (X ) R2C) have been
attracting much attention from synthetic, biological, and
theoretical standpoints.1 These active oxygen species
have similar electronic structures formulated as zwitte-
rions (1a , 1b) and/or biradical form (1c), and their
reactivities may be altered depending on the nature of
We became interested in the control or change of
reactivities of carbonyl oxides by choosing substituents.
In the present study, we have examined the structure
and reactivity of R,R,R-trifluoroacetophenone oxide, a
carbonyl oxide possessing a potent electron-withdrawing
trifluoromethyl group. Unique chemistry of the CF3-
substituted carbonyl oxide has been revealed such as (i)
an unexpected deoxygenation of sulfoxides to yield sul-
fides and (ii) an isomerization to the corresponding
dioxirane which could epoxidize olefins electrophilically.
These features are quite unique in comparison to the
known chemistry of carbonyl oxides.
X.2 Typically, ozone3 and nitroso oxides4 have an elec-
trophilic character reflecting their biradical structure
(1c). On the other hand, carbonyl oxides 2,5 which are
important intermediates in the ozonolysis3 of olefins and
as a model for monooxygenase enzymes,6 have been
shown to transfer an oxygen atom to a variety of
substrates.7 The most characteristic reaction of 2 is a
nucleophilic oxidation of sulfoxides,8 and it has been
Resu lts a n d Discu ssion
F or m a tion of r,r,r-Tr iflu or oa cetop h en on e Oxid e
3. Carbonyl oxides can be generated from diazo com-
pounds via the triplet route in Scheme 1; i.e., the
photolysis of diazo compounds yields triplet carbenes,
which react with ground-state oxygen to afford the
oxides.9 Alternatively, carbonyl oxides could be gener-
ated by the singlet oxygen oxidation of diazo precursors10
(the singlet route in Scheme 1); in this case it is necessary
to use a singlet oxygen sensitizer such as methylene blue
(MB). R,R,R-Trifluoroacetophenone oxide 3 may be gen-
erated by the reaction of phenyltrifluoromethyldiaz-
omethane 4 and singlet oxygen (the singlet route). Thus,
irradiation (>400 nm) of oxygen-saturated solution of 4
(8 mM) and MB (0.24 mM) in acetonitrile at ca. 20 °C
afforded over 90% yield of the corresponding ketone,
X Abstract published in Advance ACS Abstracts, March 15, 1997.
(1) Kuczkowski, R. L. In 1,3-Dipolar Cycloaddition Chemistry;
Padwa, A., Ed., 1984; Vol. 2, Chap. 11.
(2) Houk, K. N.; Yamaguchi, K. In 1,3-dipolar Cycloaddition Chem-
istry; Padwa, A., Ed., 1984, Vol. 2, Chap. 13.
(3) Bailey, P. S. Ozonation in Organic Chemistry; Academic Press:
New York, 1978, Vol. I; 1982, Vol. II.
(4) (a) Ishikawa, S; Tsuji, S; Sawaki, Y. J . Am. Chem. Soc. 1991,
113, 4282. (b) Ishikawa, S; Nojima, T; Sawaki, Y. J . Chem. Soc., Perkin
Trans. 2 1996, 127.
(5) Bunnelle, W. H. Chem. Rev. 1991, 91, 335, and references cited
therein.
(6) Hamilton, G. A. In Molecular Mechanism of Oxygen Activation;
Hayashi, O., Ed; Academic Press: New York, 1974; p 405.
(7) (a) Hamilton, G. A.; Giacin, J . R. J . Am. Chem. Soc. 1966, 88,
1584. (b) Nakamura, N.; Nojima, M.; Kusabayashi, S. J . Am. Chem.
Soc. 1986, 108, 4671. (c) Agarwal, S. K.; Murray, R. W. Photochem.
Photobiol. 1982, 35, 31. (d) Ando, W.; Kabe, Y.; Miyazaki, H. Photo-
chem. Photobiol. 1980, 31, 191.
(8) (a) Sawaki, Y.; Kato, H.; Ogata, Y. J . Am. Chem. Soc. 1981, 103,
3832. (b) Adam, W.; Haas, W.; Sieker, G. J . Am. Chem. Soc. 1984, 106,
5020. (c) Adam, W.; D rr, H.; Haas, W.; Lohray, B. Angew. Chem., Int.
Ed. Engl. 1986, 25, 101. (d) Adam, A.; Haas, W.; Lohray, B. B. J . Am.
Chem. Soc. 1991, 113, 6202.
(9) Werstiuk, N. H.; Casal, H. L.; Scaiano, J . C. Can. J . Chem. 1984,
62, 2391.
(10) (a) Higley, D. P.; Murray, R. W.; J . Am. Chem. Soc. 1974, 96,
3330. (b) Casal, H. L.; Sugamori, S. E.; Scaiano, J . C. J . Am. Chem.
Soc. 1984, 106, 7623.
S0022-3263(96)01728-8 CCC: $14.00 © 1997 American Chemical Society

2388 J . Org. Chem., Vol. 62, No. 8, 1997
Nojima et al.
Sch em e 1
of 4 in oxygen-saturated acetonitrile or benzene did not
yield a detectable amount of 5 but a complex mixture of
products by reaction with solvents. Thus, we used Freon-
113 as the solvent in the direct photolysis of 4 since the
longest carbene lifetime was recorded in this solvent.12
Direct irradiation with a 300 W medium-pressure Hg
lump on the oxygen-saturated solution of 4 (8 mM) in
Freon-113 afforded over 90% yield of 5, suggesting the
formation of carbonyl oxide.
