Regioselective oxygenations of s-trans dienes, silyl dienol ethers (SDEs), by triphenyl phosphite ozonide (TPPO) and its mechanistic study

Article abstract of DOI:10.1021/jo015562v

The direct oxygenation of s-trans dienes, silyl dienol ethers (SDEs) 2, by triphenyl phosphite ozonide (TPPO) has been examined in detail. The regioselective oxygenation was found to give hydroperoxide 3, alcohol 4, ketone 5, dimer 6, and peroxy phosphate 7 with concomitant formation of triphenyl phosphate 8 and diphenyl trimethylsilyl phosphate 10. The formation of peroxy phosphate 7 was found for the first time in TPPO oxygenation reactions. The low temperature³¹P and¹H NMR spectroscopic analyses proved the direct reaction of SDEs with TPPO without generation of singlet oxygen. The formation of the oxygenated products 3-7 is reasonably explained by the intervention of the zwitterion ZI, which can be formed by the nucleophilic attack of SDE to the central oxygen of the ozonide. The regioselective attack of SDE to the central oxygen of the ozonide was supported by the quantum chemical calculation (B3LYP/6-31G*).

Full text of DOI:10.1021/jo015562v

3548
J . Org. Chem. 2001, 66, 3548-3553
Regioselective Oxygen a tion s of S-Tr a n s Dien es, Silyl Dien ol
Eth er s (SDEs), by Tr ip h en yl P h osp h ite Ozon id e (TP P O) a n d Its
Mech a n istic Stu d y
Atsushi Mori, Manabu Abe,* and Masatomo Nojima
Department of Materials Chemistry, Graduate School of Engineering, Osaka University,
Suita 565-0871, Osaka, J apan
abe@ap.chem.eng.osaka-u.ac.jp
Received February 7, 2001
The direct oxygenation of s-trans dienes, silyl dienol ethers (SDEs) 2, by triphenyl phosphite ozonide
(TPPO) has been examined in detail. The regioselective oxygenation was found to give hydroperoxide
3, alcohol 4, ketone 5, dimer 6, and peroxy phosphate 7 with concomitant formation of triphenyl
phosphate 8 and diphenyl trimethylsilyl phosphate 10. The formation of peroxy phosphate 7 was
found for the first time in TPPO oxygenation reactions. The low temperature 31P and 1H NMR
spectroscopic analyses proved the direct reaction of SDEs with TPPO without generation of singlet
oxygen. The formation of the oxygenated products 3-7 is reasonably explained by the intervention
of the zwitterion ZI, which can be formed by the nucleophilic attack of SDE to the central oxygen
of the ozonide. The regioselective attack of SDE to the central oxygen of the ozonide was supported
by the quantum chemical calculation (B3LYP/6-31G*).
Sch em e 1. F or m a tion of Tr ip h en yl P h osp h ite
Ozon id e (TP P O) a n d Its Rea ctivity
In tr od u ction
Triphenyl phosphite ozonide (TPPO), formed by the
addition of ozone to triphenyl phosphite below -70 °C,
has attracted considerable attention from its unique
structure and reactivity (Scheme 1).1-3 The decomposition
spontaneously occurs at ca. -30 °C to give triphenyl
phosphate and singlet oxygen.3b,d,4 Thus, the ozonide
(TPPO) has been well recognized as a chemical source of
singlet oxygen (1O2). Alternatively, the ozonide can also
react directly with electron rich alkenes to afford the
oxygenated products, which are quite similar to those
observed in singlet-oxygen reactions, i.e. allylic hydro-
peroxides, dioxetanes, and endoperoxides.5
Sch em e 2. P r op osed Mech a n ism for TP P O
Oxygen a tion of Mon oa lk en es
(1) For reviews, see; (a) Murray, R. W. In Singlet Oxygen; Wasser-
man, H. H.; Murray, R. W., Eds.; Academic Press: New York, 1979;
Chapter 3. (b) Mendenhall, G. D. In Advances in Oxygenated Processes;
Baumstark, A. L., Ed.; J AI Press: London, 1990; Vol. 2, pp 203-231.
(2) (a) Thompson, Q. E. J . Am. Chem. Soc. 1961, 83, 845. (b) Murray,
R. W.; Kaplan, M. L. J . Am. Chem. Soc. 1969, 91, 5358. (c) Koch, E.
Tetrahedron 1970, 26, 3503. (d) Razumovski, S. D.; Mendenhall, G.