Rea ction of 3 w ith Su lfid es a n d Su lfoxid es. As
mentioned in the introduction, carbonyl oxides are shown
to transfer an oxygen atom to a variety of substrates.7
For instance, the oxides react with sulfides7d and sulfox-
ides,8 affording corresponding sulfoxides and sulfones,
respectively. Carbonyl oxides are known to oxidize
sulfoxides nucleophilically, while they act as an electro-
philic oxidant in the oxidation of sulfides. The reactivity
of carbonyl oxide 3 was examined by trapping experi-
ments with sulfides and sulfoxides.13 Irradiation (>400
nm) on oxygen-saturated solution of 5.5 mM 4, 0.1 mM
meso-tetraphenylporphine (TPP), and 0.1 M diphenyl
sulfide (Ph2S) in acetonitrile-dichloromethane (3:1) af-
forded over 90% yield of ketone 5 together with 16.0%
yield of diphenyl sulfoxide (Ph2SO) as an oxygen transfer
product (eq 2). To our surprise, the major product from
the photooxidation of 4 in the presence of 0.1 M Ph2SO
was not the oxygen-transferred diphenyl sulfone (Ph2SO2)
but the deoxygenated diphenyl sulfide (Ph2S), the yields
being 4.2 and 28.7%, respectively (eq 3). Control experi-
ments indicated that both diazo compound 4 and singlet
oxygen are necessary for this unexpected deoxygenation
and that Ph2S and Ph2SO were unreactive toward
singlet oxygen under the same conditions. These facts
clearly suggest the involvement of carbonyl oxide 3 in
the reaction of sulfides and sulfoxides as shown in
eqs 2 and 3.
R,R,R-trifluoroacetophenone 5. It is apparent that the
ketone was produced by the reaction of 4 and singlet
oxygen.
Recently, we have reported on the mechanism of
singlet oxygenation of various kinds of diazo com-
pounds.11 It was shown that 1,2,3,4-dioxadiazole inter-
1
mediates (cf. 6) are formed in the O2 oxidation of diazo
compounds and yield carbonyl oxides or ketones by
eliminating N2 or N2O, respectively, and its cyclorever-
sion was affected by the relative stability of carbonyl
oxides. Thus, the yields of carbonyl oxides in the pho-
tooxidation can be estimated from the product ratios of
N2/N2O.
Substituent effects for substituted diphenyl sulfoxides
were examined to clarify the nature of the deoxygenation
and are summarized in Table 1. It is interesting to note
that the resulting Hammett’s F-value vs σ were shown
to be negative for both sulfide and sulfone formations,
-0.74 (r ) 0.95) and -0.64 (r ) 0.80), respectively. Thus,
carbonyl oxide 3 is shown to exhibit an electrophilic
character in the reaction with sulfoxides, probably due
to the potent electron-withdrawing power of CF3. This
feature is in sharp contrast to the case of other carbonyl
oxides which nucleophilically transfer oxygen to sulfox-
ides (F ) +0.26 vs σ (r ) 0.99) in the case of fluorenone
oxide).8a The data in Table 1 also involves a negative
F-value of -0.84 vs σ (r ) 0.99) for the oxidation of
The ratio of N2/N2O from the reaction of 4 and singlet
oxygen was determined to be 0.70, which means the
formation of carbonyl oxide 3 in ca. 40% yield. The 40%
selectivity for carbonyl oxide formation is somewhat
lower in comparison to the other reported cases of
alkylphenyldiazomethane in the range of 53-78% selec-
tivities. The lower selectivity for carbonyl oxide 3 seems
to suggest the instability of 3 owing to the destabilizing
effect of CF3 group.
(12) (a) Griller, D.; Hadel, L.; Nazran, A. S.; Platz, M. S.; Wong, P.
C.; Savino, T. G.; Scaiano, J . C. J . Am. Chem. Soc. 1984, 106, 2227.
(b) Griller, D.; Montgomery, C. R.; Scaiano, J . C.; Platz, M. S.; Hadel,
L. J . Am. Chem. Soc. 1982, 104, 6813.
(13) A preliminary results on the reaction with sulfoxides are
reported: Ishiguro, K.; Hirano, Y.; Sawaki, Y. Tetrahedron Lett. 1987,
28, 6201.
Carbonyl oxide 3 may be also generated by the reaction
of ground-state molecular oxygen and carbene intermedi-
ates (the triplet route). However, the direct photolysis
(11) Nojima, T.; Ishiguro, K.; Sawaki, Y. Chem. Lett. 1995, 545.

Change of Carbonyl Oxide Reactivity by a CF3 Group
J . Org. Chem., Vol. 62, No. 8, 1997 2389
Ta ble 1. Rela tive Rea ctivities of Su bstitu ted Dip h en yl
Su lfid es a n d Su lfoxid es in th e P h otooxid a tion of
P h en yl(tr iflu or om eth yl)d ia zom eth a n e (4)
diphenyl sulfides to sulfoxides; similar substituent effects
have been reported for other carbonyl oxides.7d,8a
Relative reactivity of carbonyl oxide 3 toward sulfides
and sulfoxides was examined by competitive reaction
using a mixture of Ph2S and (p-MeC6H4)2SO.14 The
resulted reactivity of Ph2S:Ph2SO ) 1:1.64 indicates that
the carbonyl oxide 3 is more electrophilic than common
carbonyl oxides (typically, Ph2S:Ph2SO ) 1:16.7 for
fluorenone oxide8a) but the electrophilicity of 3 is not so
strong as that of ozone (Ph2S:Ph2SO ) 1:0.084a).
In order to get more information about the reactivity
of carbonyl oxide 3, the effect of concentrations of
trapping agent Ph2SO was determined in detail. The
resulting yields of Ph2S and Ph2SO2 are plotted against
the sulfoxide concentrations as shown in Figure 1A. The
combined yields of Ph2S and Ph2SO2 increased as the
increasing concentration of trapping substrate and the
extrapolated yield at [Ph2SO] ) ∞ was ca. 40%. This is
in good agreement with the prediction of 40% carbonyl
oxide formation as estimated from the N2/N2O ratio.
relative reactivitya
additive: Ar2S
additive: Ar2SO
Ar
product: Ar2SO product: Ar2S product: Ar2SO2
p-MeOC6H4
p-MeC6H4
C6H5
3.03
2.61
(1.00)
0.54
3.65
1.68
(1.00)
0.65
1.13
0.44
0.20
0.26
p-ClC6H4
Fb
-0.84
-0.74
-0.64
a
Relative reactivities toward carbonyl oxide 3 by competitive
reactions. Initial concentrations; 7.0 mM 4, 0.1 mM TPP, 0.1 M
each of sulfides or sulfoxides in MeCN-CH2Cl2 (3:1); solutions
were irradiated at >400 nm under oxygen at 20 °C for 30 min,
b
and products were determined by GLC. The Hammett F-value
vs σ.
As an another interesting point, the dramatic change
of product ratios of Ph2SO2 and Ph2S was observed as
shown in Figure 1B. The major reaction at the lower
concentration of Ph2SO is the O-transfer to the sulfoxide,
while the deoxygenation is predominant at higher con-
centration. This point will be discussed later.
Mech a n ism of Deoxygen a tion of Su lfoxid es. The
deoxygenation of sulfoxides by carbonyl oxide 3 is surely
an unexpected reaction. A possible scheme for this
deoxygenation involves, as outlined in Scheme 2, the
formation of persulfoxide intermediates, which are known
to be formed in the reaction of sulfides and singlet oxygen
and easily lose O2.15 The mechanisms as shown in
Scheme 2 were examined by two experiments as follows:
(i) It is known that 1O2 oxidation of benzyl phenyl
sulfide results in the characteristic C-S cleavage, via
persulfoxide intermediates, affording benzaldehyde (eq
4).16 We examined the reaction of carbonyl oxide 3 with
benzyl phenyl sulfoxide in polar or nonpolar solvent. As
shown in Figure 2, a considerable amount of benzalde-
hyde as well as the corresponding sulfide and sulfone
were formed in both solvents. The product ratios of
aldehyde/sulfide in acetonitrile were higher than that in
benzene, reflecting the stability of persulfoxides. That
is, in polar solvent, persulfoxides are stable enough to
proceed the abstraction of R-proton leading to the C-S
F igu r e 1. Trapping by Ph2SO in the photooxidation of 4 in
acetonitrile using MB sensitizer. Plots of % yields of Ph2S (open
circle), Ph2SO2 (open square), and (Ph2S + Ph2SO2) (cross) (A)
and plot of Ph2SO2/Ph2S (B) vs the concentration of Ph2SO.
For initial concentrations see note a in Table 2. Products were
determined by GLC, and % yields are based on 4.
(14) The yields of products were Ph2SO (8.66%), (p-MeC6H4)2S
(21.7%), and (p-MeC6H4)2SO2 (2.22%) for the photooxidation of 4 (6.7
mM) in the copresence of 0.1 M Ph2S and (p-MeC6H4)2SO in acetoni-
trile, revealing the relative reactivity of Ph2S: (p-MeC6H4)2SO ) 1:2.76.
After correction of selectivity for Ph2SO vs (p-MeC6H4)2SO in Table 1,
the relative reactivity toward Ph2S vs Ph2SO was determined to 1:1.64.
(15) Foote, C. S.; Peters, J . W. J . Am. Chem. Soc. 1971, 93, 3795.
(16) (a) Corey, E. J .; Ouann s, C. Tetrahedron Lett. 1976, 17, 4263.
(b) Ando, W.; Nagashima, T.; Saito, K.; Kohmoto, S. J . Chem. Soc.,
Chem. Commun. 1979, 154. (c) Ando, W.; Ito, K.; Takata, T. Tetrahe-
dron Lett. 1982, 23, 3909.
cleavage (eq 4a), while they are so unstable in nonpolar
solvent that the deoxygenation occurs predominantly
(eq 4b).
The aldehyde may be also generated by the secondary
reaction of produced PhSCH2Ph with singlet oxygen
during the photooxidation of 4. In order to check such
possibility, the photooxidation of 4 (2.5 mM) was carried
out in the copresence of PhSOCH2Ph (35 mM),

2390 J . Org. Chem., Vol. 62, No. 8, 1997
Nojima et al.
Sch em e 2
only a small amount of CH3C6H4CHO (1.4%).17 This
control experiment indicated that the major amount of
aldehyde was formed via the reaction of PhSOCH2Ph
with carbonyl oxide 3 during the photooxidation of 4. All
of these facts suggested the intermediacy of persulfoxides
in the deoxygenation of sulfoxides.
(ii) The fate of oxygen atom in sulfoxides during the
deoxygenation was examined by a tracer study using 18O-
labeled Ph2SO (97.8% 18O). As shown in Scheme 2, the
persulfoxides 9 may be formed via two routes, via a linear
trioxide 7 (path a) or a cyclic sulfurane 8 (path b).
According to the former mechanism, the sulfoxide 18O is
to be exhausted as molecular oxygen, while the labeled
oxygen should be transferred to ketone oxygen in the
latter case. The observed 18O-content in ketone 5 was
15.4 ( 0.1% showing that the oxygen atom in Ph2SO is
actually taken into the ketone during the deoxygenation.
Moreover, the 18O-content was in agreement with the
combined yields (16.5%) of Ph2S (13.8%) and Ph2SO2
(2.7%). These results clearly showed that the persulfox-
ide was formed via the cyclic sulfurane intermediate.