D. Can. J . Chem. 1973, 51, 1257. (e) Mendenhall, G. D.; Kessick, R.
F.; Dobrzdewski, M. J . J . Photochem. 1987, 25, 227.
(3) For other phosphite ozonides, see (a) El Khatib, F.; Tachon, C.;
Caminade, A.-M.; Koenig, M. Tetrahedron Lett. 1985, 26, 3007. (b)
Stephenson, L. M.; McClure, D. E. J . Am. Chem. Soc. 1973, 95, 3074.
(c) Schaap, A. P.; Thayer, A. L.; Faler, G. R.; Goda, K.; Kimura, T. J .
Am. Chem. Soc. 1974, 96, 4025. (d) Schaap, A. P.; Kees, K.; Thayer, A.
L. J . Org. Chem. 1975, 40, 1185.
(4) (a) Corey, E. J .; Taylor, W. C. J . Am. Chem. Soc. 1964, 86, 3880.
(b) Murray, R. W.; Kaplan, M. L. J . Am. Chem. Soc. 1968, 90, 537. (c)
Murray, R. W.; Kaplan, M. L. J . Am. Chem. Soc. 1968, 90, 4161. (d)
Wasserman, E.; Murray, R. W.; Kaplan, M. L.; Yager, W. A. J . Am.
Chem. Soc. 1968, 90, 4160.
(5) (a) Howard, J . A.; Mendenhall, G. D. Can. J . Chem. 1975, 53,
2199. (b) Bartlett, P. D.; Mendenhall, G. D. J . Am. Chem. Soc. 1970,
92, 210. (c) Schaap, A. P.; Bartlett, P. D. J . Am. Chem. Soc. 1970, 92,
6055. (d) Sam, T. W.; Sutherland, J . K. J . Chem. Soc., Chem. Commun.
1972, 424. (e) Kopecky, K. R.; van de Sande, J . H. Can. J . Chem. 1972,
50, 4034. (f) Bestmann, H. J .; Kisielowski, L.; Distler, W. Angew.
Chem., Int. Ed. Engl. 1976, 15, 298. (g) Bartlett, P. D.; Chu, H.-K. J .
Org. Chem. 1980, 45, 3000. (h) Stephenson, L. M.; Zielinski, M. B. J .
Am. Chem. Soc. 1982, 104, 5819. (i) Iwata, C.; Takemoto, Y.; Naka-
mura, A.; Imanishi, T. Tetrahedron Lett. 1985, 26, 3227. (j) Dussault,
P. H.; Woller, K. R. J . Org. Chem. 1997, 62, 1556.
The mechanistic studies on the direct oxygenation
process have been mainly concentrated on the reaction
with monoalkenes, which reveal that the mechanism
seems to be largely dependent upon the substrates. For
example, the concerted pathway has been proposed for
the formation of allylic hydroperoxides in the reaction of
alkyl-substituted alkenes (Scheme 2, a).5h Alternatively,
the intermediacy of a diradical or zwitterion has been
postulated for dioxetane formations in vinyl ether oxy-
genations (Scheme 2, route b).5c,g Although the formation
of endoperoxides has been proposed for an s-cis diene,5i
the TPPO oxygenation of s-trans dienes has scarcely been
investigated until now.
10.1021/jo015562v CCC: $20.00 © 2001 American Chemical Society
Published on Web 04/13/2001

Regioselective Oxygenations of S-Trans Dienes
J . Org. Chem., Vol. 66, No. 10, 2001 3549
Ta ble 1. Dir ect Oxygen a tion of Silyl Dien ol Eth er s 2a -e
and triphenyl phosphite at -78 °C in dichloromethane
(eq 2 and Table 1), unless otherwise stated. After 1 h
stirring at -78 °C, the mixture was warmed to room
temperature, and the products were carefully analyzed.