In the reaction of carbonyl oxide 3 with sulfoxides, the
resulting sulfides seem to be formed by the deoxygenation
of persulfoxides via cyclic sulfurane intermediate 8.
Although most of sulfuranes are not stable and quite
reactive toward trace amounts of water, some isolable
sulfuranes, such as 10, are known in which the negative
charge in apical ligands is stabilized by electron-
withdrawing CF3 group.18 Hence, the formation of cyclic
sulfurane intermediate 8 similarly stabilized by CF3 in
the present deoxygenation is not unreasonable.
F igu r e 2. Plots of yields of PhCH2SPh (open circle), PhCH2-
SO2Ph (open square), and PhCHO (cross) vs the concentrations
of PhCH2SOPh added in the photooxidation of 4 in acetonitrile
(A) containing MB or in benzene (B) containing TPP. Products
were determined by GLC, and % yields are based on 4. See
note a in Table 2 for conditions.
The well-known nucleophilic reactivity of carbonyl
oxides is understood by the formation of adduct 11
leading to sulfone formation as shown in eq 5. In the
PhSCH2C6H4CH3 (1 mM), and MB (0.2 mM) in acetoni-
trile. The products of the photooxidation were PhSCH2-
Ph (29.3%), PhSO2CH2Ph (6.9%), PhCHO (5.5%), and
(17) % Yields are based on 4 consumed.
(18) Martin, J . C.; Perozzi, E. F. Science 1976, 191, 154.

Change of Carbonyl Oxide Reactivity by a CF3 Group
J . Org. Chem., Vol. 62, No. 8, 1997 2391
Sch em e 3
present case (R1 ) Ph, R2 ) CF3), the major reaction is
the deoxygenation via cyclic sulfurane intermediates. The
resulting negative Hammett’s F-value indicates that the
carbonyl oxide can electrophilically react with sulfoxides
as in the case of ozone when a strongly electron-
withdrawing group substituted. Such a biphilicity has
been documented for a variety of 1,3-dipolar species.19 If
the terminal oxygen in carbonyl oxide is to add to the
sulfoxides, the O-O cleavage of the resulting adduct 11′
to yield sulfones (eq 6a) would be facile, and hence it is
difficult to consider that cyclic sulfurane is predominantly
formed from adduct 11′ (eq 6b). A more acceptable
picture for the formation of cyclic sulfuranes would be
the electrophilic attack of carbon atom of the carbonyl
oxide to sulfoxide to yield 12, which is facilely cyclized
to form sulfurane 8 as shown in eq 6c.
F igu r e 3. Hammett plot for the epoxidation of substituted
styrenes in the photooxidation with 4 in acetonitrile containing
MB. See text for the conditions.
acetonitrile afforded the corresponding ketone 5 (>90%)
and styrene oxide (9.1%) (eq 8); no C-C cleaved products
such as benzaldehyde were formed. The substituent
On the other hand, the negative Hammett’s F-value for
the oxidation of sulfides to sulfoxides indicates that the
carbonyl oxide oxygen would electrophilically attack
toward the sulfur atom of sulfides (eq 7).
effect for the epoxidation was studied by competitive
method, relative rates being 6.40, 2.74, 1.00, and 0.46
for styrenes with substituents p-MeO, p-Me, H, and m-Cl,
respectively. The F-value for substituted styrenes vs σ
was negative value of -1.66, showing that the epoxida-
tion occurred electrophilically (Figure 3). Under the
same conditions, trans-stilbene afforded solely trans-
stilbene oxide and cis-stilbene gave cis-stilbene oxide
predominantly, the cis/trans ratio being 85/15 as listed
as run 5 in Table 2. We assumed that the stereospecific
epoxidation proceeded as the major reaction and that the
loss of stereoselectivity might be due to a side reaction.
The characteristics of the cooxidation of olefins are
summarized as: (i) the high selectivity for the epoxide
formation, (ii) the preference for electron-rich olefins, and
(iii) the high conservation of olefin stereochemistry. It
is interesting that these features are contrasted with
those of known carbonyl oxides, which is more reactive
toward electron-deficient olefins reflecting their nucleo-
philic nature.20 Moreover, the cooxidation of styrenes
during the photooxidation of diazofluorene afforded Ph-
CHO (7.7%) and styrene oxide (2.7%), suggesting that
Rea ction w ith Olefin s. It is interesting to note the
concentration effect of diphenyl sulfoxides on the ratio
of sulfides and sulfones as shown in Figure 1B; the
oxidation of Ph2SO is predominant at lower concentra-
tions of Ph2SO, while the major reaction at higher
concentration is the deoxygenation of Ph2SO. This result
implies the presence of two different intermediates, which
was examined using olefins as an another trapping agent.
The irradiation (>400 nm) of oxygen-saturated solution
of 4 (7.7 mM), 0.24 mM MB, and 100 mM styrene in
(19) Huisgen, R. In 1,3-Dipolar Cycloaddition Chemistry; Padwa,
A., Ed., 1984; Vol. 1, Chap, 1.
(20) Pryor, W. A.; Govindan, C. K. J . Am. Chem. Soc. 1981, 103,
7681.

2392 J . Org. Chem., Vol. 62, No. 8, 1997
Nojima et al.
Ta ble 2. P r od u cts fr om th e P h otooxid a tion of Dia zom eth a n e 4 in th e P r esen ce of Ad d itives u n d er Oxygen a
run no.
additive
solventb
products (%)c
1
2
3
PhCH2SOPh (100 mM)
PhCH2SOPh (100 mM)
styrene (100 mM)
AN
benzene
AN
PhCH2SPh (28.2), PhCH2SO2Ph (9.5), PhCHO (11.2)
PhCH2SPh (26.3), PhCH2SO2Ph (8.0), PhCHO (5.1)
styrene oxide (10.4)
4
trans-stilbene (40 mM)
cis-stilbene (48 mM)
AN
AN
trans-stilbene oxide (7.0)
cis-stilbene oxide (9.0)
5d
trans-stilbene oxide (1.5)
a
Irradiated at >400 nm for 30 min at 20 °C. Initial concentrations: ∼3 mM 4 for runs 1 and 2, ∼10 mM 4 for runs 3-5; sensitizers:
0.2 mM MB in MeCN and 0.2 mM TPP in benzene. AN: acetonitrile. c % Yields based on 4 consumed. Irradiated at >560 nm to
prevent the isomerization of cis-stilbene to trans-stilbene.
b
d
F igu r e 4. Plot of styrene oxide yields vs the concentration of
styrene for the photooxidation of 4 in acetonitrile containing
MB.
the major reaction was the C-C cleavage of olefins.8a
Murray et al. reported that the oxygen transfer from
carbonyl oxides to olefins did occur, but a significantly
lower transmission of stereochemistry in epoxidation by
photochemically produced carbonyl oxides compared to
that formed with thermally generated singlet oxygen
(from (PhO)3PO3).21 Although actual oxidants in these
reactions are not characterized, the reactivity for olefins
observed in the present case is quite specific and con-
trasted to previous examples.
Dioxir a n e a s a Secon d In ter m ed ia te. As men-
tioned above, the reactivities for olefins observed for the
intermediate in the present photooxidation of 4 are quite
contrasted to those of reported carbonyl oxides. This
suggests an involvement of different type active oxygen
species. Further evidence for the present of two inter-
mediates will be shown as follows:
F igu r e 5. Competitive reactions of sulfoxides and styrene:
Plots of % yields of Ph2S (open square), Ph2SO2 (cross), and
styrene oxide (open circle) vs styrene concentrations for the
photooxidation of 4 with 10 mM (A) and 2.5 mM (B) Ph2SO in
acetonitrile containing MB.
Trapping efficiencies were determined for the various
concentrations of styrene during the photooxidation of
4. The epoxide yields increased with the increasing
concentrations of styrene as shown in Figure 4, but the
maximum yield was only 10%, based on 4, with the large
excess amount of styrene. Under the same conditions,
the yield of carbonyl oxide 3 formed was estimated to be
as much as 40%, as mentioned earlier. The disagreement
between the yield of 3 and that of epoxide might suggest
that styrenes trapped another intermediate generated in
about 10% during the photooxidation.
Intervention of two types active oxygen species was
also supported by the competitive oxidation of styrene
and diphenyl sulfoxide. The resulting product distribu-
tions were strongly depended on the concentration of
diphenyl sulfoxide as shown in Figure 5. In the presence
of 10 mM Ph2SO, the formation of styrene oxide was
significantly suppressed, and the major reaction was
deoxygenation of sulfoxide (Figure 5A). At the lower
concentration (i.e., 2.5 mM) of Ph2SO, however, the
deoxygenation of sulfoxide became only a minor reaction,
and the predominant sulfone formation was competitive
with the epoxidation, since the yields of sulfone were
decreased with increasing amount of styrene oxide
(Figure 5B). These results show that the deoxygenation
of Ph2SO was not affected by the addition of a large
excess of styrene, while the epoxidation of styrene was
inhibited by the addition of only a small amount of Ph2-
SO. These results indicate that, while carbonyl oxide 3
leads to the deoxygenation of Ph2SO as mentioned
(21) Hinrichs, T. A.; Ramachandran, V.; Murray, R. W. J . Am. Chem.
Soc. 1979, 101, 1282.

Change of Carbonyl Oxide Reactivity by a CF3 Group
J . Org. Chem., Vol. 62, No. 8, 1997 2393
previously, styrene is oxidized by an another inter-
mediate, formed from 3, which also oxidizes Ph2SO to
Ph2SO2.
in the gas phase ozonolysis of olefins and the photochemi-
cal cyclization of carbonyl oxides in low temperature
matrices is well-known.27 As for the photochemical
isomerization, a preliminary laser flash photolysis study
were carried out. It was shown that carbonyl oxide 3
(λmax ) 380 nm) was a short-lived species with a few
hundred µs lifetime, similar to the case of Ph2COO (i.e.,
λmax ) 410 nm, about 1 ms lifetime). Thus, it is improb-
able that such a short-lived intermediate could absorb
light during the photooxidation of 4 with stationary light
irradiation.
From above results, the presence of two intermediates
in the photooxidation is evident. Considering these
experimental results, (a) the presence of electrophilic
intermediate formed via carbonyl oxide, (b) stereospeci-
ficity in the epoxidation, (c) a negative F-value for
substituted styrene, a dioxirane may be considered as the
second intermediate. It is well-known that dioxiranes
oxidize olefins stereospecifically22 and the present F-value
of -1.66 for substituted styrenes is quite close to the
reported value of -1.53 for dimethyldioxiranes.23 The
limiting trapped yield of 10% for styrene oxide in aceto-
nitrile indicates the formation of dioxirane 13 by 25%
selectivity from carbonyl oxide 3 which was produced in
40% yield from 4 and singlet oxygen. The competitive
trapping experiments with Ph2SO and styrene may be
interpreted that the initially formed carbonyl oxide 3 can
isomerize to dioxirane 13 only at the lower sulfoxide
concentration in such a case as shown in Figure 5B.