The evidence for the direct reaction of SDE 2 with TPPO
without generation of singlet oxygen at such a temper-
ature (-78 °C) has been provided by the low temperature
31P NMR studies, which are presented later.
by TP P Oa
mass
balance
(%)c
products and yields (%)b
entry
2
3
4
5
6
7
1
2
3
4d
5
2a 3a (30) 4a (12) 5a (trace) 6a (20)
-
-
-
82
89
91
90
80
82
2b 3b (49) 4b (10) 5b (24)
2c 3c (60) 4c (11) 5c (20)
2c 3c (57) 4c (11) 5c (9)
2d 3d (30) 4d (13) 5d (35)
6b (trace)
6c (trace)
6c (13)
6d (trace)
-
6
2e 3e (42) 4e (11)
-
6e (trace) 7e (19)
a
The oxygenations were performed at -78 °C in CH2Cl2 by the
slow addition of a precooled solution of SDE 2 to a solution of TPPO
b
(1.5 equiv), unless otherwise noted. Isolated yields (%) after flash
column chromatography on silica gel. 1,3-Dioxin-4-ones 1 were
recovered; 1a (18%), 1b (6%), 1c (trace), 1d (2%), 1e (10%). The
isolated yields (%) of triphenyl phosphate 8 were 80-85% on the
basis of triphenyl phosphite used in the reactions. Phenol was also
obtained ca. 10% isolated yield. c The mass balance (%) was
d
determined for SDE 2, including the recovered 1. 2 equiv of SDE
2c was used for the oxygenation by TPPO.
In conjunction with our continuing investigation on the
oxygenation of silyl enol ethers6 and the synthetic ap-
proach for functionalized hydroperoxides,7 we have de-
cided to investigate in detail the TPPO oxygenation of
silyl dienol ethers (SDEs) 2a -e derived from the corre-
sponding 1,3-dioxin-4-ones 1a -e (eq 1).8 The following
pertinent questions shall be addressed in the present
study: What reaction modes will be operated in the
TPPO oxygenation of the s-trans dienes? How are the
oxygenated products formed, i.e. mechanism?
The oxygenated products 3-7 derived from SDE 2,
triphenyl phosphate 8, phenol, and 1,3-dioxin-4-one 1
were isolated and fully characterized by the careful
spectroscopic analyses. The products and their chemical
yields (%) were listed in Table 1, together with their mass
balance (%). The regioselective oxygenation (mass bal-
ance > 80%) was revealed by the structure of the
oxygenated products, in which the 1,3-dioxin-4-one skel-
eton was remained. The recovery of 1,3-dioxin-4-ones
1a -e (trace∼18%) is probably due to the lability of SDEs
2. The dimeric ether 6a (20%) was also isolated in the
TPPO oxygenation of 1a (R1 ) R2 ) R3 ) H) (entry 1).
For the other cases, it was difficult to identify the
formation of the dimers 6b-e due to their low yields
(entries 2, 3, 5, 6). However, the significant increase of
the yield of 6c (13%) was observed, when the excess
amounts of SDE 2c (2 equiv relative to TPPO) was used
for the oxygenation (entry 4). The result is quite informa-
tive for the mechanism of the dimerization (vide infra).
In the case of the oxygenation of SDE 2e (R1 ) H, R2 )
R3 ) Me), peroxy phosphate 7e (19%) was obtained
together with the oxygenated products 3-5 by the quick
column chromatography (entry 6). The labile peroxy
phosphate 7e (δ31P -10.8 ppm, relative to 85% H3PO4)
was fully characterized by the spectroscopic analyses
(including elemental analysis). Furthermore, the struc-
ture was unequivocally confirmed by the chemical trans-
formation (eq 3) and the synthesis from hydroperoxide
3e (eq 4). Namely, the peroxide 7e was quantitatively
converted to alcohol 4e and diphenyl phosphate 9 (δ31P
-9.2 ppm) under hydrogenation conditions (H2, Pd/C, eq
3), and was independently synthesized from the reaction
of hydroperoxide 3e and diphenyl chlorophosphate (eq
4).10 This is the first example for the isolation of such a
peroxide in TPPO oxygenation reactions.
Resu lts
P r ep a r a tion of Silyl Dien ol Eth er s. The silyl dienol
ethers (SDEs) 2a -e were prepared from the correspond-
ing 1,3-dioxin-4-ones 1a -e9 by treatment with base (LDA
or KHMDS), followed by the addition of trimethyl-
silyl chloride (eq 1). Since SDEs 2a -e are labile, they
should be handled and stored under dry nitrogen atmo-
sphere.