Moreover, the dramatic change of product ratios of Ph2-
SO2 and Ph2S as shown in Figure 1B (vide supra) would
indicate that, when the amount of sulfoxides was not
enough to trap 3, the isomerization of carbonyl oxide to
dioxirane became faster, resulting in the predominant
sulfone formation. These considerations support the
intervention of dioxirane intermediate 13. Other possible
cases are examined in the following.
In solutions, the isomerization of carbonyl oxides to
more stable dioxiranes does not usually proceed ther-
mally because of the high activation energy for the
isomerization28 and the faster bimolecular reaction lead-
ing to ketones.29 However, Sander et al. recently reported
the isomerization of dimesityl ketone oxide, a sterically
hindered carbonyl oxide, to corresponding dioxirane in
solution at -30 °C.30 It was also reported the isomer-
ization of carbonyl oxide to dioxirane was observed in the
ozonolysis of 1,2-dimethoxy 1,2-diphenylethene in CD2-
Cl2 at -20 °C.31 The present results suggested the
isomerization of a carbonyl oxide with a CF3 group to the
corresponding dioxirane in solution.
Th e Effect of a CF 3 Gr ou p . In order to understand
the effect of CF3 group on structure and energetics of
carbonyl oxides, we carried out correlated ab initio
calculations on H2COO and CF3HCOO. We used the
density functional B3LYP32 /6-31G** method for geom-
etry optimization, since the optimized geometry of parent
carbonyl oxide (H2COO) with this level was in good
agreement with that optimized with CCSD(T)/TZ+2P
level as shown by Cremer.28c The calculated geometries
of H2COO were R(OO) ) 1.343 Å, R(CO) ) 1.266 Å,
COO ) 119.4°, while those of CF3HCOO were R(OO)
) 1.336 Å, R(CO) ) 1.266 Å, COO ) 119.3° for the anti-
isomer and R(OO) ) 1.336 Å, R(CO) ) 1.270 Å, COO
) 120.1 for the syn-isomer, respectively. Comparing the
bond lengths, it is found that the substitution of H by
CF3 results in a decrease in the O-O bond strength and
a slight increase in the C-O bond. Such tendency was
consistent with the experimental IR spectra of Ph2COO
and PhCF3COO reported by Sander in a low temperature
argon matrices in which the O-O and C-O stretching
vibrations were significantly shifted by the substitution
of Ph by CF3.33 From these results, it may be appropriate
that the structure of the CF3-substituted carbonyl oxide
is formulated as biradical structure 2c rather than
zwitterionic ones (2a ,2b). These theoretical and spec-
troscopic interpretations are consistent with the electro-
philic reactivity of the carbonyl oxide 3 as revealed in
the present study.
First, the effect of trace amounts of water was exam-
ined since carbonyl oxides are known to be converted to
hydroperoxides in protic solvents.3 If carbonyl oxide 3
was trapped by the residual trace amounts of water,
R-hydroxy hydroperoxide would be formed which might
be electrophilic enough to epoxidize olefins.24 The 10%
yield of styrene oxide was, however, reduced down to only
0.4% when a large excess of water (0.2 M) was added in
acetonitrile (cf. run 3 in Table 2). This control experi-
ment eliminated an intervention of hydroperoxide inter-
mediates.
Second, an electrophilic oxidant might be formed by
the radical chain decomposition of diazomethanes.25
Such a reaction was shown to proceed during the pho-
tooxidation of alkyl phenyl dizaomethanes affording alkyl
benzoates. However, the attempt decomposition of 4 (9
mM) initiated by di-tert-butyl peroxyoxalate (3 mM),
which yields t-BuO• and CO2 at 55 °C in benzene,26 was
unsuccessful under air at 55 °C for 2.5 h. Consequently,
diazomethane 4 was shown not to be reactive toward the
alkoxyl radical, eliminating the participation of the
radical decomposition during the photooxidation.
From above results, the dioxirane intermediate 13 is
the most appropriate species for the electrophilic epoxi-
dation. The formation of dioxiranes has been reported
(27) (a) Bell, G. A.; Dunkin, I. R. J . Chem. Soc., Chem. Commun.
1983, 1213. (b) Dunkin, I. R.; Bell, G. A. Tetrahedron 1985, 41, 339.
(c) Sander, W. W. Angew. Chem., Int. Ed. Engl. 1986, 25, 255.
(28) (a) Cremer, D.; Schmidt, T.; Gauss, J .; Radhakrishnan, T. P.
Angew. Chem., Int. Ed. Engl. 1988, 27, 427. (b) Bach, R. D.; Andr s, J .
L.; Owensby, A. L.; Schlegel, H. B.; McDouall, J . J . W. J . Am. Chem.
Soc. 1992, 114, 7207. (c) Gutbrod, R.; Schindler, R. N.; Kraka, E.;
Cremer, D. Chem. Phys. Lett. 1996, 252, 221. (d) Anglada, J . M.; Bofill,
J . M.; Olivella, S. Sole, A. J . Am. Chem. Soc. 1996, 118, 4636.
(29) Scaiano, J . C.; McGimpsey, W. G.; Casal, H. L. J . Org. Chem.
1989, 54, 1612.
(22) Murray, R. W. Chem. Rev. 1989, 89, 1187, and references cited
therein.
(23) Baumstark, A. L.; Vasquez, P. C. J . Org. Chem. 1988, 53, 3437.
(24) Heggs, R. P.; Ganem, B. J . Am. Chem. Soc. 1979, 101, 2484.
(25) Ishiguro, K.; Hirano, Y.; Sawaki, Y. J . Org. Chem. 1988, 53,
5397.
(26) Bartlett, P. D.; Benzing, E. P.; Pincock, R. E. J . Am. Chem. Soc.
1960, 82, 1762.
(30) Kirschfeld, A.; Muthusamy, S.; Sander, W. Angew. Chem., Int.
Ed. Engl. 1994, 33, 2212.
(31) Kopecky, K. R.; Xie, Y.; Molina, J . Can. J . Chem. 1993, 71, 272.
(32) (a) Becke, A. D. J . Chem. Phys. 1993, 98, 5648. (b) Lee, C. L.;
Yang, W.; Parr, R. G. Phys. Rev. B 1988, 37, 785.
(33) Sander, W. J . Org. Chem. 1988, 53, 121.

2394 J . Org. Chem., Vol. 62, No. 8, 1997
Nojima et al.
performed with a Shimadzu GC-14A and a Yanagimoto G180
gas chromatograph, using 2.5 mm × 1 m column of carbowax
300M, 2% on Chromosorb WAW (GL Sciences).
Sch em e 4
Ma ter ia ls. 1-Phenyl-2,2,2-trifluorodiazoethane,35 benzyl
phenyl sulfide,36 benzyl phenyl sulfoxide,36 4-substituted diphe-
nyl sulfoxide,37 and di-tert-butyl peroxyoxalate26 were prepared
by the reported procedures. p-Methylbenzyl phenyl sulfide
was prepared by the reported method for benzyl phenyl sulfide.
Other reagents were of commercial sources.
Acetonitrile and benzene (Tokyo Kasei) were distilled over
calcium hydride. Spectrophotometric grade Freon 113 (Na-
calai) was used without further purification.
18O-La beled Dip h en yl su lfoxid e. A 10-mL acetonitrile
solution of 0.4 mM dicyanoanthracene (DCA) and 0.12 M
diphenyl sulfide in a 20-mL Pyrex reaction vessel with a
stopcock was degassed by repeated freeze-pump-thaw cycles,
and then 100 mL 18O2 gas (CEA 98.75% 18O) was introduced.
The solution was irradiated (>350 nm) for 65 h at ca. 20 °C.
18O-Labeled diphenyl sulfoxide (73.9 mg) was isolated from the
reaction mixture by means of silica gel column chromatography
using benzene-EtOAc as an eluent. The content of 18O in the
diphenyl sulfoxide was analyzed by GC-MS spectroscopy from
the relative time-integrated peak areas at m/e 202 (M), 204
(M + 2), the latter data being corrected by abstracting the M
+ 2 value of natural abundance in Ph2SO. The corrected
content of 18O in diphenyl sulfoxide was 97.8% 18O.
cis-Stilben e. A 20-mL dichloromethane of 1 g trans-
stilbene and 0.14 g of benzil as a sensitizer in a 25-mL Pyrex
tube with a rubber septum (Aldrich) was purged with oxygen.
After irradiation (>400 nm, ca. 16 h at 20 °C), cis-stilbene was
separated from the reaction mixture by silica gel column
chromatography using hexane as the eluent (>99% cis-
stilbene).
Typ ica l P r oced u r e of th e P h otooxid a tion . A 2.7-mL
acetonitrile solution of 8 mM 1-phenyl-2,2,2-trifluorodiazoet-
hane (4) and 0.24 mM methylene blue (MB) in a 25-mL Pyrex
tube capped with a rubber septum (Aldrich) was purged with
oxygen and irradiated with a 300 W medium pressure Hg lamp
through a 5% KNO2 filter solution (>400 nm) for 30 min at
ca. 20 °C at which time 4 was completely converted to the
corresponding ketone. In the case of the reaction in benzene
solution, 0.2 mM meso-tetraphenylporphine (TPP) was used
as the sensitizer. Products were determined by GLC and
identified by GC-MS analysis in comparison to authentic
samples.
Cremer et al. carried out ab initio calculations about
the isomerization of carbonyl oxides to dioxiranes.28a It
is reported that the conversion of parent carbonyl oxide
(H2COO) to the corresponding dioxirane is exothermic by
31.3 kcal/mol but has an activation energy of 25.0 kcal/
mol (at MP2/6-31G* level). On the other hand, in the
case of monofluorocarbonyl oxides, the activation energies
of the isomerization to monofluorodioxirane was reduced
to 17.1 and 7.9 kcal/mol (at MP2/6-31G* level), for the
syn- and anti-isomers, respectively. Moreover, the same
reduction of a barrier to ring closure of carbonyl oxide
was reported for difluorocarbonyl oxides.34 These dra-
matic effects of fluorine were explained by its π-donor
property to stabilize the transition state for the isomer-
ization. In the present case of the carbonyl oxide with
the CF3 group, however, such an acceleration is not
expected.
Unfortunately, the effect of the CF3 group on the
isomerization of carbonyl oxide 3 to dioxirane has not
been well understood, but solvents may play some of
acceleration effect. Further detailed theoretical consid-
eration about the isomerization of carbonyl oxide 3 is now
in progress.
Con clu sion s
Quite a unique character of CF3-substituted carbonyl
oxide 3 has been revealed. The oxide effectively deoxi-
dized sulfoxides affording sulfides as the main product.
When the sulfoxide concentration is low, the second
intermediate is formed from the oxide, which oxidizes
sulfoxides to sulfones and olefins to epoxides stereospe-
cifically as the major reaction. Dioxirane 13 is the most
plausible candidate for the second intermediate. The
mechanism of reactions of carbonyl oxide 3 may be
summarized as in Scheme 4.
The characteristic points of reactivity of CF3-substi-
tuted carbonyl oxide 3 are as follows: (a) The CF3 group
turns the known nucleophilic reactivity of carbonyl oxides
to electrophilic as characterized by the novel deoxygen-
ation of sulfoxides. (b) The CF3-substituted carbonyl
oxide may isomerize to dioxirane in solutions. Thus, the
reactivities of carbonyl oxides can be controlled by the
nature of substituents.