P r od u ct An a lyses in th e Oxygen a tion Rea ction s
of SDEs 2a -e w ith TP P O. The direct oxygenation was
performed by the careful addition of a precooled solution
of SDE 2 to TPPO (1.5 equiv) prepared freshly from ozone
(6) (a) Einaga, H.; Nojima, M.; Abe, M. J . Chem. Soc., Perkin Trans.
1 1999, 2507. (b) Einaga, H.; Nojima, M.; Abe, M. Main Group Metal
Chem. 1999, 22, 539.
(7) For examples, (a) Tokuyasu, T.; Ito, T.; Masuyama, A.; Nojima,
M. Heterocycles 2000, 53, 1293. (b) Tokuyasu, T.; Masuyama, A.;
Nojima, M.; Kim, H.-S.; Wataya, Y. Tetrahedron Lett. 2000, 41, 3145.
(c) Tokuyasu, T.; Masuyama, A.; Nojima, M.; McCullough, K. J . J . Org.
Chem. 2000, 65, 1069.
(8) The reaction of singlet oxygen (1O2), which was photochemically
(>400 nm, tetraphenylporphine (TPP)) generated, with SDE 2e
afforded the relatively complex mixture, including hydroperoxide 3e
(11%) and alcohol 4e (13%).
(9) Sato, M.; Ogasawara, H.; Komatsu, S.; Kato, T. Chem. Pharm.
Bull. 1984, 32, 3848.

3550 J . Org. Chem., Vol. 66, No. 10, 2001
Mori et al.
phosphate 8 (signal c2, δ31P -17.2 ppm) and peroxy
phosphate 7e (signal c3, δ31P -10.8 ppm) were clearly
observed at -80 °C together with the excess TPPO (signal
c1, δ31P -62.8 ppm). The complete consumption of SDE
2e and the formation of hydroperoxide 3e and peroxy
phosphate 7e were clearly observed by 1H NMR (400
MHz) spectroscopic analysis at -80 °C. The excess TPPO
was intact under the reaction conditions, i.e., in the
presence of hydroperoxide 3e. The results clearly indicate
that the reaction of TPPO with hydroperoxide 3e is much
slower than that with SDE 2e at -78 °C. The low
temperature NMR studies unequivocally provided the
evidence of the direct reaction of SDE 2 with TPPO
without intervention of singlet oxygen.
To clarify the mechanism for the formation of hydro-
peroxides 3a -e and alcohols 4a -e, the direct NMR (1H
and 13C) spectroscopic analyses were performed before
subjecting the reaction mixture to the column chroma-
tography on silica gel. Signals corresponding to the silyl
peroxy ether of hydroperoxide 3 were not detected. The
results suggest that the silyl peroxy ether, if it is formed,
is not stable under the reaction conditions to give
hydroperoxide 3. And also, alcohols 4a -e were not
detected by the direct NMR analyses. Thus, the silica gel-
induced decomposition of hydroperoxide 3a -e was pro-
posed for the alcohol formation. In fact, the pure hydro-
peroxide 3c, for example, was converted in part (ca. 15%)
to alcohol 4c by treatment with silica gel. The low
temperature (ca. 0 °C) column chromatography on silica
gel resulted in increasing the isolated yields of the
hydroperoxides, which also supports the silica gel-
induced decomposition of the hydroperoxides. For ex-
ample, the isolated yield of 3b (56%) was increased with
decreasing the yield of alcohol 4b (4%), compared with
entry 2 in Table 1.
Finally, to clarify the mechanism for the formation of
1
ketones 5, the low temperature 31P and H NMR studies
in CD2Cl2 have been also performed for the TPPO (ca.
1.2 equiv) oxygenation of SDE 2d (R1, R2 ) (CH2)3, R3 )
H). As shown in Figures 1d (31P NMR), the direct
oxygenation reaction was also observed, since the inten-
sity of the signal of TPPO (δ31P -62.8 ppm, signal d1)
decreased at -80 °C after the careful addition of 2d . The
1H NMR measurement supports the result. Namely, the
complete consumption of SDE 2d and the production of
peroxide 3d and ketone 5d at -80 °C were clearly
observed. Except for signal d2 at δ31P -20.5 ppm, the low
temperature 31P NMR spectrum (Figure 1d) was quite
similar to that observed in the reaction of SDE 2e (Figure
1c): the signal of triphenyl phosphate (signal d3) and a
signal at δ31P -10.2 ppm (signal d4) were detected. When
the mixture was exposed for 2 h at -80 °C, there was no
significant change in the spectrum. Thus, all of the
phosphorus compounds are stable at least for 2 h at -80
°C. After the reaction mixture was warmed to -40 °C
(Figure 1e), the ratio of signals d1 (TPPO) and d3
(triphenyl phosphate 8) did not change between the
temperatures, d1/d3 ) 28/72 at -80 °C; d1/d3 ) 25/75
at -40 °C, whose result is consistent with the stability
of the ozonide below -40 °C. However, the decrease in
intensity of signal d4 was concurrent with the increase
in intensity of signal d2; d4/d2 ) 13/87 at -80 °C, d4/d2
) 3/97 at -40 °C. A similar phenomenon was also
observed in the 1H NMR spectra. Namely, a signal
(triplet-like) at δH 4.85 ppm decreased as the intensity
of a signal (triplet) at δH 2.55 ppm increased. The latter
signal was assigned to ketone 5d by comparison with the
authentic sample. After warming the mixture up to +20
°C, the signals d1 (TPPO) and d4 completely disappeared
to give triphenyl phosphate 8 (signal d3) and a phos-
phorus compound (signal d2) (Figure 1f). Thus, the
phosphorus compound (signal d4), which possesses chemi-
cal shifts at δ31P -10.2 and δH 4.85, should be the
precursor of both ketone 5d and the phosphorus com-
pound (signal d2) that possesses the chemical shift at δ31P
-20.5 ppm. The following experiments clarified the
structures of signals d2 and d4.
1
31P a n d H NMR Stu d y for th e TP P O Oxygen a tion
of SDEs 2. As mentioned above, the oxygenated products
3-7 derived from SDE 2 were well characterized. How-
ever, triphenyl phosphate 8 (up to 85% isolated yield),
except for peroxy phosphate 7e, was the only isolable
phosphorus product from the oxygenation reactions by
using silica gel column chromatography. To clarify the
oxygenation mechanism, it is indispensable to identify
the structures of the rest phosphorus products. Thus, the
direct 31P NMR (160 MHz) spectroscopic analyses were
performed for the oxygenation reactions.
First, to confirm the formation of the ozonide TPPO
under our NMR work conditions, the ozonolysis of tri-
phenyl phosphite (δ31P +127.2 ppm, relative to 85%
H3PO4) was performed in a NMR tube at -78 °C in
CD2Cl2, until the blue color of ozone was detected (see
Experimental Section). After the excess amount of ozone
was removed by argon bubbling, the mixture was directly
analyzed by 31P NMR at -80 °C (Figure 1a). The
formation of TPPO (δ31P -62.8 ppm, relative to 85%
H3PO4; lit. -63 ppm (ref 2a)), signal a1, and small
amount of triphenyl phosphate 8 (δ31P -17.3 ppm), signal
a2, were clearly observed (Figure 1a).
The formation of triphenyl phosphate 8 has also
observed by Mendenhall as a minor product (ca. 15%) in
the ozonolysis of triphenyl phosphite.11 The ozonide was
stable at least for 1-2 h at such conditions. After
warming the solution to +20 °C (Figure 1b), signal a1 at
δ31P -62.8 ppm disappeared to give cleanly the signal of
triphenyl phosphate 8 (δP ) -17.3 ppm) with exhaustion
of molecular oxygen. Thus, our experiments well repro-
duced the reported results.2
First, to assign signal d2, diphenyl trimethylsilyl
phosphate 10 was prepared from diphenyl phosphate 9,
according to the reported method (eq 5),12 and measured
by 31P NMR spectroscopy. The 31P NMR spectrum of 10
(δ31P -20.5 ppm) was completely consistent with signal
Next, to verify the direct reaction of SDE 2 with TPPO,
a precooled solution of SDE 2e (R1 ) R2 ) R3 ) Me) in
CD2Cl2 was carefully added to a solution of TPPO (ca.
1.1 equiv) prepared in a NMR tube at -78 °C (Figure
1c). As shown in Figure 1c, the formation of triphenyl
(10) Synthesis of alkylperoxy phosphates, see: Sosnovsky, G.; Zaret,
E. H. J . Org. Chem. 1969, 34, 968.
(11) Mendenhall, G. D.; Priddy, D. B. J . Org. Chem. 1999, 64, 5783.