18O-Tr a cer Stu d y. A 0.45-mL acetonitrile solution of 8.93
mM 4, 0.24 mM MB, and 56.3 mM 18O-labeled diphenyl
sulfoxide (97.8% 18O) in a 0.5-mL Pyrex tube capped with a
rubber septum (Aldrich) was purged with oxygen and irradi-
ated with a 300 W medium pressure Hg lamp through a 5%
KNO2 filter solution (>400 nm) for 30 min at ca. 20 °C. After
that the content of 18O in the R,R,R-trifluoroacetophenone and
diphenyl sulfone formed were analyzed by GC-MS spectroscopy
from the relative peak areas at m/e 174 (M), 176 (M + 2) and
218 (M), 220 (M + 2), 222 (M + 4), respectively. Found
values: 174 (M) 84.6%, 176 (M + 2) 15.4%, 218 (M) 0%, 220
(M + 2) 66.1%, 222 (M + 4) 33.9%.
The M + 4 peak corresponds to Ph2SO2 of which the two
18O atoms involved in the starting materials and this sulfone
(M + 4) is independent of the present photooxidation. Since
the total yield of Ph2SO2 was 4.2%, the yield of Ph2SO2, which
was oxidized by carbonyl oxide, was 2.7%.
Deter m in a tion of Ga s Evolved d u r in g th e P h otooxi-
d a tion of 4. The relative sensitivity of N2/N2O on the GC-
MS spectroscopy at the ionizing voltage of 70 eV was deter-
mined to be 0.91 ( 0.02 from a mixture of authentic N2 and
N2O gasses of known ratio. A 2.95-mL acetonitrile solution
of 5.9 mM 4 and 0.24 mM MB in a 3-mL Pyrex tube capped
with a rubber septum (Aldrich) was purged with oxygen and
irradiated with a 300 W medium pressure Hg lump through
Exp er im en ta l Section
GC-MS analyses were carried out with a Shimadzu QP-5000
mass spectrometer using a 0.2 mm × 25 m capillary column
of CBP1-M50-025 (Shimadzu) and a J EOL D300 mass spec-
trometer using a 2.5 mm × 1 m column of Carbowax 300M,
2% on Chromosorb WAW (GL Sciences). GLC analyses were
(35) Robert, A. S.; Stanley, E. W. J . Org. Chem. 1967, 32, 3197.
(36) Shriner, R. L.; Struck, H. C.; J orison, W. J . Am. Chem. Soc.
1930, 52, 2060.
(34) Rahman, M.; McKee, M. L.; Shevlin, P. B.; Sztyrbicka, R. J .
Am. Chem. Soc. 1988, 110, 4002.
(37) Hampson, G. C.; Framer, R. H.; Sutton, L. E. Pro. R. Soc.
London, Ser. A. 1934, 143, 147.

Change of Carbonyl Oxide Reactivity by a CF3 Group
J . Org. Chem., Vol. 62, No. 8, 1997 2395
a 5% KNO2 filter solution (>400 nm) for 30 min at ca. 20 °C
at which 4 was completely converted to ketones. After
irradiation, the contents of N2 and N2O in solution were
analyzed by GC-MS spectroscopy from relative peak areas at
m/e 28 (N2) and 44 (N2O), respectively. Small amounts of N2
and CO2 (m/e 44) that leaked at the injection (less than 5% of
evolved gasses) were corrected for, and the analyses were
repeated for several times.
energies and geometry data reported in this paper are avail-
able as Supporting Information.
Ack n ow led gm en t. This work was supported in part
by a Grant-in-Aid for Scientific Research from the
Ministry of Education, Science and Culture of J apan.
Su p p or tin g In for m a tion Ava ila ble: A table of total
energies and geometry data reported in this paper (1 page).
This material is contained in libraries on microfiche, im-
mediately 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.
La ser F la sh P h otolysis. A preliminary laser flash pho-
tolysis experiments were carried out on air-saturated solution
of diazo compound (10-4 to 10-3 M) using a Spectron SL284G
Nd:YAG laser (266 nm, ∼6 ns, ∼25 mJ /pulse). Experiments
were carried out by flowing solution through a 10 × 5 mm2
quartz cell in order to ensure that each laser pulse irradiated
a fresh part of volume. The decay kinetics were observed by
the photomultiplier tube monitoring system. The system was
controlled by a PC-9801RX computer which was interfaced
(GPIB) to a GOULD 4072 digital oscilloscope that was used
for data acquisition.
J O961728U
(38) Frisch, M. J .; Trucks, G. W.; Schlegel, H. B.; Gill, P. M. W.;
J ohnson, B. G.; Robb, M. A.; Cheeseman, J . R.; Keith, T. A.; Petersson,
G. A.; Montgomery, J . A.; Raghavachari, K.; Al-Laham, M. A.;
Zakrzewski, V. G.; Ortiz, J . V.; Foresman, J . B. Cioslowski, J .; Stefanov,
B. B.; Nanayakkara, A.; Challacombe, M.; Peng, C. Y.; Ayala, P. Y.;
Chen, W.; Wong, M. W.; Andres, J . L.; Replogle, E. S.; Gomperts, R.;
Martin, R. L.; Fox, D. J .; Binkley, J . S.; Defrees, D. J .; Barker, J .;
Stewart, J . P.; Head-Gordon, M.; Gonzalez, C.; Pople, J . A. Gaussian
94 (Development Version, Revision B. 2) Gaussian, Inc., Pittsburgh
PA, 1995.
Th eor etica l Ca lcu la tion s. Ab initio calculations were
carried out on a DEC VENTURIS 5100 computer using
Gaussian 94.38 Density functional theory (DFT) calculation
employed the B3LYP exchange correlation functional.32 Total