(12) (a) Chojnwski, J .; Cypryk, M.; Michalski, J .; Wozniak, L. J .
Organomet. Chem. 1985, 288, 275. (b) Chojnwski, J .; Cypryk, M.;
Michalski, J .; Wozniak, L. Phosphorus Chem. 1981, 522.

Regioselective Oxygenations of S-Trans Dienes
J . Org. Chem., Vol. 66, No. 10, 2001 3551
F igu r e 1. 31P NMR (160 MHz) spectra: (a) The spectrum was measured after ozonolysis of triphenyl phosphite at -78 °C, TPPO
(signal a1, δ31P -62.8 ppm) and triphenyl phosphate 8 (signal a2, δ31P -17.3 ppm) at -80 °C. (b) The spectrum was measured
after warming the sample up to +20 °C. (c) The spectrum was measured ca.. 30 min later at -80 °C, after mixing SDE 2e and
TPPO (ca. 1.1 equiv) at -78 °C. (d) The spectrum was measure ca. 30 min later at -80 °C, after addition of SDE 2d to TPPO (ca.
1.2 equiv) at -78 °C. (e) The spectrum was measured after warming the sample up to -40 °C. (f) The spectrum was measured
after the sample was warmed to +20 °C.
d2 observed in our NMR work. Thus, the signal d2 was
assigned to the phosphate 10.
phenyl chlorophosphate according to the method for the
preparation of peroxy phosphates 7e, the formation of
ketone 5d (57%) and diphenyl phosphate 9 was observed
(eq 6). Krysov et al. reported the similar reactivity of an
alkylperoxy phosphate (eq 7).13 Namely, the thermal
decomposition of diethyl sec-butylperoxy phosphate 11
has been found to give 2-butanone and diethyl phosphite,
as shown in eq 7. The results indicate that peroxy
phosphate 7d is one of the precursors of ketone 5d .
As mentioned above, the ketone 5d has been already
formed at -80 °C, a temterature at which the peroxy
phosphate 7d was stable. The results clearly suggest that
another pathway for the formation of ketone 5d without
intervention of the peroxide 7d must exist in the direct
oxygenation reaction (see, path c in Scheme 3).
Although it was rather difficult to assign the structures
of signal d4, the signal was reasonably proposed to be
peroxy phosphate 7d by comparison of its 31P chemical
shift (δ31P -10.2 ppm) with that of the isolable 7e (δ31P
-10.8 ppm), and also by the reaction depicted in eq 6.
Discu ssion
Mech a n ism . We have performed for the first time the
detailed study on the direct oxygenation of s-trans dienes,
SDEs 2, by TPPO. On the basis of the experimental
results, the mechanism is reasonably proposed as shown
in Scheme 3.
When peroxy phosphate 7d was independently pre-
pared from the reaction of hydroperoxide 3d with di-
(13) Krysov, V. V.; Maslennikov, V. P.; Sergeeva, V. P. J . Gen. Chem.
USSR 1973, 1641.

3552 J . Org. Chem., Vol. 66, No. 10, 2001
Sch em e 3. P r op osed Mech a n ism for th e Dir ect TP P O Oxygen a tion of SDEs 2
Mori et al.
As judged by the nucleophilic character of SDEs 2 and
the electrophilic profile14 of the peroxide linkage, the
nucleophilic attack of the C1 carbon of SDE 2 to the
central oxygen of the ozonide TPPO has been proposed
to be the initial step of the direct reaction, generating
the zwitterion ZI. The selective addition on the central
oxygen can be supported by the electrostatic charge
calculation15 at B3LYP/6-31G* level of theory,16,17 which
was performed for trimethyl phosphite ozonide as a model
(Figure 2).
exists at C1 position, i.e. 2a -d , the two additional routes
(paths c and d) should be considered for the product
formations. As observed in the low-temperature NMR
analyses (Figure 1), the direct pathway for the formation
of ketone 5 and diphenyl trimethylsilyl phosphate 10
from zwitterion ZI would be involved. As can be easily
imagined from the structure of ZI, the successive proton
abstraction and elimination is proposed for the con-
comitant production of ketone 5 and the phosphate 10
(path c). Another reaction pathway (path d) for the
formation of 5 has been already mentioned in eq 6, in
which diphenyl phosphate 9 was concomitantly formed.
A question quickly arose: Why was the diphenyl phos-
phate 9 (δ31P -9.2 ppm) not observed in the 31P NMR
spectra (Figure 1)? To understand the chemical phenom-
enon, a small portion, ca. 0.1 equiv, of diphenyl phosphate
9 was added to the reaction mixture after the TPPO
oxygenation of 2d was completed. Interestingly, the
signal of 9 (δ31P -9.2 ppm) was not observed by 31P NMR
analysis, and an increase in intensity of 10 was observed.
Thus, although the reagent for the silylation of 9 is not
clear, the in-situ silylation (path e) of 9 to 10 is proposed,
which would be analogous to the reaction mentioned in
eq 5.
F igu r e 2. Charge distribution of trimethyl phosphite ozonide,
calculated by B3LYP/6-31G*.
The central oxygen atom O2 (0.00) of the ozonide
moiety has been calculated to be the most positively
charged oxygen relative to the other oxygen atoms, O1
(-0.33) and O2 (-0.29).
In the case of SDE 2e (R1 ) H, R2 ) R3 ) Me), the
mechanism for the formation of the observed products
can be concluded as follows; The eliminations of the
peroxide moiety (path a) and the phenoxy group (path b)
from zwitterion ZI competitively occur to give hydro-
peroxide 3e and peroxy phosphate 7e. When the proton
The difficult task still remains: How are the dimeric
ethers 6 formed? The following experiment gave impor-
tant information. As shown in eq 8, the analogous ether
(14) (a) Organic Peroxide; Ando, W. T., Ed.; Wiley: New York, 1992.
(b) Workentin, M. S.; Donkers, R. L. J . Am. Chem. Soc. 1998, 120,
2664. (c) Abe, M.; Inakazu, T.; Munakata, J .; Nojima, M. J . Am. Chem.
Soc. 1999, 121, 6556.
(15) (a) Chirlian, L. E.; Francl, M. M. J . Comput. Chem. 1987, 8,
894. (b) Breneman, C. M.; Wiberg, K. B. J . Comput. Chem. 1990, 11,
361.
(16) The calculation was performed within TITAN.; Wavefunction,
Inc., Schro¨dinger, Inc., 1999.
(17) (a) Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B 1988, 37, 785.
(b) Becke, A. D. Phys. Rev. A 1988, 38, 3098. (c) Becke, A. D. J . Chem.
Phys. 1993, 98, 5648.
12 (43%) was obtained in the reaction of peroxy phos-
phate 7e with SDE 2a . Thus, the nucleophilic attack of
SDE 2 to the peroxide linkage of 7 is proposed for the
ether production (path f). The mechanism is also sup-

Regioselective Oxygenations of S-Trans Dienes
J . Org. Chem., Vol. 66, No. 10, 2001 3553
intervention of singlet oxygen (1O2), initiates the direct
oxygenation reactions.
Sch em e 4. Gen er a tion of Sin glet Oxygen fr om
th e Dir a d ica l F or m of TP P O a n d P BN Ra d ica l
Tr a p p in g
Exp er im en ta l Section
P r ep a r a t ion of Silyl Dien ol E t h er s 1a -e. Gen er a l
P r oced u r e. To a solution of LDA or KHMDS (31.5 mmol) in
THF (60 cm3) was slowly added a solution of the corresponding
1,3-dioxin-4-ones 19 (30 mmol) in THF (10 cm3) at -78 °C
under argon atmosphere. After stirring for 10 min, a solution
of TMSCl (30 mmol) in THF (10 cm3) was added dropwise to
the mixture. The reaction mixture was allowed to warm to
room temperature (ca. 20 °C). After stirring for 1 h, the solvent
was removed under reduced pressure (30 °C/ca. 100 mmHg).
The distillation under reduced pressure gave the desired silyl
dienol ether 2 in 50-80% isolated yields, of which derivatives
2a 20 and 2b21 are known compound. The spectroscopic data of
the new compounds 2c-e were listed in Supporting Informa-
tion.
Gen er a l P r oced u r e for th e TP P O Oxygen a tion of Silyl
Dien ol Eth er s 2. Into a solution of triphenyl phosphite (1.5
mmol), which is freshly distilled prior to use, in CH2Cl2 (10
cm3) was bubbled a stream of O3/O2 until the blue color of O3
was detected at -78 °C. After removal of the excess O3 by
bubbling argon, a precooled solution (-78 °C) of silyl dienol
ether 2 (1 mmol) in CH2Cl2 (10 cm3) was added slowly under
argon atmosphere. The reaction mixture was stirred for 1 h
at -78 °C and then warmed to room temperature. After the
solvent was removed under reduced pressure (30 °C/100
mmHg), the mixture was subjected to silica gel column
chromatography by elution with a mixture of n-hexane (n-hex)
and ethyl acetate (EtOAc). The isolated products 3-7 were
characterized by their spectroscopic analyses, of which com-
pounds 4a ,b,22 4c,23 and 5b,c24 are known. The chemical yields
(%) are shown in Table 1. The spectroscopic data for the other
new compounds 3-7 are listed in Supporting Information.
ported by the result mentioned in Table 1, entry 4: the
use of the excess amounts of the SDE 2c increased the
formation of the dimeric ether 6c (trace to 13%) with a
decrease of ketone 5c (20% to 9%). Thus, the competitive
formation of ether 6 (path f) and ketone 5 (path e) has
been strongly proposed. The reason for the low yields of
6b-e (R2 or/and R3 ) alkyl) can be rationalized by the
steric interaction, which would suppress the SN2-type of
displacement. The retardation by the steric effect has also
been observed in a similar SN2 reaction between 1,2-
dioxetanes and nucleophiles, reported by Adam et al.18
As mentioned above, the intervention of zwitterion ZI
can reasonably rationalize the major course of the
oxygenation reactions. In this section, we would like to
discuss the possibility of other intermediates.
As described in the Introduction, the diradical inter-
mediate is often proposed for the direct reaction of
monoalkenes with TPPO. Our experimental results would
be also explained by the analogous intermediate, DR.
Gen er a l P r oced u r e for Low-Tem per a tu r e NMR An a ly-
sis. To a solution of triphenyl phosphite (0.1 mmol), which is
freshly distilled prior to use, in CD2Cl2 (0.8 cm3), was bubbled
a stream of O3/O2 through a cold trap (-78 °C) until the blue
color of O3 was detected at -78 °C. After removal of the excess
O3 by bubbling argon through the cold trap, a precooled
solution (-78 °C) of silyl dienol ether 2 (0.09 mmol) in CD2Cl2
(0.2 cm3) was added slowly under argon atmosphere. The
reaction mixture was then directly analyzed by 1H and 31P
NMR spectroscopy at -80 °C. The results are shown in Figure
1.
However, Pryor’s ESR studies19 in the reaction of TPPO
with a spin trap, e.g., R-phenyl-N-tert-butylnitron (PBN),
diminish the possibility (Scheme 4). Namely, the spin
trap reaction was only observed at around -30 °C to give
the spin adduct SA, where singlet oxygen is starting to
generate from the diradical form of the ozonide (Scheme
4). The adduct SA was not observed below -70 °C. The
results clearly suggest that the reaction between PBN
and TPPO does not occur below -70 °C. As mentioned
in our NMR study, the reaction between SDE and TPPO
was smoothly occurred to give the products at -78 °C.
Thus, the intervention of diradical DR would be excluded,
since the content of the diradical form of TPPO should
be very small.
Ack n ow led gm en t. This work was supported in part
by the grant-in-aid for Scientific Research on Priority
Areas “Molecular Physical Chemistry” from the Ministry
of Education, Science, Sports, and Culture of J apan. We
thank the Analytical Center of Faulty of Engineering,
Osaka University, for measuring 31P NMR and elemen-
tal analysis.
Su p p or tin g In for m a tion Ava ila ble: The listed spectro-
scopic data for new compounds 2-7 and 12 prepared in this
study. This material is available free of charge via the Internet
at http://pubs.acs.org.
Con clu sion
J O015562V
In the present study, we have uncovered the regio-
selective oxygenation of s-trans dienes, silyl dienol ethers
SDEs, by using TPPO as an oxygen source. The detailed
mechanistic study revealed that nucleophilic attack of
SDE to the central oxygen of the ozonide, without
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(18) (a) Adam, W.; Heil, M.; Voerckel, V. J . Org. Chem. 1992, 57,
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